Ecological and individual-level evidence indicates that there is an association between level of antibiotic exposure and the emergence and spread of antibiotic resistance. The Global Point Prevalence Survey in 2015 estimated that 34.4% of hospital inpatients globally received at least one antimicrobial. Antimicrobial stewardship to optimise antibiotic use in secondary care can reduce the high risk of patients acquiring and transmitting drug-resistant infections in this setting. However, differences in the availability of data on antibiotic use in this context make it difficult to develop a consensus of how to comparably monitor antibiotic prescribing patterns across secondary care. This review will aim to document and critically evaluate methods and measures to monitor antibiotic use in secondary care.We will search Medline (Ovid), Embase (Ovid), Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials and websites of key organisations for published reports where an attempt to measure antibiotic usage among adult inpatients in high-income hospital settings has been made. Two independent reviewers will screen the studies for eligibility, extract data and assess the study quality using the Newcastle-Ottawa scale. A description of the methods and measures used in antibiotic consumption surveillance will be presented. An adaptation of the Affordability, Practicability, Effectiveness, Acceptability, Side-effects Equity framework will be used to consider the practicality of implementing different approaches to measuring antibiotic usage in secondary care settings. A descriptive comparison of definitions and estimates of (in)appropriate antibiotic usage will also be carried out.Ethical approval is not required for this study as no primary data will be collected. The results will be published in relevant peer-reviewed journals and presented at relevant conferences or meetings where possible. This review will inform future approaches to scale up antibiotic consumption surveillance strategies to attempt to maximise impact through standardisation.CRD42018103375 This study protocol follows the recommendations outlined in the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols.This protocol has been registered on the International Prospective Register of Systematic Reviews.The selection of studies, data extraction and study quality assessments will be conducted by two independent reviewers.The exclusion of studies which do not report the total number of patients may exclude very large-scale antibiotic consumption surveillance projects.The information available in some published studies may be too limited to assess surveillance methodologies using the Affordability, Practicability, Effectiveness, Acceptability, Side-effects, Equity criteria.It is estimated that by the year 2050, 10 million deaths per year will be attributable to antimicrobial resistance (AMR).A range of strategies are being adopted to monitor and improve antibiotic prescribing in hospital. In Australia and England, surveillance systems have been established to measure antibiotic use in hospitals based on dispensing data from hospital pharmacies, converted into DDD.It is recommended that antimicrobial consumption surveillance should combine aggregate data with patient-level data to better understand patterns of prescribing.In the UK, the Commissioning for Quality and Innovation has established performance management targets to financially incentivise reductions in antibiotic use in primary and secondary care. This includes targets to promote prescribing review within 72 hours. In most hospitals, adherence to this target is monitored by auditing a sample of prescriptions.The National Antimicrobial Prescribing Survey (NAPS) measures similar antibiotic stewardship behaviours, however it goes further by estimating inappropriate prescribing. These data are collected through point prevalence surveys of all patients in the hospital where possible. Inappropriateness is defined in this survey as prescribing the wrong antibiotic spectrum, incorrect dose/frequency/duration/route and prescribing when an antimicrobial is not needed. Decisions on inappropriateness are made by a multi-desciplinary clinical team’s assessment and are reported as prevalence of prescriptions. In 2017, 17 366 patients were submitted to NAPS with 26 227 prescriptions from 314 participating hospitals which were assessed for inappropriateness.Variations exist in the length of time between data collection and publication of results across surveillance programmes. The 2016 NAUSP data were published in 2018, while the 2017 Swedish Antibiotic Utilisation and Resistance in Human Medicine (SWEDRES) and Swedish Veterinary Antibiotic Resistance Monitoring (SVARM) report published data collected in 2017 by the following year.As high-income settings answer the WHO call to increase the availability of antimicrobial use data, there is a need to reach a consensus on how to interrogate these data and be able to draw comparisons between hospital sites.The Affordability, Practicability, Effectiveness and cost-effectiveness, Acceptability, Side-effects/safety and Equity (APEASE) criteria for designing interventions provides a framework within which researchers can comprehensively consider the context-specific suitability of an intervention.This review will therefore study attempts to quantify total systemic antibiotic use, appropriate antibiotic use and inappropriate use in high-income settings in secondary care. This review will provide a summary of the ways in which antibiotic use can be measured alongside a narrative about the practicality of employing these metrics in secondary care based on an adaptation of the APEASE framework.To identify the data sources and metrics which have most frequently been used to represent antibiotic usage in secondary care.To assess the suitability of antibiotic use surveillance methodologies and metrics for use in routine surveillance of antibiotic usage based on the APEASE criteria.To document the variation in definitions and estimates of appropriate and inappropriate antibiotic usage.The aim of this review is to provide an outline of the methodologies to quantify antibiotic usage among inpatients in secondary care. The objectives are:The following methods are based on the framework provided by the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) checklist.Studies which quantify antibiotic usage in at least 100 adult patients (aged >17 years) among inpatients in secondary care will be included.This review will include studies in the adult inpatient, high-income secondary care setting as it is expected that quantities of antibiotic use and patterns of prescribing in non-adult inpatients is likely to be significantly different to those in adults.Studies which focus on antibiotic usage among individuals with specific conditions or specific demographic groups will be included.Those studies which do not provide enough information for a complete assessment using the APEASE criteria will be included in the final review, but excluded from the APEASE criteria evaluation.This review will therefore include a range of study designs which are based on both observation and intervention, and which have attempted to estimate antibiotic usage in secondary care.Study inclusion criteria:This review will not include trials of antibiotic therapies in secondary care or reviews of the literature.Articles which describe a methodology for measuring antibiotic usage and which do not attempt to implement it to estimate antibiotic usage will be excluded.Articles which are not written in English language and are based on non-human participants will be excluded.If the number of adult inpatients included in the study is not stated, the article will be excluded from the review.Study exclusion criteria: The study must be based on dispensing, prescribing, survey/audit or sales data collected from the inpatient secondary care setting. It is expected that hospitals in high-income settings will be very different to those in low-resource settings in both the availability of data and resources available for stewardship, therefore this review will focus on hospitals in high-income countries as classified by the World Bank only online .29 When 10.1136/bmjopen-2018-026792.supp1Supplementary dataThis review will consider all attempts to measure antibiotic usage among at least 100 patients in the hospital inpatient setting.There are no comparison groups for this review as it is an exploration to identify how antibiotic usage has been measured in secondary care and how this has been used to define and estimate appropriate and inappropriate antibiotic usage.Articles which report a measure of antibiotic usage in hospital will be included in this review.Data source used to represent antibiotic usage.Metrics which attempt to quantify antibiotic usage.Data Synthesis).An analysis of the suitability of existing metrics of antibiotic usage for use in routine practice to monitor antibiotic usage based on an adaptation of the APEASE framework (detailed in Quantitative definitions of appropriate and inappropriate antibiotic usage.Comparison of the definitions of appropriate and inappropriate prescribing in secondary care.Description of variations in estimates of appropriate and inappropriate prescribing in secondary care.Medline (Ovid);Embase (Ovid);Cumulative Index to Nursing and Allied Health Literature;Cochrane Central Register of Controlled Trials.The following databases will be searched for relevant articles:The search strategy will be developed in Medline and then adapted appropriately for use in each database. The search will be conducted across all databases on 2 August 2018.et al. based on discussion between SP, AJ and LS.In order to capture reports from the grey literature, the websites of relevant organisations will be searched online . The liset al. based on four concepts: antibiotics, utilisation, measure, hospital  Reviewer 4 systematic review software which will be used to remove duplicate articles. Each stage of the screening process will be carried out in EPPI Reviewer 4 using a standardised form of article eligibility. The online form for article eligibility will be piloted before the start of the screening process and amended as required to ensure it is fit for purpose. The data will be extracted and entered into a standardised, piloted, precreated online data extraction form in EPPI Reviewer 4 in duplicate by two independent reviewers (SP and AJ).The articles will be uploaded from the relevant database to The unique articles captured by the search will undergo a title prescreening by a single reviewer (SP). The remaining articles will then be screened based on title and abstract by two independent reviewers in duplicate (SP and AJ); when study eligibility is not mutually agreed on or is ambiguous from the title and abstract only, the article will be admitted into the full-text review stage. The selected articles will undergo full-text review by two independent reviewers in duplicate (SP and AJ). Any disagreements between authors at any stage will be resolved through a third reviewer (LS). The reasons for the exclusion of these studies from this review will be documented for reference and the study selection process will be presented as a PRISMA flow diagram.The data will be collected in duplicate by two independent reviewers (SP and AJ) from articles selected for inclusion in the review. The data will be entered into precreated, piloted forms on EPPI Reviewer 4: systematic review software. Any disagreement will be resolved through consultation with a third author (LS).Study .Data type used to describe antibiotic usage .Metrics used to measure antibiotic usage , level at which the metric is presented .Criteria used to define appropriate and inappropriate antibiotic usage.Data type used to quantify appropriate and inappropriate antibiotic usage .Quantitative estimates of appropriate and inappropriate antibiotic usage , level at which the metric is presented  and what the metric is currently used for .Study quality and selection bias of those studies which provide an estimate of appropriate and inappropriate antibiotic usage .We will extract data on:The main outcome of this review is a description of the data sources and metrics which have been used to measure antibiotic usage and to define appropriate and inappropriate antibiotic usage in hospitals. This will include a description of the teams most frequently involved in this type of work in order to identify those groups who are often facilitators of this surveillance.Data synthesis’.This will then be used to consider each surveillance method within an adaptation of the APEASE framework to assess the practicality of each method and metric for use in routine surveillance of antibiotic usage; this method is detailed in ‘All metrics of antibiotic consumption included in the final review must have been used in the secondary care setting to capture the antibiotic usage data for at least 100 patients. This is to ensure some level of demonstration of the feasibility of implementing the measures. For these descriptive purposes, it is not appropriate to use a risk of bias framework.For studies included in the full-text review stage and which attempt to make a quantitative estimate of appropriate or inappropriate antibiotic usage in the secondary care setting, the Newcastle-Ottawa scale to assess study quality will be used to determine the inclusion of the estimate in the review.The data will undergo a descriptive synthesis to provide insight into the methodologies to implement antibiotic usage metrics in secondary care. We will record the frequency of use of different data sources by level  and by source (such as electronic prescribing or audits). This will examine the type of data which is currently being used to monitor antibiotic usage and consequently the level detail in which we are able to examine prescribing currently. We will also identify the frequency of use of each metric to measure: volume, type, duration, stewardship activity and prevalence/incidence of antibiotic use. As well as identify the level at which these metrics are most frequently presented such as by specialty or nationally. The teams involved in these studies to collect and analyse the data will also be recorded.An adaptation of the APEASE framework will be used to assess the feasibility of metrics for use in routine monitoring of antibiotic usage. The APEASE framework was designed to aid the context-specific design and selection of interventions to promote health behaviour change.This analysis can then be used to inform recommendations based on the available literature regarding a sustainable, conventional strategy to monitor antibiotic usage and the resources which would be required to practically implement such a surveillance strategy.The variation between comparable hospital-level estimates of (in)appropriate antibiotic usage will be represented using a funnel plot of inappropriate prescribing estimates against patient numbers and 95% CIs.The systematic review will be conducted in line with this protocol and any aspects of the method which deviate from the original protocol will be reported in the final review. Only articles written in English language will be included in this review; this is due to the language spoken by the authors.This is a descriptive review to consider the methodologies which have been used to measure antibiotic usage and to define appropriate and inappropriate antibiotic prescribing in hospitals. The methodologies will be considered in terms of the APEASE criteria and it is therefore not necessary to consider the quality of quantitative evidence for all studies. For observational studies which attempt to make a quantitative estimate of appropriate or inappropriate antibiotic usage in the secondary care setting, the Newcastle-Ottawa scale to assess study quality will be used to determine the inclusion of the estimate in the review.


Misuse of antibiotics in food animals contributes to an increase of antibiotic resistant bacteria transmitting to humans. China is the largest producer and user of antibiotics in the world, of which animals share more than half of the total consumption. This study aimed to explore Chinese farmer’s practice of antibiotic use and the factors associated with their use.In this cross-sectional survey, we interviewed farmers from 88 chicken farms in northwestern China. We defined two kinds of misuse: 1) using antibiotics in the Chinese prohibited list, and 2) using antibiotics within the recommended withdrawal period. Factor analysis was used to select farmers’ knowledge variables and multinomial logistic regression was used to determine factors associated with antibiotic misuse.All the participating farmers used antibiotics on their farms. Amoxicillin was the most common antibiotic used (76.5%), followed by norfloxacin, ofloxacin, ceftriaxone and oxytetracycline. 75% of farmers used antibiotics in the prohibited list while 14.8% continued to use antibiotics during the withdrawal period. Hierarchical cluster analysis revealed three patterns of antibiotic use: 1) excessive use of non-prohibited and prohibited antibiotics or an excessive user, 2) low use of a few types of non-prohibited and moderate use of prohibited antibiotics or a low user, 3) multiple use of a variety (≥ 7 types) of non-prohibited and prohibited antibiotics or a moderate user. Farmers from medium size, family-based farms, those with a low education level and low income were more likely to misuse antibiotics. Prior formal agricultural training was associated with reducing multiple types of antibiotic use. There was a huge gap between policy and reinforcement causing antibiotic misuse in the study community.Antibiotics are commonly used on chicken farms; misuse of antibiotics is high; improvement in farm sanitation, education on antibiotic use for farmers and veterinarians/pharmacists and enforcement of the regulations may reduce antibiotic use on chicken farms in China. China’s economic growth in the past three decades has changed its agriculture system from a traditional backyard approach into intensive animal production. As a result, China has become the largest producer and user of antibiotics in the world, and animals share more than half of the total consumption , 2. ThisThe Chinese government has made a series of efforts to control antibiotic use in animals. For example, it has successively released a prohibited list of antibiotics not to be used in farming, banned antibiotic use during withdrawal periods, classified management of prescription drugs and over-the-counter drugs, forbidden the use of medically important drugs such as cephalosporin class in animals, and required farmers to record their antibiotic use –9. NeverPrevious studies mostly examined antibiotic resistant microbial strains and resistance patterns , 12 whilA survey was conducted in all 5 regions in Ningxia province, northwestern China. Each region has a high concentration of livestock  . ProbabiA structured questionnaire comprising 4 main sections was developed: 1) farm characteristics and information on farming management procedures, 2) sociodemographic characteristics of farmers, 3) farmers’ practice of chicken disease prevention and infection control  and 4) farmer’s knowledge of and attitudes to antibiotic use. Sections Three trained researchers visited the selected farms and invited a responsible farmer (owner /manager) of the farm, to participate in the study. Written informed consent was obtained from all farmers after they agreed to participate in the study. The questionnaires were self-completed and each questionnaire took about 30 min to complete.This study was approved by the ethical review committee of Ningxia Medical University, China and the Faculty of Medicine, Prince of Songkla University, Thailand.EpiData 3.1  was usedHierarchical heat map analysis was used to illustrate patterns of antibiotic use based on clustering types of antibiotics and frequency of antibiotic used. Factor analysis on knowledge about antibiotic use and antibiotic resistance was performed to reduce the number of variables and used for model adjustment. Multinomial logistic regression was used to examine associated factors for antibiotic use. All data analysis was done using R 3.5.2 .A total of 88 farmers from 88 farms agreed to participate in the study for a response rate of 100%.Table Overall, 78.4% of farmers misused antibiotics; 75.0% used antibiotics from the prohibited list, 14.8% used antibiotics during the withdrawal period, and 11% did both. Small and medium sized farms, those that had been operating for more than 20 years, and those with poor sanitation had higher rates of antibiotics misuse.Female and younger farmers were more likely to use antibiotics both in the prohibited list and during the withdrawal period while non-married farmers, those with a higher education level and with higher incomes had lower rates of antibiotic misuse. Farmers with formal training had a lower rate of antibiotic misuse while those who had more than 20 years of farming experience were more likely to misuse antibiotics.Escherichia coli bacterial infection, avian influenza, avian infectious laryngotracheitis, Newcastle disease and pullorum disease. Almost 90% of farmers immunized their chickens in combination with the use of traditional Chinese medicine. Antibiotics played an important role for prevention and/or treatment but were rarely used for growth promotion. About 15% of farmers used antibiotics during the withdrawal period, mostly due to detection of clinical signs of infection, and 75% used antibiotics from the prohibited list. About 81% of farmers purchased antibiotics from a veterinary drug store while the rest did so from a pharmacy store, online or feed factory. More than half purchased antibiotics without a prescription. Only one-third of the farmers recorded their antibiotic use. According to some farmers’ records, the antibiotics were regularly used in a cyclical pattern of continuous use followed by a period of discontinued use. Farmers mixed antibiotics into either water or feed together with some Chinese traditional medicine, or alternately used some herbal compounds, such as astragalus polysaccharide, for disease prevention. Some farmers commonly changed antibiotic types to decrease the rate of antibiotic resistance.Table A hierarchical heat map of antibiotic use pattern among the 88 farms is shown in Fig. As a whole, farmers had a good knowledge about safe antibiotic use, adverse reactions and antibiotic resistance in chickens. However, they were not aware of differences between viral and bacterial infections and only about one-third knew that inappropriate use of antibiotics in chickens could lead to antibiotic resistance in human bacteria Table .Table 3Table This study examined 88 farmers’ practice of antibiotic use on chicken farms in high density agricultural areas in Northwestern China. All the farmers used antibiotics on their farms . Amoxicillin was the most commonly used antibiotic (76.5%), followed by norfloxacin, ofloxacin, ceftriaxone and oxytetracycline. Antibiotic use could be classified into 3 patterns: 1) excessive use of non-prohibited and prohibited antibiotics or an excessive user, 2) low use of a few types of non-prohibited and moderate use of prohibited antibiotics or a low user, 3) multiple use of a variety (≥ 7 types) of non-prohibited and prohibited antibiotics or a moderate user.75% of farms used antibiotics on the prohibited list while 14.8% continued to use antibiotics during the withdrawal period. Farmers from medium sized, family-based farms, those with a low education level and lower income were more likely to misuse antibiotics. Prior formal agricultural training was associated with lower odds of using multiple types of antibiotics.Escherichia coli infection followed by three viral diseases. Most farmers immunized their chickens with compulsory and optional vaccines, and used traditional medicine as well as antibiotics. Antibiotics were excessively used for infection prevention rather than treatment. Similarly, the use of antibiotics for prevention was also reported on large chicken farms in other developing countries such as Vietnam and Thailand [The most common infection on chicken farms was Thailand , 21. UseThailand .Farmers included in the study can easily access and purchase antibiotics from local drug stores, online, and feed factories with or without prescription. The accessibility of antibiotics has a strong influence on farmers’ decision making , therefoAmong the five most popular antibiotics used in this study, only amoxycillin and oxytetracycline are allowed to be used. Although these two antibiotics were considered to have a lower risk and are most commonly used on chicken farms worldwide , 21, 24,Regardless of the regular use of non-prohibited antibiotics, three-quarters of farmers used prohibited antibiotics. One objective of farmers to use different antibiotics was to decrease the risk of development of resistance in bacteria from chickens. However, they were unaware that this may lead to multiple resistant bacterial strains in both animals and human –30. AntiUsing antibiotics as a growth promotor is a serious problem worldwide, but it was rarely reported in our study. Even though the use of antibiotics as growth promoters is banned in many developed countries , 31, ChiMajority farmers (86%) knew withdrawal period, but still part of them did not adhere to the rules. This may due to their vulnerable economy and the absence of government residual detections. However, the prevalence rate of using antibiotics within withdrawal period was not much high (14.8%), compared to other similar studies, like Cameroon poultry farms (49.6%) and Cambodian pig farms (47%) , 34. TheThe pattern of use and misuse of antibiotics in food animals can highlight the implications of the emergence of different types of antibiotic resistant bacteria and their dissemination among animals, humans and the environment. The situation has been reported in many previous studies from multiple countries, which have initiated the One Health approach for better understanding and addressing health issues around the world , 35–37.Factors associated with increased misuse of antibiotics included medium farm size, lower education levels, lower farmer’s income and lack of formal agricultural training. Medium-sized farms in our study had poor sanitation but a very intensive production model which increased the risk of infection and thus higher antibiotic use. Good hygiene, cleanliness and waste management on large farms consistently yielded reports of low use of antibiotics not only in our study but in other studies as well , 38, 39.The Chinese government has taken a series of actions to control antibiotic resistance over the past two decades, and published regulations to restrict antibiotic use in food animals. However, the gap between policy and reality can been seen in Table Some practices against national regulations might have been under-reported, for example using the antibiotics in the prohibited list or using antibiotics during the withdrawal period. Due to a lack of knowledge among farmers, some farmers did not report the types of antibiotics used, which may have underestimated the antibiotic use reported in this study.Chinese farmers use large quantities of antibiotics on poultry farms and the misuse is also high. Although national regulations to control antibiotic use are available, they are not well enforced. Improving farm sanitation, especially on small and medium sized farms, providing training about appropriate antibiotic use to farmers, educating veterinarians/pharmacists to protect the health of both animals and humans, restricting free availability as well as enforcing the national regulations may lower antibiotic misuse and decelerate the problem.


Concrete mix design is a complex and multistage process in which we try to find the best composition of ingredients to create good performing concrete. In contemporary literature, as well as in state-of-the-art corporate practice, there are some methods of concrete mix design, from which the most popular are methods derived from The Three Equation Method. One of the most important features of concrete is compressive strength, which determines the concrete class. Predictable compressive strength of concrete is essential for concrete structure utilisation and is the main feature of its safety and durability. Recently, machine learning is gaining significant attention and future predictions for this technology are even more promising. Data mining on large sets of data attracts attention since machine learning algorithms have achieved a level in which they can recognise patterns which are difficult to recognise by human cognitive skills. In our paper, we would like to utilise state-of-the-art achievements in machine learning techniques for concrete mix design. In our research, we prepared an extensive database of concrete recipes with the according destructive laboratory tests, which we used to feed the selected optimal architecture of an artificial neural network. We have translated the architecture of the artificial neural network into a mathematical equation that can be used in practical applications. Concrete mix design is an essential and abstruse topic, which requires extensive knowledge of many expert issues. Obtaining concrete with appropriate strength, and other utility parameters, allows for the reliable use of the structure. The process of concrete hardening and hydration are irreversible. Therefore, any errors in the design of the concrete mix are incredibly costly for the investor, both at the construction stage and in the subsequent exploitation of the structure due to reduced durability. By definition, concrete mix is a mixture of cement, water, and coarse and fine aggregate, mostly enriched by additives and admixtures to improve some parameters, such as concrete strength, density, durability, or workability. The final product is in which the concrete mix is transformed into concrete. The concrete hardening is started by the cement hydration process, which is an exothermic chemical reaction between cement and water. Hydrated cement forms a tobermorite gel, hydroxide, and some secondary compounds that help with bonding between the fine and coarse aggregate. In the course of the hydration process, the hydration products gradually deposit on the original cement grains and fill the space occupied by water. The hydration process stops when there is no unreacted cement or the water molecules are retracted. The hardening of concrete continues further and ends around the twenty-eighth day, when the concrete reaches full compressive strength ,2,3. TheThe primary goal of concrete mix design is to estimate the proper quantitative composition and proportion of concrete mixture components. We should use a composition which allows us to achieve the best possible concrete performance. Concrete performance is characterised by several features, from which the most significant are compressive strength and durability. Both concrete strength and durability should play an essential role in the concrete mix design. The issue of durability is essential in the case of an aggressive environment ,20,21,223 of concrete, expressed in kilograms; and 3 of concrete, expressed in kilograms. A second consistency Equation (2), is included in the water demand formula necessary to make a concrete mix with the required consistency.3 of concrete, expressed in kilograms; 3 of concrete, expressed in kilograms; 3 of concrete, expressed in kilograms; 3 per kilogram; and 3 per kilogram. The water-tightness of concrete Equation (3) is included in the simple volume formula, which indicates that a watertight concrete mix is obtained if the sum of the volume of the individual components is equal to the volume of the concrete mix.3 of concrete, expressed in kilograms, 3 of concrete, expressed in kilograms, 3 of concrete, expressed in kilograms;3; and 3.The first equation is the compressive strength equation or Bolomey formula (Equation (1)), which expresses the experimentally determined dependence of the compressive strength of hardened concrete on the grade of cement used, the type of aggregate used, and the water-cement ratio characterising the cement paste ,24. In tW) in one cubic meter of concrete mix. The system is valid, assuming that there are no air bubbles in the concrete. Another method used in the construction industry is “the double coating method” [The system of equations presented above, with three unknowns variables, allows for calculating the sought amounts of cement (C), aggregate (K), and water  from the analysis as univariate outliners. The training dataset has 395 records (53.3%), the selection dataset has 133 records (17.9%), and the testing dataset has 134 records (18.1%). The scatter plots of a target variable versus the input variables are presented in Our neural network consists of four input variables, which refers to four principal components and generates one target output. The complexity of the model is expressed by the number of hidden layers, which in our case is three. The initial architecture that we prepared is shown in We want to point out that some input variables  correspond with some input neurons and target variable (cs_28) is associated with the output neuron. To obtain a proper training rate, we used the Broyden-Fletcher-Goldfarb-Shanno algorithm ,42,43,44We have assessed the impact of individual variables on the final result, which is presented in We performed input selection by the growing inputs algorithm ,54,55,56In In our study, we created an ANN which can be used for concrete mix design. The network targets the compressive strength of concrete with the four following input variables, cement, water, fine, and coarse aggregate. We can express our ANN by a mathematical Equation (4). The Equation (4) refers to the 28 day strength of concrete, which, as we mentioned, can be considered as full strength.Auxiliary mathematical formulas are presented in Equations (5)–(14). The variables C, W, FA, CA used in Equations (15)–(18) mean cement, water, fine aggregate, and coarse aggregate, respectively. Units are expressed in kilograms per cubic meter.We simplified the mathematical formula translated from the ANN source code and presented it in the form of Equation (19), To illustrate how the equation works we presented the charts of the output variable and the single input variable, while the other input variable is fixed. The charts are shown in 3 of concrete designed for the concrete slab, with direct pouring, plastic slump, no special desired finishing, no special ambient conditions when casting, and negligible environmental aggression. To design a concrete mix, we used the following materials: Portland cement; network water; natural sand; limestone gravel 4/10 mm; and limestone gravel 10/20 mm. The tested recipes are presented in We compared the presented Formula (19) with a standard concrete mix design approach, based on the Bolomey design method. The comparison was prepared for 1 mWe observed a low resilience of the ANN formula for recipes of high strength (50 MPa and above) concrete. It may be due to the smaller number of recipes on which we trained the ANN for these ranges. This behaviour of the ANN may be a sign of underfitting ,28. We mOur study is focusing on the application of machine learning in concrete mix design and building a practical tool that could be used in engineering practice. We designed the optimal ANN architecture and fed it with an extensive database of concrete mix recipes for the study. Every concrete mix recipe record has a corresponding laboratory destructive test. While building a neural network, the goal was to predict the compressive strength of the concrete resulting from a specific composition of concrete mix ingredients, or more precisely, what ratio of ingredients should be selected to obtain concrete with an adequate compressive strength. Our database has 741 records. We excluded 79 (10.7%) concrete samples from the dataset, as univariate outliners. The specificity of machine learning requires us to divide the database into three subsets, which we split up as follows: The training subset has 395 records (53.3%), the selection subset has 133 records (17.9%), and the testing subset has 134 records (18.1%). The initially adopted ANN model has four input variables, four principal components, four hidden neurons, and one target output. The suitable training rate and the step for the quasi-Newton training direction were calculated by the Broyden–Fletcher–Goldfarb–Shanno algorithm and the Brent method, respectively. Our input contribution analysis discloses that the most significant impact on the obtained results is the amount of cement that accurately points out the significance of the water-cement ratio to reach a higher concrete compressive strength. The finally adopted ANN model has four input variables, four principal components, six hidden neurons, and one target output. The pivotal point in making the machine learning techniques more applicable was a transformation of the ANN into an actual mathematical equation, which can be used in engineering practice. The initial conversion of the ANN into the mathematical formula had fifteen equations and required fourteen auxiliary variables. We simplified the expression into one general equation for the calculation of twenty-eight-day compressive strength of concrete. The equation we developed can be used as a rapid tool for concrete mix design check. The method allows checking the composition of four main concrete mix ingredients, cement, water, fine, and coarse aggregate, for achieving the desired concrete class. However, we would like to denote that the presented mathematical expression does not adequately reflect all the relationships between the components and have certain boundary conditions. We want to further develop the presented method. In the next step, to make this method more reliable, we would like to analyse the effect of admixtures and concrete durability.


Inappropriate use of antibiotics in primary care and hospital settings is a major contributing factor to the spread of antibiotic resistance. Many microorganisms were tested in Eritrea and have proven resistant to ampicillin. The aim of this study was to investigate the prescription pattern, hospital indicator and patient care indicator of antibiotics among hospitalized patients in Halibet National Referral Hospital, Asmara, Eritrea.The data on prescription patterns showed 79% of hospitalizations had at least one antibiotic prescribed and on average 1.29 antibiotics were prescribed per hospitalization; prescribing using generic name was at 97%; all (100%) of the antibiotics were prescribed from the Eritrean National List of Medicines. On average an antibiotic was prescribed for 6.36 days (SD = 6.06). Ampicillin was the most commonly prescribed antibiotic (42.1%) and parenteral was the most common route prescribed (81.4%). The data on hospital indicators showed key antibiotics were out of stock on average for 78.18 days; 87.5% of key antibiotics were available on the day of the study. The data on patient care indicator showed patients taking antibiotics stayed in the hospital for 9.97 days (± 7.33 days).The online version of this article (10.1186/s13104-018-4000-7) contains supplementary material, which is available to authorized users. Irrational use of antibiotics in inpatient settings is an important issue that needs attention. Some causes for inappropriate drug use in hospitalized patients are; unnecessary use of antibiotic, inadequate regulation and monitoring, inappropriate dose, and multiple antibiotic prescribing –4. Lack WHO has developed key indicators to measure antibiotic use in health facilities  and manyHigh rate of antibiotic use has been reported in Eritrea , howeverE. coli was (87.5%), Klebsiella spp (75%), Citrobacter (100%), Pseudomonas (81.8%) and Salmonella (100%) [S. aureus in Eritrea found that 85% were resistant to ampicillin [A recent study  in Orotta (100%) . Anotherpicillin .The aim of this study was to investigate the antibiotic use in hospitalized patients in Halibet National Referral Hospital (HNRH) using an indicator based methodology designed by Strengthening Pharmaceutical Systems (SPS) .The study was conducted at HNRH, one of the two national referral hospitals in Asmara, Eritrea. HNRH is a 180-bed national referral and teaching hospital with Surgical, Medical, Orthopedic, Burn and Emergency wards.A cross-sectional, retrospective study design was used to evaluate three key drug use indicators viz. hospital indicators, prescribing indicators and patient care indicator  from 0 to 9, then by adding 300 to the number, a second number (X + 300) was obtained. Starting from the second number every 300th card number was included to select 100 cases from the 3654 cases. The number of prescribing encounters to be studied were chosen based on the WHO’s 1993 recommendations . The comAfter checking for data completion, the necessary computations were performed according to the formulas given  were prescribed from the EML while 97% of the antibiotics were prescribed using generic names. On average patients were treated with an antibiotic for 6.36 days  of the prescribed antibiotics were in the National Essential Medicines List (EML). This is because HNRH procures almost all of its medicines from one supplier, PHARMECORE, which only procures according to the EML. Therefore prescribers in HNRH are encouraged to adhere to the EML, resulting in 100% adherence to the EML. Numerous studies reported varying percentages of EML adherence; Lesotho 79%) , Pakista% , PakisIn HNRH an antibiotic was prescribed on average for 6.36 days (SD = 6.06) Table . HoweverOverprescribing injectable medicine is considered a case of inappropriate antibiotic use , 30. ParOn the day of the study 87.5% of the key antibiotics were available in stock in the stores of HNRH. Similar studies done in developing countries found key antibiotics were available 72.4% in Pakistan  Table 33. Our fiThe average number of hospital stay for patients in HNRH was 9.97 days Table . This isThe limitations which need to be considered are as follows. Firstly, the findings of this study could not be generalized to the whole of Eritrea since this was done in a single hospital. Secondly, this study was done in the inpatient department of the hospital and thus it does not reflect the outpatient prescribing patterns of the hospital.Additional file 1: Annex S1. Data collection forms. Annex S2. Formulas used to calculate the indicators. Annex S3. List of the three types of drug use indicators investigated in HNRH. Annex S4. Medical Director’s ethical clearance.


However, many commonly used terms, such as ‘the war against superbugs’, risk misleading people to request ‘new’ or ‘stronger’ antibiotics from their doctors, veterinary surgeons or pharmacists, rather than addressing a fundamental issue: the misuse and overuse of antibiotics in humans and animals. Simple measures of antibiotic consumption are needed for mass communication. In this article, we describe the concept of the ‘antibiotic footprint’ as a tool to communicate to the public the magnitude of antibiotic use in humans, animals and industry, and how it could support the reduction of overuse and misuse of antibiotics worldwide. We propose that people need to make appropriate changes in behaviour that reduce their direct and indirect consumption of antibiotics. Antibiotic resistance is an increasingly serious threat to public health. When bacteria can stop an antibiotic from working against them, standard antibiotic treatments become ineffective and infections with antibiotic-resistant bacteria are associated with a higher risk of death. Hundreds of thousands of deaths per year are estimated to be attributable to antibiotic resistance.,International health organizations encourage all countries to reduce their use of antibiotics in both humans and animals to a minimum, but limited public understanding of antibiotic resistance and its drivers is likely to be a major barrier to the reduction of inappropriate antibiotic use.The ‘antibiotic footprint’ has been proposed as a global tool for the public communication of the magnitude of antibiotic use in humans, animals and industry,Just as reducing the carbon footprint to a minimum is the goal, the aim of the antibiotic footprint would be to reduce antibiotic consumption to a minimum. Clear ways of communicating this to the public are important in tackling both climate change and antibiotic resistance. Formerly, the research community used life cycle assessment (LCA) as an indicator of climate change potential.As a carbon footprint measures the quantity of gaseous emissions relevant to climate change and is associated with activities such as automobile use, building heating and agriculture Figure , an anti,Simple measures of consumption are needed; carbon emissions are measured in units of mass of carbon dioxide and antibiotic consumption could be measured in units of mass of antibiotics as a total value or per head of population. Currently, many indicators are proposed and used for antibiotic consumption in human and animals, including the DDD per 1000 inhabitants per day and milligrams per population correction unit (PCU).,Nation-level carbon footprint data are now widely and openly available, with tools for their easy visualization. In comparison, the majority of national data across all sectors  on antibiotic consumption come from high-income countries.Similar to the carbon footprint, the antibiotic footprint of each country with official data could be presented and compared Figure . This in,These data visualizations Figures  and 3 caClearly, crude comparisons of the antibiotic footprint do not take account of variations in populations, risk factors for infections and different farming practices. However, data can be used to prompt people to ask questions, such as ‘I didn’t know that so much antibiotic was used in food production—is this being reduced?’. For example, in 2013, total antibiotic consumption in the UK was 957 tonnes, of which 521 tonnes (55%) was for direct human consumption and 436 tonnes (45%) was for animal use.Crude comparison of average consumption per capita could also prompt people to ask whether misuse and overuse of antibiotics occur. For example, worked out as an average per head of population in 2015, a person living in the UK is directly consuming twice as much antibiotic as a person living in the Netherlands .www.amrindustryalliance.org) is working to improve this. The quantity of environmental contamination could also be added to a country’s total consumption data where available.National data for antibiotics discharged directly into the environment, for example by pharmaceutical companies, are still largely unavailable worldwide.An antibiotic footprint could also be calculated for individuals. As antibiotic use in humans varies by age, gender, local culture and individual attitude to taking antibiotics, etc., it would be informative to compare ourselves with other people in our own country, as well as other countries. Similar to on-line calculators for the carbon footprint, on-line individual calculators for antibiotic footprint could provide information, knowledge and recommendations about antibiotic consumption that could influence individual behaviour change, such as the impact of hand hygiene, vaccination and considered food choices.The antibiotic footprint could be a tool to support global targets for reducing antibiotic consumption. The carbon footprint has been an important tool to support global targets to reduce carbon emissions. Progress in reducing global antibiotic consumption and that of individual countries is poorly described or defined. For example, colistin is currently considered as a last defence against some MDR infections. In 2016, the EU set a target for desirable levels of colistin use in food-producing animals between ≤5 and ≤1 mg/PCU.People can reduce their own antibiotic footprint to a minimum by adjusting their activities and behaviour. This could include interventions to reduce infection risk such as ensuring uptake of available vaccinations, improving hand and food hygiene, and keeping healthy through following recommended exercise and dietary guidance.,Antibiotic use in food production can be lowered by promoting good animal husbandry standards. In 2017, UK supermarkets Asda, Waitrose and Marks & Spencer published farm-level antibiotic use data.The antibiotic footprint also has limitations. The availability of open-access data on national antibiotic consumption in human and animal sectors in LMICs is still limited. For the carbon footprint, different types of energy source may have different impacts on climate change, and a formula using emission factors  to standardize carbon emission is needed.We propose that the antibiotic footprint could be one of a suite of tools to communicate information to the community on antibiotic usage. It could support global target setting to reduce the overuse and misuse of antibiotics in the future, both in people and in animals.


This mini-review summarizes the most recent progress concerning the use of surface-enhanced Raman spectroscopy (SERS) for the detection and characterization of antibiotic-resistant bacteria. We first discussed the design and synthesis of various types of nanomaterials that can be used as the SERS-active substrates for biosensing trace levels of antibiotic-resistant bacteria. We then reviewed the tandem-SERS strategy of integrating a separation element/platform with SERS sensing to achieve the detection of antibiotic-resistant bacteria in the environmental, agri-food, and clinical samples. Finally, we demonstrated the application of using SERS to investigate bacterial antibiotic resistance and susceptibility as well as the working mechanism of antibiotics based on spectral fingerprinting of the whole cells. Detection of pathogenic and spoilage bacteria is still a major concern to clinical, agri-food, and environmental agencies and laboratories . The leaAntibiotic resistance of pathogenic bacteria is still a leading concern to clinics as well as agri-food and veterinary medicine . The keyIn this mini-review paper, we will evaluate the use of SERS coupled with chemometrics as a tool to detect the trace level of antibiotic-resistant bacteria and characterize the mechanism of bacterial antibiotic resistance in an ultra-fast manner. The recent progress in this research area will be summarized and discussed mainly focusing on the following three perspectives: (1) the nanomaterials that can be used as the SERS substrates for sensing a low concentration of bacterial cells; (2) tandem-SERS technology to detect antibiotic-resistant bacteria in a sample matrix; and (3) characterizing the mechanism of bacterial antibiotic resistance and susceptibility using SERS and chemometrics.14 depending on the nanomaterials used. For additional details, the authors are encouraged to refer to serial publications from the Van Duyne research group . S. SS. Typapproach . The spe2 CFU/mL . Althoug2 CFU/mL ,85,86, w2 CFU/mL . In addi2 CFU/mL ,70,80,87strategy . Besidess manner .Salmonella or multi-drug-resistant Salmonella. High correlation coefficients and LOD of 4 and 5 CFU mL−1 were obtained using an antibody-SERS employing AuNPs via a sandwich immunoassay for detecting and enumerating E. coli  has been recently used for the identification and detection of bacteria from clinical and environmental samples. For instance, Lin and others demonstrated a filter-like SERS substrate prepared with AuNPs embedded in mesoporous silica for the detection of  samples . The tarngitidis . This bad plasma . CoverinS. Typhimurium and S. aureus were simultaneously identified using different aptamers in a sandwich-type tandem-SERS detection within 3 h [2 and 103 CFU/mL with a total detection time less than 45 min [In addition, the tandem-SERS platform can achieve multiplex detection of bacteria by integrating several different elements into a single system. By using a systematic evolution of ligands by exponential enrichment (SELEX), different aptamers can be synthesized and each one targets one species of bacteria. By conjugating the aptamers onto a substrate, such as the microchannel in a microfluidic device, the mixture of bacterial cocktails can be individually captured by each aptamer that eventually achieve multiplex detection in a simultaneous manner. For example, thin 3 h . Sandeepn 45 min .3 CFU/mL for multiplex detection of S. Typhimurium and S. aureus in spinach wash water and peanut butter. “One step” sensing indicates that the separation and detection can occur simultaneously. Once “one-step” sensing is applied, a critical parameter is to ensure that the distance of the separation element is within 10 nm from the SERS-active substrate [In comparison to the aforementioned concepts of “direct sensing” and “indirect sensing”, “two-step sensing” and “one-step sensing” is another pair of the terminologies that are related to tandem-SERS platform. Once the separation and SERS detection are separate, it refers to “two-step” sensing. An intriguing “two-step” SERS approach based on a sandwich assay for the separation and detection of multiple pathogens in food samples was demonstrated by Wang and co-authors . Figure ubstrate ; otherwiubstrate . Naja anubstrate . Furtherubstrate .Besides the detection of antibiotic resistant bacteria either in a simple matrix or a complicated environmental, agri-food or clinical sample matrix, another major research direction of using SERS is to study the working mode and mechanism of antibiotics to inactivate bacteria. Bacterial cells can develop various strategies to resist to the antibiotic treatment as the pinnacle of evolution. Although new antibiotic resistance has been continuously emerging and spreading globally, bacteria use is one of two leading genetic strategies to deal with antibiotic treatment, namely mutation in genes associated with the action of antibiotic compounds and the acquisition of external DNA for the resistance determinants through horizontal gene transfer . These gAs a three-dimensional complex surrounding the bacterial cells, peptidoglycan is the major component of the bacterial cell wall . Since aE. coli and S. aureus at the single-bacterium level [Antibiotic susceptibility testing (AST) is used to evaluate the effectiveness of antibiotic treatment against the pathogen infections. SERS-based AST could reduce the time by avoiding the need for overnight culture in MIC determination through the conventional AST methods. Liu and coauthors used an SERS-active substrate made of AgNPs imbedded in AAO to determine the antibiotic sensitivity of um level . Antibioum level . Strain-E. coli, A. baumannii, and K. pneumoniae were exposed to imipenem at the incremental concentrations. The isolates were determined as susceptible, intermediate, and resistant based on the change of the characteristic bands in SERS signals at a very early stage of antibiotic treatment, and the SERS MIC results were in excellent agreement with the standardized plate dilution methods that took upward of 24 h to complete. In a recent study, Cui and coauthors developed a homogeneous vacuum filtration-based method to improve SERS signal reproducibility and illustrated that the existence of heavy metal arsenic could increase the MIC of bacteria to the treatment of tetracycline. The authors claimed that SERS has the potential for culture-free characterization of resistome in a real microbiota system at the single cell sensitivity level [In addition, SERS-active substrate can be employed as a means to establish MICs for various bacteria. Liu and colleagues demonstrated that SERS could monitor the reduction of specific bacterial biomarkers along with the treatment of antibiotics within two hours . Clinicaty level .Lactococcus latis was investigated using SERS-active AuNPs [E. coli were tracked upon antibiotic exposure to chloramphenicol, trimethoprim, polymyxin B, ampicillin, and formalin [Furthermore, monitoring the characteristic bacteria cell wall bands in the SERS spectra allowed for a further understanding of the antibiotic degradation mechanisms. The antibiotic response of ve AuNPs . Antibioformalin . No specChemometric statistical analyses are usually required to decipher Raman spectral patterns so that minor variations in the spectral features of different biological samples can be distinguished. Multidimensional information of SERS spectra can be reduced into a few independent latent variables  that account for the most variability of the original dataset by multivariate statistical analyses . These pE. coli, S. epidermidis and four Salmonella strains exhibiting antibiotic resistance to the common therapeutics were detected and differentiated using SERS coupled with PCA [P. mirabillis and Enterococcus were quite similar despite having different cell wall structures. DFA was employed to analyze the subtle differences of SERS spectra from 6 strains of clinical urinary tract infection isolates for identification at genus-level [Enterococci. In addition, antibiotic-induced spectral changes from ampicillin and ciprofloxacin were monitored and statistically analyzed using PCA to understand the different working mechanisms of these antibiotics [Different bacterial species or strains can be segregated into distinct groups based upon different biochemical compositions reflected by the major latent variables. For example, with PCA . In anotus-level . Chemomeus-level . A SERS-us-level . One recibiotics .Raman spectroscopy and SERS have been validated for their potential in bacterial detection, typing, and characterization for almost three decades. Compared to the application of MALDI-TOF mass spectrometry for bacterial characterization, the use of Raman spectroscopy and SERS by industry is still in its infancy. This is mainly due to the relatively poor spectral reproducibility by using different types of the manufactured SERS substrates. As indicated in numerous review papers related to SERS bacterial study, to develop a stable SERS-active substrate for consistent and global use in a commercial manner is highly critical to promote this versatile technology to environmental, agri-food and clinical applications. Another major challenge is the relatively high cost of the confocal micro-Raman spectroscopic system. Although very little cost is required for purchasing consumables and instrumental maintenance compared to MALDI-TOF mass spectrometry, industries are still reluctant to purchase a bench-top Raman spectroscopic system. Therefore, a portable/handheld Raman instrument might be more affordable even though the resolution of the collected SERS spectra is relatively low. A more user-friendly software is also required for the convenient spectral interpretation as well as chemometric analyses. Several vendors have developed their own software for spectral processing and chemometrics, but a major doubt is how reliable such software for spectral analysis can be. By only clicking each “black-box” in the software, the researchers may not fully understand how each algorithm will affect the performance of the chemometric models. A standardized protocol for SERS spectral analyses and chemometric analyses therefore is critical to achieve inter-laboratory validation of the results for bacterial characterization, such as the characterization of bacterial antibiotic resistance.Albeit these aforementioned challenges and potential limitations, SERS is definitely a very promising candidate for the determination of bacterial antibiotic resistance in a high-throughput, multiplex, and ultrafast manner. We suggest that industries use SERS for the detection and characterization of bacterial antibiotic resistance as an innovative fast screening alternative that can couple with the conventional methods for a further confirmation. Along with the further advancement in optical instrumentation and machine learning, the new version of the Raman spectroscopic system will be more user-friendly and cost-effective. We also envision that SERS can be used to further illustrate the modes of antibiotic and antimicrobial resistance of bacteria. This may contribute to the design of more effective antimicrobial treatment. Although SERS itself can be regarded as the core technology for an individual project, such as the detection of antibiotic resistance bacteria in a clinical specimen, we also believe it can be integrated as part of a more complicated study to drive very fundamental scientific research questions related to bacterial antibiotic resistance.


Two additional series containing recycled aggregate without treatment and natural aggregate were also prepared. Established properties of individual aggregates have confirmed a positive effect of thermo-mechanical treatment. Then, based on the results of compressive strength, flexural strength, Young’s modulus, volumetric density, water absorption, water permeability and capillarity, the most favourable parameters of heat and mechanical treatment of concrete were determined. The test results showed that appropriate treatment of concrete rubble allows to obtain high-quality coarse aggregate and valuable fine fraction. This was also confirmed by the macro- and microscopic observations of the aggregate and separated cement paste. Works realized on the concrete recycling method resulted in obtaining a patent PAT.229887.Concrete is a building material commonly used for ages. Therefore, in the result of repairs or demolition of building structures, large amounts of concrete rubble are created, which requires appropriate management. The aim of the realized research was to determine the influence of heat and mechanical treatment of concrete rubble on the properties of recycled aggregate concrete. The research experiment included 12 series, with three variables: X Its manufacture consumes a large amount of non-renewable natural resources (aggregates: 80%), Portland cement 10%), supplementary cementitious materials (3%), and water (7%). Its production is responsible for 5% of anthropogenic worldwide CO0%, supplNatural aggregates (NAs) used in the manufacture of concrete are inert granular materials such as sand, gravel or crushed stone. Natural gravel and sand are usually dug or dredged from a pit, river, lake or seabed. Crushed aggregate is produced by crushing quarry rock, boulders or large-size gravel. Currently, the global aggregate production is estimated at 40 billion tons, which is leading to a depletion of natural resources, high energy consumption, and impacts on the environment . Countries that are consuming the largest amounts of aggregates are China 38%), India (13%), other Asian countries (12%), Africa (8%), USA (6%), EU + EFTA (8%), C&S America (6%) and Oceania 4%). Approximately 58% of aggregates are used for the manufacture of concrete and mortar. The use of recycled aggregates from construction and demolition waste (CDW) in the manufacture of concrete and mortar is a viable alternative to reduce the unsustainable level of consumption of natural aggregates worldwide and avoid landfilling CDW [8%, India%. ApproxConcrete structures are demolished at the end of their service life generating concrete waste which can be recycled in treatment plants . In thesRecycled concrete aggregates are composed of natural aggregates covered with a porous layer of cement paste. The recycled aggregate’s quality is closely related to the adhered cement paste properties, since the bond between the primitive natural aggregates and the cement paste is usually weak in the interfacial transition zone . It is wThe replacement of NAs by RCAs reduces the new concrete’s mechanical and durability properties. Nevertheless, the use of high-quality RCAs may result in concrete with similar compressive strength, flexural strength, Young’s modulus and shrinkage than conventional concrete, even with high replacement ratios. The cement paste content is the main factor influencing creep deformation, which can limit the use of RCA in structural concrete application. The conventional concrete shrinkage prediction models are also affected by the cement paste adhered to the RCA, since it modifies the internal curing conditions, especially when the aggregates are used pre-saturated. From a durability point of view, the use of RCA increases porosity, water absorption, carbonation depth, chloride ion penetration, and decreases resistance to freezing-thawing, sulphate attack or resistance to abrasion ,12.In order to improve RCA quality, many researchers have applied different techniques for removing the adhered cement paste from the original natural aggregates. The main methods used so far are: (i) acid treatment, in which the RCA are soaked in acidic solutions  ,14,15,16However, studies on the combined effect of different treatment methods are scarce. This study analyses the combined effect of thermal and mechanical treatment on RCA properties, as well as the mechanical and durability properties of the new concrete. For this purpose, three variables have been tested: roasting temperature , time of mechanical treatment  and content of coarse RCA in concrete mixtures. The best option to manufacture structural concrete with treated RCA is selected. From a practical point of view, the results of this work are especially interesting in emerging countries with a shortage of natural aggregates and where the production of high-quality RCAs is a necessity.The Portland cement CEM I 42.5R, from the Ożarów cement plant (Poland) meeting the requirements of PN-EN 197-1 standard was used for the test samples. The following natural aggregate was used for the concrete mix: sand, fraction 0-2 mm; gravel, fraction 2-4 mm; granite, fractions 4–8 and 8–16 mm. The recycled aggregate was obtained from crushing of concrete based on granite aggregate. After crushing, the debris was subjected to heat and mechanical treatment and then screened into 4–8 mm and 8–16 mm fractions. A superplasticizer based on modified polycarboxylates was used.The aggregate bulk density test was carried out in according to EN 1097-3. The density of the concrete mixture was determined according to EN 12350-6 and the consistency according to EN 12350-2. The compressive strength of concrete was tested on cubic samples of 150 mm × 150 mm × 150 mm according to EN 12390-3. Determination of modulus of elasticity was carried out on cylindrical samples of 150 mm × 300 mm based on EN 12390-13. The concrete flexural strength test was carried out on samples of 100 mm × 100 mm × 500 mm according to EN 12390-5. The concrete density and water permeability were determined on cubic samples of 100 mm × 100 mm × 100 mm according to EN 12390-7 and EN 12390-8, respectively. The concrete water absorbability test was carried out according to the Polish Standard PN-88/B-06259.The recycled aggregate was obtained from processing of 3-year old laboratory samples of the dimensions of 150 mm × 150 mm × 150 mm and 150 mm × 150 mm × 750 mm, taken as control samples during the construction of concrete pavements. The composition of the concrete mixture of these samples is presented in The preliminary crushing of the samples due to their excessive dimensions exceeding the inlet of the laboratory crusher took place during the concrete compressive and flexural strength test. The results of those tests are presented in The basic crushing of previously disintegrated concrete samples was carried out in the jaw crusher. The concrete was crushed to the grain size d ≤ 20 mm and then it was sieved in order to separate fine and dust fractions (<4 mm). The obtained coarse aggregate is shown in The recycled aggregate of 4–20 mm fraction was then roasted in a CT 100 EK ceramic laboratory furnace at a rated temperature of 1250 °C. The recycled aggregate calcination is necessary in order to dehydrate the cement paste, which reduces adhesion of the hardened mortar to the aggregate grains and finally makes it easier to remove it from the surface of the aggregate.The heat treatment time was set at 3 h. According to the plan of the experiment, the roasting temperature was set at 3 levels: 300 °C, 600 °C, and 900 °C. The heating process of recycled concrete aggregate is shown in After thermal treatment and cooling, the recycled aggregate was mechanically processed. The last stage of the recycled aggregate quality improvement was mechanical processing. The Los Angeles drum was used for that purpose. The machining time was set at 5 min, 10 min, and 15 min, respectively. It allowed for the final separation of the cement mortar from the surface of coarse aggregate grains. Then the treated material was screened in order to separate fractions of 4–8 mm and 8–16 mm required for further tests.After heat and mechanical treatment the percentage content of separated cement mortar (<4 mm) in relation to the initial mass of recycled aggregate was determined. The results are presented in Mortar obtained, after grinding, can be used as an active addition to cement composites or as a substitute for part of the binder ,18,19,20After the analysis of the results it was observed that the abrasiveness of the aggregate mortar increased gradually with temperature and time of heat and mechanical treatment until the moment of roasting the aggregate in 900 °C, where sudden and unexpected increase in abrasiveness occurred. After the mechanical treatment of the aggregate roasted at 900 °C, almost the entire series was sieved through a 4-mm screen. It turned out that roasting at such a temperature destroyed the granite structure. To confirm this, an additional previously unplanned experiment was carried out, roasting the natural granite at 900 °C for 3 h. It turned out that the granite lost its properties at 900 °C, as the aggregate was destroyed in the moment of light pressure. A significant decrease in the mechanical properties of granite and a sudden increase in its porosity due to high temperatures above 800 °C was also observed by other authors ,22. 1—temperature of recycled aggregate heat treatment; X2—mechanical treatment time; and X3—percentage amount of coarse recycled aggregate. The levels of their variability are shown in detail in An experiment based on three variables was planned in order to investigate the influence of the improvement of the quality of coarse recycled aggregate on selected concrete properties: XThe theory of statistical planning of experiments was used to determine the research plan. The experiment and calculations were carried out in accordance with the statistically determined, sequential Hartley’s PS/DS-P:Ha3 plan, built on hypercube. The Hartley’s DoE (Design of the Experiment) enables to check repeatability of results, to find which inputs and their interactions influence the output significantly, to calculate regression equation and check its adequacy with test results.Upon the basis of abovementioned variables, an experimental plan including 12 research series and 2 control series was established. For the first control series (13), the recycled concrete aggregates were used directly after crushing, without heat and mechanical treatment (RCAwt), while the next control series (14) was made with granite (NA). 3 and a constant w/c ratio.The above results indicate that recycled aggregates roasted at a temperature of 600 °C were characterized by bulk density which was closest to natural aggregate, both in dry and saturated state. Also the water absorption of this aggregate was the lowest among the tested recycled aggregates (3.11% and 3.70%). This was mainly due to the effective removal of the old cement mortar from the aggregate grains, the presence of which jeopardizes the RCA properties, in particular the increase in its water absorption. It was due because at the temperature of about 600 °C, calcium hydroxide mainly located in the contact zone between the aggregate grain and the cement paste was dehydrated, making it easier to remove the mortar during mechanical treatments. The absorbability of untreated aggregates was much higher and amounted to 6.85% and 7.83%, respectively. Slightly worse results were obtained in case of aggregates roasted in 300 °C. The results indicated that recycled aggregate not subjected to the heat and mechanical treatment was characterized by definitely the lowest bulk density, which was caused by its developed surface due to the presence of cement mortar and irregular shape hindering tight packing of grains in the container, which is in agreement with most of the studies on physical properties of recycled aggregates . The preThe results of the consistency of concrete mixtures measured by the slump test and their density are presented in Upon the basis of the analysis of the above results, it can be seen that the highest slump of 225 mm cone corresponding to the consistence class S5 was recorded for 14 control series. The lowest slump of 140 mm cone corresponding to the consistence class S3 was recorded for series 13. The reason was the use of recycling aggregate without the heat and mechanical treatment having the highest amount of cement mortar absorbing water.For the samples from series 5 and 9 containing 60% of recycled aggregate roasted in 900 °C, the consistence class was not determined, as no slump was observed here. In other series, the consistence values were similar to each other and corresponded to class S4.cm,28), flexural strength , Young’s modulus (E), volume density (D), water absorption (WA), water permeability (WP) as water depth penetration and water capillarity as increase of sample mass (WC) have been determined.The test results were statistically analyzed in order to determine an approximating function describing changes in selected physico-mechanical properties of the concretes. The analyses included variance, a calculation of regression coefficients and an assessment of the regression coefficients’ significance. The function describing changes in the physico-mechanical properties of concretes adopted a form of the second degree polynomial (1):Calculations were performed using Statistica Version 13. The equations for the concrete’s compressive strength, flexural strength, Young’s modules (E), volume density, water absorption, water permeability and water capillarity which considers only significant regression coefficients at α = 0.05, are presented in 2 was assumed at the average level . Due to the incomplete research plan the test result analysis was prepared upon the basis of established regression equations.The statistical analysis revealed that all analysed physical and mechanical properties of concrete were significantly affected by the roasting temperature and recycled aggregate content. On the other hand, the time of mechanical treatment usually did not significantly affect the obtained values of parameters, therefore the variable x1) and recycled aggregate content (x3). Upon the basis of In higher temperatures (900 °C), the aggregate structure was damaged, resulting in a sudden decrease in compression strength by about 17% on the average. It is also confirmed by the amount of cement mortar separated from the aggregate surface after its heat and mechanical treatment . As show1) and recycled aggregate content (x3), respectively, as well as the average flexural strength results obtained for the individual test series compared to the series with untreated aggregate (13), and the control series with the natural aggregate (14).1 and x3, as well as the average results compared to the series with untreated recycled aggregate (13), and the control series with natural aggregate (14).The important factors influencing the strength and deformation properties of concrete are the adhesion between cement paste and aggregate grains, and the microstructure of the transition zone in the area of stress concentration due to the difference in modulus of elasticity values of the hardened paste and the aggregate. 1 and x3, and the average results comparing to the series with untreated RA (13) and the control series with natural aggregate (14).From The results of concrete water absorption for each series of the experiment are shown in The best concrete water absorption was observed in the case of using 20–40% of recycled aggregate roasted in temperatures up to 600 °C. In such cases, the absorbability approaches the value for the control concrete (≤4% for series 2 and 6). It results from effective removal of porous cement mortar from the recycled aggregate surface. Its high absorbability causes many problems connected with determining the amount of water added to the recycled concrete aggregate in order to obtain the required consistency. In series 13 with untreated aggregate, the absorbability of concrete has increased significantly by 66%, compared to control concrete. Clearly higher absorbability of recycled aggregate concrete compared to the natural aggregate concrete was also observed by other researchers ,28. Remo1 and x3, as well as the average results in comparison with the series with untreated aggregate (13) and with the control series with natural aggregate (14).As shown in The observation of aggregates using an optical microscope was aimed for comparing changes in their surface as a result of contact with cement slurry during the hydration process, as well as after the applied heat and mechanical treatment. For this purpose, the cylindrical samples of dimensions of 50 mm × 48 mm from cement paste (CEM I 42.5R and water) of w/c = 0.45 were made, in which the natural aggregates  were immersed. Previously part of the grain was covered with stearin in order to prevent its direct contact with the paste. Samples were kept in water for 3 months before testing. After drying the samples were subjected to the heat and mechanical treatment . Then the obtained aggregates were observed under an optical microscope in order to determine the possible damage or visible changes in the external structure. In the case of the granite aggregate, the presence of grout on its surface does not significantly change the grain shape. According to other researchers, the granite aggregate is characterized by higher chemical activity in contact with cement paste than the gravel. They have also found that the microstructure of the cement paste surrounding the gravel grain is loose and porous due to higher absorbability of the aggregate. The microstructure of the paste around the granite is denser than around the gravel, small pores and defects are visible and many groups of hydrates are closely bonded with each other. It is therefore difficult to identify the paste and the aggregate . The phy2 fragments, which, being the nuclei of crystallization of this phase, causes the growth of calcium hydroxide crystals in various directions, improving mortar strength [strength .During the proposed heat and mechanical treatment of concrete rubble, in addition to high-quality recycled aggregates, a cement mortar was also obtained, which due to the induced pozzolana properties as a result of thermal treatment can be used as a cement substitute in cement composites or as a pozzolana additive ,20,33,34−1. The X-rays for unroasted and treated paste are collected, respectively, in Iwz) are also represented.In order to determine the effect of heat and mechanical treatment on the phase composition of cement slurry separated from the aggregate (experiment p. 6.1), the X-ray diffraction tests were realized. The samples were analysed by X-ray diffraction analysis (XRD) using a VEB FreibergerPragisionsmechanik TUR-M-62- with DRONEK radiation. All diffraction patterns were obtained by scanning the goniometer from 6 to 66 (2θ) at a rate of 0.05 min2. The small peak from portlandite in the sample subjected to roasting , which are responsible for reactivity with water and for the hydration process. This explains the usefulness of roasted recycling slurry as a pozzolana additive and active filler [2S), which are capable of hydration and creation of rehydration products [For both cement slurries the portlandite, calcium aluminates, belite, alite, as well as aluminate and aluminoferrite phases were identified. As expected, in case of material not subjected to the roasting process , the pearoasting  can be ee filler ,20. The products ,36,37,38According to the results of the research carried out, an appropriate heat and mechanical treatment of concrete rubble favours obtaining the coarse aggregate from high-quality recycling, of parameters similar to the natural aggregate. As a result, it can be used as a component of full value for cement concretes. The experiment revealed that when 60% of coarse natural aggregate (granite) is replaced by recycled aggregate, it is possible to obtain concrete class C55/67, i.e., a class higher than the control concrete. For comparison, using the recycled aggregate without the heat and mechanical treatment decreased the compressive strength of the concrete by three classes compared to the control concrete. In the case of other tested properties of concrete, it was observed that after roasting debris in 300–600 °C it was possible to obtain the best results, the closest to the control concrete, and sometimes even slightly better, which took place, for example, in the case of flexural strength. After the treatment, trace amounts of mortar remained on the aggregate surface, creating permanent bonds with the new cement paste and improving the investigated feature. Properly selected temperature of concrete rubble roasting determines the degree of aggregate cleaning, which is measured by the amount of cement mortar removed from the surface of the grains. Excessive temperature (900 °C) additionally caused damage of the granite grains, which was the main reason for a significant deterioration of aggregate properties, concrete mix consistence and the properties of hardened concrete. The most advantageous roasting temperature was 600 °C, which also allows to reuse the fine fraction (<4 mm). That fraction may constitute even up to 60% of concrete rubble mass. Usually such material is treated as a waste and is used for storing or filling hollows. After the heat and mechanical treatment, this fraction, rich in cement paste, partially regains its binding properties and may be successfully used as a cement substitute or as a pozzolana additive for cement composites. Moreover, a high temperature is favourable for burning the majority of impurities present in concrete rubble. Therefore, it can be stated that the proposed method of heat and mechanical treatment of concrete rubble at a temperature of 600 °C, despite the related costs, connected among other things with the necessity of building the technological line and energy costs, allows for complex use of concrete rubble for construction purposes, thus replacing non-renewable materials. Therefore, it is a highly ecological solution, in line with the idea of sustainable development of the world and requires further research in this direction.Based on the results of research on aggregate and recycling mortar obtained according to the proposed heat and mechanical treatment of concrete rubble, a prototype of a device for comprehensive recycling of concrete rubble was designed. The device in its design is similar to the rotary furnace, equipped with two chambers: one for roasting and another one for abrasion and crushing. As a result of experimentally selected processing parameters, it is possible to obtain high-quality recycling aggregate and recycling mortar of pozzolana properties. The process of separating the mortar from the coarse aggregate and its partial disintegration is realized in one device. The concrete rubble first reaches the roasting chamber, where it is simultaneously heated to 600–650 °C, assuring almost complete dehydration of cement in the mortar and cyclic lifting on four shelves embedded in equal spaces on a rotating device. As a result, the debris heats up evenly and quickly, and collides with the machine jacket and shelves when falling. Therefore, the mortar is initially separated from the aggregate. Then the material is gradually moved towards the grinding and crushing chamber, where the mortar is finally separated from the aggregate and partially crushed by passing through a system of three rollers. Then the cement mortar together with cleaned recycling aggregate goes outside the machine, e.g., onto the bucket conveyor. The device, as well as the way the concrete rubble is processed, has become the subject of patent PAT.229887 called “Method of separating the hardened cement mortar from the coarse aggregate and disintegrating this mortar, and the device for using this method” .