Enterobacterales along with prescription data for an oral antibiotic filled on the day before, day of, or day after the culture was collected. Linear probability models were used to estimate partial effects of select clinical and demographic variables on the composite outcome. In all, 4,792 patients had 5,587 oral antibiotic prescriptions. Of 5,395 evaluable episodes, 22% of patients received an antibiotic to which the pathogen was resistant in vitro, and those patients were almost twice as likely to require a second prescription (34% versus 19%) or be hospitalized (15% versus 8%) within 28 days of the initial prescription fill compared to patients who received an antibiotic to which the pathogen was susceptible. Approximately 1% of Enterobacterales isolates were resistant to all commonly available classes of oral antibiotics. A greater risk of treatment failure was seen in patients over 60 years of age, patients with diabetes mellitus, men, and those treated with an antibiotic when prior culture identified an organism resistant to that class. The increasing resistance among members of Enterobacterales responsible for outpatient UTIs is limiting the effectiveness of empirical treatment with existing antibiotics, and consequently, outpatients with UTI are more likely to require additional courses of therapy or be hospitalized.Resistance to oral antibiotics commonly used to treat outpatient urinary tract infections (UTIs) is increasing, but the implications of empirical treatment of resistant pathogens are not well described. Using an electronic records database, we reviewed the outcomes of patients >18 years of age who developed an outpatient UTI and had an outpatient urine culture result showing a member of the order IMPORTANCE Resistance rates for bacteria that cause urinary tract infections (UTIs) have increased dramatically. Regional rates of resistance to commonly prescribed antibiotics now exceed 20%, which is the threshold at which the Infectious Diseases Society of America recommends therapy be guided by culture. Our goals were to describe outcomes for outpatients with UTIs caused by bacteria resistant to empirically chosen antibiotics and to create a simple stratification schema for clinicians to identify UTI patients at increased risk of treatment failure due to antibiotic mismatch. These data are relevant to clinicians, given how common uncomplicated UTIs are, and highlight the need for clinicians to understand local resistance rates and the importance of culture-guided treatment, especially in vulnerable patients. These findings also showed that 1% of bacteria were resistant to all major classes of oral antibiotics, underscoring the need for new antibiotics to treat patients with UTIs due to resistant bacteria. Uncomplicated urinary tract infections (uUTIs) are among the most common bacterial infections in the outpatient setting, resulting in an estimated 15 million office or emergency department visits and 21 million prescriptions in the United States annually 13. AlthouDespite the rising rates of resistance, there are limited data on the consequences of inappropriate empirical therapy prescribed in the community for uUTI. Studies across numerous infection types clearly demonstrate the importance of “getting it right the first time.” However, it is unclear if the early appropriate therapy is as critically important among patients with less severe infections like uUTIs. To better understand the consequences of inappropriate empirical therapy among outpatients with UTIs due to Gram-negative uropathogens, we conducted a retrospective database analysis to describe rates of antibacterial resistance to commonly used oral antibiotics for uUTIs and quantify 28-day outcomes by appropriateness of empirical therapy.(Portions of these data were previously presented at (i) Infectious Diseases Week 2018, San Francisco, CA, 3 to 7 October 2018, (ii) European Congress of Chemotherapy and Infectious Diseases, Madrid, Spain, 21 to 24 April 2018, (iii) European Congress of Chemotherapy and Infectious Diseases, Amsterdam, Netherlands, 13 to 16 April 2019, and (iv) MICROBE, American Society for Microbiology, Atlanta, GA, 7 to 11 June 2018).5 CFU/ml.During the study period, 4,792 outpatients had 5,587 UTI episodes with oral antibiotic prescription data available, and 5,395 UTI episodes had antibiotic prescription data as well as admission and inpatient pharmacy data available . Most paEscherichia coli was the most common pathogen (75.6%), followed by Klebsiella spp. (14.5%) and Proteusmirabilis (5.3%) (In vitro resistance of these urinary tract pathogens was observed to quinolones (22.8%), β-lactams , trimethoprim-sulfamethoxazole (27.6%), and nitrofurantoin (15.9%) (s (5.3%) . In vitr (15.9%) . Ciprofl (15.9%) . Overall5 CFU/ml on the index urine culture did not distinguish between the need for a second prescription or hospitalization within 28 days relative to an organism burden of <105 CFU/ml. Diabetics were more likely to have an infection with E. coli (P < 0.001) and more likely to be treated with an antibiotic to which the E. coli isolate was not susceptible (P < 0.001).Treatment failure occurred in 34.3% of patients who received inappropriate empirical therapy, compared to 18.9% in patients who received appropriate empirical therapy. Similarly, the rates of hospitalization were higher for patients who were treated with an antibiotic to which the pathogen was nonsusceptible  . The 28-Enterobacterales isolates, 32% were pansusceptible , and treatment with a quinolone, nitrofurantoin, or β-lactam when a prior culture had identified an organism resistant to that same class. The baseline risk of treatment failure for urinary entified .in vitro resistance was identified across the antibiotics commonly used to treat community urinary tract infections, exceeding 20% for quinolones, β-lactams, and trimethoprim-sulfamethoxazole. As a consequence, 22% of patients in this study did not initially receive an antibiotic that was effective against the offending pathogen in vitro.In this cohort of over 5,000 patients at 15 institutions in the United States, significant The within-28-days antibiotic represcription rate for patients whose initial antibiotic did not match the susceptibility of the identified pathogen was approximately 34%, almost twice the rate for patients with susceptible pathogens, and did not differ significantly by baseline pathogen, CFU count at baseline, or the initial antibiotic prescribed. A similar observation was made in a small retrospective study of UTI patients treated in the emergency department with cephalexin, where resistance rates were as high as 45% and return visits for those who received mismatched therapy were more than double . These dE. coli and the E. coli isolates were more likely to be nonsusceptible to the prescribed antibiotic. A predisposition for diabetics to fail treatment may relate to an underlying immune dysfunction, although repeat treatment courses and subsequent selection of resistant pathogens may be just as important.In 2016, 9.2% of the U.S. population was diagnosed with diabetes mellitus . Relativ9–in vitro activity of the empirically chosen antibiotic based on the local antibiogram would be especially important.The parameter estimates from the linear probability models (LPMs) provide a patient-centered risk adjustment index that may help identify patients who are at significantly higher risk of treatment failure and for whom more effective initial antibacterial regimens would be advantageous. Among the risk factors for the composite failure event, empirical treatment with an antibiotic class for which there is a history of a resistant pathogen is most significant. For example, a 70-year-old woman with diabetes mellitus and a history of a quinolone-resistant organism who is treated with a quinolone has an estimated probability of failure of 47%, far exceeding the baseline risk of failure of 17%. In such a patient, a high level of confidence in the Enterobacterales other than E. coli. The remaining FDA-approved agent for uUTI in the treatment guidelines is fosfomycin, which is rarely prescribed, due in part to questionable efficacy (The 2011 treatment guidelines of the Infectious Diseases Society of America (IDSA) for uncomplicated urinary tract infection  recommenefficacy  and the This study found that 22% of patients for whom a baseline urine culture was sent were failing initial empirical antibiotic treatment for uUTI, a rate that is nearly twice as high as for those who receive appropriate empirical antibiotics. This implies that, in the United States, commonly prescribed empirical antibiotics, as recommended in IDSA’s treatment guidelines, are no longer capable of achieving their stated objective. Waiting for urine culture results before prescribing therapy is a possible solution, but this approach may be less effective, more costly , and ultThese analyses have some limitations. Patients included in the analysis had a baseline urine culture sent, which may reflect baseline patient characteristics differentiating them from patients who had no culture sent. The patients presented at a clinic associated with a hospital microbiology laboratory and may not reflect results from a freestanding clinic. While there may have been subtle differences in the methods of determining susceptibility used by the different testing sites, these differences were likely not significant, as the outcomes were consistent with other published epidemiologic studies. Due to coding limitations, other comorbidities that could have affected the LPMs could not be assessed, and omitted variables correlated with those in the model may bias model estimates. To account for the fact that symptomatology to justify a switch in antibiotic therapy was not available, we purposely excluded antibiotic switches within 1 day of the availability of culture results, which may have occurred simply because the initial regimen was adjusted after culture outcome and not because of ongoing symptoms. We cannot, however, be certain that our approach completely removed this bias. For any reason, however, the environmental effects of multiple courses of different classes of antibiotics for the same episode of infection should not be ignored. The hospitalization outcomes were not based on international classification of diseases (ICD) codes, and as a consequence, the hospitalization rates may not reflect the true rates in these communities. The definition of diabetes mellitus was conservative and limited to concomitant ambulatory prescription fills of medications to control diabetes and HbA1C measurements, although the increased proportion of patients with diabetes is consistent with other published surveys , 18. LasEnterobacterales isolates responsible for outpatient urinary tract infection are limiting the effectiveness of empirical treatment with existing antibiotics. As a consequence, outpatients, including women with uUTI, are more likely to experience a prolonged course of infection. For as many as 1% of women, or approximately 200,000 episodes every year in the United States alone, there is no commonly available oral antibiotic to treat their infection; many of these women will require intravenous therapy. In order for guidelines to continue to support empirical antibiotic therapy for UTI, there will need to be either point-of-care rapid diagnostics that identify both species and resistance determinants or new oral antibiotics effective against resistant uropathogens.Increasing rates of resistance among the Enterobacterales, including E. coli, Klebsiellapneumoniae, Klebsiellaoxytoca, Enterobacteraerogenes, Enterobactercloacae, Serratiamarcescens, Citrobacterfreundii, Proteusmirabilis, or Morganellamorganii, and (ii) received a prescription for any of the following oral antibiotics on the day prior to the urine culture collection date, the index urine culture date, or the day after a urine culture index date: fluoroquinolones, trimethoprim-sulfamethoxazole, nitrofurantoin, fosfomycin, and β-lactams . For patients with multiple urine cultures within the 28-day follow-up period, only the first episode with a corresponding antibiotic prescription was included.Patients from 15 institutions in the U.S. BD Insights Research Database  with outpatient urine culture results, demographic information, and prescription data collected between 2015 and 2017 were considered for inclusion in this study. Patients were included if they (i) had a quantitative urine culture positive for a member of the order Demographic elements included age at index date, gender, antibiotic therapy, quantitative urine culture, and susceptibility results. Laboratory data  within 7 days of the index urine culture were evaluated, when available. A patient was considered to have a diagnosis of diabetes mellitus if the patient had either a hemoglobin A1C (HbA1C) measurement of >7% or a prescription filled for a diabetic medication in the 6 months prior to urine culture collection. We also evaluated the presence of urine glucose in episodes that had a urinalysis done on the day of index culture collection as an additional possible surrogate for uncontrolled blood sugar. The CFU/mL from the quantitative urine culture was documented. Pathogens were considered susceptible or nonsusceptible to the antimicrobial class based on susceptibility testing performed at the local institution.in vitro activity (defined as “susceptible” in the database) against all identified Enterobacterales isolates on the index urine culture date ± 1 day. The primary outcome of interest was antibiotic treatment failure. Antibiotic treatment failure was defined as (i) receipt of a subsequent antibiotic prescription within 28 days of the initial prescription or (ii) a UTI-related hospital admission within 28 days of the initial prescription. When evaluating subsequent prescriptions within 28 days, prescriptions within 1 day of the availability of antimicrobial susceptibility test results were excluded to avoid including antimicrobial modifications by the clinician simply due to the availability of susceptibility results. Both all-cause and UTI-related 28-day hospital admissions were examined. Hospital admissions were considered UTI related if the patient received antimicrobial therapy  within the first 3 days and had a positive urine culture.Empirical antibiotic therapy was defined as appropriate if the patient received a prescription for an antibiotic with P < 0.01). Hospital-level fixed effects were included to control for any persistent differences between hospital and clinic policies, procedures, laboratory practices, and populations served. The model for episodes with general laboratory examination was additionally controlled for abnormal HbA1C (>7%), creatinine (>2 mg/dL), and white blood cell count (>10 × 10^9/L) measurements.Two models were estimated, one for all episodes and one for episodes that had general laboratory data within 7 days of the index culture. Model parameters were estimated by ordinary least-squares with robust standard errors . The estimated models are linear probability models (LPMs) that tested for statistical significance of estimated coefficients (


Megalobrama amblycephala to dietary methionine (Met) levels. Three practical diets with graded Met levels  were prepared to feed the juvenile fish. The results showed that the 0.84% Met diet significantly improved the growth compared with 0.40% diets. Compared with 0.84% and 1.28% Met, 0.40% Met significantly increased the hepatic lipid content, while decreasing the muscular lipid and glycogen contents. 0.40% Met decreased the protein levels of phospho-Eukaryotic initiation factor 4E binding protein-1 (p-4e-bp1), 4e-bp1 and Ribosomal protein S6 kinase 1 in the liver, compared with 0.84% diet, while an increasing trend was observed in the muscle. Met supplementation tended to decrease and increase lipid synthesis in the liver and muscle, respectively, via changing mRNA levels of sterol regulatory element-binding protein 1, fatty acid synthetase and acetyl-CoA carboxylase. 1.28% dietary Met promoted fatty acid β-oxidation and lipolysis in both the liver and muscle by increasing carnitine palmitoyl transferase 1, peroxisome proliferator activated receptor alpha, lipoprotein lipase and lipase mRNA levels. Compared with 0.40% and 0.84% dietary Met, 1.28% Met enhanced the mRNA levels of hepatic gluconeogenesis related genes phosphoenolpyruvate carboxykinase (pepck), and glucose-6-phosphatase, and muscular glycolysis related genes phosphofructokinase (pfk), and pyruvate kinase (pk). The mRNA levels of hepatic pfk, pk and glucokinase were markedly downregulated by 1.28% Met compared with 0.84% level. Muscular pepck, glycogen synthase, and hepatic glucose transporters 2 mRNA levels were induced by 1.28% Met. Generally, deficient Met level decreased the growth of juvenile Megalobrama amblycephala, and the different nutrient metabolism responses to dietary Met were revealed in the liver and muscle.A 75-day rearing trial was designed to study the response of juvenile  Megalobrama amblycephala, is the main freshwater aquaculture species in China. Our previous studies have confirmed that dietary methionine (Met) is important for the growth performance of blunt snout bream, and optimal dietary Met could improve the immunity and antioxidant capacity of dietary Met of blunt snout bream3. In addition, Met has been shown to regulate glucose and lipid metabolism in fish. The primary muscle cells of turbot  under Met deprivation showed inhibited expression of the key target of rapamycin (TOR) pathway elements, and genes related to glycolysis and fatty acid synthesis, while inducing fatty acid β-oxidation4. In cobia (Rachycentron canadum), Met deficiency suppressed hepatic lipogenesis related gene (sterol regulatory element-binding protein (srebp1) and fatty acid synthetase (fas)) mRNA expressions and upregulated fatty acid oxidation-related gene , peroxisome proliferator activated receptor alpha (pparα), and lipoprotein lipase (lpl)), phosphoenolpyruvate carboxykinase (pepck) relative mRNA expression levels6. Moreover, the nutrient metabolism response to dietary Met showed species-specific responses. Rainbow trout (Oncorhynchus mykiss) fed Met-deficient diets showed a positive relationship with hepatic fas mRNA expression, and negative with cpt1 and fructose-1,6-biphosphatase (fbp) relative mRNA expression levels7. While Met deficiency and excess diet induced hepatic lipid accumulation in yellow catfish (pelteobagrus fulvidraco)8. The increased lipid content in the liver and whole-body were observed in Takifugu rubripes fed with increasing dietary Met levels, which contradicted with hepatic relative mRNA expressions: decreased related lipogenic genes expression  and increased lipolytic genes expression (acyl-CoA oxidase 1 (acox1), hormone-sensitive lipase, and apolipoprotein b100)9. These data revealed that the response of aquaculture fish to dietary Met is complex. However, the effects of dietary Met levels on nutrient metabolism of blunt snout bream are still uncertain due to the limitation of the study.Blunt snout bream, 11. Furthermore, it was found that the metabolic polytrophic response of fish species to some dietary nutrients is tissue-specific. Kolditz et al.12 reported that the high-energy diet repressed the activity of the lipogenic enzymes and stimulated enzymes involved in fatty acid oxidation and glycolysis in the liver of rainbow trout but had little effect on related enzymatic activities in muscle. Met-restricted feeding significantly increased the liver fat content but decreased the muscle fat content of rainbow trout13. The juvenile Nile tilapia (Oreochromis niloticus) fed on diets containing 10 mg/kg clenbuterol exhibited decreased hepatic fas relative mRNA expression level but had increased fas relative mRNA expression level in the muscle14. However, in blunt snout bream, a lot of studies reported that hepatic nutrient metabolism was a response to a dietary composition including amino acids (except Met)18. Unlike the liver, there are few studies that have investigated the effect in muscle, and many of these researches focused on muscle development, composition rather than nutrient metabolism20. The response of the nutrient metabolism in the liver and the muscle to dietary administration is still unclear.The liver and muscle are important nutrient metabolism organs in animals. In fish, the liver and muscle are both main sites of protein synthesis, lipid synthesis and excess carbohydrate storageMegalobrama amblycephala and to study the different metabolic responses in the liver and muscle.Therefore, the current study was designed to investigate the effects of dietary Met levels on the nutrient metabolism of P < 0.05). FBW, SGR and WGR were significantly lowered in the 0.40% Met diet group than those in fish fed the 0.84% Met diet (P < 0.05). The values of feed conversion ratio (FCR) showed the opposite trend.As shown in Table P > 0.05). Lipid content in fish fed 0.40% Met diet was significantly higher than that in the fish fed other diets (P < 0.05). While 0.40% Met level significantly decreased the lipid content in the muscle compared with 0.84% and 1.28% Met levels (P < 0.05).As shown in Table P > 0.05), although GLU contents tended to increase with increasing dietary Met levels.As indicated in Fig. P > 0.05). However, 0.84% and 1.28% Met levels significantly increased muscular glycogen contents compared with 0.40% Met diet (P < 0.05).As shown in Fig. As shown in Fig. tor mRNA levels, while hepatic 4e-bp1 mRNA levels were significantly upregulated by 1.28% Met level (P < 0.05). The relative mRNA levels of s6k1 in both the liver and muscle were markedly downregulated by 0.40% dietary Met compared with 0.84% Met level (P < 0.05). Dietary Met levels had no significant effects on muscular tor or 4e-bp1 mRNA expressions (P > 0.05).The mRNA expression levels were shown in Fig. srebp1, fas and acetyl-CoA carboxylase (acc) mRNA levels were induced by 0.40% dietary Met level (P < 0.05). Hepatic cpt1 and pparα mRNA levels were increased with increasing dietary Met levels (P < 0.05). Dietary Met levels of 1.28% significantly reduced hepatic lipase (lp) mRNA expression levels compared with 0.84% Met level (P < 0.05). While in the muscle, the mRNA levels of srebp1, fas, acc, cpt1, pparα and lpl were significantly upregulated in fish fed 1.28% Met diet, compared with 0.40% or 0.84% Met diet (P < 0.05)   in both the liver and muscle were not significantly affected by dietary Met levels (P > 0.05).As presented in Fig. pepck and glucose-6-phosphatase (g6pase), and muscular pepck, phosphofructokinase (pfk), pyruvate kinase (pk) and glycogen synthase (gs) were markedly increased by 1.28% Met diet compared with the 0.40% diet (P < 0.05). gk, pfk and pk mRNA levels in the liver were significantly suppressed by 1.28% diet compared with 0.84% diets (P < 0.05). Glucose transporters 2 (glut2) mRNA levels in the liver were significantly induced by 1.28% Met diet compared to 0.84% diet (P < 0.05); while muscular glut4 and fbp, and hepatic gs and fbp mRNA levels were not markedly affected by dietary Met levels (P > 0.05).As presented in Fig. Pseudosciaena crocea R21; juvenile humpback grouper, Cromileptes altivelis22; blunt snout bream1; Chinese sucker, Myxocyprinus asiaticus23; and grass carp, Ctenopharyngodon idella24. Similarly, in the present study, the data related to growth performance indicated that Met supplementation (0.84% and 1.28% dietary Met) significantly improved FBW, WGR and SGR of juvenile blunt snout bream compared with the diet without Met supplementation (0.40% Met diet). This result was consistent with the conclusion in Liao et al.1 that dietary Met played an important role in the growth performance of juvenile Megalobrama amblycephala. In our present study, the juvenile fish fed diets containing graded dietary Met levels showed no significant difference in whole body composition. Similar results were also reported in large yellow croaker and juvenile cobia25. In addition, although the slight change in body protein and lipid contents had a similar trend with the results observed in Liao et al.1, which found the significant effects on body protein and lipid contents in response to dietary Met level. The reason maybe partly attributed to the different culture environment. A similar comparison result was also observed in cobia fed dietary Met diets25. In other related studies, some studies revealed that optimal dietary Met levels markedly increased crude protein and decreased crude lipid content in whole body composition such as in Chinese sucker and Indian major carp 26. Whereas Yan et al.27 reported that whole body protein and lipid contents were significantly increased with increasing dietary Met up to 1.58% in juvenile rockfish (Sebastes schlegeli). These results suggested that the various change of whole body composition of fish species in response to dietary Met maybe species-specific, due to the different metabolic systems of fish species. However, the mechanism of the specific-metabolism response to dietary Met is unclear, and needs to be further investigated. In addition, 0.40% Met level significantly increased the lipid content in the liver compared with high Met diets. A Met-deficient diet was also found to increase the hepatic lipid content of broiler28 and P. fulvidraco8. In the present study, it was observed that the lipid content in the muscle was very low (< 1%), and 0.40% dietary Met level as well decreased lipid content in muscle. Therefore, the lack of dramatic difference in crude lipid content of body composition might be related to the differences in lipid accumulation in tissues, which also implied that the tissue-specific metabolism in blunt snout bream fed graded methionine diets.The optimal Met levels in diets could improve the growth performance of fish, which has been proven in many fish species, such as large yellow croaker, 29, in the 0.40% diet group. This result indicated that the liver of blunt snout bream is sensitive to Met via TOR pathway, and 0.84% Met diet could promote hepatic protein synthesis compared with the 0.40% diet. Before this study, Dai et al.30 reported that trout hepatocytes treated with four-fold amino acids (4 × AA) combined with insulin significantly activated the TOR pathway compared with the control. The present study was also consistent with the finding that TOR pathway key genes in porcine mammary epithelial cells were significantly increased by a mix of d- and l-Met compared with no Met31. However, TOR pathway response to dietary Met in blunt snout bream showed a tissue-specific and dose-dependent response in this study. Increased protein levels of S6k1, 4e-bp1 and p-4e-bp1 in the muscle of blunt snout bream were observed in the 0.40% Met diet but not in the 0.84% diet that is similar to the liver. Additionally, the trends in the mRNA expression levels of TOR pathway key genes were different from the trends at the protein level. Similar phenomena were also observed in the study by Zeitz et al.32, which may be due to the temporal and spatial differences between transcription and translation.The present study also investigated the response of TOR pathway related protein synthesis to dietary Met. 0.40% dietary Met level  decreased TOR signaling in the liver of blunt snout bream; this was evidenced by reduced protein levels of hepatic S6k1 and p-4e-bp1, the downstream of TOR that regulate protein synthesissrebp1, acc and fas mRNA expression levels were markedly induced by 0.40% dietary Met compared with 0.84% or 1.28% Met levels, which was consistent with the result in lipid content of liver. SREBP1 is an important nuclear transcription factor in lipid synthesis, that controls the synthesis of enzymes involved in ACC and FAS34. Met restriction enhanced whole lipogenic capacities of growing pigs36. The current results might indicate that low Met (0.40%) promoted liver lipid synthesis via increasing related genes in blunt snout bream. Similar results were also found in other fish species. In Atlantic salmon , Met deficiency contributed to high Fas activity and triglyceride accumulation in the liver37. Met deficiency also induced fas and srebp1 expression in rainbow trout38. Recent studies report that PI3K/Akt activates SREBPs, major transcriptional regulators of lipid metabolism40. Akt activation was reported to be the necessary and sufficient factor for the increase of SREBP1C and lipid accumulation in the liver42. Yecies et al.43 found that Akt could induce hepatic SREBP1C and lipogenesis via parallel mTORC1-dependent and mTORC1-independent pathways. In the current study, the protein levels of p-Pi3k and Akt in the liver were increased by 0.40% Met, consistent with srebp1 but not tor, which might imply that low dietary Met level (0.40%) potentially increased hepatic lipid accumulation in a Pi3k/Akt-srebp1 independent TOR manner.Hepatic srebp1, acc, and fas, as well as the lipid content in the muscle, were markedly induced by 0.84% and 1.28% dietary Met. The results were in line with turbot primary muscle cells treated with Met deprivation, which significantly reduced the relative mRNA expression of fas and srebp1 compared to those in the control group4. Latimer et al.13 demonstrated similar results: rainbow trout fed Met restricted diets for 8 weeks showed increased fat accumulation in the liver and decreased fat accumulation in the muscle. Meanwhile, compared with the elevated Pi3k/Akt in the liver induced by the 0.40% diet, the protein levels of p-Pi3k and Akt in the muscle were both very low compared with those in the liver in the 0.40% and 0.84% Met dets. The results indicated that Met regulated lipogenesis was species-dependent in fish.In contrast to the lipid synthesis promoted by 0.40% Met in the liver, high dietary Met levels (0.84% and 1.28%) tended to promote lipogenesis in the muscle in this study. The evidence was that the mRNA levels of muscular lipogenesis genes including Megalobrama amblycephala, which was demonstrated by the expression levels of pparα (except in muscle) and its downstream: cpt144, were significantly upregulated by 0.84% and 1.28% Met compared with the 0.40% diet. Induced muscular pparα mRNA levels were found in the fish fed the 1.28% Met diet, higher than that in fish fed the 0.40% diet. Rolland et al.7 reported similar results in rainbow trout that hepatic cpt1 expression levels in the low Met group were lower than those in the high Met group. In juvenile tiger puffer (Takifugu rubripes), lipolytic gene (acox1 and hsl) expression levels were significantly induced by high dietary Met9. In the present study, 0.84% dietary Met increased hepatic lp mRNA levels compared with the 1.28% diet, and could catalyze triglyceride45. High Met preferentially improved muscular lipolysis, as evidenced by the muscular lpl mRNA level being induced by 1.28% Met in this study. The results of the present study implied that high dietary Met levels (0.84% or 1.28%) were more conducive to promoting lipolysis in the liver and muscle than the 0.40% dietary Met. These results also revealed the different lipolysis responses to dietary Met in the liver and muscle of juvenile blunt snout bream. The induced lipolysis and β-oxidation not only provide energy for the growth of juvenile blunt snout bream but also may partly contribute to the plasma TG and TC contents that did not show significant differences among the experimental groups. Similar results were also reported in juvenile silver pompano, Trachinotus blochii 46.Unlike lipogenesis, β-oxidation is a process of fatty acid degradation, which supplies energy for the body. In the present study, higher dietary Met levels (0.84% and 1.28%) induced fatty acid β-oxidation in both the liver and muscle of 48. In the present study, the highest mRNA levels of glut2 were found in the 1.28% Met diet, which promoted glucose transfer between blood and liver and glucose metabolism, which might be helpful for stable plasma glucose content49. Hepatic gk, pfk and pk relative mRNA expression levels were significantly induced by dietary 0.40% and/or 0.84% Met levels, suppressed by 1.28% dietary Met; while pfk and pk mRNA levels in the muscle were increased by the 1.28% diet compared with the control diet (0.84%). The present data about glycolysis revealed that lower dietary Met (0.40–0.84%) potentially promoted hepatic glucose utilization while muscular glucose utilization was enhanced by 1.28% dietary Met. Similar results were observed in cobia, in which 1.24% dietary Met enhanced hepatic glycolysis by increasing pk mRNA levels compared with an 0.70% diet5. Primary muscle cells of turbot treated with Met deprivation exhibited decreased gk and pk expression levels compared with the control4. The energy released by enhanced glycolysis in both the liver and muscle may contribute to the growth of blunt snout bream. In addition, the increased muscular glycolysis in the 1.28% diet may provide a substrate for lipid synthesis as shown in this study50. Additionally, in the current study, 0.40% dietary Met significantly induced hepatic gk and pfk expression levels compared with 1.28% Met level, while pk was not impacted. This result indicated that 0.40% Met potentially promoted the preparation stage of glycolysis but did not promote entry into the energy release stage50, which may be part of the reason that low dietary Met led to poor growth.The liver, as the main tissue responsible for glucose homeostasis and plays a key role in regulating intermediary metabolism in response to nutritional statuspepck and g6pase in the liver. Also, the study was in line with the findings of Skiba-Cassy et al.51, who equally found that feeding rainbow trout with a high Met diet significantly enhanced the expression of hepatic g6pase2 and pepck 2 h after a meal. And the results were also in agreement with Dai et al.30 and Lansard et al.52, also reported that high levels of amino acid could markedly up-regulate hepatic gluconeogenic gene mRNA levels in trout compared with those in fish treated with one-fold amino acid. Interestingly, combined with the hypothesis about glycolysis in the muscle described above, Megalobrama amblycephala fed 1.28% diet may activate the Cori cycle, that increased gluconeogenesis in the liver and resulting glucose is transported through the blood to the muscle where it is either utilized through glycolysis to supply energy demands of muscle contraction or build up muscle glycogen stores through glycogenesis54. The muscular glycogen synthesis was promoted by dietary Met supplementation (0.84% and 1.28%) that significantly increased muscular gs expression and glycogen contents in the present study. Higher dietary Met tended to enhance glucose and glycogen synthesis, which might be partly due to Met being a glucogenic amino acid7. In the muscle, 1.28% dietary Met markedly increased pepck mRNA relative expression levels in the current study to promote the production of phosphoenolpyruvate, which might help to activate PK and potentially link with lipid metabolism55.Regarding gluconeogenesis, another way of glucose metabolism, juvenile blunt snout bream fed 1.28% Met diet showed marked mRNA levels of the rate-limiting enzymes: srebp1 independent TOR manner. 0.84–1.28% Met markedly increased the contents of lipid and glycogen in muscle by increasing related genes’ expression levels. The 0.40% dietary Met downregulated hepatic key TOR signaling genes, while improved muscular TOR signaling. The influence of nutrient metabolism in blunt snout bream in response to dietary Met levels in a tissue-specific and dose-specific manner  2011–0036]. All experiments on animals were performed following the Standardization Administration of China protocols and guidelines (GB/T 35892-2018). And the researchers declared that complied with the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines.1, three isonitrogenous (35% protein) and isoenergetic (18 kJ/g) feeds with the followed graded dietary Met levels were formulated: 0.40% (deficient), 0.84%  and 1.28% (excess). The composition of the basal feed was shown in Table 3. It is worth noting that blunt snout bream, as an herbivorous fish, can digest plant protein well as fish meal57. Therefore, we used rapeseed meal and soybean meal as the main protein source in this study, which was to obtain more knowledge in practical situation, and to provide data support for practical production. As described in our previous study1, the pellet diets were processed by F-26 (II) , air-dried, and finally stored in a refrigerator at − 20 °C until feeding.Given the dietary Met requirement of juvenile blunt snout bream was determined by Liao et al.3, the experimental fish were obtained from the breeding farm of Freshwater Fisheries Research Center (FFRC) of Chinese Academy of Fishery Sciences . After a 15-day acclimation period, the juvenile fish consistent with health and specification  were randomly distributed into nine nylon cages in the pond, and every cage (1 m × 1 m × 1 m) with 20 fish. Each diet was randomly assigned to triplicate cages. Fish were hand-fed three times daily at 7:30, 12:00 and 16:30 for 75 days, until apparent satiation based on visual observation of fish feeding behavior. The water quality was tested weekly , the water temperature was maintained at 28 to 31 °C, pH was maintained from 7.0 to 7.8, ammonia nitrogen was not higher than 0.05 mg/L and dissolved oxygen was higher than 6.0 mg/L. And the photoperiod was the same as natural light (12 h:12 h).As mentioned in our previous study24 h after the fish were fasted, the total weight and number of fish in every cage were counted to calculate the relative growth indices at the end of the experiment. Five fish from every cage were anesthetized by using MS-222 (100 mg/L), and then to collect blood from the caudal vein with disposable medical syringes. After drawing blood, the abdominal cavity of the fish was cut from the cloaca along the lateral line, and then the liver was sampled. And muscle was taken from the dorsal white muscle. Plasma was obtained by centrifugation of blood samples . The other two fish from each cage were collected to test whole body composition. The samples were stored at -80 °C until analyzed.58. The lipid contents in the liver and muscle were extracted by using chloroform: methanol (C–M)  according to the methods described in Peng et al.59. The concentrations of amino acid in feeds and ingredients were analyzed by using an amino acid analyzer .The content of moisture, crude protein and lipid, and ash of feeds, whole body and ingredients were analyzed according to the methods described in AOACPlasma GLU, TC, and TG were tested by using Mindray BS-400 automatic biochemical analyzer , and the assay kits  purchased from Shanghai Zhicheng Biological Technology Co. Ltd . Glycogen contents in the liver and muscle were tested by kits (A043-1-1) purchased from Nanjing Jiancheng Bioengineering Institute .60. The assay used β-actin as the reference gene, and the target gene expression levels were analyzed using the 2−∆∆ct model.Total RNA from the liver and muscle from three fish in each cage was extracted by RNAiso Plus  Co., Ltd, Dalian, China). The quality and quantity of RNA were tested by a spectrophotometer . Finally, qRT-PCR was performed according to the instructions of One Step TB Green PrimeScript Plus RT-PCR Kit  Co., Ltd, Dalian, China) on a CFX96 Touch Real-Time PCR Detection System . Specific primers of target genes Table  were des4P2O7, 2 mM β-glycerophosphate, 1 mM Na3VO4, 0.1 mmol/L PMSF, and protease and phosphatase inhibitor cocktail . The supernatant was collected after centrifugation at 12,000 × g for 10 min at 4 °C. The protein contents were tested by the BCA method . Quantified samples were added to prefabricated SDS-PAGE gels for electrophoresis and then transferred to NC membrane . The blot was blocked with 5% nonfat dry milk in TBST for 2 h at room temperature. After overnight incubation of the membrane and primary antibodies, the membrane was incubated for 1 h with appropriate secondary antibodies. A Beyo ECL Star kit (Beyotime Biotechnology) was used to develop the signal. The bends were scanned and quantified using a chemiluminescence imaging system . Antibodies against the following proteins were used: phospho-phosphatidylinositol 3-kinase  (Cat# 4228), phospho-eukaryotic initiation factor 4E binding protein-1  (Cat# 9459), and 4e-bp1 (Cat# 9452) were purchased from Cell Signaling Technology Inc. Pi3k , ribosomal protein S6 kinase 1  and protein kinase B  were purchased from Proteintech Group, Inc. And β-actin (Cat# AY0573) was purchased from Abways Technology. Among them, antibodies Pi3k, S6k1 and Akt were successfully used in our previous study16. The densities of the protein bands were normalized to that of β-actin, which served as an internal control. In addition, the need is, the blots were cut prior to hybridization with antibodies, therefore, original images of full-length blots cannot be provided.50 mg liver and muscle samples from one fish in each cage were rinsed twice with ice-cold PBS, the PBS was removed by centrifugation, and then the tissues were put into ice-cold RIPA buffer  with 5 mM NaF, 2 mM NaParameters were calculated as followed:P < 0.05 indicates a statistical significance.Data were analyzed by one-way analysis of variance (ANOVA) and Tukey's multiple comparisons with SPSS 16.0 software. The results are presented as the means with SEM and Figures Supplementary Information.


Over the years, prestressing concrete has become a well-known technique to improve the ultimate and serviceability state of RC members. Besides steel reinforcement, relatively new materials such as carbon fiber reinforced polymers (CFRP) or especially shape memory alloys (SMA) can be used to active strengthening. The main scope of this paper is to compare various prestressing methods using carbon composites and memory steel alloys. A description of SMA, shape memory effect, its utilization for prestressing, and CFRP materials are presented in the paper. Moreover, current state-of-the-art developments in the field of both materials, considering prestressing systems and available anchorage, material behavior, creep and stress relaxation, durability issues, thermal compatibility with concrete, and fire behavior, are described. A general revision of previous studies based on flexural strengthening using both materials is conducted and the selected results of these studies are briefly presented. The behavior of RC beams after strengthening with mentioned techniques is compared and discussed. Selected on-site applications are described to confirm the feasibility and practicality of the strengthening systems. Finally, the main advantages and disadvantages of CFRP and SMA materials for prestressing concrete structures are summarized and further recommendations for the future research are listed. Plenty of existing structures require retrofitting and strengthening. This is most often important due to the deterioration of structures, changes in using their functionality, or increasing design requirements. In the case of concrete structures in Poland, traditional methods of strengthening are still the most popular. These methods of retrofitting  are well known and described by Al-Mahaidi et al. . HoweverStrengthening with prestressed CFRP materials requires a mechanical anchorage that properly transfers prestressing force to the strengthened member to avoid debonding of composite material from the concrete surface. The anchorage systems are highly complex due to additional devices based on the hydraulic jacks, which are used for prestressing the CFRP laminates ,9,10,11.A promising alternative for the prestressing methods of existing concrete members, which substantially reduces these expenses, is prestressing using shape memory alloys (SMA). Several research studies about the most popular nickel-titanium based alloys (NiTiSMA), have been tested for decades and confirmed their capabilities for retrofitting concrete members ,13. HoweThis paper aims to present the current state-of-the-art developments in the topic of flexural strengthening of RC structures with prestressed SMA materials in comparison to that with CFRP. This comparison contains an analysis of materials behavior, available prestressing systems, and previous studies with applications of both memory steel and carbon composite materials. The paper provides a background for further research in this field which can be of significant interest. Shape memory alloys are metallic alloys  that have a unique property which allows them to return to their initial shape after having been permanently deformed. Examples of FeSMA materials are presented in s, (martensite start) and the process finishes at the temperature, Mf, (martensite finish). The reverse transformation (RT) is induced by heating the material (in absence of stresses), begins at temperature known as, As, (austenite start) and has the end at the temperature, Af, (austenite finish) [Change of deformability is called the shape memory effect (SME) and has to be activated by heating . If the  finish) . These p finish) .Depending on the ambient and transformation temperatures profile of the alloy material, different phenomena occur in the material ,20. It cs, the reverse transformation begins. As strain-stress curves for martensite and austenite are different, a change of stiffness takes place. An increase in the stiffness of the alloy causes the strain decreases against a constant force . The reverse transformation occurs automatically after unloading. This phenomenon is called superelasticity or pseudoelasticity and it exhibits some stress-strain hysteresis , as showf. This phenomenon is called the one-way shape memory effect or pseudoplasticity [max, tensile stress develops in the material. The stress obtained by cooling the specimen down is referred to as “recovery stress”  are composite materials composed of at least two components, namely fibers and a polymer matrix. The matrix performs the role of binder, distributes the uniform load, and protects the fibers against environmental effects . The fibUnidirectional pultruded laminates (strips)—Sheet (with fibers in one direction) or fabrics (fibers are arranged in at least two directions) that are usually impregnated in-situ;Rods of bars that are made by pultrusion;Profiles —The properties of CFRPs depend on the volume of each component and the orientation of fibers. CFRPs are available for strengthening of civil engineering structures in the form of ,35:UnidiThe first application of CFRP materials was in the United States at the California Department of Transportation, Caltrans . ApplicaMost research and field applications on the flexural strengthening of RC members were carried out on simply supported beams and slabs strengthened on the bottom surface of the RC members without additional anchorage in the support region.The existing research on reinforced concrete members flexurally strengthened with FRP materials can fail in several different ways, which are completely different in comparison with original RC members. There is a wide literature referring to classification of the failure modes published for the last two decades. The most common classification based on test results of the existing research was presented in . Eight cThe most common failure mode is debonding of the FRP laminate from the concrete surface which may proceed as intermediate crack induced interfacial debonding (ICD) initiates at the flexural/flexural-shear cracks in the highest bending moment region f and proCritical diagonal crack (CDC) debonding occurs after the formation of a major shear crack intersecting the plate near its end and develops along with the laminate-concrete interface to the plate end b;Concrete cover separation (CCS) c;Plate end interfacial debonding (PEI) d.When debonding occurs at or near the end of a laminate it may proceed in three different ways:Two additional failure modes refer to the FRP rupture and concrete crushing. However, the second one is possible only for the RC members of low concrete strength and high reinforcement ratio.The effectiveness of the flexural strengthening depends on several factors including FRP type; axial stiffness and the number of CFRP layers; a distance of the CFRP end from the support; the existing longitudinal and shear steel reinforcement ratio; and bending moment distribution. Although EBR CFRPs increase the load-bearing capacity of an RC member, they do not significantly change the cracking load and deflections under the service loads. To gain the greatest advantage of the EBR technique, CFRP prestressing has been proposed to improve the serviceability of strengthened structures in order to reduce crack widths effectively, to relieve stress in the internal reinforcement, to enable control the crack distribution, limit deflection, and to increase the stiffness and the load capacity of RC members.This section is focused on a comparison of CFRP and SMA behavior and techniques of their applications to the strengthening of RC structures. The important parameters considered in this analysis contain tensile strength, Young’s modulus, creep and relaxation, thermal compatibility, durability, behavior at elevated temperatures, prestressing procedure, prestressing force, and anchorage systems.Memory steel based on iron has reasonable production cost, higher elastic modulus, and lower activation temperature in comparison with other types of SMA materials . FeSMA mExternally applied reinforcement (EAR) which include both externally bonded reinforcement (EBR) and unbonded reinforcement (without adhesive between composite and concrete); the unbonded reinforcement system is much less popular, but the applications can be found in ,54;Near-surface mounted reinforcement (NSMR) ,59,60,61Externally post-tensioned (EPT).The state-of-the-art strengthening with prestressed FRP materials was published in ,51,52,53In the EAR technique, CFRP reinforcement is in most cases prestressed to reduce existing deflections and to extend the flexural capacity of the existing concrete structures (direct prestressing method ). CFRP pIn most cases, the MA systems are based on anchor plates. A direct prestressing system consists of the passive anchorage (dead end), while the second end is the active one ,72 whichReinforced concrete beams strengthened with prestressed CFRP laminates show three groups of failure modes: under-reinforced RC members failed due to FRP rupture (R); over-reinforced RC members with composite reinforcement applied excessively, resulting in concrete crushing (CC). However, this failure mode is possible only for the RC members characterized by low concrete strength and high reinforcement ratio; intermediate crack induced by interfacial debonding (ICD), which initiates at the flexural/flexural-shear cracks in the highest bending moment region and propagates by gradual debonding of the laminate from the flexural crack to the FRP end and the group of RC members with the reinforcement not anchored sufficiently, in which leads debonding of FRP ends (plate end debonding (PE), concrete cover separation (CCS), anchorage failure (AF)) published in ,76,77,78The parameters affecting strengthening efficiency with externally bonded FRP prestressed materials contain type of FRP material ; FRP stiffness; existing flexural tensile reinforcement ratio; existing shear reinforcement ratio; stiffness of the strengthened RC member ; the size of the strengthened RC member; type of strengthening system  or partially efficient (FRP sliding from the anchored system) and preloading level.The flexural strengthening of RC members strengthened with pretensioned NSM FRP stirps or bars confirms the much higher efficiency of this technique compared to the passive strengthening. The main effect of pretensioning is based on the higher utilization of the tensile strength of the FRP materials, which contributes to the higher load-bearing capacity under service and ultimate load ,56,57. TFor externally applied strips, the direct fastening system is used . This meThe NSM strips or bars can be inserted into the concrete grooves which are filled with cement-based grout ,24,81. TThe NSM bars can be also embedded in the shotcrete layer ,24.The prestressing procedure for all types of SMA reinforcement is quite similar and it does not require using the hydraulic jacks. In the beginning, the SMA materials are initially prestrained at room temperature, and then the reinforcement (with permanent deformation) is applied and fixed to the concrete surface and the activation of the alloy is conducted by heating to the required temperature. The heat supply can be provided by infrared heating, electrical resistive heating  or usingFeSMA materials exhibit a similar stress-strain response as steel. The memory steel properties are affected by the alloy composite and the thermomechanical treatment during the production process . In geneact, than for the material in elastic state, Einit, see The initial elastic modulus of FeSMA is similar to low modulus CFRP and is lower than steel and the high modulus CFRP strips. It should be mentioned that Young’s modulus of the alloy depends on its actual state, which is about two times lower for the material after activation, EThe creep behavior of FRP materials was investigated by Goertzen et al.  in the tA mount of tests referring to FeSMA relaxation has been carried out over the last years published in ,94,95,96The prestressing force in the SMA technique depends on the recovery stress of the alloy which is obtained after activation. It highly depends on the alloy composition, thermo-mechanical training, level of prestraining, and activation temperature. Based on data from research conducted by Cladera et al. , it has The prestressing level in CFRPs should be at least 25% and does not exceed 65% of the ultimate strength  see Sec. PrestreDue to the non-metallic nature of CFRPs, these materials are fully corrosion-resistant. This is why environment exposure does not affect the decrease in the tensile CFRP strength ,101.corr), the higher the corrosion resistance of the material in the tested solution. Lee et al. [3 + 5 mM Na2CO3) and with chloride (15 mM NaHCO3 + 5 mM Na2CO3 + 2.8 M NaCl) was conducted by Lee et al. [The corrosion resistance of memory steel has been investigated for various iron-based SMAs in ,109,110.e et al.  and Joo e et al. . Dias ete et al. . As it ce et al. ,108, seee et al.  and Lante et al.  or a smae et al. . Neverthe et al. .−6 K−1 [−6 K−1. The current study has demonstrated that the CTE of FeSMA is in the range of 14–16 × 10−6 K−1 that is closed to other austenitic steel materials [In the case of strengthening applications, proper thermal compatibility between the reinforced material and concrete is of great importance. A significant difference in the thermal expansion coefficients (CTE) imposes the additional stresses in the strengthened element that causes a decrease in the strengthening efficiency . CTE of −6 K−1  and the aterials ,95. The aterials  confirmeaterials  as a resaterials ,115,116.aterials , the lonThe complex study on the structural fire behavior of the prestressed FeSMA was carried out by Ghafoori et al. . The serThe fire behavior of CFRP materials applied for strengthening concrete structures was investigated by Bisby et al.  and FirmA limited number of research studies containing a comparison of flexural strengthening using CFRP and FeSMA materials have been conducted so far. The experiments and computational analysis based on literature ,130,131 Analysis of previous studies (mentioned in the above tables) revealed that different failure modes are exhibited for RC beams strengthened with FeSMA and CFRP materials. The majority of FeSMA beams failed due to concrete crushing after yielding steel (as unstrengthened reference beams) which is connected with their low longitudinal steel reinforcement ratio. In two prestressed beams , one of Selected results from the previous studies are presented in To highlight the better ductility of the FeSMA strengthened beams compared to that strengthened with the CFRP reinforcement, the ductility index was introduced in Michels et al.  comparedFive RC beams strengthened with NSM reinforcements and one reference beam without strengthening were analyzed by Shahverdi et al. in . The beaA study by Raad and Parvin  presentsA numerical comparison of RC beams strengthened with the NSM techniques was conducted in . One refThe first flexural strengthening strips of real structure with prestressed FeSMA happened in 2017 in Villigen, Switzerland ,79. The Another possibility of activation FeSMA strips is infrared heating, which was used during strengthening a slab in Arrau, Switzerland . A new cModernization of reinforced concrete bridge in Komańcza, Poland was required due to its deterioration and narrow roadway ,44. The The NSM technique was used to strengthen a four-span bridge in Gyeonggi-do, South Korea . The briThe strengthening of concrete structures with prestressed CFRP and SMA materials is significantly efficient in serviceability states, including higher cracking load and reduced deflections. The effectiveness of flexural strengthening was confirmed both in laboratory tests and practical implementations.Prestressing using SMAs can be an interesting alternative to prestressing with CFRP materials, especially due to the future price reduction of SMAs.SMA materials can be used as prestressed near surface mounted or externally applied reinforcement. In both cases, they are much easier to apply anchors and activate SMA compared to CFRP materials, which usually require specialized equipment. The FeSMAs are activated by heating to the temperature, which is usually in the range of 130–200 °C.The activation process can be performed using different methods: resistive heating, infrared heating or heating using a gas burner. The prestressing level may be affected by the activation method, however further research on this topic is recommended.The prestressing level of SMAs depends on the type of the alloy, activation temperature and the initial prestraining level. In the presented state of the art, the shape recovery stress was in the range of 130–450 MPa, which resulted in 2–4 times lower prestressing forces than by using CFRP reinforcement. Hence, the flexural capacity of the beams strengthened with CFRP bars and strips is higher than SMAs.The most common failure mode for beams strengthened with CFRP reinforcement was CFRP rupture or CFRP delamination, while the beams strengthened with FeSMAs exhibited usually a failure due to concrete crushing after the steel yielding. A proper design of strengthening using CFRP reinforcement is needed to utilize their high tensile strength and to prevent the brittle failure mode.The behavior of SMA is very ductile that allows the RC members to obtain much higher deflections. The ductility index for all beams strengthened with SMA was much higher than for CFRP strengthened beams.Two important factors should be considered during the design of strengthening using prestressed memory steel. In first the elasticity modulus depends on the actual state of the alloy since the initial value is twice higher than the value after activation. The latter is appropriate for design purposes. Secondly, the compressive strains in concrete should be limited to 2–2.5‰ as the SMA reinforcement behaves similarly as the external prestressed unbonded tendon.The thermal compatibility with concrete is much better in the case of SMAs, since they have a slightly higher coefficient of thermal expansion than concrete. As the coefficient of thermal expansion of CFRP is close to 0 or even negative the stress changes occur along with the bonded CFRP reinforcements due to the temperature changes.The memory steel exhibits much better performance compared to CFRP when is subjected to elevated temperatures. Additionally, heating and toxic gases are released due to thermal decompositions of the FRP matrix when exposed to a temperature of 300–400 °C. Hence, it is necessary to provide proper fire protection not only due to the strength degradation but also due to the smoke toxicity.The prestress losses in the RC members strengthened with prestressed CFRP materials occurs in the first 100 h and a further decrease in prestressing is negligible, while the memory steel is affected by long-term creep and stress relaxation. The current studies estimate that the prestress losses due to relaxation are about 15%. However, they might be retrieved by second or multiple activations.The CFRPs are fully corrosion resistant due to their non-metallic structure, while SMAs are susceptible to corrosion and that should be taken into account in long-term durability. Memory steel is especially sensitive to chloride ions, which intensifies the pitting corrosion. Hence, additional corrosion protection should be applied for structures in aggressive environments.On-site tests confirmed the practicality of flexural strengthening using prestressed CFRPs for RC bridge structures under dynamic load conditions.Strengthening with FeSMA materials can be combined with other strengthening techniques  to ensure maximum gains in serviceability and ultimate limit states.In this paper, current state-of-the-art developments in terms of prestressed concrete structures using SMA or CFRP reinforcement is presented. Both materials are compared in terms of the material level considering tensile behavior, durability aspects and effects of elevated temperature. Moreover, the prestressing methods and anchorage systems are briefly described. Additional item concerns previous studies considering both experiments and numerical analysis and summary of CFRP and SMA strengthened RC members. The following conclusion can be drawn:The prestress losses and long-term behavior of SMAs used for prestressing of RC structures.The prestressing losses due to the slippage at anchorages should be analyzed.Developing more precise methods of determining prestressing level in memory steel after its application to RC structure.Effects of different heating methods on the prestressing level in SMA materials.The possibility of multiple activations should be developed.The behavior of SMA in chemical environments considering effects on recovery stress or bonding behavior should be investigated in more detail.Feasibility of SMA materials for flexural strengthening of RC structures under dynamic load conditions.Effectiveness of corrosion protection applied to SMA materials.Design guidelines for prestressing with SMA should be organized.Comparison of prestressing techniques using SMA and unbonded CFRP reinforcement with end-anchorages.Future research is necessary to develop the current knowledge of strengthening RC structures with prestressed SMA materials. The following recommendations should be taken into future research:


IgG4-Related Disease (IgG4-RD) is a fibroinflammatory condition characterized by a typical histopathological pattern , which may involve the kidney both directly  or indirectly, as a consequence of post-renal ureteral obstruction due to retroperitoneal fibrosis (IgG4-RD RF). The most frequent presentation of IgG4-RKD is IgG4-related tubulointerstitial nephritis (TIN), but a glomerular disease can be present, in most of the cases a membranous nephropathy. Albeit steroid-responsive, in some cases renal manifestations may lead to progressive and permanent organ damage. In this review we describe four clinical cases representative of typical and less typical renal manifestations of IgG4-RD, emphasizing a potential, subclinical, early involvement of the kidney in the disease. IgG4-RD is a rare fibroinflammatory disorder that can affect almost any organ, characterized by lymphoplasmocytoid infiltrate, obliterative phlebitis, and storiform fibrosis often associated with eosinophilia and increased levels of IgG4 . RigorouThe pathogenesis of IgG4-RD is not clear: according to a generally accepted view, a persistent antigenic stimulus, perhaps from chronic infection, induces an increased polyclonal expansion of B cells under the influence of M2 macrophages, CD4+ (mainly cytotoxic) T cells and Tfh, in a milieu of IL-4, IL-10, IL-1beta, and TGF-beta cytokines. These signals promote IgG4 class switching, somatic mutation, and plasma cells expansion, as well as a local fibrotic response .Clinical manifestations are various and can affect almost any organ, with pancreas, retroperitoneum, lymph nodes, and salivary glands as the most frequently involved ones. Disease presentation is usually chronic, sometimes paucisymptomatic and insidious, without high inflammatory manifestations, and characterized mainly by the development of mass lesions that exhibit the same histological pattern in all the organs affected. The rich infiltrate of IgG4+ plasma cells and CD4+ T cells is embedded in extensive fibrosis that assume the typical, distinctive whirled arrangement called “storiform.” Obliterative phlebitis is another feature of the disease. Eosinophils are frequently detected, while necrosis is rare; in fact, the presence of necrosis or granuloma or giant cells should rather suggest a different diagnosis , by whicRecently, ACR/EULAR classification criteria were proposed . DevelopAs soon as the multisystem involvement of IgG4-RD became clear, it was appreciated that kidney was a prominent target organ. Reported frequency of renal involvement is in fact comprised between 10 and 27% of the cases , 9.We report 4 cases of IgG4-RD with renal involvement that exemplify the different pattern of renal disease that can be observed in this disorder, outlining the clinical course and therapeutic approach.Informed consent was obtained from each patient, for every procedure performed.bright cells) were highly increased . An abdominal echography showed a hypoechogenic aspect of renal cortex. Urinary Retinal Binding Protein (RBP) and beta2microglobulin were increased , urinary light chain were present and urinary electrophoresis showed a mixed proteinuria (glomerular and tubular). Daily proteinuria was above 700 mg/24 h. Urinary sodium excretion, as well as potassium, calcium, and phosporous, were slightly reduced.A 39 years old clergyman with a history of asthma, arterial hypertension and gastroesophageal reflux came to our attention for exophthalmos, previously treated with steroid boluses, and submandibular tumefactive lesions. His right parotid had echographic signs of parenchymal subversion and a Positron emission tomography/computed tomography (PET/CT), performed 3 years before admission, showed enlargement and high uptake of multiple lymph nodes in neck, mediastinus, tracheal, periaortic, and interaortocaval regions (SUVmax 7.3). To exclude hematologic malignancy, a lymph node needle biopsy was performed and showed hyperplasia with reactive plasmocytosis (IgG4 staining not performed). Blood tests showed hypergammaglobulinemia (19.6%), rheumatoid factor positivity (72.7 <30) and hypocomplementemia . Creatinine levels progressively increased from 1.19 to 1.92 mg/dL. At hospital admission the patient presented left eye exophthalmos and swelling of neck lymph nodes in the right side. Serum IgG4 were 1,300 mg/dL (49-66), IgG4/IgG ratio was 44.45% and circulating plasmablasts . Immunohistochemistry for IgG4 demonstrated 22 IgG4 ± plasmacells/HPF. Only 2 out of 9 glomeruli were sclerotic, while tubuli were diffusely reduced and atrophic. Small and medium vessels showed mild thickening. No complement deposits were detected by immunofluorescence .Histopathology of a neck lymph node had similar histological characteristics, with fibrotic areas enriched in plasmocytes (IgG4+/IgG+ ratio > 40%). The diagnosis of IgG4-Related Disease was made and treatment with monoclonal anti CD20 was started, with a progressive reduction of lymph node swelling and exophthalmos and a mild creatinine reduction, up to 1.4 mg/dL in 3 months.A 47 years old woman was evaluated in our outpatient clinics for AIP diagnosed 3 years before in another hospital . She had been treated with budesonide 9 mg/die and was under treatment with anti-IL-5 (Mepolizumab) for severe asthma. Blood tests showed increased ESR , fibrinogen  and pancreatic amylase 150 U/L (n.v. 15–53); urinalysis showed microalbuminuria and increased number of white and red cells in the sediment. Urinary electrophoresis showed mixed proteinuria, mainly tubular. A PET/CT scan detected only low uptake on aortic arc, while abdominal RM did not show parenchymal involvement. Anti IL-5 therapy was stopped. Slowly, within 4 months, she developed lower limbs edema, and a rapid decay of her health status. At hospital admission she had proteinuria in the nephrotic range (6 g/L), increased ESR and fibrinogen, hyperamylasemia, ANA 1:160 speckled, normal creatinine level, normal C3 and C4, total IgG 301 with IgG4 81 mg/dL. Anti PLA2R and ANCA were negative and urinary electrophoresis showed mixed proteinuria. An echography showed globular aspect of pancreas, hyperechogenicity of renal cortical and medullary columns, linear hyperechogenic bands in salivary glands. A renal biopsy was performed, showing mild thickening of glomerular basal membrane and focal mesangial expansion; minimal interstitial fibrosis and IgG4-negative lymphomonocytic infiltrate; minimal tubular atrophy (5% of tubuli) in the absence of vascular abnormalities. IgG4 staining showed focal IgG4 on glomerular basal membrane, while by immunofluorescence deposits of IgG and C3 were detected on basal membrane , with veA 74 year-old man was admitted to our hospital because of chronic cough, dysphonia, dysphagia, hypoacusia, fever, and weight loss. He presented chronic arterial hypertension, atrial fibrillation, and no history of allergy. At admission ESR and CRP were elevated ; mild anemia, neutrophilic leucocytosis, and hypergammaglobulinemia were also present. Initially, a diagnosis of cryptogenetic bronchiolitis was made on the basis of CT scan findings  and the patient was treated with broad-spectrum antibiotics and low dose steroids. For the recurrence of fever with an increase of acute phase reactants and a progressive weakness, further examinations were performed. Autoantibody evaluation demonstrated ANA 1:80 (speckled pattern) and ANCA-MPO highly positive . The rapid decline of renal function with an increase of creatinine levels from 0.81 to 2.69 mg/dL, albuminuria (100 mg/dL), micropyuria, and microhematuria strongly suggested the diagnosis of ANCA-associated vasculitis . The patient was referred to our Unit in order to complete diagnostic workout and start adequate therapy.Urinary RBP and beta2microglobulin were increased  and urinary electrophoresis showed a mixed proteinuria (glomerular and tubular) with epithelial, granular, and erythrocytic cylinders. A PET/CT scan showed a moderate 18F-fluorodeoxyglucose (18F-FDG) uptake of mediastinic, parathracheal, ilar, and axillary lymph nodes. Electroneurography and electromyography showed neurogenic damage with signs of denervation. Gadolinium-enhanced magnetic resonance imaging (MRI) of the brain disclosed a mastoiditis without other significant lesions.bright cells) were slightly increased . We then revised the histology of a “benign lesion” of the gallbladder removed 2 years before, that was 9 cm long and induced a duodenal stenosis and a cystocolic fistula. Histologically, lymphoplasmacytic infiltrate rich of eosinophils with areas of fibrosis was detected. Immunohistochemistry for IgG4 showed abundant IgG4-positive plasma cells , consistent with IgG4-RD.Interestingly, serum IgG4 level was 529 mg/dL  with an IgG4/IgG ratio of 27% and circulating plasmablasts  and a previous pulmonary lobectomy with lymphadenectomy for a giant cell carcinoma, performed a total body CT scan during his oncologic follow-up. A nodular lesion (19 mm) was detected between pancreas and duodenum with contrast enhancement, and a focal pyeloureteral hypercaptation compatible with urothelial carcinoma. An abdominal MRI demonstrated 2 pancreatic lesions of the pancreas head, suspicious for malignancy. Due to the oncologic history, the patient underwent a Whipple's pancreaticoduodenectomy and left nephroureterectomy. Surgical resection was complicated by sepsis with pneumonia and a pancreatic fistula with ascites, positive for Pseudomonas Aeruginosa, that subsequently underwent surgical treatment. He then developed portal thrombosis, heparine-induced thrombocytopenia and, after 2 months, chilotorax, intraepathic aerobily, and abdominal abscess.The histologic analysis of surgical specimens demonstrated a low-grade urothelial carcinoma, while pancreatic parenchyma showed fibrosis areas with lymphoplasmocytic infiltrates, periduttal infiltration, follicular-like aggregates, venulitis, acinar atrophy. Immunohistochemistry for IgG4 demonstrated >10 IgG4+ plasmacells/HPF and IgG4/IgG ratio >40%.Given the aforementioned histological findings, the patient was admitted to our inpatient clinic with the suspect of IgG4-RD. Clinical and laboratory signs of sepsis were present and broad-spectrum antibiotic treatment was started, with slow improvement. During the recovery, serum IgG4 were increased . Interestingly, daily proteinuria was low (<100 mg/24 h) but urinary electrophoresis showed a tubular proteinuria with a small increase in urinary RBP . Histological re-examination of resected kidney revealed thyroidisation of tubules, sclerotic glomeruli, severe, fibrosis of arterial walls, and interstitial lymphocytic infiltrate. An immunostaining for IgG4 showed >10 plasma cells IgG4+/HPF and a IgG4/IgG ratio >40%. Due to the frailty of the patient, a steroid therapy regimen was started in association with antibiotics. After surgical drainage of abdominal abscess, the patient's conditions improved and no relapse of IgG4-RD in any localization was observed in follow up.TIN is the most frequent renal manifestation of IgG4-RD and is diagnosed according to the criteria developed by the Mayo Clinic group and the Japanese Society of Nephrology , 11. At Histologically, the hallmark is a diffuse or multifocal lymphocytic infiltrate with a predominance of IgG4+ plasma cells, an IgG4/IgG-positive plasma cell ratio >40% and >10 IgG4-positive plasma cell per high-power field . HoweverBy immunofluorescence, granular deposits of IgG and C3 can be detected on tubular basal membrane; C1q can occasionally be present and electron microscopy shows electron dense deposits in the membrane.Serologically, patients affected by TIN have no distinguishing feature except for hypocomplementemia, present in 60% of the patients, with decreased levels of C3 and/or C4, and higher serum levels of IgG and IgG4. CRP is rarely elevated, at variance with other forms of TIN . Acute oRadiographic lesions of IgG4-RD TIN are best visualized by contrast-enhanced computer tomography scan. Multiple low-density lesions with mild enhancement in delayed phase on enhanced CT are the most common radiological findings , 16. By PET/CT, useful to evaluate retroperitoneal involvement, is not advised to study renal disease, because of the interference due to kidney excretion of radio-labeled drug.Multiple and bilateral lesions are usually detected, predominantly involving the renal cortex. Four patterns of parenchymal lesions are described: small, sub-centimetrical peripheral cortical nodules, round, or wedge- shaped lesions, diffuse patchy involvement, or (more rarely) a solitary mass . NephromDifferent types of glomerular involvement are described in IgG4-RD, but membranous glomerulonephritis, occurring in roughly 7% of the patients, is the most frequent. In fact, only anecdotical reports of IgA nephropathy, endocapillary proliferative glomerulonephritis and membranoproliferative glomerulonephritis have been published –22.In most cases, glomerular involvement coexists with TIN but occasionally it occurs in the absence of tubular involvement. Proteinuria in the nephrotic range is the usual manifestation of the disease. IgG and C3 deposits are detected in glomeruli by immunofluorescence and abundant electron dense deposits are shown in subepithelial space by electron microscopy . In a loDifferential diagnosis from primary membranous nephropathy is based on the simultaneous presence of TIN, on the detection of other localizations of the disease (the kidney is very rarely the only organ affected), on the absence of antibodies specific for phospholipase A2 receptor. However, it is important to take into account that this autoantibody, marker of primary membranous nephropathy, is present in only 70% of the patients . The recRecently, the coexistence of IgG4-RD and primary membranous nephropathy has been described in a patient positive for antibodies to the phospholipase A2 receptor .Idiopathic retroperitoneal fibrosis (IRF) is a rare fibro-inflammatory disease of unknown etiology characterized by periaortic and peri-iliac fibrosis. It was described for the first time in 1905 and classified in 1948 by Ormond . It was The expansion of fibrosis can entrap any of the structures in the retroperitoneum, especially ureters, inducing obstructive nephropathy. Clinical features are often non-specific: lower back and flank dull pain in over 90% of patients, anorexia, weight loss, fatigue. Legs edema associated to deep venous thrombosis can be detected when vena cava obstruction is present.Recently, it has been reported that IgG4-RD RF is characterized by lower serum IgG4 levels and a lower IgG4-RD Responder Index at disease onset if compared with other clinical phenotypes of IgG4-RD , 30. HisTo evaluate retroperitoneal lesions, enhanced CT scan, MRI, or PET/CT are the preferred tools; hydronephrosis can easily be detected by ultrasound. Other localizations of the disease can be more easily biopsied and can suggest the correct diagnosis.When acute ureteral obstruction occurs, ureteral stent, percutaneous nephrostomy, or ureteral stricture surgery are necessary to overcome hydronephrosis and progression to end-stage renal disease. However, many patients can still suffer from chronic kidney disease, because of late or ineffective medical treatment .The coexistence of IgG4-RD and AAV has been reported and a biopsy-proven overlap was described in several cases.Chang et al. , 33 descIn AAV-IgG4-RD overlap, kidney lesions attributable to both disorders can coexist and cooperate to induce anatomical and functional damage. Under this respect, the case we describe in this report is of particular relevance, because renal histology shows a glomerulonephritis compatible with AAV, with rupture of Bowman capsulae and fibrinoid necrosis, together with a tubulointerstitial involvement and IgG4+plasmacells, more typical of IgG4-RD. The coexistence of TIN with eosinophilic infiltrate has been previously described in AAV, before the identification of IgG4-RD as distinct nosological entity . In the ANCA are critical for the differential diagnosis between AAV and IgG4-RD, but low titer ANCA are present in several autoimmune disorders including IgG4-RD. Thus, the detection of IgG4 ANCA has been taken into account as possible tool for diagnosis.ANCA positivity is one of the exclusion criteria proposed for the diagnosis of IgG4-RD in ACR/EULAR IgG4-RD classification criteria .However, IgG1 and IgG4 ANCA are reported by Della-Torre et al.  in a casComparing the subclass distribution of ANCA MPO in AAV and IgG4-RD, we found that ANCA MPO of any subclass, and not only IgG4, can be detected in IgG4-RD sera. However, the titer of these antibodies is very low in comparison with AAV; moreover, antibody titer and the number of ANCA subclasses are not correlated to clinical activity, at variance with the results obtained in AAV. Thus, ANCA titer seems more relevant than subclass distribution for differential diagnosis and the detection of ANCA-MPO at high titer, without analyzing ANCA subclasses, is sufficient to corroborate serologically the clinical suspect of an AAV-IgG4-RD overlap .Due to the rarity of the disease, no randomized trial specifically addressing IgG4-RKD has been conducted so far. Only single case reports have been published, and the renal involvement in IgG4-RD is treated according to the therapeutic approach used for the other localizations of the disease. Since the kidney is a critical organ, early therapy is recommended to prevent long-term fibrotic damage.2, as well as advanced histological stage, still present an improvement after steroid treatment, albeit limited  and oral Cyclophosphamide (CFX) , 52. BotB cell-targeted therapy with Rituximab (RTX), a monoclonal antibody anti CD-20, leads to an excellent response, with a remarkable reduction of mass lesions and a variable regression of fibrosis even in a steroid-free regimen . RTX admIn contrast, there is no clear demonstration that an exclusive steroid regimen is an effective approach for IgG4-membranous nephropathy . PatientNotably, the disease can recur in the transplanted organ, as reported by Chibbar et al. Despite therapy with prednisone (5 mg daily), tacrolimus 6–8 mcg/L, and mycophenolate mofetil 2 g daily, a 25 year old patient had relapse of IgG4-TIN 5 years after renal transplant, concomitant with chronic active antibody mediated rejection .IgG4-RD RF benefits of the same treatments already described. Notably, recent reports of MMF and RTX treatment in RF show efficacy whether or not it is a manifestation of IgG4-RD , 61. SomRenal involvement in IgG4-RD is a dangerous condition that can lead to a chronic organ damage, potentially life-threatening. Multiple reports suggest the need of an aggressive therapy in order to avoid a fibrotic remodeling and a functional damage.Describing four clinical cases, we moved from sunlight to twilight, going from the classical pattern of renal involvement of case 1 and 2 to the more complex picture of case 3 and finally to the subclinical involvement of case 4.These four patients enlight the heterogeneity of clinical manifestations as distinguishing feature of IgG4-RD also when affecting the kidney.Thus, a careful periodic assessment of kidney function with evaluation of filtration rate and urinary sediment, in association with adequate imaging, is mandatory for each IgG4-RD patient. Presently, urinary markers that allow an early diagnosis and follow up of renal involvement in IgG4-RD are not available.More investigations are needed to define biomarkers  able to correctly profile the type and extent of renal involvement in IgG4-RD.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study.RC, DG, and PM conceived the work and wrote the paper. DG, DM, and ME were in charge of nephrological evaluation of the patients. DG performed renal biopsies. AB performed biopsies examination. CC and FP performed immunohistochemical and cytofluorimetric evaluations. RC, IP, and AT were in charge of the patients and collected clinical data. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Based on a literature review, four parameters, w/c ratio, binder content, ground granulated blast-furnace slag (GGBS) and fineness of cement, which show a significant influence on the electrical resistivity of plain concrete, were identified, and their influence on the electrical resistivity as well as interaction effects were investigated. The results of the experiments highlight that the addition of fibres leads to a significant decrease in electrical resistivity, independent of all additional parameters of the concrete composition. Additionally, it was shown that a higher porosity of the concrete, e.g., due to a higher w/c ratio, also results in a lower electrical resistivity. These results are in agreement with the literature review on plain concrete, while the influence of the concrete composition on the electrical resistivity is weaker with the increase in fibre content. The influence of fibre reinforcement is thus not affected by changes in the concrete composition. In general, a higher fibre dosage leads to a decrease in electrical resistivity, but the impact on the electrical resistivity varies slightly with different types of steel fibres. Based on this study, the potential of determining the fibre content using electrical resistivity measurements could be clearly presented.This paper presents a systematic study of the electrical resistivity of different steel fibre-reinforced concretes with fibre contents from 0 kg/m As a commonly used composite material for civil construction steel fibre-reinforced concrete (SFRC) combines the positive aspects of both basic materials with respect to its load bearing behaviour e.g., ,3,4,5,6),4,5,63,4While the fibre content in new construction projects can easily be determined by washing fibres out of a defined fresh concrete sample or by checking the weighing protocols, in hardened concrete or existing constructions, to date, there is no easy method to calculate the exact fibre content. One non-destructive test method that seems to be suitable for the determination of fibre content and orientation in concrete is to measure the electrical resistance of the concrete  significantly decreases the porosity of the concrete, thus leading to an increase in electrical resistivity. Mainly due to the pozzolanic or latent-hydraulic reaction of SCMs, such as GGBS, silica fume or fly ash the pore structure becomes finer and less permeable, and thus the conductivity of the pore solution is reduced. The same phenomenon can be observed using finer cements, such as cements with higher strength classes . It . It 61])One additional parameter that may have a large effect on the electrical resistivity independent of the concrete composition is the aging of the concrete as a function of service exposure, which is paired with changes in the pore structure and also impacts leaching and drying processes. Furthermore, the continuing hydration process leads to a refinement and densification of the pore structure, thus increasing electrical resistivity. The same effect occurs due to ion leaching effects .,65.39,65Measurements of the electrical resistivity of the concrete show a high potential for use as non-destructive test method for the determination of the fibre content of SFRC, and thus possible negative effects of other parameters have been known to enable sufficient and accurate results by the use of an easy test setup. Even though, in the past, investigations have been performed to show the influence of fibres on the electrical resistivity  nor changes in clinker composition for the different cements should take place. Additionally, the use of GGBS was investigated in different mixtures. Quartzite gravel with a grain size distribution of A/B 16 in accordance with DIN 1045-2 )3 and fibre contents of 10 to 30 kg/m3 seemed to deviate from the constant decreasing behaviour, but this can be explained by the scatter of the experiments.In addition to the water/cement ratio, the binder content, which in this case was synonymous to the cement content due to the lack of SCM in the basic concrete mix design, directly influenced the total amount of water and hydrated cement paste in the concrete mixture. Hence, the total porosity of the concrete varied, whereas the pore size distribution was only marginally impacted. In The cement type, in this case, the strength class, synonymous with the specific surface of the cement, was varied to identify the effects of a finer pore structure of cement on higher strength classes. Comparing the results of CEM I 32.5 R and CEM I 42.5 R, this expected behaviour could be observed, but the finest cement (CEM I 52.5 R) does not fit into those expectations a. As desIn In addition to the different cement strength classes, GGBS was used as a concrete component due to its well-known ability to significantly alter the pore structure of the concrete. To identify the effects of GGBS without any interactions with different cement clinkers, the same base cement (CEM I 32.5 R) was blended with GGBS at a constant water/binder ratio. The contents of GGBS were chosen considering the limits for additives for slag cements.The use of a GGBS content of 35% of the total binder content did not result in any significant changes in the electrical resistivity a. For smThe summarising main effect plot b shows tA statistical design of experiments was used to detect possible interactions among different parameters to check the possibility of the superposition of the single effects of different parameters on the global electrical resistivity. Comparing the results of the single parameter variation to the results of the multiple parameter variation, it is clear that there were differences in the main effects of the analysis of Minitab . All fouThe results of the first three parameters, w/c ratio, binder content and cement type, of the multiple parameter variation differed from that of the single parameter variations, which shows that a superposition of these parameters is not possible in every case. Only the results of the addition of GGBS content are slightly similar to those of the single parameter variation.In sum, it is clear that the results of single parameter variation and multiple variation completely differ. This result can be confirmed by observing the interaction plot of the multiple parameter changes . There, One problem of the statistical design of experiments was the low number of tested concretes, since a full matrix of 81 possible mixtures was investigated and approximated by the analysis of only 9 mixtures. Through the partially low influences of single parameters and the presented interactions, a more detailed analysis of interaction effects was not possible.The last parameter that was analysed via single parameter variation was the fibre type. Two macroscopic fibres with fibre lengths of 60 mm and 35 mm, respectively, and one microfibre with a fibre length of 8 mm were used. The results of the variation show that there was almost no influence on the electrical resistivity for all three types of fibres. While all three plain concrete mixtures are almost identical, which indicates comparable basic mixtures, with an increasing fibre content, only the addition of the smaller macrofibre (35 mm length) led to a slightly higher electrical resistivity a. The loWhile there was almost no visible effect on the global electrical resistivity of the concretes with different types of fibres, possible variations in the distribution of different specimen directions, depending on the fibre type and manufacturing process, were identified, which was performed by the use of a vibrating table. Comparing the global electrical resistivity a and thaIn contrast to the electrical resistivity in the horizontal, the vertical electrical resistivity was significantly higher than the global electrical resistivity, and the spread of the curves of the different fibres was wider than seen for global electrical resistivity or in the horizontal direction a. This pIndependent of fibre content, a difference between the electrical resistivity of the concretes with the macrofibre with a length of 60 mm and the microfibre in the vertical direction b was cleIn addition to the investigated influencing factors, concrete composition and fibre content, the age of the concrete and the storage conditions can influence the electrical resistivity of the concrete. To show the effects of these factors, specimens from the same mixing batch were used. The influence of concrete age, independent of the storage medium, on the electrical resistivity is presented in 2O over Ca(OH)2 to synthetic pore solution, the electrical resistivity decreased, which is in agreement with the increasing initial conductivity of the used storage media. An analysis of the effect of different storage media on the electrical resistivity is presented in The effect of the age of the concrete and the storage conditions independent of fibre content are presented in 3 of fibres resulted in a reduction in the electrical resistivity from approximately 43.5 Ωm to 13.8 Ωm for the mean values, which is equivalent to a reduction of approximately 70% and has the main influence on the electrical resistivity, and no interactions between the fibre content and other varied parameters on the electrical resistivity could be observed. The variation of the concrete composition also led to effects on the electrical resistivity, but compared to the fibre content, the effect is much smaller, which can be seen in The aim of this study was to identify the relevance of the influencing parameters on the electrical resistivity of SFRC. Hence, variations of the concrete composition as well as changes in storage conditions and concrete age were analysed. To enable the possibility of using electrical resistivity measurements for the detection of the fibre content of SFRC, the fibre content is the most influencing parameter on the electrical resistivity. As presented in As steel fibres are metallic conductors, their conductivity exceeds the ionic conductivity of concrete pore solution, even if the concrete is fully saturated, and so the huge impact of the amount of steel fibres that was identified can be explained. In addition, a high amount of fibres leads to a higher permeability of the concrete . For a 3, which is uncommon in practice, no such influences could be detected. In summary, it can be concluded that the electrical conductivity of SFRC is mainly influenced by the amount of fibres, respectively, steel and not by the number of fibres, so differentiation between a continuous conductive path via one fibre or a discontinuous conductive path via a plurality of fibres and concrete with transition zones between both materials is not possible.The use of different fibre types, two macrofibres with different lengths of 60 mm and 35 mm and one microfibre with a length of only 8 mm, which was coated with brass, showed almost no effects on the global electrical resistivity of the concretes . This inThe only effects of different fibres that were observed resulted from an expected slightly varying distribution and orientation of the microfibres through the mixing and compacting processes. Due to the limited specimen dimensions, long fibres can freely align in the formwork but are extremely influenced by the production procedure. Since the concrete formworks were filled in accordance with European standards, two layers of concrete were filled in and long fibres tended to align more horizontally. In addition, the compaction process via the vibrating table led to a vertical compaction force and thus also supported a horizontal orientation of the fibres. On the contrary, microfibres are sufficiently small to align in the concrete almost freely and are mostly not influenced by aggregates, manufacturing processes in layers or vertical compaction. However, a difference between the macrofibres could not be observed. Therefore, it can be concluded that there is a critical fibre length and a number of fibres per kg, which leads to effects on the fibre orientation, and when this critical value is not reached, no influences will be visible.The age of concrete, in the investigated range of 7 days to 185 days, led to changes in the electrical resistivity between 40 Ωm and 70 Ωm for plain concrete, and 10 Ωm and 20 Ωm for SFRC, but again, the effects of fibre addition dominated the influence of concrete age. These results confirm the observations of , where eEven though the initial conductivity of the pore solution had an impact on the electrical resistivity of the concrete, for SFRC, the storage medium only had a minor influence on the electrical resistivity. A higher initial alkalinity slightly reduced the electrical resistivity of the concrete. For future analysis, this implies the necessity to use constant storage conditions, namely, a certain conditioning of the specimens before the measurement of the electrical resistivity should be performed, but unknown conditions of concrete in structural elements are not an exclusion criterion for this test method.As expected, a variation of the concrete also influenced the electrical resistivity, mostly due to changes in the pore structure of the concrete. The observed parameters, w/c ratio, binder content, cement type and GGBS content, all caused changes in the electrical resistivity.As stated in several studies , ,38, 37,33, in comparison to plain concrete. Nevertheless, since there are also influences from the concrete composition, such as on the w/c ratio and binder content, the application field of this test method requires previous calibration on concrete mix designs without the addition of fibres. Otherwise, the effects of the concrete composition, which can influence the electrical resistivity by approximately 15% to 25%, can induce significant errors in the analysis of the fibre content. Investigations of existing structures in the case of repair or maintenance work can only lead to sufficient approximations for the fibre content if either the composition or electrical resistivity of the plain concrete are well known, e.g., with the help of an extensive database or the characterisation of plain concrete without fibres. Both possible methods of extending the test setup to enable its use for the characterisation of existing structures and additionally in the evaluation of fibre orientation are the subject our future studies.This study showed that the determination of the electrical resistivity of SFRC is a suitable test method for the monitoring of fibre content, e.g., in precast factories or for new construction buildings where the electrical resistivity of the plain concrete composition can be characterised. The large difference between the conductivity of steel as a metallic conductor and concrete as an ionic conductor led to significant influences of the fibre content on the electrical resistivity, which resulted in a 70% lower electrical resistivity of SFRC, 80 kg/m