The representation of the metrics of the hands is distorted, but is susceptible to malleability due to expert dexterity (magicians) and long-term tool use . However, it remains unclear whether modulation leads to a stable representation of the hand that is adopted in every circumstance, or whether the modulation is closely linked to the spatial context where the expertise occurs. To this aim, a group of 10 experienced Sign Language (SL) interpreters were recruited to study the selective influence of expertise and space localisation in the metric representation of hands. Experiment 1 explored differences in hands’ size representation between the SL interpreters and 10 age-matched controls in near-reaching (Condition 1) and far-reaching space (Condition 2), using the localisation task. SL interpreters presented reduced hand size in near-reaching condition, with characteristic underestimation of finger lengths, and reduced overestimation of hands and wrists widths in comparison with controls. This difference was lost in far-reaching space, confirming the effect of expertise on hand representations is closely linked to the spatial context where an action is performed. As SL interpreters are also experts in the use of their face with communication purposes, the effects of expertise in the metrics of the face were also studied (Experiment 2). SL interpreters were more accurate than controls, with overall reduction of width overestimation. Overall, expertise modifies the representation of relevant body parts in a specific and context-dependent manner. Hence, different representations of the same body part can coexist simultaneously. Distortions in body representation, such as perceiving parts of our body shorter or wider, are part of healthy experience. Using the well-known localisation task, researchers have been able to collect information on the body model of the hands . Indeed, fine motor control of the hands for signing causes structural differences in the volume of the hand knob .d) from a previous study with baseball experts were considered for this calculation  with an effect size of 1.65, alpha of 0.05, and power of 0.8 indicated the adequate sample size would be of 7 per group .An a priori power analysis was run to determine the required sample size by using G* Power 3.1  between 24 and 63 years of age  took part in this study. Ten of them  were recruited as expert SL interpreters  from SL associations and educational settings, such as Heriot-Watt University, and through snowball sampling. SL use is associated with different activation patterns in the brain; however, plasticity of these networks varies depending on the hearing status of the user, when language acquisition occurs and the levels of exposure to the SL  = − 2.04, p = 0.06, d = 0.91], handedness , or education  between groups. Frequency of females in each group was identical , gender , and handedness  . For this, a programme developed with Borland C++ Builder (2007) was used, allowing conversion of pixel units into centimetres.Information on the coordinates for single pointing responses was used to calculate the misallocation judgements of each landmark. Thus, from each individual picture taken, the The coordinate data were further used to calculate the inferred hand size (lengths and widths). Previous studies have used the information on the coordinates for single pointing responses to calculate distance between landmarks, and decode the so-called body model . Pairwise t tests were used to test differences in the representation of different dimensions within participant groups . Alpha level was set at p > 0.05. Effect size was estimated using Cohen’s d calculation. Finally, a set of 2 (Group: SL interpreters and controls) by 2 (Distance: near-reaching and far-reaching space) mixed-model ANOVAs were run to compare size distortion between conditions for each dependent variable . Alpha level was again set at p > 0.05 and partial eta square (ηp2) values were calculated for the effect size.The results on the representation of the hands are considered in Condition 1 (near-reaching space), and again in Condition 2 (far-reaching space). First, the overall distortion for each condition was calculated and tested against zero (no distortion) for each group. Differences between groups were tested by means of independent two-tailed x and y coordinates, showing the differences between the real and perceived hand sizes between conditions and groups ; hence, size (percentage of over/underestimation) was averaged across hands for further analyses.Differences between left- and right-hand size estimations were not significant  = − 5.97, p < 0.001, d = − 1.88] and controls . Differences between groups did not reach significance .There was an overall underestimation of finger lengths, with SL participants underestimating their length by a − 21.23% (SD = 11.24) and controls by a − 12.53% (SD = 14.11). The distortion of length was significant for both SL . Controls underestimated in similar magnitude  but in this case not significantly so . Differences between groups did not reach significance . These results taken together confirm a similar general pattern of distortions in length perception between groups in the near condition. To compare if the length distortion was different between fingers and the dorsum, a pairwise t test was run within each group . Interestingly, there were significant differences in the SL group , whereas no differences were found for controls .The length of the hands’ dorsum was calculated as the distance between the second interspace (H5) and the interior part of the wrist H1)  = 7.62, p < 0.001, d = 2.41] and controls ;  showing a significant distortion. The difference between groups was significant , confirming that the SL group was more accurate than controls in the representation of the width of their hands  and fourth interspace (H9) was calculated as a measure of overall width of the hands see Fig. b. Both gt(9) = 2.01, p = 0.08, d = 0.63]. In contrast, controls perceived their wrists to be wider than their real size ; . Group differences were significant , confirming that the SL participants were more accurate when estimating the size of their wrists. As with lengths, the perceived width distortion was compared between hands and wrists . There was a trend in the SL group , indicating a more distorted representation of the hand in comparison with the wrist. This was also the case for controls, who also perceived the hand significantly more distorted than the wrist . Hence, it appears that the hand width overestimation is more accentuated in the hand than the wrist in both groups.To explore the effect on width representation further, we considered the width of the wrists see Fig. . SL partt(9) = − 3.62, p = 0.006, d = − 1.14], whilst controls did not show a significant distortion of their finger length ;   = 1.61, p = 0.13, d = 0.72].In the far distance, SL participants significantly underestimated the length of fingers ; . Similarly, controls showed underestimation of the size of the dorsum  but not significantly so . Differences between groups did not reach significance . Differences between the underestimation of finger lengths and dorsum were not significant for either the SL group  or the control group .When considering hands dorsum’s lengths, SL participants underestimated by − 10.91% (SD = 22.09), but the distortion was not significant . Similarly, controls also showed a distortion for the width of their hands, and was found to be significant ;   = 1.78, p = 0.09, d = 0.8].In the far distance, SL participants perceived the width of their hands significantly overestimated in size ;  and the control group ; . As with the hands, differences between groups did not reach significance , and are in contrast with the near space condition. Finally, differences between the perceived width of the hands and wrists were not significant in either the SL  or the control groups , confirming that hands and wrists were equally distorted in far-reaching space condition.Similarly, overestimation of width was present for the wrists in both the SL group ; , as there was an overall reduction of the underestimation in the far-reaching space condition. Results did not reach significance for the Group factor , or for the Distance-by-Group interaction .The ANOVA for the length of fingers showed a trend for the Distance factor , Group , nor Distance-by-Group interaction  were significant.For the dorsum’s length, neither Distance . However, there were significant results for the main effect of Group , confirming a better overall estimation of hand width in the SL group. Finally, there was a trend for the Distance-by-Group interaction , as the SL group perceived the width of their hand less distorted in the near space condition.When considering the hand width, the ANOVA did not reveal significant results for the main factor of Distance , Group , or for the Distance-by-Group interaction .Finally, the ANOVA for the wrist did not reveal significant results for Distance  or control groups ; . An independent samples t test confirmed these differences were not significant between groups   = 11.87, p < 0.001, d = 3.75]; whereas the SL group overestimated by 36.55% (SD = 19.92), again, significantly so .SL and control participants showed opposite trends in length perception, but the distortion was not significant  for either the SL ; , indicating different width size representation depending on the landmark considered. Bonferroni corrected pairwise comparisons , showed that the mouth was more overestimated than the right eye  and the between eyes area . It also showed that the nose width was more overestimated than the between eyes area . No other comparisons reached significance . Furthermore, there was a main effect of Group , confirming that SL participants represented the width of the face more accurately than controls (mean difference = 36.12). Finally, the Landmarks-by-Group interaction was significant , with different distortion of landmarks depending on the group considered. Independent Bonferroni-corrected t tests  revealed that SL participants perceived the right eye , the nose , and the mouth , significantly more accurately than controls. There were no significant differences for the left eye (p = 0.08) or between eyes area (p = 0.4).Figure Previous studies have shown that metric distortions of hands and faces are intrinsic to healthy representation of the body and can be modulated by intensive long-term training (Cocchini et al. In Experiment 1, SL experts considerably outperformed controls at estimating the width of their hands in near-reaching space, but not in far. These results confirmed the link to functional workspace and size representation (Fraser and Harris In the second experiment, the metric representation of the face was explored. In this case, SL users perceived the width of face features more accurately than controls, whereas no differences were found in length perception. Hence, it is also the case that the representation of the face tends to be smaller for SL, which is, overall, more accurate. These differences with hands representations may be due to the differences in their mobility and use. Indeed, hands can change position and shape in more degree than the face. Moreover, SL practitioners experience these body parts in different ways. They do not visually track the movement of their hands when signing, and vision is instead used to calibrate the signing space, relying on somatosensory, kinaesthetic, and tactile feedback (Emmorey et al. The size distortions found in the second experiment support the previous studies that reported overestimation of width perception for the face, consistently found with a variety of methods (D’Amour and Harris Finally, attentional components cannot be completely disregarded from the improved performance by SL practitioners in the hand task. Similarly to the face, it may be that more attention focused to the hands in near space is linked to the improved representation of width. However, it is also true that, if attention was the only factor influencing the representation of hands, a general improved representation should have also been found for finger lengths, which was not the case. Hence, it is unlikely that a general attentional mechanism only can explain these results.To sum up, these results confirm that an embodied visual language can influence non-linguistic cognitive processes, indicating that mechanisms related to SL are not domain-specific and, instead, interact (Bettger et al.


IgG4-related inflammatory pseudotumors are very uncommon and are characterized histologically by the presence of inflammatory swellings with increasing IgG4-positive plasma cells and lymphocytes infiltrating the tissues. As reports of intracranial IgG4-related pseudotumors are very rare, we report a case of an IgG4-related inflammatory pseudotumor involving the clivus mimicking meningioma. A 46-year-old male presented with intermittent headache for 2 years and a sudden onset of dysphagia and dysphonia of 7 days’ duration along with lower limb weakness. Enhanced magnetic resonance imaging (MRI) of the skull base revealed an isointense signal on T1- and T2-weighted images from an enhanced mass located at the middle of the upper clivus region, for which a meningioma was highly suspected. Then, an endoscopic transsphenoidal approach was adopted and the lesion was partially resected, as the subdural extra-axial lesion was found to be very tough and firm, exhibiting fibrous scarring attaching to the brain stem and basal artery. After the surgery, brain stem and posterior cranial nerve decompression was achieved, and the patient’s symptoms, such as dysphagia, dysphonia and lower limb weakness, improved. Pathological findings showed many IgG4-positive plasma cells and lymphocytes surrounded by collagen-rich fibers. The patient was sent to the rheumatology department for further glucocorticoids after the diagnosis of an IgG4-related inflammatory pseudotumor was made. This case highlights the importance of considering IgG4-related inflammatory pseudotumors as a differential diagnosis in patients with lesions involving the clivus presenting with a sudden onset of symptoms of dysphagia and dysphonia along with lower limb weakness when other more threatening causes have been excluded. IgG4-related inflammatory pseudotumors are etiologically enigmatic and unpredictable, and total resection might not be warranted. Glucocorticoids are usually the first line of treatment after diagnosis. Although intracranial hypophysitis is well known and relatively common, IgG4-related disease (IgG4-RD) is very rare and characterized histologically by the presence of acute or chronic inflammatory swellings of involved organs with increasing IgG4-positive plasma cells and lymphocytes infiltrating the tissues . AlthougThe patient was a 46-year-old male who presented with intermittent headache for 2 years and a sudden onset of dysphagia and dysphonia of 7 days’ duration along with lower limb weakness upon physical examination. His visual acuity and fields for both eyes were relatively normal. He had no past history of autoimmune disease or other illness. Magnetic resonance imaging (MRI) of the skull base revealed a predominantly hypointense signal on T1- and T2-weighted images from a mass located in the middle of the upper clivus area, and it was homogenously enhanced after contrast MRI; meningioma was highly suspected  for the publication of any potentially identifiable images or data included in this article.All these four authors were involved in patient treatment, data collection and analysis, and manuscript writing. All authors contributed to the article and approved the submitted version.The financial support for this study was provided by the Scientific Research Project of Capital Health Development in 2018 (grant number: 2018-4-4018). The funding institutions played no role in the design of the study, data collection or analysis, decision to publish, or preparation of the manuscript.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.


Soft tissue infections in open fractures or burns are major cause for high morbidity in trauma patients. Sustained, long-term and localized delivery of antimicrobial agents is needed for early eradication of these infections. Traditional  antibiotic delivery methods are associated with a variety of problems, including their long-term unavailability and possible low local concentration. Novel approaches for antibiotic delivery via wound coverage/healing scaffolds are constantly being developed. Many of these approaches are associated with burst release and thus seldom maintain long-term inhibitory concentrations. Using 3D core/shell extrusion printing, scaffolds consisting of antibiotic depot  surrounded by a denser biomaterial ink (shell) were fabricated. Denser biomaterial ink  retained scaffold shape and modulated antibiotic release kinetics. Release of antibiotics was observed over seven days, indicating sustained release characteristics and maintenance of potency. Inclusion of Laponite in shell, significantly reduced burst release of antibiotics. Additionally, the effect of shell thickness on release kinetics was demonstrated. Amalgamation of such a modular delivery system with other biofabrication methods could potentially open new strategies to simultaneously treat soft tissue infections and aid wound regeneration. Patients with open fractures and severe burns (with >20% burned body surface), are often presented in clinics with extensive soft tissue damage. Such soft tissue wounds are often at a high risk of infection, as the soft tissue of the skin is directly exposed to contaminants after a high-energy trauma . These contaminants and/or surgical treatment procedures can introduce microorganisms at the damaged soft tissue, potentially leading to an invasive infection . In case5 colony forming units) [S. aureus, Gram-positive, opportunistic bacteria), Pseudomonas aeruginosa and Acinetobacter (Gram-negative), are reported to be the most common cause of death in burn patients [S. aureus [Infections that develop in soft tissues after an extensive trauma or burn injury are the predominant reason for complications, morbidity, and mortality ,2,5,6,7.. aureus , potenti. aureus ,9. Bacte. aureus ,2. Hence. aureus ,9,10.Currently, clinical care of infected soft tissues in open fractures and burns includes systemic and local treatments for managing infection at the injury site along with facilitating regeneration of bone ,9 and skHowever, as the concentration of the locally applied antibiotics drastically reduces in a short time, falling below minimum inhibitory concentration (MIC), multiple applications of the antibiotic at the injury site are usually required to completely eradicate the infection and its recurrence. As a result of such a procedure, local antibiotic concentrations vary over a wide range, leading to low efficiency in treating the infection. Additionally, as the local application of antibiotics involves physical contact with the wound, multiple applications can potentially interfere with healing of the wound and can introduce new infection, in addition to the excruciating pain experienced by the patient during such a treatment .Searching for alternatives, the development of new approaches to sustainably deliver antibiotics at soft tissue infection sites—hydrogels, nanofibers, and nanoparticles, etc.—are being actively pursued . Many syIn recent decades, 3D bioprinting has defined a new paradigm in regenerative medicine and tissue engineering approaches. A plethora of hydrogels  have been developed, which potentially can be laden with cells  and processed by 3D bioprinters to generate tissue substitutes of defined shape and structure, intended to be used clinically. In regard to skin tissue engineering, Cubo et al. have shown that fibrin based bioinks containing either fibroblasts or keratinocytes could be 3D bioprinted as bilayered structures to produce functional skin equivalents that can be potentially used in burn wound treatment . When suIn the current work, we aimed to develop an antibiotic loaded hydrogel delivery system, generated by 3D core/shell extrusion printing that can be flexibly used to produce wound coverage or to be integrated in a tissue substitute. The 3D core/shell printing method combines two hydrogels by coaxial extrusion such that one hydrogel is encapsulated by the other, resulting in scaffolds with core/shell architecture of the strands . The corAntibiotics commonly used for treating soft tissue infections  are loaded in the scaffolds during fabrication: Efficient antibiotic loading strategies in the core depot were initially developed and their suitability with core/shell 3D printing was evaluated. The release of loaded antibiotics through the shell was studied, whereby the effect of Laponite (when included in the shell) and thickness of the shell was explored.w/v) of sodium alginate  were prepared by dissolving autoclaved powder in sterile double distilled water (ddH2O). Biomaterial ink composed of alginate and methylcellulose (ALG-MC) was prepared as described previously [w/w). Similarly, biomaterial ink composed of alginate, methylcellulose and Laponite (ALG-MC-LAP) was prepared by first making a blend of 3% alginate and 3% Laponite ; followed by addition of 6% methylcellulose. The prepared shell biomaterial inks were stored overnight at 4 °C to allow swelling of methylcellulose, and then used for fabrication of scaffolds by 3D core/shell printing  alginate sol in ddH2O was prepared. Antibiotic solutions were added drop wise to the stirring 6% alginate solution. An equal volume of both the solutions was used, so that the final concentration of the antibiotics and alginate in the resultant suspension was 10 mg/mL and 3% (w/v), respectively. The antibiotic loaded alginate solution was used as a core part to fabricate 3D core/shell scaffolds  were first dissolved in ddHcaffolds .−1 was applied for 100 s. Similarly, to assess the effect of the addition of antibiotics to alginate and Laponite to ALG-MC, their viscosity was measured when a constant shear rate of 10 s−1 was applied for 100 s.The biomaterial inks were subject to dynamic and constant shear rate using a parallel-plate rheometer . Antibiotic loaded alginate solution (500 µL), ALG-MC or ALG-MC-LAP (1 g) were placed in between the plates with a distance of 0.1 mm. To assess the shear thinning behaviour of the biomaterial inks, viscosity was measured, while shear rate at an increment of 1 s2;Carl Roth, Karlsruhe, Germany) solution for 10 min, followed by washing with sterile 0.9% sodium chloride  solution to remove excess CaCl2.The biomaterial inks were loaded into 10 mL plotting cartridges  which were fixed onto a core/shell adapter, attached to the print head of the BioScaffolder 3.1 . The BioScaffolder was placed inside a laminar air flow cell culture bench, so that the printing process was performed under sterile conditions. Self-made coaxial needles were used; the inner cylindrical metal needle with an outlet diameter of 200 µm  was connected to the cartridge filled with antibiotic-alginate suspension. The outer conical plastic needle with various outlet diameters  was connected to the cartridge filled with ALG-MC or ALG-MC-LAP biomaterial ink. Both the biomaterial inks were simultaneously extruded such that ALG-MC or ALG-MC-LAP biomaterial ink (shell) encapsulates antibiotic-alginate suspension (core). 3D scaffolds were fabricated by meandering deposition of the extruded core/shell strand in a layer-by-layer fashion  leading to a continuous single strand scaffold of 4 layers. After completion of the extrusion process, C/S scaffolds were immediately stabilized by alginate crosslinking in sterile 100 mM calcium chloride (CaClAntibiotic-loaded C/S scaffolds with a size of approximately 14 × 14 × 3 mm (l × b × h) were put in 12 well plates containing 1 mL of 0.9% NaCl solution, so that the loaded antibiotics could be released; C/S scaffolds without antibiotic loading served as control samples. After time intervals of 2 and 6 h, 1, 2, 3, 7 and 14 d, the release solution was collected and fresh NaCl solution was added to the scaffolds. The released antibiotic solution was stored in sterile 1.5 mL tubes  at 4 °C until used for quantification.® M200 Pro, Tecan, Menendorf, Switzerland). Absorbance of pure clindamycin and release solutions was measured in quartz cuvettes  at 198 nm using a spectrophotometer . Gentamicin was quantified by using Ninhydrin assay [® M200 Pro, Tecan, Menendorf, Switzerland).Vancomycin and clindamycin in solution were quantified by measuring their absorption at 230 and 198 nm, respectively, after determining their peak absorbance at these wavelengths. Pure vancomycin (0–250 µg/mL) and release solutions were loaded in a quartz 96-well microplate  and the absorbance at 230 nm was measured using a spectrophotometer (Infinitein assay . NinhydrS. aureus (ATCC 27853) and S. epidermidis (ATCC 12228) with an OD600 of 0.1 corresponding to 107 CFU/mL were prepared in 0.9% NaCl solution. 2 mL of the bacteria suspensions were pipetted onto the agar surface and spread by moving the plates in circular motion for 30 s. The plates were then rested for 5 min to let the bacteria sediment onto the surface. Residual liquid was removed, and the plates were dried at room temperature for 10 min. Each plate was previously marked into 6 equal sectors to accommodate 6 samples (standard antibiotic concentrations or release solutions). Autoclaved Rotilabo®-sample carrier  were placed at the approximate centre of each sector. 20 µL of defined antibiotic solutions or release solutions were pipetted on to the middle of the sample carrier. The plates were then incubated for 18 h at 36 °C so that the loaded antibiotics in the sample carrier could diffuse radially outwards. The plates were then imaged using a camera system . A clear circular zone around the sample carrier is defined as the zone of inhibition (ZOI). Area of the ZOI is determined from the acquired images using ImageJ . By comparing the ZOI areas determined for the release solutions with a standard curve obtained by plotting ZOI areas resulting from solutions with known antibiotic concentrations, the calculated effective concentration (CEC) of antibiotics in the release solutions was determined. To avoid deviations caused by batch variations of bacterial suspensions, Mueller-Hinton agar, etc., standard curves were determined for each set of experiments.Agar diffusion assay (according to DIN 58940-3:2007-10) was adapted to allow quantifying the amount of antibiotics in the release solution. For preparation of the agar plates, Mueller-Hinton broth (21 g/L) was added to dissolved agar  in equal volumes. The pH of the solution was adjusted to 7.2–7.4 by adding HCl or NaOH. After autoclaving (20 min at 121 °C) and cooling to approx. 70 °C, 20 mL of liquid Mueller-Hinton agar each time was dispensed into sterile Petri dishes . Approximately 3 mm thick solidified agar was formed in the Petri dishes after cooling down to room temperature. The agar plates were stored in sterile plastic bags at 4 °C until further use. Bacterial suspensions of n = 3–6, indicated in the figure captions). Results are presented as mean value ± standard deviation. One-way analysis of variance was used to evaluate statistical significance at a level of p < 0.05 .All experiments were performed using replicates (2O (two times concentrated) and then, equal amounts of these antibiotic solutions and 6% alginate solution were mixed while stirring. The resultant antibiotic-alginate suspensions did not form any agglomerates and had uniform consistency , followed by gentamicin-alginate , unloaded alginate  and vancomycin-alginate   A.n = 3), followed by unloaded Laponite , gentamicin-Laponite  and clindamycin-Laponite  (n = 3) compared to vancomycin and unloaded Laponite  was observed (n = 3) was significantly higher than that of ALG-MC-LAP . Though total polymer/clay content of ALG-MC and ALG-MC-LAP was 12% (w/v), viscosity .In case of antibiotic loaded Laponite, shear thinning behaviour was also observed, with vancomycin-Laponite showing highest decrease in viscosity with increasing shear rate  C. Lower observed D, indicaobserved E similar2, the C/S scaffolds maintained their architecture for 14 d in 0.9% NaCl, independent of loaded antibiotics and shell material composition.As there is a significant difference in the viscosities of antibiotic loaded core and shell biomaterial inks, an ideal combination of extrusion pressure was needed to achieve similar flow rate of both core and shell biomaterial inks during 3D C/S printing. An extrusion pressure of 20–40 kPa for antibiotic-alginate suspension (core), 160–180 kPa for ALG-MC and 120–140 kPa for ALG-MC-LAP  was found to be optimal at an extrusion/printing speed of 5 mm/s. At these parameters, the core could be uniformly localised at the centre of the strand without rupturing the shell . After cPreviously established methods, described in the literature, were initially used to quantify antibiotic concentrations in release solutions obtained from the ALG-MC scaffolds. With these spectrophotometric methods, measured absorbance of pure antibiotic solutions at specific excitation wavelengths resulted in very good fitted standard curves A,C,E. HoS. aureus or S. epidermidis) developed clear areas, i.e., zones of inhibition (ZOI), around the sample carriers indicating that the loaded antibiotics had diffused radially outwards from the sample carriers and had killed the bacteria , as determined by using Release solutions collected from ALG-MC scaffolds at initial time points (2 h and 6 h) developed large ZOI, indicating a burst release of the loaded antibiotic. For release solutions collected at later time points, a progressive decrease in the developed ZOI was observed. Importantly, even though a higher burst release of antibiotics from ALG-MC scaffolds was observed, a ZOI still developed for release solution collected after 7 day, indicating that the released antibiotics maintained their potency at least till day 7 B,D,F. ThComparison of the different antibiotics quantified in the release solutions of ALG-MC scaffolds revealed that initial burst release (release solution collected after 2 h) of clindamycin (148.23 ± 18.34 µg/mL) was significantly higher compared to gentamicin (83.09 ± 2.05 µg/mL) and vancomycin (68.3 ± 17.1 µg/mL). At later time points, the average release (from d 2 till d 7) of clindamycin (2.7 ± 1.7 µg/mL) was significantly lower than gentamicin (11.31 ± 1.15 µg/mL) and vancomycin (27.4 ± 9.9 µg/mL). Quantification of vancomycin and clindamycin in release solutions obtained from ALG-MC-LAP scaffolds revealed a sustained release of both the antibiotics over the observation period of 7 day .S. aureus strain were also used for S. epidermidis: A similar trend in CEC of vancomycin and gentamicin from release solutions obtained from both ALG-MC and ALG-MC-LAP scaffold types was observed with S. epidermidis  in the agar diffusion assay. Moreover, clindamycin release solutions obtained from ALG-MC-LAP scaffolds did not result in ZOI formation  with different shell thickness were fabricated by using coaxial needles having a combination of inner needle with constant outlet diameter of 200 µm with outer needles with varying outlet diameters of 600 µm, 840 µm and 1200 µm. Thus, a theoretical shell thickness of ~165 µm, 235 µm and 585 µm, respectively, was achieved A. InitiaIn the current work, alginate-based hydrogels, along with the 3D core/shell extrusion printing method, were used to develop a hydrogel based antibiotic delivery system intended for treating soft tissue infections in open fractures and burn wounds. The spatially separated organization of low viscous antibiotic loaded hydrogel within a high viscous hydrogel, i.e., in core/shell architecture, has three distinctive advantages: (1) The core compartment serves as a depot of antibiotics. Varied concentrations of antibiotics, according to the clinical demand, can be loaded into the core and the core material can be adapted to allow efficient loading with antibiotics, without the need of strongly considering shape fidelity after printing. The latter is ensured by the shell material that additionally acts as a diffusion barrier for antibiotics loaded in the core, leading to their retention and release over a longer time. Furthermore, by varying the shell thickness, the release of loaded antibiotics can also be tuned. (2) A variety of biomaterials can be flexibly combined to fabricate core/shell scaffolds, thus this fabrication method can be adapted to various target tissues, for example, also to fabricate scaffolds intended for bone tissue engineering. Additive effects of intrinsic advantages of both the biomaterials used in 3D core/shell printing can be expected. In our present study, changing the composition of the shell components, i.e., the addition of Laponite to ALG-MC to shell biomaterial ink resulted in the reduction of burst release and enhanced sustained release behaviour of the loaded antibiotics, implying that the intrinsic adsorptive property of Laponite played a deterministic role in tuning the release kinetics. Additionally, other scaffold properties can be tailored: In another example showing such a synergy, Raja et al. demonstrated that core/shell scaffolds composed of brittle ceramic (α-TCP) core and 6% alginate (softer) shell had significantly better mechanical properties compared to pure alginate scaffold and were less brittle compared to an exclusive ceramic scaffold . In our To prepare antibiotic loaded core biomaterial ink, a simple approach of dissolving antibiotic powder in a 3% alginate solution was not feasible, especially for clindamycin and gentamicin, as they formed agglomerates. The alternative approach, where two times concentrated antibiotic solution was slowly added to a continuously stirred two times concentrated alginate solution, was successful: The addition of clindamycin to alginate yielded a clear solution, indicating that it had completely dissolved in alginate. A translucent solution of vancomycin and gentamicin alginate indicates that these antibiotics were not completely soluble in alginate. Heriot et al. observed the development of opaque alginate gel beads when incubated in gentamicin solutions . This is−1; an opposite observation with respect to our previous work. This can be attributed to the different swelling regimes for MC (overnight at 4 °C in this study compared to 2 h at room temperature in our previous work), the main component that gives the biomaterial inks their high viscosity. However, both the biomaterial inks were found perfectly suitable for 3D printing and maintained high print fidelity. Additionally, high printing speed of 5 mm/s could be achieved, thus relatively large scaffolds . An increase in area of ZOI was observed when increasing antibiotic concentrations were loaded onto the sample carrier  of the released antibiotics was directly confirmed in this assay. It can be postulated that the diffusion of antibiotics majorly determined their release kinetics from ALG-MC scaffolds, hence the intrinsic molecular properties of the antibiotics and scaffold porosity must play a dominant role in determining the release kinetics of the loaded antibiotics. Additionally, molecular interactions between loaded antibiotics and scaffold components  must have an influence on their release kinetics. For ALG-MC scaffolds loaded with antibiotics, the average burst release (at 2 h) of clindamycin was significantly higher compared to vancomycin and gentamicin . Comparincomycin . To the In contrast to the high variability in the amount of released antibiotics at different time points from ALG-MC scaffolds, consistent amounts of antibiotics were released from ALG-MC-LAP scaffolds over time. Thus, electrostatic interactions between Laponite and antibiotic molecules must have played a major role in their release. Addition of Laponite lowered the release of vancomycin and clindamycin and in the case of gentamicin, a complete arrest was observed. This observation can be attributed to the high adsorptive property of Laponite particles, consisting of a layered silicate structure housing a central magnesium core , which has a highly negatively charged face and a positively charged rim . High pKDelivery of antibiotics from hydrogels  have been extensively studied and their applicability for treating infections in open fractures and burn wounds was evaluated ,53,54,55Similar to the study of Aldrich et al., the core/shell 3D printing method can be used to incorporate antibiotics or drugs in the core and viable cells in the shell compartment (or vice versa) to deliver both at the defect site. Additionally, the combination of antibiotics such as of gentamicin, vancomycin and clindamycin, proven for efficient antibacterial activity in bone related infections , can be Using 3D core/shell extrusion printing, a unique antibiotic delivery system has been developed, wherein a high viscous (shell) hydrogel encapsulates the low viscous antibiotic loaded (core) hydrogel. The shell component provides mechanical stability to the scaffolds and can modulate the release kinetics of the loaded antibiotic. Microbiological agar diffusion assay was adapted to quantify and simultaneously assess the potency of the released antibiotics. A sustained and potent release of the tested antibiotics  was observed for seven days. We demonstrated that by changing the composition of the shell hydrogel, i.e., by adding Laponite to ALG-MC, the release kinetics can be significantly slowed down. Additionally, by changing the shell thickness, the release of antibiotics can be modulated. Further work can focus on developing hybrid constructs, aiming at the integration of core/shell antibiotic loaded scaffolds with soft tissue regeneration. With many possibilities to tailor release kinetics of loaded antibiotics, such a versatile antibiotic delivery system could potentially open new treatment procedures for soft tissue infections and regeneration in open fractures and burn wounds.


Ecological problems such as natural resource depletion and massive quantities of waste for disposal are now guiding progressive civilization towards sustainable construction. The reduction of natural resources and the discarding of debris into open landfills are the two main environmental concerns. As a result, managing these solid wastes is a major challenge worldwide. In comparison to disposal, insufficient landfills, ecological degradation and the economic load on the relevant agencies, recycling and reusing waste materials have a considerable influence. Waste fiber has been studied for use as a cement-based composite (CBC) ingredient. Recycling waste fibers not only makes the cement composite more cost-effective and long-lasting but also helps to reduce pollution. Plastics, carpets and steels are among the various types of waste fibers reviewed in this study for their applications in cement-based materials. The mechanical properties of CBCs with different kinds of recycled-waste fibers were explored, including their compressive, flexural and splitting tensile strength and durability properties. The use of recycled fibers in the construction industry can help to ensure sustainability from environmental, economic and social standpoints. As a result, additional scientific research is needed, as well as guidance for more researchers and experts in the construction sector to examine the unknown sustainability paths. The barriers to the effective implementation of waste fiber recycling techniques in the construction sector were reviewed, and various solutions were proposed to stimulate and ensure their use in CBCs. It was concluded that CBCs containing recycled fibers provide a long-term and cost-effective alternative for dealing with waste materials. Concrete is a composite material composed of various constituents, including cement, sand, coarse aggregates, additives and water . ConventThe addition of RFs to concrete may be a step towards making the material more environmentally friendly. Plastic packaging production is a significant contributor to the total municipal waste generated. Plastic waste is non-biodegradable, and is disposed of in landfill sites, where it negatively impacts the environment . Efforts2 releases and 3% of global greenhouse gas emissions [One of the century’s major challenges is to adopt a sustainable development direction in order to balance current and future generations’ environmental, economic and social needs . From thmissions ,58. Addimissions . In ordemissions . In thismissions . Given tmissions . Many ofmissions . Municipmissions . Accordimissions . In mostmissions . Waste rmissions ,65,66. Gmissions .The primary focus of this research is on environmentally friendly construction materials. Furthermore, this state-of-the-art study examines the influence of RFs on the MPs of CBCs. The key aim of this review is to evaluate and thoroughly examine the existing literature on the impacts of various kinds of RFs on the overall behavior of composites. The compressive, flexural and tensile strength, and the durability of RF-reinforced CBCs are analyzed. This study will provide a baseline for future studies on RF-reinforced CBCs. Researchers will benefit from the study’s comprehensive overview of RF output characteristics.3 [The waste RFs used in CBCs are broadly classified into three categories, namely, WRPF, WRCF and WRSF. In order to produce WRPF, post-consumer plastics are processed and washed before being sliced manually through a paper shredder or a compact disk (CD) cutter device. The bottom and neck of the plastic bottles are removed for other uses ,68,69,703 . Some sc3 . The was3 . A porti3 , [44,45,3 . The majThe addition of WRSF may be advantageous for the CS of CBCs. If a higher RF content is required, extra water to address workability concerns may have a negative impact on the CS of CBCs because of an increase in porosity . ComparaThe addition of silica fume (SF) creates a dense and compact cement matrix, and increases the bond strength among the fiber surface and the surrounding matrix, thereby improving the CS and ductility of WRSF concrete ,106. HowIn general, the addition of WRPF resulted in the decreased CS of CBCs ,71,113. The influence on MPs of concrete incorporating distinct amounts of WRCF ranging from 0.25 to 1.25% was investigated. It was discovered that increasing the fiber content decreased the CS. However, this decrease was not excessive, and the CS remained within the permissible limit for structural applications. The results indicated that the concrete CS decreased by 2.14%, 6.14%, 10.23%, 14.8% and 20.76% at fiber fractions of 0.25%, 0.50%, 0.75%, 1.0% and 1.25%, respectively . The dec2 at 7 and 56 days. The composite with 10% TW fibers had the lowest values, between 43.2 and 88.9 N/mm2 at 7 and 56 days. This decrease may be explained by the fact that increasing the fiber fraction results in an increase in voids, which weakens the material [In the comparison of the CS of mixes, a control mix containing natural coarse aggregate only represented by CNC, and a control mix containing natural fine aggregate only represented by CNF with and without fibers is shown in material .The effect of manufactured steel fiber (MSF) and WRSF on the CS of SCC is displayed in Numerous research studies found an increase in FS when WRPF was added to the concrete. A study was conducted to determine the effect of waste high-density polyethylene fibers on the MPs of concrete. Two distinct sizes of fiber and content in the range from 0.4 to 1.25% were utilized. The results revealed a steady rise in the FS of the CBCs. The specimens with smaller fiber lengths and diameters resulted in a greater FS than the specimens with longer fibers and higher diameters . SimilarThe FS might decrease due to the improper pouring and placement of concrete, which results in the formation of voids and pores within the matrix ,128. Dif2 of TW fiber-reinforced samples was less than the MOR of CRT samples of 19.8 N/mm2, which was 9% for an 8% content of both fibers at 56 days. Therefore, a fiber content of 8% was found to be optimal for both fibers in terms of MOR. Additionally, an increase in the MOR was observed as the composite aged from 7 to 56 days; for TW, the increase was 15%, and for CTR, the increase was 26% [ was 26% .Over the last few years, extensive research has been performed on the MPs of WRSF composites ,132,133.On the other hand, several studies on the use of WRSF in concrete STS have reported inconsistent results ,142,143.According to several scholars, the STS improvement of concrete with WRPF was greater with the addition of fiber percentage contents ranging from 0.25% to 2.0% by volume ,31. A 12The influence of MSF and WRSF on STS of SCC is shown in Increased porosity was observed in reinforced concrete with WRSF, and the ultra-sonic pulse velocity results showed that the addition of 2% WRSF volume content reduced the ultra-sonic pulse velocity by 3–7% . Due to A similar trend was noticed in fiber-reinforced concrete with different types of fibers, as presented in The environmental impact of waste RF used in cementitious materials is shown in Based on the existing literature on WRSF-reinforced CBCs, several current issues and possible future trends can be discussed. Although tires are one of the highest ample waste materials for SF recovery, the inconsistency in their recycling procedures makes it hard to attain a regular geometry in recycled SFs and achieve a homogeneous concrete blend with evenly distributed SFs. There is a need to develop standards to obtain the finest feasible WRSF and to eradicate concerns associated with the inconsistency of the available WRSF geometries. The sustainable impact analysis of different recycling techniques must be conducted in order to determine the best cost-effective and sustainable method for recycling regular and high-quality SFs. There is a dearth of data on the properties of WRSF. The work could be expanded to include a more detailed examination of the qualitative and quantitative analysis of WRSF reprocessed from various sources.Furthermore, bulk density and porosity are directly related to the compaction of fresh FRC and rubber affixed to the surface of recycled SFs from tires. As a result, there is a requirement to specify the specifications for the recycling of SFs from tires, and recycling factories should follow them. Additionally, WRSFs should be sorted by diameter and length prior to their application in CBCs. According to the literature, a fiber size of 0.15–0.26 mm (diameter) and 25–40 mm long fibers are preferred, as these parameters have been shown to be promising for enhancing the various MPs of WRSF-reinforced CBCs.The CS of WRSF-reinforced composites was found to be inconsistent and depends on the fiber content, optimal dosage and fiber geometry. CS was observed to be proportional to the quantity of fibers, instead of their geometry. In general, increasing the WRSF content was observed to be favorable for improving the CS, but inconsistent outcomes have been found in past studies, necessitating additional research in the future to fully understand the effect of WRSF on the CS of concrete. The addition of secondary cementitious materials to WRSF is beneficial for increasing the CS of composites. A lower fiber content does not provide matrix homogeneity, and only the cement matrix performs its function under compressive load.The literature contains relatively consistent data on the STS of CBCs when WRSF is added. It was stated that WRSF can convert the brittle breaking of samples to ductility, and can enhance the concrete’s STS. In order to enhance the tensile behavior of concrete, the optimal content of fibers needs to be added. The addition of less WRSF than the optimum content does not provide a sufficient reinforcing effect, whereas fiber contents greater than the optimum value have a detrimental effect on the WRSF dispersion into the mix, resulting in increased porosity and weak points in the matrix, which eventually influence the MPs of CBCs. Though the optimum content of WRSF is critical, no definite conclusion about the optimal content of WRSF can be drawn due to the variability of the results.Flexural and tensile strength is influenced by fiber geometry, with longer fibers providing a more effective reinforcing mechanism and increasing the concrete’s flexural and tensile strength. The quantity of rubber affixed to the WRSF from tires and heat treatment are highly dependent on one another. Minimal heat in recycling is ineffective at removing the rubber from the fibers, whereas excessive heat can damage the WRSF. As a result, caution should be exercised during the treatment of SFs with heat recycled from waste tires in order to ensure that any rubber particles that adhere to the surface are removed. Any deterioration in the MPs of the fibers affects the properties of the resulting composite.The research assessed in this study demonstrated that when waste recycled steel fiber (WRSF) is utilized in cement-based composites (CBCs) under optimal conditions, it can provide equivalent mechanical properties (MPs) to industrial steel fiber (ISF) without impairing the workability significantly. Thus, the utilization of WRSF in the construction sector may provide economical and sustainable composites that possess adequate crack resisting ability and enhanced MPs. Additionally, recycling steel fibers (SFs) from waste tires creates a new revenue stream for reusing expired and waste tires, which is more eco-friendly, provides cost-effective energy, and reduces mosquito-propagating places that circulate deadly infections like dengue fever and malaria.Recent advances in WRSF-reinforced concrete, as well as its MPs and durability, were discussed in this study. The concluding remarks include the fact that recycling SFs from waste tires is not only environmentally friendly but also a cost-effective method of generating energy during the cement manufacturing process. The incorporation of hybrid fibers, i.e., a combination of WRSF and ISF in CBCs, provides a more robust mechanism for structural loadings. In accordance with ISF, WRSF-reinforced CBCs can provide comparable performance under flexural loading.The addition of recycled-waste fibers (RFs) has no discernible effect on the water permeability of CBCs. The corrosion of WRSF was observed in chloride-rich environments, resulting in the weakening and deprivation of matrix interaction and eventually a reduction in the composite’s performance. Additionally, WRSF was more corrosive than ISF, which could result from WRSF’s longer use than ISF. Likewise, rubber fragments affixed to the surface have no effect on corrosion, which may be due to rubber’s obstructive impact on water and other chlorides.The research interest in WRF-reinforced CBCs has increased significantly over the last few years, and the subject is primarily approached experimentally to determine the composite’s mechanical properties. There is a particular emphasis on the utilization of recycled construction materials, with plastic and metals being the most extensively studied. Additionally, the significance of the construction industry’s transition of concrete to sustainability is extensively recognized. There is a disparity in investing in the potential of waste RF-reinforced composites in addressing its triple bottom line. Accelerated aging conditions were applied to textile waste fibers and reference composites. The results for the textile waste FRCs demonstrated a significant improvement in their mechanical performance (at least 10%) over the reference samples.The experimental tests, including the workability and compressive, splitting tensile, and flexural behavior, exhibited that incorporating waste recycled plastic fibers (WRPFs) in CBCs produces residual strength capacity, with a scarce effect on its volumetric weight and ultimate flexural and compressive strength. The study supports the use of concrete with WRPF by understanding its behavior, which could help to understand the mechanical strength of fiber-reinforced concrete structures with WRPFs.The effects of waste RFs on the slump, compressive, splitting-tensile, and flexural strength, energy absorption, ductility and durability of concrete were reviewed. A huge number of publications were collected and examined for this purpose. The current study prompts the building sector to adopt a new type of concrete made from various RFs recovered from waste plastics, carpets and steel. Further research on the influence of fiber orientation during placement is possible. For the better applicability and suitability of this material, the fiber orientation ratio, and top and bottom alignment angles of the fibers could be examined. SFs collected from discarded tires in concrete could be a beneficial material in the building sector.


Concrete mix design methods are used to determine proportions of concrete ingredients needed for certain workability and strength. Each mix design method operates under certain assumptions and suggests slightly different proportions. It is of great importance that site/construction engineers know the method by which the mix was designed. However, it can be difficult to know the designing method based solely on mix proportions. Hence, in this work, a decision trees model was used to classify high strength concrete mix design methods based on their produced concrete mix proportions. It was found that the trained decision tree model is capable of classifying mix design methods with high accuracy. Further, based on dimensionality reduction methods, the amount of cement in a concrete mix was found to be the paramount predictor of the used mix design method. In this work, a novel high-accuracy model for determining a mix design method based only on mix proportion is proposed. There are many methods for designing normal and high strength concrete mixes. The objective of designing a concrete mix is to determine the amounts of concrete mix constituents. Depending on how and where concrete is going to be used, its compressive strength and workability are determined, taking into account durability requirements. Normal strength mix design methods are used for designing concrete mixes, having strengths ranging from 20 to 55 MPa. Concrete having compressive strength higher than 55 MPa is considered to be high strength. For high strength concrete mix design, many methods can be used, including the American Institute of Concrete, ACI 211.4R-08, Guide for Selecting Proportions for High-Strength Concrete Using Portland Cement and Other Cementitious Materials . For a sThese methods are used by concrete manufacturers all over the world to design and make concrete mixes according to customers’ needs. It is of great importance that site/construction engineers know the method by which a concrete mix was designed, so that they can correctly adjust concrete mixes according to field conditions, interpret fresh concrete test results, as well as satisfy quality control requirements. However, determining the method by which a concrete mix was designed can be a difficult task, because design methods usually suggest similar mix proportions for required properties. In addition, to the best of the author’s knowledge, existing literature does not provide a solution to this problem. Hence, the objective of this work is to use machine learning models, in particular, decision trees to classify high strength concrete mix design methods based on their produced concrete mix proportions. The following section discusses the past and current implementations of machine learning algorithms in concrete technology.2 values [2 values.At the present time, a considerable attention is directed towards machine learning and deep learning techniques, for their capability of solving complex problems. Some of these techniques were utilized to solve civil engineering problems including concrete mix design problems, such as the prediction of concrete’s 7, 14 and 28-day compressive strengths. Many researchers investigated the usefulness of using artificial neural networks (ANN) and linear regression models in the prediction of the strength of normal and high strength concrete ,7,8,9,102 values . More efIn addition to regression models, classification models have also been used in the field of concrete technology; for instance, Akpinar and Khashman  used ANNDespite these efforts, classification of high strength concrete mixes based on their ingredients is still an open issue. Thus, in this work, we test the hypothesis that given enough training data, a trained machine learning model can accurately classify mix design methods based on mix proportions. Specifically, a decision tree model will be used to classify high strength concrete mix design methods based on their produced concrete proportions, namely, the amounts of cement, water, gravel, sand, and chemical admixtures. The following section discusses the machine learning model used in this work, i.e., decision trees.Decision tree models  are a grThe example tree in The rest of the paper is organized as follows: methods are described in Data is considered to be the backbone of any machine learning model; in this work, thousands of mix designs were generated and used to train a decision tree model. As designing thousands of concrete mixes to train the model is a tiresome process, computer programs that implement high strength concrete mix design methods were used. Particularly, MATLAB  was used to develop high strength concrete mix design programs to generate the dataset for the machine learning model. The developed programs design high strength concrete mixes using three mix design methods . OutputsInput: The required strength, material properties , maximum nominal size of coarse aggregates, required workability (slump), whether fly ash and/or admixtures (HRWRA) are used, cost of concrete constituents, casting quantity, and whether previous test records are available.Output: Weights (per cubic meter and per provided casting quantity) of cement, water, fine and coarse aggregates as well as fly ash, admixtures (HRWRA), and the associated cost.Input: The required strength, material properties, properties of superplasticizer, aggregate shape, whether slag or/and silica fumes and/or fly ash are used, moisture content of fine and coarse aggregates, cost of concrete constituents, casting quantity, and whether previous test records are available.Output: Weights (per cubic meter and per provided casting quantity) of cement, water, fine and coarse aggregates as well as fly ash, silica fume, slag cement, superplasticizers, the calculated water/cement ratio, and the associated cost.Input: The required strength, material properties, maximum cement content, types of coarse and fine aggregates, type of cement, cost of concrete constituents, casting quantity and whether previous test records are available.Output: Weights (per cubic meter and per provided casting quantity) of cement, water, fine and coarse aggregates as well as superplasticizers (HRWRA), suggested ratios for coarse aggregate and the associated cost.The tree models make use of data features to be trained and fitted. In this work, the features used to train the model were the concrete mix proportions per one cubic meter of each mix design and the corresponding compressive strength. In particular, the amounts of cement in kg, water in liter, sand in kg, gravel in kg and HRWRA in liter, as well as compressive strength in MPa.MATLAB  was used to preprocess and visualize the dataset, as well as train and test the model.Before training the dataset, it was standardized using mean and standard deviation.The dataset (3000 mix designs) were split into training (2400 mix designs) and testing (600 mix designs).Three types of decisions trees were used, according to the number of nodes in the tree, namely, fine, medium, and coarse trees. Further, during model training, 5-fold cross validation was used to prevent overfitting. For fine tree models, the number of maximum splits was specified to be 100 splits and the splitting criterion to be Gini’s Diversity Index .TP and true negative TN) to the total number of predictions :To evaluate the performance of the decision tree model, accuracy measure was used, which is defined for binary classification as the ratio of the correct predictions  was used, which shows true positive rate versus false positive rate for the tree classifier. It is usually used for evaluating binary classification performance but can be used in multi-class classification, as is the case in this work, by evaluating one-vs-rest. A perfect classifier is one that correctly classifies all data to their actual classes; this perfect classifier appears in the ROC as a right-angle curve whose right angle is in the upper left-corner portion of the curve. ROC shows a poor classifier as a curve close to a line inclined at 45 degrees. The area under the ROC (AUC) is a sign of the performance of the classifier; a perfect classifier will have an AUC of 1.Confusion matrix was also used to further evaluate the tree classifier, which is a matrix whose rows correspond to the predicted class, and columns correspond to the true class. The diagonal of the confusion matrix shows instances that were correctly classified and the off-diagonal shows instances that were incorrectly classified.A machine learning model shall be efficient as well as accurate; therefore, the number of features used to train the model shall be optimized. This can be performed by using principal component analysis (PCA) , and minPCA reduces the dimensionality of the model by linearly transforming predictors, removing redundant predictors, and keeping only principal predictors .MRMR algorithm determines the importance of each feature in the dataset to the classification process. The MRMR algorithm’s goal is to find an optimal set of features whose relevance to outcome variable is maximum and whose redundancy is minimum .After all models were fitted to training data, they were tested using the testing dataset, which contains 20% of the entire dataset i.e., 600 mix designs. The classification accuracies of all models on training data and testing data are summarized in From the accuracy values presented in In Accuracy of the fine tree model that was tested using testing data is shown in the lower right corner in the confusion matrix shown in The trained tree model can be viewed it its actual form, however, I only show the coarse tree model herein because the fine tree and the medium tree models are too dense to be interpreted properly. The coarse tree classifier is shown in The fine tree classifier was re-trained, however, with enabling principal component analysis this time around, to determine feature importance. The PCA-enabled fine tree classifier kept two features, which can explain 95% variance. Explained variance per feature was found to be the amount of cement: 80.5%, amount of water: 18.7%, amount of sand: 0.7%, amount of gravel: 0.1%, and 0.0% for both the amount of HRWRA and concrete’s compressive strength. Results of PCA is shown in Degree of importance of each feature was determined using the MRMR algorithm, which assigns scores to each feature, indicating its importance. The amount of cement was found by MRMR to be the most important feature, with a score of 0.6, followed by the amount of water: 0.44, amount of sand: 0.43, gravel: 0.4, HRWRA: 0.23 and compressive strength: 0.0. The drop in score between the amount of cement and amount of water is relatively large, which emphasizes that cement is the most important predictor of the mix design method. On the other hand, the amount of gravel and compressive strength were found to be weak predictors of the mix design method. The results of MRMR is shown in Based on the results of the PCA analysis, only the two most important features (amount of cement and amount of water) were used in fitting reduced tree models. As can be observed in In concrete technology, we seldom talk about the amount of cement and amount of water separately; instead, we use the water/cement ratio or (W/C) for short. It can be speculated that the W/C can be of importance in the determination of mix design method; however, as it is merely a linear combination of two features, then its information is already embedded in the training dataset and hence its contribution to the outcome variable may be limited. In addition, the current set of features aided in classifying the mix design methods with very high accuracy, eliminating the need for more features.After only using principal predictors (amounts of cement and water) in training the tree model, ROC was used to test the performance of the reduced models. While this study successfully developed a model that is capable of classifying mix design methods with very high accuracies, a few shortcomings exist. For example, the training data used in training the decision tree model are synthesized. This approach works perfectly, provided that the proportions of the mix are exactly per the mix design recommendations, before any field adjustments. However, sometimes field conditions necessitate that concrete consistency is adjusted, which distorts original mix design. Hence, it is necessary that the developed model is trained/tested using real experimental data (training/testing the model using field-adjusted concrete proportions). Another limitation is that only one machine learning model is used in this work, while many more models can be tested and compared to determine the most accurate and efficient model.Machine learning, specifically decision tree models were trained to classify high strength concrete mix design methods based on concrete mix proportions with high accuracy. It was shown that knowledge of the basic amounts of the basic ingredients of high strength concrete mix is enough for the model to accurately determine the mix method by which it was designed.Feature importance analyses demonstrated that the amount of cement and water in the concrete mix are the most important predictors of the used mix design method.In this work, a novel high-accuracy model for determining the mix design method, based only on mix proportion, was presented.Mix design methods are used by concrete manufacturers all over the world to design and make concrete mixes according to the customers’ needs. It is of great importance that site/construction engineers know the method by which a concrete mix was designed, so that they can correctly adjust concrete mixes according to field conditions, interpret fresh concrete tests results, as well as satisfy quality control requirements. However, determining the method by which a concrete mix was designed can be a difficult task because design methods usually suggest similar mix proportions for certain required properties. This work solved this classification problem via the use of machine learning. In particular, this work achieved the following:Future work includes training and testing machine learning models using real experimental data (training/testing the model using field-adjusted concrete proportions). Further, the author intends to experiment with more machine learning models to determine the most accurate and efficient model for classifying mix design methods.


Physicians are constantly asked to evaluate inpatients for possible antibiotic treatment. As part of antibiotic stewardship it is imperative to understand the decision-making process behind a physician’s choice to prescribe antibiotics appropriately in an inpatient setting. Fuzzy Trace Theory (FTT) suggests that physicians use one of two methods in medical decision making; verbatim, employing a comprehensive risk benefit analysis, and gist, considering a bottom line analysis. Seventy-six hospitalists at Weill Cornell Medicine in Manhattan, New York received a survey with two reminders to evaluate their decision-making process. Five basic demographic questions regarding participant gender, race, background, age, and years in practice were asked. A clinical vignette describing an inpatient with a possible urinary tract infection (UTI) was followed with statements framing hypothetical antibiotic prescription. A seven point Likert scale with response choices from Strongly Disagree scored as one to Strongly Agree scored as seven was used to assess degree of participant agreement with each statement. Questions were presented in a random order to eliminate possible effects of questions clusters or question order. Twenty-six hospitalists completed the survey. Consistent with previous literature, the hospitalists surveyed displayed a gist interpretation of the risks and benefits of antibiotics, with a mean Likert scale score of 5.54 agreeing that there are benefits to antibiotic prescription, and a mean Likert scale score of 6.04, agreeing that there are risks to antibiotic prescription. . However, the clinicians surveyed ultimately found antibiotics to be a necessary risk given the possible benefit of improving patient health. The hospitalists surveyed also did not view antibiotic prescription to be a product of pressure from patient families, agreeing by a mean Likert scale score of 5.08 that the patient’s family will trust their physician to prescribe antibiotics if needed. These findings suggest that physician education to reduce overprescribing of antibiotics should underscore possible antibiotic risk, despite potential benefit. Marshall J. Glesby, MD, Enzychem (Consultant)Gilead (Grant/Research Support)ReAlta Life Sciences (Consultant)Regeneron Sobi (Consultant)Springer UpToDate  Justin J. Choi, MD, Allergan Roche


The compressive, flexural, and tensile strengths were determined at 28 days and considered as the responses for the response surface methodology (RSM) analyses. The results revealed that the workability properties were increased with an increase in FA but decreased with CR replacement and the addition of NS. The pore-refining effect and pozzolanic reactivity of the FA and NS increased the strengths of the composite. Conversely, the strength is negatively affected by an increase in CR, however ductility and deformation capacity were significantly enhanced. Response surface models of the mechanical strengths were developed and validated using ANOVA and have high R2 values of 86–99%. The optimization result produced 36.38%, 4.08%, and 1.0% for the optimum FA, CR, and NS replacement levels at a desirability value of 60%.Producing high-strength self-compacting concrete (SCC) requires a low water-cement ratio (W/C). Hence, using a superplasticizer is necessary to attain the desired self-compacting properties at a fresh state. The use of low W/C results in very brittle concrete with a low deformation capacity. This research aims to investigate the influence of crumb rubber (CR), fly ash (FA), and nanosilica (NS) on SCC’s workability and mechanical properties. Using response surface methodology (RSM), 20 mixes were developed containing different levels and proportions of FA (10–40% replacement of cement), CR (5–15% replacement of fine aggregate), and NS (0–4% addition) as the input variables. The workability was assessed through the slump flow, T Self-consolidating concrete (SCC) is defined as concrete that flows freely under its weight and does not require compaction or vibration during casting ,2. SCC wOn the other hand, SCC is brittle and has a poor yield strength because of its low W/C and compact microstructure ,7. PreviWith the increase in population growth, the transportation industries increased the production of vehicles to meet increasing demands, which ultimately led to increased tire production ,14,15. TFibers and steel from tires are removed before ground to smaller sizes called CR. CR is proposed for use as a partial substitute to fine aggregate in concrete ,22, asphHowever, concrete’s mechanical and durability behaviors are significantly affected by incorporating CR. The strength of the concrete decreases with an increase in CR proportion in the mix ,26. SimiIn order to overcome the poor bonding problem, different CR surface pretreatment methods have been proposed, such as the use of NaOH ,30,31, pThe use of nanosilica (NS) to enhance the properties of rubberized cementitious composites in fresh and hardened states is now gaining ground. NS has the same favorable reaction as micro silica or silica fume, and it can improve the strength and durability of concrete, regardless of its size . ShahrulHence, despite the available literature on the use of materials such as FA, NS, SF, and CR in SCC, it is evident that there is no research yet on the combined influence of FA, NS, and CR together on the properties of SCC. Some of the current authors have partially covered some aspects of this topic , leaving2/kg, respectively, was used. Class F fly ash (FA) having a specific gravity of 2.38 and loss on ignition of 1.87% was used. The chemical composition of the OPC and FA is presented in 2 content, loss on ignition of 6%, specific surface area of 100 ± 25 m2/g, PH of 6.5–7.5, surface density of 0.2 g/mL, and an XRD pattern as shown in The materials used in this research include chipping stones and river sand as coarse and fine aggregates, respectively conforming to ASTM C33-18 requirements . The CR 3 and 0.35 were used in all the mixes. Experimental investigations on the mixes were carried out to determine the responses under consideration. The workability properties of the concrete were assessed through the slump flow (flow diameter and T500), L-box, and V-funnel tests. At the hardened state, the responses considered were the compressive, flexural, and tensile strengths. The details of the tests performed on the concrete at fresh and hardened states are explained in the next sections.The RSM input variables considered were the FA  replacement of cement by weight, CR  replacement of fine aggregate by volume, and NS  addition by weight of cement. Using the central composite design of the RSM, 20 experimental runs were generated with different combinations of the three levels of the input factors . The RSM-generated mixes and quantities of materials used are presented in Mixing was done following the requirements of BS 1881-125: 1986. After mixing the dry aggregates and CR for 2 min, the cementitious materials and half of the mixing water were added. After mixing for two more minutes, the remaining water containing the superplasticizer was added and mixed for an additional two minutes to ensure a consistent and homogenous mix.The workability of the mixes was assessed using the slump flow, L-box, and V-funnel tests following the specifications of EFNARC 2005.500 flow time. The maximum diameter of flow spread was also recorded in two directions at 90° as slump flow (dmax).Slump flow test: This was performed by filling a slump cone placed at the center of two concentric circles marked on a nonabsorbent platform. The slump cone was then removed, and the time taken for the mixture to reach a 500 mm spread circle was recorded as TL-box test: This is done to test the concrete’s ability to pass through obstacles without the constituents separating. The passing ability is calculated by dividing the concrete height at the end of the horizontal segment by the height of the remaining concrete in the vertical section. The blocking ratio must not be less than 0.8, and it is calculated using the formula :Height V-funnel test: This is used to test the viscosity and filling ability of the SCC mixture. The trap door at the bottom of the funnel is closed, and the fresh mix is filled into the funnel without tamping. Once the concrete mixture is level at the top of the funnel, the trap door is opened, and the time taken for the mixture to discharge is recorded as the flow time.Compressive strength: For each of the 20 mixes developed, three 100-mm cube samples were cast and tested at 7, 14, and 28 days of curing based on the requirements of BS 1881: Part 116:1983. The cubes were subjected to a gradually increasing axial load using the 300-kN universal testing machine until failure. The average of the three results was reported as the compressive strength of the mix at that particular curing day.3, based on the provisions of the Japan Society of Civil Engineers (JSCE). Using a universal testing machine (UTM), a direct tensile load was applied through the axis of the sample at a rate of 0.15 mm/ minute until failure. The average of three results was reported as the tensile strength of the mix at 28 days accordingly.Direct tensile strength test: The tensile strength of the concrete mixes was determined using a dog-bone specimen having a dimension of 420 × 120 × 30 mm3 beam samples at 28 days of curing, the flexural strength of the mixes was determined using the center point testing method based on the ASTM C78/C78M requirements at a loading rate of 5 mm/ min. The average of three results was reported as the flexural strength of the mix at 28 days accordingly.Flexural strength: Using three 500 × 100 × 25 mm500 for all the mixes ranging between 4 and 21 s. Hence, for having a T500 of more than 2 s, all the mixes fall within the V2 viscosity class based on the EFNARC classification [500 results show that the FA significantly reduced the viscosity of the mix, making it spread to 500 mm at a lower time. FA10CR0NS0 has the lowest T500 of all the mixes, at 4 s, and comprises FA solely without CR or SF. It is followed by FA40CR0NS0, having a T500 of 5 s. It is reported that FA increases the workability of cement composites through the “ball bearing” effect due to the nature of its smooth spherical particles [500 was observed. FA25CR0NS2 and FA10CR0NS04 have a 33.33 and 16.67% increase in the T500 compared to FA10CR0NS0 and FA40CR0NS0, respectively. The inclusion of NS increases the viscosity of the mixtures, resulting in a higher T500 due to the tiny size and large surface area of its particles, which increases the water demand, as described by Guneyisi et al. [500 drastically increased with an increase in the CR replacement, indicating a reduction in the viscosity of the concrete. Mixes having the highest CR of 15% exhibited the highest T500, as can be observed from FA10CR15NS0, FA40CR15NS0, FA10CR15NS0, FA25CR15NS2, and FA10CR15NS4. It is attributed to the CR particles’ rough surface texture, leading to internal friction that significantly reduces the fresh concrete flow rate, as reported by Wanasinghe et al. [fication . The T50articles . Howeveri et al. . The T50The slump flow is presented in The L-box result shown in On the other hand, the influence of FA on compressive strength can be seen in mixes with only FA (no CR and NS), such as FA10CR0NS0 and FA40CR0NS0, which have compressive strengths of 58.82 Mpa and 53.66 Mpa, respectively. FA particles being smaller than cement have a filling effect resulting in the densification and increased compact microstructure of the concrete, increasing the strength. Furthermore, the pozzolanic effect of FA increases the compressive strength, especially at lower dosage due to the secondary hydration reaction, as confirmed by Posi et al. . The dro2, to produce calcium-silica-hydrate (C-S-H) gel [2/AlO3 ratio of high volume fly ash concretes, leading to early strength gain. This may be the reason behind FA40CR0NS4 having the highest strength at 28 days despite having a 40% FA replacement. In the same vein, despite the CR replacement levels, all mixes having 2–4% NS content have strengths of more than 17.23 MPa minimum compressive strength for structural concrete specified by ACI 318. This is attributable to the ITZ densification effect of the NS. Mohammed et al. [The addition of NS in the mix significantly increased the compressive strength, especially for mixes with no or low CR amounts. Mixes having the highest NS content of 4% (FA40CR0NS4 and FA10CR0NS4) exhibited the highest compressive strengths of 59.67 and 59.1 MPa, respectively. NS is reported to enhance the compressive strength of cement composites due to its high reactivity with cement hydration products, including Ca(OH)S-H) gel . SimilarS-H) gel . In addiS-H) gel  and MohaS-H) gel  stated td et al.  reportedThe failure mechanisms of samples from FA40CR0NS4 and FA40CR15NS4 mixes are shown in The flexural strength values of the RSCC mixes are shown in The addition of NS has played a vital role in enhancing the flexural strength of the concrete. An increase of 221% was recorded between FA40CR15NS0 (1.4 MPa) and FA40CR15NS4 (4.5 MPa) as the NS content increased from 0 to 4%. Similarly, an increase of 17.8% between FA10CR15N0 (4.5 MPa) and FA10CR15NS4 (5.3 MPa) was observed. These enhancements in strength with the addition of NS are consistent with prior research findings. As supported by Mohamed , Yu et aAs presented in the stress deflection curves in 2 that weakens the ITZ and affects the strength. In addition, it is worth mentioning that the high amount of FA in the mix is likely to lower the strength due to the reduction in the cement content, as explained by Abdulkadir et al. [With the addition of NS in the mix, there are noticeable improvements in the strength. Almohammad-albakkar and Behfarnia  reportedr et al. .The FESEM images of some selected mixes are presented in The goal of employing the RSM is to develop response surface models and analyze the developed models using analysis of variance (ANOVA). The mechanical strengths of the developed rubberized self-compacting concrete (RSCC) mixes were considered for RSM modeling and optimization. In this case, the quadratic models were deemed more suitable for all three responses  and are presented in coded terms in Equations (1)–(3). The Equations in terms of coded factors may be used to predict response for different amounts of each variable. The high levels of the factors are represented as +1 by default, whereas the low levels are −1. By comparing the factor coefficients, the coded Equation may be used to determine the relative importance of the variables. A, B, and C represent the input factors . 2, and C2 are statistically significant for the compressive strength model. Similarly, B, AB, and BC are the significant model terms for the flexural strength model. The significant model terms for the tensile strength model are B, AB, AC, and A2.The ANOVA was performed at a 95% level of significance, and any model or model term having a probability of less than 5% is considered significant. In this regard, all the developed models are significant for having a probability of less than 0.05. Considering the individual model terms, C, BC, B2). The R2 assesses the model’s fit to the empirical data, ranging from 0 to 1 or a percentage (0 to 100%). Higher values indicate better fit and vice versa. The R2 and the other model validation parameters are presented in 2 of 99%, 87%, and 96% for compressive, flexural, and tensile strength models, respectively. Furthermore, the signal-to-noise ratio is measured by “Adeq. Precision.” A ratio larger than four is preferred. As can be observed from One of the essential measures of the quality of a model is the coefficient of determination  is used to evaluate the optimization. The greater the value’s proximity to one, the better the outcome [An optimization attempt is conducted to find appropriate levels of the independent variables to achieve an optimum level of the response of interest. This is accomplished by establishing goals for the variables (input factors and response) with varying criteria and levels of importance in order to achieve the objective function. The desirability value (0 ≤  outcome .The optimization goals and criteria set in this case are presented in Finally, experimental validation was performed by producing RSCC samples using the optimum input variables recommended by the optimization to determine the CS, FS, and TS values at 28 days. 500, slump flow, L-box, and V-funnel tests increased with an increase in the FA replacement due to its smooth spherical particles, while the opposite effect was observed with CR replacement and NS addition. Due to the rough surface texture and low density of the rubber particles, CR caused the most significant loss in all the workability parameters. The reduction in the workability with the NS addition is ascribed to the large surface area of the particles, which absorbed much of the mixing water, reducing the mix’s fluidity.In the fresh state, the RSCC workability properties measured through TIncreases in NS and modest levels of FA boosted the concrete’s compressive, flexural, and tensile strengths, which was ascribed to the physicochemical effects of the NS and FA, resulting in a dense and compact microstructure. On the other hand, increases in the CR resulted in a considerable reduction in the concrete’s mechanical strengths, which was attributed to the CR’s low stiffness and poor bonding at the CR-cement interface. However, at all CR replacement levels, all mixes containing NS attained the compressive strength beyond the minimum specified by ACI318 for structural concrete due to its enhancement of the bonding between the CR and hardened cement paste at the ITZ. In addition, the brittleness of the concrete is reduced owing to the CR.A closer look at the interaction of the FA, NS, and CR through FESEM revealed a formation of more S-C-H gel and densification of the concrete microstructure due to the FA and NS. In addition, the densification of the ITZ between the CR and cement paste by the NS was observed. Similarly, the images revealed the propagation of microcracks around the CR due to the stress concentration.2 values of 99%, 87%, and 96% for CS, FS, and TS, respectively. An optimization produced 36.38%, 4.08%, and 1.0% for the optimum FA, CR, and NS replacement levels at a desirability value of 60%. Experimental validation demonstrated a strong correlation between predicted and experimental results, with a percentage error of less than 5% for all three responses analyzed.Response surface models for predicting the mechanical strengths were developed and validated using ANOVA. The models have RIt is evident from the results that a rubberized self-compacting concrete with FA and NS can be produced to have good workability properties in the fresh state and appreciable mechanical strengths at the hardened state.This research was performed to determine the effect of CR and a ternary blend of cement, FA, and NS on the fresh and mechanical properties of SCC. The following conclusions were drawn at the end of the investigations: