A re-analysis of single cases of culture-proven or culture-negative sepsis failed to demonstrate any association between deaths and a delay or insufficient antibiotic use in the intervention period. In conclusion, AS is feasible in preterm VLBW neonates and antibiotic use can be safely reduced.There is insufficient data regarding antimicrobial stewardship (AS) and outcomes of very low birth weight (VLBW) neonates after AS programs. This observational, retrospective study addressed AS and outcomes of VLBW neonates admitted to an Italian level-three center. Two periods were compared: (i) baseline, before AS (January 2011–December 2012) and (ii) intervention, after AS (January 2016–December 2017). Between these two periods, procedures were put in place to inform medical and nursing staff regarding AS. There were 111 and 119 VLBW neonates in the baseline (6744 live births) and in the intervention period (5902 live births), respectively. The number of infants exposed to antibiotics (70%) during the hospital stay did not change, but the total days of therapy  and DOT/1000 patient days (302 vs. 215) decreased in the intervention period ( Neonatal sepsis is a serious and potentially fatal illness; early diagnosis and prompt treatment is essential to prevent life threatening complications. Antibiotics play a pivotal role in the treatment of neonatal infections and are the most commonly used drugs in the neonatal intensive care unit (NICU) . Both eaAntimicrobial stewardship (AS) refers to a series of coordinated interventions, which aim to minimize the unintended consequences of antimicrobial use , while maintaining the safety of the patient . AS progThere are insufficient studies regarding AS in neonates. Impact and safety of AS programs for neonates are not clearly defined, particularly in neonates with a lower birth weight , who aren = 2; transfer to another hospital prior to discharge, n = 6) and two neonates in the intervention period .A total of 230 VLBW neonates (111 in the baseline and 119 in the intervention period) were enrolled. A few neonates were excluded from the study because of missing data on antibiotic treatments: eight neonates in the baseline (late admission from another center p = 0.68) VLBW neonates admitted to the hospital. During the intervention period, 48 h rule-out courses of first antibiotic treatment increased (antibiotic treatments lasting ≤ 72 h are shown in the footnote) and the median duration of first antibiotic treatment decreased. Furthermore, in the intervention period the total days of treatment (DOT) and DOT/1000 patient days decreased. There was a 29% reduction in DOT/1000 patient-days.p < 0.01) and a 37% decrease in the use of gentamicin . Furthermore, use of teicoplanin decreased  and oxacillin use increased . The use of piperacillin and tazobactam decreased . There was no significant change in the use of vancomycin, third generation cephalosporin, and carbapenem between the baseline and intervention periods.p < 0.01), and higher median days of therapy .A sub-analysis was carried out in neonates with a low risk of sepsis. Case fatalities  within 72 h of birth were six at baseline and eight in the intervention period. All cases were given broad-spectrum antibiotics from birth to death. Case fatalities  after 72 h of life were five at baseline and nine in the intervention period. There were four case fatalities due to LOS (one at baseline and three in the intervention period). A re-analysis of single cases of culture-proven or culture-negative sepsis failed to demonstrate any association between the deaths and a delay or insufficient antibiotic use. In both periods, no deaths were due to culture-proven sepsis that presented within 14 days after discontinuing a previous antibiotic treatment. One death at baseline was due to a culture-negative sepsis. Finally, two neonates (one at baseline and one in the intervention period) died because of LOS presenting at three and four days of life, respectively. These newborns were not given antibiotics at birth because of a cesarean section before labor with intact membranes.Recently, safe strategies have allowed a significant reduction of unnecessary antibiotic use in apparently healthy full-term newborns at risk of EOS through quantitative risk estimates and serial physical examinations ,17. In cIn the current study, the total number of infants exposed to antibiotics (70%) during the entire period of hospitalization did not change. This is not surprising, since VLBW infants are a small but high-risk infectious population, in which the use of antibiotics, albeit by short courses, is common. However, the antibiotic use decreased significantly, and DOT/1000 patient days were reduced by 29%. The decline in antibiotic use is comparable to the 27% observed in a recent prospective study which, however, focused on the AS strategy for neonates with a higher gestational age (less than 35 weeks of gestation) admitted to a US NICU . The stuIn this current study, the decrease in antimicrobial therapies in the intervention period was mostly driven by the reduction of the prolonged antibiotic treatments at birth. This decline was more apparent in neonates with a higher birth weight and occurred without any significant increase in re-institution of antibiotic therapies. Although the rate of short antibiotic courses was only 44% in the intervention period (likely because the intervention was close to a training period), the clinicians’ awareness regarding the safety of an early discontinuation of antimicrobials was reached gradually by the staff. Indeed, during the intervention period most neonates (59%) undergoing a prolonged antibiotic course actually received antibiotics for ≤72 h, and a further reduction in the duration of antibiotic courses continued even after the study period. However, the vast majority of 48 h rule-out courses at birth were unnecessary. It remains a challenge for future studies to investigate and identify the few infants at very high risk of EOS that need to be treated with antibiotics. Furthermore, some glycopeptides  not recommended by AS programs were fully replaced, while reduced antibiotic use was particularly evident for some drugs ; however, the use of third generation cephalosporins and vancomycin was not reduced. The unchanged use of vancomycin was not unexpected, since even in the baseline period the first-line antibiotic for LOS was not vancomycin, but rather teicoplanin, which was fully replaced by oxacillin during the intervention period. Finally, because culture-negative sepsis by definition requires an antibiotic treatment of at least five days, and because some antibiotic courses during the intervention became shorter, the number of cases who met the definition of culture-negative sepsis obviously decreased (from 22% to 11%).Each case of culture-proven or culture-negative sepsis was also re-analyzed; in fact, one of the major concerns of clinicians regarding AS is that giving shorter antibiotic treatments at birth or narrowing the antibiotic spectrum may be associated with an increased risk of infectious relapses and neonatal deaths. We failed to demonstrate any association between deaths and insufficient antibiotic use. However, two neonates with a low risk of EOS died in the baseline and in the intervention period because of a very early LOS . Both were untreated at birth because of a low risk of EOS, as also recently suggested by others ,23. HoweThis study has some potential limitations. Firstly, our results may not be generalizable to other settings with different personnel, structures, and patient mixes . Furthermore, there is a limitation inherent to retrospective studies with historical comparison. From the baseline to the intervention period additional changes in the therapeutic management of VLBWs (such as improved care) may have occurred. However, the time interval between the two periods in the study is very close, making it unlikely that relevant additional changes had occurred. In addition, although some large studies have shown a reduction in LOS after AS programs , we weren = 6744) and (ii) intervention (after AS was implemented), from 1st January 2016 to 31st December 2017 (live births n = 5902). Between these two periods, procedures were put in place to inform the medical and nursing staff of the NICU regarding the AS. A review of the EOS and LOS cases and antimicrobial susceptibility of pathogens was initially launched in the entire region [This observational, retrospective study was carried out in the NICU of the University Hospital of Modena, Italy; this is a high-volume level-three facility, with inborn neonates accounting for most admissions. The NICU contains 20 cots, receives 450 admissions per year, and the medical staff consists of 12 physicians. The study project was approved by the local ethics committee (Protocol AOU 0002163/19). The study concerns VLBW neonates, who were admitted to the NICU during two periods: (i) baseline (before AS), from 1st January 2011 to 31st December 2012 . Among these were newborns that were referred from another hospital or transferred to another center, since it was difficult to assess a possible re-institution of antibiotic therapies. Neonates who were given topical antibiotics were also excluded from the analysis.Data were collected retrospectively by accessing the following sources: Vermont Oxford Network (VON) database and the NICU computerized medical records . The following maternal and neonatal characteristics were evaluated: intrapartum antibiotic prophylaxis (IAP) administration, mode of delivery, group B streptococcus antenatal screening , risk faThe following data were recorded: the timing of the initiation of the first antibiotic treatment and its duration, the drug used as the first course and any reinstitution and, finally, the overall duration of antibiotic therapies during hospitalization.Very low birth weight (VLBW): neonates with a birth weight under 1500 g.Adequate intrapartum antibiotic prophylaxis (IAP): antibiotics  administered ≥4 h prior to delivery .CRIB score : neonatal mortality risk estimate score based on variables such as birth weight, gestational age, presence of congenital malformations, maximum negative base excess (BE) in the first 12 h, minimum and maximum oxygen fraction (FiO2) administered in the first 12 h .EOS or LOS: clinical sign of sepsis and yield of a pathogen from blood or cerebrospinal fluid prior to (EOS) or after 72 h of life (LOS).Coagulase-negative staphylococci (CoNS) were included in the list of pathogens causing sepsis if infants had clinical signs of sepsis, 2 positive blood cultures (collected within 48 h) or antibiotics (glycopeptide or semisynthetic penicillin) were given for ≥5 days ,32,33.Culture-negative sepsis: sterile cultures and clinical signs or abnormal laboratory values that could be consistent with sepsis in a neonate who received ≥5 days of antibiotics .Low risk of EOS: neonates born before labor and with an intact membrane, delivered for maternal reasons , without a clinical or histological diagnosis of chorioamnionitis.Sepsis-related death: death occurring within 7 days from the positive blood culture or clearly related to complications due to sepsis .First antibiotic treatment: indicates the first treatment during the hospital stay, whether at birth or in the following days.48 h rule-out course: antibiotic administration for 48 h in neonates with clinical signs of sepsis or abnormal laboratory test results and sterile cultures.Reinstitution of an antibiotic treatment: a new antibiotic course administered within 14 days after discontinuing (for at least 24 h) the previous course . For eac® version 9.3 .Analyses were performed using STATA/SE 14.2  and MedCalcp < 0.05 for 2-sided tests.For descriptive data comparisons, the Mann–Whitney test was used for non-parametric continuous data and the χ2 test or Fisher exact test for categorical data. Non-parametric continuous variables are summarized as medians with quartiles (25th and 75th percentiles). Categorical variables are presented as percentages. The threshold for statistical significance was Days of therapy (DOT): number of doses of antibiotic multiplied by the time interval between doses then divided by 24 h .DOT/1000 days of hospitalization-patient: DOT divided by the total duration of hospitalization of all patients then multiplied by 1000 .The use of antibiotics was calculated as follows:This study shows that AS is feasible in preterm VLBW neonates and antibiotic use can be safely reduced. Nevertheless, close monitoring of antibiotic therapies and careful and continuous vigilance of neonatal outcomes are necessary.


Our results show a strong correlation (R² = 0.78) between fragmentation (seff) within and around N2k sites. This result applies to all biogeographical regions in Europe. Only a narrow majority (58.5%) of N2k sites are less fragmented than their surroundings. Remote and mountainous regions in northern Europe, the Alps, parts of Spain, and parts of eastern Europe show the lowest levels of fragmentation. These regions tend to hold the largest N2k sites as measured by area. In contrast, central and western Europe show the highest fragmentation levels within and around N2k sites. 24.5% of all N2k sites are classified as highly to very-highly fragmented. N2k PA age since initial protection does not correlate with the difference in exterior and interior fragmentation of N2k PAs. These results indicate that PAs in Europe are not sheltered from anthropogenic pressures leading to fragmentation. Hence, we argue that there is a high potential for improving PA efficacy by taking pre-emptive action against encroaching anthropogenic fragmentation and by targeting scarce financial resources where fragmentation pressures can be mitigated through enforced construction bans inside PAs.Habitat loss from anthropogenic development has led to an unprecedented decline in global biodiversity. Protected areas (PAs) exist to counteract this degradation of ecosystems. In the European Union, the Natura 2000 (N2k) network is the basis for continent-wide conservation efforts. N2k is the world’s largest coordinated network of protected areas. However, threats to ecosystems do not stop at the borders of PAs. As measured by a landscape fragmentation metric, anthropogenic development can affect the interiors of PAs. To ensure the long-term viability of the N2k network of PAs, this paper attempts to quantify the degree to which N2k sites are insulated from development pressures. We use a comprehensive dataset of effective mesh density ( Theory of Island Biogeography .s.sseff)2 and contains a value representing effective mesh size (meff) calculated via CBC procedure [Nomenclature des unités territoriales statistiques, NUTS), which divides each EU Member State into three hierarchical regions. The data set comprises all countries at a 1:1 million scale. We used NUTS level 3 to investigate landscape fragmentation across the EU. Data on N2k sites encompass the Special Areas of Conservation (SAC) and the Special Protection Areas (SPAs) of the European Union, including the UK. In addition, each N2k site has information listed on its location within Europe’s biogeographical regions. To determine the age of N2k PAs, we used information provided by the World Database of Protected Areas (WDPA)  . From thmeff values for each N2k site, we first filtered the N2k site dataset to ensure each N2k covers at least one cell center of the meff raster dataset. To do so, we rasterized all N2k sites via cell center coverage using the 1-km2-resolution of the original meff dataset. This method entailed excluding N2k sites which did not cover at least one raster cell center. These were particularly small and elongated N2k sites. We also reduced our analysis to terrestrial PAs by excluding marine N2k sites. These exclusions resulted in a dataset comprised of 15390 N2k sites of the original 27845 N2k sites (55.3%).All spatial data were processed using ESRI ArcGIS 10.6.1 and QGIS 2.18.25 in ETRS 89 Lambert Azimuthal Equal Area (LAEA) Projection. To calculate 2-resolution of the original meff dataset. This approach has the advantage that each cell of the meff dataset is assigned only once and never to both a N2k site and a buffer. For fine-scale analyses focusing on the effects of PA surroundings on specific species, buffer size is often determined by migration or dispersal distances or habitat size requirements of those species [We created a buffer zone of 5 km around each of these N2k sites. We further applied the same rasterization process to these buffer zones as to the N2k sites using cell center coverage based on the 1-km species . However species  have sho species  and surr species . As in tmeff) and effective mesh density (seff) for each N2k site individually, we first summed up the meff values of all grid cells (1-n), the cell centers of which fell within the N2k site. Since meff is area-proportionately additive [meff value for each N2k site by dividing the sum of meff values within the N2k site by n, the total number of cells within the N2k site  and added We further calculated the median vidually . This prMany of the N2k sites were already protected prior to the establishment of the N2k network in 1992. We used each site’s age since first designation as a PA. To determine the age of N2k sites, data on protected areas from the World Database of Protected Areas (WDPA)  were intStatistical analysis was performed in R v. 3.6.2 . We assiseffsurrounding) served as the predictor variable and the effective mesh density within the N2k sites (seffwithin) as the response variable. The data were log (x+1) transformed to meet normality requirements. We also created nine individual linear regression models relating seffsurrounding and seffwithin to the nine biogeographical regions covered by N2k sites. To analyse the relationship between the area of N2k sites and fragmentation within N2k sites, we conducted linear regressions using N2k site area as the predictor and seffwithin as the response variable.We conducted linear regressions using the lm function to examine the relationship between fragmentation of N2k sites and their surroundings. The effective mesh density of the surroundings of N2k sites (seffwithin) and outside a N2k site (seffsurrounding) by subtracting seffwithin from seffsurrounding for each N2k site separately ) showing linearity, homoscedasticity, and no substantial influence of extreme values.To test for correlation between site age and the difference of fragmentation within and around N2k sites, we first calculated the difference between mesh density inside a N2k site  and mainly located in northern Europe, the Alps, and parts of Romania (seffwithin and seffsurrounding ≤ 0.9 meshes per 1000 km2) (6.9%) are almost exclusively found in remote and mountainous regions of the EU  are negatively correlated .The sizes of the N2k sites analysed in this study vary greatly between the smallest (1 km²) and largest site (5556 km²). The majority (90.1%) of all N2k sites cover an area between 1 km² (5% quantile) and 243 km² (95% quantile). Large N2k sites are mainly located in remote and mountainous regions of the EU . N2k sitrn Spain . N2k areWe also compared the number of N2k sites to the cumulative area covered by N2k sites for the different fragmentation categories . N2k sitseffwithin) based on the fragmentation of their surroundings (seffsurrounding). The results show a strongly significant relationship between seffsurrounding and seffwithin  , Macaronesian (R2 = 0.32) and Pannonian (R2 = 0.46) regions, which are also characterized by relatively small sample sizes  . We also regions . seffsurle sizes . For allffwithin .N2k sites analysed in this study differed in age between 2 and 37 years. Young N2k sites are predominantly located in eastern European member states, especially Croatia, which joined the EU in recent years. In contrast, the oldest N2k sites are predominantly located in Spain, France, Italy, Greece, Denmark, and the Netherlands .seffdiff) within and around N2k sites . In other words, N2k sites are not significantly less fragmented compared to their surroundings the longer their protected status has been in place. This result contradicts our original hypothesis.There is no significant correlation between N2k age and the absolute difference in effective mesh density  and effective mesh density (seff), with a resolution of 1 km². However, it was necessary to apply a filter to ensure that each N2k site analysed covers at least one 1 km2 raster cell-center containing information on meff and seff. This led to the exclusion of several small or elongated N2k sites. Despite their requisite exclusion, these small N2k sites are an important component of the N2k network. They can be vital habitats for confined or for small-range species, or they may contribute to landscape complementation and overall habitat diversity [meff and seff directly using OpenStreetMap (OSM) data [While our data show that the vast majority of N2k sites 93.1%) are fragmented to some degree, limitations in our study design led to the exclusion of a large number of sites from our analysis. We used pre-processed data on the effective mesh size (3.1% are iversity . Furtheriversity  and mighiversity –65. TherSM) data ,—we coulPrevious studies have demonstrated the N2k network’s low effectiveness in protecting certain target species –69. Our seffdiff) was found. It is possible that too little time has passed since PAs within the N2k network gained PA status for protection to have had a measurable effect in mitigating fragmentation pressures. The oldest PAs tested are no more than 37 years old and many N2k sites have only recently acquired protected status. This is especially true for N2k sites located in eastern European member states such as Bulgaria, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia and Slovenia, which have been members of the EU only since 2004 [We hypothesized the difference between exterior and interior fragmentation of N2k PAs to be bigger the longer protected status has been in place, reflecting effective PA management even if anthropogenic fragmentation in PA surroundings continues unabated. However, contrary to our original hypothesis, no correlation between PA age and the difference of fragmentation outside and inside the PA  inscribing a ban of additional development inside N2k sites into law; b) putting additional resources into enforcing bans on constructions inside N2k sites; and c) where possible, removing extant fragmenting infrastructure.Our data show that large N2k sites of low fragmentation tend to be located where topography limits human infrastructure development. One reason for this phenomenon might be that establishing PAs in sparsely populated, mountainous, and far-northern landscapes is often easier and cheaper than in alternative locations. There is typically less pressure to use this land for agriculture or urban expansion. Low fragmentation is mainly found in remote regions, such as the Black Sea, Steppic, Macaronesian, Pannonian, or Boreal regions, as well as in mountainous regions such as the Alpine region. In fact, many N2k sites in mountainous regions have escaped anthropogenic fragmentation altogether, within and around N2k sites, highlighting the effect of topographical constraints.At the country level, Sweden, Finland, and Romania manifest low or very low levels of fragmentation. However, in contrast to Sweden and Finland, Romania is in the process of expanding its road and rail infrastructure which will increase fragmentation in the future . Some ofTarget 11 of Aichi Biodiversity Targets, which aims to protect 17% of terrestrial area in each signatory country, results in a common and politically expedient conservation strategy of protecting those areas in which political and economic development pressures are weakest . ProtectS1 Figseffwithin (A) and seffsurrounding (B) for each N2k site. The coloration of N2k sites represents one of five fragmentation categories (http://www.esri.com/software/arcgis/arcgis-for-desktop).Fragmentation within N2k sites (A) and in their surroundings (B). We calculated tegories . Map gen(TIF)Click here for additional data file.


An online nationwide survey was applied to 153 specialists, who were selected randomly. A descriptive, bivariate analysis and a logistic regression model were undertaken. In total, 88.9% of the specialists reported TDM availability and 21.57% reported access to results within 6 h. TDM was available mainly for vancomycin. We found that 85.62% of the intensivists had some type of institutional protocol; however, only 39.22% had a complete and socialized protocol. The odds of preferring extended infusions among those who did not have institutional protocols were 80% lower than those with complete protocols, OR 0.2 (95% CI: 0.06−0.61). The most important perceived barriers to performing continuous infusions and TDM were the lack of training and technologies. This pioneering study in Colombia could impact the quality of care and outcomes of critically ill patients in relation to the threat of antimicrobial resistance.Therapeutic drug monitoring (TDM) and continuous infusion strategies are effective interventions in clinical practice, but these practices are still largely unknown in Colombia, especially in the critical care setting. This study aims to describe the practices involved in the administration and TDM of  Antibiotic therapeutic drug monitoring (TDM) refers to the individualization of drug dosages by maintaining plasma drug concentrations within a targeted therapeutic range, which is based on pharmacokinetic (PK) and pharmacodynamic (PD) properties ,2,3. TDMβ-lactams are the antibiotics most frequently used and measured in plasma in the intensive care unit (ICU) setting, because of their antimicrobial spectrum and their PK/PD characteristics [Vancomycin and eristics ,8. Vancoeristics ,10. The eristics . Rybak eeristics .β-lactams increased the achievement of the target plasma concentrations and significantly improved the clinical cure rate [With reference to β-lactam’s TDM literature status, studies have shown positive results in terms of clinical cure rates , a shorter mean duration of invasive ventilation, the achievement of PK parameters and an easier dose guidance process, particularly in critically ill patients or patients undergoing renal replacement therapy ,14,15,16ure rate .β-lactams [Clinical practice guidelines recommend the use of extended or continuous infusions and the use of TDM with early obtainment of plasma concentration results between 24−48 h after the start of treatment with vancomycin or -lactams ,18,19,20-lactams ,22,23. L-lactams ,26,27,28-lactams ,31,32,33Antibiotic TDM is a novel intervention which is expanding and gaining a place in clinical practice, especially in the critically ill patient context . SeveralA descriptive cross-sectional study with an analytical component was conducted. A national survey was designed based on 12 general questions from the ANTIBIOPERF study  , PI if between 2 to 4 h, and intermittent infusions if less than 30 min. Each participant provided only their email address as the only personal data collected and they all voluntarily provided informed consent for the completion of the survey. To improve the response rate, participants were informed that they would enter a sweepstakes for 3 gift vouchers after the end of the study to avoid bias in the results. The resources for these incentives were provided by the researchers and do not represent any conflict of interest. This study was approved by the research and ethics subcommittee  of the Universidad de La Sabana.® electronic platform Data were exported from the SurveyMonkeyA variable of interest, entitled “approach to clinical cases”, was created based on the seven questions of the clinical knowledge section of the survey (question 16–22). This variable was calculated by assigning a value of 1.5 to a correct answer for question 16–21 and a value of 0.1 to a correct answer for each of the ten vignettes of the 22 questions, giving a total score of 1 for this question. The last question (question 22) had less value because it was related to non-clinical issues that do not usually belong to the intensivist’s field of experience. The final continuous score was between 0 and 10. A dichotomous outcome variable was created based on questions 17, 18, and 20, according to the respondent’s preference for using continuous infusion or PI. If a participant reported the use of continuous or prolonged infusions in 2/3 or 3/3 questions, they were recorded as having a preference for prolonged infusions; otherwise, they were categorized as having a preference for intermittent infusions. Correct answers were based on the literature ,34.p-value < 0.05 in Wald tests). Odds ratios (ORs) were calculated based on the the exponentials of the coefficients obtained by the final model. A significance level of 0.05 and a confidence level of 95% were chosen.Initially, a descriptive analysis of the information was performed using means and standard deviations for continuous quantitative variables with a normal distribution, and medians with interquartile ranges for continuous quantitative variables with another distribution. Categorical variables were described with absolute and relative frequencies. The association between administration practices and TDM was explored with the “approach to clinical cases” variable  and a variable based on the preference for the use of continuous or prolonged infusions (Mann-Whitney U test and Chi-squared test). A logistic regression model was used to explore associations in which the preference to use continuous or PI was included as an outcome variable. Sociodemographic and clinical practice data were the independent variables. Questions about perception were excluded from the model due to their absence of biomedical and epidemiological significance . VariablOf the 255 registered intensivists, 153 were selected randomly, with a response rate of 100%. Participants had a median age of 43.11 years with a median of 10 years of experience; 67.97% were men; 53.59% worked in a university hospital, most of them in a medical ICU. Only 30.72% had received formal education about the use of antimicrobial therapies and 19.60% (30/153) did not report any type of training in this area. The participation by cities was distributed as follows: Bogotá 31.37% (48/153); Medellin 11.11% (17/153); Manizales and Pereira 7.19% each (11/153); Cali 5.88% (9/153); Cartagena and Cúcuta 3.92% each (6/153); Bucaramanga and Sincelejo 3.27% each (5/153); Armenia, Barranquilla, and Pasto 2.61% each (4/153); Floridablanca and Popayán 1.96% each (3/153); Montería, Neiva, and Piedecuesta 1.31% each (2/153); and Chía, Chinchiná, Dosquebradas, Girardot, Ibagué, Magangué, Puerto Colombia, Santa Marta, Soledad, Valledupar, and Villavicencio only registered participation of 0.655 each (1/153) .β-lactams TDM , with a low proportion of tams TDM .Of the specialists, 22.2% reported pharmaceutical support, with a median of 3 visits per week of the infectious disease specialists. The results showed that 131/153 (85.62%) of the intensivists had some type of institutional protocol; however, only 39.22% had a complete and socialized protocol. Likewise, the specialists who have protocols in their institution but without information related to the stability of the drugs (incomplete protocols) represented 35.29% of the total of specialists surveyed (54/153) . In 8.5%Pseudomonas aeruginosa and sepsis, with 78.43% (120/153). Regarding the objective value of the area under the curve over the minimum inhibitory concentration (AUC24/MIC) in critically ill patients with methicillin-resistant Staphylococcus aureus infections, only 54.24% (83/153) gave the correct answer (400−600 mg H/L). In regard to the last question, regarding the maximum number of hours  that an antibiotic is stable in an infusion solution, meropenem was the antibiotic on which the intensivists had the most knowledge, with 40.52% (62/153), and cefazolin was the one that they knew the least, at 11.11% (17/153).We found that 71.9% of the intensivists involved in the study preferred prolonged or continuous infusions. The median of the clinical cases approach score was 4.9/10, obtained based on the sum of the scores of each question regarding the loading dose and preference as to the use of PI in clinical cases and PK/PD targets. Only 10 people obtained a score greater than eight (the highest was 9.55). In regard to these questions, 33.33% of intensivists (51/153) reported the use of β-lactam loading doses for all types of infusions in cases of severe infections, compared to 20.26% (31/153) who said they never used them. The clinical case in which there were more incorrect answers was the prescription of vancomycin for bacteremia with MRSA and sepsis, at 72.54% (110/153), and the clinical case that had the most correct answers was the prescription of piperacillin-tazobactam for urinary tract infection by β-lactams improved the prognosis of patients with severe sepsis and that the scientific evidence pointed in this direction (The main perceived barrier for choosing continuous or PI was the lack of training of personnel in this practice (35.29%). On the other hand, 56.21% of those surveyed considered that the lack of technologies for measuring antibiotic levels was the main barrier to performing TDM in their hospitals. Finally, most intensivists (69.28%) considered that the prolonged and continuous infusion of vancomycin and irection .p-value < 0.05) , p-value < 0.05.Regarding the bivariate approach, crude analysis suggested an association between the use of institutional protocols and TDM availability with the score obtained by the “approach to clinical cases” ( < 0.05) . Initial < 0.05) . Our finβ-lactams and vancomycin in ICU settings in Colombia, representing an approach towards understanding the preferences and decisions made by critical care specialists in their daily practice. Its results could impact clinical practice, quality of care, and possibly the outcomes of critically ill patients within the framework of the antimicrobial stewardship strategies.ANTIBIOCOL was the first nationwide survey evaluating the administration of prolonged and continuous infusions and drug monitoring of In our study, most of the participants were men between the ages of 21 and 40 in a 2:1 ratio compared to women, with informal education about antimicrobial stewardship, a median clinical experience of 10 years, and a monthly dedication of approximately 200 h, which demonstrated a high level of experience and workload. The origins of the surveyed physicians were diverse and included the main cities of Colombia, which shows that the random selection of the participants allowed the inclusion of different geographic territories and different levels of clinical experience.β-lactams and vancomycin above other administration methods [Concerning administration practices, the majority of participants considered that a prolonged or continuous infusion of beta-lactam antibiotics and vancomycin improved the prognosis of their patients, and this is sustained by current evidence. This information is consistent with the proportion of physicians that use continuous infusion in Colombia (71.9%). Nevertheless, there are still many physicians who prefer bolus infusions over prolonged or continuous infusions, and this finding correlates with the lack of training of medical staff in this practice. We can find similar results in France, where 77% of the participants were convinced of the value of using continuous infusion for  methods . Nonethe methods ,36,37.β-lactams remains an underused practice in Colombia, with the usage of TDM restricted to vancomycin and only in some cases to β-lactams, such as meropenem, piperacillin tazobactam, ampicillin sulbactam, and ceftazidime. Similar findings were obtained in other studies, especially in the only paper that included countries from Latin America [β-lactams [Regarding TDM, we conclude that performing TDM for  America . Other s-lactams . In our Not only is the availability of TDM among the hospitals vital, so are the waiting times between sampling and the obtainment of results. Our study showed that results took more than 24 h to arrive in 30% of the reports. This should be considered another barrier to the use of TDM, since long waiting times to receive the results discourage clinicians from performing it; the main objective of TDM usage is to optimize dosing, meaning that results should be immediately available or at least take less than 24 h to enable decision-making as quickly as possible. Another obstacle found was the general knowledge gap regarding the use of continuous infusions in real clinical contexts, as well as PK/PD therapeutic targets and the stability of antibiotics, which could be explained by the lack of technology in many cases, because the evidence is recent and there are no clinical practice guidelines at a national level.Even though conducting an analytical exploration was not the main objective, striking data were found. The main analytical result of this research indicates that the availability of complete institutional protocols with additional information significantly predicts the preference for continuous infusion and PI by intensivists. The availability of these protocols, even if they were incomplete, was above the values reported in other studies ,30,31,32This is a cross-sectional study that has limitations in determining causal association. In consequence, this research is an initial approach to describing practices and barriers, suggest possible action areas, and acting as the starting point for future research. Moreover, due to the absence of a list of every intensive care specialist in the country, the selection of the sample was made through the specialists registered in the AMCI, which is recognized as a limitation of this study. Additionally, non-significant results do not necessarily indicate a lack of association but may be due to the sample size that was initially calculated to obtain proportions . However, despite the above, the significant associations found reflect the strength of the association. Another strength of this study is the representativeness of the random sample that support the external validity of the study for Colombia, which included big and small cities, unlike similar studies from other countries that performed convenience sampling.β-lactams, vancomycin, and other antibiotic groups in the ICU setting. Likewise, future experimental or observational research should be carried out to assess clinical outcomes with the implementation of protocols involving continuous infusion and TDM practices, along with encouraging physicians to follow clinical guidelines or internal protocols to increase the accuracy of antimicrobial use among critically ill patients. Considering the barriers found among clinicians concerning the use of continuous or extended infusions, these should also be assessed in order to achieve higher rates of clinical cures and to reduce toxicity based on the available evidence on this practice.This study is the first of its type in a Latin American country and included the design of a survey adapted to the Colombian context and its needs, as well as addressing barriers pertaining to public health decision-making. In addition, this study can provide a starting point for further research regarding the correct methods used to perform TDM of β-lactams was not available, which reflects a lack of relevant technologies in the country, recognized by specialists as the main barrier for its use. This technological gap not only affects the applicability of the evidence in the clinical context, but also impacts the degree of general knowledge about these practices. Other hurdles, such as scarce training and socialization of complete protocols, predict the possibility of choosing this type of administration for antibiotics. The findings described above may facilitate the development of interventions that influence these practices and the outcomes of critically ill patients, in favor of current antimicrobial stewardship strategies.This present paper is the first of its class in Colombia, involving a representative sample of intensive care specialists with vast clinical experience, who recognize continuous infusions as the preferred administration strategy to improve the prognosis of patients. Vancomycin was the most frequently monitored antibiotic and, for the most part, TDM for


Differentiation between cerebral glioblastoma multiforme (GBM) and solitary brain metastasis (MET) is important. The existing radiomic differentiation method ignores the clinical and routine magnetic resonance imaging (MRI) features.To differentiate between GBM and MET and between METs from the lungs (MET-lung) and other sites (MET-other) through clinical and routine MRI, and radiomics analyses.t-test or the chi-square test was used to assess the differences in the clinical and radiological characteristics between the training and internal validation cohorts. Receiver operating characteristic curve analysis was performed to assess the performance of developed models with the area under the curve (AUC).A total of 350 patients were collected from two institutions, including 182 patients with GBM and 168 patients with MET, which were all proven by pathology. The ROI of the tumor was obtained on axial postcontrast MRI which was performed before operation. Seven radiomic feature selection methods and four classification algorithms constituted 28 classifiers in two classification strategies, with the best classifier serving as the final radiomics model. The clinical and combination models were constructed using the nomograms developed. The performance of the nomograms was evaluated in terms of calibration, discrimination, and clinical usefulness. Student’s The classifier fisher_decision tree (fisher_DT) showed the best performance  for distinguishing between GBM and MET in internal validation cohorts; the classifier reliefF_random forest (reliefF_RF) showed the best performance  for distinguishing between MET-lung and MET-other in internal validation cohorts. The combination models incorporating the radiomics signature and clinical-radiological characteristics were superior to the clinical-radiological models in the two classification strategies . The nomograms showed satisfactory performance and calibration and were considered clinically useful, as revealed in the decision curve analysis.The combination of radiomic and non-radiomic features is helpful for the differentiation among GBM, MET-lung, and MET-other. Cerebral glioblastoma multiforme (GBM) and solitary brain metastasis (MET) are the most common brain tumors in adults . Both GBTo date, studies aimed at the differentiation between GBM and MET have mainly shown two tendencies. The first tendency is to improve the performance of imaging modalities, and the second is to explore the differences among METs from different primary sites. For the first tendency, many imaging modalities have been proposed, including routine MRI and various advanced MRI modalities, such as magnetic resonance spectroscopy, diffusion-weighted imaging (DWI), diffusion tensor imaging, diffusion kurtosis imaging, perfusion-weighted imaging (PWI), arterial spin labeling, and amide proton transfer-weighted imaging . For theRadiomics analysis has been proven to be useful in the diagnosis, prognosis assessment, and prediction of therapeutic responses in cancers by extracting exhaustive features from medical images . It has To date, the existing studies on the differentiation between GBM and MET have only focused on radiological data without consideration of clinical factors. Analyses of MET subtypes mainly considered the radiomic features without the routine MRI features. In addition, the subtypes of METs to be differentiated were not consistent in the existing studies. Of all METs, the top primary tumor is lung cancer (>50%) . TherefoThis retrospective study was approved by the committees of two institutions; the need for obtaining informed consent from the patients was waived.Cerebral GBM was searched in the pathological database of our institution between January 2014 and December 2015. The inclusion and exclusion criteria are shown in Solitary supratentorial MET was searched in the pathological database of the two institutions between January 2010 and December 2017. The inclusion and exclusion criteria are shown in 1. The edema ratio was calculated by dividing the peritumoral edema by the tumor size. The location (left side/right side) was also reviewed by an experienced radiologist. The detailed scanning protocol and parameters are shown in All patients underwent MRI scanning within 2 weeks before cerebral operation. The tumor size was represented by the maximal diameter on the postcontrast axial image. Peritumoral edema was represented by the maximal diameter of the high signal around the tumor on the axial T2-weighted image (T2WI). The two parameters were manually measured using the Neurosoft PACS software2 version 3.x, we opened the postcontrast axial sequence for each case and manually drew the outline of the enhanced lesion on each slice showing the tumor, which was saved as the segmented region of interest (ROI). The segmentation was performed by a radiologist with 14 years of experience and reviewed by another radiologist with 28 years of experience. Any discrepancy was resolved through discussion. The details of the drawing are illustrated in Using the ITK-SNAP softwareThe radiomic features were extracted using PyRadiomics, which is an open-source python package for the extraction of radiomic features from medical images . For eacFirst, we randomly selected 50 patients and translated  and rotated (3° in clockwise and anticlockwise directions) their ROIs to evaluate the stability of the features through the intraclass correlation coefficients (threshold = 0.8). After the prescreening, all features were standardized using the z-scores derived from the training cohort. Thereafter, seven feature selection methods were used, including information theoretical-based feature selection: conditional mutual information maximization (CMIM), minimal-redundancy and maximal-relevance (MRMR), and double input symmetrical relevance (DISR); similarity-based feature selection: Fisher score and reliefF; and sparse learning-based feature selection: multi-cluster feature selection (MCFS) and robust feature selection (RFS), to recognize the most discriminating features. For each feature selection method, we ranked the features by their relevance score, and the best features were selected for the later classifiers.Four algorithms were used to build the radiomics model: logistic regression (LR), support vector machine (SVM), decision tree (DT), and random forest (RF). These algorithms were implemented on the basis of the selected features and classification categories. The LR algorithm was used by tuning the regular term and penalty term. The SVM algorithm was used by tuning the penalty and gamma of the kernel function, where the kernel function is “rbf.” The DT algorithm was used by tuning two parameters: the maximum sample of the leaf and the maximum node. The RF algorithm was used by tuning the number of DTs and the maximum sample of the leaf. Fivefold cross validation was used for all 28 classifiers. The optimal classifier served as the final radiomics model. These algorithms were implemented using the Python version 3.6.5 “scikit-learn” package.GBM model). To distinguish MET-lung from MET-other, we used the same method to obtain the clinical-radiological model . The clinical and routine radiological characteristics and radiomics signature were integrated to construct the combination models using the LR algorithm, and the optimal model was selected using AIC with a stepwise regression algorithm .The clinical characteristics (patient age and sex) and the routine radiological index  were used to construct the clinical-radiological model for differentiating between GBM and MET using an LR model  curve analysis of each model was performed, and the areas under the curve (AUCs) were calculated in both the training and validation cohorts. The optimal cutoff value in the training cohort was applied to obtain accuracy, sensitivity, and specificity. The DeLong test was used to evaluate the statistical differences between the models. All assessments were performed in both the training and validation cohorts.Nomogram analysis was applied to assess the potential clinical utility of the combination models. Calibration curves were drawn to evaluate the degree of deviation between the predictions and actual outcomes obtained using the Hosmer–Lemeshow test. Additionally, to evaluate the clinical utility of the nomograms, we performed a decision curve analysis by calculating the net benefits at different threshold probabilities .t-test or the chi-square test between the training, internal and external validation cohorts. P- values of <0.05 were considered to indicate a significant difference. The Spearman correlation coefficient was used to assess the relationship between the clinical and radiolocial characteristics and radiomic features. Statistical analysis was performed using IBM SPSS Statistics version 22.Patient age and sex, tumor size, and edema ratio were compared between the patients with GBM and MET and between those with MET-lung and MET-other using Student’s n = 193) and an internal validation cohort (n = 97) with a ratio of 2:1. In addition, the patients with MET were also randomly divided into the training (n = 92) and validation cohorts (n = 46) at a ratio of 2:1. The second institute included 30 patients with GBM and 30 patients with MET, which were used as the external validation cohort.The first institution included 152 patients with GBM and 138 patients with MET, which were randomly divided into a training cohort  and 0.759 (95% CI: 0.548-0.971) in the internal and external validation cohort, respectively . The violin figures of all models in the training and validation cohorts are shown in We summarized the performances of the clinical-radiological characteristics in the two classification strategies in ectively . For disl models . In partP > 0.05 for all cohorts, Hosmer–Lemeshow test, GBM nomogram when the threshold probability was >6% . In addition, the predictive performance of the combinationGBM model improved compared with that of the clinicalGBM model when the radiomicsGBM signature and clinical-radiological factors were combined. However, the DeLong test showed no significant improvement . This indicates that the radiomics signature can be used as a signal predictor to obtain satisfactory results. For differentiation between MET-lung and MET-other, and the performance of radiomicsMET model significantly better than that of the clinicalMET model . The combinationMET model also showed a better predictive performance than the clinicalMET model, and the DeLong test showed significant improvements in the internal validation cohorts (P = 0.019), which suggested that the radiomics signature can increase the predictive power of clinical factors. Based on the results of the two classification strategies, we observed that radiomics analysis has a superior classification ability in differentiating tumor types, which is consistent with previous study findings  not on other images, such as T2WI, et al. This is due to the different findings on different MRI images. For low-grade gliomas, they usually show no or partial enhancement, without or with minimal peritumoral edema. They are low signal intensity on post-contrast T1WI. Therefore, it is difficult to outline the border of the tumor on post-contrast T1WI images. On T2WI, however, low-grade gliomas are high signal intensity and prone to the identification of the tumor border. That is why many research studies segmented low-grade gliomas on T2WI . GBM, hoThere are several limitations of this study. First, the radiomic imaging data used were only T1 enhanced sequences. Other sequences, including T2WI, DWI, and PWI, may contain additional functional and biological information; therefore, more imaging modalities should be taken into account for future research. Second, although the number of cases in our study was relatively large, the MET-other cases involved many origins, with each origin having a small case number. More detailed subgroups based on the primary origin of METs should be considered in future studies. Finally, this was a retrospective study. Although we used external validation to reduce the impact, the prospective multi-center study was still required.Our study suggests that radiomics analysis has a superior classification ability in the differentiation among GBM, MET-lung, and MET-other. The combination of radiomic and non-radiomic features is helpful for the differentiation of these three types of tumors.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Beijing Tiantan Hospital. Written informed consent for participation was not provided by the participants’ legal guardians/next of kin because: As a retrospective study, it was approved by our institute committee without the informed consent of the patients.YH and LZ performed the study design, information collection, statistical analysis, and manuscript editing. HZ, YX, and XC guided and study design, reviewed images, and revised the manuscript. SN, SC, and BY provided the technical support. HC, FZ, and YZ collected the images and clinical information. 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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Corrosion of reinforced concrete (RC) structures costs the UK GBP 23b annually and is one of the main durability problems contributing to the development of rust, spalling, cracking, delamination, and structural deterioration. This paper intends to demonstrate the benefit of using tailored self-healing bacteria-based concrete for RC corrosion minimisation and service life increase. The purpose was to evaluate the enhancement in the lifespan of the structure exposed to a harsh marine microenvironment by utilising a probabilistic performance-based method. Comparison is made with the performance of a commercially available solution and in terms of embodied carbon impact. Three different concretes, using CEM I 52.5N, CEM II/A-D, and CEM III/A, were tested with and without an iron-respiring bioproduct (BIO) and an added admixture corrosion inhibitor (AACI). Results show that bioproduct significantly contributes to service life increase of RC structures with CEMIII/A. The repair solution with self-healing behaviour not only increases RC service life, but also enables us to decrease the required cover thickness from 60 mm to 50 mm in an XS2 chloride environment. In both XS2 and XS3 environments, a comparison of CEMIII/A+BIO and CEMII/A-D+AACI concrete shows the benefit of using bioproduct in corrosion inhibition context, besides contributing to an embodied carbon reduction of more than 20%. The durability of reinforced concrete (RC) structures in terms of corrosion is now of significant concern. The maintenance and repair cost of the UK’s existing structures is approximately ~GBP 40 billion/year, with the majority of structures being made using RC. High labour costs related to infrastructure maintenance are incurred; on the other hand, damage to nature may typically be self-healed, and the durability of structures increased; therefore, learning from nature is crucial. Such impacts on infrastructure occur globally, for instance, in India, where RC corrosion costs between 3–4% of the annual national gross domestic product (with an upward trend due to increased construction levels and lack of regulation).There is currently a significant gap between predicted and real behaviour of structures, as real behaviour is not yet well understood ,2. As a The concepts of durability design of RC structures ,7,8,9 anThis economic and environmental burden can be reduced through better evaluation of RC lifecycles and by using durable materials. Performance parameters allow the desired functions of the constructive solutions to be identified and clearly defined, contributing to the optimisation of the quantity of materials needed and reducing carbon consumption. Performance-based approaches are the future of standards; however, to support the designer in the decision-making process, a great deal of knowledge is required.Structures mimicking nature and self-healing are of great interest, with the durability assessment of concrete being crucial for understanding the expected service life. Self-healing materials have the capability to repair themselves back to their original state . In the Corrosion of steel is the primary cause of these structures’ degradation and is caused by the environmental conditions around them. Apart from For an autonomous self-healing function, materials could be categorised as bacterial, polymers, and chemical compounds  . Little (a)Anode-acting inhibitors: sodium nitrate (inorganic compound) and calcium nitrite.(b)Oxygen reaction inhibitors surrounding cathodes: sodium carbonate and sodium hydroxide (inorganic compounds).(c)Anodic and cathodic region-acting inhibitors: amino alcohols and amino carboxylates (organic compounds).Alternative or supplementary techniques to traditional repair of RC are well known ,13,14,15Inhibitors of corrosion for repairing RC structures could be used as a sole measure or combined together with conventional repair methods, enabling a multi-barrier approach; therefore, they may be incorporated as a fresh concrete admixture (AACI) or applied on the surfaces of repaired hardened concrete, acting as an inhibitor of migrating corrosion. Their effect relies on acting mainly on the initiation period of corrosion and less on the propagation part ,18.(a)Precipitation of calcium carbonate for self-healing of concrete impact on corrosionBacillus genus, which contains species that are highly resistant to the alkaline environment [To provide a source of bacterial nutrients.The production of calcium carbonate as a consequence of the organic processes, such as: urea hydrolysis production, sulphate reduction, and photosynthesis.Microbiological precipitation of calcium carbonate (MICP) is a biotechnological healing technique that utilises the ability of certain types of bacteria to induce the formation of calcium carbonate inside the cementitious matrix. One of the most extensively studied and used bacterial genera for this purpose is the ironment  and are ironment ,21, an aThe working hypothesis is that these bacteria are able to produce the precipitations of calcium carbonate and of biologically inducing chemical precipitations in which the organism develops an ideal mineral phase extracellular micro-environment, identified as bio-mineralization. Sometimes, the metabolic pathway for calcium carbonate generation can have an impact on the corrosion of cement-based materials ,27,28,29The existing state-of-the-art emphasises that the production of ammonium through the ureolytic pathway could cause the production of ammonium salts, which could lead to corrosion or conversion of ammonium to nitric acid, which might damage the structure of the concrete . Aerobic(b)Microbial iron respiration as a contribution to corrosion inhibition in self-healing concreteAlthough certain bacterial strains are known to be able to induce or promote the corrosion of steel , other strains can inhibit corrosion either by directly depleting the educe O2 . It is cThe most common form of corrosion is rusting in the presence of water and oxygen, which can be described using well-known chemical reactions, starting with the reduction of metallic iron to Fe(II)—Equation (1):Fe(II) is further reduced to Fe(III)—Equation (2)—which then forms amorphous iron(III)-hydroxide—Equation (3):Finally, after dehydration, rganisms .The Fe(III)-respiring bacteria usually couple the oxidation of the organic substrate, such as acetate or lactate, to reduce Fe(III) to Fe(II). In a study performed by Dubiel et al. , electroThis research work intends to demonstrate that the most effective repair method for RC structures should be regarded as a long-term environmental impact feature. Particularly, this should take into account the embodied carbon expenditure and the longevity of the maintenance. The purpose was to evaluate the enhancement in the lifespan of a structure exposed to a harsh marine microenvironment by utilising a probabilistic performance-based method. The best alternative repair method for RC structures was selected by considering 100 years of service life and a maximum appropriate probability of achieving steel reinforcement corrosion of 2.3%, in compliance with Eurocode 0 requirements for the durability class RC3. Performance-based design using a probabilistic approach was utilised to compare the long-term behaviour of three different concrete compositions repaired with an iron-respiring bioproduct and a chemical-corrosion inhibitor.®  with a concentration of 0.60 L per m3 of concrete. The performance results of the AACI are included in the Andrade Report [Shewanella-like strain (iron-respiring bacteria), In the laboratory, three distinct compositions of concrete were manufactured in order to simulate the actual characteristics of concrete that can be used in the RC structures repair situation , such ase Report ,37. The Three samples per composition with 150 mm size concrete cubes were loaded to failure according to EN 12390-4 . CapillaControl—plain concrete;Concrete containing admixture inhibitor;Concrete containing bioproduct for the purpose of self-healing behaviour.For each concrete composition, three scenarios were then defined:Lt), when exposed to corrosion, is the sum of the initiation period (it) and propagation period (pt), where the Lt must present higher values than the predicted working life (gt) that was decided to adopt for a structure. The performance is a function of the actions (S), such as Cl− migration, and resistance (R), such as the cover of concrete and the concrete characteristics. The risk measure associated with the particular event of R(t) < S(t) could be defined as the likelihood of failure [L-tgt) is negative.A probabilistic approach was used for the design lifetime calculations, where assumptions, parameters, and mathematical models for the lifetime computation are based on fib Bulletin 34 (2006) , EN 206- failure ,18. Thisc is the cover of concrete, erf is the function of error, RC is the amount of chloride threshold by weight of the cement (%), SC is the amount of surface chloride by weight of cement (%), iC the initial amount of chloride within the concrete mass by weight of cement (%), k is the product of parameters that considers curing , temperature , relative humidity , and n is the factor of ageing. These values are a function of the exposure class (XS2 or XS3) and are available at the Technical Specification LNEC E 465 from EN 206-1 regarding the methodology for estimating the service life of RC structures.The initiation period resulting from the actions of chlorides follows the recommendations of fib Bulletin 34 , adoptinpt (years) is the period of propagation, 0φ (mm) is the original steel reinforcement diameter, and 0φ = 10 . The factor of radius reduction y (mm) is presented as:td is the tensile strength of the concrete cover.Equation (5) presents the variables and equation for estimating the propagation period in the chloride environments. Faraday’s law was used to calculate the propagation period, where the radius reduction factor of reinforcement the steel was attained from the empirical equation (Equation (6)).®, Cortec® Corporation, St. Paul, MN, USA), it is shown that it increased the chloride threshold (CR) by 54% and reduced the corrosion velocity (corri) by 46% when compared to the reference concrete mix in the report.According to the experimental results obtained in the Andrade Report  on the aThe concrete performance was assessed in terms of service life, with respect to steel reinforcement corrosion, with and without the presence of the bioproduct and AACI corrosion inhibitor in two different microenvironments: XS2 and XS3 . The calfP as a time function [fP, compared to concrete mixes without inhibitors, there is an increase in the design service life values for concrete compositions with bioproduct and AACI.The probabilistic study of the distribution of service life was conducted utilising the statistical parameters of the involved variables: function ,18. FiguThe previous results show that the bioproduct provides a significant contribution to the increase of the service life of RC structures with CEM III/A. CEM III/A and CEM II/A-D concretes are commonly used for structures exposed to maritime environments such as bridges. CEM I concrete  is preseThe impact of the use of a bioproduct or other type of corrosion inhibitor does not relate only to the service life of a structure. The use of resources and the environment needs to be taken into consideration as well. On top of ensuring a service life of 50 or 100 years, structures also need to use larger quantities of systems and materials. Choosing an appropriate composition of concrete increases the LCA impact and relevance when it is correlated to the durability of the structure. Here, the efficacy of a low carbon project should therefore be considered by its expected service life along with the energy expenditure and embodied carbon ,48.2 associated with heavy replacement infrastructure. The average embodied CO2e effect of concrete in the UK is approximately 100 kg CO2e/tonne. The previous modelling results show that the bioproduct leads to a significant contribution to the increase of RC service life with CEM III/A and cover reduction. Even if the bioproduct leads to a reduction in the concrete cover of 10 mm (from 60 to 50 mm), with approximately 5% less RC section, this means that there is an embodied carbon reduction equal to 472 kg CO2e/m3 of OPC concrete × 0.05 = 23.6 kg CO2e/m3 reduction (9.4 kg CO2e/tonne). Adding the CO2 savings from the use of CEM III/A instead of OPC means a total saving of approximately 20 kg CO2e/tonne of RC. The data within 2 (ECO2) figures for water, CEM I, GGBS, silica fume, sand gravel from Bath, and SIMAPRO inventories of carbon and energy [The results show that the bioproduct creates more opportunities to use low-carbon concretes with improved service life. The increase of RC service life via self-healing techniques delays the need for COd energy ,49,50.2e emissions per m3 of concrete.The previous results show the environmental benefit of CEM III/A in comparison to CEM II/A-D, more specifically an embodied carbon reduction of more than 20% in comparison to CEM II and half of the CEM I, corresponding to a decrease of 250 kg of COA study was implemented to analyse the benefit of an iron-respiring bioproduct used to create self-healing behaviour in concrete in order to minimise corrosion in structures in maritime environments. Three different concretes, CEM I 52.5N, CEM II/A-D, and CEM III/A were tested with and without an iron-respiring bioproduct (BIO) and an added admixture corrosion inhibitor (AACI). The results show that the bioproduct had a significant contribution to the increase of the service life of RC structures with CEM III/A.Concrete CEM III/A had 30% less embodied carbon than concrete CEM II/A-D. It is shown that the use of bioproduct in CEM III/A concrete enabled a probability of steel reinforcement corrosion lower than 2.3% for 100 years of service life, with a significant impact on the environment. The repair solution with self-healing behaviour increased RC service life and enabled the decrease of the cover thickness from 60 mm to 50 mm in an XS2 environment. In both the XS2 and XS3 environments, the comparison of CEM III/A+BIO and CEM II/A-D+AACI showed the benefit of the use of the bioproduct in the corrosion inhibition context, besides contributing to an embodied carbon reduction of more than 20%.The presence of cracks leads to a lack of integrity of RC structures, compromising their safety, serviceability, and durability. At the first stage in maritime environments, the migration of chlorides is a major cause for that, and the development of flexible solutions able to mimic nature is essential to increase the initiation and propagation periods of RC corrosion. Self-healing concrete provides RC structures and infrastructures with the ability to adapt to different environments. In this paper, a bacteria-based solution is explored in the chloride environment context. Its potential for the improvement of a structure’s resilience is emphasised. It is demonstrated that the potential of self-healing concrete to improve RC structures’ service life is combined with a reduction of the use of resources such as energy and, ultimately, with significant benefits for the environment.


The main objectives of this study are to evaluate the effect of geometrical constraints of plain concrete and reinforced concrete slabs on the Wenner four-point concrete electrical resistivity (ER) test through numerical and experimental investigation and to propose measurement recommendations for laboratory and field specimens. First, a series of numerical simulations was performed using a 3D finite element model to investigate the effects of geometrical constraints  on ER measurements of concrete. Next, a reinforced concrete slab specimen (1500 mm (width) by 1500 mm (length) by 300 mm (thickness)) was used for experimental investigation and validation of the numerical simulation results. Based on the analytical and experimental results, it is concluded that measured ER values of regularly shaped concrete elements are strongly dependent on the distance-to-spacing ratio of ER probes . For the plain concrete, it is inferred that the thickness of the concrete member should be at least three times the electrode spacing. In addition, the distance should be more than twice the electrode spacing to make the edge effect almost negligible. It is observed that the findings from the plain concrete are also valid for the reinforced concrete. However, for the reinforced concrete, the ER values are also affected by the presence of reinforcing steel and saturation of concrete, which could cause disruptions in ER measurements. Civil infrastructure systems, such as buildings, bridges, and pavements, are the backbone of modern society and the global economy growth, leading to the sustainable development of several countries . ConcretElectrical resistivity (ER) method is among the most popular non-destructive evaluation (NDE) techniques for in-situ evaluation of durability performance of concrete because of its simplicity, speed, and low-cost during field inspections ,10,11,12However, special cares are needed to obtain reliable and accurate interpretation of ER data in concrete. It is mainly because ER values of concrete are sensitive to various parameters related to material properties of concrete and environmental factors, which include water/cement ratio ,28, age K (see Equation (2)).Specifically, a functional relationship between the apparent resistivity of concrete and its shape/geometrical composition should always be considered ,47,48. Ispecimen . For exaspecimen  suggestespecimen . It is dThis correction factor varies and is dependent on the sample’s thickness, geometric dimensions, surface area, and probe configuration . HoweverThe main objectives of this research are to evaluate the effect of geometrical constraints of plain concrete and reinforced concrete slab on the electrical resistivity measurements through numerical and experimental investigation and to propose measurement recommendations for laboratory and field specimens. This research will discuss the effect of the geometrical constraints in the ER measurements such as the dimensions of concrete slabs, the electrode spacing and configuration, and the distance of the electrode to the edges of concrete slabs. This study will also analyze the effect of the presence of steel reinforcement and concrete saturation condition. The findings in this study will further improve the understanding of the geometrical constraint effect on ER values measured on the regularly shaped concrete elements and enable more reliable and accurate interpretation of ER values in the laboratory and field applications.3.A 3D finite element model was developed to investigate the variation of electric potential field in concrete slabs with various geometrical dimensions using a commercially available code, AC/DC module in the COMSOL Multiphysics v5.5. Using an input true resistivity of 100 kΩ-cm and an external current of 200 μA placed at the two external electrodes, the electric potential difference (in V) was measured using two boundary probes placed at the location of the two internal electrodes. Similar to the four-point Wenner probe, the four electrodes had an equal spacing (s) in the numerical simulation models. For comparison to the experimental data, the simulated potential difference was used to compute for the apparent ER using Equation (1).In this study, a series of numerical simulations was conducted to investigate the effect of geometrical properties and constraints of both the plain and reinforced concrete slabs to the measurement of electrical resistivity of concrete. Main variables in the numerical simulation included the dimensions of concrete slabs , the spacing of sensors (electrodes), and the presence of reinforcing steel in concrete slabs. The variables are summarized in For all the numerical simulation models, three different electrode spacings were used to investigate the effect of the spacing of electrodes on the apparent ER measurements. To analyze the effect of increasing electrode spacings and to simulate the commercially available Wenner Probe devices, probe spacings, s of 38 mm, 50 mm, and 76 mm are used. In addition, another set of numerical simulation was performed by using reinforced concrete slabs to evaluate the effect of reinforcing steel on the ER measurements as shown in A reinforced concrete slab with 1500 mm length, 1500 mm width, and 300 mm height manufactured at Dong-A University was used for this experiment. The concrete used for the fabrication of the concrete slabs was composed of Type I Portland cement, river sand and crushed coarse aggregate, and water. The mixture was designed to 28-day compressive strength of 35 MPa. A commercially available Wenner Probe device (Resipod Proceq), with an electrode spacing of 38 mm, was used in measuring ER at the surface of the reinforced concrete slab as shown in The measurement locations for gathering the ER values of the reinforced concrete slab are shown in It is of importance to figure out the effect of saturation conditions on ER measurements on concrete slabs since ER of concrete is strongly dependent on water content in concrete. To evaluate and minimize the effect of the degree of saturation of concrete, the electrical resistivity of concrete was measured in three saturation conditions: no saturation, one-day saturation, and two-day saturation of the surface of the concrete. ER values of dried concrete are extremely high and often exceed the capacity of measurement devices. Accordingly, a number of researchers specified to wet the surface by using a sponge or spraying a small amount of water before making a measurement ,57,58,59K, of the plain concrete model with varying slab thickness, H  over the true ER values for the simulation model (100 kΩ-cm in this study). It is observed that the K value is dependent of slab thickness and electrode spacing. For the same electrode spacing, the value of K decreases as the slab thickness increases. For the same slab thickness, greater electrode spacing results in greater K value. In addition, K value with normalized slab thickness (H/s), the slab thickness H divided by the electrode spacing, s. Three graphs from different electrode spacings shows a good agreement with each other, which demonstrates that the geometrical correction factor, K, is mainly dominated by the normalized slab thickness, H/s, for the plain concrete model. This supports the results of previous researches that as the probe spacing increases, a thicker region of concrete would be involved in ER measurements [H ≥ 2 s) to minimize the correction factor less than 10% (K ≤ 1.1). Furthermore, the normalized thickness should be greater than 3.0 to completely suppress the thickness effect on the ER measurements (H ≥ 3 s). This results of this part of the also validates the findings of Gowers and Millard (1999) and Yilmaz (2015) that as the thickness increases, the geometrical correction factor decreases [s, H see a, measururements ,59. Baseecreases ,46.K, obtained from the numerical simulation cases 2 and 3 for the plain concrete model with increasing the normalized distance of a probe array from a slab edge, α/s and β/s, respectively. This follows the recommendation of Chen et al. (2014) that the geometrical correction factors should be based on the ratio of the length of the specimen over the electrode spacing [K, decreases and becomes steady. To reduce the correction factor to less than 10% (K ≤ 1.10), α/s and β/s should have a minimum value of 1.58 and 0.72, respectively. In particular, an ER probe should be located farther away from a slab edge, with the α/s and β/s greater than 2.0, to suppress the K values less than 5% (K ≤ 1.05). It should be taken into account that other material properties and environmental factors such as the presence of rebars and degree of saturation in concrete were not considered in this part of the analytical study. spacing . Note α K, obtained from the numerical simulation case 1 using reinforced concrete slab models with respect to the normalized slab thickness (H/s). The orientation of the two layers of steel reinforcement was arranged in the reinforced concrete slab models in accordance with the actual concrete slab shown in K value with increasing thickness. However, simulation of reinforced concrete shows that both the slab thickness and steel reinforcements affect the K values. It can be interpreted that for the normalized slab thickness of reinforced concrete less than 2.0 (H/s < 2.0), the governing factor on the relative ER is the slab thickness, where it shows the similar trend as the relative ER of plain concrete. In contrast, for H/s ≥ 2.0, fluctuating values in ER were observed, attributed to the disturbance of current flow due to the presence of rebars in concrete. Different electrode spacings show different trends. There have been intensive studies on the effect of the presence of rebars in concrete on the electrical resistivity measurements of concrete through experimental and numerical investigation [tigation ,44,45,60tigation ,36. Resetigation ,44,45. TK, obtained from the numerical simulation cases 2 and 3 for the reinforced concrete models with respect to the normalized distances from slab edge, α/s and β/s, respectively. K values obtained on the reinforced concrete models were lower than those obtained from the plain concrete models. The differences in the K values of different electrode spacings range from 22% to 40%  has less effect on size correction factor K compared to the change of α .K values. It was observed that the relative ER generated through numerical simulation for a 76 mm electrode spacing yielded lower resistivity values as compared to 38 mm and 50 mm electrode spacings. The simulation using an electrode spacing of 38 mm produced a graph closest to the normalized graph of plain concrete, whereas 76 mm probe spacings produced the farthest. It can be interpreted that larger probe spacings cover more rebars, resulting in lower relative ER values. Therefore, the location of the rebar and its orientation with respect to the probe has a significant effect to ER measurements, as mentioned in previous paragraphs.Interestingly, it can also be deduced that a normalized graph was not formed in the numerical simulation for the reinforced concrete models. The result of the numerical simulation for reinforced concrete model showed that the increasing electrode spacing resulted to lower K, as variables for comparing the experimental and numerical data, the relative ER (ratio of apparent ER measured at the slab edge over apparent ER of solid concrete) is used. With reference to Equation (2), the geometrical correction factor of the reinforced concrete specimen cannot be derived since the Wenner device only displays the apparent ER and not the true ER of concrete. To fully understand the edge effect of plain and reinforced concrete slabs, an experimental investigation was also conducted considering an electrode spacing of 38 mm. In this part of the study, instead of using the geometrical correction factor, K ≈ 1.0). For a commercially available Wenner probe device with an electrode spacing, s = 38 mm, the minimum value for both α and β is 76 mm. This also means that the minimum dimensions (L × W × H) for a concrete slab is 266 mm × 152 mm × 114 mm. This slab dimensions when simulated in COMSOL generates a geometrical correction factor of 1.0032, validating the recommendation of this study.The findings of the experimental investigation and numerical simulation of reinforced concrete slab confirmed that the ER probe should be located far enough away from the bottom and the edges of concrete elements to reduce the geometrical constraint effect on ER measurements, consistent with the recommendations of existing studies ,43. The It was observed in this study that the apparent ER values are strongly affected by the presence of reinforcing bars when ER measurements are done on the reinforced concrete slabs. The results from numerical simulations and experiments show that the guideline to avoid the geometrical constraint effects for the plain concrete may not be effective for the reinforce concrete slabs.One interesting finding in this study is that concrete in the wet condition decreased the disruptions caused by the presence of steel reinforcement. As discussed, H ≥ 3 × s). Using numerical simulation of plain concrete model, to make the edge effect almost negligible, the distance should be more than twice the electrode spacing (α and β ≥ 2 × s).Numerical simulation shows that to minimize the effect of the slab thickness in the measurement of apparent electrical resistivity, the thickness of the concrete slab should be three times the electrode spacing  measurements are evaluated in this research study. The researchers utilized the four-point (Wenner Probe) method in determining the electrical resistivity of a reinforced concrete specimen. A numerical simulation through COMSOL Multiphysics was also conducted to be compared to the experimental data. Generally, it can be concluded, that the slab dimensions  contribute to the varying geometrical correction factor of the specimen. The specific conclusions and recommendations derived from this study are summarized below: