Of the 159 pet owners among the respondents, only half had administered antibiotics to their animal and 64% (n = 102) knew that veterinary prescription is mandatory when administering antibiotics to animals. All groups statistically agreed that the AMR is a major public health problem and the antibiotics should be administrated for bacterial infections and used until the whole pack has been finished (p = 0.00). As expected, only groups B and C demonstrated a higher level of knowledge to recognize the antibiotic name and their active ingredient than undergraduate students (p = 0.00). About the antibiotic use on pets, only group B was statistically significant to no used antibiotics on their pets (p = 0.00). However, groups A, C, and D were statistically significant for the knowledge about the mandatory veterinarian prescription and groups C and D were significantly statistics for fully aware of the transmission of bacteria between animals and humans. In conclusion, in matters related to AMR, the behavior, education, and training of the general public and health professionals, including those who prescribe antibiotics for humans and animals, need to be improved.Antimicrobial resistance (AMR) is an urgent and complex problem worldwide, exacerbated by the frequently inappropriate use of antibiotics. The purpose of this study was to survey the levels of knowledge and awareness about antibiotic use and stewardship, among human and veterinary health professionals or students in Portugal, and the associations between antibiotic knowledge factors and socio-professional groups. In cross-sectional survey design, a total of 449 online structured questionnaires were completed in 2018–2019. The statistical analysis was performed dividing the respondents into four groups, A (undergraduate students), B (PhD students and researchers), C (lecturers), and D (technicians and other occupation). Among all respondents, 17% ( The use of antibiotics has brought about a revolution in human and veterinary medicine and has contributed to saving millions of lives . With thIn recent years, multiple international strategies and campaigns have been developed, and recommendations have been published to reduce or at least stabilize levels of AMR ,11,12. TA key public health priority on a global scale is thus to conserve antibiotics by optimizing how they are prescribed and taken in order to reduce AMR spread  and to iAlthough the causes of AMR are complex, the main factors described as being responsible for AMR encompass inappropriate prescription practices, inadequate animal owners education, limited diagnostic facilities, unauthorized sale of antimicrobials, lack of appropriate functioning drug regulatory mechanisms, and non-human use of antimicrobials, such as in animals . SeveralThe study was carried out in northern Portugal. Two public universities were selected based on their size and location to ensure a diversity of socioeconomic contexts. One university offering both veterinary and medical courses is located in a metropolitan area near the coast that is very attractive to incomers, partly due to its better transport access and higher population density. The other university is set in a rural inland context, where population densities are lower, but has the strong attraction of the integrated veterinary medicine master’s degree course it offers. Combined, about 3550 students were enrolled in the veterinary and medical courses at the two institutions for the academic year of 2017/2018 .The conceptual framework that represents this work was based on the findings of previous studies in this area, as described by Dyar et al. , NapolitThe data were obtained by means of a sample survey conducted in the two higher education institutions of northern Portugal. These institutions were also selected because they include future health professionals (students of the above courses), and working professionals  with varying levels of responsibility and experience in the subject, some of whom are also pet owners. The differences between perspectives and behaviors of both groups could hence allow for a comparative analysis. The study population includes professionals with different profiles, allowing for representativeness of the sample to be considered in terms of gender and age.No register of the population under study was available to support the sampling, other than the students’ enrolment on the mentioned courses, so non-random sampling techniques were used . In addiData were collected through the realization of an online questionnaire entitled “Antibiotic use survey”. In the absence of a standardized enquiry tool, the questionnaire was developed and built by a multidisciplinary group of health students and experts on responsible antimicrobial use, taking into account the results from previous studies ,26, as wThe structured questionnaire consisted of 28 closed-ended questions (dichotomous or multiple choice) organized into two main sections . The firAll respondents, current and future health professionals of the study population from the respective university departments of human and veterinary health, were invited to participate in the study by its institutional email. The questionnaire was preceded by a brief introductory note, which set out the request for cooperation, the reason for the survey, a description of the questionnaire, the institution conducting the investigation, ensuring the anonymity. At the end of section I of the questionnaire, the respondents that had pets continued to section II. Whoever did not identify themselves as pet owners were directed politely to the end of the questionnaire. The survey was self-completed in 2018–2019 and the participation was voluntary without any compensation. All subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of University of Trás-os-Montes e Alto Douro .2) tests, using the JMP 7.0  software, in which the respondents were joined into four socio-professional groups, A (undergraduate students), B (PhD students and researchers), C (lecturers), and D (technicians and other occupation).Descriptive statistics, primarily, were used to summarize all information, presenting the results as number and percentage. In the second step of statistical analysis, a proportion of categories was performed in comparison with the socio-professional group responses by qui-square  were more likely to be female gender. The 18–30-year-old respondents were more likely to be found in the undergraduate group than in other analyzed health professional groups (p = 0.00). However, of the 449 individuals, the undergraduate students corresponded to a 5% response rate, and groups B, C, and D corresponded to 34%, 19%, and 62% response data, respectively .In all socio-professional groups, respondents of female gender were predominant, in which the statistical analysis  showed tectively . Addition = 280) of respondents thought antibiotics should be administered for bacterial infections. Revealingly, 9% (n = 42) of the respondents considered the prescription of antibiotics by a doctor to be a sign of competence to treat a patient presenting with fever, headaches, runny nose, cough, and muscular pains for three days. Most respondents consider re-evaluation  or test analysis  as the appropriate course of action.All results obtained on the general level of knowledge of antibiotics use and some of the care (or lack of care) that respondents took with antibiotics are shown in n = 336, 75%), which included individuals from all groups in the population, stated that they had not bought and/or taken an antibiotic without it having been prescribed by a doctor, in opposite a quarter , and 12% (n = 54) stated that they use unfinished boxes of antibiotics to treat relatives and/or friends, and this occurred several times in the year.Three quarters of the respondents (n = 395), indicated that the prescribed antibiotic should be used to the end of the pack or course prescribed, but 18% (n = 79) considered it appropriate to keep any leftover antibiotic for future use or to throw it away, while only 60% (n = 270) claimed to always check the pack for instructions on how to use the antibiotics. Knowing the socio-professional groups represented in the study has responsibilities and education in the field. Moreover, there may be several reasons for these data, and a closer look allowed the following factors to be distinguished: (i) Medical instructions for taking the antibiotic correctly were always followed by 53% (n = 238) of respondents but this proportion rises to 92% (n = 409) if the statement is qualified by the word “sometimes”; (ii) Instructions on the leaflet in the antibiotic pack were fully heeded by only 46% (n = 207) of respondents; (iii) Experience and/or confidence with the use of different antibiotics varies as 64% (n = 286) of respondents have never had to take more than one antibiotic for treatment of a disease; and (iv) A large proportion of respondents  recognize the names of some antibiotics and their active ingredient, which may indicate the level of knowledge and possibly autonomy when taking the product.Most respondents, 88%  or through their doctor . Only 1% (n = 10) of the respondents obtained their antibiotics by other sources. Regarding the antibiotics taken by respondents in the last year, responses were split almost equally between those who took antibiotics between one to five times  and those who had not taken any product of this type .Respondents usually bought their antibiotics from community pharmacies (p = 0.00) and the antibiotics should be administrated for bacterial infections (p = 0.00) and used until the whole pack has been finished (p = 0.00). Additionally, all groups (p = 0.00) agreed that the elimination of leftover antibiotics should be returned to the pharmacy or never left unused. Although the four socio-professional groups showed a significant statistic when the respondent or a family member have been ill for 3 days, 60% of lecturers agree to return to the consultation after 2–3 days to be reassessed while 55% of undergraduate students wait for the doctor to test before prescribing an antibiotic.The statistical analysis of general knowledge and personal use of antibiotics relative to analyzed socio-professional groups was presented in p = 0.00), groups B and C were more likely to follow the totally clear instructions for antibiotic use than groups A and D. However, 35% of lecturers (p = 0.00) and 32% of undergraduate students (p = 0.00) had correctly taken a pack of antibiotics prescribed by the doctor but needed a different antibiotic to continue treatment.A majority of respondents of each group do not get antibiotics without a prescription and these usually get them in community pharmacies or through their doctor, showing statistically significant results. As expected, only groups B  and C (lecturers) were statistically significant to recognize the antibiotic name and their active ingredient. In spite of all groups being significant statistic (p = 0.00) and technicians plus health professionals with other occupations (p = 0.00) were less likely to have pets than other groups  had already used antibiotics for their animals. The proportions of specific knowledge and experience of the use of antibiotics to treat pets by the socio-professional group responses (n = 143) answered no and only 8% (n = 13) of the pet owners answered in the affirmative (One hundred and fifty-nine (35%) respondents had pets and their answers to questions regarding antibiotics use in pets are summarized in r groups . About hesponses  showed tirmative .n = 96) of respondents with pets completed the course of treatment recommended by the veterinarian and about 81% (n = 129) gave the recommended doses (n = 70) of pet owners indicated that the situation occurred only once, 9% (n = 15) a frequency of up to five times. The statistical analysis confirmed that all socio-professional groups, only stopping the pet’s antibiotic treatment when indicated by the veterinary doctor, showing a statistically significant results (p = 0.00) to not change the recommended dosage or antibiotic during the treatment.Only 60% (ed doses . However results . Althougn = 102) thought that the use of antibiotics in animals is only allowed with prescription from a veterinarian. However, only three socio-professional groups  were significantly statistic with the knowledge about the veterinarian prescription. In addition, 40% (n = 63) did not always disclose to the veterinarian their availability/willingness to correctly administer the antibiotic to their pet, including some  who indicated that they did not think this factor was important for the success of the treatment. The unavailability of information  on the proper use of antibiotics in veterinary clinics attended was reported by 46% (n = 73) of respondents. Only 41% (n = 66) of the respondents who owned pets had a notion of the possibility of spreading antibiotic resistant bacteria from animals to humans and vice versa, which was surprising considering the different socio-professional groups represented in the survey. Of these, lecturers and technicians plus professional with other occupations of groups C and D  were significantly statistic for being fully aware of the transmission of bacteria between animals and humans.Among the pet owners, only 64% , and the bacterial resistance to antibiotics is a major public health problem . Another study including university students demonstrated that 63% kept antibiotic in their home and 28% were leftover from a previous prescription by a doctor but 69% had purchased antibiotics over the counter, consequently, students keeping antibiotics at home were more likely to engage in self-medication when ill and as a prophylactic measure than other students [n = 24, p = 0.00) of undergraduate students and 10%  of doctoral students plus researchers (group B) of our analyzed health universities stored leftover antibiotics for future use. In addition, a majority of respondents of these two groups demonstrated not getting antibiotics without prescription and these usually were obtained in community pharmacies or through your doctor.Wayne et al.  stated tstudents . Howeverstudents . In oppop = 0.00). Optimizing the prescription of antibiotics to reduce the spread of AMR is a key public health priority both globally and nationally and all clinicians surveyed considered that prescribing an antibiotic to a patient may influence the onset of resistance [The realization of testing of antimicrobial susceptibility to identify possible antibiotic resistances before the antibiotic administration is essential, as well as the participation and collaboration of health professionals in integrated programs related to antibiotic resistance or other epidemic-vigilance studies . Igrejassistance . Consistsistance . Even insistance , in EnglThis type of survey has many advantages, but mainly that it is economical and efficient in terms of the time needed for sending out questionnaires and collecting data . The limThe true scope of antimicrobial stewardship surveys among health professionals is uncertain, but it is a reasonable starting point as a way to tackle the problem from both human and pet welfare standpoints. In the present study, many factors related to antibiotic prescription have been identified as abnormal situations or even misuse of these substances, like stopping the antibiotic before finishing the box or course prescribed, reusing leftover substances in later situations and the lack of explanation of the importance of the correct dose by the doctor.The control and management of antibiotic prescriptions should also be coupled with top-down strategies to enable and enhance monitoring of prescribing data at a national level and to improve engagement of the healthcare stakeholders  with antimicrobial stewardship training and resources. The competent authorities have practical experience and knowledge of national antimicrobial stewardship interventions and policy, and can refine and adapt the approaches. However, both these mechanisms are slow and long-term processes, the results of which are not immediate in terms of the participatory involvement of stakeholders and the operational effects of an active public participation policy. This can still be a viable way towards more effective antimicrobial stewardship as it may help reduce conflicts within the healthcare community, particularly in an interdisciplinary context.In conclusion, this study identified a number of shortcomings in prescribing and taking antibiotics. Although groups B and C demonstrated a higher level of knowledge about antibiotic use, antimicrobial resistance concern, and recognizing the antibiotic name and their active ingredient than undergraduate students (group A), the respondents demonstrated to lack information and formation. More representative studies are urgently needed to understand the real-national and real-world situation about the prescription and use of antibiotics by medical and non-medical populations, respectively. The solution to this problem requires a concerted One Health approach to mitigate future risks to humans, animals, and the environment.


For decades, antibiotics have been excessively consumed around the world, contributing to increased antimicrobial resistance (AMR) and negatively impacting health outcomes and expenditures. Antibiotic use in China accounts for half of worldwide antibiotic consumption, which mainly takes place in outpatient and community settings, and often unnecessarily for self-limiting community-acquired infections. This study aimed to identify and assess factors of inappropriate use of antibiotics in the Chinese context to inform the development of interventions to mitigate inappropriate consumption in the absence of clinical indications.We conducted a mixed-methods systematic review and included empirical studies with original data conducted in mainland China, Hong Kong and Taiwan that investigated factors of antibiotic use in the community including outpatient care among patients, caregivers and prescribers. We searched MEDLINE, EMBASE, the Cochrane Library, PsycINFO, Google Scholar and one Chinese database CNKI (China Knowledge Resource Integrated Database), using a combination of the key terms ‘antibiotic’, ‘antimicrobial’, ‘use’, ‘consumption’, ‘behaviour’, ‘prescribe’ and related syntax for all peer-reviewed publications published before June 2020. Health Belief Model was employed for data synthesis.Fifty-four studies were included in the full-text review: 44 quantitative, 5 qualitative and 5 mixed-methods studies. Despite a high AMR awareness, public perception/misconception of antibiotic efficacy and easy access to antibiotics for self-limiting conditions drive inappropriate demand and use in the community including primary care setting. Providers’ prescribing behaviours are influenced by financial incentives, lack of diagnostic capacity and concerns over complications.Inappropriate outpatient and community antibiotic use is influenced by non-biomedical factors at the individual, community, health system and societal levels in mainland China, contributing to a high antibiotic use rate. This study calls for context-tailored One Health interventions, restrictive antibiotic drug policy and multifaceted antibiotic stewardship programmes that simultaneously address drivers of inappropriate use from both the supply-side and demand-side within and beyond clinical settings.CRD42019139591. Human use of antibiotics in China accounts for a quarter of worldwide antibiotic consumption, which mainly takes place in outpatient and community settings.Many of the antibiotic uses were inappropriate and often unnecessarily for self-limiting community-acquired infections.Inappropriate use of antibiotics is prevalent across China with significant regional variation influenced by non-biomedical factors within and beyond clinical settings.Multifaceted, interactive personal and environmental factors shape antibiotic use for both the supply-side and demand-side of China’s healthcare system.Inappropriate antibiotic consumption is unlikely to decrease without multifaceted, context-tailored strategies targeting patients, prescribers and healthcare systems.Future strategies should incorporate an evidence-based, context-tailored design that simultaneously addresses drivers of antibiotic misuse from both the supply-side and demand-side within and beyond clinical settings.For decades, antibiotics have been excessively consumed around the world, contributing to increased antimicrobial resistance (AMR) and negatively impacting health outcomes and expenditures.This mixed-methods review aimed to identify determinants for inappropriate antibiotic use in the community, including primary care and hospital outpatient settings, in Mainland China, Hong Kong and Taiwan. We systematically searched the following databases: MEDLINE, EMBASE, the Cochrane Library, and PsycINFO, Google Scholar and one Chinese database CNKI (China Knowledge Resource Integrated Database), using a combination of the key terms ‘antibiotic’, ‘antimicrobial’, ‘use’, ‘consumption’, ‘behaviour’, ‘prescribe’ and related syntax for all peer-reviewed publications published before June 2020.As a primary outcome of interest, ‘inappropriate antibiotic use’ included unnecessary antibiotic use for self-limiting viral infections (treatment or prophylaxis), self-medication with antibiotics by consumers and unnecessary antibiotic prescriptions for self-limiting viral infections by providers. Relevant behaviour outcomes, such as household storage of antibiotics, over-the-counter purchases and demands for antibiotic prescriptions, were also identified. No restrictions were applied to language, populations or antibiotic use for specific medical conditions. The search strategy for each database is presented in 10.1136/bmjgh-2020-003599.supp1Supplementary dataA standardised form based on Cochrane Review and behavioural theories including the Health Belief ModelBMJ survey appraisal toolsThree reviewers  independently assessed the risk of bias in all included studies using predetermined tools and reached consensus through discussion when discrepancies arose. The quantitative studies and quantitative components from mixed-methods studies that met inclusion criteria were assessed by adapted Patient and public were not involved in this systematic literature review.We identified 54 studies: 37 focused on the consumers of healthcare, 13 on providers and 4 on both, involving a total of 104 619 participants. In The likelihood of being prescribed with antibiotics for presumed self-limiting illnesses during an outpatient clinic visit varied from 53.3%25–27Demand for antibiotic prescriptions from patients and/or caregivers was reported in 21 studies, ranging from 1.8%26 39The practice of self-medication with antibiotics for treatment was widely reported in 32 studies, all in mainland China. The overall prevalence of antibiotic self-medication (for therapeutic purposes) ranged from 7.6%20 28 34 40 41 43 44 48 49 51Patterns were similar for associations withself-medication with antibiotics as prophylaxis—often for URTI to prevent deterioration—measured in 11 studies,5253-56 The geographic location of the pharmacy,52Access to non-prescription antibiotics, either via over-the-counter purchases or household storage, was strongly associated with antibiotic self-medication for therapeutic purposesThe prevalence of household storage of antibiotics ranged from 25.3%Factors of antibiotic use identified from nine qualitative and mixed methods studies56Among the 54 included studies, 11 studies52The results of quality appraisal of the 54 studies were reported in In this systematic review, quantitative synthesis showed that inappropriate antibiotic use is pervasive throughout mainland China, given the relatively easy access to antibiotics, with or without a prescription. Access to non-prescription antibiotics, either via over-the-counter purchases or household storage, was strongly associated with antibiotic self-medication.To the best of our knowledge, this is the first mixed-methods systematic review of the prevalence, measures and factors of antibiotic use across China. This comprehensive review included studies across different regions of mainland China, Hong Kong and Taiwan, published in English and Chinese. It captured statistically assessed factors of actual antibiotic use behaviours by both healthcare providers and consumers, rather than only considering their knowledge, attitudes or intentions in isolation of these influencing factors. We further synthesised the findings using the Health Belief Model, which could identify a critical knowledge gap with a lack of evidence on several key factors on antibiotic use practice see  and infoInappropriate use of antibiotics is influenced by non-biomedical factors within and beyond clinical settings that are unique to mainland China, yet common among low-income and middle-income countries, including public misconceptions,58 Such a phenomenon might be explained by the non-rational strategies people lean on while managing the type of risk and uncertainty associated with an acute infection: so-called tacit or experiential knowledge such as trust, intuition, emotion and prior ‘successful’ experiences with similar symptoms for healthcare decision making.This study found an urgent need to take an evidence-based approach to identify determinants of antibiotic use practices within the target context, programme parameters for improvement and intervention components to optimise the use of antibiotics. These insights will be critical to tailor contextualised, multifaceted interventions for reducing inappropriate antibiotic use. For example, despite the AMR awareness campaigns invested in by the Chinese government, the inappropriate use of antibiotics was found to be prevalent across the country. Moreover, a study reported that well-intentioned government publicity about antibiotic abuse may have had the unintended consequence of increasing antibiotic prescriptions and exacerbating resistance.This review revealed the impact of non-biomedical factors at individual, community, health system and societal levels on outpatient and community antibiotic use by healthcare users and providers in the Chinese context and demonstrated that they impact each other in an interactive manner. Given the large population size and consumption volume, the threat to human health from the adverse side effects of inappropriate use and drug resistance calls for immediate action. This study calls for multifaceted antibiotic stewardship programmes and strictive antibiotic drug policy, with a One Health framework. Future AMR strategies should incorporate an evidence-based, context-tailored design that simultaneously addresses drivers of antibiotic misuse from both the supply-side and demand-side within and beyond clinical settings.


This study investigates the feasibility of collaborative use of recycled carbon fiber reinforced polymer (RCFRP) fibers and recycled aggregate (RA) in concrete, which is called RCFRP fiber reinforced RA concrete (RFRAC). The mechanical properties of the composite were studied through experimental investigation, considering different RCFRP fiber contents  and different RA replacement rates . Specifically, ten different mixes were designed to explore the flowability and compressive and flexural strengths of the proposed composite. Experimental results indicated that the addition of RCFRP fibers and RA had a relatively small influence on the compressive strength of concrete (less than 5%). Moreover, the addition of RA slightly decreased the flexural strength of concrete, while the addition of RCFRP fibers could significantly improve the flexural performance. For example, the flexural strength of RA concrete with 1.5% RCFRP fiber addition increased by 32.7%. Considering the good flexural properties of the composite and its potential in reducing waste CFRP and construction solid waste, the proposed RFRAC is promising for use in civil concrete structures with high flexural performance requirements. With the growing process of urbanization, a huge amount of construction waste is discarded annually, which poses a great threat to the ecological environment. Research of Huang et al.  shows thMany researchers have carried out various attempts to extend the application of RA in civil infrastructures, such as sidewalks, highways, tunnels, and building foundations ,5,6,7,8.Carbon fiber reinforced polymer (CFRP) is a widely used material in automobile, aviation, aerospace, sports equipment, and wind energy industries, owing to its high strength, relatively low density, good dimensional stability, and good corrosion resistance . Since CTo date, some exploratory works have been reported on the development of recycled carbon fiber reinforced concrete. Experimental results show that the addition of a small number of recycled carbon fibers can significantly improve the mechanical properties of concrete ,29. In tFrom the discussion above, it can be concluded that the mechanical properties  of RA concrete are lower than those of conventional concrete, while these strengths can be increased by the addition of carbon or CFRP fibers. Therefore, an eco-friendly RCFRP fiber-enhanced RA concrete is proposed in this study, and the mechanical properties of the composite are examined. Specifically, the design details of different mixes and the adopted test methods are presented in 3. The particle-size distribution of sand is shown in Ordinary Portland cement (OPC) 42.5R was adopted for all concrete mixes. The chemical composition of the selected cement is shown in The nominal size of the coarse natural aggregate (NA) a was betThe RA b was use3, 4292 MPa, 236 GPa, and 92.5%, respectively. The waste CFRP sheets were cut into dimensions of 35 × 2 × 0.2 mm using the shredding machine, as shown in In this study, the RCFRP fibers were recovered from waste CFRP sheets with a thickness of 0.2 mm. The shredding tool shown in The objective of this experiment was to investigate the influence of RA and RCFRP fiber additions on the mechanical properties of concrete. This study maintained the absolute water amount constant for all mixes. Although the nominal water/cement ratios of different mixes were identical, the strong water absorption of RA could result in a lower actual water/cement ratio for mixes with high RA replacement rates. Even though the effects of water absorption of RA were not eliminated, the experiment of RA specimens with the same absolute water amount could still provide useful insights into the synergetic effect of RA replacement rate and water absorption of RA on the mechanical properties of RAC. According to the work of Poon et al. , if the 2, was adopted. The mass ratio of HRWR to cement was 0.194%. The content of each ingredient is given in 3, which was slightly smaller than that of RA0RF0 (2400.5 kg/m3).In this study, RAC mixes with the aggregate replacement rates of 0%, 10%, 20%, and 30% were investigated. To further study the performance of RAC with RCFRP fibers, the representative RA replacement rate of 20% was selected. This is because the 10% RA replacement rate was relatively small, and the effect of saving natural aggregate was not obvious in this replacement rate. Moreover, RA has the characteristic of low density, low wear resistance and compressive strength, high water absorption, and porosity . Too mucThe concrete preparation procedure, based on the Chinese standard , is illuThe flowability of each mix was evaluated through the slump test, according to the Chinese standard . The slufcc is the cubic compressive strength of concrete (MPa), F is the applied peak load, and A is the sectional area of the specimen.A compressive strength test was performed according to the Chinese standard . Three cff is the flexural strength (MPa), F is the maximum applied load (kN), l is the span of the prismatic beam (300 mm), b is the width of the prismatic beam (100 mm), and h is the height of the prismatic beam (100 mm).A flexural test was conducted according to the Chinese standard . In thisThe slump results of different mixes are shown in The compressive strengths of different mixes are illustrated in The compressive strengths of fiber-reinforced concrete and RFRAC specimens with different RCFRP fiber contents are shown in The failure observations of different specimens are shown in The flexural failure patterns of different mixes are presented in The size effect can influence the strength and brittleness of fiber-reinforced concrete materials. According to the work of Nguyen et al. , the fleThe effect of RA replacement rate on flexural strength is given in The flexural strength results of fiber-reinforced concrete and RFRAC specimens are presented in The cross sections of specimens after the flexural test are shown in According to the load–deflection curves in As shown in δ to that when the deflection is δ, where δ is the initial crack deflection. Specifically, the flexural toughness index I can be calculated according to Equation (3).SOAB and SOACD represent the enclosed areas of the load–deflection curve at the deflections of δ and 3.0 δ, respectively; δ is the initial crack deflection; Fcra is the initial crack strength.Flexural toughness can be used to quantify the energy dissipation capability of a material. The method according to the Chinese standard  was adopThe calculated flexural toughness indexes of all mixes are presented in R was used to describe the flexural ductility of the material. As shown in Equation (4), FR represents the residual load at the deflection of 3.0 δ, and FMAX represents the maximum load–bearing capacity.Moreover, the residual load ratio The residual load ratio of all mixes are shown in The above test results show that the RFRAC concrete proposed in this paper exhibited better flexural performance than plain concrete, which makes it promising for use in civil concrete structures with high flexural performance requirements.(1)The addition of RCFRP and RA decreases the flowability of concrete. Specifically, the slump value of specimen RA20RF15 (with 20% of RA replacement rate and 1.5% volume content of RCFRP fibers) is 36.0% less than that of the plain concrete specimen RA0RF0.(2)The proposed concrete composite exhibits similar compressive strength to that of plain concrete. The compressive strength of the fiber-reinforced specimens RA20RF5, RA20RF10, and RA20RF15 are 1.027, 1.005, and 0.958 times that of the reference specimen RA20RF0, respectively.(3)The addition of RA slightly decreases the flexural strength of concrete. For specimen RA20RF0, the flexural strength dropped by 6.7% compared to that of plain concrete. Nevertheless, the addition of RCFRP can largely enhance the flexural strength of concrete. For example, the flexural strength of specimen RA20RF15 increased by 23.8% compared to that of plain concrete.(4)The addition RCFRP fibers can significantly improve the flexural toughness and residual load-bearing capacity of concrete. For RFRAC specimens with 0.5%, 1%, and 1.5% of RCFRP fiber addition, the flexural toughness indexes are 1.32, 1.80, and 2.60 times that of the plain concrete specimen. Furthermore, the residual load ratio of specimen RA20RF15 is 0.69, which is significantly improved compared to the residual load ratio of 0.0 for the plain concrete specimen RA0RF0.(5)The failure patterns of mixes with/without RCFRP fibers are notably different. For the compressive test, the extent of concrete spalling of RFRAC was alleviated compared to RAC and plain concrete mixes, and the RFRAC specimens were still in one piece owing to the bridging action of RCFRP fibers in concrete. For the four-point bending test, the RFRAC specimens remained in good integrity at the ultimate displacement, and the specimen could still sustain the applied load, while the RAC and plain concrete mixes broke into two pieces when a flexural crack occurred.The development and mechanical properties of an eco-friendly concrete composite synthetically combined by RCFRP fibers and RA are experimentally investigated in this work. The proposed concrete composite can make extensive use of waste CFRP fibers and RA, which is beneficial to the environment. Moreover, the addition of RCFRP fibers and RA can significantly improve the flexural performance of concrete. Therefore, the eco-friendly concrete composite RFRAC is promising for use in civil infrastructures with high flexural performance requirements. Detailed conclusions can be drawn as follows:


MET-deregulated non-small cell lung cancer represents an urgent clinical need because of the lack of specific therapies. Although recent studies have suggested a potential role for crizotinib in patients harboring MET gene alterations, no conclusive data are currently available. Therefore, we designed the Co-MET study, a single-arm phase II study to assess the efficacy and safety of crizotinib in patients with advanced non-small cell lung cancers harboring MET gene alterations.Co-MET is an open-label, multi-center, single-arm, phase II trial to assess the safety and efficacy of oral crizotinib in patients with advanced non-small cell lung cancer harboring MET exon 14 skipping mutation (cohort 1) or a high MET gene copy number of ≥ 7 (cohort 2). We will identify MET gene alterations using RT-PCR and/or next-generation sequencing. Oral crizotinib 250 mg BID will be administered until disease progression or unacceptable toxicity. A radiology committee will review tumor scans according to the RECIST criteria. The primary endpoint is the objective response rate. Assuming a null hypothesis of 20% objective response rate and an alternative hypothesis of 50% objective response rate for cohort 1, and a one-sided alpha error of 0.05 and 80% power based on the exact binomial distribution, the required number of evaluable patients is 19. We set the exploratory sample size for cohort 2 at 10 patients.The results of this study are expected to provide evidence regarding the usefulness of oral crizotinib for advanced MET exon 14 skipping mutation-positive or MET high gene copy number-positive non-small cell lung cancer.UMIN000031623 on 3 March 2018.This study was registered with the University Hospital Medical Information Network Clinical Trials Registry as  Non-small cell lung cancer (NSCLC) is a common cause of cancer mortality worldwide. The histological diagnoses include ~ 85% of non-small cell and ~ 15% of cell lung cancers. The majority of patients with NSCLC have a metastatic disease at diagnosis, for which no curative treatment exists. Platinum-based chemotherapies were standard for patients with NSCLC and good performance status. Phase III randomized trials of tyrosine kinase inhibitor (TKI) therapy for EGFR-mutant and anaplastic lymphoma receptor tyrosine kinase (ALK)-rearranged lung cancers have shown documented improvements in response and progression-free survival (PFS) , and TKIc-Met is the tyrosine kinase receptor for hepatocyte growth factor (HGF). Binding of HGF to MET stimulates downstream signal pathways, such as the RAS/ERK/MAPK, PI3K/AKT, Wnt/β-catenin, and STAT signaling pathways. These pathways are known to involve cell growth, migration, angiogenesis, and survival. MET gene alterations, including MET exon 14 skipping mutation-positive or MET high gene copy number, generate oncogenes via activation of c-MET signaling pathway , 6.Crizotinib is a selective ATP-competitive small-molecule inhibitor of c-Met, ALK, and ROS1 (c-ros) tyrosine kinases. Dramatic and durable responses to crizotinib were first reported in mid-2015 in patients with advanced NSCLC harboring MET exon 14 skipping mutation –9. CrizoSince MET-deregulated NSCLC represents an urgent clinical need because of a lack of approved specific therapies, we designed a trial to assess the efficacy and safety of crizotinib in patients with advanced NSCLCs harboring MET gene alterations. The planned protocol will include 29 response-evaluable patients with advanced NSCLC whose tumors contain MET exon 14 skipping mutations or high MET gene copy number. We will use a validated reverse transcription polymerase chain reaction (RT-PCR) and/or NGS assay (multi-screening using oncomine comprehensive assay (OCA) panel) to identify MET gene alterations.https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035817). In this study, academic hospitals where at least one investigator-initiated clinical trial has been conducted in accordance with GCP standards will be recruited. Therefore, this study will be conducted at National Hospital Organization Kyushu Cancer Center, Okayama University Hospital, Hyogo Cancer Center, Nagoya University Hospital, Shizuoka Cancer Center, Kanazawa University Hospital, National Cancer Center Hospital, National Cancer Center Hospital East, and Hokkaido University Hospital, Japan.This is an open-label, multi-center, two cohort, single-arm, phase 2 trial of oral crizotinib in patients with advanced NSCLC harboring MET exon 14 skipping mutation (cohort 1) or high MET gene copy numbers of seven or more (cohort 2) , timing, seriousness, and relatedness. Adverse events are defined as the appearance of (or worsening of any pre-existing) undesirable sign, symptom, or medical condition that occurs after the first dose of the study treatment. Adverse event monitoring should be continued for at least 28 days following the last dose of the study treatment or until the start of subsequent antineoplastic chemotherapy.All data will be recorded in a case report form (CRF) by investigators or clinical research coordinators. The completed CRFs will be submitted to the data center at the Five Rings Company. All study documents will be regarded as confidential. In the data center, the data will be stored and handled in a secure server maintaining the anonymity of participants.In cohort 1, an ORR of 20% is a clinically meaningful threshold for this study. We based the sample size on the exact binomial distribution. Assuming a null hypothesis of a 20% ORR and an alternative hypothesis of a 50% ORR, and a one-sided alpha error of 0.05 (one-side) and 80% power, the required evaluable patients with MET exon 14 skipping mutation-positive NSCLC is 19.We expect cohort 2 to include mostly second- or later-line patients. The ORR of second-line single-agent chemotherapy in that clinical setting is approximately 10%. The ORRs of second- or later-line treatment with PD-1/PD-L1 inhibitor for patients previously treated with platinum-based chemotherapy are 18–20% –15.We determined the sample size for cohort 2 based on the precision of ORR as a primary endpoint.An independent Data and Safety Monitoring Committee has been established to assess the safety data when serious adverse events may occur. A qualified and independent auditor is appointed to audit the trial systems, and the trial was conducted before and during the study in accordance with a written procedure.This clinical trial will adopt clinical trial insurance; if serious harm occurs following the clinical trial, the affected participants will receive appropriate coverage.MET-TKIs being developed target the MET exon 14 skipping+ NSCLCs . With the safety data of crizotinib firmly established, we expect its imminent approval as the first MET-TKI.A sensitive, reliable molecular test should be incorporated into the trial to obtain a compendium of approved diagnostics for MET alterations. Therefore, we allowed enrollment of patients positive for MET exon 14 skipping mutation or high MET copy number of seven or greater, as determined by a validated RT-PCR and/or NGS assay by a designated central testing laboratory (LC-SCRUM) in this trial.If crizotinib demonstrates a meaningful clinical benefit in Japanese patients with MET exon 14 skipping mutation-positive NSCLC in this trial, our results will help crizotinib receive approval for these patients in Japan.In conclusion, our study will evaluate the efficacy and safety of oral single-agent crizotinib for the treatment of advanced MET exon 14 skipping mutation-positive or MET high gene copy number-positive NSCLC.https://www.umin.ac.jp/ctr/index.htm). Recruitment started in March 2018 and is expected to finish in May 2020. The protocol version number is 1.0.The trial has been registered at the University Hospital Medical Information Network Clinical Trials Registry (registration number: UMIN000031623; registration date: 3 March 2018;


Thoracic aortic aneurysm and dissection (TAAD) affects many patients globally and has high mortality rates if undetected. Once thought to be solely a degenerative disease that afflicted the aorta due to high pressure and biomechanical stress, extensive investigation of the heritability and natural history of TAAD has shown a clear genetic basis for the disease. Here, we review both the cellular mechanisms and clinical manifestations of syndromic and non-syndromic TAAD. We particularly focus on genes that have been linked to dissection at diameters <5.0 cm, the current lower bound for surgical intervention. Genetic screening tests to identify patients with TAAD associated mutations that place them at high risk for dissection are also discussed. Thoracic aortic aneurysm (TAA) is a dangerous, deadly, and silent disease that is notoriously difficult to detect and diagnose prior to complications . It is bDue to the difficulty of diagnosing TAA based on symptoms alone, efforts have been undertaken to determine which patients are at higher risk of harboring TAA and therefore, warrant preemptive screening for early diagnosis of aneurysm, monitoring, and appropriately tuned surgical intervention . BecauseTraditionally, TAAD is divided into syndromic—with other organ system abnormalities other than the aorta—and non-syndromic—with no other systemic abnormalities present. Non-syndromic disease is then further subdivided to include familial non-syndromic TAAD, where one or more family members are diagnosed with TAAD, and non-familial TAAD, where no other family members are affected . HoweverSeveral causes of syndromic TAAD are well described, such as Marfan syndrome (MFS), Loeys–Dietz syndrome (LDS), and Ehlers-Danlos Syndrome (EDS) . While tCases of non-syndromic TAA are more prevalent, but identifying these patients can be challenging. Some cases can be explained by mutations in genes involved in syndromic TAAD . ApproxiIn this review, we describe the genetic and molecular mechanisms of common syndromic and non-syndromic manifestations of TAAD, examine the clinical management of both classes of TAAD, and discuss the future applications of genetics to guide the screening, diagnosis, and management of patients. Many genes play a role in the development of TAAD and each requires unique considerations and gene specific surgical intervention guidelines . HoweverSyndromic conditions that cause an increased risk of TAAD have been well described for decades, although the causative mutations have only just recently been verified. Typically, syndromic TAAD is linked to dysfunction of the extracellular matrix (ECM) , medial http://www.umd.be/FBN1/—last updated 28 August 2014). Most mutations in FBN1 are heterozygous but recent evidence suggests that both homozygous and compound heterozygous mutations exists in approximately 0.5% of MFS patients utations . Other mutations ,65. Mousild type . As a reild type . Gastroiild type .COL3A1 or missense variants in the triple helix region may have milder cases of EDS but their vascular risk may remain high [The clinical course of patients with EDS is fraught with complications from unstable vasculature prone to rupture. The median survival for all patients with EDS is 51, with females living slightly longer than males . The medain high . Howeverain high . Prognosain high .BGN (Meester-Loeys syndrome) [EFEMP2  [ELN  [SLC2A10  [Several other genes have been linked to developing cases of syndromic TAAD, including yndrome) , EFEMP2 type Ib) ,74, ELN AD type) , and SLCyndrome)  among otyndrome) . TherefoUnderstanding the causes of non-syndromic TAAD has advanced significantly after decades of study. Because 21% of TAAD patients have another family member that is affected, positive family history significantly increases the severity of TAAD and the likelihood of aortic dissection . A genetFBN1 as previously discussed) are also known to cause non-syndromic TAAD [Familial TAAD appears to be more virulent than sporadic TAAD: age at first presentation is younger (58.2 vs. 65.7) and growth rates are faster (0.21 vs. 0.16 cm/year) . The tenmic TAAD  without mic TAAD ,84. Simimic TAAD .Sporadic TAAD remains a challenge to detect, diagnose, and manage, as many cases do not have as clear a link to genetic causes as familial or syndromic TAAD. Approximately 10% of early age sporadic aortic dissection cases have a mutation in causative syndromic or familial TAAD genes . In totaHere, we review the aforementioned four genes that cause TAAD at aortic diameters <5.0 cm and briefly discuss other genes that have been linked to non-syndromic TAAD and sporadic TAAD.ACTA2 encodes SMC specific α-actin, which polymerizes to form thin filaments in the smooth muscle contraction element [ACTA2 is the most common mutation linked to familial TAAD, with about 50% penetrance and accounts for between 12% and 21% of all cases seen, by far the most common genetic defect linked to familial TAAD to date [ element . ACTA2 i to date ,84,88,89 to date . The med to date . HoweverACTA2 mutations that have been identified are DN mutations that prevent proper polymerization of actin or ATP hydrolysis that mediates SMC contraction [ACTA2 mutant patients are characterized by proteoglycan accumulation, decreased and disorganized SMCs, and fragmented elastic fibers [ACTA2 mutations cause [ACTA2 does not lead to aneurysm [A majority of the traction . Missenstraction ,91. Aortc fibers . Increasns cause . Patientns cause ,93. Thisns cause . Surprisaneurysm ; aneurysaneurysm .ACTA2 mutations tend to cause aortic dissection without preexisting aneurysm. As a result, one third of patients with ACTA2 mutations have acute Type A dissections at aortic diameters <5.0 cm [ACTA2 mutants are at even higher risk of small-diameter dissection, with dissections occurring between 3.8 and 4.7 cm in one study [ACTA2 mutations are therefore recommended for surgical intervention between 4.5 and 5.0 cm.Notably,  <5.0 cm . Pregnanne study . PatientMYLK, is another gene that has been causatively linked to non-syndromic TAAD. MLCK is known to phosphorylate regulatory light chain (RLC), which, in turn, increases myosin II ATPase activity, endocytosis, and stress fiber response [Myosin light chain kinase (MLCK), encoded by response . Phosphoresponse .MYLK mutations were shown to produce a significant reduction in MLCK activity via a HI mechanism that decreased MLCK activity by 85%, resulting in impaired SMC contraction [MYLK mutations associated with TAAD have lower penetrance compared to other syndromic and non-syndromic mutations; only 38% of mutant individuals in one study experienced aortic events [Two traction . Furthertraction . Althougtraction . In termtraction . Anothertraction . MYLK muc events .Due to a high risk of dissection at diameters <5.0 cm, the current guidelines suggest surgical intervention between 4.5 and 5.0 cm. Further prospective validation regarding this suggestion is needed.MYH11 encodes smooth muscle myosin heavy chain (SM-MHC), a contractile component produced by SMCs [ACTA2, mutations in MYH11 results in dysregulation of SMC contraction, which is critical for maintaining aortic wall stability. by SMCs . Much liMYH11 mutations are thought to cause 1% of all familial TAAD cases [MYH11 mutations reveals focal fibromuscular dysplasia in the vaso vasorum, which may be suggestive of an inflammatory immune response consistent with what has been observed in other TAAs [MYH11 mutations did not segregate with TAAD in one Dutch pedigree, suggesting that other unidentified genetic modifiers may play a role in the development of aneurysm [AD cases . This isAD cases ,105. SpeAD cases  and evidAD cases . Histoloher TAAs ,106. In her TAAs . One stuaneurysm ,104.PRKG1 encodes the type I cGMP-dependent protein kinase (PKG-1), which controls SMC contraction by regulating phosphatases that dephosphorylate the RLC [ the RLC . The maj the RLC . A gain- the RLC . This ac the RLC . Recentl the RLC .PRKG1 mutations are limited but suggest a devastating aortic phenotype. In the one variant that has been identified to cause TAAD, penetrance of dissection is high (63%) and aortic enlargement was seen as good (37%). The average age at dissection was 37 years old, with the youngest occurring at 17 [Clinical data on ng at 17 . Similarng at 17 . Of the ng at 17 . TherefoFOXE3) [LOX) [MAT2A) [MFAP5) [NOTCH1) [Many other genes have been implicated in familial TAAD. These include the forkhead transcription factor (FOXE3) , lysyl o3) [LOX) , methion [MAT2A) , microfi [MFAP5) , and not[NOTCH1) . AlthougROBO4 (roundabout guidance receptor 4), a gene that contributes to endothelial function [Work over the past five years has identified additional genes that have implicated in causing familial TAAD. These include function , ARIH1 , a protein involved in endocytosis and intracellular signaling, and unc-51-like kinase 4 (ULK4), involved in endocytosis and axon growth, were also identified in another large cohort study, further suggesting that other genes may play a role [CLU (Clusterin), DES (Desmin), MYH10, and FBLN5 (Fibulin 5)—related to sporadic TAA [TGFBR, COL3A1, SMAD, ACTA2, TGFB2, or TGFBR2), indicating that genetic screening would benefit these patients and their families [Recent work investigating the genetic risk factors of sporadic TAAD has generated further insights into this seemingly random disease that accounts for a large majority of cases of non-syndromic TAAD . A cohorfor TAAD . Novel vy a role . A recenadic TAA . Anotherfamilies . In addifamilies . Therefofamilies .Due to the virulence of TAAD, early detection, diagnosis, and intervention for high risk aneurysms would significantly decrease the morbidity and mortality that is observed upon dissection ,123,124.Genetic panels conducted via Sanger sequencing that directly sequence known causative genes for TAAD were once considered the standard of care to identify high risk patients . HoweverResults from these studies show that between 71% and 87% of all patients screened did not have medically meaningful mutations, either likely benign or benign ,131,132.LOX gene showed a 16% decrease in enzymatic activity compared to wild type while known pathogenic variants showed up to a 50% decrease in activity. Similar results were seen in the MYLK gene. However, other VUS did not show a phenotype in animal models. The authors conclude that a new category—low-penetrant “risk variants”—may be appropriate to capture this kind of variable influence on patient phenotypes [Of particular note for VUS related to TAAD genes, recent evidence suggests that many variants that are classified as VUS may be pathogenic in a low-penetrant and less damaging fashion than pathogenic variants . For exaenotypes . In summenotypes .Another potential genetic test to identify TAAD involves quantifying RNA signatures in the blood as a biomarker and screening tool. In a study with 94 individuals, RNA signatures were able to classify TAAD patients compared to controls with high sensitivity (72%) and specificity (90%) . This apmiRNAs (MicroRNAs) have also been investigated as biomarkers for TAAD. In a recent study, an miRNA microarray assay identified miR-574-5p as a biomarker that was successfully able to differentiate between TAA patients and controls in a small cohort . AnotherDetermining the indications for routine genetic testing to detect thoracic aneurysms will need to consider the aforementioned limitations. One potential screening program is outlined in When doing genetic testing, it is important to remember that several genes that predispose patients to higher risk for TAAD also places patients at risk for other arteriopathies, such as AAA, cerebral aneurysms, or coronary artery aneurysms. Some genes that have been specifically implicated in causing other arteriopathies outside of the thoracic aorta include FBN1, LOX, PRKG1, SMAD2, SMAD3, TGFB3, TGFBR1, and TGFBR2, although experimental evidence is weak for some genes ,142,143.FBN1 as the causative variant for MFS [Dramatic strides have been made in understanding the underlying genetic risk factors for TAAD in the past three decades since the discovery of  for MFS . Since t for MFS , elucida for MFS ,145.


Higher antibiotic consumption was associated with poor or very poor self-perceived health status, no polypharmacy and not having been in hospital during the previous twelve months, while a lower consumption was linked to being limited but not severely due to a health problem and not being at all limited.Elderly people are a particularly important population with regard to antibiotic overuse, using around 50% more antibiotics per capita than younger adults. The aim of this study was to analyze the prevalence, associated factors and evolution over time of antibiotic consumption among the Spanish population aged ≥ 65 years from 2006 to 2017. A descriptive cross-sectional study was conducted using data from the Spanish National Health Survey in 2006, 2011/2012 and 2017, and from the European Health Survey in Spain in 2009 and 2014. The sample consisted of 26,891 non-institutionalized individuals ≥ 65 years. Antibiotic consumption was the dependent variable, and sociodemographic variables, lifestyle habits and health status were analyzed using a logistic regression model. The prevalence of antibiotic consumption was 4.94%, with a marked increase from 2006 (4.64%) to 2017 (5.81%) ( Antibiotics are essential drugs in the prevention or treatment of microbial infectious processes . NeverthInappropriate antibiotic therapy in older people entails significant risks and potentially adverse consequences, including the risk of drug interactions, side effects related to age or disease-related changes in metabolisms, as well as risks associated with multidrug-resistant organisms and Clostridium difficile infections ,11,12. IBetween 2000 and 2015, the consumption rate of antibiotics increased 39% globally . AccordiIn view of this situation, a number of studies have investigated the role of sociodemographic and clinical factors in the increasing antibiotic consumption around the world, so that prompt action aimed at encouraging appropriate antibiotic use can be taken ,18,19,20A cross-sectional study was carried out from December 2019 to February 2020 using the data obtained from the records of the Spanish National Health Survey (SNHS) 2006 , the EurThe sample was representative of the older population residing in Spain and, originally, consisted of 33,306 subjects, but due to a lack of data for some of the variables studied, 6415 (19.26%) were excluded when the descriptive, bivariate and multivariate statistical analyses were carried out. For the current study, the total sample of participants numbered 26,891: 5322 in 2006; 4125 in 2009; 5244 in 2011/2012; 5862 in 2014; and 6338 in 2017.2), normal-weight (BMI ranged between 18.50– and 24.99 kg/m2), overweight (BMI ranged between 25.00 and 29.99 kg/m2), and obesity (BMI ≥ 30 kg/m2). To identify subjects with an associated chronic condition, we used the self-reported affirmative answer to the presence of any of the following physician-diagnosed diseases : arterial hypertension, hypercholesterolemia, asthma, chronic bronchitis, diabetes and cancer.The dependent variable was “antibiotics consumption”. This variable was assessed through the question “Have you taken antibiotics during the last two weeks?”. Participants who answered “yes” were considered consumers of antibiotics. The independent variables were: year of the surveys , gender , age , level of education , marital status , nationality , size of town of residence . The variables related to lifestyle and health status used in the study were self-perceived health , currently smoking , consumption of alcoholic beverages in the two weeks prior to the survey , hospitalization during the past twelve months , degree of limitation due to a health problem for at least six months  and polypharmacy . Polypharmacy was calculated using an identical question in all the questionnaires: “From the following list of types of medication, please tell me which one(s) you have consumed in the last two weeks?”. Subjects were classified as polypharmacy if they answered “yes” in five or more different medication groups . Although no consensus has yet been reached on the number of medications that must be consumed to be considered polypharmacy, this figure (five medications) has been used in recent studies conducted in different countries ,30,31. TThe data obtained from these surveys are available in the National Institute of Statistics and Ministry of Health, Consumer Affairs and Social Welfare websites ,26,27,28p ≥ 0.15 . All the hypothesis contrasts were bilateral and in all the statistical tests, those with a 95% confidence level (p < 0.05) were considered significant values. The statistical power for all analyses conducted was 80%. The statistical analysis was carried out using IBM SPSS Statistics version 25 , licensed to the University of Córdoba and University of Seville.A descriptive analysis was performed by calculating the counts and percentages for the qualitative variables. The proportions of categorical variables were compared using the chi-square test for contingency tables or Fisher’s exact test if the number of expected frequencies was greater than 5. In addition, a logistic regression was performed to identify the variables associated with antibiotic consumption. All variables with a significant association in the bivariate analysis were included in the multivariate analysis. Raw and adjusted odds ratios were calculated with 95% confidence intervals. The Wald statistic was used to exclude one by one from the model any variables with a Of the 42,157 subjects aged ≥ 65 years who were invited to participate in the SNHS 2006, EHSS 2009, SNHS 2011/2012, EHSS 2014 and SNHS 2017, 8851 individuals were excluded due to the following reasons: 383 refused to participate, 268 were absent from their homes and 23 were unable to participate in SNHS 2006; 1213 refused to participate, 825 were absent from their homes and 83 were unable to participate in EHSS 2009; 1488 refused to participate, 931 were absent from their homes and 71 were unable to participate in SNHS 2011/2012; 154 refused to participate, 40 were absent from their homes and 28 were unable to participate in EHSS 2014; 1841 refused to participate, 1435 were absent from their homes and 68 were unable to participate in SNHS 2017. Thus, the study was based on data from 33,306 individuals who accepted to participate. Of them, a total of 6415 (19.26%) not answered, at least, one variable, so that they also were excluded. In that sense, in SNHS 2006, 2520 individuals were excluded who did not answer to the following variables: antibiotic consumption (1.47%), level of education (0.84%), BMI (65.20%), marital status (0.39%), nationality (0.32%), polypharmacy (30.01%), chronic condition (1.05%) and consumption of alcoholic beverages (0.74%). In EHSS 2009, 1900 individuals were excluded who did not answer to the antibiotic consumption (0.31%), level of education (0.53%), BMI (40.43%), marital status (0.22%), polypharmacy (6.42%), chronic condition (0.22%), currently smoking (25.95%) and consumption of alcoholic beverages (25.92%). In SNHS 2011/2012, 652 individuals were excluded who did not answer to the antibiotic consumption (0.42%), BMI (86.35%), marital status (0.97%), polypharmacy (8.64%), chronic condition (0.70%), currently smoking (1.25%), consumption of alcoholic beverages (1.11%), hospitalization over the past twelve months (0.28%) and degree of limitation due to a health problem (0.28%). In EHSS 2014, 658 individuals were excluded who did not answer to the antibiotic consumption (1.17%), BMI (71.43%), marital status (0.70%), polypharmacy (21.66%), chronic condition (1.29%), currently smoking (1.64%), consumption of alcoholic beverages (1.87%) and degree of limitation due to a health problem (0.24%). In SNHS 2017, 685 individuals were excluded who did not answer to the antibiotic consumption (0.26%), BMI (83.72%), marital status (1.42%), polypharmacy (10.21%), chronic condition (0.90%), currently smoking (1.55%), consumption of alcoholic beverages (1.81%) and degree of limitation due to a health problem (0.13%).n = 15,865) women and 41%  men between 65 and 104 years old. The most frequent sociodemographic, lifestyle and health status characteristics of the participants were that they were married (51.90%), lived in towns with a population of over 100,000 inhabitants (41.70%), had no studies (44.67%), were Spanish (97.55%), had a fair self-perceived health status (35.03%), had no polypharmacy (78.53%), had, at least, one chronic condition (71.73%), were overweight (43.78%), were not current smokers (88.23%), had not consumed alcohol in the last two weeks (65.06%), had not been in hospital during the last twelve months (86.25%) and did not report any limitation due to a health problems in the last six months (57.50%).Finally, the total sample was 26,891 records of older people, including 59% (p < 0.0001). There was also a decrease in the number of participants who were overweight .Regarding the sociodemographic, lifestyle and health status variables of the sample according to the year of the survey , a decrep < 0.0001)  .p < 0.01) and currently being a non-smoker . A lower prevalence of antibiotic consumption was found in participants who had a very good self-perceived health status , had no chronic diseases , were severely limited  or had been in hospital in the last twelve months . In the multivariate analysis, from the year of 2014, the probability of antibiotic consumption in older people was higher than in 2006 and also in those had not been in hospital in the last twelve months. This probability was more than double in participants with no polypharmacy and a poor or very poor self-perceived health status. In contrast, a clear downward trend was observed in the probability of antibiotic consumption as the degree of limitation due to a health problem decreased. The antibiotic consumption is distributed differently according to the sociodemographic, lifestyle and health status variables . The bivThe overall prevalence of antibiotic consumption in older people from 2006 to 2017 in Spain was 4.94%. This percentage was lower compared to previous studies conducted among the non-institutionalized elderly population, which ranged from 11% to 45%, with a significant rise over the past decade ,34,35,36The trend of increases in antibiotic use from 2006 to 2017 among older adults shown in our study supports previous reports ,38. One Although women are about 27% more likely than men to receive antibiotic prescriptions due to the greater frequency of symptomatic infections of the urinary tract in women than in men, genetic and the over-use of primary healthcare services by women , this waDespite the fact that we did not find any relationship between the BMI and antibiotic consumption, people who are overweight or obese are more likely to acquire an infection and thus need antibiotics compared with normal weight adults ,60. As fAlthough hospitalization has been reported as a risk factor for antibiotic consumption , in our The results of this study should be taken into consideration by health authorities when designing (or improving current) guidelines and strategies for promoting the correct use of antibiotics, especially considering the elderly population. Improving antimicrobial stewardship is an international priority due to the evolving threat of antibiotic resistance. Continuous reassessments of the medication regime and current clinical status of older people by physicians and nurses are required to avoid the increase of antibiotic consumption and resistance.The present study also has some limitations. First, due to the cross-sectional design, it is not possible to assign causality between the variables. Second, it should be remembered that the data collected in the survey was obtained indirectly from the informants’ self-reporting, which can be affected by memory and/or social desirability bias. Third, individuals can overestimate or underestimate their antibiotic consumption due to the self-reported measure of antibiotic consumption. Fourth, it was not possible to take into account the influence of seasonal factors in the antibiotic consumption and elderly people in institutions or hospitals have not been included. Fifth, since neither the SNHS not the EHSS identified specific active pharmaceutical ingredients (only groups of medicines for specific diseases or disorders) or the adequacy of antibiotic prescription, it would be advisable to include specific active pharmaceutical ingredients and a correct assessment of antibiotic prescription in future studies. Sixth, the amount of the total variance explained by the logistic regression model was modest, suggesting the importance of additional variables not explored by the different surveys. Seventh, BMI was calculated from height and weight reported by the participants, which may not be accurate. Lastly, although participation rate was relatively high, a non-participation bias cannot be ruled out, as it was not possible to compare the characteristics of the patients included in the study and those of who did not consent to participate. One strength of our study is that since the data were derived from a national survey, they have been obtained using carefully planned methodology, including sampling, well-designed forms, preparation of the survey participants, and supervision of the survey and filtering of the data, all of which guarantee a representative sample of the population.In conclusion, the prevalence of antibiotic consumption in the Spanish population aged ≥ 65 years increased significantly from 2006 to 2017 and is still within the normal range of consumption. Nonetheless, it could potentially become a serious public health concern if the trend of antibiotic consumption continues to increase over time. The probability of antibiotic consumption is higher in older people with poor or very poor self-perceived health status, no polypharmacy and who had not been in hospital in the last twelve months, and is lower as the degree of limitation due to a health problem decreases.


Garcinia mangostana L.), as a natural source of bioactive phytochemicals, is a potential AGP, but the effect of mangosteen-based treatment on antibiotic resistance in poultry has not been reported to date. Therefore, the aim of this study was to evaluate the effects of mangosteen peel extract as an AGP on body weight gain, feed conversion rate (FCR), and the antibiotic resistance in broilers.Antibiotic resistance poses a risk to human health and has therefore been the focus of research. One of the causes of this resistance is the use of antibiotics as feed additives for animal nutrition. The development of antibiotic resistance in poultry through nutrition feed has drawn attention to the need for alternative antibiotic growth promoters (AGPs). Mangosteen  was not administered any treatment in the feed, Group B was treated with 0.3 g/kg colistin as the AGP in the feed, and Group C was treated with 2% mangosteen peel extract as the AGP in the feed; the treatments were administered for 30 days. The observed parameters included the effect of the treatments on body weight gain, feed intake, FCR, and the presentation of antibiotic resistance before and after the treatments .Post-treatment, the body weight gain, and feed intake in the broilers were not significantly different among all the groups; however, the body weight gain and FCR were significantly different between the control group and the treatment groups in the 3rd week of treatment and were not significantly different between Groups B and C. The rate of antibiotic resistance to chloramphenicol increased significantly by 40% in Group B post-treatment, but no such increase was observed in Groups A and C.The findings of our study indicate that compared with using colistin as an AGP using mangosteen peel extract as a natural AGP did not have any significantly different effect on body weight gain, feed intake, and FCR (p>0.05) but had a significantly different effect on the rate of antibiotic resistance in broilers (p<0.05). This study indicates the usefulness of mangosteen for improving the overall growth and production performance of broilers without increasing their antibiotic resistance. Escherichia coli had increased to 52% in Indonesia [Antibiotic resistance is a serious global concern that has become a major challenge in human and animal research . In the ndonesia . Antibiondonesia . In the Based on the data of the application of antibiotic growth promoters (AGPs) in animal production consist neomycin, erythromycin, oxytetracycline, streptomycin and colistin, particularly in chicken production, the global consumption of antimicrobials has been predicted to increase by 67% between 2010 and 2030 ,6.Garcinia mangostana L.) peel, which comprises bioactive phytochemicals such as xanthones, benzophenones, flavonoids, bioflavonoids, phenols, and triterpenes [The development of antibiotic resistance in chickens has drawn attention to the need for alternative AGPs. AGPs from natural sources could play a key role in improving the growth and production performance of chickens. One of the natural plant sources that can be used as AGPs is mangosteen , feed intake, and antibiotic resistance in broilers.All experiments of this research study were approved by the ethical committee of our institution (reference number: 00034/04/LPPT/VII/2019).in vacuo using Rotary Evaporator . The extract was stored in a refrigerator.The mangosteen peel extract was prepared, as described previously . BrieflyThe study was conducted from June to August 2019 at Department of Microbiology, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia.A total of 30 1-day-old broiler chicks (Cobb500) were divided into three groups. The chicks were kept for seven days to acclimatize. Within this period, they were fed commercial broiler starter diet only and given plain water. The number of 1-day-old chicks included in this study was calculated, according to Federer’s method . Group AEight standard antibiotic disks for ciprofloxacin, colistin, amoxicillin, streptomycin, chloramphenicol, tetracycline, ampicillin, and gentamicin were used against the isolated bacteria after the preparation of standardized bacterial inoculums matching the 0.5 McFarland standards (2×108 cfu/ml). The inoculum was spread on sterile Mueller-Hinton agar plates and incubated at 37°C for 24 h. The degree of sensitivity was determined by measuring the inhibition zone diameter, as described previously ,16. The The quantitative data from the different treatments in this study were statistically analyzed using analysis of variance (ANOVA), Kruskal–Wallis test, and marginal homogeneity test with p<0.05 were considered statistically significant.The results of the Kruskal–Wallis test showed that all the groups did not show significant differences in feed intake (p>0.05), but the control and the treatment groups showed significant differences in FCR in the 3rd week (p<0.05) . HoweverThe marginal homogeneity test showed that the broilers who were treated with colistin as an AGP (Group B) showed a significant increase in the rate of antibiotic resistance to chloramphenicol (p<0.05) between pre-treatment and post-treatment. However, the broilers who were treated with 2% mangosteen peel extract (Group C) did not show any increase in the rate of antibiotic resistance .st, 2nd, and 4th weeks of treatment; therefore, their nutritional efficiency was considered low because of the pathogenic microorganisms that remained in the digestive tract. This finding is similar to that reported by a previous study [The present study analyzed the effects of adding mangosteen peel extract to broiler feed on body weight gain, feed intake, FCR, and the presentation of antibiotic resistance. Colistin is widely used as a growth promoter in poultry production, but with the increasing incidence of antimicrobial resistance, natural sources such as mangosteen have been explored for their potential as AGPs. We found that the control and treatment groups showed significantly different body weight gain in the 3rd week of treatment. This finding is similar to that reported by a previous study , whereinus study  stating The rate of antibiotic resistance to ciprofloxacin, colistin, amoxicillin, streptomycin, tetracycline, ampicillin, and gentamicin pre-treatment and post-treatment was not significantly different (p>0.05) among all the groups. However, the rate of antibiotic resistance to chloramphenicol in Group B (colistin-treated group) was significantly different (p<0.05) from that in Groups A and C. The rate of resistance to chloramphenicol increased by 40% after the administration of colistin. This finding is consistent with that reported by a previous study , whereinAntibiotic resistance can occur through various mechanisms such as antibiotic inactivation, membrane permeability reduction, antibiotic target modification, and antibiotic transport modification . Furtheret al. [E. coli isolated from 1-day-old chicks showed resistance to penicillin and ciprofloxacin. A previous study [et al. [E. coli isolated from 1-day-old chicks is resistant to antibiotics, including tetracycline, ampicillin, gentamicin, enrofloxacin, ciprofloxacin, and streptomycin, with rates of antibiotic resistance reaching >80%.In this study, the rate of antibiotic resistance to chloramphenicol was found to be increased in the treatment group with colistin added as an AGP. According to a previous study , the admet al. , who shoet al. , whereinus study  has show [et al. , who shoAs stated previously , the preThe findings of our study suggest that compared with colistin, mangosteen peel extract used as an AGP did not have any significantly different effects on the body weight gain and FCR of broilers. However, the mangosteen peel extract significantly affected the antibiotic resistance of broilers. While the colistin-treated group showed a significant increase in the rate of antibiotic resistance to chloramphenicol post-treatment, no such increase was observed in the mangosteen peel extract-treated group, indicating significant differences in the rate of antibiotic resistance between these two groups. Therefore, mangosteen peel extract can be considered a useful natural AGP that can promote the growth and production performance of broilers without increasing the rate of antibiotic resistance.OH and TU designed and managed the study. OH and MA collected and analyzed samples. SA, OH, TU, and MA arranged, analyzed, and wrote the manuscript. All authors have read and approved the final manuscript.


An RFID-based wireless system to measure the evolution of the setting process of cement-based materials is presented in this paper. The system consists of a wireless RFID temperature sensor that works embedded in concrete, and an external RFID reader that communicates with the embedded sensor to extract the temperature measurement conducted by the embedded sensor. Temperature time evolution is a well known proxy to monitor the setting process of concrete. The RFID sensor consisting of an UWB Bow Tie antenna with central frequency 868 MHz, matched to the EM4325 temperature chip through a T-match structure for embedded operation inside concrete is fully characterized. Results for measurements of the full set up conducted in a real-scenario are provided. Concrete is the most widely used construction material in the world. Appropriate monitoring of its setting process is necessary to guarantee that it has reached the required structural strength. Having reliable procedures to assess the state of the setting process on-site and in a non-invasive way, can be helpful in speeding up the construction process through an accurate prediction of formwork stripping, post-tensioning, and opening pavement to traffic times. This is also true in the manufacturing of precast concrete structures in which demolding can be done once the setting process is advanced to the point that the structure can self-sustain and as a consequence molds can be reused at a higher pace and production can increase.In , it is sIn this paper a small-size low-cost RFID sensor designed to be embedded into concrete to monitor the setting process is presented. The operation principle is based on the known correlation between temperature peaks that occur in the concrete mixture and the evolution of the hydration process. When cement, water, aggregate, and additives are mixed together, a significant heat increase occurs due to the exothermic process in the reaction between cement and water (hydration reaction), once the strong exothermic process is completed (1–3 h) the temperature decreases and stabilizes providing an estimation of the mechanical strength reached by the concrete sample. Hence, by measuring the temperature evolution of a concrete sample it is possible to assess the maturity and therefore the strength of a concrete sample throughout its setting process. The most significant temperature changes take place during the first 12 h of the reaction ,11.The sensor is designed to sample the temperature and record a temperature log that can be wireless read by a commercial RFID reader. The analysis of the temperature evolution provides an indication of the setting process of the concrete. Due to its small size and low cost, sensors can be embedded into the concrete while it is poured. Its data logging features allow an asynchronous reading of the sensors. As shown in , in the The paper is organized as follows: The RFID wireless system to monitor the internal temperature of concrete sample during the setting reaction is structured as depicted in the block diagram in When designing a RFID sensor to work embedded in a medium whose properties change over time, there are certain constrains that must be taken into account as they will have an impact on the performance of the device that cannot be neglected.From an industrial point of view, it is desired to come up with a design that is as compact and small as possible. In the construction industry for example, robustness is a must, as a device embedded in a block of concrete has to withstand a tremendous amount of weight and pressure. Taking this into account, a thin planar design is quickly off the table, and a shift towards a more “rock-like” device is preferred as it mimics the shape of aggregates already present in concrete mixtures. A considerable amount of water will be present at the first stages of the setting process of concrete, so it is important to assure that the device is waterproof to prevent damage on the electronics. Nevertheless, the main goal of this device is to monitor the temperature of the surrounding medium, which implies that the sensor must be exposed to the medium somehow for accurate temperature measurement. RFID tags, typically operate as passive devices, which means that they are powered by the RF energy transmitted from a reader. However when they incorporate “sensing” capabilities, working in battery operated mode generally provides more processing capabilities and higher reading range and reliability. The RFID sensor layout must be then designed in a way that simultaneously ensures compactness and robustness, isolation, and an accurate temperature measurement.The EM4325 RFID chip is a Radio Frequency Identification Integrated Circuit from EM Microelectronic that can be either battery powered or beam powered by RF (Radio Frequency) energy transmitted from a reader. In a Battery Assisted Passive (BAP) configuration, the EM4325 chip offers better sensitivity (−30 dBm) that translates into a superior reading range, compared to purely passive operation. When designing sensors intended to operate inside of lossy materials, as it is the case of concrete, maximizing the Dynamic Range (DR) between the transmitting and receiving antenna is of great interest to cope with the high propagation losses produced as a consequence of concrete’s attenuation. This can be either achieved by increasing the transmission power, or as done in this case, by improving the sensitivity of the embedded passive device. The integrated temperature sensor supports temperatures in the range of −40 lacement .The EM4325 RFID chip does not include the capability of storing temperature measurements. Meaning that these should either be acquired on demand, or by installing a micro-controller. For the current application, the chip has been configured to operate as a radio-frequency front-end and to perform on demand temperature readings when requested by the external reader.This chip, when configured in BAP operation mode, has an input impedance of FID chip ,15.In order to provide the aforementioned required compactness and robustness, the proposed design is printed on top of a bendable substrate of 0.125 mm thickness from Rogers (An important factor when assessing the performance of the antenna is the Impedance Coupling Factor (ICF), computed as:It is known from  that the4 and 18 .To enable the temperature sensing capability of the chip, a small hole is drilled on the section of the cylinder that acts as a “cover” for the T-match and chip. This hole is placed right on top of the chip and has dimensions equivalent to those of the sensor. Then a small aluminum cylinder is placed right on top of the temperature sensor b. One faTo assure that the whole device is completely isolated from the surrounding medium, the sensor is dipped in a liquid solution of PlastiDip and an air-dry rubber solution is applied to provide at the same time for protection and isolation to the RFID sensor. The Nordic ID eNUR-10W reader The patch antenna connected to the Nordic eNUR reader has a 9 dBi gain and a bandwidth ranging from 840 MHz to 960 MHz b. It hasThe software in charge of establishing, controlling, and monitoring communication between the reader and RFID sensor has been developed by WiTekLab following Nordic ID semiconductors’ recommendations for the development of software solutions for their RFID Embedded Reader Modules.When the reader is connected to the computer and powered on, the control software scans for tags within the reading distance of the RFD reader, and displays parameters such as tag configuration, sensor data, and current temperature. As the EM4325 sensor does not have the capability of storing temperature measurements, the software tracks the temperature readings of a given tag, and stores it on a CSV file in the computer.The propagation loss between a RFID sensor located inside a concrete structure, and a RFID reader placed outside is represented through Equation . This exIn , the firrding to ) and it We have extracted from  the relaEquation . The radFrom The RFID temperature sensor characterized in the previous section , has beeA total of four sensors were placed inside two wooden containers. Two sensors were inserted at the center of each container , by placing the reader’s antenna right next to the interface with the container. The input power received at the time from this sensor was −62 dBm. Twenty-four hours later, the sensor located at mid-height next to the corner (s3) was also detected. At this time, the input power received from this sensor was −60 dBm, while the one received from s4 had risen to −50 dBm.The sensors located at the center of the concrete containers (s1 and s2) were not detected during this test. We were able to retrieve them after concrete compression tests had been conducted, and it was possible to find out that the concrete’s chemical corrosive effect had in fact damaged the isolating rubber covering the sensors, water had then leaked to the electronics and permanently damaged the sensor.The results exhibited in The results of the peak temperature values achieved during the first hours of the hydration reaction in The good agreement between the temperature read obtained with the thermocouples and that obtained with the RFID sensor, and the fact that it was possible to maintain a stable communication link between the embedded sensor and the external reader, are proof of the feasibility of transmitting a microwave signal in this kind of scenario without it being interfered by the attenuation and changing dielectric properties inherent of cement-based materials. These results are in agreement with those presented in , where tOnce validated, the feasibility of the proposed RFID system for wireless monitoring of the setting reaction produced in concrete over time at 0.868 GHz, it could be of interest for potential designers to compare the attenuation parameter TMUT see  obtainedThe results presented in this manuscript are proof of the possibility of employing wireless technology to remotely monitor the physical and chemical processes produced during the setting reaction of concrete using temperature measurements as a proxy for the evolution of a hydration process that occurs during the setting of concrete. This information can be of use at construction sites to reduce construction time, as well as for safety purposes such as building’s structural strength monitoring.The reading distances obtained during in-field measurements were in line with the propagation attenuation values employed for propagation loss over distance in air estimation. This means that available data to describe this communication scenario accurately represents the real propagation conditions.The results presented in this paper for the proposed RFID sensor validate its adequacy for remote wireless monitoring of the hydration reaction of concrete during its curing process by means of a stable temperature measurement conducted with a fully-embedded wireless RFID sensor. The wide band capabilities of the presented device make it possible to set up a precise and stable communication link with an external reader from the beginning of the hydration reaction, which validates that the sensor remains well matched despite the change produced in the dielectric properties of a concrete mixture throughout the setting reaction.This system using active RFID technology can be easily adapted to integrate further sensors to the electronics of the embedded device  and conduct a broader characterization of the physical and chemical properties of the concrete sample. By tuning the energy consumption of the RFID device, it is also possible to conduct long term monitoring of the medium. The same wireless system can also be used in other construction materials such as self-leveling mortar for similar purposes.The patent entitled “SISTEMA DE TRANSMISIÓN ENTRE UN MEDIO DE TRABAJO Y UN MEDIO DE DESTINO CON DIFERENTES PERMITIVIDADES” with application number P202030087 is currently being processed.