The main purpose of the study was to propose a modification of Larrard’s formula for both the design and compressive-strength evaluation of ultra-high-performance concrete. The proposed modification consisted of the introduction of new parameters into the original formula that allowed it to consider the amount of binders and fine-grained aggregates, the amount of reinforcing fibers, the specimen shape and size, the curing time, and a reinterpretation of the water/cement ratio. The proposed modification was verified based on comparative analysis with the results of our own experimental studies and results taken from the literature. A very good convergence of these results was demonstrated, indicating the validity of the proposed modification. Ultra-high-performance concrete (UHPC) is defined by the American Concrete Institute (ACI) Committee 239 as “concrete that has a minimum specified compressive strength of 150 MPa  with specified durability, tensile ductility, and toughness requirements” in which “fibers are generally included to achieve specified requirements” [Reactive powder concretes (RPC) are a specific type of UHPC concrete. Larrard  presentsThe W/C ratio within the range of 0.16–0.23, depending on the consistency required.2/g [The CEM I 52.5 type of cement with a low C3A content and Blaine value of about 4000 cmThe amount of silica fume (SF), with dimensions of 0.1–2.5 µm and C/SF = 1:0. 25 .The amount of glass powder (GP) or other filler, with dimensions of 0.8–4 µm and similar material parameters, C/GP = 1:0.25 [The proportions of sand A (80–200 µm) and sand B 400–800 µm) at 30%/70% [00–800 µmThe type of superplasticizer used—polycarboxylate based ,8, idealA sand-to-cement ratio of 1.1–1.4 .The amount and type of steel fibers. Zemei et al.  tested tThe mixing method, speed and duration. Mazanec et al.  presentsThe type and size of aggregate. Collepardi et al.  showed tThe main factors determining the final mechanical performance parameters of UHPC concretes are:In addition to the many factors mentioned above, the curing conditions are important. The effects of the vacuum mixing and curing conditions are presented, among others, in ,22,23,24Considering that so many factors affect concrete’s strength parameters, it is difficult to predict the best values. The basic formula for designing the compressive strength of concrete is Feret’s law, which relates the compressive strength of high-strength concrete (HSC)  to the water/cement ratio, silica/cement ratio, class of cement and characteristics of the aggregate . A furthIn the current literature, the test formulas used do not take into account the type of aggregate, the weight ratio between steel fibers and other aggregate compositions and the strength increase over time. The literature often lacks information about the actual characteristic strength of cement, and only the class is given, which makes it difficult to compare with the results of other authors.The main purpose of the work was to develop and propose a modification of Larrard’s formula for designing ultra-high-performance concrete. The essence of the proposed modification is the introduction of new parameters to the original formula that allow it to include the amount of binders and fine-grained aggregates, the amount of reinforcing fibers, the specimen shape and size, the curing time, and a reinterpretation of the water/cement ratio. Moreover, the proposed modification was verified on the basis of experimental studies, and a broad comparative analysis was performed with results from the literature. A very good convergence of the results was demonstrated, indicating the validity of the introduced modification.2/g Blaine fineness. A polycarboxylic-ether-based superplasticizer (SP) was used to adjust the workability of the UHPC. Two types of microsilica were used: the first (MS1) was a powder with an average particle size (d50) of 0.15 µm, and the second (MS2), with d50 = 65 µm. Both types of microsilica have the same chemical composition because MS2 is formed by the compaction of MS1. One type of the glass powder was selected with d50 = 50 µm. Basalt aggregate with a grain size of 0.125–0.25 mm was used. The chemical compositions of the used powders were determined by X-ray fluorescence (XRF) (The cement used in this study was CEM I 52.5 R white with 4725 cmce (XRF) . The uncThe presented materials were used in part of own experimental research, which was carried out for four types of concrete mixes; the mix proportions of these specimens are shown in In this study, the modified Funk and Dinger model, following the Andreasen and Andersen model, was used in the design of concrete mixes:As presented in the literature, different types of concrete can be designed using Equation (1), by applying different values of the constant ended by , consideObtaining high-strength concrete requires the selection of concrete components in proportions and particle sizes ensuring maximum packing density and minimum porosity of the hardened concrete. For this purpose, a modified Funk and Dinger model, well-established in concrete design practice, is commonly used. However, it should be taken into account that the use of very fine cement components and silica fume need not lead to the highest dry packing density due to the electrostatic forces between these components. Detailed information on the model selection and comparison with other modeling methods of mixtures are presented by Sohail et al. .The compressible packing model (CPM) originally developed by Larrard  was usedIt should be emphasized that the value of the designed concrete’s compressive strength according to Larrard’s Equation (2) was determined after 28 days for a cylindrical sample with dimensions of 160 mm × 320 mm.3 of the concrete, and 3); The proposed modification of the formula for designing ultra-high-performance concrete in our study consists of introducing into Equation (2) parameters describing the amount of binders and fine-grained aggregates, the amount of reinforcing fibers, the specimen shape and size, the curing time, and a reinterpretation of the water/cement ratio, in the following form:fLt=kk kfGraybeal , where t3 form for the B1 series and 40 × 40 × 40 mm3 form for the B2, B3 and F3 series. A variable-speed planetary mixer was used in the mixing procedure for sample preparation:Cement and dry silica fume (5 min);A combination of 80% water and 100% SP ;Sand and glass powder (1 min) + 20% water (5 min).The samples were prepared in 100 × 100 × 100 mmAfter 24 h, samples were disassembled and cured in water at 20 °C in accordance with EN 12390-2:2009 . The mixThe experimental results for four series  are shown in  are show3 and limestone powder filler, which significantly differs from the guidelines presented in the introduction. The use of limestone powder also affects the water supply of the mix composition, which may also affect the final result. It should also be emphasized that the obtained results presented in the paper were determined for the characteristic compressive strength of cement on standard samples. If a standard value is used, e.g., 52.5 MPa, for each of the presented recipes, we obtain correspondingly lower values for the designed compressive strength, which allows for the practical application of the presented formula with a safety margin for concrete. The verification of the formula in relation to the results of other authors showed very good agreement.The observed differences should increase the compressive strength of the concrete. In the case of , where tDue to the fact that Pourbaba et al. , the chaIt should be noted that the experimental results obtained for the amounts of steel fibers 1% and 2% differ slightly from the sample made without the addition of dispersed fibers. The difference between Series 0 and 2 is 2.2 MPa (1.96%), which significantly differs from the data—for example, from own research, where a 15.8% increase in compressive strength was obtained, and from the data available in the literature. However, the difference between Series 2 and 3 is already 7.4% and similar to that in [In order to compare the results obtained with the original Larrard formula (2) with those with the modified formula (3), it is necessary to introduce correction factors to the formula (2) that allow the influence of the shape and size of the samples and the influence of fibers on the compressive strength of the concrete to be determined:The analysis of the designed compressive strength of concrete  indicateThe greatest discrepancies in Formula (4) in relation to the experimental compressive strength of concrete were obtained for Columns 22—64.2%; 21—51.8%; and 5—40.6%. It should be noted that these are recipes that add 8%, 5% and 8% steel fibers, respectively, which the basic formula of Larrard does not take into account. In the case of Formula (5), the differences are, respectively, Column 22—25.1%; 21—28.1%; and 5—7.1%. However, for the formula modified by the authors, the differences are Column 22—6.8%; 21—9.4%; and 5—3.8% and show the greatest accuracy in relation to the experimental results. For Formula (8), the greatest discrepancies occur in Columns 20—28.2%; 21—28.1%; and 22—25.1%, for which, using the modified formula, 20—10.6%; 21—9.4%; and 22—25.1% were obtained, respectively.The average differences in the results for selected papers are shown in We can note that the modified formula obtained the highest accuracy among all the considered publications and the authors’ experimental research.As a result of comparing 28 different mix designs by many authors, using the formula modified by the authors, the best compliance was obtained for 25 results. For the remaining three results, Columns 4, 25 and 26 in A modified formula for the analytical design of the expected compressive strength of UHPC concretes was proposed. The effect of the amount of steel fibers, the type and amount of aggregate, the grain size, and fillers, as well as the size and shape of the prepared samples, were taken into account. The formulas available in the literature do not take these into account, which significantly affects the experimental results. Thus, the proposed modification of Larrard’s formula enables an objective comparative analysis of the experimental and analytical results obtained for various parameters of UHPC samples. The modified formula can also be used to design high-strength concretes and other cement-based composites.In many papers concerning the use of Larrard’s formula, the authors do not provide information that this is the compressive strength for a cylindrical sample of 160 mm × 320 mm dimensions. This formula also does not take into account the amount of steel fibers used, which is found in almost every UHPC formula, hence the large discrepancies between the experimental and theoretical results are stated.The paper presents results of the own experimental tests of four concretes with different compositions, including the use of a combination of steel fibers. The tested concretes were designed using the modified Larrard’s formula. The compressive strength results  MPa for samples without fibers and 161.0 MPa for samples with fibers, were obtained. The obtained experimental results differ by those determined on the basis of the modified Larrard’s formula by % respectively for the samples without fibers and +6.2% for the sample with fibers.The paper shows a positive verification of the modified Larrard’s formula, obtaining a very good agreement of the calculated results with the experimental results available in the literature.Using the original Larrard’s formula without taking into account the specimen shape and size coefficient ented in  shows a Nevertheless, Larrard’s equation requires further modifications to adapt to the currently used recipes containing more and more steel fibers. The subsequent modification levels should concern in-depth verification and refine the curing time coefficient


Staphylococcus aureus (CA-MRSA), particularly skin and soft tissue infections (SSTIs), in Indigenous communities in Canada. The objectives of this analysis were to explore the prevalence of SSTIs due to CA-MRSA and patterns of antimicrobial use in the community setting.Previous publications indicated an emerging issue with community-acquired methicillin-resistant A retrospective chart review was conducted as part of an environmental scan to assess antibiotic prescriptions in 12 First Nations communities across five provinces in Canada including Alberta, Saskatchewan, Manitoba, Ontario, and Québec. Charts were randomly selected from nursing stations and patients who had accessed care in the previous 12 months and were ≥ 18 years were included in the review. Data was collected from September to December, 2013 on antibiotic prescriptions, including SSTIs, clinical symptoms, diagnostic information including presence of CA-MRSA infection, and treatment.A total of 372 charts were reviewed, 60 from Alberta, 70 from Saskatchewan, 120 from Manitoba, 100 from Ontario, and 22 from Québec. Among 372 patients, 224 (60.2%) patients had at least one antibiotic prescription in the previous 12 months and 569 prescriptions were written in total. The prevalence of SSTIs was estimated at 36.8% (137 cases of SSTIs in 372 charts reviewed). In 137 cases of SSTIs, 34 (24.8%) were purulent infections, and 55 (40.2%) were due to CA-MRSA.This study has identified a high prevalence of antibiotic use and SSTIs due to CA-MRSA in remote and isolated Indigenous communities across Canada. This population is currently hard to reach and under-represented in standard surveillance system and randomized retrospective chart reviews can offer complimentary methodology for monitoring disease burden, treatment and prevention. The health of First Nations populations is a priority for the Canadian government, and for First Nations themselves . DispropStaphylococcus aureus (MRSA) has been rising, with disproportionate rates of community-associated (CA) MRSA documented among First Nations populations living in remote or rural areas, in Canada [S. aureus isolates were CA-MRSA. They also found that in 2011, the rate of CA-MRSA infection was 2482 per 100,000 people [In Canada, the Federal Action Plan on Antimicrobial Resistance (AMR) and Use was launched to monitor AMR, determine the full magnitude of the problem, and to evaluate the appropriate use of antibiotics . The incn Canada . Muilebon Canada  reports 0 people . Further0 people . The appCapturing timely and accurate information from remote and isolated First Nations communities remains an ongoing challenge for infectious disease surveillance systems. As a result, more information is needed on prevalence of CA-MRSA infections, SSTIs, including information on clinical presentation, diagnoses and treatments. The objectives of this analysis were to: 1) Identify the prevalence and patterns of SSTIs, including those caused by CA-MRSA, and antibiotic prescriptions; 2) Estimate the prevalence, clinical presentation and diagnostic information of SSTIs, and 3) Assess the appropriateness of antibiotic prescriptions for SSTI cases.n = 96 rounded to 100. Based on the estimate from the internal audit, we assumed 1 in 4 charts would contain an antibiotic case, hence the number of charts required was calculated as n = 400 to find 100 charts containing an antibiotic case. Charts were randomly selected at a rate of approximately 20 per 1000 population in the nursing station catchment area. Upon reviewing 372 charts, we found 224 charts that documented at least one antibiotic case in the previous 12 months, we ceased collecting additional data.This study was a retrospective chart review conducted at nursing stations in First Nations communities in five Canadian provinces . As part of a quality improvement project at Health Canada, communities were invited to participate on a voluntary basis and were enrolled in consultation with the Regional Nursing Officers (RNO). At the request of the communities, the facility names and communities are not identified to ensure confidentiality. A simple random sample of patient paper charts was selected by choosing a random starting point in the charts drawer and pulling out the charts to be reviewed in an evenly-spaced manner until the required number of charts to be review was reached. The review was conducted by research team  independent of the nursing stations. Patients charts were included in the review if they had accessed care in the previous 12 months and were ≥ 18 years of age. Any time an antibiotic was prescribed during this one-year period, it was captured in the Antibiotic Tracking Case Report Form (CRF) for analysis. Patient names and unique identifiers were not recorded on the antibiotic tracking data sheet, as each antibiotic tracking data sheet was assigned a number. There was no personal information or personal identifiers in the data collection. At the time of the study design, there were a total of 85 nursing stations with the First Nations and Inuit Health Branch (FNIHB) at Health Canada. The sample size calculation was based on 12 nursing stations (14.1%) being able to participate in the study and calculated the estimated proportion of antibiotic use. SSTIs were measured as both a patient-based estimate (e.g. the number of patients with at least one SSTI in the previous 12 months) and case-based estimate .Demographic variables included gender and age. Clinical variables included pre-existing conditions such as diabetes, cardiac disease, alcohol use disorder, renal disease, pregnancy, liver disease, Chronic Obstructive Pulmonary Disease (COPD), immune-compromise, and/or asplenia, and presence of a medical device .Staphylococcus aureus (MSSA), other organism, or unknown.Information on etiologic agent was collected for each unique SSTI case. CA-MRSA was defined based on the standardized epidemiological case definition proposed by US Centers for Disease Control and Prevention (CDC) , and thePrimary SSTI symptoms were categorized as purulent , non-purulent , skin breakdown , wounds , or unknown. All cases were considered SSTI in the present analysis as they were treated as infections with antibiotic(s) prescription at the nursing stations. Treatment options included wound care, incision and drainage, prescribed antibiotic, type of antibiotic , antimicrobial combination therapy, and adjunctive therapy. Clinical outcomes were categorized as cure, failure, improvement and unknown. Data was extracted on diagnostic tests including wound culture, blood culture, complete blood count (CBC), no diagnostic test, and missing.An evaluation of appropriateness of antibiotic use for SSTI was conducted by subject experts  using two guidelines - the Clinical Practice Guidelines (CPG) administered by the FNIHB  and the Patient-based analyses calculated the prevalence of antibiotic use by dividing the number of patients with any antibiotic prescription by the total patient-charts sampled. Case-based analyses used the total number of unique SSTIs to summarize etiologic agents, diagnostic testing, clinical symptoms, outcomes, and appropriateness of the prescribed antibiotics. All data were analyzed using SAS statistical software, version 9.3 .A total of 372 patient-charts from 12 nursing stations were randomly selected and reviewed, 60 from Alberta, 70 from Saskatchewan, 120 from Manitoba, 100 from Ontario, and 22 from Québec (Table n = 86) vs. all 224 patients, the groups were characteristically similar, except the prevalence of pregnancy, as there were no pregnant women in the SSTI patient populations (p = 0.0416).Table streptococcus (n = 9), Viridans group streptococcus (n = 1), Enterobacter cloacae (n = 2), and Serratia marcescens (n = 1). In 69 cases of SSTI, the organism was unknown as culture was not applicable or test results were missing. Among the 137 SSTIs, 34 (24.82%) were purulent, 15 (10.95%) were non-purulent, 34 (24.82%) were classified as wounds and 37 (27.01%) infections remained unknown. Incision and drainage was performed on 12 (8.76%) SSTIs: on eight purulent infections , and on one non-purulent infection . Oral antibiotics were the most commonly prescribed (62.77%), then topical only (17.52%) followed by IV (8.76%) and both topical and oral (8.76%).Table n = 21). Only 29% of MRSA isolates were susceptible to erythromycin, but most were susceptible to clindamycin and co-trimoxazole (90.5 and 95.2%), which also suggests that most MRSA infections were probably due to CA-MRSA phenotypically, in addition to the epidemiological case definition [Table finition .Table 4Table Delivering health care to remote and isolated Indigenous communities continues to be a public health priority in Canada. Almost 37% of our patients were seeking care for SSTIs at nursing stations. Most patients were presenting with purulent or open wounds. Of critical concern, CA-MRSA was documented in over 40% of SSTIs, either by wound culture or presumed by previous colonization. Although research around skin infections in Indigenous communities is limited, this high burden of infection aligns with the current literature; in Australia, researchers have found that 75% of residents from two remote Australian Indigenous communities visited a primary healthcare centre with a skin infection at least once in a year, and skin infections were the dominant reason for visiting a primary healthcare centres in Indigenous communities . They alThis study has identified a high annual prevalence of antibiotic use in nursing stations with over 60% of patients having at least one antibiotic prescription over the previous 12 months. In Canada, it was reported that 660 to 683 antibiotic prescriptions per 1000 inhabitants were dispensed in the communities between 2010 and 2012 . In thisAppropriateness of antibiotic prescription was evaluated in terms of choice of agent, dose, frequency and during using Health Canada CPG and the IDSA clinical guidelines. While there was a high degree of agreement between CPG and IDSA with regards to choice of antibiotic, there was considerable discordance with respect to dosing and duration. This should be taken into consideration for providers and surveillance systems when conducting comparative analyses. In addition, higher incidence of purulent SSTIs (e.g. abscesses), highlight the importance of antibiotic sparing treatment approaches, such as incision and drainage.Staphylococcus aureus infections were CA-MRSA strains, and 25% were re-infections [In Canada, the proportion of CA-MRSA strains have been steadily increasing . Investifections . While hParticipation in this study was voluntary and it is possible that communities with higher SSTIs or CA-MRSA prevalence would be more or less likely to participate, limiting the generalizability of our findings. Antibiotic utilization patterns were defined by prescription only and we are unable to comment on uptake or adherence, introducing measurement bias. The chart review only includes patients who accessed and received care, potentially excluding patients who are most vulnerable. Additionally, the blinding of reviewers was not possible as we had to review paper charts in the nursing station. However, the authors had no previous interaction with patients and staff in the visited nursing stations and have no conflict of interest. As this was a retrospective analysis, the availability of data was limited: inconsistent availability of microbiology reports, lack of consistent description of the clinical presentation, lack of documentation of follow-up (lack of information on patient outcomes), missing information about patient’s allergies (missing or not updated) and current prescriptions (e.g. for chronic diseases). This large proportion of missing information may have biased the results. For example, missing information on the etiologic agent (about 40% of SSTI cases were confirmed as MRSA infections and the etiologic agent remained unknown in 50% of the cases) might underestimate the prevalence of MRSA in SSTIs and the true proportion might be higher than estimated in this study. Prevalence of MRSA has been documented as high as 50% in some regions . PatientThis study is filling an important data gap on SSTIs, CA-MRSA, and antibiotic use in First Nations communities in Canada. We have observed a high annual prevalence of antibiotic use among inhabitants living in remote and isolated communities seeking treatments in nursing stations. Many of these community members are seeking care for SSTIs, with over 40% of cases attributable to CA-MRSA infection. In addition to appropriate and timely medical treatment, a comprehensive approach to infection control and prevention is needed to ensure that First Nations living in remote and isolated communities achieve equitable healthcare services.


When any problems related to civil engineering structures appear, identifying the issue through the usage of only one measuring method is difficult. Therefore, comprehensive tests are required to identify the main source. The strains and displacement measurements, as well as modal identification, are widely used in the nondestructive testing of structures. However, measurements are usually carried out at several points and confirm or exclude only one of many potential causes of the problem. The main aim of this paper is to identify the causes of miter gates’ excessive vibration. The research includes displacement measurements using a tachometer and a laser scanner, acceleration measurements connected with modal analysis, and calculations with the finite element method (FEM) model. The numerical model underwent verification regarding test results. Particular attention was paid to evaluate the practical use of a laser scanner for diagnosing miter gates. Unlike classical methods, it measures many points. The analysis eliminated a number of potential causes of excessive vibration and highlighted the field of excessive deformation. The identified anomaly could be associated with bearings’ misalignment after closing the door. This construction part should be subjected to further research using classical methods. The laser scanning has been proven to be a method that can only generally present the deformation of the structure. The aim of this paper is to indicate the causes of the poor operation of the water gates at the river barrage on the Vistula river in Wloclawek (the city located in the center of Poland). The problem had been identified by lock operators during normal operations of the chamber filling and emptying. It was related to a “sudden movement” that caused vibrations and shocks of the lock lower gates. The vibrations were transformed to other structural elements and were also noticeable in the control room building. The administrator of the facility failed to identify the main cause of the excessive vibration. Long-time and intensive vibrations can cause structural damage to a river barrage. Control structures related to the damaged strategic facilities pose a serious hazard and can cause enormous human and material losses. Due to these concerns, the facility owner commissioned an engineering evaluation regarding the cause of the vibrations and a proposed method of repair. Given the high importance of facilities in the form of locks on waterways, the detection of possible failures and appropriate monitoring of the facilities has a significant impact on the economic situation in the region. Their inspection usually involves the use of visual methods using surveying techniques combined with numerical calculations which are presented in . In our For the purpose of structure static analysis, first, a three-dimensional 3D) numerical model was performed using the finite element method (FEM) SOFiSTiK environment. Numerical modeling with FEM is commonly used for different issues related to construction and the determination of limit states of the structure of materials. FEM is an all-purpose tool used for structure numerical analyses. The basic concepts of the method are presented in D numeric. AlthougTo determine displacements during in situ tests, some surveying measurements were performed. Surveying services relate to a standard procedure, determining any displacement caused by different forces. Our tests employed two methods, i.e., tachymeter measurements and 3D laser scanning. The assessment of structure displacements resulting from test load using monitoring is specified in the work of , where sIt is worth mentioning that measurements directly related to engineering structures are of great importance in the world. Any development of measurement methodology in the essence of a multidisciplinary approach means that we are able to use the acquired information for the general good of society. For the analysis of the literature in this area, special attention should be paid to , in whicWe divide the structure of our work into an introduction regarding the determination of the purpose of our work and the proposal of a comprehensive measurement service to determine the optimal conclusions with a numerical calculation base. Next, we present the concept of our methodology, together with an appropriate description of the sensors and instruments. Subsequently, we present the results of the measurements and analysis. Lastly, the obtained results are discussed, and appropriate conclusions are formulated.The lock was delivered mainly for navigation purposes, raising and lowering boats, ships, and other watercraft between different levels on the river. The maximum designed drop was 12.80 m, and the actual drop was 14.40 m. The lock, including roadstead, was located on the left bank. It was provided by a chamber with a size 115.00 × 12.00 m, at a downstream bar min. depth of 3.50 m (1.10 m at present). The lock featured a chamber, including the upper head and bottom head . The topSince lock erection, no works were performed that could have impacted on its structure or performance. In 2005, works related to renovation were delivered, including repair of concrete surfaces, sealing of expansion joints, delivery of head crown top surfaces and chamber walls, delivery of curbstones, and application of the concrete protective coating. During the following few years after the renovation, some irregularities were evident during gates’ operation, namely, sudden vibrations during water level change in the lock. The so-called sudden movement occurred only sometimes and was an accidental and occasional phenomenon.y = 235 MPa. Additional elements included bracing, rubber sealing, arched bearings, and rotating bearings, and top deck. Gates closing and opening were provided by hydraulic cylinders.The support gates of the bottom head were related to the movable double-leaf  feature When totally emptied, the structure of the lock chamber underwent inspection based on visual examination, including photo records. The examination indicated misaligned miter bearings. Additionally, consultations followed with operators regarding any noticed cases related to interruption of lock filling and emptying. Operators reported some factors contributing to the sudden movement such as high temperature, strong wind blowing from the east (top water), and the irregular position of miter bearings after gates closing. According to the received information, the following goals of this research were set: To assess the static work of the lock during filling and emptying and assess work and condition of rotational bearings on the top and bottom. To achieve the goals, surveying and dynamical field tests were planned . Before A, maximum top water level (57.30 m above sea level) and bottom water zero level (41.80 m above sea level);B.1, top water level 1/3 and bottom water level + 1 m;B.2, top water level increase from 1/3 to 2/3 and bottom water level + 1 m;B.3, top water level increase from 2/3 to 3/3 and bottom water level + 1 m.Firstly, static analysis was performed with the numerical model. For this purpose, the 3D model was created with FEM SOFiSTiK. Since the structural geometry of the gates’ leaves and the hydrostatic loading are symmetric about the leaf center line, only one of the gates’ leaves was modeled. Two-dimensional, four-nodal shell elements and one-dimensional beam elements were used for the construction . The gatIn both models, mesh convergence analysis was established. For the applied load with maximum magnitude, displacements in representative nodes were checked. The maximum dimension of the element was reduced iteratively until the displacements in subsequent steps did not change by more than 3%. In each subsequent step, the element size was reduced twice.Surveying measurements were based on measurements performed with Leica TS30  (with a precise mode about 0.6 mm + 1 ppm / typ. 7 s) at data recording precision of 0.1 mm. For comprehensive survey and assessment regarding the entire gate deformation, measurements were performed with laser scanning. All measurements were performed using the Faro branded device, Focus 3D X130  (with an accuracy of about 2 mm and a measurement speed up to 1 million points per second). Survey results allowed assessment regarding gates’ element deformation during lock filling. Before measurement, stabilization followed 6 flat marks a to ensuMeasurements with a tachymeter and a laser scanner were performed at the following 4 different water levels : (1) lev2. The acquisition sampling rate was established to be 300 Hz. If predicted, interesting natural frequencies of the gates were below 30 Hz, it was evaluated as high enough to ensure the obtainment of all information about vibrations. In addition, acceleration measurements were performed on the gates’ steel structure. As mentioned, the dynamic measurements had two main purposes, i.e., validation of the numerical FEM model and detecting of the unexpected movements of bearings. The measuring system consisted of the HBM PMX Amplifier  system, 4 MEMS  Direct Current (DC) response accelerometers, and wires. The amplifier was connected by an Ethernet wire to a PC computer. HBM CatmanEasy  software installed on the PC was used in the configuration of the system and data acquisition. The used amplifier was designed for, and typically utilized in, industry control systems. However, after some modifications, its parameters allowed researchers to use it in laboratory and field tests. Improvements were carried out by the crew of the Field Test Laboratory of the Technical University of Gdansk. The amplifier was covered with a stiff box to protect it from mechanical damage and adverse weather conditions. Additionally, a battery was inserted into the box. Therefore, after connection with the PC computer (notebook type), it created a stand-alone, portable, 16-channels measuring system, which could be used for up to 8 hours without access to electricity. Another advantage was the elimination of redundant, additional vibrations coming from the electric generator’s work. It was especially significant to use low-noise sensors when low-magnitude vibrations are measured. Thus, the created acquisition system is very universal and convenient for field tests on bridges and other infrastructure constructions. In the system, following MEMS DC response, 4 to 20 mA signal output sensors were used as follows: 2 tri-axial accelerometers TE 4332M3-002  and 2 one-axial accelerometers TE 4312M3-002. The following characteristic parameters of these accelerometers were: range ± 2 g, sensitivity 4.0 mA/g, frequency response 0 to 200 Hz, and natural frequency 700 Hz. The noise measured on the gates’ leaf, if no intentional load was applied, was in the range of ± 0.005 m/s2, the shaking stopped. For analysis, when the shaking stopped and vibrations were damped to about 0.5 m/s2 was used as a signal.In each of the 6 positions, the gates’ leaf was excited three times to natural vibrations, and then was left until vibrations damped. The measurements were carried out separately for the left leaf and separately for the right, as shown in During dynamic tests, time-domain free-response data were obtained. There exist numerous techniques for identifying the modal parameters from free vibration signals ,50. In tWe consider the state-space representation of a discrete-time, linear time-invariant system in the form of:These matrices in the sequence are known as the Markov parameters and describe the pulse response of the system. A system realization is the estimation of the set of matrices In ERA, the first step is the formulation of the block Hankel matrix, composed from the Markov parameters in the form:The shape of the Hankel matrix is equal The second step is the factorization of System matrices, which are minimum realization, can be calculated as:Modal damping rates and damped natural frequencies can be obtained from the real and imaginary parts of the enerated . It can enerated ) and MPCenerated ) were emBefore static analysis, the model underwent verification provided by comparing model eigenforms and eigenfrequencies with those identified in the field tests. Among all measuring series, for both gates’ leaves, in the range to 10 Hz, two eigenmodes always occurred. Sometimes, in the results, one more stable mod appeared and its frequency was below 1 Hz. Subsequent analysis confirmed that it was the first mod of opened gates. However, it did not show up in all measurements, and cannot be taken into account for comparisons and diagnostics. The “opened model” was used for the purpose of modal analysis. The model was validated by adding non-structural masses to the top deck and the miter bearings. First, three eigenfrequencies and eigenforms were determined  and bothAfterward, the verified FEM model was loaded with static water pressure at different water levels in the lock. A “closed model” was used for this analysis. The calculated load cases were as specified previously: A, B1, B2, and B3. During chamber emptying, measurements with a tachymeter were performed at the following points: R1, R2, R3, R4, R5, and R6. During chamber filling, measurements with a tachymeter were performed at the following additional points: R7, R8, R9, and R10. Reading was performed four times . Calculations regarding the displacement of measuring points at X, Y, and H direction for emptying were based on the difference between final and initial coordinates (the difference between water levels 3/3 and 0/3). Calculated displacements during filling were based on the difference between 1/3 and 3/3 water levels. The following tables include displacement measurements .Note, at minimal water level, the minimal opening of the lock gates followed as a result of wind. During the initial filling phase, the displacement was also affected by the deformation of the gaskets. This fact explained the difference between dY displacements during filling and emptying. In addition, because of this, the diagram regarding top water increases from the 1/3 to the 3/3 level was used, as the most representative for the comparative analysis of displacements. The comparative analysis was performed regarding displacements at Y direction  obtained during surveying measurements and laser scanning against numerical calculations. Dynamic measurements in different positions of the gates’ leaves do not indicate any relevant displacements of the support bearings. A small difference between the identified, normalized modal displacements can be a consequence of adherence of the gasket to concrete elements. Differences occur, especially in the case of point K6, which is located near the bottom part of the gates, where the gasket is mounted. In addition to this, eigenfrequencies and eigenforms confirm matching between real structure and the numerical model.During lock filling and emptying, the gates’ operation followed under stress and the numerical analysis did not indicate any excessive stress. The comparative analysis was performed regarding measurements and calculations of structure displacement resulted from water level change from 1/3 to 3/3. Horizontal displacements, at a direction parallel to the gates’ surface obtained based on the numerical model and the measurements with the tachymeter, were similar. Insignificant variance resulting from gates additional displacements resulted from pressure and gasket deformation at the initial phase during lock filling, which is a natural effect. Thanks to the miter gasket’s deformation the sealing of gates was provided. The numerical model did not include this phenomenon; only points close to the miter axis indicate an anomaly. Displacements measured with tachymeter in points R5 and R4 (miter top corner) are significantly different than those obtained with the numerical model. However, the remaining results indicate that structure operation was consistent with the numerical model (design input). Therefore, we could exclude any significant damage to the main structural elements. The displacements indicated by laser scanning were bigger than the results obtained using two other methods. The work provided an example regarding measurement accuracy difference during the elaboration of differential maps . AdditioIn summary, the visual examination and analysis regarding surveying measurements, vibration measurements, and laser scanning indicate that miter gates work properly, although all of the field tests were conducted without the occurrence of sudden movement. Thus, we concluded that only in the case of normal conditions does the operation of the gates work properly. All of the comprehensive measurements allow researchers to conclude that the rotating bearings work without redundant lose, and if sudden movement does not occur, the miter gates are characterized by elastic behavior. The differences between the measured and calculated displacements in the R5 and R4 points could indicate that boundary conditions close to these points can vary in structure and in the numerical model. During the visual examination, misaligned positions of the miter bearings were noticed. Unfortunately, no sudden movement was observed during the measurements. However, photographic documentation was taken before and after the example of sudden movement. The research of the analyzed structure was performed using multiple methods that allowed assessment regarding different performances of the structure. The comprehensive analysis of all results enabled us to exclude some potential causes of excessive vibrations. Dynamic measurements were used to assess the condition of rotational bearings and confirmed their lack of redundant lose during operation. The correct operation of the rotational bearings was checked by comparing the eigenforms of the gates’ leaves in different opening positions. Additionally, thanks to the dynamic results, the numerical FEM model could be validated. The tachymeter measurements provided information about the generally elastic behavior of the gates during operation. Although, as compared with the FEM results, they also indicated points at which behavior is inappropriate. Deformations of these parts of the structure (near points R4 and R5) probably are caused by misalignment of miter bearings. The results from laser scanning are consistent with the FEM results in terms of direction and shape of deformation, also in both cases, an order of magnitude of displacements are similar. The laser scanning has been proven to be a method that can only generally present the deformation of the structure. Due to the subtraction of coordinates from two different point clouds, the accuracy of this measurement is insufficient to assess displacements in detail. In the authors' opinion, laser scanning can be used to measure displacements if they are significantly bigger than error arising from point clouds subtraction. However, it should be pointed out that all of the conducted measurements are significantly faster and cheaper in execution than is typical for cases utilizing strain gauges. Additionally, all of the employed methods provided mutual verification. The new combination of comprehensive measurement methods in nondestructive testing of the miter gates excluded some potential reasons of excessive vibrations. Nevertheless, further investigation should focus on researching how misalignment of miter bearings influences sudden movement existence. A possible option is to utilize inductive sensors between miter bearings to acquire mutual displacements. Another one is to use strain gauges and to detect indirectly the bearings without adherence.


Sand has been considered to be something of an immeasurable quantity. There are many indications that this view is no longer valid and that the limiting of natural aggregates usage is doubly justified. Firstly, the extraction of natural aggregates is expensive and has a huge impact on the environment. The main issues in sand and gravel mining are the large areas that are affected, ground water level changes, illegal mining, unsuitability of desert and marine sand, and costs of transport. Secondly, metallurgical waste can be used as a substitute for natural aggregates. This is doubly beneficial—the waste is recycled and the use of natural aggregates is reduced. Waste is stored in landfills that take up large areas and there is also the possibility of ground and groundwater pollution by hazardous compounds. The research presented in this article focuses on the technological conditions of using metallurgical waste in its original form and as a component of recycled concrete aggregate (RCA). The use of metallurgical sludge waste or crushed or round RCA to produce concrete deteriorates the consistency and does not significantly affect the air content and density of the concrete mix. RCA lowers the density of hardened concrete. Metallurgical sludge waste or RCA usage adversely affect the absorbability and permeability of concrete. Concrete containing metallurgical sludge waste is of higher compressive strength after 7 and 28 days, with up to 60% of waste as a sand replacement. RCA concrete achieved higher compressive strength also. Global production of aggregates was 21 B tonnes in 2007 and 40 B tonnes in 2014 . AccordiFirstly, natural aggregates are, as the name suggests, a natural resource. Their extraction is expensive and has a huge impact on the environment ,7,8. SanSecondly, metallurgical waste—sludge, slag and dust from blast-furnace, steel and sintering processes can be used as a substitute for natural aggregates. This is doubly beneficial—the waste is recycled and the use of natural aggregates is further reduced. This waste is deposited in landfills that take up large areas. There is also a danger of hazardous compounds leaking to the ground and groundwater ,18,19,20Therefore, it is worth considering the recovery and use of other materials as an alternative to natural aggregates—various types of industrial waste and demolition rubble from buildings such as bricks or concrete ,22. Recycled concrete aggregate (RCA) is a shredded waste generated during the demolition of concrete and reinforced concrete structures. The resulting aggregates are the subject of research to reduce the need for natural aggregates for concrete applications.The use of RCA increases the demand for water and decreases the consistency of the concrete mix with the same effective water-cement ratio. This applies to mixtures containing 50% and 100% RCA . SimilarNo effect of the substitution of 50% and 100% RCA on the air content of the concrete mix was found . The stuThe full replacement of the natural aggregate with RCA results in a lower concrete mix density . The denThe use of RCA may result in deterioration of the mechanical properties of concrete—this depends on the quality of the concrete used. It is stated that the use of 30% RCA as a substitute for natural aggregate has not resulted in a decrease in compressive strength . IncreasThe use of RCA as a replacement for natural aggregate results in increased concrete absorbability. The absorbability increases from about 5.5% for concrete without RCA to about 8% at 100% replacement level. Increase of absorbability and porosity by 15%–38% and decrease of density by 4%–7% for HPC is described in . StudiesThe capillary action and permeability of concrete containing RCA is increased by about 20% compared to the reference concrete . The perThe use of fine RCA causes a decrease of the durability properties of concrete—an increase of absorbability and permeability, increase of carbonation depth and chloride migration rate . HoweverOther uses of the RCA include: roads substructures, earth dam construction ,36,37, pRecycled aggregate concrete (RAC) is a concrete in which all or part of the natural aggregate is replaced by waste materials . Many reA lot of waste from the metallurgical industry has been involved in concrete technology. The main example is the use of ground granulated blast furnace slag and fly ash as a component of cement and concrete . Blast fAnother steel making process by-product is sludge. The use of sludge as an aggregate or aggregate component is not widely recognized. It is related to the fineness of the material causing a huge increase in water demand and the content of heavy metals, which may cause an extension of the initial setting time of the cement . Thermally treated steelmaking sludge was used to manufacture the lightweight aggregate . Sludge The research presented in this article focuses on the technological conditions of using metallurgical waste in its original form and as a component of RCA. Such an approach to the possibilities of metallurgical waste management has not been widely studied before.Dried and ground material see Component of rounded RCA as a partial replacement of fine aggregate see Component of crushed RCA as a partial replacement of fine aggregate see Metallurgical sludge waste was added to concrete in three forms:The former method is generally suitable for manufacturing of non-structural concrete elements, weak concrete layers or curb fixing, etc. Both latter methods may be used in situation while the concrete mix is left on the building site or the concrete do not meet requirements and need to be recycled. Then the metallurgical sludge waste together with admixture is added to concrete mix to form RCA. Additionally, the second method may be used to recycle elements manufactured with concrete containing metallurgical sludge waste and reuse it as RCA after crushing.During research concrete with RCA containing metallurgical sludge waste, concrete with metallurgical sludge waste as a partial replacement of fine aggregate and the reference concrete were prepared. RCA was manufactured in two forms—rounded and crushed.For the preparation of RCA containing metallurgical sludge waste and all concrete types following materials were used: Portland cement, natural coarse and fine aggregate, metallurgical sludge waste, admixtures (superplasticizer and concrete mix recovery agent) and tap water. All ingredients were stored in temperature 20 ± 1 °C.Portland cement CEM I 42.5 R that is complying with requirements of EN 197-1:2012 was used. Phase composition of cement is given in Superplasticizer containing polycarboxylate ethers used for consistency enhancement. It was used both for crushed and rounded RCA preparation and execution of concrete with dried metallurgical sludge waste and containing RCA.Concrete mix recovery agent—two-component, powdered special agent for recovery of concrete mix and form rounded RCA.Natural aggregate both coarse and fine were used. Coarse aggregate that was used is natural gravel and fine one was a natural quartz sand. Aggregate mix was composed of three separate fractions 0–2, 2–8 and 8–16 mm. For the grading curve of the aggregate mix see Metallurgical sludge waste used in research was obtained from one of polish steel manufacturers. As by-product it was stored on the landfill. It consists of sintering sludge, blast furnace sludge and converter sludge in varying proportions. The appearance of unprocessed and ground dried metallurgical sludge waste is shown in 3)2∙2H2O phase [Chemical composition of metallurgical sludge waste from this landfill depends on exact point from which it was taken. Chemical composition is given in 2O phase .Both rounded and crushed RCA were prepared using the same recipe. The only difference is presence of concrete mix recovery agent in former one. Four preliminary recipes were prepared to obtain optimal proportions of components. Description of mixes used for RCA preparation are given in Preparation of mix according to recipe 1  and formCover with foil for first 24 h to avoid excessive evaporation of water.Curing of composite for next 27 days in water at temperature 20 ± 1°C.Hammer crushing of aggregate to grain size <60 mm see a.Mechanical crushing of aggregate see b.Sieve analysis of crushed RCA see .Stages of crushed RCA manufacture:Preparation of mix according to recipe 1  in free 3 of concrete mix).Mixing for 3 min at high speed after adding concrete mix recovery agent component A (0.5 kg for 1 m3 of concrete mix).Mixing for 2 min at medium speed after adding concrete mix recovery agent component B  in comparison to the reference mix. However, this is not a significant difference and can be related to the vibration time and accuracy of the test method. The results of the air content in concrete mixes tests are shown in 3. All mixes containing metallurgical sludge waste showed a slightly higher density (2.36–2.39 kg/dm3). This is caused by a higher degree of structure tightness by introducing a very fine material. The degree of compactness can be significantly higher due to the large difference in density between metallurgical sludge waste and sand, which is significantly lower for the former material. The results of the concrete mix density test are shown in The density of the concrete mixture is related to its air content. The reference mixture had a density of 2.32 kg/dm3. This similarity is connected to denser structure of concrete containing metallurgical sludge waste, despite of lower density of metallurgical sludge waste itself in comparison to sand that it replaced.Density of hardened concrete is presented in Concrete is a porous material. The pores it contains, in particular the capillary ones, are filled with water in damp and wet environments. Concrete’s absorbability is one of the properties affecting its durability—the higher the absorbability, the greater the possibility of penetration of aggressive chemicals dissolved in water. Testing the absorbability of concrete consists in determining the amount of water that concrete is able to absorb until the pores are completely filled. The absorbability of the reference concrete was 6.5%. With an increase in the content of metallurgical sludge waste, the absorbability of the concrete increased up to 8.5% when 90% of the sand was replaced by metallurgical sludge waste. The air content study showed no difference between the individual concrete mixes that could explain this relationship. This means that during the hardening and drying of the concrete, water evaporates not only from the cement matrix but also from the metallurgical sludge waste, which is part of the aggregate. This can be caused by the absorbability of the aggregate, which is considerably higher for metallurgical sludge waste compared to sand. The results of the concrete absorbability test are shown in The permeability of concrete is related to its density and absorbability. It is defined as the depth of water penetration under pressure. Apart from permeability, it is another factor influencing the durability of cement composites. Compressive strength of concrete is one of the most important properties of concrete. The results of compressive strength tests of concretes containing metallurgical sludge waste as a replacement of sand is shown in The reference mixture showed a slump of 105 mm, and is qualified aa S3 consistency class according to EN 206-1. Results of consistency tests are presented in In concretes using crushed and round RCA as a replacement for natural aggregate, the amount of air in the concrete mix increases. Test results are given in 3. Densities of concrete mixes containing RCAs are given in For concrete mixes containing metallurgical sludge waste as a sand replacement, the density of concrete mix was independent of the replacement level. In case of concrete mixes containing RCA, the situation is similar. All mixes densities are in range of 2.24–2.32 kg/dm3) than natural gravel aggregate (2.65 kg/dm3)—this reduces the density of the composite. However, it is necessary to be aware of a much greater replacement level in terms of volume—here the coarse aggregate is changed and in the previously described case only sand, which occupies much less volume in the concrete mix.In the case of concretes where sand was replaced by metallurgical sludge waste, the density of concrete was independent of the degree of replacement. In case of concretes containing RCA, the density decreases with increasing RCA content. It is shown in Water absorbability of concrete containing crushed RCA as 25% replacement of coarse aggregate is higher in comparison to reference concrete. However, with a greater replacement level, the absorbability decreases. This is surprising because of the higher absorbability of the RCA compared to natural aggregates. In the case of round RCA, the absorbability of concrete increases as the replacement of coarse aggregate by metallurgical sludge waste increases. Absorbability of concrete with coarse aggregate substitution by RCA is presented in Permeability of concrete containing 25% and 50% crushed RCA replacement of gravel is similar to reference concrete. 75% of crushed RCA in concrete leads to increase of permeability. However, the increase is not very evident. Permeability of crushed RCA concrete is shown in The results of compressive strength tests of concretes containing both crushed and round RCA as a replacement of coarse aggregate is shown in To summarize the research, the authors draw attention to the technological possibilities and environmental benefits of using both metallurgical sludge waste in a least processed form and aggregates made with its content.The first possibility is the disposal of metallurgical sludge waste itself in concrete. Metallurgical sludge waste is originally stored in landfills that take up space that can be used in another, more favorable way. In addition, it can cause soil or groundwater contamination. Therefore, using it as a partial substitute for sand is environmentally beneficial. In addition, the consumption of sand, which is a natural resource, and its reserves are limited and its excavation is regulated in many countries by law. One could go further in this consideration and think that once the lifespan of concrete structures or elements containing metallurgical sludge waste has expired, such concrete could be used as RCA, after crushing.For the production of ready-mixed concrete and its use on the construction site, there are two possibilities if there is an excess of mix or the mix does not meet the requirements. The first is to add waste and superplasticizer to the mix to improve consistency and then pour it onto a foil-covered surface and after hardening, crush the resulting composite and use it again as crushed RCA. A second option is to use a special admixture to recover the excess concrete mixture and process it into round RCA.The use of metallurgical sludge waste or crushed or round RCA to produce concrete deteriorates the consistency. This is associated, in the case of metallurgical sludge waste, with its high water demand, and fineness and, in the case of RCA, with its high absorbability.The use of the superplasticizer will result in additional costs, but without its use it will not be possible to use metallurgical sludge waste over 60% or RCA over 50% due to the deteriorated concrete consistency. Additionally, concrete mix recovery agents can increase costs. However, it is certain that the use of waste will have a positive environmental effect.The use of metallurgical sludge waste as a replacement for sand in concrete does not affect the air content, density of the concrete mix or the density of the hardened concrete.Using RCA as a replacement for coarse aggregate increases the air content in the concrete mix. This is due to the high porosity of RCA. RCA does not have a significant effect on the concrete mix density, but it does affect the density of the hardened concrete. This is due to the fact that RCA has a lower density compared to natural aggregate and, when present in the mix, contains water which evaporates during curing.The use of metallurgical sludge waste as a replacement for sand in concrete increases its absorbability and slightly increases the depth of water penetration under pressure. It is connected with its higher porosity. If round RCA is used, the absorbability of the concrete is also increased. The permeability of the concrete increases as well. This may jeopardize the durability of components made of such concrete and requires further testing.The use of metallurgical sludge waste as a replacement for sand in concrete improves the mechanical properties after 7 and 28 days of curing up to 60% of metallurgical sludge waste content. However, even replacing 90% of the sand with metallurgical sludge waste does not adversely affect the compressive strength. RCA’s use as a replacement for natural aggregates has a positive effect on the compressive strength of the concrete at all testing dates. The improvement in mechanical properties is associated with a reduction in the effective water-cement ratio. This is due to the high water demand of both metallurgical sludge waste and RCA. Water absorption by the aggregate reduces the amount of water in the cement paste and thus the porosity and strength of the resulting cement matrix.According to the advantages and disadvantages the best performance of concrete containing RCA are while crushed RCA is used. However, it has to me mentioned that different methods may be used accordingly to situation.The authors present below the technological aspects of using metallurgical sludge waste and recycled concrete aggregate:


Diets were formulated to contain 0 (CON), 300 (LOW), 600 (MOD), or 1200 (HIGH) mg/L of 6′-SL sodium salt. On days 8 and 22, samples were collected for hematological and histological analyses. Supplemental 6′-SL sodium salt at all doses supported growth and development comparable to those observed in control animals. In addition, serum chemistries, hematology, and organ microscopic structure were unaffected by 6′-SL (p > 0.05). Thus, addition of enzymatically-synthesized 6′-SL to a milk replacer formula supported growth and clinical outcomes similar to the control formula in the neonatal piglet.Oligosaccharides are complex, non-digestible glycans found in large abundance in human milk. The abundance and the profile of bovine milk oligosaccharides and bovine milk based in infant formula differ from those in human milk. Recently, some human milk oligosaccharides (HMOs) have been supplemented to infant formula, however, not all forms have been available in large scale. The objective of the study was to investigate the dose-dependent effects of an enzymatically-synthesized 6′-sialyllactose (6′-SL) sodium salt supplemented to swine milk replacer on growth, hematological parameters, and organ microscopic assessment in our pre-clinical neonatal pig model. Two-day-old male and female pigs ( The milk of all species contains a complex mixture of soluble oligosaccharides that differ in their size, structure, and specific linkages. The backbone is lactose, which can be fucosylated or sialylated, in either alpha or beta configurations. The main milk oligosaccharides are 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), 3′-sialyllactose (3′-SL), 6′-sialyllactose (6′-SL), and lacto-N-tetraose (LNT) . Human mConcentrations of 3′- and 6′-SL in human milk are higher in colostrum than mature milk. Samuel and colleagues measured HMO concentrations at 6 time points over the first 4 months of lactation in a sample of ~300 mothers . At 2-daMost infant formulas are produced with bovine milk as the starting material, which contains much lower concentrations of milk oligosaccharides than human milk; 1–2 g/L in bovine colostrum and 100 mg/L in mature bovine milk . A totalEscherichia coli (E. coli) BW25113 and a series of enzymes, as described by Gurung and coworkers [Some studies have investigated supplemental sialylated HMO using whey fractions from bovine milk that are enriched with 3′-SL and 6′-SL, but also contain lactose and other whey components . Having oworkers . The objE. coli K-12 strain . The 6′-SL sodium salt preparation also contained lactose (0.09%) and N-acetylneuraminic acid (1.13%) [The test ingredient, 6′-SL sodium salt (>98% purity), was produced by enzymatic synthesis and was provided in powdered form by GeneChem Inc. . The 6′-SL sodium salt was synthesized using a set of enzymes derived from an  (1.13%) .n = 48; an equal proportion of males and females from 12 different litters; 4 piglets per litter) were obtained from Carthage Veterinary Services and were transferred to the AAALAC-approved animal facilities in the Edward R. Madigan Laboratory on the University of Illinois campus. Upon arrival to the animal facility, piglets were randomized to dietary treatments described below, to balance initial body weight and sex. All animal and experimental procedures were in accordance with the National Research Council Guide for the Care and Use of Laboratory Animals [The study design and animal protocol were identical to that previously described by Monaco et al. . Briefly Animals  and apprN = 12) was a commercially available non-medicated sow-milk replacer formula , which was formulated to meet or exceed nutrient requirements for 3 to 5 kg piglets [N = 12), 600 mg/L , and 1200 mg/L . When correcting for the sodium content, these concentrations corresponded to 289.9, 579.8, and 1159.7 mg/L of 6′-SL, respectively. Daily animal care and formula preparation has been described in Monaco et al. [Piglets were fed one of four diets with varying amounts of 6′-SL sodium salt. The control diet  to perform chemistry, complete blood count (CBC), and coagulation time analyses, respectively. On d22, animals were sedated with an intramuscular injection of Telazol®  and blood was collected via cardiac puncture for chemistries, CBC, and coagulation time analyses 3–6 h after the final feeding. Piglets were then euthanized by an intravenous injection of 86 mg/kg BW sodium pentobarbital . Urine samples for urinalysis, spleen, stomach, kidneys, heart, lungs, intestine, and liver were collected and fixed for analysis as previously described [On d8 of the study , blood was collected via jugular vein in either plain, Kescribed .A board-certified pathologist with Veterinary Diagnostic Pathology, LLC , performed microscopic histological analyses on formalin-fixed tissue samples obtained from piglets fed the CON (0 mg 6′-SL/L) and HIGH (1200 mg 6′-SL/L) diets. The slides were examined for tissue-specific lesions, including lymphocyte infiltration, congestion, perfusion, and hemorrhage. Lesions were reported as absent, minimal, mild, moderate, marked, or severe. Microscopic examinations included semiquantitative severity scoring of histopathology lesions and microscopic histologic features. A five-level severity scoring system was employed in which: 0 = absent; 1 = minimal; 2 = mild; 3 = moderate; 4 = marked; and 5 = severe. When uncertainty existed between scoring groups in assigning a value, half values were given.® 3700  while diagnostic lab trained technicians performed the differential analysis. The variables evaluated in our study were: red blood cells count (RBC), hemoglobin concentration, hematocrit value, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and corpuscular hemoglobin concentration mean. Total white blood cell (WBC) count and differential WBC analyses (neutrophils and lymphocytes) were also performed. Platelet indices were analyzed and included platelet count and mean platelet volume (MPV). Urinalysis was performed with the CLINITEK Advantus® Urine Chemistry Analyzer , which provided readings of pH, protein, glucose, ketones, bilirubin, and blood. Specific gravity was measured on a refractometer and analyses of urine sediments and cells were done microscopically.Serum chemistries, coagulation time, and CBC analyses and urinalysis followed protocols described in Monaco et al. . Brieflyp < 0.05.Analysis of variance (ANOVA) was conducted using the MIXED procedure of SAS 9.4  to differentiate dietary treatment effects on young pigs. Depending on the outcome, one of two statistical models were used: 1) data collected at a single time-point  were analyzed by 1-way ANOVA, and 2) data collected from the same animal on more than one occasion  were analyzed by ANOVA with repeated-measures in which dietary treatment, time, and treatment by time interaction were added to the statistical model. When dietary treatment or time was significant, with no interaction, data were pooled for statistical representation. When no effect of 6′-SL sodium salt treatment was observed, serum chemistry data were combined and analyzed for differences between d8 and d22. Normality was checked by the Shapiro-Wilk test and outliers were identified by a studentized residual procedure where values of >3 or <−3 were considered as potential outliers. Categorical data  were presented in frequency tables. Data was expressed as mean ± standard error of the means (SEM) and statistical significance was defined at Dietary supplementation of 6′-SL sodium salt at the concentrations of 300 (LOW), 600 (MOD), and 1200 (HIGH) mg/L to a milk replacer formula resulted in no significant differences in growth patterns  or totalNeither absolute  nor normSome minimal or mild, and a few marked microscopic findings were detected in the neonatal piglet tissues . The braPT and aPPT were measured on study d8 and d22 to characterize blood coagulation time . AdminisCBC analysis with differential were performed on days 8 and 22 and all values were within expected ranges. There was no statistically significant treatment effect on the parameters RBC, hemoglobin, hematocrit, MCV, MCH, MCHC, platelet, MPV, WBC, neutrophils, and lymphocytes, . Age hadAdvances in metabolic bioengineering have permitted the scalability of HMOs production for their use as a food ingredient. Large quantities of HMOs are now available, which will facilitate their addition to infant formula. However, the safety and efficacy of these novel components must be determined prior to their use in infant diets. The present study demonstrated that consumption of formula supplemented with 6′-SL sodium salt was well tolerated and supported growth compared to that observed in piglets receiving unsupplemented formula during the first 3 weeks of life. The doses of 6′-SL utilized in the study were comparable to those found in human milk, and reflected concentrations found in the colostrum  and mature milk  . In addiPseudomonas aeruginosa K—induced pneumonia mouse model [Oligosaccharides are increasingly recognized as bioactive components of milk, and are believed to have an impact on the early development of the neonate . Sialic se model . In termse model ,29. Jacose model  reportedse model  demonstrse model .The purpose of this study was to examine the safety of enzymatically-synthesized 6′-SL sodium salt supplementation in various clinical and morphological parameters in the neonatal piglet model. Blood count and chemistry, and coagulation time values were all within ranges expected for pigs. Significant differences were observed for both serum chemistry and coagulation time between study days 8 and 22. These differences were not unexpected, as hematological and biochemical parameters are affected by a variety of factors including age, sex, and breed, and reflect developmental stage of the organs and their metabolism ,30. TissThe data herein show that supplementing formula with 6′-SL sodium salt at concentrations up to 1200 mg/L did not affect formula intake and fecal scores, and growth was similar to those reported in previous studies including a supplementation with enzymatically-synthesized 3′-SL . In addiTremendous progress has been made in recent years in the area of synthetic oligosaccharide production. Chemoenzymatic methods combine the flexibility of chemical synthesis, and the efficiency and selectivity of enzymatic methods to obtain diverse complex carbohydrates, including sialylated compounds. As such, the availability of enzymatically-synthesized forms of SL will facilitate the supplementation of infant formula to bring its oligosaccharide content and composition in line with human milk. This study demonstrated that the 6′-SL sodium salt tested herein supported normal growth and development of piglets at concentration up to 1200 mg/L. Furthermore, all clinical parameters were within reference ranges and no dose-dependent effects were observed.


Antibiotic use prior to seeking care at a hospital may reduce the sensitivity of blood culture for enteric fever, with implications for both clinical care and surveillance. The Surveillance for Enteric Fever in Asia Project (SEAP) is a prospective study of enteric fever incidence in Nepal, Bangladesh, and Pakistan. Nested within SEAP, we evaluated the accuracy of self-reported antibiotic use and investigated the association between antibiotic use and blood culture positivity.Between November 2016 and April 2019, we collected urine samples among a subset of SEAP participants to test for antibiotic use prior to the hospital visit using an antibacterial activity assay. All participants were asked about recent antibiotic use and had a blood culture performed. We used mixed-effect logit models to evaluate the effect of antimicrobial use on blood culture positivity, adjusted for markers of disease severity.We enrolled 2939 patients with suspected enteric fever. Antibiotics were detected in 39% (1145/2939) of urine samples. The correlation between measured and reported antibiotic use was modest (κ = 0.72). After adjusting for disease severity, patients with antibiotics in their urine were slightly more likely to be blood culture positive for enteric fever; however, the effect was not statistically significant .The reliability of self-reported prior antibiotic use was modest among individuals presenting with fever to tertiary hospitals. While antibiotics are likely to reduce the sensitivity of blood culture, our findings indicate that there is still considerable value in performing blood culture for individuals reporting antibiotic use. Salmonella enterica subspecies enterica serotypes Typhi and Paratyphi A, is a major cause of morbidity in South Asia [Enteric fever, caused by uth Asia . Antibiouth Asia . Unfortuuth Asia , and theuth Asia , 7. Bloouth Asia .Antibiotic use prior to seeking care at a hospital may reduce the sensitivity of blood culture for enteric fever , 9, withSalmonella. Therefore, measuring patterns of antibiotic use for febrile illness in enteric-fever endemic settings may enhance our understanding of the drivers of antimicrobial resistance.Easy access and indiscriminate use of antibiotics prior to formal care may be an important contributor to the emerging threat of antimicrobial resistance. Rising rates of antimicrobial resistance may undermine treatment effectiveness for enteric fever as well as other infectious diseases . CriticaTo investigate patterns of antibiotic use among patients with acute febrile illness, we conducted a substudy among patients presenting to outpatient departments who were enrolled in the Surveillance for Enteric Fever in Asia Project (SEAP) study sites in Bangladesh, Nepal, and Pakistan. Our objectives were to characterize prehospital antibiotic use among patients with suspected enteric fever in South Asia according to demographic and clinical characteristics, evaluate the accuracy of self-reported antibiotic use, and investigate the relationship between antibiotic use and culture positivity.This study was nested within the SEAP study, a longitudinal surveillance study for typhoid and paratyphoid fevers in Bangladesh, Nepal, and Pakistan. SEAP study methods are presented elsewhere , 17. IndSEAP patients presenting to the outpatient department at any of the 6 study hospitals with 3 or more consecutive days of fever were eligible to participate. Participants were enrolled consecutively from September 2016 through April 2019 until the target sample size was reached. All study hospitals were tertiary facilities: 2 in Dhaka, Bangladesh; 1 in Kathmandu, Nepal; 1 in Kavrepalanchok, Nepal; and 2 in Karachi, Pakistan. While participants of any age were eligible to participate, the hospital study sites in Bangladesh serve primarily pediatric populations.The eligibility criteria of 3 or more consecutive days of fever in the previous 7 days was assessed by self-report or caregiver report. We interviewed all study participants, using a standardized questionnaire to ascertain demographic and clinical history. A sample of peripheral venous blood was collected from each participant, inoculated into a BACTEC Aerobic bottle or PED Plus bottle, and incubated in a BACTEC system for 5 days. One blood culture was performed per patient. Samples that indicated positivity in the BACTEC system were subcultured onto MacConkey agar plates and nonselective media (sheep blood agar). We identified the species with biochemical testing and confirmed serologically, using O and H antisera (BD laboratories), when available.We also requested a sample of at least 3 mL of urine in a sterile collection cup from the participants before any antibiotics were prescribed or administered at the study facility. Urine was collected the same day blood was drawn for culture. These samples were either processed immediately or stored at 2°C–8°C and processed the following day or stored at −80°C and processed within a month. In an internal validation study of 10 samples, there was no difference in susceptibility between fresh samples and samples stored at −20°C and −80°C for up to 3 months’ storage time.Kocuria rhizophila (previously Micrococcus luteus) (ATCC:9341) on Mueller-Hinton agar (Oxoid: CM033) with 5% sheep’s blood. Kocuria rhizophila has been previously used to detect low concentrations of antibiotics in biological fluids because of its high susceptibility to antibiotics [To test for the presence of antibiotics, we prepared a bacterial lawn of ibiotics , 19. We We inquired about care-seeking and antibiotic use in the 7 days prior to presenting for care at the study facility by asking the following questions to all participants: “For this febrile illness, before arriving for this visit, did you/the participant seek any type of medical advice or treatment for your/their symptoms, such as a health clinic, other hospital, pharmacy, or private healthcare provider?” and “Before arriving for this visit, did you/the participant take any of the following medications, such as antibiotics, antipyretics, analgesics, and antidiarrheals?”We did not collect additional information on the specific antibiotics consumed. We also collected information about household assets, education and self-reported clinical symptoms. If the participants were <15 years old, we asked these questions to their caregiver or guardian.The primary outcome was the presence of antibiotics in the urine as measured by the biological assay described above. We reported the proportion of participants with antibiotics detected in their urine samples, along with 95% confidence intervals (CIs), stratified by country and age. We used principal component analysis to construct a wealth index variable from the household asset data for these analyses. We used binomial mixed-effect logit models for all the remaining analyses with random effects for hospital site and country to account for clustering. We report the results as prevalence ratios, calculated from the probability-logit transformations from the mixed models . We calcS. Typhi/S. Paratyphi. We ran an unadjusted model (model 1) alongside a model adjusted for markers of disease severity , days of fever, and age, which we hypothesized might confound the association between the antibiotic use and culture positivity.We evaluated the relationship between antibiotics detected in the urine and blood culture positivity for We anticipated that 30% of the study patients would have antibiotics detected in their urine. To estimate prevalence across the 3 age groups with a width of the 95% CI of ±5% required 969 participants per site.We used R version 3.6.0 software for all our analyses.All participants gave informed consent; in the case of minors, verbal assent and informed consent were provided by a parent or guardian. The study was approved by the Nepal Health Research Council, Bangladesh Institute of Child Health Ethical Review Committee, Pakistan Ethical Review Committee, the US Centers for Disease Control and Prevention, and the Institutional Review Board at Stanford University.S. Typhi or S. Paratyphi. Culture positivity was higher in Bangladesh (20.1%) and Pakistan (14.5%) and lower in Nepal (3.6%).We recruited 2939 individuals presenting to the outpatient department at SEAP study hospitals with a fever of 3 or more days in the past week. This included 999 participants in Bangladesh, 1001 in Nepal, and 939 in Pakistan. The median age of the participants was 10 years , and 1246 (42.4%) of the participants were female. The median temperature at hospital presentation was 37.2 C , and patients reported a median of 4 days  of fever . All parOverall, we detected antibiotics in the urine samples of 1145 (39%) participants: 377 (37.7%) in Bangladesh, 264 (26.4%) in Nepal, and 504 (53.8%) in Pakistan. In contrast, 1259 (43.7%) participants reported taking antibiotics prior to seeking care: 412 (42.4%) in Bangladesh, 417 (42.4%) in Nepal, and 430 (46.2%) in Pakistan . In BangWhen asked about care-seeking for the current illness prior to presentation at the study hospital, the most common location reported was a pharmacy, followed by a hospital or clinic. However, there were substantial differences between countries. For example, only 2.4% of the participants sought care at a pharmacy in Pakistan compared with 56.7% in Bangladesh and 59.6% in Nepal . In NepaAntibiotic detection in urine was positively associated with having ≥7 days of fever , temperature of 38.3 C at presentation , having ≥3 days of being unable to conduct normal activities , and having diarrhea  . SeekingS. Typhi or S. Paratyphi A compared with individuals who had no antibiotics in their urine . When adjusting for the duration of fever, days in bed, diarrhea, age, and wealth, the prevalence ratio decreased to 1.22  and was no longer statistically significant (P = .065) .Individuals who had antibiotics detected in their urine were more likely to be blood culture positive for  = .065) . When reThe sensitivity and specificity of reported antibiotic use compared to the detection of antibiotics in the urine were 70.2%  and 72.6% , respectively. Correlation between measured and reported antibiotic use was modest in all 3 countries but was higher in Bangladesh (κ = 0.74) and Nepal (κ = 0.73) than in Pakistan (κ = 0.62). The sensitivity of reported antibiotic use was slightly higher for parents and guardians compared to self-report .Antibiotic use prior to presentation to hospitals may have important implications for diagnostic evaluation by clinicians and for pathogen surveillance systems. However, the reliability of self-report of recent antibiotic use is unclear, and whether individuals who report prior antibiotic use should be included in blood culture–based surveillance systems has been debated. To address these knowledge gaps, we evaluated antibiotic use, self-report, and blood culture positivity among a subset of outpatients presenting to hospitals in Bangladesh, Nepal, and Pakistan. Antibiotic use across all 3 countries was high, with 1 of every 3 participants having antibiotic activity confirmed in their urine assay upon presenting at the tertiary care study site. Patients presenting with more severe disease  were more likely to have taken antibiotics than those with less severe disease. Many patients had sought care at other facilities prior to presenting at the study-site facility; of these, those who sought care at other hospitals or with physicians were more likely to have taken antibiotics. In contrast to what is often presumed, patients who had taken antibiotics prior to presentation were more likely to be culture positive than those who did not have evidence of antibiotics in their urine. Finally, the accuracy of self-reported or caregiver-reported antibiotic use compared to antibiotics detected in the urine was modest in all 3 countries.S. Typhi and S. Paratyphi is not well characterized [The impact of antimicrobial use on the sensitivity of blood culture of cterized . A recencterized , 23.S. Typhi or S. Paratyphi A isolate was not susceptible. Because antimicrobial resistance was widespread and fairly homogeneous within study sites, and the assay we used could not distinguish between specific antibiotics, we were unable to assess whether antimicrobial resistance mediated the effects of prior antibiotic use on culture positivity.While we found higher culture positivity among individuals with prior antibiotic use, we believe that this was due to confounding whereby individuals who continued to have fever despite continued antibiotic use are more likely to have typhoid than other illnesses. The duration of fever in typhoid is characteristically longer than the other common causes of fever. Even after antibiotic use, the average fever clearance time in clinical trials for enteric fever treatment is around 5 days . PersistWhile self- or caregiver-reported antibiotic use is widely thought to be inaccurate, few studies have documented the validity of reported antibiotic use against a urine antibacterial assay in the South Asia region . Our resKocuria growth, leading to false-positive results [The results of this study should be interpreted within the context of the limitations of the design and study procedures. Biologic assays for antibiotic metabolites in urine may have limited sensitivity, which could lead to underestimation of prior antibiotic use and bias associations between demographic and clinical features, likely toward the null . Their a results . AlthougSalmonella [Despite these limitations, this is the largest study to date evaluating prior antibiotic use among enteric fever suspects and the associations with culture positivity and self-reported use. We unexpectedly found that individuals with reported antibiotic use were more likely to be culture positive for enteric fever; however, this relationship was confounded by disease severity. While antibiotics may reduce the sensitivity of blood culture, our findings indicate that there is still considerable value in performing blood culture among individuals reporting antibiotic use. Given the continuing emergence and spread of antimicrobial resistance among typhoidal lmonella , 30, a b