Fever in neutropenia (FN) is a potentially life-threatening complication of chemotherapy in pediatric cancer patients. The current standard of care at most institutions is emergency hospitalization and empirical initiation of broad-spectrum antibiotic therapy.in vitro antibiotic susceptibility patterns, and their trends over time.We analyzed in retrospect FN episodes with bacteremia in pediatric cancer patients in a single center cohort from 1993 to 2012. We assessed the distribution of pathogens, the Escherichia coli , Klebsiella spp.  and Pseudomonas aeruginosa  were the most common pathogens. Comparing the in vitro antibiotic susceptibility patterns, the antimicrobial activity of ceftriaxone plus amikacin , cefepime , meropenem , and piperacillin/tazobactam , respectively, did not differ significantly. The addition of vancomycin to those regimens would have increased significantly in vitro activity to 99% for ceftriaxone plus amikacin, cefepime, meropenem, and 96% for piperacillin/tazobactam (p < 0.001).From a total of 703 FN episodes reported, we assessed 134 FN episodes with bacteremia with 195 pathogens isolated in 102 patients. Gram-positive pathogens  were more common than Gram-negative . This proportion did not change over time (p = 0.26). Coagulase-negative staphylococci , viridans group streptococci , in vitro antimicrobial activity.Over two decades, we detected a relative stable pathogen distribution and found no relevant trend in the antibiotic susceptibility patterns. Different recommended antibiotic regimens showed comparable  Pseudomonas aeruginosa, broad coverage of Gram-positive and Gram-negative pathogens is recommended for initial empirical antibiotic therapy in FN [The most frequent potentially lethal complication of chemotherapy in pediatric patients with cancer is fever in neutropenia (FN) . The curpy in FN . Becausepy in FN –7 and Ampy in FN  guidelinpy in FN –8. Antibpy in FN , 10.in vitro antibiotic susceptibility patterns against selected antibiotics, and their trends over time in a single center retrospective cohort study spanning two decades in a pediatric oncology center using only oral trimethoprim/sulfamethoxazole or inhaled pentamidine diisethionate antimicrobial prophylaxis.This study aimed to examine the distribution of pathogens isolated during FN with bacteremia, their in vitro antibiotic susceptibility patterns were available from the laboratory database of the local Institute for Infectious Diseases. During the anonymization process the study time period was divided into 4-year intervals  [This retrospective single-center cohort study was conducted at the Division of Pediatric Hematology and Oncology, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Switzerland. All children and adolescents less than 17 years old at diagnosis of malignancy and treated with chemotherapy from 1993 to 2012 were eligible. Details of patient identification and the data acquisition process have been published elsewhere . For thito 2012) . This stto 2012) , and 200to 2012) .Pneumocystis jiroveci. Patients who did not tolerate oral trimethoprim/sulfamethoxazole were switched to inhaled pentamidine diisethionate. No other antibiotic prophylaxis was used [Most patients were treated for their malignancy according to established international phase III protocols or therapy recommendations. Clinical management regarding prophylaxis and treatment of FN remained unchanged during the complete study period. All patients received oral trimethoprim/sulfamethoxazole as primary prophylaxis for was used . Routinewas used . Aerobicwas used .®, bio-Mérieux, Geneva, Switzerland) [in vitro antibiotic susceptibility. To determine the penicillin and ceftriaxone minimum inhibitory concentrations of viridans group streptococci (VGS) we used the Etest® . For in vitro susceptibility testing of vancomycin in Enterococcus spp. a brain heart infusion agar screen plate containing six micrograms of vancomycin per milliliter was used. During the entire study period, the Clinical and Laboratory Standards Institute standards were used at our Institute for Infectious Diseases [Neutropenia was defined as an absolute neutrophil count ≤ 0.5 G/L . Until Jzerland) . We usedDiseases . Polymicin vitro antibiotic susceptibility patterns of bacteria isolated in blood culture against antibiotics commonly used for empirical therapy in pediatric FN [in vitro if the susceptibility pattern showed full susceptibility to the selected antibiotic and the isolated pathogen did not harbor intrinsic resistance to the selected antibiotic. We considered combination therapy (e.g. ceftriaxone plus amikacin) to be active in vitro if the susceptibility pattern showed full susceptibility to at least one of the antibiotics and did not harbor intrinsic resistance against all antibiotics of combination therapy. Enterococci spp. were considered intrinsic resistant to cephalosporins and carbapenems.We assessed the atric FN . We evalin vitro antibiotic susceptibility patterns.Due to technical difficulties in retrieving data from the microbiology database, results of susceptibility testing were not available from 1993 to mid 1998. Therefore, we excluded the time period from 1993 to 1996 and all other isolates without available susceptibility testing from analysis of in vitro antibiotic susceptibility patterns with the Fisher’s Exact Test.We presented continuous variables as median and interquartile range (IQR) and nominal data as frequencies with 95% confidence intervals (95% CI). We used the exact Kruskal-Wallis Test to analyze trends over time for nominal data and exact Jonckheere-Terpstra-Test for continuous data with Monte Carlo approximation. We compared the For all statistical analyses, 2-sided P-values below 0.05 were considered significant. The exact Kruskal-Wallis test and exact Jonckheere-Terpstra test were calculated with StatXact 10 . All other analyses and plots were done using R 3.3.3 .Candida spp. in three. We thus analyzed 134 FN episodes with bacteremia caused by 195 bacteria isolated in blood culture in 102 patients  received chemotherapy to treat their malignancy. Of 703 eligible FN episodes, bacteremia was detected in 148 (21%). Specific information on the clinical course was available in 138 (90%) of these episodes . Four . Clinical characteristics and evolution over time of the 134 FN episodes with bacteremia are presented in Klebsiella spp. during the last time period.  Gram-positive and 71  Gram-negative bacteria were isolated in blood culture . This pr period. . If we e period. .The majority of pathogens, 134 of 195 (69%) were detected on day 0 only. All 71 Gram-negative bacteria were isolated in blood cultures taken before day 3, 61 (86%) in the first blood culture taken on day 0, nine (13%) on day 1, and one (1%) on day 2.Enterococcus faecalis and two other Gram-positive pathogens (Subsequent bacteremia was detected in 46 of 134 (34%) episodes . All 20 athogens . Over tiathogens . This tiP. aeruginosa in two episodes, none had a fatal outcome. In 15 (11%) episodes polymicrobial growth was noted in blood culture.Prolonged bacteremia was detected in 12 of 134 episodes (9%), caused by CoNS in 10 and in vitro antibiotic susceptibility patterns of 143 of 169 (85%) bacteria isolated in blood culture between 1997 and 2012. The combination of ceftriaxone plus amikacin was active in vitro in 64% , cefepime 64% , meropenem 64% , and piperacillin/tazobactam 62% . Adding vancomycin to any empirical antibiotic therapy would have increased activity to 99% for ceftriaxone plus amikacin , cefepime , and meropenem , while it would have increased activity to 96% for piperacillin/tazobactam  . No significant trend over time was noted  and one Gram-negative pathogen (P. aeruginosa isolate resistant to Amikacin). None of the respective patients died.The isolates not covered in vitro susceptibility rates for the examined antibiotic regimens were increased to 89% for piperacillin/tazobactam, 92% for ceftriaxone plus amikacin, cefepime, meropenem. In combination with vancomycin in vitro susceptibility rates reached 93% for piperacillin/tazobactam, 98% for ceftriaxone plus amikacin and 99% for cefepime and meropenem -producing Enterobacteriaceae. Of note, one vancomycin-resistant E. faecalis  and two VGS isolates resistant to ceftriaxone (ceftriaxone E Test ≥ 4 μg/ml) were detected. Among E. coli and Klebsiella spp. 18% and 10%, respectively, were resistant to piperacillin/tazobactam . However, in one of five episodes with P. aeruginosa bacteremia susceptibility testing revealed resistance to ceftriaxone and amikacin, whilst the isolate would have been susceptible in vitro to cefepime, meropenem, and piperacillin/tazobactam.Current guidelines—which were not available at the time of this study—do favor monotherapy with an antipseudomonal beta-lactam or a carbapenem as first-line treatment –8. In ouE. coli was the most prevalent Gram-negative pathogen in our study [Enterobacteriaceae infections. This is in contrast to other studies in pediatric patients with cancer and FN that have reported increased rates of multi-resistant bacterial infections [All Gram-negative pathogens detected in our study were isolated in blood cultures taken before day 3, underscoring the need for a broad coverage of Gram-positive and Gram-negative pathogens by empirical therapy regimens for FN in pediatric cancer patients. Similar to other studies, ur study , 25. Whiur study , we did fections , 25–27.in vitro antibiotic susceptibility patterns and their trends over two decades in pediatric cancer patients.The strengths of the study are the long observation period and a large number of FN episodes with bacteremia in a setting without relevant changes in clinical management during the study period. To the best of our knowledge, our study is the longest observational study examining the pathogen distribution, the in vitro antibiotic susceptibility patterns were not available for some pathogens due to a change in the data storage system during the study period. Second, clinical data was incomplete which prevented us from drawing firm conclusions on reasons and nature of adaption of antibiotic therapies and classification of pathogens as contaminants. Third, the use of Kirby-Bauer disk diffusion test might be less sensitive to the detection of changes in susceptibility rates than determining minimum inhibitory concentrations. However, given the long observation period of the study, we do not think this affects the interpretation of the results. Fourth, several FN episodes per patients were allowed and analyses were not formally corrected for multiple episodes per patient.Given the retrospective nature of the study, several limitations need to be mentioned. First, data on in vitro activity that was comparable to other recommended treatment regimens and was stable over time. In our setting, a fourth-generation cephalosporin would be preferred as antipseudomonal monotherapy, given the lack of ESBL-resistance and the relatively high rate of resistance against piperacillin/tazobactam observed in Enterobacteriaceae.In conclusion, this study showed a stable local distribution of pathogens causing bacteremia during FN episodes in pediatric cancer patients with FN over a 20-years period. The currently used empirical treatment, with its advantage of once daily application, had an S1 Fig(TIF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


When an additive is used to replace a certain amount of cement, a concrete pore structure becomes dense. Thus, it results in inhibiting the penetration of chlorine ions and suppressing corrosion of reinforcing bars. However, the pH level of the concrete decreases, and it deteriorates the performance of the passive film formed on the surface of the rebars embedded in the concrete. Therefore, in this study, the service lives of reinforced concrete containing different types of concrete binders were predicted and compared. The chloride ion diffusion coefficients of concretes with various binders were measured, and the critical chloride content of the rebar was assessed by the real-time monitoring on the corrosion initiation time of the rebar embedded in concrete. Moreover, Fick’s 2nd law was applied to predict when the chloride content at the 40 mm depth of cover reached the critical chloride content based on the chloride ion diffusion coefficient. It was observed that the service life of S6 (OPC 40% + GGBFS 60%) was the highest, followed by TBC (OPC 40% + GGBFS 40% + FA 20%), S3 (OPC 70% + GGBFS 30%), and OPC (OPC 100%). With the durability of concrete emerging as a social issue, the need to develop concrete with high durability has been coming to the fore. Of particular concern are concrete structures in areas affected by the marine environment are subject to immense maintenance costs due to the corrosion of rebars caused by the penetration of chloride ions ,2.In recent years, the demand to construct concrete structures around port facilities has increased due to the increase of goods transported by sea, so it is becoming important to build concrete structures with excellent resistance to marine environments both in terms of structural stability and in terms of economics ,4,5.Methods using such admixtures as ground granulated blast furnace slag (GGBFS) and fly ash have been proposed to improve the durability of concrete exposed to chloride attack ,23,24,25However, studies have shown that replacing the cement used in concrete with admixtures such as GGBFS and fly ash can reduce the critical chloride content of rebars embedded in the concrete ,32,33,342. The penetration rate of chloride ions was calculated using Fick’s 2nd law, and the time when the chloride content at the 40 mm depth of cover reached critical chloride content was considered as the point at which the service life of concrete terminated.In this study, the variation of the service life of reinforced concrete was evaluated according to the different types and replacement ratios of additives. The chloride ion diffusion coefficient of concrete was measured based on NT BUILD 492. In addition, the corrosion initiation time and the critical chloride content of the rebar embedded in reinforced concrete were assessed by using an embedded reference electrode with MnO3  was used. And Grade-80 Ground Granulated Blast Furnace Slag (GGBFS) of ASTM C989/C989M [2/g  was used. Class-N Fly-Ash (FA) of ASTM C 618 [2/g was also used. Ordinary Portland Cement (Type 1) of ASTM C150/C150M  with a d89/C989M  with a BTM C 618  with a BTo reduce the effect of coarse aggregates between the rebar and cover of concrete, the maximum size of coarse aggregates was limited to 13 mm and the fine aggregates were prepared by mixing crushed sand and washed sea sand. In Korea, it is common to use a combination of crushed aggregates and washed sea sand (decontaminated chloride) owing to the depletion of river sand ,58. The For this study, four types of concrete specimens were prepared according to the GGBFS and FA replacement ratio: OPC 100% (OPC), GGBFS 30% + OPC 70% (S3), GGBFS 60% + OPC 40% (S6) and GGBFS 30% + FA 30% + OPC 40% (TBC).As for the experimental level, normal GGBFS cement (replacement ratio 30%), high durability GGBFS cement (replacement ratio 60%), and three-binder combination cement (replacement ratio 60%) were compared with 100% OPC. After the concrete was mixed for specimen fabrication, it was poured into a cylinder mold (Ø100 mm × 200 mm) and sealed. The specimen was demolded 24 h later and cured for 28 days. After curing 28 days, the specimen was cut into samples 50 mm and the 2 samples from the middle of the specimen were used. 2 sensor, and finally placing concrete. Reinforced concrete specimens were fabricated to evaluate the critical chloride contents of rebars according to the concrete mixture. The reinforced concrete specimens were prepared by placing rebars in a rectangular mold (size: 100 mm × 100 mm × 200 mm) using acrylic, arranging the MnO2 sensor was placed close between two rebars and embedded in concrete along with the rebars to allow more accurate measurement with fewer errors.SD400 rebars (Ø13 mm) were used to fabricate the specimens. The foreign substances and corrosion products on the surface of the rebars resulting from long-term exposure to air were removed by using grit-blast and sandpaper. The MnOAfter mixing the concrete, it was poured into the mold and demolded after 24 h. Then, the concrete specimens were cured by air-dry curing for 28 days. The air-dry curing conditions were a temperature of 20 °C ± 2 °C and relative humidity of 60% ± 5%. In order to simulate the curing conditions of the concrete poured on the site, air-dry curing was performed, not under-water curing.The concrete compressive strength was evaluated according to ASTM C 39  for curiThe most exact method of measuring the resistance to chloride ingress of concrete is to perform an exposure test. However, exposure tests required a very long time. Therefore, it is common to evaluate the chloride ion diffusion coefficient and resistance to chloride ingress of concrete using the electrochemical acceleration method. Typically, NT BUILD 492 and ASTM C 1202 are used to evaluate chloride ingress of concrete. In this study, among the resistance to chloride ingress evaluation methods, the chloride ion diffusion coefficient was obtained from non-steady-state migration experiments conducted according to NT BUILD 492 , a Nordi2 saturated solution was filled in a desiccator and the concrete specimen was immersed in the saturated solution. The inside of the desiccator was maintained in a vacuum state by using a vacuum pump, and the pores of the concrete were filled with Ca(OH)2 saturated solution. After pretreatment, chloride ion diffusion cells were prepared as shown in l30V). Next, according to the initial values in NT BUILD 492 is a non-steady-state electric migration experiment to determine the chloride ion diffusion coefficient of the repair material composed of concrete, mortar, and cement. Concrete specimens (size: Ø100 mm × 50 mm) were prepared, Ca(OH)3 solution was sprayed on the split section, discolored parts appeared on the specimen depending on the penetration depth of the chloride ions. The chloride ion diffusion coefficient was determined using the average of seven measurements of the chloride penetration depth, in 10 mm intervals.After the test, the concrete specimen was split vertically into two pieces. When 0.1 N AgNOnssmD: non-steady-state migration coefficient (×10−12 m2/s), U: absolute value of the applied voltage (V), T: average of the initial and final temperatures in the anolyte solution (°C), L: thickness of the specimen (mm), xd: average value of the penetration depths (mm), T: test duration (h).Equation (1) is used to estimate the chloride ion diffusion coefficient at the depth of chloride ion penetration .(1)DnssThe potential (OCP) monitoring test of rebars was performed according to the NaCl supply time, and 2 sensor, an NaCl supply cell was installed on top of the specimen using acrylic, and the potential of the rebars was monitored in real-time using a Data-logger  according to the supply time of 10 wt.% NaCl solution. The wires were soldered to the rebars to monitor changes in the potential of the rebars. The rebars were connected to the anode (+) of the data-logger and the MnO2 sensor to the cathode (−) to collect and store data by measuring the potential of the rebars to the MnO2 sensor every 10 min. While observing the potential of the rebars according to the 10 wt.% NaCl solution supply time, the rebars were evaluated as corroded if the potential of the rebars dropped below −515 mV, in which case, the test was ended by stopping potential measurement and the supply of NaCl solution [After connecting wires to the rebars of the specimen and the MnOsolution . Then, tsolution ,62.The supply of NaCl solution was stopped for the 20 mm concrete cover specimens in which rebar corrosion had started and the 25 mm concrete cover specimens in which rebar corrosion did not occur. The concrete specimens were collected after cutting the specimens at 5 mm intervals from the NaCl solution supply surface, and the chloride content was measured according to ASTM C 1218  to profiAfter measuring and profiling the chloride content according to the concrete cover depth, the chloride content between the 20 mm concrete cover depth of corroded rebars and the 25 mm concrete cover depth of non-corroded rebars was estimated as the critical chloride content of the rebars embedded in concrete.V1: Volume of 0.05 N silver nitrate solution used for titration in the specimen , V2: Volume of 0.05 N silver nitrate solution used for blank titration , N: The exact normal concentration of 0.05 N silver nitrate solution (N), W: The mass of the specimen (g).Titration with silver nitrate was used to measure the chloride ion concentration in the concrete, and Equation (2) shows how to calculate the chloride content for the mass of concrete according to the appropriate amount of silver nitrate .(2)Cl− p-value is the cement mass ratio (%) in mortar or concrete, and this study used the cement mass ratio.After calculating the chloride content (%) for the mass of concrete, the chloride content (%) for the cement or binder was obtained by multiplying the chloride content (%) by 100/P. The C: Chloride ion concentration (kg/m3) at depth x (cm) and time y (year), C0: Chloride ion concentration on the surface (kg/m3), D: Chloride ion diffusion coefficient, erf: Error functionFick’s Second Law was used to evaluate the service life of the reinforced concrete structure, as shown in Equation 3) below [ below 3.(3)C of concrete can be ranked in the order of OPC > S3 > S6 > TBC, while the compressive strength after 28 days can be ranked in the order of OPC 29.2, S30 28.2, S60 27.4, and TBC 21.8 MPa, showing the same trend as the initial compressive strength. The compressive strength of concrete decreased as the admixture replacement rate increased, and with the same 60% replacement ratio, the GGBFS 60% specimen showed higher compressive strength than the TBC specimen. The development of concrete compressive strength was limited because of the insufficient hydration process under air-dry curing conditions and the absolute quantity of cement (40%), which reduced the production of Ca(OH) fly ash ,13,15. IAccording to the measurement results, the chloride ion diffusion coefficient of concrete can be ranked in the order of OPC > S3 > TBC > S6, and replacing OPC with GGBFS or FA was shown to be effective in reducing the number of ions penetrating the concrete. However, when replacing GGBFS 40% + FA 20%, the chloride ion diffusion coefficient was not significantly different from the GGBFS 30% specimen even though the replacement rate was 60%. This is because the latent hydraulic property of GGBFS and the pozzolanic reaction of FA did not occur sufficiently due to the decrease in the absolute quantity of cement and the hydration products under the high admixture replacement rate and air curing conditions, so the structure of the cement matrix was not completed properly ,18,19,202) as the NaCl solution supply time increased, and rebar corrosion occurred accordingly. On the other hand, the potential of the rebars with 25 mm concrete cover depth was stable and rebar corrosion did not occur. The time it took for the rebars with 20 mm concrete cover to corrode according to the NaCl solution supply time was 76 days for OPC, 96 days for TBC, 112 days for S3, and 119 days for S6, which has the same trend as was shown in the evaluation of the concrete chloride ion diffusion coefficient in 2 sensor was considered to be valid and accurate. In addition, improving the precision of the MnO2 sensor should allow us to correct this difference in the future [e future .In particular, since the surface of the rebars with 25 mm concrete cover depth remained intact and without corrosion, the critical chloride content that induces rebar corrosion in concrete can be roughly estimated by measuring the chloride content in the 20–25 mm concrete cover.The specimens in which the rebars started to corrode were cut at 5 mm intervals from the NaCl solution supply surface to collect the concrete samples and evaluate the amount of chloride content, and the results are shown in 3. This shows that critical chloride content for rebars embedded in concrete decreases as the replacement rate of GGBFS or FA increases. Compared to the specimen using 100% OPC, the critical chloride content of the specimen using OPC 40% + GGBFS 60% decreased by 51.37%.The concrete chloride content tended to decrease as the cover depth increased at all of the experiment levels, and the chloride content in concrete decreased as the cement admixture replacement rate increased. Among the chloride content measurement results, the chloride content between the 20 mm cover depth with rebar corrosion and the 25 mm cover depth without rebar corrosion was estimated as the critical chloride content that induces corrosion of rebars embedded in concrete. From highest to lowest, the calculated critical chloride content for rebar corrosion can be ranked in the order of OPC 1.46, S3 0.98, TBC 0.74, and S6 0.71 kg/m2 produced by hydrated OPC stimulates a latent hydraulic reaction or is consumed by the pozzolanic reaction, so the total amount of Ca(OH)2 in the concrete decreases and the pH of concrete decreases accordingly. The reduced amount of Ettringite and Ca(OH)2 produced by the decrease in the absolute quantity of cement also has a direct effect [This is because as the replacement rate of GGBFS or FA increases, the Ca(OH)t effect ,33,34,353), and the results are shown in the table below. In addition, This study evaluated the service life against chloride attack for reinforced concrete structures with 40 mm concrete cover using the results of assessing the concrete chloride ion diffusion coefficient according to the admixture replacement rate and admixture type measured in Based on the results shown above, the 3) is applied, the service life of the structures can be evaluated as 26 years for OPC concrete, 53 years for S3 concrete, 80 years for TBC concrete, and 102 years for S6 concrete. However, after critical chloride content according to the admixture replacement rate and the type of admixture is applied, the service life of the structures changes to 26 years for OPC concrete, 51 years for S3 concrete, 60 years for TBC concrete, and 89 years for S6 concrete. In the case of OPC, the service life tended to increase compared to when the conventional critical chloride content in the Korean specification was applied, but in general, the service life tended to decrease when replacing cement with admixtures.When the critical chloride content in the Korean concrete standard specification By measuring the chloride ion diffusion coefficient of concrete, it was found that the chloride ion diffusion coefficient decreased as the additive replacement ratio increased. It is judged that the pore-filling effect of concrete was due to the high fineness of GGBFS and FA. This was considered to be due to the effect of blocking the penetration of chloride ions while filling the capillary pores according to the formation of C–S–H hydrate by the latent hydraulic properties.Through evaluating the critical chloride content of the rebars embedded in concrete, it was found that the critical chloride content to induce rebar corrosion decreased as the admixture replacement rate increased. This was because the pH of concrete was reduced before hardening as the absolute quantity of cement decreased, and the performance of the passive film formed on the surface of the rebars was reduced.Applying the concrete chloride ion diffusion coefficient according to the additive replacement ratio and the additive type and the critical chloride content that initiates rebar corrosion in this study will enable a more accurate evaluation and prediction of service life compared to the use of conventional standards (0.4% of binder). As a result, the calculated service life of concrete was S3 89 years, TBC 60 years, S3 51 years, and OPC 26 years.It was confirmed that the service life of reinforced concrete is more affected by the chloride ion diffusion coefficient than the critical chloride content. However, it was confirmed that the effect of reducing the amount of critical chloride content of reinforced concrete according to the additive replacement ratio. In order to accurately design the durability of reinforced concrete structures using additives, it is considered that continuous research on critical chloride content is necessary.


This experimental research investigated the applicability of the liquid crystal display (LCD) by-product of the refining process as a sustainable and alternative alkali activator for ground granulated blast-furnace slag (GGBFS) blended cement concrete. Three levels of binder replacement using the industrial by-product, and four water/binder ratios were considered in order to evaluate the effects of the replacement in fresh and hardened properties of the blended concrete. XRD and TG analyses confirmed that the by-product that contains abundant alkali compounds promotes the reactivity of GGBFS. The test results indicated that the incorporation of the by-product results in delayed setting and degraded workability due to the highly porous nature of the by-product, yet shows rapid early-age strength development of the blended concrete as conventional alkaline activators for GGBFS. These characteristics shed light on a simple yet effective and practical means of reusing the industrial by-product as an alternative alkaline activator. It is well known that the replacement level of cement with SCMs depends on the reactivity, local availability, and legislation . For theproducts ,4,5,6,7—products ,9. 2O·rSiO2), sodium carbonate (Na2CO3), and sodium sulphate (Na2SO4) are effective and common ones used to activate GGBFS [Various alkali activators have been suggested for adequately promoting strength of blended concrete using SCMs to either partially or fully replace ordinary Portland cement (OPC). For example, it is well known that sodium hydroxide (NaOH), sodium silicate  waste glass to partially replace OPC [The current mainstream liquid crystal display (LCD) design primarily consists of color filter (CF) substrate glass on which RGB pixels are deposited and of thin-film-transistor (TFT) substrate glass that is painted with thin film circuitry that delivers signals to liquid crystal. In order to maintain a high quality and a high resolution, TFT uses an alkali-free glass that is obtained through a high refining process that involves the generation of by-product. Because the by-product of this refining process contains a large amount of alkali ingredients—such as SOlace OPC ,16,17,18lace OPC  tested uIn this study, the applicability of the LCD by-product of the refining process as an alkali activator was evaluated by characterizing the reactivity of GGBFS with OPC under a normal curing condition with the aim of developing practical applications. The binary paste was prepared by mixing GGBFS and OPC with the LCD by-product-based activator (LCDBA) and the variation of the hydration products in the paste, according to the curing age, was characterized through X-ray diffraction (XRD) as well as through thermogravimetry and differential thermal analysis (TG-DTA). In addition, fresh and hardened properties of OPC-slag concrete, activated by the alkali by-product, were assessed by examining the slump, bleeding, setting time, and compressive strength of concrete. The applicability of the LCDBA was investigated with the aim of developing practical applications as a sustainable and alternative alkali activator for GGBFS blended cement concrete. The activation effects of the LCDBA were characterized using GGBFS blended cement paste. In addition, the fresh and hardened properties of GGBFS blended cement concrete incorporating LCDBA were investigated.2/kg and 449 m2/kg and a density of 3150 kg/m3 and 2910 kg/m3, respectively. The major chemical components of GGBFS were CaO, SiO2, and Al2O3, as shown in 2 + Al2O3)) was 0.977, which is similar to the neutral value of 1.0 for ideal alkali activation [2O3)/SiO2) of GGBFS, was 1.92. This was higher than the value of 1.4, which is required for good hydration properties of GGBFS [2/kg and a density of 2540 kg/m3. XRD analysis was performed to determine the nature of LCDBA, as shown in 2SO4 and Na2SO4. The particle size distributions of GGBFS and LCDBA are shown in OPC (ASTM C 150 Type I) and GGBFS were used as binders to prepare the paste and concrete and their chemical compositions are summarized in tivation . The hydof GGBFS . The LCDNon-reactive river sand, with a specific gravity of 2.62, a fineness modulus of 2.77, and an absorption capacity of 1.1%, was used in preparation of all mortars and concrete. The crushed basalt aggregates were adopted as the coarse aggregate for the concrete mix in which the maximum size, specific gravity, absorption capacity, and fineness modulus were 25 mm, 2.63, 0.8%, and 6.4, respectively. In addition, a polycarboxylate-based superplasticizer with 17% solid content by weight was used to enhance particle dispersions within the mixture. The characterization of the reactivity of the binders was carried out based on XRD and TG-DTA tests using GGBFS blended cement paste with the OPC/GGBFS ratio of 55:45 and the water/binder ratio of 30%. LCDBA replaced the binder by 0%, 3%, and 5%. The reactivity of the paste with different LCDBA substitution levels was investigated through XRD and TG analysis. GGBFS blended cement pastes were cured at 20 ℃ and 90 ± 2% relative humidity for a predetermined curing duration . Thereafter, the samples were ground and immersed in acetone to stop hydration and were suction filtered using an aspirator. The crushed samples that stopped hydration were ground further and powdered to particles smaller than 106 μm for the XRD and TG measurements. XRD was conducted using a D/MAX 2500V/PC  with a scan range of 5°–65° 2θ. TG was conducted using a NETZSCH STA 409 C/CD  with a heating rate of 5 ℃/min in the 20–1000 ℃ range. The fresh properties of GGBFS blended cement concrete were measured using the slump, bleeding, and setting time. The slump of fresh concrete were measured in accordance with ASTM C 94 . The bleThe diffraction patterns of the hardened pastes were analyzed by characterizing the crystal phases in order to investigate the applicability of LCDBA with high alkali content for stimulating GGBFS. The activation effect of LCDBA for GGBFS can be demonstrated by investigating the generation of hydration products for different curing ages. 2Mg(Si2O7)) with strong peaks in the XRD analysis. It has been reported that akermanite exists in a crystalline form in raw materials and hardened GGBFS pastes [As can be seen in S pastes ,25 and t2)—is known to play a role in promoting the activation reaction of GGBFS [2 at 3 days decreases as the curing age increases through the consuming necessary for the activation of the GGBFS to form calcium-silicate-hydrate (C-S-H) gel. The pastes of the two series containing LCDBA also had high Ca(OH)2 at their early age and the amount decreased as the age increased. However, the decrease of Ca(OH)2 was smaller than that of LCDBA-0% series, although the C-S-H gel peak increased significantly. This phenomenon was the likely cause of the high alkaline LCDBA activator. In the section where 2θ is around 9°, it is known that ettringite peaks result from the hydration of cement [3, as with the high SO3 content in LCDBA, at 47.1%. In addition, Mohammed and Safiullah [3. In addition, the strong alkali compound of the cement hydration product—calcium hydroxide (Ca(OH)f cement . It shouafiullah  revealed2 to CaO [The degrees of hydration of GGBFS blended cement pastes were evaluated using the thermogravimetry method and the results are presented in 2 to CaO . 2, was relatively less consumed in the LCDBA-3% and LCDBA-5% mixtures due to the additional supply of alkaline compounds by LCDBA. In the meantime, it should be noted that the differences in mass change between the pastes with LCDBA and without LCDBA at 28 days were relatively large in Section I in comparison to those in Section II. This might be attributed to the fact that, as curing age increases, the alkali components supplied for the pozzolanic reaction of GGBFS in the LCDBA-3% and LCDBA-5% series were also consumed, resulting in a Ca(OH)2 decrease and reaching similar remaining levels of Ca(OH)2 as those of the LCDBA-0% series at 28 days of curing. From the results for Sections I and II, it can be seen that the weight losses of the LCDBA-3% and LCDBA-5% series are more pronounced than those of the LCDBA-0% series for all curing ages. Therefore, the large mass change in Section I implies that a large amount of C-S-H gel initially forms due to the incorporation of LCDBA that contains abundant alkali compounds that promote the reactivity of GGBFS. The large mass change in Section II can be explained that the cement hydration product, Ca(OH)The slump test is widely used and the most well-known test to assess the workability of concrete. In this study, the effect of the LCDBA usage on workability was evaluated using the slump test. The bleeding of concrete, a necessary part of the life of concrete, was considered to occur when the mix water would raise to the surface of freshly placed concrete. It has been reported that the bleed rate and capacity of GGBFS blended cement concrete highly depends on the GGBFS replacement level and the water/binder ratio . Figure The effect of the LCDBA replacement level on the initial and final setting times of GGBFS blended cement concrete is shown in The compressive strength development of GGBFS blended cement concrete with different LCDBA replacement levels and with water/binder ratios at 3, 7, 28, and 91 days is shown in The rates of increase in the compressive strength of the concrete incorporating LCDBA relative to the strength of concrete without LCDBA were evaluated for each curing age, with the results summarized in a and b are material constants considering the type of binders and curing methods, calculated in this research based on regression analysis using measured values. In addition, t and 28 days, respectively. In order to quantitatively analyze the strength developing characteristics of GGBFS blended cement concrete incorporating LCDBA, the compressive strength prediction model suggested in ACI 209 was used. The ACI Committee 209  recommenThe concrete mixtures with 5% LCDBA replacement and without LCDBA were considered to quantitatively illustrate the effect of LCDBA on the development of the compressive strength of concrete. a and b were used to further analyze the strength development patterns of the tested concrete. The calculated material constants a and b are illustrated in a and b considerably correlate with the strength development of concrete at early age and at long-term age, respectively [a is inversely proportional to the initial strength development and b is inversely proportional to the increase in compressive strength according to the curing age. As shown in the figure, a and b tend to decrease and increase, respectively, as the water/binder ratio increases. As the water/binder ratio decreases, the initial strength development rate becomes high, which leads to a decrease in a. On the other hand, the material constant b is related to the long-term strength development, where the lower b value stands for the higher long-term strength increment. The constant b values for the mixtures with LCDBA were similar, regardless of the water/binder ratio, and higher than those for the mixtures without LCDBA. The higher b values for the mixture with LCDBA were attributed to the higher initial strength development activated by LCDBA and to relatively less long-term strength development. This is similar to the strength development characteristics of GGBFS and/or fly ash blended cement concrete activated using conventional alkali activators. Therefore, it can be concluded that LCDBA is an effective and sustainable alternative to alkali activators for GGBFS blended cement concrete.As a result of the regression analysis of the compressive strength, according to the ACI 209 model, the R-squared values for the mixtures with and without LCDBA were higher than 0.985, indicating a high goodness of fit. With the high goodness of fit, the material constants ectively . Mathema(1)2 due to the stimulation of GGBFS hydrations with LCDBA as days of curing increase, were characterized using XRD analysis. This finding highlights the role of LCDBA as an activator for GGBFS blended cement concrete by providing the essential chemical evidence.The effectiveness of LCDBA as an alternative and sustainable alkaline activator for GGBFS blended cement concrete was demonstrated for the first time in this study. The formations of akermanite and ettringite, as well as the consumption of Ca(OH)(2)2, was relatively less consumed due to the incorporation of LCDBA that contains abundant alkali compounds that promote the reactivity of GGBFS. As curing age increased, the remaining amount of Ca(OH)2 in the pastes with LCDBA became similar as to the one in the pastes without LCDBA, which is another implication of the relatively less long-term strength development.The thermogravimetric analysis was employed to evaluate the degrees of hydration. The results highlight that a large amount of C-S-H gel was initially formed and that the cement hydration product, Ca(OH)(3)It is identified from this research that by incorporating LCDBA, the fresh GGBFS blended cement concrete showed degraded workability, delayed bleeding ends, reduced bleeding capacity, and delayed setting times, attributed to the porous nature of LCDBA that led to mix water absorption.(4)The series of compressive strength tests conducted in this research concluded that LCDBA was an effective alkaline activator for GGBFS blended cement concrete, showing early-age strength developing characteristics, especially for mixtures with lower water/binder ratios. The compressive strength model, suggested by the ACI Committee 209, also highlighted the early-age strength developing characteristics of the blended concrete activated with LCDBA.This experimental study evaluates the LCD by-product of the refining process, LCDBA, as an alternative and sustainable alkaline activator for GGBFS blended cement concrete. To investigate the applicability of this the alternative activator, the tested experimental parameters were set at three LCDBA replacement levels and four water/binder ratios. The activation effects were characterized based on XRD and TG analyses using GGBFS blended cement paste. The fresh and hardened properties of GGBFS blended cement concrete incorporating LCDBA were investigated using slump, bleeding, setting time, and compressive strength tests. The key observations and findings of this research can be summarized as follows:The results obtained in this study provide a simple, yet effective and practical, means of reusing an industrial by-product as an alternative alkaline activator for GGBFS blended concrete. Further studies are, however, necessary to determine its long-term durability and dimensional stabilities, such as shrinkage and creep.


Monodon monoceros) are considered to be among the most sensitive of Arctic endemic marine mammals to climate change due to their limited prey selection, strict migratory patterns and high site fidelity. In the context of climate change, we assume that the population dynamics of narwhals are partly influenced by changes in environmental conditions, with warm areas of increasing sea temperatures having lower abundance of narwhals. Using a unique large dataset of 144 satellite tracked narwhals, sea surface temperature (SST) data spanning 25 years (1993–2018) and narwhal abundance estimates from 17 localities, we (1) assessed the thermal exposure of this species, (2) investigated the SST trends at the summer foraging grounds, and (3) assessed the relationship between SST and abundance of narwhals. We showed a sharp SST increase in Northwest, Mideast and Southeast Greenland, whereas no change could be detected in the Canadian Arctic Archipelago (CAA) and in the Greenland Sea. The rising sea temperatures were correlated with the smallest narwhal abundance observed in the Mideast and Southeast Greenland , where the mean summer sea temperatures were the highest (6.3 °C) compared to the cold waters of the CAA (0.7 °C) that were associated with the largest narwhal populations . These results support the hypothesis that warming ocean waters will restrict the habitat range of the narwhal, further suggesting that narwhals from Mideast and Southeast Greenland may be under pressure to abandon their traditional habitats due to ocean warming, and consequently either migrate further North or locally go extinct.Arctic top predators are expected to be impacted by increasing temperatures associated with climate change, but the relationship between increasing sea temperatures and population dynamics of Arctic cetaceans remains largely unexplored. Narwhals ( Arctic marine mammals have the potential to move over long distances to adapt to changing and erratic resource availability. However, their capacity to adjust long-term adaptations, like site-fidelity and fixed migratory patterns, to climate-induced perturbations remains poorly known5.Climate change is affecting almost all regions and ecosystems, with the Arctic demonstrating the greatest, irreversible consequences on marine life. Rapid sea-ice loss and increasing temperaturesMonodon monoceros) has a large geographic range extending from the Canadian Arctic Archipelago (CAA) to East Greenland, Svalbard and the western part of the Russian Arctic11. Narwhals are known to exhibit a high degree of site-fidelity and to be closely associated with specific migratory corridors during spring and fall movements between summer and winter grounds12. During winter, narwhals are mainly found in offshore areas over deep water and often in areas completely covered with pack-ice with only leads available for breathing. In spring the narwhals move towards coastal areas. The inshore summer foraging grounds, where they congregate during the open water season, are considered the primary basis for identifying separate population units of narwhals13.Among Arctic cetaceans, the narwhal  compared to West  and East Greenland (~ 6400)18. In comparison, East Greenland is characterized by the southward flowing East Greenland Current which transports cold water masses that are originally derived from the Arctic Ocean but are mixed with coastal runoffs from melting glaciers along East Greenland19. In addition, warm and saline Atlantic waters flowing northward between Iceland and East Greenland (the Irminger Current) in the Denmark Strait occasionally reach the East Greenland shelf break20. In a context of climate change, we therefore might assume that the population dynamics of narwhals are partly influenced by changes in environmental conditions, with warm areas with increasing sea temperatures having lower abundance of narwhals. This is supported by the narrow temperature habitat usage observed in narwhals in East Greenland21.Cold and buoyant waters from the CAA enter northern Baffin Bay and are transported southward towards Davis Strait along the western part of Baffin Bay along the Canadian coast, while a warm and salty subsurface current along the West Greenland coast transports dense Atlantic waters northward towards northern Baffin Bay23.Live-capture operations of narwhals were conducted in collaboration with Inuit hunters in Northeastern Canada, West and East Greenland. Set nets of 40 to 80 m length and 5 to 8 m deep were deployed from shore to an anchor at suitable sites. Lookouts for whales were maintained from land-based promontories, from which the nets were kept under constant diurnal surveillance. As soon as there were indications of a whale being entangled, the net was released from the anchor and the whale pulled to the surface and towards the shore where instrumentation took place. Sex of the whales was determined based on presence  or absence  of a tusk. Various generations of Wildlife Computers  SLTDR, SPOT tags and FastLoc transmitters were mounted on the tusk or for the majority of the whales on the keratinized dorsal ridge of the whales with 2–3 delrin nylon pins (8 mm diameter) secured with nylon washers and bolts on each end24. The modelling approach of Albertsen et al.25 implemented in the R package argosTrack26 was applied to the tracking data to improve the estimation of the whale’s actual tracks from Argos locations. Tracks were estimated separately for each individual using a step-wise approach simplifying the estimation model if convergence issues were encountered, for instance for short tracks. Initially, the estimation assumed a continuous time-correlated random walk movement model with t-distributed measurement error. Variance parameters were estimated for each Argos location class. If the model did not converge properly, the ratio between variance parameters was fixed following the results of Albertsen et al.25. Subsequently, a multivariate normal distribution was used for the measurement error with and without free variance parameters. Finally, if a model still had not converged, a random walk movement model was used with and without free measurement variance parameters. In 2015, 2017 and 2018, Fastloc GPS transmitters were used and no estimation model was applied to their more precise GPS positions28. In order to assess temporal patterns, seasons were discriminated as follows: autumn from October to December, winter from January to March, spring from April to June and summer from July to September. To assess the influence of rising sea temperatures on narwhals we focused on the summer period which corresponds to peak of ocean temperatures in the Arctic.Location data were relayed through the Argos Data Collection and Location System and decoded using Argos Message Decoder . The least-square filtering algorithm was used for the Argos data until 2011, after which Kalman filtering was used. All statistical analyses were performed using R software version 3.6.2Global Ocean Physics Reanalysis Glorys S2V4 (PHYS 001-024) and the Global Ocean Physics Reanalysis Glorys12v1 (PHY-001-030) at a resolution of 0.08° (from E.U. Copernicus Marine Service Information) at each whale location. In order to generate time-series of SST and SIC between 1993 and 2018, monthly grids of both variables were also extracted from the products Global Ocean Physics Reanalysis Glorys12v1 (PHY-001-030) and Global Ocean and Physics Analysis Forecast (PHY-001-024) and averaged over the extension of each of 17 summer foraging grounds with narwhal aggregations. The monotonic SST trends were then assessed for each summer ground using the trend package29.We extracted environmental variables from model simulations to characterize the habitat experienced by the narwhals. The associated Sea Surface Temperature (SST) and Sea Ice Concentration (SIC) data were first extracted daily from the products 30. Abundance estimates that were obtained in previous studies  to SST, and assess the effect of temperature on the abundance and densities of narwhals. SST data in August (month of the abundance surveys) were extracted at each summer ground for each sampled year. The relationships between abundance and SST and whale density and SST were then investigated using a linear non-parametric Theil-Sen regression model from the mblm package31. To assess the relation between SST change over time and the abundance of narwhals, the SST slope derived from each summer ground over the entire period (1993 to 2018) was related to the estimates of narwhal abundance and density separately.Narwhals have strong site fidelity to their coastal summer grounds and narwhal aggregations are defined based on their summer distributionFrom 1993 to 2019, a total of 144 narwhals were satellite-tracked in summer in Canadian Arctic Archipelago (n = 68), West Greenland (n = 21) and East Greenland (n = 55)—see Fig. In summer, narwhals tracked from populations in West Greenland and in the CAA dispersed widely across Baffin Bay, northern Baffin Island and within the fjords of the CAA. The narwhals that were tracked from populations in East Greenland remained close to or just south of the Scoresby Sound summer ground (Mideast of Greenland).p < 0.001, Fig. p < 0.001). By comparison, narwhals in East Greenland experienced significantly warmer SSTs  and no sea-ice concentrations in summer  and ES  whereas it was steady for GS —see Fig. The SST trends on the summer grounds differed according to the areas Fig.  and are To test this hypothesis, we used a large dataset comprised of 144 satellite-tracked narwhals , sea sur−2), and lowest in the Mideast Greenland —See Table p < 0.001 for abundance and p < 0.05 for density). Similarly, Theil-Sen regressions were significant when considering only the latest estimate for each locality  in the same region32, and suggest a limited thermal preference of Arctic cetaceans. Despite the limited thermal range on both sides of Greenland, the temperature exposure was four degrees higher in East Greenland compared to West Greenland and the Canadian Arctic Archipelago (CAA). Increasing water temperatures and sea-ice loss are expected to strongly modify the seasonality, distribution, and concentration of prey targeted by apex predators such as the narwhal and the bowhead whale, thus, potentially threatening the survival of these Arctic cetaceans33.We have demonstrated that narwhal densities are highest for a narrow range of sea temperatures. These results are in agreement with a previous study conducted on bowhead whales (Boreogadus saida), Arctic cod  and squid (Gonatus fabricii) in all areas, and in Baffin Bay they also target Greenland halibut (Reinhardtius hippoglossoides)34. A recent study in the Chukchi Sea showed that the abundance of the small-size cod  peaked between 4 and 5 °C35, and cold temperatures (< 2 °C) are known to favour the growth of the juvenile Arctic cod36. On the wintering grounds in Baffin Bay, narwhals are assumed to be feeding on Greenland halibut that are most abundant at cool bottom temperatures of 0.5–1.0 °C37. Over the long-term, increasing water temperature might therefore reduce the prey biomass available for narwhals, forcing this species to shift habitat or prey.Narwhals feed on polar cod  that prevents excessive heat loss and functions as thermal insulation and energy reserve39. Cetaceans dispose excess heat from poorly insulated peripheral areas, such as fins and tail flukes, that are utilized as thermal windows through which heat can be exchanged via conduction and convection40. Similar to bowhead whales, narwhals maintain thick blubber layer and lack a dorsal fin to serve as a thermal window for dissipating excess heat. As oceanic temperatures rise, these extreme adaptations that enable polar living may serve as a liability for narwhals, especially as the ice cover becomes more unpredictable41, and preferred prey move to new areas or depths. Their limited physiological flexibility also prevents them from adjusting their swimming and diving behaviour to climate change via shifts in habitats and prey selections41.A question also remains regarding the direct consequence of oceanic warming on the physiology of this cold-adapted species by over-heating. With a thermal conductivity of water 25 times that of air, heat loss in marine mammals is much faster than in air of the same temperature21. The blubber insulation evidently protects the whales from hypothermia but the thermal niche also suggests that excess heat production during elevated locomotion activity can be a problem for the whales. Unlike bowhead whales, narwhals show a limited behavioural plasticity in their movement patterns30. Bursts of high levels of exercise and consequent heat production in connection with normal foraging behaviour or due to anthropogenic disturbance exacerbate the problem of temperature regulation. Together, thick blubber insulation, the lack of a dorsal fin coupled with a warming environment may limit the ability of Arctic cetaceans to remove excess heat and prevent hyperthermia. The strong site fidelity to their summer grounds might also limit their ability to adapt to a changing environment. Narwhals from East Greenland are in a particularly challenging situation due to the elevated temperature optimum compared to West Greenland and the CAA. Based on this, further studies are needed concerning the thermal physiology of Arctic cetaceans in general.Studies of thermal habitat preference in narwhals have shown an extreme selection of a very narrow temperature range where the whales avoid water masses with temperatures above 2 °C18, the cold CAA waters originate from the polar basin, ice melt and river discharges42, which explains the stable temperatures. Similarly to the Northwest, Mideast Greenland was characterized by a sharp temperature increase over time, as the result of warm Atlantic waters flowing northward between Iceland and East Greenland20. In addition, the southward transport of multiyear sea ice from Fram Strait along East Greenland has been severely reduced over the three past decades43.A sharp increase in sea temperature was observed in the Northwest, Mideast and Southeast of Greenland, whereas no change occurred in the CAA, which is in agreement with the predictions of thermal suitable habitats. Unlike the warm and saline Atlantic waters that are responsible for the rising temperatures in Northwest Greenland44. Similarly, new abundance estimates of about 16,000 and 13,000 narwhals in the cold regions of Smith Sound and Jones Sound have not been documented before and these estimates are extremely high compared to past information from these areas47.Considering the extreme dependency of narwhals on cold water habitats, it is perhaps not surprising that the largest narwhal abundances are found in areas that meet these specifications, and that localities where increasing sea surface temperatures have been detected, host the smallest populations. Recent survey efforts have documented surprisingly large abundances of narwhals in areas that have not been surveyed before, but from where little or no historical evidence of narwhal concentrations is available. These areas include Dove Bay, Northeast Greenland, Smith Sound and Jones Sound, and although no systematic efforts to document narwhal populations in these areas have been conducted, the new abundance estimates indicate a possible shift in distribution. In Dove Bay, for instance, a 3-year expedition from 1906 to 1908 failed to detect any narwhals, whereas a survey conducted in 2017 estimated approximately 2000 narwhals in the bay49. Trajectories of trends for narwhal populations in Mideast and Southeast Greenland show with high probability that these populations have never been large compared to populations in CAA and Northwest Greenland. Due to their low present abundance they are particularly vulnerable to overexploitation13. Southeast Greenland is at the same time the area with the most pronounced increases in SST. In comparison with the larger narwhal populations in the CAA and Northwest Greenland. The small size of the populations and increasing SST emphasizes the need for restrictive management of the exploitation of the populations in Mideast and Southeast Greenland. Independent of the history of exploitation, the magnitude of the differences in population sizes reflects the actual importance and habitat suitability of the localities. Of particular significance is the narwhal population in Southeast Greenland that is affected by a regime shift in oceanography with warming temperatures in coastal areas and a reduced transport of polar pack-ice along the East Greenland coast. Although excessive hunting occurs in Southeast Greenland, the decline or disappearance of narwhals from previously used summer grounds and the shift of hunting effort to more northern and presumably colder areas indicates that Southeast Greenland may no longer be a suitable habitat for narwhals50.Trends in narwhal populations due to habitat changes are difficult to assess as some of the populations are also hunted, which affects population trends to varying degrees51 or a blubber layer52. Cetaceans endemic to the Arctic also lack a dorsal fin, which in boreal species serves to dissipate heat53. These morphological specialisations allow travel in ice-covered areas, but may represent a morphological handicap for transferring excess body heat compared to sub-Arctic cetacean species54 such as the harbour porpoise and humpback whale. Warmer temperatures could therefore represent a potential thermal challenge for Arctic cetaceans with no dorsal fin such as narwhals and bowhead whales, and warrants further investigation.By combining telemetry data to abundance estimates and sea surface temperatures we were able to assess (1) the thermal exposure, (2) the SST trends at the summer foraging grounds, and (3) the relationship between SST and abundance of a cold-adapted species, the narwhal. Despite the observation of widespread increase in temperature over the Arctic, the SST time series (from 1993 to 2018) indicate different trends across the summer grounds, with a noticeable correlation between increasing sea temperatures and the whales’ abundance. These results support the hypothesis that warming ocean waters will restrict the habitat range of this Arctic cetacean, further suggesting that narwhals from Mideast and Southeast Greenland may be under pressure to abandon their traditional habitats due to ocean warming, and consequently either migrate further North, or locally go extinct. In addition to indirect effects on their distribution, rising temperatures may affect the whales through physiological stress. To survive in cold environments, polar marine species have developed morphological adaptations to provide thermal insulation through dense plumage, thick furSupplementary Information


Two hypotheses were described to explain the change of pore structure change expansive mortar. The results also indicate that the carbonation resistance and frost resistance were improved by the uniaxial restrained condition. Furthermore, the effect of the restrained condition must be considered to evaluate not only the experimental results of the expansive concrete with a high EX replacement level but also the expansive concrete combining other cement replacement materials.This paper presents the results of an experimental investigation of the effect of the restrained condition on the mechanical properties, frost resistance, and carbonation resistance of expansive concrete with different water–binder ratios. In this study, length change ratio test, expansion strain test, compressive strength test, mercury intrusion porosimetry test, underwater weighing test, freezing–thawing test, and accelerated carbonation test were performed to evaluate the mechanical properties, pore size distribution, total porosity, and durability of expansive concrete under both restrained and unrestrained conditions. The test results indicate that the length change ratio and expansion strain of the expansive concrete were controlled by the restrained condition. The compressive strength of expansive concrete was enhanced by the triaxial restraining when the amount of expansive additive was 40 kg/m Concrete is one of the most common widely used materials in structure construction because of its advantages, such as high performance, durability, and low cost. However, concrete has a major unfavorable property, which is drying shrinkage . It is wExpansive concrete has been applied to slabs, pavements, shrinkage-compensating concrete structures, etc. . Conside3 of concrete. However, as a standard amount in Japan, EX is known as 20 kg/m3 of concrete. Similar to the results reported by Tsuji et al., Nguyen et al. [Several studies were conducted to investigate the effect of restrained conditions on the expansive concrete properties. Tsuji et al.  reportedn et al.  found thn et al.  found a Therefore, the main objectives of this research are: firstly, studying the influence of both uniaxial and triaxial retrained conditions on the mechanical properties, pore structure change, carbonation resistance and frost resistance of expansive concrete; secondly, grasping these effects to obtain a correct assessment of the experiments on expansive concrete in a laboratory. The mold was designed to restraint the expansion of the expansive concrete in a triaxial restraint for the compressive strength test. A restrained mold was used to evaluate the length change ratio and the expansion strain of cement and expansive concrete according to JIS A 6202 . The undThe material properties are arranged in 3. Concrete and mortar were prepared with water–binder ratios of 0.3 and 0.5, respectively. The concrete samples were used for the tests on the length change ratio, expansion strain, underwater weighing, compressive strength, and accelerated carbonation under both free and restrained conditions. The mortar samples were used to determine the pore size distribution using the MIP test.3 and 75 3 were used. The specimens were demolded at 24 h after casting to avoid steel mold confinement. An embedded strain gauge was installed into the center of the unstrained specimens to measure the expansion strain for the free condition . The unrestrained mortar was cast in prism molds measuring 40 × 40 × 160 mmed molds . At the 3); 3); 3); Many studies ,10,11,122 cylinders at different conditions  to evaluate the effect of the restrained condition on the compressive strength of concrete. The unrestrained concrete was demolded 24 h after casting and covered by a plastic sheet to cure at 20 3, which was restrained using two steel bars to connect with a steel plate at the specimens’ ends. However, these molds could only confine the concrete in one direction  and did not consider the vertical direction. To address this limitation, the concrete was cast in the steel molds to restraint three directions. The vertical direction was restrained by connecting the two-steel plate using four steel bars (The compressive strength was measured on eel bars . Both th3 under the free and restrained conditions (n cycle (Hz); In this test, the frost resistance of concrete was determined according to the JIS A 1148  with dimnditions . The fun3. The carbonation depth was measured by spraying a phenolphthalein solution on the test surface after 13 weeks of exposure to an accelerated carbonation condition  for 13 weeks The length change ratio and expansion strain of concrete with and without an expansive additive were controlled by the restrained condition.(2)Under the restrained condition, the pore size distribution of the expansive mortar shifted to a smaller size, which can be explained by two hypotheses. First, the microspore in the cement–expansive paste is filled with crystal ettringite. Second, the effect of chemical stress is caused by the expansive additive hydration.(3)3 of concrete at a w/b ratio of 0.5. The compressive strength of the restrained concrete was 12% higher than that of the unrestrained concrete at 28 days.The total porosity of the expansive concrete was decreased by the restraining when the amount of EX was 40 kg/m(4)The enhanced frost resistance of the expansive concrete was clearly observed at the w/b ratio of 0.3. However, at the w/b ratio of 0.5, the frost resistance of the expansive concrete was enhanced by restraining for EX40.(5)The concrete carbonation depth was not observed at the w/b ratio of 0.3. For the w/b of 0.5, the carbonation resistance of the expansive concrete was improved by restraining.(6)3 concrete) or concrete combining EX with other cement replacement materials .It is essential considering the effect of the restrained conditions in evaluating the various experimental results of the expansive concrete with a large expansive additive dosage (i.e., over 20 kg/mThe following major conclusions are drawn based on the results and discussion in this study:


This prospective cohort study aims to investigate the incidence, related factors and prognosis of IgG4-related disease (IgG4-RD) with malignancies in the Chinese cohort. We prospectively analyzed the IgG4-RD patients recruited in Peking Union Medical College Hospital from January 2011 to August 2018 and identified patients diagnosed with IgG4-RD complicating malignancies. Data regarding demographics, clinical features, treatment and prognosis of IgG4-RD patients complicating malignancies were collected and compared to those of age- and sex-matched controls. Among the 587 Chinese patients with IgG4-RD, 17 malignancies were identified. Ten of them developed malignancy after the diagnosis of IgG4-RD, given a standard incidence ratio (SIR) of 2.78 (95%CI 1.33–5.12). Multivariate logistic analysis indicated that autoimmune pancreatitis  was positively associated with malignancy, whereas eosinophilia  was negatively related with malignancies. During a median follow-up period of 61.4 ± 26.4 months, all patients with IgG4-RD and malignancies survived. We conclude that an increased incidence of malignancy was found in Chinese IgG4-RD cohort. Autoimmune pancreatitis is a potential risk factor, whereas eosinophilia is a possible protective factor for complicating malignancies. Their mass-like clinicopathological presentations and radiologically 18F-FDG-avid hypermetabolic lesions has made it to be one of the great malignancy mimickers2. Previous studies have reported that a spectrum of malignancies occur in association with IgG4-RD, including solid tumors located in the lung, pancreas, gastrointestinal tract, and prostate, as well as lymphoma10. Moreover, it is difficult for clinicians to make a diagnosis of IgG4-RD because it can manifest as mass lesions, leading to an occasional misdiagnosis of malignancy. The relationships between these two diseases remain unclear and are the subject of on-going research. However, the mechanism underlying the co-occurrence of IgG4-RD and malignancies has not been fully determined to date.ImmunoglobulinG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that is typically diagnosed by clinicopathological presentations of enlarged organs, elevation of serum concentrations of IgG4 and pathological findings such as a typical dense lymphoplasmacytic infiltration enriched in IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis5, while studies from Asia, Europe and America have also suggested an increased standardized incidence ratio of malignancy in patients with IgG4-RD10. However, one study from Japan reported no significant increase in the risk of malignancy8. No epidemiological data for malignancies in Chinese IgG4-RD patients is available. It is also important to know the risk factors and prognosis for IgG4-RD patients harboring malignancies.Wallace reported an increased standardized prevalence ration of malignancy history in IgG4-RD patients11, sex disparities12, radiographic presentation13 and histopathologic features14 of patients with IgG4-RD in our cohort. The present study focused on the association between IgG4-RD and malignancies. We sought to describe the incidence and clinical characteristics of malignancies in patients with IgG4-RD. Based on these results, significant factors were evaluated to determine whether they were related to malignancy. Treatments and survivals were also generated to characterize the prognosis.Our team at Peking Union Medical College Hospital (PUMCH) established an IgG4-RD cohort in 2011. In previous studies, we prospectively described the clinical characteristics1. Malignancies were diagnosed histopathologically by biopsy or resected specimens according to the International Classification of Disease (ICD-10) criteria. Patients with IgG4-RD and malignancy diagnosed at the same time were defined as malignancy diagnosis within 1 year’s duration of IgG4-RD diagnosis. Patients with malignancy history or newly diagnosed malignancy were defined as >1 year before or after the diagnosis of IgG4-RD. To identify the risk factors for malignancies in patients with IgG4-RD, We randomly selected sex and age match IgG4-RD patients without malignancies as controls at a ratio of 3:1 from our cohort. This study was approved by the Medical Ethics Committee of Peking Union Medical College Hospital (No. S-K412) and was complied with all ethics committee requirements. Written informed consent were obtained from all patients and/or their legal guardians.We consecutively collected data on patients with IgG4-RD and malignancies who were prospectively enrolled in the IgG4-RD cohort in PUMCH from January 2011 and June 2018. IgG4-RD was diagnosed according to the 2011 comprehensive diagnostic criteria for IgG4-RDBaseline data concerning demographics, past medical and personal histories, organ involvement and laboratory findings were recorded. Past medical histories included allergy, smoking histories. Laboratory findings were obtained from individual patients when they first diagnosed with IgG4-RD at our institution. Treatments for both IgG4-RD and malignancies were documented. All patients recruited in our cohort were consecutively followed-up in our rheumatology clinic every 3 to 6 months. Death and causes of death were determined by direct contact with the attending clinician or reported by telephone followed-up.16. Continuous variables were summarized as the means ± standard deviation (SD) or medians and interquartile range (IQR), and categorical data were presented as frequencies (percentages). The Wilcoxon rank sum test and chi-squared tests for independence were utilized to evaluate significant differences in continuous data and categorical data, respectively. To identify risk factors for malignancy in IgG4-RD patients, univariate and stepwise multivariate logistic regression analyses were performed. All statistical analyses were performed with SPSS software (version 23.0).The standardized incidence rate (SIR) was calculated by dividing the observed newly developed malignant rate by the expected rate. Expected malignancies were calculated by age-stratified malignancy incidence (cases per 100000 person-year) in general Chinese population multiplying the corresponding number of patients in each age-group. The data of sex- and age- stratified cancer incidence in general population were published before by the Chinese National Cancer CenterA total of 587 IgG4-RD patients in the PUMCH cohort were consecutively enrolled in this study. Seventeen patients were identified as having malignancies Table , Fig. 1.There were 4 (23.5%) patients reported a previous history of malignancy, and the other 13 (76.5%) patients developed malignancies at or after the diagnosis of IgG4-RD. According to the 2011 comprehensive diagnostic criteria for IgG4-RD, 8 (47.1%), 8 (47.1%) and 1 (5.8%) case were diagnosed as definite, probable and possible IgG4-RD cases, respectively  in this Chinese cohort. Figure Baseline clinical characteristics in patients with and without malignancies were compared as shown in Table Based on initial comparison results listed above, head and neck involvement, autoimmune pancreatitis and eosinophilia were related factors for having malignancies in IgG4-RD patients. As shown in Table The mean initial dosage of corticosteroids  was 40.1 ± 10.0 mg/d in IgG4-RD complicating malignancy patients comparing to 32.4 ± 17.5 mg/d in controls. Among the seventeen IgG4-RD complicating malignancy patients, ten (58.8%) patients received immunosuppressive agents, including cyclophosphamide , mycophenolate mofetil , azathioprine , iguratimod  leflunomide  and methotrexate . Sixteen patients underwent resection therapy, with one lymphoma received chemotherapy. During a median follow-up period of 61.4 ± 26.4 months, all patients with IgG4-RD and malignancies survived. Two IgG4-RD patients without malignancy in the control group died due to liver failure and respiratory failure caused by other comorbidities.To our knowledge, the present study is the first to report reliable data of Chinese IgG4-RD patients complicating malignancies and describes the largest cohort of IgG4-RD patients. We demonstrated malignancy incidence and distributions in IgG4-RD patients. Clinical characteristics of IgG4-RD patients with malignancy were compared, and potential risk and protective factors for IgG4-RD patients with malignancy were detected. We also summarized the prognosis of these patients.8. In contrast, other studies from Japan, the United States, the United Kingdom and South Korea10 have reported that IgG4-RD patients have a higher prevalence or incidence of malignancies. Similar to those studies, our study confirmed a total malignant SIR of 2.78 (95%CI 1.33–5.12) in Chinese patients.The question of whether IgG4-RD patients are at an increased risk of malignancy has not been fully answered yet. As shown in Fig. 8 gastric cancers17 and prostate cancers5, respectively, which may be due to geographic differences. Only one lymphoma case out of 17 malignancies were observed in our study, whereas a South Korean cohort reported 4 lymphoma cases 3.When clinical physicians treat IgG4-RD patients, it is important to know what malignancy is most likely to occur. Our study reported that in Chinese IgG4-RD cohort, the most prevalent solid tumour was located in the gastrointestinal tract, followed by the thyroid, urinary system and breast. Different malignancy distributions were observed in studies from other countries, with the highest reported incidences of lung cancers8 and IgG4-RD onset age >65 years8. This difference might be due to selection of controls, and the results need to be confirmed by larger and prolonged observational studies. Previous study detected that the presence of AIP was more closely associated with extra-pancreatic cancer than pancreatic cancer itself 20. And most cancer cases detected in AIP occur at or within a year of diagnosis19. These results are in line with our findings that AIP is a potential risk factor for complicating malignancies. K-ras gene mutations have been detected in the gastrointestinal tract in AIP patients, indicating pancreatic tissues of AIP patients might share similar immune responses with cancer21. Furthermore, cancer and pancreatic tissues of AIP patients with cancer share key immune responses leading to the enhancement of IgG4 antibody production17. These might contribute to the pathogenesis of AIP complicating with malignancies. Notably, we also found a potent independent protective indication for malignancy in IgG4-RD patients: eosinophilia. It was reported that a high proportion of patients have longstanding allergies, peripheral blood eosinophilia and serum IgE elevation and T helper type 2 responses was presumed to be pathogenic in IgG4-RD, which might indicate a close relationship between allergy and IgG4-RD22. Elevated serum IgE and peripheral eosinophilia may predict risk of flare after treatment, while a dominant eosinophilic infiltrate is not common in IgG4-RD involved organ23. In the present study, multivariate logistic regression analysis confirmed eosinophilia were significantly negative related to malignancy in IgG4-RD . This indicates the heterogenetic characteristics of IgG4-RD patients and subgroup analysis are needed24. No difference was observed between the serum IgG4 level between IgG4-RD patient with and without malignancies in this study. Prior findings demonstrated that mild elevation  of IgG4 has been observed in 5% to 15% of pancreatic carcinoma patients, and high levels of IgG4 were more specific for autoimmune pancreatitis (AIP)26. Controversially, Wallace5 and Asano6 reported that IgG4-RD patients with malignancy demonstrated a higher IgG4 serum level than IgG4-RD patients without malignancy. One possible explanation for the lower serum IgG4 levels in IgG4-RD-CA patients is that IgG4-RD, as a paraneoplastic syndrome, is able to induce limited elevations of IgG4 and atypical IgG4-related disease6. Additional studies evaluating the appropriate cut-off level of serum IgG4 concentrations affecting IgG4-RD prognosis and what kind of malignancies are more likely to accompany mild IgG4 elevation are required.Chinese IgG4-RD-CA patients have distinct clinical features. In this study, they were more prone to have autoimmune pancreatitis (AIP) and less likely to have head and neck gland involvement. Moreover, eosinophilia was less common in IgG4-RD-CA patients than in controls. Of note, other risk factors were reported including DM by Hirano’s groupTo our knowledge, no report has previously described the mortality and prognosis of IgG4-RD-CA patients. In the present study, during 61.4 ± 26.4 months of continuous follow-up, all IgG4 patients with malignancies survived. Although IgG4-RD patients had an increased incidence of malignance, the periodical follow-up and detailed examination of the recruited patients in our cohort might lead to an early detection and treatment of malignancy and improved the prognosis.27. Our study showed that almost half of patients developed malignancies in the IgG4-RD background. Moreover, Asano et. al reported 12 patients experiencing malignancies in the same organ affected by IgG4-RD out of 27 IgG4-RD-CA patients6. It could be because IgG4-RD causes sustained inflammation that may induce preferable cancerous microenvironments, which resembles the mechanism of lymphoma development in association with Sjögren’s syndrome28. However, it has been reported that surgical resection of cancer was able to cause remission of IgG4-RD29, indicating that IgG4-RD might be a type of paraneoplastic syndrome1. Overall, it is still too early to draw a definitive conclusion of the pathogenesis of IgG4-RD and malignancies. Nevertheless, our study provides the critical information for physicians that IgG4-RD-affected organs should be carefully screened for potential malignancy occurrence during follow-up.The pathophysiology of IgG4-RD complicating malignancy is still under investigation. It is well established that long-standing chronic inflammation plays a critical role in the development of cancer through the process of inflammation-associated carcinogenesisThere are some limitations of this study. First, we only included consecutive patients from 2011 to 2018, and had not conducted an extensive long-term follow-up to the endpoint of death. Second, this is a single-center cohort study, and an increased number of patients should be continuously recruited. Third, this is a clinical observational study, and we did not investigate the detailed pathophysiology of these two disease entities, and further research in this field should receiving more attention.In conclusion, this prospective cohort study demonstrated that Chinese IgG4-RD patients have a 2.78-fold increased risk of having malignancy over a median of 61.4 months of follow-up. The most common malignancy site was the gastrointestinal tract. Autoimmune pancreatitis was identified as a potential risk factor for IgG4-RD patients having malignancy, while eosinophilia as protective indicators.