Antibiotics constitute one of the emerging categories of persistent organic pollutants, characterised by their expansion of resistant pathogens. Antibiotic pollutants create a major public health challenge, with already identifiable detrimental effects on human and animal health. A fundamental aspect of controlling and preventing the spread of pollutants is the continuous screening and monitoring of environmental samples. Molecular imprinting is a state-of-the-art technique for designing robust biomimetic receptors called molecularly imprinted polymers (MIPs), which mimic natural biomolecules in target-selective recognition. When integrated with an appropriate sensor transducer, MIP demonstrates a potential for the needed environmental monitoring, thus justifying the observed rise in interest in this field of research. This review examines scientific interventions within the last decade on the determination of antibiotic water pollutants using MIP receptors interfaced with label-free sensing platforms, with an expanded focus on optical, piezoelectric, and electrochemical systems. Following these, the review evaluates the analytical performance of outstanding MIP-based sensors for environmentally significant antibiotics, while highlighting the importance of computational chemistry in functional monomer selection and the strategies for signal amplification and performance improvement. Lastly, the review points out the future trends in antibiotic MIP research, as it transits from a proof of concept to the much demanded commercially available entity. The study also found that the antibiotic environmental concentrations could be above the threshold predicted for driving the development of antibiotic resistant bacteria 3−/[Fe(CN)6]4− is common, but positively charged ones, such as [Ru(NH3)6]3+/[Ru(NH3)6]2+, are also available, depending on the charge expected to accumulate on the MIP-based sensor  redox marker on the electrode  or AFFINISEP, they are only suitable for applications involving separation (including antibiotics separation) by solid-phase extraction, whereas MIP-based sensors ideal for onsite monitoring of environmental contaminants, e.g., antibiotics or medical diagnostics, are difficult to find. Typically, commercialising a lab-based technology is not a straightforward process, but this constitutes a significant hurdle to be crossed if MIP-based sensors are to be translated to the market. To facilitate progress towards the achievement of this aim, there is an increasing number of patents and patent applications on MIP-based sensors for antibiotics analysis. A quick search on the Espacenet database returns 13 such patents within the last 5 years. However, despite concerted efforts and the accompanying success witnessed in surpassing fabrication technicalities arising from the need for portability, usability and cost of MIP-based sensors, the challenges encountered in its design and applications must be overcome to adequately compete with commercially available sensors and diagnostic devices.One of the main drawbacks to the commercial implementation of antibiotic MIP, as well as other MIPs, is the incomplete elution of the template during MIP preparation, thereby causing template leakage during MIP usage. Generally, it is perhaps difficult to ensure a 100% template extraction from the polymer. Thus, during MIP-based sensor utilisation, the entrapped template is being released continuously from the MIP and interacts with target sensing, affecting assay accuracy, especially for the trace analysis of small molecules, such as antibiotics. In addition, low selectivity may arise due to an incomplete template removal that further prevents efficient analyte detection in complex environmental samples. This effect could be more pronounced for MIPs designed by covalent imprinting, where the covalent bond may lead to a slower template removal. Therefore, possible maximum template removal is an obligatory step in MIP preparation. However, it was found that not many reports focus on optimising this parameter during MIP preparation. To overcome this challenge, the use of dummy templates bearing close resemblance in size and shape to the targets is a common overriding strategy . In addiOn the other hand, the performance of MIP prepared on the basis of noncovalent imprinting may also be affected when used in aqueous samples, where water affects H-bonds between the template and functional monomer, thereby disrupting the binding equilibrium and limiting the practical application of the MIP-based antibiotic sensor. To circumvent such limitations, the use of organic solvents during MIP synthesis prior to rebinding in an aqueous environment is conventional. However, such an approach may also result in some compromise in the performance of the MIP-based sensor, since it was found that the use of the same solvent during synthesis and rebinding is critical for optimal performance . Other sMoreover, for a reliable characterisation of the performance of an MIP-based chemosensor, a homogeneous distribution of the binding sites within the polymer that is uniformly immobilised on the transducer is required. However, MIPs have a certain degree of heterogeneity in the binding sites, arising from the preparation protocol. The polymer matrix, by nature, can adsorb the target molecules through weak interactions. This allows for additional contribution from non-specific binding to the obtained signal, hence the variation in the binding constants . While tLastly, another conceivable obstacle could be the challenge of using these materials in the media where the target antibiotics are naturally found, without the need for a laborious sample preparation step. This is essential in the consideration of the possible incompatibility and/or cross-reactivity of the matrix components. Therefore, vigorous and continual efforts are still needed in MIP research to achieve the aim of commercialised MIP-based sensors in the shortest space of time.The increasing threats of antimicrobial resistance has accentuated the call for robust sensing systems that combine both sensitive and selective properties, as well as portability. Certainly, MIP presents a convincing alternative to natural biomolecules as receptor layers for sensors. Their capacity to facilitate the fabrication of recognition elements for analytes with no natural receptors makes them appealing for designing monitoring devices for multidisciplinary applications. This explains the increase in research attention and scientific reports in the development of MIP-based sensors as environmental monitoring tools for antibiotic pollutants. However, despite the copious potential benefits of fabricating antibiotic MIP-based sensors, their commercial implementation has suffered significant setbacks mostly related to template leakage, due to incomplete template removal, complications in fabricating robust and homogeneous MIPs on electrodes, as well as the challenges of mass production and real sample analysis without laborious sample pretreatments. This review evaluates the significant efforts towards the development of commercially viable antibiotic MIP sensors.To ensure preparation simplicity, performance accuracy and ease of usage, several studies have focused on sensing platforms, including optical , piezoelectric (QCM and SAW) and electrochemical transducers that support label-free molecular detection and that can be miniaturised. Among these, electrochemical sensors were revealed as the dominant platform on which antibiotic MIPs are frequently integrated, suggesting their low production cost, ease of operation, portability, as well as their potential for realising commercialised POCT devices. The sensors examined here largely demonstrated sensitive and selective capacities to detect antibiotic pollutants in real samples at the relevant concentration levels, thanks to the valuable computational approach that assists in efficient functional monomer selection and the various signal amplification methods that enhance sensitivity.Following technological advancement, publications describing computational studies of molecular imprinting systems for pre-polymerisation have increased significantly. The computational tool has enhanced experimental optimisation, allowing appropriate selection of the type and molar amount of functional monomer and crosslinker for a specific template. However, not much detailed attention has been given to possible template–template interactions and their significance to a successful imprinting process and subsequent target recognition . This isThe performance of MIP-based sensors described in this review was compared with those of conventional chromatography techniques for antibiotic analysis in water samples. The result demonstrated that although the reported LOD values of MIP-sensors range from 103 to 105 nM, the lowest values are still comparable with the LOD values reported for the HPLC technique (0.031–0.047 nM) . MoreoveMoreover, to overcome some of the challenges of antibiotic MIP-based sensor commercialisation, certain compelling solutions were identified. Firstly, the implementation of nanoMIPs being developed by MIP Diagnostics Ltd. represents a viable solution, provided a robust integration with the sensor transducers is achievable. In addition, the adoption of disposable multiplexing transducers, such as SPEs, in combination with mobile controllable miniaturised electrochemical devices, would further accelerate efforts toward the actualisation of portable antibiotic monitoring devices.Thus, the fabrication of MIP-based label free sensors for antibiotic monitoring channels a novel path in the development of portable devices for environmental screening. Such sensors have demonstrated compelling performances in terms of sensitivity and selectivity as revealed by this review; hence, the adaptation of the outstanding strategies identified herein could help in achieving scalable antibiotic MIP-based monitoring devices.


After four cycles of neoadjuvant chemotherapy (FOLFIRINOX),she underwent a total pancreatectomy, lymphadenectomy, total mesopancreas excisionA 40-year-old woman presented with ductal adenocarcinoma in the body of the pancreas,involving the celiac trunk (CT) completely (encasement), superior mesenteric artery(SMA) (>180,,Pancreatoduodenectomy after neoadjuvant chemotherapy is the current treatment inpatients with borderline pancreatic ductal adenocarcinoma in the head of thepancreasHackert et al


Biodegradable materials are appropriate for the environment and are gaining immense attention worldwide. The mechanical properties  of some natural fibers  are comparable with those of some synthetic fibers . However, the toughness of coconut fibers is comparatively more than other natural fibers. Numerous studies suggest coconut fibers perform better to improve the concrete mechanical properties. However, the knowledge is dispersed, making it difficult for anyone to evaluate the compatibility of coconut fibers in concrete. This study aims to perform a scientometric review of coconut fiber applications in cementitious concrete to discover the various aspects of the literature. The typical conventional review studies are somehow limited in terms of their capacity for linking different literature elements entirely and precisely. Science mapping, co-occurrence, and co-citation are among a few primary challenging points in research at advanced levels. The highly innovative authors/researchers famous for citations, the sources having the highest number of articles, domains that are actively involved, and co-occurrences of keywords in the research on coconut-fiber-reinforced cementitious concrete are explored during the analysis. The bibliometric database with 235 published research studies, which are taken from the Scopus dataset, are analyzed using the VOSviewer application. This research will assist researchers in the development of joint ventures in addition to sharing novel approaches and ideas with the help of a statistical and graphical description of researchers and countries/regions that are contributing. In addition, the applicability of coconut fiber in concrete is explored for mechanical properties considering the literature, and this will benefit new researchers for its use in concrete. Moreover, the availability of natural fibers is worldwide, which cost very little compared to artificial fibers [Typical cementitious concrete is usually excellent under compressive loading but weak under the application of tensile forces. However, steel reinforcement is incorporated if the concrete structure is intended to bear tensile forces. The steel reinforcement overcomes the said deficiency in concrete, and the respective concrete is known as reinforced cementitious concrete. The typical brittle nature of cementitious concrete can be altered by having effective modifications in it ,2. Therel fibers . In the l fibers ,27. Flaxl fibers ,29,30,313 [Among all natural fibers, coconut fiber is a famous one that is extracted from the coconut fruits husks  and is u3  and 130–3 , respect3 ,42,44 an3 ,40,44, r3  studied 3  reportedHowever, due to the organic/biodegradable nature of coconut fibers, their durability is still a concern. Hence, efforts are made to enhance the durability of coir either by soaking it in hot water or some chemical solutions . AccordiThe increasing environmental problems have led to the development of research on environmentally friendly construction materials such as coconut-fiber-reinforced concrete. Several researchers studied coconut fiber in concrete instead of artificial/synthetic/steel fibers. However, the research knowledge on coconut-fiber-reinforced concrete is still scattered, and there is no easy way to assess the importance of coconut-fiber-reinforced concrete. The difficulties in creative investigation and scholarly collaboration are aroused due to the information limitations of researchers. For this purpose, establishing and employing a technique for scientists/researchers to acquire the necessary information from reliable sources is essential. To the best of the author’s knowledge, no scientometric review has yet been conducted on the literature regarding the utilization of coconut fibers in concrete. Hence, employment of a scientometric method with the help of a software tool can assist in overcoming this gap. The fundamental purpose of this research is to provide an in-depth literature review on incorporating coconut fibers in cementitious composites, focusing on its mechanical properties, applications, and current state in the construction industry. The research gaps and challenges in applying coconut-fiber-reinforced concrete are also elaborated in the present work. The scientometric analysis of published research in coconut-fiber-reinforced concrete up to 2022 is aimed in the current study. The bulk research database may be assessed quantitatively by undertaking scientometric analysis with the help of a suitable software tool. The conventional review-based research is weak to some extent in its capacity for connecting numerous segments of the literature wholly and precisely. Co-citation, science mapping, and co-occurrence are a few main investigation parameters in the modern era ,52,53. TThe scientometric analysis is performed in the current study for the research database to determine the various features of bibliographic data ,55,56. MIn the academic field, the bibliometric data are analyzed by developing scientific mapping that is generally applied for analyzing scientometric investigations . Using aA Scopus analyzer is employed for the analysis to extract the most relevant research areas. The sources of publication are determined from the collected bibliographic data using VOSviewer. “Unit of analysis” is taken as “sources”, whereas “kind of analysis” is opted as “bibliographic coupling” during the analysis. The vital focus of a research domain is elaborated and defined by the keywords . For theThe number of citations depicts the influence of that particular researcher in a specific research area . Hence, A specific research area is usually influenced by the quantum of citations for an article. The articles with more citations are recognized as pioneers in that particular research area. To assess articles, “kind of analysis” is set as “bibliographic coupling”, whereas “unit of analysis” is adopted as “documents”. An article with at least 30 citations is set as a limit. In the coconut-fiber-reinforced concrete research field, the leading ten articles concerning citations are listed in The involvement of numerous regions/countries is higher toward coconut fiber in concrete research, and there is still potential for increasing this contribution. The network map is established to aid scientists in accessing coconut-fiber-reinforced concrete research areas. Here, “kind of analysis” is set as “Bibliographic coupling”, and “unit of analysis” is designated as “countries”. The least number of articles per country is set at two, and 2 emissions [2 emissions [In this work, the statistical and mapping overview of diverse aspects of the available literature on coconut-fiber-reinforced concrete is presented. The manually conducted conventional review research has limited comprehensiveness and a less accurate inter-relation between different segments of the literature. Further, in this study, the assessment of journals having the most published articles, the most widely used keywords in published articles, the main contributing countries, and articles and authors having the most citations in the coconut-fiber-reinforced concrete research field is carried out. The keywords analysis reveals that coconut-fiber-reinforced concrete has primarily been discovered for its mechanical properties ,73,75,76missions . Accordimissions ,34,75,79It is well known that concrete is basically a majorly utilized material in the construction industry worldwide. However, in natural/conventional form, concrete lacks in strain capacity and resistance against tensile loading and cracking, and behaves more brittle ,80,81,82The analysis of publication sources on coconut-fiber-reinforced concrete reveals that the leading three journals are “Construction and Building Materials”, “IOP Conference Series: Materials Science and Engineering”, and “Materials Today: Proceedings”, comprising 21, 9, and 8 articles, respectively. Moreover, the three leading journals regarding citations are “Construction and Building Materials”, “Materials”, and “Materials Today: proceedings”, having 876, 122, and 56 citations, respectively.The keywords analysis in the under-studied field of research shows that fibers, concretes, compressive strength, reinforced concrete, tensile strength, and coconut fibers are the six most widely appearing keywords. This analysis further reveals that fiber-reinforced concrete having coconut fibers is majorly explored for the construction industry.Based on the publications and citations, the leading authors are classified. Chouw N. and Ali M. are the two leading ones with 18 and 17 articles, respectively. Having 600 citations, Ali M. leads the field, followed by 569 citations from Chouw N. and 216 citations from Khan M. by 2022.The analysis of coconut-fiber-reinforced concrete-related articles shows that Ali et al.  have theThe analysis for exploring the leading contributing countries is also conducted for the field of coconut-fiber-reinforced concrete research. India, Malaysia, and New Zealand have contributed 41, 28, and 20 articles, respectively. Moreover, the countries of New Zealand, Malaysia, and Pakistan have received citations of 603, 473, and 367 citations, respectively.2 emissions and saving natural sources.Sustainable development can be attained by using coconut-fiber-reinforced concrete in the construction industry by declining COThe applicability of coconut-fiber-reinforced concrete on a broader scale is still quite limited. Its structural applications are still under exploration due to limited knowledge of its long-term durability. Additional analysis on its long-term durability is also vital for widening the applications of coconut-fiber-reinforced concrete toward structural members.This research aims to conduct a scientometric analysis of the available literature in the coconut-fiber-reinforced concrete field for evaluating different measures. The 235 articles are assessed via the Scopus database, and the VOSviewer program is employed to determine the results. The conclusions made are as follows:


Neoadjuvant therapy improves overall survival compared with a surgery-first approach in patients with borderline resectable pancreatic cancer (BRPC). Evidence of higher quality is required to determine whether neoadjuvant therapy has potential benefits and improves survival for patients with resectable pancreatic cancer (RPC). Most randomized controlled trials (RCTs) have explored short-course neoadjuvant chemotherapy (SNT), but total neoadjuvant chemotherapy (TNT) is now the experimental arm of ongoing RCTs. This article reviews the current status of SNT and TNT in RPC and BRPC, and provides perspectives of future challenges and research directions in this field. Pancreatic ductal adenocarcinoma is a lethal malignancy, and surgical resection remains the only potential for cure. Data from population-based registries show resection rates of 13–21.7% . For BRPNeoadjuvant chemotherapy is sometimes used for RPC, especially in patients with high-risk features, i.e., radiographic findings are suspicious but not diagnostic for metastatic disease, potentially reversible performance status or comorbidity profile that is not currently appropriate for major surgery, or a carbohydrate antigen 19-9 (CA19-9) level suggestive of metastatic disease . For patp = 0.025) (p = 0.015) , found that neoadjuvant therapy improves survival compared with upfront surgery in patients with BRPC . However= 0.015) . Both gr= 0.015) . Of note= 0.015) .Ongoing or completed RCTs in RPC and BRPC include different perioperative chemotherapy regimens, and the duration of neoadjuvant and adjuvant chemotherapy differs between studies . Most trThe added value of radiotherapy following neoadjuvant chemotherapy in patients with RPC and BRPC is unclear. Radiotherapy, in the treatment of RPC and BRPC, is more common in the United States . Only PRFor BRPC, neoadjuvant therapy has been established as routine practice in many centers and countries , 27. In p < 0.01). The study suggests that patients who can tolerate SNT would likely benefit from TNT. The rate of completion of all intended neoadjuvant therapy and surgery was not statistically different between the two groups . Thus, TNT did not seem to risk the loss of a window of operability, which is an important finding when TNT is extended to patients with RPC. Thus, most RCTs in RPC administer SNT for 2–3 months; PREOPANC-2/3 and ALLIANCE-021806 have prolonged the duration of neoadjuvant therapy and administered neoadjuvant mFOLFIRINOX for 4 months in the experimental arm , also termed the surgery-last approach for RPC and BRPC , 30–32. ntal arm , 18, 19.ntal arm , 33. Thintal arm , 35. Patntal arm .Patients undergoing neoadjuvant chemotherapy may benefit from a chemotherapeutic switch before resection if the response evaluation shows tumor progression , 36. Thep < 0.01)] ] . A progn< 0.01)] .During neoadjuvant therapy, the patients are evaluated for treatment toxicities and objective clinical, radiologic, biochemical, or metabolic responses, typically every 2 months , 36. If p = 0.001), whereas no differences were observed in the median change in tumor volume, the rate of local tumor downstaging, or the CA19-9 levels. In recent studies on TNT, a radiographic downstaging of 28% has been found, maybe due to the use of modern chemotherapy regimens , circulating tumor DNA (ctDNA), cell-free RNA (cfRNA), and exosomes are explored, with the potential to be applied to the clinical setting . SeveralMore patients with pancreatic cancer might benefit to undergo tumor molecular profiling or receive targeted therapies . Some noMost RCTs in RPC and BRPC have explored SNT, but TNT is now evaluated in several ongoing trials. The chemotherapeutic switch could be incorporated into neoadjuvant treatment sequencing in future trials. Components of an objective response include clinical, biochemical (CA19-9 decrease), radiologic (decreased tumor size/less vascular involvement), or metabolic responses . In the future, biomarker hypothesis-driven clinical trials and better-circulating biomarkers  and imaging techniques  to evaluate treatment responses are needed to guide personalized therapy and improve outcomes for patients with pancreatic cancer.KJL contributed to conception and design of the review, wrote the first draft of the manuscript and revised, read, and approved the submitted version.This work was supported by the South-Eastern Norway Regional Health Authority (grant number 2019029).The author declares 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.


The expansion of cracks in 3D printing concrete materials may lead to structural failure, so it is essential to monitor crack propagation development. Coda wave interferometry (CWI) has been proven to be sensitive to microcracks, however, the evolution pattern of ultrasonic coda waves during crack growth is still not clear. This paper reports a numerical study of the sensitivity and feasibility of CWI for monitoring microcrack growth in heterogeneous materials. A two-phase concrete model, which contains microcracks with different angles and lengths, was developed using the finite element analysis software ABAQUS. The relative velocity change  Three-dimensional printing is a rapid prototyping technology that uses three-dimensional digital models and mechanical equipment to form materials in piles ,2,3. ThrCoda wave interferometry (CWI) is a new method for micro damage identification in civil engineering. Ultrasound propagation in a multiple scattering medium is subject to strong scattering, resulting in the rapid attenuation of ultrasound energy in the medium . ConcretCoda waves analysis techniques have been actively studied and reported in recent decades due to the high sensitivity of coda waves in detecting early and small damages. R. Snieder  was the The coda waves observed in the laboratory tests are often affected by multiple factors, thus the parametric study of factors that may affect the change of coda waves during the crack propagation process is of significant meaning to understand. For this issue, using the numerical simulation method is a good research idea. Numerical simulations have been extensively studied in the simulation of ultrasonics ,17,18. NBefore studying the propagation process of ultrasonic waves in concrete, it is necessary to understand the properties of the concrete medium. Concrete is a heterogeneous multiphase composite condensate composed of hardened cement paste, sand, gravel, and other aggregates. In simple terms, concrete can be considered as a two-phase composite composed of cement mortar matrix and aggregate fillers. Ultrasound propagation in concrete is bound to be affected by heterogeneous scatterers such as aggregates. Therefore, it is crucial to establish a concrete model to simulate the wave propagation process more practically. This paper aims to deepen the understanding of the scattering wave propagation rule during damage development in heterogeneous media using numerical simulations.In this paper, a two-dimensional heterogeneous concrete model with damage, which is set to be cracks with different angles and lengths, was developed, and the evolution of the coda wave during crack propagation was observed. The relationship between the relative velocity change and decorrelation coefficient during the expansion of microcracks and the crack expansion was quantified. In addition, the effect of crack angles was analyzed. The arrangement of this paper is as follows: In CWI is a technique that detects small changes in a medium by using multiple scattering waves, allowing the determination of the relative velocity change of a diffuse wavefield measured from a fixed source and a fixed receiver at two different moments . UltrasoAccording to the path summation theory of CWI, the waveform in the reference wavefield le paths , the refCWI can be used to assess the correlation and relative velocity change of two signals. The stretching method is a powerful tool for estimating the difference between signals, which calculates the correlation ε that makes the maximum value of d single  or multid single .X defines the set of n randomly distributed perturbation locations within the inner kernel volume The total scattering coefficient g0  can be uo et al.  used difmaterial ,34 leadij are finite element position indices, The simulation of scattering waves is a stress wave propagation problem that should be dealt with using a dynamic solver. In this paper, the scattering waves are simulated using the ABAQUS/Explicit solver . Stress In this paper, concrete was simulated by considering it as a two-phase heterogeneous medium composed of coarse aggregate and cement mortar. The heterogeneity in the concrete causes a strong scattering of ultrasonic waves in the wavelength range of the aggregates. To make the scattering waves in concrete more realistic, concrete aggregates were materialized by multiple randomly distributed circular areas with different material properties, and local damage was achieved by inclusions with high aspect ratios. The technical route adopted in this paper is shown in the flowchart in  to void . The modf is the center frequency, n indicates the signal duration period, the larger the value of n, the narrower the frequency band, which is conducive to reducing the dispersion effect. The signal emission source was placed at  to simulate the ultrasonic waves emitted by the piezoelectric transducer. The acceleration within 0–4 ms at  was extracted as the receiving scattered signal. The ultrasound source and mesh division are shown in In the numerical simulation of elastic waves, especially in the field of seismic exploration, the source signal is mainly simulated using a Reckonic or Gaussian function and its first-order derivative; while in the numerical simulation of high-frequency ultrasonic waves, the excitation source signal often uses a convex cosine function to resemble more closely the impulse signal from the ultrasonic transducer, as in Equation (7) :(7)ft;n=5 steps [Finite element simulation of the stress wave propagation process was performed using an explicit solver. The explicit method achieves satisfactory accuracy provided that the time increments are small enough, and it is very effective in solving for a large number of time increments, which are typically upwards of 105 steps . The exp−8 s. The number of finite elements per wavelength is an essential factor while modeling wave propagation with the finite element method. According to Drozdz’s study , each waIn total, 77 configurations with different crack angles and lengths were numerically investigated. The variation of lengths indicates the process of crack expansion. The exemplary waveforms of The stretching method was applied to all 77 signals, and the selection of the time window in the calculation process of this method is crucial. The longer the time window, the higher the cost of CWI calculation, the relative velocity change tends to stabilize when the window centroid is sufficiently late, improving the robustness of CWI ,47,48. AThe propagation path of the incident wave into the interior of the medium is affected by the scatterer, resulting in a change in propagation direction and redistribution of energy. The change in the scatterer cross-section causes a complex path transition inside, resulting in a change in the According to Equations (11) and (12), the values of n et al.  in theirIn this paper, a two-dimensional heterogeneous medium has been modeled by the finite element method, and the quantitative assessment of material damage by the CWI technique is investigated. The variation of This paper reveals the change rule of


Correction: Stem Cell Research & Therapy (2017) 8:17https://doi.org/10.1186/s13287-017-0476-7When sorting out the original data, the authors noted the representative masson images for MI + MET/CDC and MI + MET + MET/CDC groups in Fig.


Extraocular muscle is usually affected by thyroid disease or inflammatory pseudotumor, but seldom by neoplastic process. Primary malignant lymphoma involving isolated extraocular muscle is very rare, especially after 6 years of chronic myositis.A middle-aged female presented with swelling of the lower lid of the right eye for 2 months. Magnetic resonance imaging showed significant enlargement of the right inferior rectus muscle belly. The patient first presented 6 years prior with upper eyelid swelling. A total of 5 surgical biopsies of the right eye were performed during 6 years with the following successive findings: inflammatory pseudotumor, chronic inflammation, inflammatory lesions, IgG4-related ophthalmic disease, and lastly, extraocular muscle extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma).MALT lymphoma may have occurred as a result of chronic extraocular myositis. Malignancy should be considered in patients with recurrent painless extraocular muscle hypertrophy. Differential diagnosis can rule out thyroid-associated ophthalmopathy (TAO), whose symptoms are similar. Diagnosis confirmation by biopsy is warranted if necessary. Isolated extraocular muscle enlargement is typically associated with thyroid disease and idiopathic orbital inflammation, but seldom with neoplastic process. These etiologies may share similar clinical and radiological features, making the correct diagnosis challenging. Primary malignant lymphoma involving isolated extraocular muscle is extremely rare. Here, we describe the clinical, radiological, and pathological features of a biopsy-confirmed mucosa-associated lymphoid tissue (MALT) lymphoma of the inferior rectus muscle after 6 years of myositis. We include an analysis of a possible association between the lymphoma and IgG4-related inflammation.A 55-year-old female presented with swelling of the lower lid of the right eye for 2 months without redness, ocular pain, or decreased visual acuity. This patient had a long and complicated course for 6 years, as shown in Table Incisional biopsy under general anesthesia was performed. The enlarged right inferior rectus muscle appeared friable with a greyish cut surface. A biopsy was taken from the muscle belly and the hematoxylin-eosin staining of the lesion showed diffuse and dense infiltration by small lymphoid cells with slight nuclear atypia Fig. . In someAfter the operation, the patient was treated with oral methylprednisolone with an initial dosage of 24 mg per day for 1 week and a taper over 6 weeks. Besides, it was recommended that the patient take radiation therapy in a general hospital. The patient was followed up after 4 months and reported she did not take radiotherapy and had a recurrence of proptosis of the right eye 2 months after the operation. Additionally, the patient had elevated IgG4 levels (124.6 mg/L) in another hospital 1 month after the MALT lymphoma diagnosis. A whole-body PET/CT scan post 18F-FDG administration was conducted and revealed a hypermetabolic retro-orbital mass in the right orbit, considered to be residual tumor after resection, and slightly increased uptake in bilateral submandibular lymph nodes, considered to be inflammation. No abnormally hypermetabolic lymph nodes were seen systemically.Malignant lymphoma is the most common malignancy in the ocular adnexa, and MALT lymphoma has the highest incidence . The orbHere, we describe a case of primary MALT lymphoma involving the inferior rectus muscle after 6 years of chronic myositis. During that time, the patient underwent 5 incisions in the right eye with the following successive histopathological findings: inflammatory pseudotumor, chronic inflammation, inflammatory lesion, IgG4-related ophthalmic disease, and MALT lymphoma. A progressive increase in the inflammation was noticeable: lymphocytic proliferation evolved from focal to diffuse infiltration, plasma cells increased from scattered to massive infiltration in certain areas, and lymphoid follicle formation occurred throughout the course of the disease. Mesenchymal hyperplasia also gradually intensified, evolving from a small amount of collagenous tissue to mesenchymal fibrosis. The findings at the patient’s first and fourth visits indicate to us that she met the 2014 diagnostic criteria for probable IgG4-related ophthalmic disease .IgG4-related disease (IgG4-RD) is an immune-mediated disease characterized by infiltration of IgG4-immunopositive plasmacytes accompanied by mass-forming lesions in one or more organs. At the first visit of the patient in our case report, serum IgG4 was mildly elevated 132.0 mg/dl) and immunohistological findings showed the ratio of IgG4+/IgG+ plasma cells as 40%, with more than 50 IgG4+ plasma cells/HPF. At the fourth visit, the patient refused to take serum IgG4 examination due to the high price. Immunohistological findings showed the ratio of IgG4+/IgG+ plasma cells as 30%, with more than 50 IgG4+ plasma cells/HPF. Both visits met the diagnostic criteria for probable IgG4-related ophthalmic disease 2.0 mg/dl. Cheuk eAt the time of diagnosis of lymphoma, the immunohistological finding of the patient in our report was IgG4-negative, but serum IgG4 was elevated. We believe there are two reasons to explain this phenomenon. First, the patient received glucocorticoid therapy after surgery 1 year prior. The subsequent IgG4-negative result might be an indication of effective treatment. However, a transition from positive to negative IgG4+ cells in orbital tissue within 1 year did not mean that the overall disease had subsided. IgG4-related disease is an immune-mediated disease that can cause fibroinflammatory lesions in nearly any organ. Therefore, high serum IgG4 level might be due to disease in other organs. Second, it is often difficult to evaluate IgG4-positive versus IgG-positive cells due to the background staining, especially in very small samples. According to the 2020 revised comprehensive diagnostic criteria for IgG4-RD, poor IgG and/or IgG4 staining cannot completely exclude IgG4-RD [The clinical and radiological features of this patient lack specificity. Five visits over 6 years showed prominent enlargement of the right inferior rectus muscle belly, which is similar to the presentation of thyroid-associated ophthalmopathy (TAO). However, by carefully analyzing the patient’s imaging and exam results, there were differences between the patient’s condition and TAO. First, the typical radiological finding of TAO is a fusiform enlargement of the muscle belly, whereas this patient’s muscle had an oval change. Second, in TAO, if the right inferior rectus muscle develops to such a severe level, the rest of the extraocular muscles are also likely to be heavily involved, which was not observed in this patient. Third, the thyroid function was normal in any of all five of the visits. Fourth, the biopsy found a friable mass with a grayish fish-like cut surface, which is more consistent with the gross characteristics of malignant tumors. Even in patients with a confirmed diagnosis of TAO, continued deterioration should raise a suspicion of malignancy. Zoran et al. reported a patient with unilateral, low-grade marginal zone B-cell lymphoma simulating unilaterally worsening TAO. His previous symptoms worsened with progressive unilateral exophthalmos resistant to the previously applied glucocorticoid therapy .This case demonstrates an atypical manifestation and course of disease in ocular adnexal lymphoma. There are two implications of our findings. First, we found that the long-term extraocular myositis may evolve into lymphoma and elevated IgG4 levels may be a precursor to the disease. Therefore, clinicians should not underestimate the potential severity of chronic myositis and should treat it proactively. Second, the clinical and radiological presentations of isolated lymphoma involving extraocular muscles are similar to those of TAO. In patients with painless extraocular muscle hypertrophy who lack systemic features of hyperthyroidism or hypothyroidism, malignancy should be considered and diagnosis confirmation by biopsy is warranted if necessary.


In this paper, we show the influence of stone powder content on the mechanical properties of concrete by experiments and numerical simulations. In numerical simulation, this paper proposed a method whereby the stone powder in the numerical simulation of concrete is considered by the mechanical performances of mortar with the stone powder. The results of numerical models established based on inclusion theory and random aggregate distribution were basically consistent with the experiment, which indicated that the simulation method of concrete under different stone powder was feasible. In the range of stone powder content from 0% to 15%, the model based on inclusion theory is very close to the experimental results, and the model based on 2D random aggregate distribution is closer to the experimental value once the stone powder content is 7%. The research showed that with increased stone powder, cubic compressive strength had greater dispersion between the simulation and the experiment; axial compressive and split tensile strength reached the best levels at 5%. The best stone powder content was 5% for C80 high-strength concrete by comprehensively considering concrete’s consistency and its mechanical properties. With the development of the building material researches, high-performance and ultra-high-performance concrete are widely used in construction engineering, and some admixtures are added to the concrete to improve the strength . FurtherGuizhou Province, China has a typical karst topography in which carbonate rocks are widely distributed. Due to the special geographic environment and the scarce resources of river sand, machine-made rock sand can be used as a building material by removing soil and crushing and screening rocks . Accordi2 emissions, and all of the low-cement HSC they studied presented high workability. Yang et al. [At present, the influence of stone powder content on the mechanical properties of concrete is mainly based on experimental methods. Belebchouche et al. , Chajec g et al.  researchThe artificial intelligence and machine learning techniques are also capable of modeling the mechanical behavior of concrete. Nafees et al.  used macMost scholars have adopted experimental methods to research the mechanical properties of concrete with different stone powder contents. This paper proposes a method to simulate the influence of these mechanical properties. We mixed different contents of stone powder into mortar for testing and obtained the basic performance of the mortar to demonstrate the influence of stone powder, so as to determine the influence on the mechanical properties of concrete with different stone powder contents. These data were used in model 1, based on inclusion theory, in which concrete is regarded as a composite material of mortar and coarse aggregate wrapped in an interface, and model 2, the random aggregate model, in which concrete is considered as a composite material of mortar, coarse aggregate, and interface transition zones (ITZs). Comparing the results of model 1, model 2, and experimental values, the best stone powder content of C80 concrete was 5%. Both simulation methods can effectively simulate the impact of different stone powder contents on the mechanical properties of concrete. This paper proposes a new method to simulate the influence of stone powder content on the mechanical properties of concrete and uses the inclusion model and random aggregate distribution model to verify the feasibility of the method through comparison with experimental values.In this section, we introduce the raw materials and experimental methods used in the experiment and analyze the results, including cubic compressive strength, axial compressive strength, elasticity modulus, split tensile strength, and flexural strength of concrete. The flowchart is shown in Conch brand P·O 42.5 cement  was used in the test, and the main properties are shown in The cubic and axial compressive, split tensile, flexural strength and elastic modulus of concrete  of concrete based on Digimat, it was necessary to determine the mechanical parameters of the matrix phase, which were measured by experiments, as shown in Inclusion model c: accordFor the 2D random aggregate distribution models d, the thThe 3D random aggregate distribution model was similar to the 2D model, but the eight-node reduced integral solid element (C3D8R) was adopted for the concrete and steel plate in the model.As shown in Research on the flowability of C80 concrete with stone powder content showed that flowability was the best when the content was 7%. With increased stone powder content, the slump and slump-flow decreased, and an agglomerated phenomenon occurred in the concrete. The changes in compressive, split tensile, and flexural strength of C80 concrete with different stone powder content were as follows.2).The cubic compressive and axial compressive strength of concrete are calculated by Equation (3):2).The split tensile strength of concrete is calculated by Equation (4):The flexural strength of concrete is calculated by Equation (5):The mechanical parameters of cement mortar and concrete were measured by the above methods, and each group of experiments had three specimens. The test result was the average value of the three specimens according to Chinese Codes JGJ/T 70-2009  and GB/Tg and Du  and Huang and Du .Cubic compressive strength is an important criterion to divide the grades of concrete. From The axial compressive strength test of concrete can reflect the stress and failure state intuitively. It can be seen from The split tensile strength test is one of the methods to test the tensile strength of concrete which can reflect its tensile performance indirectly. It can be seen from Flexural strength can reflect the toughness of concrete. As shown in The stress–strain curves of concrete with different stone powder contents are shown in This section mainly includes two parts: analysis and discussion. The analysis includes a comparative analysis of the experimental value and two simulated values and a comparison of damage and failure modes under compression in two models. The discussion includes the main research results of this paper, some abnormal data analysis, and the limitations of the paper.In the following figures, M1 and M2 represent the simulation result of the numerical model based on inclusion theory and the 2D random aggregate distribution model, respectively. For cubic compressive strength, the experimental results are similar to the two simulation results, but the change trend is different. The test reaches the maximum result when the stone powder content is 10%, the simulation result based on the inclusion theory reaches the maximum at 5%, and the 2D random aggregate model reaches the maximum when the stone powder content is 15%. For axial compressive strength, the variation trends of the experimental results and the simulation results are the same, but the results of the model based on the 2D random aggregate distribution are smaller than those of the test when the stone powder content is 7%. For splitting tensile strength, the model based on the 2D random aggregate distribution has some difference when the stone powder content is 5%. The elastic modulus and flexural strength results of concrete are not much different between experiments and simulations.It can be seen that the two simulation results are in good agreement with the experiment, but the model based on inclusion theory can better reflect the macro-mechanical properties of concrete, because this method is based on inclusion theory, homogenization theory, and progressive damage theory to calculate the constitutive relationship of concrete with a certain content, and then the stress–strain curves are directly imported from Digimat into Abaqus as a material parameter. Meanwhile, the model as a whole could exhibit its macroscopic mechanical properties accurately. However, the model did not consider the distribution of aggregates and mortar, and as a result, it could not reflect the mesoscopic failure mode of concrete; therefore, the establishment of a random aggregate distribution model is significant.There are some differences between the two failure modes. In the model based on inclusion theory, whose first crack occurs at the four corners, the failure develops toward the middle of the specimen with increasing load. In the damage to a 2D random aggregate distribution, whose first crack appears in the ITZ, the microcracks are connected and develop into macroscopic cracks with increasing load. The final failure mode of the two models is an X shape, which is consistent with the experiment. Therefore, the nonlinear characteristics of concrete at the macro level are closely related to the initiation and propagation of microcracks in concrete.At present, there is little research on stone powder in concrete through numerical simulations. Therefore, based on previous studies, this paper proposes a simulation method for stone powder, adding different contents of stone powder to the mortar and testing its mechanical properties. The changed mechanical properties of mortar indicate the impact of the stone powder content, and the inclusion model and 2D random aggregate distribution model were established to verify the method in comparison with experimental values. The experimental and simulation results show the influence of stone powder content on the mechanical properties of concrete, and the best stone powder content of C80 concrete is 5%.The experimental results show that with increased stone powder content, the cubic compressive strength first increases and then decreases, reaching 97 MPa when the content is 10%, which is too large compared with the other groups. This is due to the influence of concrete size. In this experiment, the size of the cube compressive specimen is 100 mm × 100 mm × 100 mm, and the sizes of the axial compressive strength and elastic modulus are both 100 mm × 100 mm × 300 mm. The smaller the specimen size, the greater the probability of uneven distribution of the coarse aggregate, which is the reason for the greater difference in the cubic compressive strengths. Comparing the experiment and the simulation, when the stone powder content was less than 7%, the values of cubic compressive strength were close, but the result of the S10 group was large. When the stone powder content exceeded 7%, the thick mortar led to uneven distribution of the coarse aggregate in the specimen during the experiment, and the coarse aggregate was concentrated in the middle. Han et al.  also fouThe model established based on inclusion theory was closer to the experiment . This isAlthough this paper has proposed a method to simulate different contents of stone powder, it cannot be completely separated from the experiment, and the basic data of the experiment still need to be provided. Meanwhile, the model does not consider that the coarse aggregate in thick mortar would be distributed unevenly. Therefore, it is necessary to establish a simulation method for concrete with different stone powder contents according to the actual distribution of coarse aggregate and to analyze the influence of different distributions of coarse aggregate on the mechanical properties of concrete with different stone powder content.Experimental analysis and numerical simulation methods based on inclusion theory and random aggregate distribution were used to study the influence of stone powder content on the mechanical properties of C80 concrete in this paper. The conclusions are as follows:With increased stone powder, the cubic compressive strength of concrete showed different changes. The experimental value reached the maximum at 10%, the numerical model based on inclusion theory reached the maximum at 5%, and the 2D random aggregate distribution model reached the maximum at 15%. There was greater dispersion between experiment and simulation.In the range of stone powder content from 0% to 15%, the model based on inclusion theory was very close to the experimental results, and the model based on 2D random aggregate distribution was closer to the experimental value after the stone powder content was 7%.The simulated values were consistent with the experiment in the axial compressive, split tensile, and flexural strength of concrete. The model based on inclusion theory reflected the macroscopic mechanical properties of concrete, and the 2D random aggregate model emphasized the meso-level failure mode.Considering the mechanical properties and flowability of concrete comprehensively, the best stone powder content of C80 concrete was 5%.The final failure mode of the two models was an X shape, which was consistent with the experiment. Therefore, the nonlinear characteristics of concrete at the macro level are closely related to the initiation and propagation of microcracks in concrete. The 2D random aggregate distribution model can better show the mesoscopic mode of the compression failure of concrete.


Between-country differences have been described in antibiotic prescribing for respiratory tract infection (RTI) in primary care, but not yet for diagnostic testing procedures and prescribing confidence.To describe between-country differences in RTI management, particularly diagnostic testing and antibiotic prescribing, and investigate which factors relate to antibiotic prescribing and GPs’ prescribing confidence.Prospective audit in 18 European countries.n = 4982), and GPs' confidence in their antibiotic prescribing decision. Factors related to antibiotic prescribing and confidence were analysed using multi-level logistic regression.An audit of GP-registered patient, clinical, and management characteristics for patients presenting with sore throat and/or lower RTI  testing , and in laboratory or hospital-based testing . Antibiotic prescribing was related to illness severity, comorbidity, age, fever, and country, but not to having performed a POC test. In nearly 90% of consultations, GPs were confident in their antibiotic prescribing decision.Despite high confidence in decisions about antibiotic prescribing, there is considerable variation in the primary care of RTI in European countries, with GPs prescribing antibiotics overall more often than is considered appropriate. POC testing may enhance the quality of antibiotic prescribing decisions if it can safely reverse decisions confidently made on clinical grounds alone to prescribe antibiotics. A large between-country variation in antibiotic prescribing for RTI exists in European primary care. Despite huge variation in management variables, such as POC and laboratory or hospital-based diagnostic testing and antibiotic prescribing, GPs expressed high confidence in their antibiotic prescribing decisions. Antibiotic prescribing was attributed to patient-related factors and country, but not convincingly to POC testing. POC testing may enhance the quality of antibiotic prescribing if it can safely reverse decisions confidently made on clinical grounds alone. and there is evidence that this variation is not warranted on clinical grounds. Despite antibiotic surveillance and stewardship programmes in many countries, these differences persist. Prudent use of antibiotics is fundamental to contain antimicrobial resistance, reduce unnecessary exposure of patients to its side effects, contain costs, and guide patients expecting antibiotics for common infectious syndromic illness.Sequential studies by the European Centre for Disease Prevention and Control (ECDC) have identified important between-country differences in the numbers and class of antibiotics used, Moreover, RTI is often of viral aetiology and self-limiting, making this condition the main target for improving the quality of antibiotic prescribing decisions. Challenges facing prescribers include uncertainty about aetiology, unavailability of POC diagnostic testing to aid prescribing decisions, unfamiliarity with current guidelines, risk-adverse prescribing behaviour, and non-evidence based patients’ expectations about effectiveness of antibiotics. Additional influences include healthcare system and cultural factors.About 80%–90% of antibiotics are prescribed in primary care, where overprescribing is common for RTI. and to use the biomarker CRP to inform antibiotic prescribing for acute cough. These POC tests have been shown to decrease antibiotic prescribing for patients with sore throat and acute cough in clinical trials. Uptake of POC testing into national guidelines and clinical practice varies, but the extent to which this explains between-country differences in antibiotic prescribing is unknown.POC testing for RTI management has been introduced in primary care thus far mainly to identify a strep A throat infection,A point-prevalence audit survey (PPAS) was conducted of GPs’ management of patients presenting with symptoms of an RTI in 18 European countries. This enabled the authors to: 1) describe between-country differences in management of RTI, with focus on antibiotic prescribing and the use of POC and laboratory or hospital-based diagnostics; and 2) to investigate which factors relate to antibiotic prescribing and GPs’ confidence in their prescribing decisions.This was a PPAS of patient, clinical, and management characteristics of patients presenting with symptoms of an RTI in 18 European countries that differed with respect to healthcare organisation, antibiotic use, and income level . Data on presentation and management, including confidence in their antibiotic prescribing decision, were anonymously registered by GPs. Patients were not informed, nor asked to provide informed consent as no personally identifiable information was collected. This procedure was approved by research ethics committees in all participating countries.https://www.value-dx.eu). The registration period was January and February 2020, and each national team was asked to involve practices to enable delivering 200–250 registrations per country. As a formal power analysis was not considered needed for an audit, it was assumed that this number would provide enough information to describe management and between-country variation.The PPAS was performed in an established European Primary Care Research Network (n = 5), Belgium (n = 6), Croatia (n = 6), Germany (n = 2), Denmark (n = 20), Spain (n = 6), France (n = 18), Georgia (n = 5), Greece (n = 6), Hungary (n = 5), Ireland (n = 6), Moldova (n = 4), the Netherlands (n = 12), Norway (n = 18), Poland (n = 8), Romania (n = 5), Ukraine (n = 4), and the UK (n = 7).Practice size (number of GPs working in the practice) and the national teams’ preference to ask GPs to register a pre-defined number of consultations,or during a short period, or the complete period resulted in a different number of practices involved per country: Armenia  and/or acute cough (duration <28 days), and to not register patients with only nasal or ear symptoms.Data were entered directly during the consultation in an online data capture system, Research Online, or entered later using paper Case Report Forms (see Supplementary Appendix S1). Data registration covered the following: patient characteristics ; clinical presentation ; GPs’ measurements ; diagnostic testing ; prescribing ; advice provided; and referral to hospital. At the end of the consultation, being aware of the result of the POC test but unaware of the result of laboratory or hospital-based testing, GPs rated their level of confidence in their decision whether or not to prescribe antibiotics using a 5-point Likert scale. Unknown and missing data, which was <1% for each variable, was regarded as ‘no’ or ‘not present’, and both immediate and delayed prescribing were considered as antibiotic prescribing.Patient and management data are presented for the full sample as percentages with 95% confidence intervals (CIs) and ranges, and by country .Factors related to antibiotic prescribing were analysed with mixed-effects logistic regression analysis where country, use of strep A and/or CRP POC testing, illness severity, age, presence of any comorbidity, fever, and duration of illness were included as fixed effects. Practice was included as random effect to take into account that patients were nested within practices. The same analysis was performed for two subgroups: 1) patients with diagnoses of a throat infection  with strep A testing as fixed effect; and 2) patients with a lower respiratory tract diagnosis  with CRP testing as fixed effect.As the outcome for confidence in the antibiotic prescribing decision indicated low frequencies for the options moderately certain and (very) uncertain it was decided to collapse these into ‘less certainty’, and compare with consultations where GPs indicated both degrees of certainty ([very] certain). Factors related to less certainty were analysed with mixed-effects logistic regression analysis where country, diagnostic testing , illness severity, age, presence of any comorbidity, fever, antibiotic prescribing, patient request for an antibiotic, suspected viral aetiology, and unclear aetiology were included as fixed effects, and practice as random effect. Results are presented as odds ratios (ORs) for each variable with 95% CIs. The statistical analyses were performed with IBM SPSS Statistics (version 26) and SAS Enterprise Guide (version 7.13).A total of 4982 consultations of patients presenting with symptoms of an acute RTI were registered (from 211 in Norway to 355 in Armenia) between January and February 2020. Patients of all ages and with different comorbidities were registered. Their main symptoms, clinical assessments, severity rating, diagnoses, GPs’ confidence in their antibiotic prescribing decision, provided advice, and hospital referral are shown in Supplementary Table S1. Country variation in these variables is provided in Supplementary Table S2. Influenza-like illness, pharyngitis, and bronchitis were the most frequently used diagnostic categories. Only 3.2% of patients were classified as having severe illness and 2.3% were referred to hospital. Nearly 80% of patients received advice regarding symptomatic treatment and nearly 40% were advised or prescribed to take days off work or school.The proportion of patients prescribed antibiotics ranged from 18% (Belgium and Denmark) to >50% (Hungary and Ireland). Overall, 12.3% of patients requested an antibiotic prescription, ranging from <5% in Germany, Spain, and Croatia to >20% in Greece, Ireland, and Ukraine. Delayed antibiotic prescribing was highest in Belgium, Denmark, Ireland, and Ukraine. Broad-spectrum penicillins were most often prescribed (29.0%), followed by co-amoxicillin/clavulanate  and macrolides . Narrow-spectrum penicillins  were mainly prescribed in Denmark, Norway, and the UK. Cephalosporins  were more frequently prescribed in Hungary and Ukraine. Antivirals were frequently prescribed in Georgia, Greece, Moldova, and Romania , while more often for patients with sore throat infection diagnoses when a strep A POC test was done .GPs were generally confident in their antibiotic prescribing decision; in 88% of consultations, they rated their level of confidence as (very) certain (Supplementary Table S1). Unadjusted data show that GPs expressed lower confidence when they prescribed an antibiotic for patients with a suspected viral or an unclear aetiology, both relatively small subgroups . Confide There was also considerable variation in clinical assessments, POC, and laboratory or hospital-based testing, and in non-antibiotic prescriptions. However, GPs consistently expressed a high level of confidence in their decision whether or not to prescribe antibiotics. Antibiotic prescribing differences were explained most by country-level factors and individual illness severity, rather than whether or not POC testing was used.This prospective 18-country audit of nearly 5000 primary care consultations for RTI confirms considerable variation in both the proportion and the class of antibiotics prescribed.The strength of this study is the uniform, prospective data capture, implemented in many contrasting European countries, including some that have not previously been included in prospective international studies of RTI in primary care. The PPAS provides insight in various management variables and enables between-country comparisons. The anonymous, audit-type procedure of registering sequentially presenting patients avoided selection bias as to whom to register or not. Therefore, it is considered that the study population is a representative sample of patients presenting with RTI symptoms in the participating countries, without enrichment for patients with certain characteristics or management variables. Filling out the CRF could easily be done during or immediately after the consultation without practical constraints of informing patients and taking informed consent. Owing to this minimal study burden on GPs, the PPAS can easily and usefully be repeated to capture changes in care provision, which was done at the start of the COVID-19 pandemic. Finally, the audit did not follow-up patients, so the clinical outcomes and hospital or laboratory-based test results were unknown. These data could have been helpful to determine whether GPs’ prescribing confidence was justified.Several weaknesses need to be considered. First, with respect to the generalisability of the results that have been presented at country level. Given the limited number of general practices participating in each country, outcomes might not represent primary care provided in the country. For instance, in Moldova, four practices in a university-linked primary care clinic participated, and these practices may have therefore been atypical. Second, concerning POC testing, heterogeneous data were dealt with. In some practices and/or countries, POC testing was not available, in some, GPs could choose whether or not to use the testing, while in others it was part of the guidelines. Whether POC testing was at the discretion of the GP, or not, the PPAS did provide an extensive dataset of consultations with and without POC testing and antibiotic prescribing. This allowed for comparing consultations with and without POC testing. This group-wise comparison indicated that overall confidence was not higher when POC had been used. However, reasons for deciding whether or not to perform a test and confidence before testing were not captured. Such information could have added to the understanding of the influence of performing a POC test on antibiotic prescribing and on changing confidence within the consultation. A Swedish study, for instance, indicated the influence of CRP testing on GPs’ degree of suspicion of pneumonia. The prescribing proportion in the PPAS were not always congruent with the ranking in ECDC reports in which, for example, the Netherlands ranks lowest and Belgium considerably higher. However, overall antibiotic use is not only determined by the prescribing proportion, but also by the number of patients that yearly present to a GP, the denominator. In countries with a high threshold to consult the GP, fewer patients overall, but probably with relatively more severe illness, will present, as opposed to, for example, a country where all patients with RTI consult their GP for a sick note. The PPAS captured data from a pre-defined number of consultations per country and not on total numbers of consulting patients in the 2 months‘ registration period.Several other studies have described the differences in numbers, types, and appropriateness of prescribed antibiotics between European countries. but not in a prospective multi-country study using the same data capture form.Variation in the use of POC testing for RTI has been described for practices and GPs within some countries, However, pragmatic studies on the use of POC testing in general practice show smaller, often statistically non-significant effects. The routine care data captured in the audit pointed towards a different effect of CRP and strep A testing. CRP testing tended to decrease antibiotic prescribing and the non-significance might have been owing to using routine care data and/or the sample size. Strep A testing on the other hand was associated with higher antibiotic prescribing; testing might have been used to confirm an antibiotic prescribing decision. Although the PPAS was not designed to specifically investigate factors influencing antibiotic prescription, the results indicate that trial results need to be confirmed with data from routine primary care practice.Randomised controlled trials have found that strep A and CRP POC testing reduce antibiotic prescribing at the index consultation. However, this association is not necessarily causal. The PPAS highlighted a strong ‘country factor’ associated with antibiotic prescribing. This country factor is no doubt the product of many interacting factors, such as antibiotic prescribing levels before the implementation of POC testing, national prescribing guidelines, antimicrobial stewardship programmes, and culturally determined GP and patient-related factors.Countries where POC testing is widely used, including Denmark, Norway, Sweden, and the Netherlands, have lower antibiotic use compared with countries where POC testing is not widely implemented. In implementing POC testing in guidelines and primary care practice, this expressed confidence would support the advice to use POC testing when the GP is in doubt to increase their confidence in diagnosis and/or prescribing. Additionally, POC testing for RTI might have more impact as a standard antibiotic stewardship intervention implemented to safely deviate from a (confidently made) yes-antibiotic prescribing decision.GPs have high confidence in their antibiotic prescribing decisions, including when POC testing was not used or available. It can be questioned whether the confidently made yes-antibiotic prescribing decisions are correct, given that antibiotics were prescribed in 70% of patients with tonsillitis, 45% of patients with bronchitis, and 19% of patients with pharyngitis, which is higher than considered appropriate.In conclusion, despite high confidence of GPs in their decisions about antibiotic prescribing, there is considerable variation in primary care management of RTIs in European countries, with many GPs prescribing antibiotics more often than considered appropriate. POC testing may enhance antibiotic prescribing stewardship even in the face of GPs being confident in prescribing, if it can safely reverse an antibiotic prescribing decision made on clinical grounds alone. The PPAS is considered a valuable research tool and its country-specific information can aid in designing and implementing interventions for RTI management taking the country’s specific context into account.


Moreover, using 3D printing phase change aggregate reduced concrete’s early peak hydration temperature by 7.1%. The thermal insulation capacity of the experiment cube model with phase change concrete has been improved. The results show that the novel 3D printing change aggregate concrete has good mechanical properties and latent heat storage, providing a guideline for applying PCMs in building materials.The use of phase change materials (PCMs) in concrete is a double-edged sword that improves the thermal inertia but degrades the mechanical properties of concrete. It has been an essential but unsolved issue to enhance the thermal capacity of PCMs while non-decreasing their mechanical strength. To this end, this work designs a novel 3D printing phase change aggregate to prepare concrete with prominent thermal capacity and ductility. The work investigated the effects of 3D printing phase change aggregate on the compressive strength and splitting tensile strength of concrete. The compressive strength of phase change aggregate concrete is 21.18 MPa, but the ductility of concrete improves. The splitting tensile strength was 1.45 MPa. The peak strain is 11.69 × 10 The development of human society is inseparable from energy. With the growth of the world population and the improvement of living standards, energy consumption in human society has increased steadily. In developed countries, building energy consumption accounts for 20–40% of the total energy consumption, and the energy consumption for HVAC  systems can reach 50% ,2,3. PhaThe combination of phase change materials and civil engineering materials is an important research field . There hTherefore, given the disadvantages of poor thermal stability and reduced mechanical properties of phase change materials used in building materials, this paper is committed to proposing a new macro-encapsulated phase change concrete aggregate. Combining PCM with concrete aggregate realizes the function of phase change energy storage without significantly reducing the mechanical properties of concrete. Based on bionic technology and imitating the shape of a virus, the concrete aggregate with an external tentacle and the internal cavity is designed and prepared by 3D printing. Paraffin, as phase change material, is encapsulated in the internal cavity of 3D printed aggregate. The strength of phase change aggregates mortar, and the strength of continuously graded phase change aggregate concrete are studied, respectively. The effect of reducing hydration heat and heat preservation and temperature regulation function of phase change aggregate concrete were studied.The spherical structure was selected as the basic configuration of phase change aggregate to reduce the adverse effects of the aggregate shape on the workability and mechanical properties of concrete. Based on bionic technology, imitating the structure of the bacteria and viruses, a tentacle-like secondary structure was designed on the surface of the sphere to increase the contact area. A cavity was set inside the spherical structure to accommodate the PCMs, and two small holes were reserved on the surface to facilitate the injection of PCMs. The detailed structural information of phase change aggregate is shown in Good gradation can make the aggregate stack more compact and enhance the mechanical properties of concrete. The phase change aggregate of each particle size is shown in A JennyLight 1 + LCD light curing 3D printer prepared the phase change aggregate. The prepared parameters include the bottom exposure time of 30 s, the bottom layer number 5, and the common layer exposure time of 10 s. The printing materials are bisphenol F epoxy acrylate resin, TPGDA as the diluent, and TPO as the light initiator. After printing, it was cleaned with anhydrous ethanol, put into the curing box, and irradiated under a purple lamp for 30 min to improve the strength. Finally, the melted paraffin was filled with the cavity of the phase change aggregate, and the holes reserved on the surface were sealed with epoxy resin glue. The encapsulation process is shown in 3, fineness modulus of 2.4, and water absorption rate of 1.0%. 5–20 mm continuous graded basalt gravel was used as coarse aggregate. Polycarboxylic acid series superplasticizer with a solid content of 39.9% was used.The cement used in the test was P·II 52.5 cement produced by Nanjing Jiangnan Onoda Cement Co., Ltd., Nanjing, China. and its chemical composition is shown in w/c) = 0.4, as shown in The cement-based material system of cement and fly ash is adopted with a mass-based water-to-cement ratio ((1)Mechanical properties: the loading rate of the cementitious composite sample is 1200 N/s, and three parallel tests are carried out for each group. According to GB/T50081-2019, the concrete compressive and splitting tensile performance tests are carried out. Maintain an ambient temperature of 20 ± 5 °C during the stress test.(2)Early hydration temperature rise: Set all the raw materials at 20 °C for 24 h until constant temperature, prepare fresh phase change aggregate concrete, and pour into a 1 L cylindrical container with a temperature sensor vertically fixed in the center of the lid and connected to the SV3000 environmental monitoring system on the computer. After measurement, close the lid and make a temperature sensor insert to the core of fresh concrete, put the container as a whole into the incubator, and record the temperature every 1 min.(3)Temperature regulating performance: paste thermocouple in the center of the two largest planes of basalt aggregate concrete slab and phase change aggregate concrete slab and use a high-power heating lamp to simulate sunlight irradiation on one side. The thermocouple is connected to the ToprietP700 multichannel data recorder and records the temperature at the center of the inner and outer surface of the concrete plate every 5 s. At the same time, RNO PC160 infrared imager produced by Meiketsu E-Commerce Co., Ltd., Shanghai, China, was used to take infrared images of the backlit surface of the concrete slab every 20 min. The test device for the concrete slab is shown in (4)Thermal insulation performance: the phase change aggregate concrete slab and the basalt aggregate concrete slab were, respectively, combined with five polystyrene thermal insulation boards to make a cube model. All cracks in the model were filled with polyurethane foam sealant. High-power heating lamps were used to simulate sunlight irradiation. Thermocouples are installed in the center of the inner and outer sides of the concrete slab, the body center of the model, and the center of the polystyrene thermal insulation board on the bottom and connected with the TOPEIE TP700 multi-channel data recorder. The temperature is recorded every 5 s. The schematic diagram of the whole test device is shown in The effects of aggregate type and paraffin filling on the compressive property of the phase change cementitious composite sample are shown in As shown in The damage to the cementitious composite under compression is shown in The compressive stress–strain curve of concrete prepared by phase change aggregate replacing basalt aggregate with volume ratios of 0%, 50%, and 100% are shown in −3. The peak strain of concrete PCC−50 with a 50% phase change aggregate substitution rate is 6.85 × 10−3, 56.2% higher than that of basalt aggregate concrete. The peak strain of concrete PCC−100 with a 100% phase change aggregate substitution rate is 15.64 × 10−3, which increases by 70.5% compared to basalt aggregate concrete. The incorporation of phase change aggregate makes the concrete show good ductility. The compressive strength decreases while the ductility increases because the cavity inside the phase change aggregate reduces the mechanical properties and improves the deformation property of aggregate. Moreover, when the partial phase change aggregate replaces basalt aggregate, they disperse each other, which significantly weakens the function of the “self-locking” tentacle structure added to the aggregate design.The stress–strain curves of concrete prepared with two kinds of aggregate are further analyzed. As shown in The splitting tensile properties of concrete prepared with two kinds of aggregate are shown in The hydration reaction of cement is exothermic, and the poor thermal conductivity of concrete is easy to produce temperature differences inside the concrete, which leads to cracking of concrete due to temperature stress. Incorporating phase change materials in concrete reduces the early hydration temperature rise rate. Kim et al. , pointedThe inhibition effect of printed phase change aggregate on early temperature rise of concrete is shown in The temperature distribution of the shady surface of concrete slabs with the two kinds of aggregate varies with illumination time, as shown in The temperature of the concrete slab on the phototropic surface and the shady surface changing with time is plotted, as shown in The temperature change of phase change aggregate concrete presents relatively complex fluctuations because the paraffin inside the aggregate has phase change in both the heating and cooling stages, which affects the heat transfer in the direction of the temperature gradient. The addition of PCM leads to the difference in the temperature variation pattern of concrete. During the heating process, paraffin stores heat through a phase change, resulting in a slow temperature rise. At the same time, the temperature of phase change concrete is always lower than that of basalt concrete, and the final temperature is also lower. In the cooling process, it is also due to the heat released by the phase change of paraffin, which delays the temperature reduction process of the phase change concrete slab.The phase change process also significantly influences the temperature difference between the phototropic and shady surfaces of concrete, as shown in Temperature changes at each point in the cube model are shown in The maximum temperature difference at each temperature measuring point in the heating and cooling stages is shown in (1)Increasing phase change materials in the cavity of phase change aggregate will improve its mechanical properties. Compared with the phase change aggregate without paraffin adsorption, the compressive strength of the phase change cementitious composite with the internal cavity filled with paraffin increased by 9.9%.(2)−3, nearly 13 times that of basalt aggregate concrete.The compressive strength of phase change aggregate concrete is 21.18 MPa, and the specific strength is 11.48 kN·m/kg. The concrete experiences ductile failure with the addition of phase change aggregate of 3D printing. When the replacement rate is 50% and 100%, the compressive peak strain of concrete increases by 48.6% and 239.3%, respectively. The splitting tensile strength was 1.45 MPa. The peak strain is 11.69 × 10(3)The addition of phase change aggregates reduces the hydration heating rate while improving thermal regulating and thermal insulation properties. The phase change aggregate reduced concrete’s early peak hydration temperature by 7.1%. For concrete slabs, phase change aggregates can effectively delay heat transfer. In the thermal insulation experiment, phase change aggregate can effectively store thermal energy, maintain the internal temperature of the model, and improve the thermal insulation performance of phase change concrete.In this work, 3D printing technology and macro encapsulation prepared a phase change aggregate containing paraffin. The shell of phase change aggregate is formed by curing with high-strength resin. The surface of the shell has a tentacle structure to enhance mechanical properties. The cavity inside the phase change aggregate is filled with molten liquid paraffin, and the filling hole is sealed with epoxy resin glue. The mechanical and thermal properties of the phase change aggregate concrete were studied. The following conclusions were drawn:


Defining the gold standard for appropriate antibiotic prescribing is challenging due to the subjective nature of evaluating quality in prescribing. In 2017 the UK Government Scientific Advisory Committee on Antimicrobial Prescribing, Resistance and Healthcare Associated Infection (APRHAI) used the Delphi process to define appropriate antibiotic prescribing, and developed an audit tool that supports patient-level assessment of antibiotic appropriateness in NHS hospitals.To quantify excess antibiotic use in a 750-bed acute hospital in the south-west of England , and to determine where in the prescribing process the opportunity to safely reduce antibiotic use is: (A) initiation, (B) the pre-72 h review, or (C) course length optimization.The EPMA system was used to identify patients discharged from medical specialties in August 2020 who had received at least one dose of antibiotic. Patients were grouped by discharging medical specialty, as follows: acute medicine, elder care, renal, endocrine, gastroenterology, respiratory and cardiology. Medical notes for 25% of discharges from each specialty were requested and audited against the APRHAI audit tool. A junior doctor completed the audit form for each patient with the case then discussed by two infection specialists until consensus was reached. Excess days of antibiotic therapy (DOTs) were calculated for each of the three timepoints (A–C).In total, 184 of 647 (28%) patients discharged from medical specialties were audited: 85 female, 99 male, median age 69 years (IQR 60–82), total DOTs 1658 of which 403 (24%) were excess. Excess DOTs by timepoint: A (initiation) 112 (28%), B (pre-72 h review) 184 (46%), C (course length) 107 (27%). Ninety-four of 187 (50%) of patients recorded zero excess DOTs.We did not identify any excess DOTs in half of all patients initiated on antibiotics. However, in the other half we identified a significant proportion of excess DOTs with most excess DOTs at the pre-72 h review.