The geopolymer concrete mix proportions based on the ANN algorithm model and contour plots developed were experimentally validated. Thus, the proposed method can be used to determine mix designs for high calcium fly ash geopolymer concrete in the range 25–45 MPa at 28 days. In addition, the design equations developed using the statistical regression model provide an insight to predict tensile strength and elastic modulus for a given compressive strength.Despite extensive in-depth research into high calcium fly ash geopolymer concretes and a number of proposed methods to calculate the mix proportions, no universally applicable method to determine the mix proportions has been developed. This paper uses an artificial neural network (ANN) machine learning toolbox in a MATLAB programming environment together with a Bayesian regularization algorithm, the Levenberg-Marquardt algorithm and a scaled conjugate gradient algorithm to attain a specified target compressive strength at 28 days. The relationship between the four key parameters, namely water/solid ratio, alkaline activator/binder ratio, Na It is essential in the urbanisation of society in order to improve human living standards . The expemployed ,5,6, andemission ,8,9,10.2 emissions by 25‒45% by utilizing waste coal combustion products [Many researchers have been exploring alternative sustainable cementitious binders that can reduce the dependence on Portland cement (PC) in construction ,12,13. Fproducts . High caproducts ,16. Europroducts . Greece products .2 rich rice husk ash had an adverse effect on the postfire residual strength. Wongsa et al. [Nuaklong et al.  investiga et al.  examineda et al.  illustra2/Na2O ratio, the alkali activator concentration, the liquid/fly ash ratio and curing temperature, on the setting time and compressive strength development of high calcium fly ash geopolymer. Test results confirmed that as the SiO2/Na2O ratio increased, the setting time was accelerated but the compressive strength was reduced. As activator concentration increased, the setting time for geopolymer mixes with SiO2/Na2O of 1.0 and 1.5 were prolonged but were shortened when SiO2/Na2O equalled 2.0, while the compressive strength of these geopolymer mixes increased. The data also showed that an elevated curing temperature increased the compressive strength. Zhang and Feng [2SiO3/NaOH ratio, fly ash/alkaline activator ratio and curing temperature affected the compressive strength of fly ash geopolymers. The test results revealed that a 12 M NaOH solution and mass ratios of fly ash/alkaline activator and Na2SiO3/NaOH of 2.0 and 2.5, respectively, yielded the highest compressive strength. Literature [2SiO3/NaOH ratio was 1.5. Rattanasak et al. [2SiO3/NaOH ratio of 1.0 produced a product with a compressive strength as high as 70 MPa. However, Hardjito [2SiO3/NaOH ratio of 2.5 gave the highest compressive strength, whereas a ratio of 0.4 resulted in lower compressive strength. In addition, researchers have reported that compressive strength increases as the molarity of the NaOH increases from 8 to 16 M [Research has shown that a range of mix design parameters influence the compressive strength of fly ash geopolymer concrete. Ling et al.  studied and Feng  reportedand Feng  noted thterature ,26 has rterature  stated tk et al.  concludeHardjito  showed t to 16 M . However to 16 M  reported2O/Na2O molar) using ANN to predict the compressive strength of alkali-activated metakaolin concrete. In another study [2O/Na2O molar ratio. Researchers have been attempting to optimise the layers by using different functions for the hidden and output layers [Despite the past research on performance and mix design parameters of high calcium fly ash in geopolymers, there is no widely accepted procedure to determine the proportions to be mixed in concrete. Optimization by artificial intelligence tools with different algorithms ,32 has ber study , ANN modt layers . Ling ett layers  showed a2SiO3/NaOH ratio and NaOH molarity were identified as the most influential parameters for compressive strength prediction. Although the curing temperature was reviewed and analysed for the database, the strength development over time did not identify it as an influential parameter. Based on the parameters identified, a novel standard process to find the mix proportions for a high calcium fly ash geopolymer concrete was developed, and the effectiveness of achieving a specified compressive strength was tested and validated through laboratory experiments.In this study, ANN was used with three algorithms and different numbers of neurons in the hidden layer for the prediction of compressive strength of high calcium fly ash geopolymer concrete based on the data obtained from the literature. Having assessed the available mix design parameters, the water/solid ratio, alkaline activator/fly ash ratio, NaAlthough fly ash geopolymer concrete has been used in structural members and commercialised as a construction material, the mix design process is still unclear because of the many variables involved. Almost all the proposed methods employ different techniques specific for the particular situation and cannot be used as a standard method. The missing link identified is that there is no unique mix design guideline for high calcium fly ash geopolymer concrete. This research addresses the identified gap and proposes a standard mix design procedure using a machine learning technique. The validation of the technique demonstrates that the novel method developed can be used with confidence to calculate mix proportions for compressive strength in the range of 25–45 MPa.A database was established using the published research/literature up to 2019 (inclusive) on high calcium fly ash geopolymer concrete scrutinising it for compressive strength at 28 days. The database included only 100% high calcium fly ash concrete mixes and did not consider mortar or phase mixes, and excluded the blended high calcium fly ash composites. This selection criteria was adopted to develop a mix design procedure that could predict the standard 28-day compressive strength for high calcium fly ash geopolymer concrete more accurately. The present database consists of compressive strength values obtained from 166 concrete mix designs, 2SiO3/NaOH ratio for this study) [The kurtosis values in s study) . Skewnesnet)j is the weighted sum of the jth neuron for the input received from the preceding layer with n neurons, ijw is the weight between the jth neuron in the preceding layer, ix is the output of the ith neuron in the preceding layer, b is a fixed value as internal addition, α is a constant used to control the slope of the semilinear region.ANN has three main layers, namely input layer, hidden layer and output layer with weights . The inpThe ANN toolbox in MATLAB was used with three different algorithms, namely the Bayesian regularization algorithm, Levenberg-Marquardt algorithm and scaled conjugate gradient algorithm to predict the compressive strength of high calcium fly ash geopolymer concrete. The developed database was divided into two subsets as training subset and testing subset. It was noted that 63−80% of data was used for a training subset while the remainder was used for the testing subset ,52,53. TThe model performance with 8 hidden neurons along with the Bayesian Regularization algorithm is shown in 2SiO3/NaOH ratio and NaOH molarity) with the target output of compressive strength. Hence, these contour maps can be used to design mix proportions for a target 28-day compressive strength for high calcium fly ash geopolymer concrete.The contour plots shown in Water/solid ratio—Activator/fly ash ratio—2SiO3/NaOH ratio—2SiO3/NaOH ratio was decreased, the compressive strength was increasing faster due to the increment in the activator/fly ash ratio. Further, by increasing the Na2SiO3/NaOH ratio with decreasing NaOH molarity, higher compressive strength could be achieved, NaNaOH molarity—2SiO3/NaOH ratio = 3.7 and NaOH molarity = 10 M. The 460 kg fly ash was used which is the median of database, For model validation, four high calcium fly ash geopolymer concrete mixes were designed with the targeted compressive strengths of 25, 30, 40 and 45 MPa at 28 days. A detailed calculation procedure for 45 MPa concrete mix is illustrated below. The calculated mix design variables obtained from the contour plots of (a)Alkaline activator content:2SiO3 = 307.8 kg; NaOH = 83.2 kg.After solving: Na(b)Added water content:After solving: Added water (w) = 2.82 kg .(c)Aggregate content:After solving: Similarly, 2 absorption. The crystalline and amorphous content, specific surface area, and particle size distribution are shown in The high calcium fly ash obtained from an Indonesian coal power station was used for this study. The chemical composition of the fly ash, 2O = 14.7% and SiO2 = 29.4% by mass, specific gravity = 1.53) were used as alkaline activator in the geopolymer production. The fine aggregate and coarse aggregate were prepared with respect to the Australian Standards, AS 1141.5 [Commercially available sodium hydroxide solution (8–10 M) and sodium silicate solution , then compacted using a vibration table for 1 min to remove air bubbles. All prepared concrete cylinders were kept in the laboratory under ambient conditions (23 °C temperature and 70% relative humidity) for 24 h. Afterwards, all concrete specimens were heat cured at 60 °C temperature for one day. After demoulding, all specimens were clearly labelled and stored in laboratory conditions (23 °C temperature and 70% relative humidity) until the 28 day testing. Compressive strength testing was undertaken in accordance with the ASTM C109/C109M standard using a Technotest concrete testing machine . A totalThe experimental results, noted in 2 values for selected regression models were used together with the least square method to obtain the linear regression lines to match the experimental data. Each best fit line is linked with the confidence and prediction interval bands. The prediction interval is concentrated on the specific data point while prediction lines are the focus of the confidence interval. There is a 95% chance that the actual regression line will be in the confidence interval band calculated using Equation (5) [0,) is located within this interval, Equation (6) [The high calcium geopolymer concrete experimental data available in tion (5) . Hence, tion (6) .(10)Yprpred. is the predicted Y values, t0.05 is the t critical value for 95% interval, n is the sample size, X is the true value while x is the sum of the squares of standard error of X values. The proposed regression model for the relationship between compressive and flexural strength is shown in The Y2 value of the regression model was 0.97, this indicates that a more accurate modulus of elasticity could be achieved if the density was also considered in the equation. AS 3600 [A linear regression line with prediction and confidence interval bands to demonstrate the relationship between compressive strength and elastic modulus is shown in  AS 3600  and ACI 2SiO3/NaOH ratio and NaOH molarity, and the 28-day compressive strength of geopolymer concrete.The algorithm for the predictive model for high calcium fly ash geopolymer concrete mix design was developed using artificial neural networks in order to determine the relationship between the four key parameters identified, namely water/solid ratio, alkaline activator/binder ratio, NaA new standard mix design procedure was developed for high calcium fly ash geopolymer concrete using contour plots generated in the MATLAB programming environment, and demonstrated through detailed calculation to ascertain the mix proportions for 45 MPa target compressive strength at 28 days.Good correlation between the experimental results and the compressive strengths calculated from contour plots validated the developed novel mix design method for high calcium fly ash geopolymer concrete. Thus, the proposed method is suitable for calculating mix proportions with confidence for a target compressive strength at 28 days in the range of 25–45 MPa.A statistical regression model was developed using the database to provide new design equations to predict tensile strength and elastic modulus of high calcium fly ash geopolymer concrete based on the 28-day compressive strengths obtained.The design equations available in AS 3600 and ACI 318 standards for Portland cement concrete provide a conservative design for tensile strength in high calcium fly ash geopolymer concrete. However, AS 3600 design equation overestimates the elastic modulus for geopolymer concrete.The present study suggests preliminary amendments to the available design standards for Portland cement concrete to design high calcium fly ash geopolymer concrete structural elements with better serviceability performance. However, further investigations are required prior to implementing them in the standards/codes.


In poultry production, consuming diets with low or excessive methionine levels leads to negative effects on growth performance. The requirements of methionine may differ among the fast and slow-growing breeds; therefore, the optimal dietary methionine level should be estimated for each. In this study, six dietary methionine levels were evaluated to estimate the optimal level for fast and slow-growing yellow feathered chicken breeds. The quadratic polynomial and exponential asymptotic regression showed that the optimal methionine requirements for maximal growth performance were 0.50% and 0.53% in the fast-growing breed, and 0.48% and 0.52% in the slow growing breed.Two experiments were carried out to investigate the dietary methionine requirement for fast and slow-growing Chinese yellow-feathered breeds during the starter phase, based on growth variables and regression models. In Experiment 1, a total of 2880 one-day-old Lingnan chicks (fast growing breed) were used to test the methionine requirement from 1 to 21 days of age for males and females separately. Of each gender, 1440 birds were allocated into 6 dietary methionine levels , each with 6 pen replicates of 40 chicks. Experiment 2 had the same design with Guangxi chicks (slow growing breed) from 1 to 30 d of age. Results indicated that significant nonlinear or quadratic responses to increasing dietary methionine levels were observed in body weight, daily gain, feed intake and feed conversion ratio of both breeds. In summary, the quadratic polynomial regression showed that the optimal methionine requirements for maximal growth performance of Lingnan chickens were 0.52–0.58% in males, 0.51% in females, and 0.53% in mixed genders. The corresponding values for Guangxi breed were 0.53% in males by quadratic polynomial regression and 0.43% in females, and 0.48% to 0.49% in mixed sexes by exponential asymptotic models. With the rapid development of economy in China, the second largest worldwide producer of chicken meat, market demands for nutrient-rich and tasty meat have been in continuous increase, which is boosting the industry of Chinese yellow-feathered chickens. The contribution of such chicken type in production has been growing; 3.7 billion birds annually with more than 30% of whole chicken meat shares in recent years . The indSome essential amino acids are often added as pure to poultry diets to ensure the optimal balance required for poultry in order to maximize the production efficiency. Globally, methionine (Met) is considered to be the first limiting amino acid for poultry fed on typical corn–soybean meal-based diets . Met is Chinese yellow-feathered chicken is a general name, which consists of quite a few breeds, mainly referring to Chinese local breeds and the improved breeds. Chinese yellow-feathered chickens grow slowly and are reared for a longer time compared with white-feathered broilers. The Lingnan yellow-feathered chicken breed is classified according to its growth rate to fast , medium , and slow growing  ,16. The The Met requirement of feeding standard of chicken (CNY/T33-2004) is mainly for medium-growing yellow-feathered broilers . As the Two experiments were carried out to estimate the Met requirement for Lingnan (Exp1) and Guangxi (Exp2) yellow-feathered chicken breeds following the same experimental design. Before trial, the Met content of the basal diet ingredients used in both experiments was determined by ion-exchange chromatography on an automatic amino acid analyzer , according to the procedures described by Xi et al. . In eachPelleted feed and drinking water were freely available to chicks. The different diets were prepared three weeks prior to the trial to allow time for checking content homogeneity, in terms of dry matter, ash, crude protein, ether extract, crude fiber, and amino acid concentrations.Birds were weighed at the beginning (day 1) and end of each experiment to record the initial and final body weights (FBW), which were used to calculate the average daily gain (ADG). Average daily feed intake (ADFI) was measured on a per pen basis for the entire experimental period, and the feed conversion ratio (FCR) was calculated. Mortality was checked daily and dead birds were weighed in order to adjust the feed intake calculations.p < 0.05. All data were expressed as means and SEM, derived from ANOVA error mean square. When the main effect was significant (p < 0.05), linear and quadratic effects of Met content were determined. For key performance variables, the dietary methionine requirement of the birds was estimated using quadratic polynomial (QP) or exponential asymptotic (EA) models by the NLIN procedure of SAS .Data were subjected to one-way ANOVA using the GLM procedure of SAS . Tukey–Kramer test was used for means comparison, and pairwise comparisons among the means were assessed by Duncan’s multiple-range tests at QP model:2), Akaike information criteria (AIC) and mean square error values (MSE).EA model:ic point ,19,20. Tp < 0.01; quadratic, p < 0.01) of males; and final BW, ADG and FCR  of females; and final BW, ADG and ADFI  of mixed genders. According to the EA and QP regression, the optimal dietary Met level for the highest body weight were 0.54% and 0.55% in males, 0.47% and 0.51% in females, and 0.50% and 0.53% in mixed genders. The corresponding EA and QP values for the highest ADG were 0.54% and 0.55% in males, 0.47% and 0.51% in females, 0.50% and 0.53% in mixed genders. With regard to these results, it is worth mentioning that obtaining the same optimum Met requirement value for maximal final BW and ADG is logically expected; certainly, because these two variables are linearly correlated, where the ADG is calculated as the  /days. This, therefore, led to the same values of R2 and the same calculated Met requirements for these two variables , ADG  and ADFI  of males; final BW, ADG, and ADG  of females; and final BW , ADG , and ADFI  of mixed genders. According to the EA and QP regression models, the optimal Met for the highest final BW were 0.51% and 0.53 in males, 0.43% and 0.51% in females, and 0.48% and 0.52% in the mixed males and females. The EA and QP indicated that the optimal Met for the maximal ADG were 0.51 and 0.53% in males, 0.43% and 0.51% in females, and 0.48% and 0.52% in mixed genders. Additionally, the QP model showed that 0.49% was optimal for the best FCR in mixed genders. Fitness of the two growth performance models are shown in 2, lower AIC and MSE values, in estimating the optimal Met requirement , but the EA function was better fitting for females and mixed sexes. The QP models predicted the requirement of Met for males as 0.53%, and the EA models predicted the requirements of Met for females and mixed genders as 0.43% and 0.48% to 0.49%, respectively.The growth performance results of male, female and mixed genders of Guangxi yellow-feathered chickens as affected by dietary Met levels between 1 and 30 days of age are shown in uirement a,b for gDiets having low or excessive Met levels could engender important influences on poultry performance . An optiThe Met requirement of Chinese yellowed-feathered chicks (unsexed) was 0.46% at the starter phase, according to the old estimations of . AccordiSupplementation of graded Met levels in basal diets of yellow feathered broilers during the starter period showed beneficial influences on their growth performance indices. The results indicated that the optimal Met requirement differed between the fast (up to 21 d of age) and slow-growing (up to 30 days of age) yellow-feathered chicken breeds as well as between males and females of each breed. The QP regression model was more appropriate for estimating the optimal Met requirements for the best body weight, average daily gain, feed intake and FCR indices of Lingnan (fast-growing) males (0.52% to 0.58%), females (0.51%), and mixed genders (0.53%), as well as for Guangxi (slow-growing) males (0.53%), whereas the EA model was found to be better for estimating the optimal Met requirement of Guangxi females (0.43%) and mixed genders (0.48% to 0.49%).


Allergen specific IgG4 levels have been monitored as a surrogate marker for the tolerance inducing effect of subcutaneous immunotherapy (SCIT) in many studies. Its accuracy at group level has been well established, but IgG4 has not yet found its place in the daily care of immunotherapy patients.Intralymphatic immunotherapy (ILIT) is a novel route for allergy vaccination against pollen allergy, where an ultrasound-guided injection of 1000 SQ-U Alutard is given directly into a groin lymph node. The suggested standard dosing so far has been one injection with 4 weeks in-between. In total 3000 SQ-U with the treatment completed in 2 months. IgG4 was measured with Immulite technique and rhinoconjunctivitis symptoms were estimated with daily online questionnaires. Mann–Whitney U-test and Wilcoxon Signed Rank test were applied for comparisons between groups and within groups, respectively.®, re-increases the allergen specific timothy-IgG4 levels, in patients already treated with ILIT before the previous pollen season. It also shows the feasibility of the ILIT-route for allergy vaccination of rhinitis patients, with or without concomitant asthma, with low degree of side effects and reconfirms high and sustained patient satisfaction.The present study demonstrates that a single, preseason ILIT booster of 1000 SQ-U Alutard 5-grassesIt is tempting to suggest that the allergen specific IgG4 levels can be used to build an intuitive algorithm for future clinical guidance of ILIT patients.Trial registration Is Intralymphatic Allergen Immunotherapy Effective and Safe?, ClinicalTrials.gov Identifier NCT04210193. Registered 24 December 2019—Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT04210193?term=NCT04210193&draw=2&rank=1 Pollen induced allergic rhinoconjunctivitis is a worldwide heterogenic disease with underestimated morbidity. It is often accompanied by pollen induced asthma, or deterioration of chronic asthma . The his®.Increase of allergen specific IgG4 has been suggested as a general maker of successful SCIT –27, even® (ALK-Abello) with 4 weeks in-between. One woman became pregnant shortly after the 3d injection. In January 2016, the remaining 12 patients were double-blindly randomized by independent nurses with help of an online computer program, to receive either an intralymphatic booster injection of 1000 SQ-U ALK Alutard 5-grasses® or placebo (given as ALK diluent®). , were recruited during the autumn of 2014, from the SCIT waiting list. Two participants were lost due to pregnancy and moving, respectively. 13 participants were treated with three injections of 1000 SQ-U Alutard 5-grassesNo patient hesitated to receive all 4 injections. All injections were performed inside an outpatient asthma and allergy clinic, operating at South Alvsborgs Central Hospital, without assistance from other departments. The unit is well equipped to handle anaphylactic reactions.The study was approved by the ethics committee of Lund, registered with Clinical Trials gov ID NCT04210193, and was conducted according to good clinical practice. All participants signed a consent form.A needle guide was used in combination with ultrasound  to direct the injections directly into the lymph node. All injections were performed by the corresponding author, assisted by the same two nurses, all with practical training from the ENT research unit at Karolinska University Hospital, Stockholm. All injections were recorded and saved on video. Examples of successful and failed injections are displayed online— to timothy and birch measurements, were obtained at 5 occasions and stored frozen at minus 20 degrees: In January 2015 (baseline), in April 2015 (1 month after the 3d injection), in December 2015 , in March 2016 (approx. 2 months after booster injection), and in October–November 2016. In these 12 participants, all but one IgG4-sample has been included in the final analysis. One IgG4-sample was omitted due to a several months relapsing leg- erysipelas during the summer and autumn of 2016, preceding the last blood sampling.10 of the 12 participants (6 with active booster and 4 with placebo booster), answered a daily online Google form questionnaire during the grass pollen seasons of 2015 and 2016 . The questionnaire scored the rhinoconjunctivitis symptoms , and use of medication, without dose specification.Finally a repeated retrospective survey was sent out eleven times during the summers of 2015–2018, with 5 identical questions, asking the participants to estimate in a subjective manner, how they had responded to the treatment in general , and if they wanted to recommend ILIT to a friend.p value of 0.05 or less was considered statistically significant.Statistical inference was calculated, using the mean of two independent analyses of all timothy IgG4-measurements with a coefficient of variance between 5 and 9%  and mild nasal congestion at 24 h . Transient local reactions at the site of injection were common and they consisted mainly of acute redness, swelling and itching. Generally, the 6 booster injections 2016 caused fewer local problems then the primary set of three injections 2015  to 1937 (IQR 560–2183), resulting in a median increase of 686 (IQR 245–1338), p < 0.001 (n = 12). No such median increase was seen for birch IgG4 , that decreased slightly from 1451 (IQR 452–2835) to 1289 (IQR 453–2727), giving a median decrease of 130 , p < 0,05 (n = 12).), but the relative change did not remain significant in November 2016 ). This discrepancy remained at re-testing 8 months later ), ).This difference was not statistically significant in November -2016, neither for absolute, nor for relative change.Expressed as relative change from December 2015, a non significant trend was found All exact p-values and 95% CI:s are displayed in Additional file The daily seasonal symptom evaluation (daily rhinoconjunctivitis score and symptom free days) did not reveal any significant difference between the group with active booster (n = 6) and placebo booster  during the grass pollen season of 2016, in relation to the season of 2015. Neither did the skin prick test reactivity (with respect to histamine control) change.However, within the active booster group, the total conjunctivitis symptom score decreased significantly during the summer of 2016 compared with 2015 . The corresponding decrease was much smaller within the placebo booster group , . Both displayed a clear re-rise in IgG4 after the active booster in Jan 2016 . Three participants claimed no or only a marginal improvement in symptoms and these individuals all showed limited increase of their timothy specific IgG4-levels. In contrast one participant , reported a very good clinical response consistently during 2015–2018, but displayed no rise in Timothy-IgG4.The systemic side effects noted were generally few and mild, dominated by tiredness and nasal congestion at 24 h post injection. The number of the latter appears presently to be a little more frequent than in previously reported studies , somethiThe theoretical reason for a beneficial role of high specific IgG4 levels in SCIT has been expanded by Aalberse et al. –33, notaThe major advantages of ILIT over the current standard approved SCIT and SLIT routes, are the comparatively short treatment duration and the low allergen doses administered, which makes ILIT appeal both to patients and to healthcare givers. Even if the inconvenience factor is reduced substantially, there is still a need to identify prognostic biomarkers that can be utilized to assist patient selection, identification of responders and non-responders as well as detection of relapse and selection of patients who will benefit from a booster injection , 40. As The argument that the affinity to the allergen does not correlate to the immunological level of IgG4, and therefore IgG4 cannot be used to monitor or steer immunotherapy in the individual patient, has been debated, as well as the concept of IgG4 being merely a surrogate biomarker reflecting other more general tolerance -inducing mechanisms , 42. OneTo conclude, the presented allergen specific IgG4 data, together with the eye symptoms reported, indicate that the use of a pre-seasonal booster in conjunction with three basic injections of ILIT might be beneficial. It is enticing to speculate that further benefits from pre-seasonal boosters could be expected in terms of an increased duration of the treatment efficacy. However, the concept of a seasonal booster needs to be further developed, before it can be introduced into clinical praxis.It may be easier, despite the considerable heterogeneity, to establish a clinical algorithm based on the specific high IgG4 dose response to ILIT, than for SCIT. The algorithm may include a combination of absolute and relative increase in specific IgG4. Based on our specific IgG4 levels that fluctuates in relation to tiny intralymphatic allergen injections, it is tempting to suggest that monitoring change of IgG4 have the potential to become a future tool, that can be used to decide the number of booster injections that an individual patient might need, to experience a sufficient and maintained clinical effect.Additional file 1: Figure S1. Consort flow diagram.Additional file 2: Photo S1. Two lymphatic nodes above the inguinal artery, in the left groin. The right nodule is 7 mm in diameter. The lymphatic core with micro vessels, verified by color doppler and surrounded by hypoechoic paracortical area (black).Additional file 3: Video S1a. Shows a failed injection.Additional file 4: Video S1b. Visualizes a successful injection.Additional file 5: Photo S2. One larger lymphatic node, 10 mm in diameter with more prominent micro vessels, verified by color doppler.Additional file 6: Video S2a. Shows a needle penetration of the capsule into the lymphatic tissue.Additional file 7: Video S2b. illustrates an allergen injection into this lymph node, that is even more didactic, since the core of the lymph node is splitted for a short moment and simultaneously a transient swelling of the whole lymph node, is visualized.Additional file 8: Table S1. CV% and other statistical measurements of IgG4-Timothy (ug/L). Double analyses 1 and 2 from 5 separate samplings (January 2015 until November 2016).Additional file 9: Table S2: Specific IgG4 timothy by active booster/placebo booster (pregnant excluded).Additional file 10: Table S3: Symptoms 2015 and 2016 and change in symptoms by booster Jan 2016.Additional file 11: Table S4: Percent symptom free days 2015 and 2016 and change in percent symptom free days by booster Jan 2016 and symptom.Additional file 12: Table S5: Survey, repeated 11 times during the grass pollen season 2015–2018.


Misguided prescription of antibiotics is an important contributor towards the emergence and spread of antibiotic resistance. The absence of effective interventions to control antibiotic use leads to increased consumption beyond the needed requirements. Antibiotic stewardship interventions must be appropriately targeted and assessed to enhance the controlled use of antibiotics. The objective of this study was to determine the factors associated with antibiotic prescription to febrile outpatients who seek care in health facilities within the Greater Accra region of Ghana.Secondary data obtained from the medical records of 2519 febrile outpatients, consecutively sampled at the outpatient department of 6 health facilities in 3 municipalities during the baseline survey of a quasi-experiment in 2015 was used. The primary outcome was prescription of any antibiotic. Independent variables included patients’ demographics, symptoms, laboratory investigations , diagnoses, and prescribers’ demographics. Crude and adjusted logistic regression analyses were used to determine the factors associated with antibiotic prescription.p <  0.001). Integrated Management of Neonatal and Childhood Illnesses (IMNCI) training was associated with a 2.3  fold odds of antibiotic prescribing. Patients aged 5 years or more were 60% less likely to receive antibiotics compared with those under 5 years . Patients referred for laboratory investigations were 29% less likely to be prescribed antibiotics than those not referred. The presence of cough as a presenting symptom was associated with a 3.5  fold odds of antibiotic prescription.The prevalence of antibiotic prescription was 70.1% (95% CI: 67.7–72.4). Prescribers with more years of practice (> 5 years) were more likely to prescribe antibiotics compared to those with less than 3 years of practice (Prescription of antibiotics to febrile outpatients was high. Promoting laboratory testing can potentially reduce irrational antibiotic prescription. Prescribing antibiotics for children under five and the prescribing practices of prescribers with longer years of practice should be targeted with interventions to reduce high use of antibiotics. Antibiotic resistance is a major global health challenge. Frequent or misguided consumption of antibiotics are critically important facilitators of the emergence and spread of antibiotic resistance , 2. HighDeveloping countries contribute disproportionately more to the increasing trend of antibiotic consumption than developed countries , 4, 7. OInterventions which have been introduced to reduce irrational prescription of antibiotics in Ghana include the Standard Treatment Guidelines (STG) and Essential Medicines List (EML), provision of training and supervision for health care providers and mass education of the public . To ensuFor these interventions to be successful, the determinants of the prevailing undesirable patterns of antibiotic use need to be identified and appropriately targeted in local antibiotic stewardship education . In the To these ends, the objective of this study was to determine the factors associated with prescription of antibiotics for febrile outpatients who sought care in health facilities within the Greater Accra region of Ghana using data from the last quarter of 2015.Data for the current study was obtained from the baseline survey of a quasi-experimental study, which sought to develop and assess the effectiveness of a one-way text messaging intervention on health providers’ adherence to malaria case management guidelines . The surIn the Ghanaian health care delivery system, patients’ medical records are usually captured in booklets and cards called folders. They are kept on shelves and retrieved manually at every visit by a patient to the health facility. Some health facilities store patient medical information using electronic folders. With the exception of Pentecost Hospital, which operates an electronic patient folder management system, the remaining 5 health facilities  membership, presenting symptoms, laboratory investigations requested , stool examination for parasitic infections (stool routine examination) and simple urine examination for protein and haematuria (urine routine examination), diagnoses and prescribed drugs including information on the dosage regimen. Further to that, the 82 prescribers who saw the outpatients were interviewed using a structured questionnaire. This questionnaire captured information on prescribers’ demographics, exposure to in-service training on malaria case management (MCM) and integrated management of neonatal and childhood illnesses (IMNCI), access to guidelines or other reference materials on MCM, and exposure to supervision in the past 6 months.Febrile outpatients included in this study were neither detained for observation nor admitted on the ward but treated on ambulatory basis at the outpatient departments. Based on recommendations by the WHO and the STG, being febrile was defined as having a recorded body temperature of 37.5 °C or higher and/or having fever recorded in clinical notes on a survey day , 24. RecTotal enumerative sampling was used to select folders of all eligible febrile outpatients daily until the sample size allocated to each municipality was reached. Details on the data extraction tools and detailed methodology of the baseline survey has been published elsewhere .N = 2519) and 0.3% (N = 2519), respectively.The entire data obtained from the primary study was validated and analysed using Stata Version 14 . For theThe outcome variable, prescription of antibiotics, was derived based on whether or not at least 1 antibiotic was prescribed for the patient. A prescribed medicine was considered an antibiotic if it was so classified by the WHO Anatomical Therapeutic Chemical classification, J01  and P01AB (nitroimidazole derivatives) .p <  0.05) were used to fit a multivariable logistic regression model. Although sex of patient was not significant in the crude analysis it was included in the adjusted model because it was considered a potential confounder. The factors in the adjusted model were checked for multicollinearity using the “Collin” command in Stata 14. A variance inflation factor (VIF) of less than 10 was considered acceptable. There were 1.2% of missing values for patient age and 1.5% for years of practice, totalling 2.7% of the 2519 observations. This was anticipated and adjusted for in the determination of the sample size in the original study. Missing data was addressed using list-wise deletion. Adjusted Wald test was used to determine the significance of multilevel categorical variables in the model. Cluster-Robust standard errors were estimated for all models. Statistical significance was set at p <  0.05.The distribution of categorical variables such as sex, the presenting symptoms, the diagnoses and laboratory investigations were assessed using frequencies. For continuous variables such as age, normality was assessed using histograms. To adjust for clustering, unique identifiers for each patient folder and for the municipalities were chosen as primary sampling units and stratum identifiers, respectively. Univariable logistic regression analyses were used to estimate unadjusted odds ratios for all the independent variables. The variables which were significantly associated with antibiotic prescribing  among those who were not prescribed antibiotics and 35.6% (628/1766) among those who were prescribed antibiotics.A total of 1109 (44.0%) of patients were referred for laboratory investigations, 1007 (40.0%) were tested for malaria, 909 (36.1%) took the full blood count test, 9 (0.4%) took the stool routine examination, and 146 (5.8%) took the urine routine examination. 74.6% of those for whom no laboratory investigation was requested were prescribed with antibiotics. Also, 40.4% of those who received antibiotics were tested.Results of the multivariable logistic regression analyses Table  identifip <  0.05).The clinical factors significantly associated with antibiotic prescription as identified from the multivariable logistic regression Table  include The age-stratified analyses in both crude and adjusted models showed that prescriber training on IMNCI was not significantly associated with antibiotic prescription in patients under 5 years but significantly associated among patients who were 5 years or more Table .Table 7The most prevalent diagnosis among the patients was ARTI Fig. . The diaThe variance inflation factor (VIF) for the exposure variables in the model were all less than 10 Table , as suchWe aimed to determine the factors associated with antibiotic prescription for febrile outpatients. The major factors identified were prescriber’s profession and years of practice, age of patient, presenting symptoms including cough, watery stool, dizziness, difficulty in swallowing, laboratory tests, diagnoses including typhoid fever, urinary tract infection and skin disease.Other studies have identified acute bronchitis, fever, sputum, tonsillar exudate, patient gender, time spent during prescriber-patient interaction and type of insurance, smoking, rhinorrhoea, sore throat, cough as significant predictors of antibiotic prescription among different populations –29. OtheA high prescription of antibiotics for febrile outpatients was observed in our study. The prevalence of prescribing antibiotics, which was 70.1% (95% CI: 67.7–72.4) was higher than was found among febrile outpatients in Zambia . An impoThe prevalence of antibiotic prescription in our study is higher than has been reported by other studies in Ghana, and other developing countries , 34, 35.Elsewhere, respiratory tract infection has been shown to be predictive of antibiotic prescription , 38, 39.The finding in our study is suggestive of prescribers appreciating that these diseases are more likely to be caused by viruses rather than bacteria , 44 or tThat prescribers with more than 5 years of practice experience are more likely to prescribe antibiotics than those with less experience is at variance with a study conducted in Italy  but simiThough inadequate training of prescribers has been shown to worsen antibiotic prescribing  we foundRegarding age, we found that patients aged 5 years or more had lower odds of being prescribed antibiotics. A similar observation was made in Cameroon . ChildreWe conducted a literature search on PubMed and Google scholar, and to the best of our knowledge this is the largest published study on antibiotic prescription in Ghana. The relatively large sample size allowed for the inclusion of several factors in the assessment. One limitation of this study is that the period of the data collection was short (3 months). As such, seasonal variations in antibiotic prescription was not accounted for. Another limitation of this study is the assumption that all documented actions were carried out. Similarly, all undocumented actions were assumed not to have been taken. This may have introduced misclassification bias but was considered more acceptable than direct observation which may have caused prescribers to vary their usual prescribing habit. Also, behavioural factors such as physician perception of patient desire, patient expectation and smoking were not assessed. Finally, findings of this study may not apply to febrile patients who were admitted due to disease severity.The factors associated with antibiotic prescription for febrile outpatients were prescriber’s profession and years of practice; age of patient; some presenting symptoms which included cough, watery stool, dizziness, difficulty in swallowing, laboratory tests; some diagnoses including typhoid fever, urinary tract infection and skin disease. In contrast, ARTI and pneumonia were not significantly associated with antibiotic prescription.The rate of antibiotic prescription for febrile outpatients is high compared to practices from settings with similar burden of communicable diseases. To reduce this, advocacy for the increased use of laboratory testing prior to prescribing antibiotics is key. Also, more experienced prescribers and treatment for children under five should be targeted with interventions aimed at reducing antibiotic prescribing. IMNCI training appears to be counterproductive for controlling antibiotic prescribing in adults.


The rise in antibiotic resistance is a global public health concern, and antibiotic overuse needs to be reduced. Earlier studies of out-of-hours care have indicated that antibiotic prescribing is less appropriate than that of in-hours care. However, no study has compared the out-of-hours treatment of infections to in-hours treatment within the same population.This retrospective, descriptive study was based on data retrieved from the Kronoberg Infection Database in Primary Care (KIDPC), which consists of all visits to primary care with an infection diagnosis or prescription of antibiotics during 2006–2014. The purpose was to study the trends in antibiotic prescribing and to compare consultations and prescriptions between in-hours and out-of-hours.The visit rate for all infections was 434 visits per 1000 inhabitants per year. The visit rate was stable during the study period, but the antibiotic prescribing rate decreased from 266 prescriptions per 1000 inhabitants in 2006 to 194 prescriptions in 2014 . For the out-of-hours visits , a similar reduction in antibiotic prescribing was seen. The decrease was most apparent among children and in respiratory tract infections.When antibiotic prescribing during out-of-hours was compared to in-hours, the unadjusted relative risk of antibiotic prescribing was 1.37 (95% CI 1.36 to 1.38), but when adjusted for age, sex, and diagnosis, the relative risk of antibiotic prescribing was 1.09 (95% CI 1.08 to 1.10). The reduction after adjustment was largely explained by a higher visit rate during out-of-hours for infections requiring antibiotics . The choices of antibiotics used for common diagnoses were similar.Although the infection visit rate was unchanged over the study period, there was a significant reduction in antibiotic prescribing, especially to children and for respiratory tract infections. The higher antibiotic prescribing rate during out-of-hours was small when adjusted for age, sex, and diagnosis. No excess prescription of broad-spectrum antibiotics was seen. Therefore, interventions selectively aiming at out-of-hours centres seem to be unmotivated in a low-prescribing context. The rise of antibiotic resistance is a global public health threat according to the World Health Organization , and antIn primary care in-hours (IH) are usually office hours (in Sweden 08:00 to 17:00) during business days, and out-of-hours (OOH) are the remaining hours. Earlier studies of OOH care have suggested that compared to IH care there are lower adherence to antibiotic guidelines , 7, a hiAlthough Sweden belongs to the European countries with low levels of antibiotic prescriptions, there is still room for improvement . PreviouBecause visits for infectious diseases are common at OOH centres, it is important to evaluate whether OOH visits are associated with increased antibiotic prescribing rates because this would warrant interventions in OOH settings.The purpose of the study was to describe the trends in antibiotic prescribing over time and to compare diagnosis-linked prescribing in general and in detail between IH and OOH in the same population.In 2014, Kronoberg County in southern Sweden had 189,128 inhabitants, which was equal to 2% of the Swedish population . During During the study period, the number of primary healthcare centres (PHCCs) varied between 28 and 35, with 1–8 family physicians each. There were approximately 100 family physician positions and 50 junior physician positions. At the study start, all PHCCs were publicly run, but since March 2009 a third of the PHCCs have been privately run due to new legislation allowing publicly funded private PHCCs.At the PHCCs, the patient normally booked an appointment through a telephone call with an office nurse who assessed if the patient needed a physician visit. IH were business days 08:00 to 17:00. In the region there were two OOH centres (OOHCs), and the PHCCs staffed the OOHCs with physicians. Patients were supposed to call a nurse triage first, but could also walk in. The visit fees were the same as for IH visits. Home visits were rare, and usually only performed for urgent cases at elderly care homes. Nurses at the OOHCs were responsible for phone advice, and there was also a national phone advice number for patients where nurses provided medical advice. At the time of the study, no Internet services were available.OOHC 1 served approximately 125,000 inhabitants and was situated in the neighbourhood of the hospital in city 1. During 2006–2007 the centre was open from 17:00 to 24:00 on weekdays and from 08:00 to 24:00 on weekends and holidays. From 2008 the centre closed at 21:00. Walk-in patients met a nurse who assessed whether a meeting with a physician was warranted.OOHC 2 served approximately 63,000 inhabitants and was situated at the emergency department of the hospital in city 2. During 2006–2007 the centre was open from 17:00 to 08:00 on weekdays and around the clock on weekends and holidays. From 2008 the centre closed at 21:00. Walk-in patients generally got to see a physician.This retrospective, descriptive study was based on data from the KIDPC database, which contains information on all visits with an infection diagnosis and all antibiotic prescriptions with or without a visit in primary care in Kronoberg County in 2006–2014. Annually, there were on average 86,000 visits for infections and 43,000 antibiotic prescriptions reported in the database.International Classification of Disease and Related Health Problems – Tenth Revision (ICD-10) [The data in the KIDPC were extracted from the electronic medical records (EMR) used in Kronoberg County  at one instance in 2015 using BusinessObjects . These data contain detailed information about the patients , the visits , the care providers , the investigations , and the prescriptions . The data were linked together using the anonymous patient ID and visit date. For all physician visits, at least one diagnosis was registered according to the simplified Swedish primary care edition of the (ICD-10) . The dia(ICD-10) . The maiAntibiotic prescriptions were identified according to Anatomical Therapeutic Chemical Classification (ATC) code group J01, which includes all oral and parenteral antibiotics, but not antibiotics in ointments or eye drops. Antibiotic prescriptions were linked to diagnoses if within a week after a visit. Antibiotic treatment without a diagnosis of an infection could also result from consultation with a care provider other than a physician or from a non-infection diagnosis at a visit. Information on whether the patients collected the medication at the pharmacies was not available in the present study.All physician visits with an infection diagnosis and all antibiotic prescriptions were extracted from the KIDPC database, resulting in a data set with 702,048 physician visits and 389,263 prescriptions over 9 years. For each visit, data on the patient’s age and sex, infection diagnoses, antibiotic treatments, and PHCC were extracted.A visit was defined as a physical visit to a physician, and a consultation was defined as a phone, mail, e-mail or nurse contact. It was compulsory for the physician to code the diagnosis when documenting the visit. Only physician coded diagnoses were used in this study for consistency. In 3% of the visits more than one infection diagnosis was recorded, and in these cases the main diagnosis was selected based on the severity and the likelihood of the diagnosis resulting in an antibiotic prescription. Consultations were not coded for diagnoses, but could in some instances result in antibiotic prescriptions, for example treatment for UTI or repeat prescriptions.This study presents descriptive annual data and mean annual change for infections and antibiotic prescribing per 1000 inhabitants divided per main infection group, age group, sex, and per IH and OOH Tables , 3, 4. TThe IH and the OOH cohorts were compared. The relative risk of receiving antibiotics during OOH was calculated Table . The proP-values ≤ .05 were considered statistically significant.All analyses were performed using Excel 2013  and SPSS Version 23 . For descriptive statistics, means, and proportions were used. For annual trends, linear regressions were calculated and presented as mean annual change with 95% confidence interval. Comparisons between groups after adjusting for sex, age, and diagnosis were presented as relative risks with 95% confidence interval. Comparisons between proportions of categorical variables in two independent groups were performed with the chi-square test. The physician visit rate for infections varied during the study and reached a maximum of 469 visits per 1000 inhabitants per year in 2011 and a minimum of 398 visits in 2014. Female patients have more infection visits than male patients, 502 and 366 visits per 1000 inhabitants per year respectively. Children 0–4 years and adults over 80 years had the highest visit rates, 995 and 576 visits per 1000 inhabitants per year respectively. No significant trends were observed in total visit rate nor in visit rate by sex, but the mean annual change in visit rate per 1000 inhabitants per year decreased in children 0–4 years (− 33.7 (95% CI − 56.0 to − 11.5)), increased in adults 65–79 years (7.7 (95% CI 1.1 to 14.3) and in adults over 80 years (13.9 (95% CI 7.6 to 20.2)) ). There was no sex difference, but the decrease in antibiotic prescriptions was more pronounced in children 0–4 years ) and in children 5–19 years . The antibiotic prescribing frequency decreased mainly for RTIs ), explaining 76% of the total reduction. Antibiotic prescriptions without an infection diagnosis and prescriptions for UTIs also decreased, explaining a further 11 and 8% of the total reduction, respectively ). Also, the antibiotic prescribing decreased from 43 prescriptions per 1000 inhabitants in 2006 to 26 prescriptions in 2014 ).The diagnoses and antibiotic prescription rates between IH and OOH are shown in Table For the six most common diagnoses treated with antibiotics, a comparison of treatment choice per diagnosis with IH and OOH visits was made. The prescription rate was higher during OOH for pneumonia, acute otitis media, and pharyngotonsillitis. Although the difference was statistically significant, the choices of treatment for each diagnosis were comparable between IH and OOH prescriptions Table .During the study period, the level of infection visits was constant, but the antibiotic prescription rate decreased. Fewer prescriptions in children and for RTIs were the main reasons for the reduction. During OOH, there was a reduction both in infection visits and in antibiotic prescribing. The antibiotic prescription rate was higher during OOH than during IH, and when adjusting for age, sex, and diagnosis the difference was significant but small. The choices of treatments were similar.This study showed that women visited primary care for infections more often than men and also received antibiotic treatment more often than men. The same pattern has been seen in other studies from Denmark, the Netherlands, and the United Kingdom , 27, 28.Our data on visit rates per 1000 inhabitants per years for infections were similar to the Primary Care Record of Infections in Sweden (PRIS) database , which cThe total antibiotic prescribing in primary care decreased by 27% in this study. However, in the PRIS database  the reduSeveral explanations are possible for the reduction in antibiotics prescriptions. For example, there might be increasing awareness among the general public that the use of antibiotics should be avoided when they are not needed. Also, physicians might have become more restrictive in prescribing. Another reason might be due to the antibiotic stewardship work performed by the Strama group, the Swedish strategic programme against antibiotic resistance . In 2005During the period studied here, the number of OOH infection visits decreased by a third. Factors contributing to the decrease were shorter opening hours at the end of the study, a penalty fee (100 euros) introduced in 2008 for the PHCC for each patient attending the OOHC, and the introduction of a nurse triage system for walk-in patients at OOHC1.The OOH antibiotic prescription rate per 1000 inhabitants per year was at the same level in the Netherlands, Sweden, and England , but higher in Denmark (80 prescriptions) , 13, 27.The main explanation for excess prescribing during OOH is that infections that are often treated with antibiotics were more common during OOH visits such as acute media otitis, pharyngotonsillitis, and lower UTIs. The relative risk of antibiotic prescribing was decreased when adjusting for diagnoses. For SSI, the relative risk of receiving antibiotics during OOH remained elevated 1.20 (95% CI 1.18–1.23). It was uncommon to prescribe UTI antibiotics without a visit with infection diagnosis during OOH service (9% of UTI antibiotic prescriptions were without a visit during OOH compared to 39% during IH) although it was in line with current guidelines. This fully explained the higher UTI visit rate during OOH.These results are similar to other European studies when comparing OOH and IH. A Norwegian comparison of tonsillitis and acute media otitis showed no difference in the prescription rate at OOHCs , and a DThe remaining excess prescriptions during OOH after adjusting for diagnosis were estimated, leading to 2.2 more prescriptions per 1000 inhabitants per year compared to IH, which corresponds to 7.9% of the prescriptions during OOH and to 1.2% of all prescriptions during IH and OOH together. These prescriptions could partly be explained by sicker patients in need for urgent evaluation and an absence of control visits in the OOH setting. On the other hand, a reason could be a lower threshold to prescribe during OOH for example due to high workload or due to limited possibility to arrange for follow-ups.Apart from the high relative risk of receiving antibiotics for SSI during OOH, there are no apparent areas to intervene. But because the total decrease of antibiotic prescriptions during the study period is 27% and the excess prescriptions during OOH are just above 1% of all antibiotic prescriptions, there would be limited gain from intervening in the OOH setting.There were no differences in treatment choice, which corresponds with other quantitative studies from Norway and the Netherlands , 33 and The data set was complete for infection visits and antibiotic prescriptions in primary care in a region in Sweden. Because the whole region was included, the data were real-life data without any selection due to study participation. Also, the same EMR system was used during the study period thus decreasing the risk for information errors. Because writing a diagnosis was compulsory for all visit records, very few diagnoses were missing. All OOH infection visits and prescriptions were included, which enabled comparisons between IH and OOH, adjusting for sex, age groups, and diagnoses. The comparison between IH and OOH is relevant for Sweden as a whole and for other countries with similar OOH settings.Limitations of the study include that no validation of diagnoses by examining the EMR was done. Also, the reason why some antibiotics are prescribed without a coded infection diagnosis has not been explored. A lower threshold to diagnose infections and to prescribe antibiotics in the OOH setting cannot be ruled out but would also be hard to verify in the EMR. Other antibiotics than oral and parenteral antibiotics (ATC code J01) are missing in the dataset, such as antibiotics in topical skin and eye preparations. The antibiotic rate for the elderly (> 80 years) might be underestimated due to partly missing data for patients with medication administered through a dispensing system. Furthermore, we could not measure the rate of delayed prescribing because we did not have access to pharmacy dispensing data. The common way of delayed prescribing in Sweden is that the patient receives an electronic prescription but is recommended to wait a few days before collecting the prescription .Although the infection visit rate was unchanged, there was a significant reduction in antibiotic prescribing, especially to children and for RTIs. The increased antibiotic prescribing rate during OOH was small when adjusted for age, sex, and diagnosis, and no excess prescribing of broad-spectrum antibiotics was seen. Therefore, interventions selectively aiming at OOHCs seem to be unmotivated in a low-prescribing context.Additional file 1. Infection diagnoses selected to be included in the Kronoberg Infection Database in Primary care 2006–2014. Description: The total number of patients and visits are shown for all providers  and for physicians only.


Many practical aspects of processing fresh concrete depend on its rheology, such as the pumping of the material. It is known that a lubricating layer is formed in the process, which significantly reduces the pumping pressure. However, these phenomena can hardly be considered in the usual rheological measurements. A main problem is the optical inaccessibility of the material, which prevents estimations about, e.g., the thickness of the plug flow or particle migration. In this paper, the pneumatic pumping of a transparent model concrete is performed by means of a test plant. The flow profile over the entire pipe cross-section is resolved in time and space via Particle Image Velocimetry (PIV) measurements. This allows the comparison with the analytical flow profile from rheological measurements of the material using the Buckingham–Reiner equation. A reduction of the pressure loss to around 60% induced through segregation of the material is found. These measurements reflect the rheology of the material under realistic pumping conditions including particle migration. This makes it possible for the first time to observe a transparent material with concrete-like rheology under pulsating pumping conditions and to compare the true and calculated time-resolved pressure loss. Concrete is one of the most frequently used building materials worldwide. This substance enables us to construct state-of-the-art buildings and technologically sophisticated structures such as bridges and dams. One of the material’s key properties is its ability to be processed in its liquid state first and obtain a high-strength material afterwards. In the last few years, the development of new processing technologies like 3D-printing has led to a high interest in predicting the concrete’s rheological properties ,2. For aAt the construction site, concrete is usually transported to its destination by means of double piston pumps . Unlike Concrete is a highly complex material consisting of a number of individual components, mainly cement, water, sand, and coarse aggregates, as well as chemical additives to influence the rheology to the desired extent ,7,8. TheAnother well-known phenomenon that leads to drastic changes in the flow behavior is the segregation of the coarse material during the transport process ,15. EspeThe formation of the lubricating layer has been frequently investigated in recent years, for example by ultrasonic velocimetry , pressurOne of the biggest problems in the investigation of concrete is the poor optical accessibility of the material. Because of this, many assumptions have to be made for rheological measurements. For example, a fluid with yield stress will not be sheared over the entire range. The estimation of the thickness of the shear layer and the plug-flow is error-prone. In addition, the flow behavior under pumping conditions is different from the behavior in the rheometer. To solve these problems, a transparent model concrete was employed, whose basic rheological properties were comparable to those of real concrete.In this paper, the optical and rheological investigation of such a model concrete flowing through a pipe at a pulsating velocity is described. Due to the optical accessibility, it is possible to determine temporally and spatially resolved velocity data using PIV and thus to describe the flow profile during the pumping process. The flow profile obtained in this way contains system-relevant mechanisms such as the migration of particles. These phenomena can hardly be considered in a rheometer. Furthermore, in the present case, no assumptions about the thickness of the sheared zone or the plug-flow have to be made. The resulting data reflect the flow behavior under realistic pumping conditions. By using the Buckingham–Reiner equation, the resulting flow profile can be compared with the theoretical values obtained by rheological measurements. The influence of segregation on pump pressure and pressure drop is thus clearly shown. For the first time, the pressure loss and flow profile of a non-Newtonian, densely packed granular material under pulsating pumping conditions can be correlated with rheological data. These findings provide valuable information for the practical application of pumping concrete and for granular materials in general.For the optical investigation of the model concrete under realistic pumping conditions, it was necessary to develop an experimental setup that allowed, on the one hand, the optical investigation of the material and, on the other hand, a time-dependent pumping process. Furthermore, the pressure loss in the system should be detectable as accurately as possible. This setup was called PulsaCoP ; see It consisted of a reservoir that could contain up to five liters of fluid. From this reservoir, the material flowed through an elbow into the measuring section, which had a diameter of 20 mm, a length of 1470 mm, and a thickness of 2 mm. The material then flowed through another elbow and through a ball valve into a container. The measurement pipe is further depicted in The model concrete was pumped pneumatically in the PulsaCoP apparatus. The pressure in the reservoir could be oscillated in a sinusoidal manner by selectively introducing and blowing out compressed air with the help of three solenoid valves attached to the reservoir. In this way, the pumping process could be simulated similar to the double piston pumps commonly used for concrete.The heart of the system was a cylindrical pipe made of borosilicate glass. The pipe was enclosed by an outer channel with an octagonal cross-section, filled with glycerin. The refractive index of all materials: glycerin, borosilicate glass, and the model concrete were nearly identical in order to allow undisturbed optical access to the whole flow domain. Due to the adjustment of the refractive index inside and outside the curved glass tube, there was no distortion of the image. All measurements were carried out at room temperature of about 20 The camera was a MIKROTRON Motion BLITZ EoSens mini2  with a resolution of 15 The measurement setup included three independent pressure sensors. One of them was located in the storage vessel and recorded the reservoir pressure For the investigation, a model concrete is employed whose principal rheological properties are comparable to those of concrete. It consists of borosilicate glass particles and a Bingham liquid based on a 1% Carbomer solution in water. Additional additives are used to match the refractive index of all constituents. Details of the model concrete and its preparation will be published elsewhere .Both the viscosity and the yield stress could be tuned with the Carbomer concentration with respect to the values of these parameters for real concrete. The model concrete did not show any time dependency of the rheology, thus the material showed neither rheopexy nor thixotropy. To observe the behavior of the individual particles in the fluid, the glass beads and the liquid must have the same refractive index. For borosilicate glass, this index was The borosilicate glass spheres in the experiment presented here had a diameter of 0.5 mm to 1.0 mm and were produced by Schäfer-Glas. In order to obtain the densest possible packing, 70% of the 1.0 mm beads were mixed with 30% of the 0.5 mm beads. Afterwards, enough of the liquid was added to give a final solid content of The rheological data were determined in a Haake Mars II  rheometer. The flow curve obtained was fitted with the Bingham model:Here, the effective viscosity r et al. . The visD, and the effective viscosity In order to be able to compare different Bingham materials, it is useful to refer to dimensionless numbers. For flowing Bingham fluids, the Reynolds number Re, and the Hedstrom number He are the most suitable. The former describes the ratio of inertial to viscous forces. It is defined as:−1 through a pipeline of a diameter As an example, the Reynolds and Hedstrom number is Re = 5.7 and He = 1.76, respectively, for a real self-compacting concrete (SCC) with material parameters d τ=31Pa , which i−1 in the measuring pipe, a Reynolds number Re = 4.6 and a Hedstrom number He = 0.6 were obtained. Thus, both the Reynolds number and the Hedstrom number of our model system fit very well to those of the real concrete pumping process taken from the literature.For the model concrete in this study, which was pumped with a constant velocity The flow of the model concrete in the pipeline was pressure driven. For this purpose, a pulsating pressure The results presented here were determined at a pulsating flow velocity. A mean pressure of 2 bar was set and the pressure oscillates with an amplitude of 0.2 bar and 2.5 Hz, as shown in The pressure was initially built up in a buffer container to prevent later fluctuations in the system caused by an insufficient pressure reservoir. After the inlet pressure was reached, the solenoid valves were closed automatically. Then, the ball valve at the end of the measurement section was opened. As soon as the pressure drop was detected, the pulsation of the pressure started automatically.The pressure was recorded during the entire measuring time. The optical recordings were started by a manual trigger. In addition, this trigger signal was also forwarded to the pressure measurement. In this way, pressure and speed could be correlated exactly. The measurement was started after five oscillations and recorded over another six oscillations. This ensured that the system had adapted to the pressure fluctuations. After the end of the oscillating regime, the flow was additionally recorded during linear conveying.The image data obtained in this way were evaluated with the cross-correlation, and thus, the flow profiles resolved in time and space were generated. These in turn were correlated with the pressure data and used for the evaluation.First of all, the velocities and pressure losses were measured to investigate the pumping process. Velocity data were extracted from optical investigations with PIV. The pressure loss was measured directly. Finally, the pressure loss would be determined from the measured rheological data for the model concrete and be compared with the measured data.A typical picture taken by the camera is shown in r was obtained.By cross-correlating the individual images with known An example of such a velocity profile is shown in A typical profile for a non-Newtonian fluid could be observed. The characteristic shear zone at the pipe wall is shown, as well as the zone of the plug-flow, from around −3 mm to 3 mm. The velocity at the pipe wall was not exactly zero here, as it would be with a classic Bingham fluid. Due to the presence of glass spheres directly at the wall, a finite velocity of about 0.05 m/s was still measured there. The classical no-slip condition did not apply to the granular material at this point.Furthermore, a very slight asymmetry of the curve became apparent. It was assumed that this was caused by sedimentation of the glass spheres under gravity. Even if the high yield stress did not lead to segregation in the unsheared state, the yield stress was very well exceeded during pumping. As a result, the glass spheres could sediment, but much more slowly than in a fluid without a yield stress.The advantage of the optical evaluation of the flow profile was that the profile was exactly known at any time of the measurement. This was a significant benefit, especially for non-constant flows, such as those that occur during the pumping of concrete, which could hardly be achieved by any other methods.A three-dimensional representation of the flow profile of the measurement shown here can be found in R. Again, the average speed over the entire pumping process was thus known.From the flow profiles obtained in this way, the average flow velocity In parallel to the optical measurements, the pressure loss D, pipe length L, and the Fanning friction factor f [f could be done without knowing the rheological parameters.For the dependence of the pressure loss on the flow velocity, the equation:factor f . In thisQ and the reduced pressure loss L. The application of the Buckingham–Reiner equation on concrete was possible, although problematic due to the assumptions of the equation: a fully developed, laminar, and isothermal flow of an incompressible fluid in 1D was needed, which was fulfilled here; however the concrete was not homogeneous, and a slip layer (lubricating layer) was found, which made the application problematic; see [However, if the values for viscosity and yield stress were known, an analytical solution existed for the dependence of the pressure loss on the mean flow velocity, the so-called Buckingham–Reiner equation :(7)Q=v¯·tic; see . Furtherf was obtained [Considering the above-introduced dimensionless ratios Re and He, the dimensionless Buckingham–Reiner equation:obtained . With thFor further discussion of the results in this paper, the friction factor from the calculation of the rheological data with Equation  is denotEquation  is referIn addition to the time dependence, the friction factor is plotted against the Reynolds number in Equation . There wFurthermore, estimated values The values for the model concrete and the real concrete showed a very good agreement. This indicated the suitability of the material as a model substance. Please note that the scaling to SCC was done by Hedstrom number He (rheology) and Reynolds number Re (flow rate) only. For real pumping experiments with SCC, effects such as the compressibility of real concrete by entrapped air and time-dependent rheological effects have to be considered, as well.It was clearly noticeable that Under the assumption that a lubricating layer was formed, the pumping pressure, and thus During the pumping of the model concrete, we could observe this segregation process. After a certain time of pumping, nearly no larger particle could be found any longer at the pipe wall. Thus, the packing density of the system was changing. According to Equation , this woIt should be noted that the model concrete could not represent all the properties of real concrete, and therefore, compromises must be made in favor of optical adaptation. For example, the carrier fluid and the particles were not of the same density, which could change the segregation properties. Likewise, non-spherical particles with a polydisperse distribution are present in real concrete, which could change the segregation behavior.The behavior of a concrete under pulsating pumping conditions was investigated in the new experimental setup PulsaCoP. A transparent model concrete was employed, which allowed detailed analysis of velocity profiles and segregation phenomena in the concrete flow. Material and operation parameters were selected in order to meet the important dimensionless parameters of the Reynolds and Hedstrom number of real pumped concrete flows.During the pumping experiments, pressure values were recorded at several locations along the pumping pipeline. Velocity data in the flow were obtained with the help of particle image velocimetry measurements in the model concrete. Pressure losses and mean flow velocities were correlated with respect to the Fanning friction factor and the Buckingham–Reiner equation, respectively. It was found that experimentally and semi-analytically obtained friction factors of the model concrete flow were in reasonable agreement. An estimation of friction factors in corresponding real-world flows of self-compacting concrete was given as well. Quantitative deviations between the different friction factors were caused among others by segregation and further particulate phenomena.These effects are the subject of further investigations within the priority program Opus Fluidum Futurum of the German Research Foundation DFG. Among others, a more rigorous validation of the PulsaCoP experiment by comparison with data from large-scale pumping experiments with real concrete is planned. From these experiments, better correlations of the friction factors, segregation, concrete rheology, and concrete flow rates should be researched as well. Furthermore, these considerations are not limited to the flow in straight pipes, but will be applied to complex geometries in the future.