Normal saline (NS) and Ringer’s lactate (RL) are the most common crystalloids given to hospitalized patients. Despite concern about possible harm associated with NS , few large multicenter randomized trials focused on critically ill patients have compared these fluids. Uncertainty exists about the effects of these fluids on clinically important outcomes across all hospitalized patients.The FLUID trial is a pragmatic, multicenter, 2×2 cluster crossover comparative effectiveness randomized trial that aims to evaluate the effectiveness of a hospital-wide policy that stocks either NS or RL as the main crystalloid fluid in 16 hospitals across Ontario, Canada.All hospitalized adult and pediatric patients  with an incident admission to the hospital over the course of each study period will be included. Either NS or RL will be preferentially stocked throughout the hospital for 12 weeks before crossing to the alternate fluid for the subsequent 12 weeks. The primary outcome is a composite of death and hospital readmission within 90 days of hospitalization. Secondary outcomes include death, hospital readmission, dialysis, reoperation, postoperative reintubation, length of hospital stay, emergency department visits, and discharge to a facility other than home. All outcomes will be obtained from health administrative data, eliminating the need for individual case reports. The primary analysis will use cluster-level summaries to estimate cluster-average treatment effects.The statistical analysis plan has been prepared “a priori” in advance of receipt of the trial data set from ICES and any analyses.We describe the protocol and statistical analysis plan for the evaluation of primary and secondary outcomes for the FLUID trial.ClinicalTrials.gov NCT04512950; https://classic.clinicaltrials.gov/ct2/show/NCT04512950DERR1-10.2196/51783 Crystalloid resuscitation fluids, including normal saline (NS) and Ringer’s lactate (RL), are among the most common interventions administered in hospitalized patients ,2. TheseIn observational studies, NS has been associated with acute renal injury as compared to RL and other balanced crystalloid fluids, hypothesized to be due to higher chloride concentration and resultant metabolic acidosis that can occur with NS administration -5. HowevIn total, 2 large single-center multiple crossover trials conducted in the intensive care unit (ICU) and the emergency department (ED) among patients who did not require admission to the ICU, found that balanced crystalloid fluids as compared to NS were associated with lower major adverse kidney events at 30 days, which is a composite outcome of mortality, new renal replacement therapy, or persistent renal dysfunction . In contCrystalloid fluids are administered to the majority of patients admitted to the hospital and continued throughout their hospital stay. To address ongoing uncertainty on this topic, and address this evidence gap about fluid administered outside the ED and ICU, we designed a cluster randomized crossover trial. Our objective was to compare a hospital-wide strategy to preferentially stock NS or RL as the main crystalloid resuscitation fluid, aiming to have all admitted patients receive the allocated crystalloid from the time they enter hospital to hospital discharge, evaluating the primary composite outcome of death or readmission to hospital in the first 90 days. The design of the FLUID trial is novel because it involves a pragmatic cluster randomized crossover design, a waiver of patient informed consent to include all hospitalized patients, hospital-based randomization, and the use of routinely collected electronic health administrative data for the description of baseline characteristics and all study outcomes. FLUID will generate data at low risk of bias, providing key evidence about the consequences of crystalloid fluid on clinically important outcomes, and informing patient care and health care policy. It will also provide insight into a novel approach to the conduct of large pragmatic clinical trials.This manuscript describes the protocol and statistical analysis plan for the evaluation of primary and secondary outcomes for the FLUID trial.The protocol and feasibility results for the FLUID pilot trial have been published ,30. The The study is a pragmatic, multicenter, 2×2 cluster crossover comparative effectiveness randomized trial. A completed PRECIS-2 table and wheel have been attached as Table S1 and Figure S1 in FLUID has two 15-week study periods. For each study period, week 1 will serve as a run-in, weeks 2-13 (12 weeks) as the study period during which all patients with index admissions to the study hospital will be included for analysis. Weeks 14 and 15 are the run-out period during which time the study fluid remains stocked in the hospital for use by patients admitted during weeks 2-13; however, new patients admitted during weeks 14 and 15 will not contribute to the analysis. After the 2-week run-out period, sites will have 1 week to switch out the study fluid and cross over to the period 2 study fluid. See Inclusion criteria for participating clusters include (1) level II or III ICU capacity  and (2) All admitted patients to participating study sites for the first time  over the duration of the study period will be included under a waiver of informed consent obtained from the research ethics committee; only neonatal patients (age <1 month) will be excluded as RL is not recommended for use in this population . PatientThe order of treatment allocation for each hospital site (cluster) will be randomly assigned using computer-generated random numbers, using a permuted block design of length 2, at the coordinating center. The allocation sequence will be prepared by a statistician not familiar with the participating sites, which will be randomized in a 1:1 ratio. Half of the sites will be allocated to sequence 1 and begin the trial with NS as the control, while the other half will be allocated to sequence 2 and begin the trial with RL as the treatment. Each site will cross over to the other fluid after the 12-week study period. To control for period effects, while balancing logistical considerations, randomization will proceed in batches of 4 sites. The allocation sequence will be maintained on a password-protected computer and concealed from investigators until the next batch of sites have been enrolled and are ready to receive their allocation.No serious adverse events were reported to the coordinating center during the 4-center pilot trial. A Data and Safety Monitoring Committee conducted a review of the data from the 4-center pilot trial, reporting no reason to suspect harm resulting from either fluid. For the main trial, participating hospitals monitor serious adverse events via routinely scheduled meetings of safety committees or morbidity and mortality rounds. Site Principal Investigators report to the coordinating center any serious adverse event occurrence related to study fluid administration.A total of 16 hospital sites (including the 4 pilot sites) will yield data on approximately 144,000 hospital admissions. It required 12 sites in a 2-period cluster crossover trial over 6 months to achieve 80% power with a 2-sided α of 0.05 to detect a minimum clinically important absolute difference of 1% in the primary outcome in favor of RL, assuming a proportion of 0.16 in the NS condition, a within-period intracluster correlation coefficient of 0.006, a cluster autocorrelation coefficient of 0.95, and an average of 1500 patients per hospital per month . These eAs a risk to participants in FLUID is minimal, and given the delayed availability of data from the Ontario provincial health administrative databases needed for outcome assessment, no interim analyses are planned in the FLUID trial.Protocol adherence will not be measured at the individual patient level. Adherence will be measured according to the aggregate use of the study fluid throughout the hospitals using the hospital inventory system. Adherence will be monitored at 2-week intervals over the study period and reported according to each study group across all participating hospitals, combined and according to major fluid user groups in specific settings . Overall adherence will be defined as the total use of the allocated study fluid divided by the total combined use of NS and RL.We will not be collecting individual patient-level data, as all data will be collected through the ICES provincial database. As informed consent is not being sought, only clinically available data are being analyzed, and no unique research data are being collected, participants cannot withdraw from the study.We anticipate near 100% follow-up since all clinical data and outcome measures from participating sites in Ontario will be available at ICES, except for a very small number of patients who leave the province of Ontario within 90 days after enrollment.Data will be obtained and housed using Ontario’s population-based health administrative databases at ICES. ICES is an independent, nonprofit research institute whose legal status under Ontario’s health information privacy laws allows the collection and analysis of health care and demographic data. The data sets identified in All follow-up and data collection for patients at the participating sites will be captured by ICES. The approach to analysis will be supervised by the study statistician and principal investigator; however, the final analysis will be conducted by an independent statistician not involved as a coinvestigator in the FLUID trial.All study outcomes will be tested for superiority.All statistical tests will be 2-sided and performed using a 5% significance level. We will report all CIs as 95% and 2-sided. Results will be expressed as absolute differences produced by analyses described below.Our primary analysis will use the intention-to-treat approach and will include all enrolled patients in the treatment groups to which their cluster was randomized at the time of the index hospitalization. Because true fluid exposure status is not recorded in administrative databases, all admitted patients will be included in the analysis, regardless of actual fluid administration.The primary outcome is a composite of death or readmission to the hospital within 90 days of the index hospitalization. All-cause death will be obtained at a patient level using the Registered Persons Database, while hospital readmission will be measured from Discharge Abstract Database (DAD). Cluster randomized trials can address 2 types of estimands: the participant-average or the cluster-average treatment effect . The forThe secondary outcomes are 90-day death, hospital readmission within 90 days of the index hospitalization, and requirement for new dialysis within 90 days; and for surgical patients, requirement for reoperation, postoperative reintubation in the postoperative assessment unit, ED visits within 90 days, hospital length of stay, and discharge to facility other than home. All secondary outcomes will be obtained at the patient level from DAD and National Ambulatory Care Reporting System.The tertiary outcomes relate to the health economic analyses and include the incremental cost per one death averted and incremental cost per one quality-adjusted life year (QALY) gained.Baseline data will be collected and summarized as means and SDs for continuous variables or counts and percentages for categorical variables as shown in All analyses will be conducted according to recommendations for cluster randomized crossover trials, accounting for clustering to ensure correct type I error rates and CIs ,40. In tThe primary outcome will be analyzed within the following subgroups of patients who are at a higher risk for exposure to fluids and with greater risk profiles and or severity of illness than other patients. These include age ; sex; type of hospital admission ; elective and urgent or emergent surgical admissions, surgical admissions <24 hours, surgical subgroups , those who are otherwise healthy , and those who may have been exposed to both types of study fluids (lengths of stay spanning both FLUID study periods).We will conduct a cost-effectiveness analysis of RL and NS from the perspective of the Canadian public health care payer using a hybrid decision tree and Markov models. A decision tree with a 90-day time horizon will be used to determine the effects of each fluid on mortality, requirement for dialysis, and health system costs. Baseline characteristics will be based on the concurrent trial. Surviving patients will enter a Markov component of the model  in whichThe model outcomes will include incremental cost per one death averted and incremental cost per one QALY gained. An annual discount rate of 1.5% will be applied to both costs and health outcomes, as recommended by Canada’s economic evaluation guideline . ScenariThe prevalence of missing data is expected to be minimal as outcomes will be obtained from ICES. Nevertheless, missing data for each outcome will be summarized by the treatment group. If substantial missingness is observed (>10%), sensitivity to missing data will be examined under a range of missing-not-at-random scenarios by assuming first that all patients with missing outcomes had the event of interest and then that all patients with missing outcomes did not have the event of interest.The statistical analyses will be performed with SAS  and R .Guided by a theory and evidence-informed dissemination planning guide , the plaThe FLUID Trial was approved at all participating sites through Clinical Trials Ontario (#0778) and the Queensway Carleton Hospital Research Ethics Board (#16-05). Waivers of patient consent were obtained to receive the study intervention and for data collection from ICES, as the risks of study participation are minimal, and requiring informed consent would render the study infeasible.At the time of this submission, a total of 7 centers have completed recruitment into FLUID. The statistical analysis plan has been prepared “a priori” in advance of receipt of the trial data set from ICES and any analyses.The results of this trial will determine whether a hospital-wide policy of stocking predominantly NS versus RL reduces the composite of death and readmission to hospital, as well as other adverse secondary outcomes. We provide a detailed statistical analysis plan which will reduce the risk of data-driven approaches and biased interpretation and increase the transparency of our analyses and results.There are several challenges related to the design and conduct of the large FLUID trial. These include a risk of study fluid contamination due to a lack of awareness of FLUID, noncompliance to the study protocol, and carryover due to the crossover design. Hence, our team first conducted the FLUID pilot trial in advance of the large trial with the aim of evaluating strategies to address these challenges . In the We describe the protocol and statistical analysis plan for the evaluation of primary and secondary outcomes for the FLUID trial. FLUID will determine whether RL as compared with NS reduces death or requirement for hospital readmission by an absolute difference of 1%. In contrast to trials that have generated evidence in specific populations with fluid interventions limited to geographic locations in the hospital , the results of FLUID will apply broadly to patients who are admitted throughout the hospital. As such, FLUID will provide important evidence-based guidance at the hospital and system level as to what fluids could be predominantly stocked for use throughout the hospital and the associated health care resources required for such supply.The results of FLUID will help define clinical practice for physicians who care for patients admitted to the hospital regardless of whether differences between the 2 fluid groups in the proposed clinical outcomes are found. The question of the selection of optimal crystalloid fluid is, as evidenced by contemporaneous studies on this theme, an international one, and the results of FLUID will impact hospital management practices around the world. Should FLUID reveal a difference in clinical outcomes for patients, reflected in lives saved and hospital admissions avoided, then one fluid will become the dominant fluid stocked in centers; it may also result in significant savings to the health care system through bulk purchasing of one type of fluid. If no differences are found, then the less expensive crystalloid fluid may become the dominant fluid stocked in centers.


September 22, 2021, one author’s funding was not listed. Géraldine Coppin was supported by an Eccellenza Grant from the Swiss National Science Foundation (Grant 181094). The full funding statement appears below and the online version has been corrected.In the article “3D-Printed Pacifier-Shaped Mouthpiece for fMRI-Compatible Gustometers,” by David Munoz Tord, Géraldine Coppin, Eva R. Pool, Christophe Mermoud, Zoltan Pataky, David Sander, and Sylvain Delplanque, which published online onThis work was supported by the Firmenich SA Research Grant UN9046. G.C. was supported by Swiss National Science Foundation Eccellenza Grant 181094.


Si tips coatedwith dopeddiamond and solid doped diamond tips are more durable, but they aresignificantly more expensive and their high stiffness often damagesthe surface of most samples. One growing alternative is to use solidPt tips, which have an intermediate price and are expected to be moredurable than metal-coated silicon tips. However, a thorough characterizationof the performance of solid Pt probes for CAFM research has neverbeen reported. In this article, we characterize the performance ofsolid Pt probes for nanoelectronics research by performing varioustypes of experiments and compare them to Pt/Ir-coated Si probes. Ourresults indicate that solid Pt probes exhibit a lateral resolutionthat is very similar to that of Pt/Ir-coated Si probes but with thebig advantage of a much longer lifetime. Moreover, the probe-to-probedeviation of the electrical data collected is small. The use of solidPt probes can help researchers to enhance the reliability of theirCAFM experiments.Conductive atomic force microscopy (CAFM) is a powerfultechniqueto investigate electrical and mechanical properties of materials anddevices at the nanoscale. However, its main challenge is the reliabilityof the probe tips and their interaction with the samples. The mostcommon probe tips used in CAFM studies are made of Si coated witha thin (∼20 nm) film of Pt or Pt-rich alloys (such as Pt/Ir),but this can degrade fast due to high current densities (>10 To citea few, in 1995, O’shea et al. improved the lateral resolutionof the CAFM to 10 nm using enhanced probes;RTIP), in most cases below 50 nm.16 The most widely used CAFM probes are made of bulk silicon, as thismaterial is cheap and easy to sharpen using dry and wet etching techniques,which is then coated with a thin (<50 nm) Pt film to supply highconductivity16—the Pt film mustbe thin to maintain a low RTIP in orderto obtain images with a high lateral resolution. However, these probesdegrade very fast due to mechanical frictions and high current densities,which generate heat and melt the metallic coating.15 Toavoid this problem, one possible solution is to coat the Si probeswith doped diamond17 or to use solid doped-diamondprobes18 .20 However, doped-diamond probes are more expensiveand, more importantly, often damage the surface of the samples dueto their high stiffness. Using graphene to protect the apex of metal-coatedsilicon probes has been proposed,21 but theseprobes are still not commercially available.CAFM employs conductivenanoprobes terminated in a small tip radius.21 However, there is still no thorough statistical quantification ofthe performance of solid Pt probes compared to traditional Pt/Ir-coatedSi probes. In this article, we statistically analyze the conductivity,resolution, and durability of solid Pt probes during CAFM measurementsand under different working conditions. We find that the resolutionof topographic and current maps obtained with solid Pt probes is verysimilar to those obtained using Pt/Ir-coated Si probes, but the solidPt probes show the advantage of being much more durable in all kindsof experiments performed. Our study provides useful knowledge forall CAFM users that could help to enhance the reliability of theirinvestigations.Using solid Ptprobes is an option that in the past few years hasgained more and more adepts,2RTIP = 8 nm, and k = 40 N/m);24 these are Si probes usuallyemployed for topographic measurements in tapping mode. Note that tappingmode provides the highest resolution in topographic AFM measurementsdue to the small radius of the tip and the lack of lateral frictions;26 hence, the topographic measurements obtained with this type of probesare taken as a reference to evaluate the quality of the other probes.The second type is the ContV-Pt from Bruker ;27 these are Si probes with a Pt/Ir-coating onthe tip and cantilever frontside for electrical measurements in contactmode. The manufacturer of these tips did not give information aboutthe thickness and composition of the Pt/Ir-coating, i.e., we cannotknow if the term Pt/Ir refers to one layer of Pt on a Ir layer orif the Pt/Ir refers to an alloy  and in such a case, what the proportion is. The third type is theSCM-PIT-V2 from Bruker ;29 these are also Pt/Ir-coated Si probes similar to the ContV-Pt, withthe main difference of a higher spring constant. Lastly, the fourthtype is the RMN-25Pt300b from Rocky Mountain Nanotechnology ;30 these are probes with both the tip and cantilevermade from solid Pt, also for electrical measurements in contact mode.We analyze multiple ContV-Pt and RMN-25Pt300b probes using a scanningelectron microscope  and estimate RTIP by fitting the apex of each tip with a circle,as proposed in the reference.31 As depictedin RTIP = 25 nm), we observe that the real RTIP varies from 20.7 to 28.9 nm, and when measuring 10 solid Pt tips, we observethat the real RTIP varies between 10.9and 28.5 nm. We cannot know if these values fall within the specificationsbecause none of the manufacturers indicate the variability of RTIP in their websites. In any case, the variabilityof RTIP for both types of tips seems tobe reasonable and acceptable.In this study, weuse a Dimension Icon AFM from Bruker operatingin an air atmosphere , which is providedwith four types of probes. The first type is the NCHV-A from Bruker silicon . These samples represent the state-of-the-art in SiO2 dielectrics, i.e., they are very homogeneous, exhibit a lowconcentration of local defects, and key parameters like electron massand barrier height are well understood. This is useful to reduce thenumber of uncertainties in the tip/sample system and allows us tobetter understand what is producing the differences in the currentsignals registered. The use of a highly conductive substrate belowthe SiO2 is beneficial because it removes the potentialthat normally would fall on a standard silicon substrate.32 Sample 4 consists of a multilayer MoS2 flake produced by mechanical exfoliation and transferred on a 300nm SiO2/Si wafer.33 This sampleis ideal to test the ability of the probes to measure the thicknessof a material by scanning at the edge of the flake. Also, sample 5consists of a 10-layers-thick  hexagonal boronnitride (h-BN) stack grown by chemical vapor deposition on a Cu foil.34 This sample is rougher than the SiO2, which allows us to evaluate the ability of the solid Pt probesto map topographic-current correlations. Moreover, this sample containsmultiple local defects, whose size can be quantified with differentprobes.We perform different experiments to quantify thequality of topographicmaps, current maps, and spectroscopic measurements recorded with eachtype of probe. To do so, we used five different samples with differentproperties. Samples 1, 2, and 3 consist of 3.4, 4.7, and 5.6 nm SiO2/Si samples using a transmission electron microscope, although prior to that, wehad to extract a thin lamella using a focused ion beam . The images show that the thicknessof the SiO2 film is exactly the expected one . The surface of the sampleis very flat, with a root mean square (RMS) roughness of 0.2 nm (see 35 When the topographyof the same SiO2 sample is measured in contact mode withthe Pt/Ir-coated Si probe (ContV-Pt) and the solid Pt probe, the detectedRMS roughnesses of the surface are 0.16 and 0.12 nm, respectively leading to a flatter surface profile. However,in RTIP of solid Pt tips is in generaleven slightly smaller than the one of the Pt/Ir-coated Si tips. Anotherpossibility could be that the higher spring constant of the solidPt tip could be improving the tip/sample contact, leading to a lowersurface roughness. In any case, the differences observed are smalland all tips can effectively map the surface topographic of the ultraflatSiO2/Si sample.First, we evaluatethe topography of the SiO2 nm see 2b, in agvelysee 2c,d.All36 polymers,37 and deoxyribonucleic acid ,38 among many others. 2 flake produced by mechanical exfoliation and transferredon a 300 nm SiO2/Si wafer. We analyze the thickness ofthe flake detected with each probe by post-processing the images;instead of making a cross-section at a single line, we use the reliablemethod presented in the reference,39 whichconsists of analyzing the spectrum of the topographic images. Thethicknesses of the MoS2 flake detected with the Si probeat areas 1 and 2  during the scans, which is 2 V for the solidPt probe and 6 V for the Pt/Ir-coated Si probe. This difference shouldbe again related to the fact that the solid Pt probes have a muchhigher spring constant, which could produce a better contact. Since the goal of this experiment is to check the abilityof these two types of probes to map the weak spots of the h-BN sample,the scan parameters for each probe should be adjusted individually.Note that, despite many manufacturers offer Pt/Ir-coated Si probes,there is no single manufacturer that offers a model with k = 18 N/m  for electricalmeasurements in contact mode (see Table S1); but even in the hypothetical case of having probes with identicalnominal k, each of them should be employed with theoptimum scanning parameters, which could vary from one probe to another.Hence, in our experiment, measuring with different voltages is acceptable,as far as they produce similar tunneling/leakage current across thesample under test—measuring the sample with identical scanparameters to compare the probes would be erroneous, as they wouldnot be measuring at their optimum conditions and the currents drivenwould be different. We intentionally apply positive bias to the CAFMprobe (with respect to the substrate) to avoid local anodic oxidationdue to water splitting produced by electron injection from the tip.40Next, we analyze the lateralresolution of the current maps collectedwith Pt/Ir-coated Si probes and solid Pt probes by scanning the h-BN/Cusample. For both types of probes, we apply to the tip the minimumvoltage needed to observe current above the noise level  of the SiO2 film, often inducing surfaceepitaxy.42 To ensure that the electrical stress producedby one RVS does not affect the current registered during another RVS,we keep a safe distance of 1 μm between them.Next, we analyze the durability of the solid Pt probes and compareit to the Pt/Ir-coated Si probes by applying ramped voltage stresses(RVS) from 0 to 10 V to the CAFM tip (keeping the substrate grounded)at 100 randomly selected locations on the 3.4 nm SiOI–V curves witha Pt/Ir-coated Si probe .We then carried out the same experiment using asolid Pt probethat initially has 1 nm see 5e. The fV curves 5f show tV curves 5g shows RTIP see 5h the ti6I–V curvesat different locations of a 5.6 nm SiO2/n++Sisample using three different new solid Pt probes and a current limitationof 100pA. The results —similar,if not smaller, than observed when using Pt/Ir-coated Si probes,43 indicating a very good reproducibility. Hence,despite the obvious and unavoidable deviation of k and RTIP , the variability of the data obtained from one solidPt probe to another is not a concern.Finally,we analyze the deviation of the measurements from oneprobe to another by collecting 100 ults see 6 show th7RTIP < 20 nm, k ≈ 18 N/m) is an excellent solution because theyprovide a lateral resolution that is very similar to that of Pt/Ir-coatedSi probes but with the big advantage of a much longer lifetime. Moreover,the probe-to-probe variability of the electrical data collected issmall. Solid Pt probes could be the solution for many scientists toimprove the reliability and reduce the costs of their CAFM investigations.In CAFM, the reliabilityof the measurements is compromised bythe poor reliability of Pt/Ir-coated Si probes. Diamond-coated/solidprobes are more durable, but they are much more expensive and areso stiff that they cause damage on most samples. We found that theuse of solid Pt probes (


This secondary analysis of a placebo-controlled, randomized clinical trial investigates the diagnosis of acute kidney injury when correcting serum creatinine for fluid balance and its association with short-term and long-term clinical outcomes in extremely low gestational age neonates. Does correcting serum creatinine for fluid balance identify previously missed episodes of acute kidney injury (AKI) in premature neonates?In this post hoc cohort analysis of a placebo-controlled, randomized clinical trial of 923 premature neonates, fluid correction increased the number of premature neonates with a diagnosis of AKI. Correction for fluid balance was associated with increased odds of adverse clinical outcomes, including ventilation and severe lung disease.These findings suggest that failing to correct serum creatinine for fluid balance underestimates the prevalence and severity of AKI in premature neonates, and future studies should consider correcting serum creatinine for fluid status to improve identification of AKI in premature neonates. Acute kidney injury (AKI) and disordered fluid balance are common in premature neonates; a positive fluid balance dilutes serum creatinine, and a negative fluid balance concentrates serum creatinine, both of which complicate AKI diagnosis. Correcting serum creatinine for fluid balance may improve diagnosis and increase diagnostic accuracy for AKI.To determine whether correcting serum creatinine for fluid balance would identify additional neonates with AKI and alter the association of AKI with short-term and long-term outcomes.This study was a post hoc cohort analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT), a phase 3, randomized clinical trial of erythropoietin, conducted at 19 academic centers and 30 neonatal intensive care units in the US from December 2013 to September 2016. Participants included extremely premature neonates born at less than 28 weeks of gestation. Data analysis was conducted in December 2022.Diagnosis of fluid-corrected AKI during the first 14 postnatal days, calculated using fluid-corrected serum creatinine .2 test or Fisher exact test. The t test and Wilcoxon rank sums test were used to compare continuous and ordinal variables, respectively. Odds ratios (ORs) and 95% CIs for the association of exposure with outcomes of interest were estimated using unconditional logistic regression models.The primary outcome was invasive mechanical ventilation on postnatal day 14. Secondary outcomes included death, hospital length of stay, and severe bronchopulmonary dysplasia (BPD). Categorical variables were analyzed by proportional differences with the χA total of 923 premature neonates  were included, of whom 215 (23.3%) received a diagnosis of AKI using uncorrected serum creatinine. After fluid balance correction, 13 neonates with AKI were reclassified as not having fluid-corrected AKI, and 111 neonates previously without AKI were reclassified as having fluid-corrected AKI . Therefore, fluid-corrected AKI was diagnosed in 313 neonates (33.9%). Neonates with unveiled AKI were similar in clinical characteristics to those with AKI whose diagnoses were made with uncorrected serum creatinine. Compared with those without AKI, neonates with unveiled AKI were more likely to require ventilation . In multivariable analysis, a diagnosis of fluid-corrected AKI was associated with increased odds of adverse clinical outcomes, including ventilation  and severe BPD .In this post hoc cohort study of premature neonates, fluid correction increased the number of premature neonates with a diagnosis of AKI and was associated with increased odds of adverse clinical outcomes, including ventilation and BPD. Failing to correct serum creatinine for fluid balance underestimates the prevalence and impact of AKI in premature neonates. Future studies should consider correcting AKI for fluid balance.NCT01378273ClinicalTrials.gov Identifier:  Creatinine is distributed between the intracellular and extracellular compartments, and the measurement of its concentration is inversely related to fluid balance.8 Fluid balance can delay the diagnosis of AKI by diluting  or concentrating  the measured serum creatinine concentration, impacting the severity of diagnosed AKI, and complicating the association of AKI with outcomes.10Acute kidney injury (AKI) commonly occurs in extremely low gestational age neonates (ELGANS)12 and clarifies the association between AKI and outcomes .13 Evaluating fluid balance in neonates is particularly complicated because they are born with high total body water and quickly experience an expected physiologic diuresis.14 Correcting serum creatinine for fluid balance allows assessment of true changes in kidney function independently of fluctuations in fluid balance. Such correction may allow for earlier AKI diagnosis and faster implementation of medical therapy  or kidney support therapy. Conversely, correcting serum creatinine in patients with appropriate diuresis may decrease the rate of AKI diagnosis, decreasing unnecessary interventions. To our knowledge, the epidemiology and impact of correcting for fluid balance on the diagnosis of AKI in ELGANS has not been evaluated in a prospective or multicenter study.In critically ill children and adults, correcting serum creatinine for fluid balance increases the precision and accuracy of AKI diagnosis15 In this secondary analysis of the PENUT study, we sought to (1) describe fluid-corrected serum creatinine curves in ELGANS during the first 2 postnatal weeks, (2) describe the prevalence of AKI before and after fluid correction, and (3) evaluate the associations with short-term and long-term outcomes of AKI before and after fluid correction. Our primary hypothesis was that the correction of serum creatinine for fluid balance would identify previously undiagnosed AKI episodes. Furthermore, we hypothesized that fluid-corrected AKI would clarify the association of AKI with clinical outcomes.The Preterm Erythropoietin Neuroprotection (PENUT) study captured robust data on kidney function and fluid status, as well as short-term and long-term outcomes in ELGANS.15 The University of Washington institutional review board served as the central institutional review board, and each center received approval from their institutional review board. Written informed consent was obtained from the parent or legal guardian. The inclusion criteria were (1) infants born between gestational ages of 24 weeks and 0 of 7 days and 27 weeks and 6 of 7 days, (2) enrolled within less than 24 hours after birth, and (3) arterial or venous access. Exclusion criteria included (1) major life-threatening anomalies, (2) hematologic crises, (3) hematocrit greater than 65%, (4) hydrops fetalis, and (5) congenital infection. Participant race and ethnicity were determined by maternal self-report as part of the original PENUT study and included Black, White, other race , unknown race, Hispanic or Latino ethnicity, and non-Hispanic or Latino ethnicity. These characteristics were included as part of the parent randomized clinical trial to allow investigators to balance study groups with regard to multiple factors, including race and ethnicity.15 See the PENUT study protocol in STROBE) reporting guideline for observational studies.16Performed in December 2022, this study was a post hoc analysis of the PENUT Trial (NCT01378273), a phase 3, placebo-controlled, randomized clinical trial of erythropoietin in ELGANS in 19 academic centers and 30 NICUs in the US.18 and calculated as change in weight from birth weight using the following equation:8 If no daily weight was available on the day of serum creatinine assessment, the daily weight was imputed from surrounding days weights; weights were available for 97% of potential patient days. Fluid-corrected serum creatinine was calculated for each clinically available serum creatinine with the following equation:The PENUT trial included daily weights for the first 14 postnatal days. Fluid balance was based on recent consensus guidelines19 For this analysis, we assessed AKI during the first 14 postnatal days because this was when daily weights were available. Urine output criteria were not used due to incomplete reporting.20 Stage 1 AKI was defined as a 1.5- to 1.9-fold increase in serum creatinine or an increase of 0.3 mg/dL within 48 hours; stage 2 as a 2.0- to 2.9-fold increase; and stage 3 as a more than 3-fold increase in baseline serum creatinine or serum creatinine greater than 2.5 mg/dL. As with previous PENUT publications,1 AKI was determined using the lowest prior creatinine measurement as the baseline, and creatinine had to surpass a threshold of 0.5 mg/dL or more for diagnosis. Assessment of AKI began on postnatal day 3.1 Severe AKI was defined as KDIGO stage 2 or 3.AKI was defined using the serum creatinine criteria neonatal modified Kidney Disease: Improving Global Outcomes (KDIGO) definition.We defined class switching as neonates who moved from 1 stage of AKI to another after correcting for fluid balance. For example, a neonate with a positive fluid balance with no AKI by uncorrected serum creatinine may have had stage 2 AKI after correcting serum creatinine for fluid balance . Conversely, a neonate with substantial diuresis and stage 1 AKI based on uncorrected serum creatinine may have been recategorized to no AKI after correction for a negative fluid balance  (eTable 1 in 21 (2) grade 3 BPD defined as neonates receiving invasive mechanical ventilation at 36 weeks postmenstrual age,21 (3) hospital length of stay, and (4) death. Long-term kidney-related outcomes were evaluated at 24 months corrected gestational age (+2 months), and included decreased estimated glomerular filtration rate, albuminuria, and elevated blood pressure.22 Estimated glomerular filtration rate was defined by the serum creatinine and cystatin CKiD (chronic kidney disease in children) equation.23 Albuminuria was defined as an albumin-to-creatinine ratio more than 30 mg albumin per gram of creatinine. Elevated blood pressure was defined as values exceeding the 90th percentiles for age-related and sex-related norms.24The primary outcome was the need for invasive mechanical ventilation  on postnatal day 14. Our secondary short-term outcomes included (1) BPD, defined by Neonatal Research Network definitions and Jensen criteria as neonates receiving respiratory support at 28 days of age,2 test or Fisher exact test. The t test and Wilcoxon rank sums test were used to compare continuous and ordinal variables, respectively. Odds ratios (ORs) and associated 95% CIs for the association of exposure with outcomes of interest were estimated using unconditional logistic regression models. Multivariable logistic regression models, which used a backward selection process and were based on variables with P < .05 in bivariate analysis, were used to account for potential confounding variables; findings were reported as adjusted ORs (aORs). A repeated measures ANOVA with a 3-way interaction of fluid adjusted status, day of life and day of life category  was used to compare fluid-corrected and uncorrected curves. In all analyses, a 2-sided P < .05 was considered statistically significant. Data visualization including Sankey diagrams were constructed using Flourish Studios.25 Analysis was performed using SAS statistical software version 9.4 (SAS Institute) in December 2022.Categorical variables were analyzed by proportional differences with the χOf the 941 neonates who were enrolled in the PENUT trial, 923  were included in this analysis  of 11 (7 to 13) values per patient. The median (IQR) peak negative fluid balance was −10.3% (−14.6% to −5.6%) on median (IQR) postnatal day 3 (2 to 5). Median (IQR) peak positive fluid balance in the first 2 postnatal weeks in this population was 11.1% (4.3% to 19.6%) and occurred on median (IQR) postnatal day 12 (8 to 14). A total of 93 (10.1%) neonates never dropped below their birth weight.21 = 9.79; P = .002) whereas the serum creatinine curve increased . From postnatal day 4 to 7, the fluid-corrected serum creatinine curve flattened whereas the uncorrected serum creatinine curve decreased . After postnatal day 7, fluid-corrected serum creatinine curve increased  whereas the uncorrected serum creatinine curve continued on a downward slope .Uncorrected and fluid-corrected serum creatinine curves are shown for the entire cohort and by gestational age group . CorrectAKI diagnosis using uncorrected serum creatinine occurred for 215 neonates (23.3%), which included 154 neonates at stage 1, 45 at stage 2, and 16 at stage 3. No neonates in this study were treated with dialysis. Correcting for fluid balance increased the incidence of AKI to 33.9% (313 neonates), of which 101 neonates (32.3%) had severe AKI . There wAfter correcting serum creatinine for fluid balance, 124 neonates switched AKI classes. A total of 111 neonates were newly classified as having unveiled AKI, including 104 who went from no AKI to stage 1 AKI, and 7 who went from no AKI to stage 2 or 3 AKI. In 36 neonates, AKI severity increased from stage 1 to stage 2 or 3 AKI. After correcting for fluid balance, 16 neonates had their AKI stage decrease (13 patients went from stage 1 AKI to no AKI and 3 went from stage 2 or 3 AKI to stage 1 AKI). A summary of the shifts in the AKI staging before and after fluid correction is shown in 2, 155 neonates (35.6%) with albuminuria, and 160 neonates with elevated blood pressure (32.6%).A total of 408 neonates (52.0%) were mechanically ventilated at postnatal day 14 . The secThe bivariable associations with our primary outcome of mechanical ventilation on postnatal day 14 is described in eTable 2 in Although the association of AKI with the short-term outcomes of BPD and prolonged hospital stay were not statistically significant after multivariable adjustment, exposure was associated with increased odds of adverse outcomes after adjustment for fluid balance . The oddWith regard to most demographic and clinical characteristics, neonates with unveiled AKI were similar to those with AKI diagnosed using uncorrected serum creatinine . NeonateCompared with those without AKI, neonates with unveiled AKI were more likely to require invasive mechanical ventilation on postnatal day 14 (81 neonates [75.0%] vs 254 neonates [44.3%]) and have longer hospital stays . There was no difference in mortality between these groups. Neonates with unveiled severe AKI were more likely to require ventilation on postnatal day 14 (33 neonates [82.5%] vs 400 neonates [50.7%]) compared with those without AKI, but we saw no difference in hospital length of stay or mortality .26In this secondary analysis of a large, prospective, multicenter, randomized clinical trial of ELGANS, we evaluated the impact of fluid correction of serum creatinine on AKI diagnosis and its association with short-term and long-term outcomes. We found that fluid correction identified many neonates with previously undiagnosed AKI, and that correcting for fluid balance changed AKI staging in many patients. Fluid-corrected AKI correlated better with clinically relevant outcomes and was associated with increased odds of short-term clinical outcomes, including mechanical ventilation and grade 3 BPD. Furthermore, correcting serum creatinine for fluid balance created a new serum creatinine curve for neonates over the first 2 weeks of life, with a slow improvement in kidney function over time, which challenges the often cited peak and then fall serum creatinine trajectory over the first several postnatal days.19 In recent years, opportunities for improving AKI diagnosis have been identified, including incorporating fluid balance into AKI diagnosis. In critically ill adults, fluid-corrected AKI better identifies AKI associated with increased mortality.13 In critically ill children, correction of AKI status for fluid balance increases the odds of experiencing adverse outcomes.10 To date there have only been 2 small single-center studies evaluating fluid correcting AKI in neonatal populations. In 1 small retrospective study11 of neonates undergoing cardiac surgery, it was found that correcting for fluid balance increased AKI diagnosis. In a second small single-center retrospective study14 of ELGANS, it was found that correcting for fluid balance decreased the incidence of AKI. We note that our findings are in contrast to this study and hypothesize this is due to our novel approach to the correction of both peak and trough serum creatinine. The correction of the trough creatinine, which serves as the baseline to diagnose and stage AKI, adds precision and accuracy to the novel method previously described.14 Our study underlines the importance of careful attention to fluid balance, including frequent measurement of weights in premature neonates because episodes of AKI associated with poor short-term outcomes may be diagnosed only after correcting for fluid balance.17Over the past several decades, the study of AKI has been most impacted by consensus definitions for diagnosis and staging.8 This phenomenon is unique to the neonatal population because correcting serum creatinine for fluid balance can encompass the full spectrum from dilution to concentration. The current study suggests that accounting for changes in fluid balance when diagnosing AKI in the first 2 postnatal weeks improves the precision and accuracy of the AKI diagnosis in premature neonates. Confirmation of these findings and further study is warranted, particularly in specific neonatal populations where fluid balance may be particularly relevant.Our findings should be interpreted in the context of the unique physiology of the premature neonate. Premature neonates differ from older children in that they are subject to the full spectrum of fluid balance during the first 2 postnatal weeks including positive fluid balance, physiologic diuresis, and diuretic-induced diuresis, which impacts the diagnosis of AKI in neonates, because changes in fluid balance complicate the AKI diagnosis when using serum creatinine diagnostic criteria.This multicenter prospective study has several strengths, including the robust high-quality data available in a large, prospective, multicenter study allowing for the detailed exploration of the impact of fluid balance on AKI diagnosis. Furthermore, the study has long-term kidney-specific outcomes for the cohort.27 Because the neonatal modified KDIGO definition relies on creatinine, factors such as maternal kidney function, gestational age, and infant growth also impact the interpretation of creatinine as a marker of kidney function. Additionally, we assumed a static percentage of weight as water (80%) across a range of gestation ages and during the first 2 postnatal weeks. Although this approach is consistent with previous studies8, it assumes that all changes in weight during the first 2 weeks are due to changes in water and does not take into account the physiologic natriuresis that occurs in the first several days after birth or any postnatal growth. Although using birth weight as an anchor weight for the first 14 postnatal days is currently the standard approach, this method may overestimate the fluid balance, especially during the first postnatal week. Further studies are needed to better assess the changes in body composition and body water in premature neonates.7Despite these strengths, there are several limitations of this secondary analysis. Our findings were limited by clinically obtained serum creatinine, and weights and urine output were not collected. However, weights were available for 97% of potential patient days, and this analysis imputed missing values; therefore, misclassification is likely infrequent. Because the PENUT database only included daily weights from the first 2 postnatal weeks, our conclusions are limited to this period. Longer observation periods are necessary to extend our findings. We note that there are other variables, such as clinical conditions and management practices, that may result in changes in weight and are not captured in this analysis. Third, although defining AKI by neonatal modified KDIGO definitions is the current standard for this patient population, this may not be the optimal marker for detection of kidney dysfunction in premature neonates.In this secondary analysis of the multicenter PENUT trial, we describe fluid-corrected AKI and evaluate associations with short-term and long-term outcomes in premature neonates with fluid-corrected AKI. Taken together, the current study suggests a paradigm shift in how we describe kidney function in premature neonates in the first 2 postnatal weeks. The current study suggests that fluid balance should be considered in future definitions to improve the diagnosis of AKI in premature neonates. Failing to correct serum creatinine for fluid balance underestimates the prevalence and severity of AKI in premature neonates. Future studies should consider correcting AKI for fluid balance in the first 2 weeks to improve identification of neonates at high risk for poor outcomes.


The purpose of this theoretical study is to explore the behavior of an electrically conducting micropolar fluid when subjected to a uniform magnetic field along the vertical axis between two stretching disks as the structure of the problem changes. In this context, structural changes refer to alterations in the distance between the two discs or the stretching rate of the two discs. The governing equations of this problem are a set of nonlinear coupled partial differential equations, which are transformed into a nonlinear coupled ordinary differential equation set by a similarity transformation. The transformation results in four dimensionless quantities and their derivatives that appear in the equations. Nine dimensionless parameters are derived via similarity variables, including stretching Reynolds number, magnetic parameter, radiation parameter, Prandtl number, Eckert number, Schmidt number, and three micropolar parameters. Previous similarity solutions focused on analyzing the effect of changes in each parameter on the four dimensionless quantities. However, this type of analysis is mainly mathematical and does not provide practical results. This study’s primary novelty is to redefine the magnetic parameter, Eckert number, stretching Reynolds number, and two micropolar parameters to analyze physical parameters that depend on the stretching rate of the two discs or the distance between them. The semi-analytical hybrid analytical and numerical method (HAN-method) is used to solve the equations. The results demonstrate that structural changes affect all five quantities of radial velocity, axial velocity, microrotation, temperature, and concentration. The study’s most significant finding is that an increase in the stretching rate of the two disks causes a sharp increase in temperature and Nusselt number. Conversely, increasing the distance between the two disks causes a sharp decrease in micro-rotation and wall couple stress. They were compared to a previous study in a specific case to validate the results’ accuracy. More recent results were obtained by Cochran3 by modifying von Karman’s problem because Von Karman’s answers contained errors. The Von Kármán swirling fluid flow problem was solved more accurately later by Abdou4 with the homotopy perturbation method (HPM) and also by Yao and Lian5 with the Runge–Kutta method. The Von Karman rotational viscous flow problem, which was created by a rotating disk with an infinite radius, has the simplest physics among the problems related to fluid flow resulting from disks. Turkyilmazoglu6 improved the physics of Von Kármán’s rotating fluid problem, which Abdou studied4 and Yao and Lian5, and this time considered holes on the rotating disk that made the medium porous. Turkyilmazoglu7 improved the physics of the previous study6 by considering the magnetic field in the constitutive equations. The improvements of the Doh and Muthtamilselvan8 were in considering the micropolar fluid as the rotating fluid, and unlike other studies7, the considered constitutive equations were time-dependent. The obtained results showed that the Nusselt number increases with the increase of the instability parameter. Also, the results showed that as the magnetic parameter increases, the tangential velocity of microrotation decreases. The improvements of Sahoo et al.9 were in considering the non-Newtonian Reiner–Rivlin fluid as the rotating fluid, and unlike other studies8, the disk was stationary, and the fluid was rotated at infinity. Srivastava10 investigated the incompressible micropolar fluid between two rotating disks in a magnetic field. The most prominent novelty of this study was the use of two rotating discs instead of one rotating disc. Das and Sahoo11 improved the problem that was studied by Srivastava10 by considering the non-Newtonian Reiner–Rivlin fluid as the rotating fluid instead of regular micropolar fluid. Iqbal et al.12 improved the problems that were studied by Srivastava10 and Das and Sahoo11 by considering the transient constitutive governing equations, choosing electrically conducting incompressible water-based nanofluid instead of regular micropolar fluid and considering the porous medium for fluid flow. The structure of two rotating disks studied by Srivastava10, Das and Sahoo11, and Iqbal et al.12 was later improved by Jalili et al.13 and Agarwal14, and instead of two rotating disks, two stretching disks were used with the difference that Jalili et al.13 used the semi-analytical HAN method while Agarwal14 used HPM for solving the constitutive equations. As different methods were used, different results were concluded. The Agarwal14 results showed that the nature of the flow of radial velocity for different values of Reynolds number and the magnetic parameter is similar i.e. radial velocity decreases with an increase in both parameters near the central plane. The Jalili et al.13 results showed that The average error between HAN method and HPM, for radial velocity is 3.1%, for axial velocity is 0.69%. Akhter et al.15 improved the studies that applied by Jalili et al.13 and Agarwal14 with considering the porous medium for fluid flow. Hayat et al.16 used Jeffrey nanofluid between two rotating stretchable disks. Compared to previous studies15, this innovation was the simultaneous rotation and expansion of two disks and the use of Jeffrey’s non-Newtonian nano-fluid.The Von Kármán rotational viscous flow is a well-known classical problem in fluid mechanics, and Von Kármán24. In the similarity solutions, five physical quantities such as radial velocity, axial velocity, micro-rotation, temperature, and concentration profiles, with the addition of nine physical parameters such as radiation parameter, Eckert number, Prandtl number, stretching Reynolds number, magnetic parameter, Schmidt number, vortex viscosity, micro-inertia density, and spin gradient viscosity parameter. The structural properties are the stretching rate of the two discs and the distance between the two discs. In this study, the changes in structural properties are investigated due to the effectiveness of these properties in all five mentioned quantities.This study shows the effect of structural changes of two coaxial stretching disks in the heat and mass transfer problem that fluid is micropolar, viscous, incompressible, and the fluid flow is steady, laminar, and axisymmetric. A uniform magnetic field along the z-axis is applied perpendicularly to the disks. So, the fluid flow model is MHD due to the electrically conducting fluid flow and the magnetic field. The governing equations of this problem are a set of nonlinear coupled PDEs. The similarity transformation is applied for converting the constitutive equations into a set of nonlinear coupled ODEs. The HAN method is used in this study due to its brilliant reputation for solving problems with nonlinear constitutive equations24 and can also be applied in many recent numerical studies35. Understanding this method and reaching to analytical solutions is possible and quicker than other studies37 that have used other semi-analytical methods.We chose the HAN method because of its mathematical process for reaching the solution. Many numerical techniques exist, but the main disadvantage of a numerical method is its lack of analytical solution. The HAN method has corrected this disadvantage of the numerical solutions in many problems13 and Agarwal14. The fluid flow resulted from two stretchable disks with a uniform magnetic field along the z-axis. The geometry of the problem is demonstrated in Fig. The governing equations of the electrically conducting fluid are micropolar, viscous, and incompressible, and the fluid flow condition is steady, laminar, and axisymmetric. The governing equations related to this physics are explained in detail in the studies of Jalili et al.38:The circular cylindrical coordinate system of 39:Where d in Eq.  as follo14:Here, ning Eq. , and subning Eq. , the \dor in Eq.  gives hir in Eq. . The posmentclass2pt{minim14.Here, mentclass2pt{minimmentclass2pt{minimThe similarity transformations of Eq.  also aff24 for solving nonlinear ordinary differential equations, and its methodology was given in detail. We have used this method due to its flexibility advantage compared to other semi-analytical methods. The word “flexibility” is for this reason: many numerical methods can handle solving nonlinear differential equations, and when one numerical method doesn’t give us an answer, the other numerical methods do. And this is why it is so-called flexible. Another advantage of this method is that it is analytical and gives a more accurate analytical solution with fewer terms than other semi-analytical methods. To use the HAN method to obtain the semi-analytical solution of the system of ordinary differential equations of Eqs. (The HAN method was applied in several studies of Eqs. –13, we fAs can be seen in Eq. , there aEquations –26 are nAs numerical solutions are approximated, we can consider them as approximated boundary conditions. As the problem’s boundary conditions make ten algebraic equations, the approximated boundary conditions of Table 13 are existed in Figs. Comparing analytical solutions of Eqs. –30 with In this part, some physical parameters that depend on the stretching rate of the two disks or the distance between the two disks, including the magnetic parameter, Eckert number, stretching Reynolds number, and two of the micropolar parameters, are redefined. This redefinition is a reason to investigate the effect of structural changes on the physical quantities of the problem. After redefining the parameters, some of the parameters that depended on structural changes were written in terms of Among the structural parameters, when the stretching rate of the two disks changes, the temperature profile will change the most, while the profiles of velocity, micro-rotation, and concentration do not change significantly when the stretching rate of the two disks changes. This high sensitivity of the temperature contour to the stretching rate of the two disks is shown in Fig. In continuation of the physical argument quantitatively, statistical analysis can also check the effect of increasing the stretching rate of the two disks on each quantity. In the statistical analysis method, the absolute value of the average change of each quantity is checked by the stretching rate of the two disks, and the contribution of each quantity change is shown in a pie chart. In Figs. Among the structural parameters, when the distance between the two disks changes, the micro-rotation velocity profile will change the most, while the profiles of axial and radial velocities, temperature, and concentration do not change significantly when the distance between the two disks changes. This high sensitivity of the micro-rotation velocity profile to the distance between the two disks is shown in Figs. Changing both structural parameters will affect all five radial and axial velocities quantities, micro-rotation, temperature, and concentration.Variation in the stretching rate of two disks strongly affects the temperature profile.The temperature profile will increase extremely as the stretching rate increases.Variation of the distance between the two disks strongly affects the micro-rotation velocity.The micro-rotation velocity will decrease extremely as the distance between the two disks increases.This study examines how an electrically conducting fluid flows in the presence of a magnetic field between two disks being stretched apart. When the distance between or the rate of stretching of the disks changes, the behavior of the fluid also changes. To investigate this, the researchers used a set of equations that describe the fluid’s behavior. They found four sets of quantities that describe the fluid’s behavior by simplifying these equations. The researchers also found nine other numbers that describe the fluid’s behavior as it interacts with the vertical magnetic field and the two stretchable disks. So far, similarity solution strategies have focused mostly on how changes in these numbers affected the fluid’s quantities. However, in this study, we only focused on physical parameters that depend on the distance between or the disks’ stretching rate. By doing so, we redefined some of the numbers in the equations to better describe these physical parameters. This redefinition is the main new and novel contribution of the study. The results of changing structural parameters in this study are derived from the HAN solution, and a summary of the results in qualitative form is concluded as follows:According to the assumptions of this study, only structural parameters such as


Kangaroo rats are small mammals that are among the most abundant vertebrates in many terrestrial ecosystems in Western North America and are considered both keystone species and ecosystem engineers, providing numerous linkages between other species as both consumers and resources. However, there are challenges to studying the behavior and activity of these species due to the difficulty of observing large numbers of individuals that are small, secretive, and nocturnal. Our goal was to develop an integrated approach of miniaturized animal-borne accelerometry and radiotelemetry to classify the cryptic behavior and activity cycles of kangaroo rats and test hypotheses of how their behavior is influenced by light cycles, moonlight, and weather.We provide a proof-of-concept approach to effectively quantify behavioral patterns of small bodied (< 50 g), nocturnal, and terrestrial free-ranging mammals using large acceleration datasets by combining low-mass, miniaturized animal-borne accelerometers with radiotelemetry and advanced machine learning techniques. We developed a method of attachment and retrieval for deploying accelerometers, a non-disruptive method of gathering observational validation datasets for acceleration data on free-ranging nocturnal small mammals, and used these techniques on Merriam’s kangaroo rats to analyze how behavioral patterns relate to abiotic factors.We found that Merriam’s kangaroo rats are only active during the nighttime phases of the diel cycle and are particularly active during later light phases of the night . We found no reduction in activity or foraging associated with moonlight, indicating that kangaroo rats are actually more lunarphilic than lunarphobic. We also found that kangaroo rats increased foraging effort on more humid nights, most likely as a mechanism to avoid cutaneous water loss.Small mammals are often integral to ecosystem functionality, as many of these species are highly abundant ecosystem engineers driving linkages in energy flow and nutrient transfer across trophic levels. Our work represents the first continuous detailed quantitative description of fine-scale behavioral activity budgets in kangaroo rats, and lays out a general framework for how to use miniaturized biologging devices on small and nocturnal mammals to examine behavioral responses to environmental factors.The online version contains supplementary material available at 10.1186/s40462-023-00433-x. Small mammals are among the most abundant vertebrates in many terrestrial ecosystems, providing numerous linkages between other species as both consumers and resources –7. Many next generation natural history biologging techniques provide a much deeper understanding of the behavior and ecology of species that are both easy to observe in nature and ones that are not amenable to direct observation [Detailed fine-scale data on the activity and behavior of keystone species represents an important component of community ecology, as this information provides invaluable insight into interactions with other species and broader ecological niche parameters –14. Howeervation , 20.The use of accelerometers to quantify behavior and activity has its own set of limitations, including the need to create detailed validation datasets, relatively crude classifications of behavioral states, the lack of broader ecological context for behavioral expression, and the inability of smaller species to carry large enough devices for long enough periods of time . These lTamias alpinus and T. speciosus), diurnal sciurid rodents weighing ~ 50 g. Hammond et al. [To date, the smallest mammals that have been studied using advanced biologging techniques to quantify activity and behavioral patterns are Western chipmunks .Dipodomys merriami), a nocturnal heteromyid rodent (< 50 g) that is the most abundant terrestrial mammal in many arid regions of North America [Here, we use animal-borne accelerometry to classify the behavior of free-ranging kangaroo rats  using Sherman live traps and marked captured individuals with 10 mm Biomark pit-tag injected subcutaneously on the dorsum. Kangaroo rats were weighed to the nearest gram, and individuals that were > 40 g in mass  and then released at their point of capture. Individuals were then periodically relocated via radiotelemetry  for validation recording and to verify retention of bio-loggers. If bio-loggers were still retained after 6 days, individuals were re-trapped for removal of the device and then immediately released at point of capture.The study was carried out May-August 2021 at Marathon Grassland Preserve (MGP), a 1093-ha Chihuahuan desert grassland habitat located in West Texas, USA. The site was dominated by Trans-Pecos loamy plains grassland and sparse creosote scrub. We captured Merriam’s kangaroo rats (We used VHF radio tracking (Advanced Telemetry Systems R410 Receiver) and a handheld flexible 3-element Yagi antenna to locate tagged kangaroo rats. Once individuals were located, two observers would work together with a telephoto video camera  with infrared (IR) recording capability (Sony Handycam Model DCR-SR80) and an IR flashlight  to video record behaviors of kangaroo rats at a distance over 10 m, moving slowly and carefully to avoid unnecessary disturbance. Individuals were filmed for as long as they were visible. We spent approximately 3 h per night throughout the sampling period tracking kangaroo rats and recording videos for behavioral validation when they were active on the surface. From these efforts, we scored all videos that showed clear and unambiguous examples of kangaroo rats exhibiting the behaviors described in our ethogram, resulting in 122 m of validated video observations  to generate annotated acceleration datasets by recording a video of the exact time  as the accelerometry device began logging data . We then also recorded the ExactTime™  to the nearest second at the outset of all validation video recordings of kangaroo rats wearing accelerometry devices , and as. AdditioWe used the open-access web application AcceleRater to train classification algorithms based on our free-ranging kangaroo rat acceleration datasets . First, The stepwise methodological workflow for behavioral classification of accelerometry data and assessment of activity budgets is depicted in Fig. suncalc package in R to retrieve daily light phase times, moonrise and moonset times, and sunrise and sunset times for our study site [Specifically, we determined behavioral activity budgets at different light phases, moon intensity and illumination, and moon position . We udy site . Moon iludy site –52, we iudy site , 54.χ2) tests [We examined the effect of moonlight and environmental variables on behaviors in a generalized linear mixed effects modeling (GLMM) framework. First, we investigated the diel activity patterns of kangaroo rats by examining whether the proportion of time spent in each behavioral state  was influenced by light phase  and sex as fixed effects. Next, we examined whether the proportion of time spent in each behavioral state was influenced by moon intensity , moon position (up or down), and their interaction, as well as sex, as fixed effects. This analysis only included light phases when the sun was > 0° below the horizon . Lastly, we used a GLMM to investigate how the abiotic factors of temperature, wind speed, and relative humidity affected kangaroo rat behavioral state at a nightly scale. Additionally, we included moon illumination as a nightly continuous variable in this model to corroborate any patterns found prior regarding the influence of moonlight on kangaroo rat behavior. For each behavior, we explored multiple distribution families, aiming to identify the most suitable family for modeling the data. The candidate distribution families considered were Gaussian, Poisson, Binomial, and Gamma. We employed the Akaike Information Criterion (AIC) as the primary model selection criterion, and then used the top model with the associated best family as the GLMM for each behavior  tests .The random forest model at a window size of 6 s that used all summary statistics available in AcceleRater (see methods above) produced the greatest average accuracy, precision, and recall values compared to all other algorithms across all other window sizes  compared to daytime light phases (when the sun is above the horizon) and they rarely travel at all during daytime light phases Fig. . Thus, tχ2 = 397.82, df = 7, P < 0.001, model R2(c) = 0.60; motionless: χ2 = 470.31, df = 7, P < 0.001, model R2(c) = 0.58; foraging: χ2 = 68.34, df = 7, P < 0.001, model R2(c) = 0.47; and grooming χ2 = 267.13, df = 7, P < 0.001, model R2(c) = 0.51 ). Interestingly, kangaroo rats spent significantly more time traveling during night and morning twilight compared to all other nighttime light phases . Additionally, kangaroo rats spent more time traveling at dawn compared to all other nighttime light phases except for night and morning twilight . Thus, although the sun is below the horizon, kangaroo rats are not traveling as much at the beginning of the night (dusk and evening twilight) compared to the mirrored light phases at the end of the night (morning twilight and dawn). We found a similar pattern when examining motionless behavior in kangaroo rats across light phases. Kangaroo rats spent significantly less time motionless at night and morning twilight compared to all other light phases . Moreover, kangaroo rats spent significantly more time motionless during evening twilight and dawn compared to morning twilight and night (P < 0.01 across both comparisons), but significantly less time motionless during evening twilight and dawn compared to morning, day, evening, and dusk . Similarly, kangaroo rats spent significantly more time foraging during night, morning twilight, and dawn compared to all other light phases . Lastly, kangaroo rats spent more time grooming during evening twilight, night, morning twilight, and dawn compared to all other light phases . Corroborating other activity patterns, kangaroo rats spent significantly more time grooming at night and morning twilight compared to all other light phases .To further understand the proportion of time kangaroo rats spent performing each behavior, we investigated differences across nighttime light phases . The proportion of time spent in each behavioral state during different nighttime light phases differed significantly  = 0.50), but their interaction was significant  = 0.50). Kangaroo rats typically traveled more during medium moon intensity nights and when the moon was visible  = 0.52) and the interaction between moon position and moon intensity  = 0.52) significantly impacted the proportion of time kangaroo rats spent motionless. When the moon was visible, kangaroo rats spent significantly less time motionless, and they spent less time motionless during a medium moon intensity compared to high and low moon intensities  = 0.85; Fig. χ2 = 11.5575, df = 1, P < 0.01); however, there was no effect of moon intensity and the moon position/moon intensity interaction on the proportion of time spent grooming  = 0.65; Fig. We examined if the proportion of time spent motionless, traveling, foraging, and grooming was influenced by moon intensity and moon position. When we removed all nights (n = 4) with a precipitation rate > 0 to account for cloud cover, no relationships changed—thus we retained all values in the dataset. For the proportion of time kangaroo rats spent traveling, we found that moon intensity and moon position had no impact on their own  = 0.63), but other behaviors were not influenced by humidity. Temperature, wind speed, and moon illumination had no effect on the proportion of time kangaroo rats spend foraging, traveling, grooming, or motionless , nocturnal, free-ranging mammals. Our work represents the first continuous detailed quantitative description of fine-scale behavioral activity budgets in kangaroo rats, a diverse group of highly abundant rodents that are widely recognized as keystone species in arid regions of North America. After obtaining highly accurate models for ecologically relevant behaviors such as foraging and traveling, we were able to assess behavioral responses to diel light phases, moonlight, ambient air temperature, average windspeed, and average relative humidity. We confirmed that kangaroo rats are highly nocturnal, but are also much more active in some phases of the night cycle than others. Somewhat surprisingly, although we found that behavioral activity cycles are largely independent of several major abiotic factors (most notably moonlight), kangaroo rats did show a significant increase in time spent foraging on more humid nights, an abiotic factor that has received only limited attention in the ecological literature on heteromyid rodents.Dipodomys spp.) behavioral responses to moonlight . BecausD. merriami. However, we noted some lunarphilic tendencies. In particular, we found that kangaroo rats spent more time traveling and less time motionless when the moon was up during intermediate moon phases , indicating a preference for activity during the lighter, rather than darker, periods of these nights  that kad Owings  would enD. merriami would make compensatory shifts in foraging behavior on nights with higher moon illumination by foraging at dawn. Our accelerometry data shows that individuals were more active at dawn than other light phases of the day  regardless of moon phase and that, when variation in moonlight is available , they prefer to travel more when the moon is visible. However, our study took place during the summer period (May-August), whereas Daly et al. [D. merriami indicates that this species is generally active throughout the year, but does shift toward a diet consisting mostly of cached seeds in hotter and drier periods when green vegetation is not available [This pattern is in contrast to the findings of Daly et al. , who usey et al.  analyzedvailable —a shift Dipodomys merriami, D. ordii, D. panamintinus, D. microps, [D. spectabilis, [D. ordii, [Other studies have also concluded that kangaroo rats avoid moonlight, using various methods across different species , includWe expected other major abiotic factors, such as temperature, wind speed, and humidity to potentially influence activity cycles of kangaroo rats (we were unable to examine precipitation due to the very limited rain occurring at our study site). Although temperature and wind speed did not influence activity cycles, increased foraging was associated with higher levels of humidity. In general, kangaroo rats are highly adapted to arid, desert-like conditions and are thought to select microclimates that avoid thermal extremes and evaporative water loss –68. PastOur analyses of acceleration data to determine diel activity patterns of kangaroo rats confirmed that they are exclusively nocturnal. We relocated individuals using radiotelemetry at least once a day during daylight hours, and because we never observed kangaroo rats outside their burrow systems, we assume that the limited daytime movement logged by accelerometry devices largely represents fossorial activity. This corroborates other studies that used direct observation via radio-telemetry and determined almost exclusively nocturnal/crepuscular activity in kangaroo rats  are warmer and more active (and thus likely more dangerous) during the early portion of the night when the temperature is highest. Additionally, ectothermic predators are a seasonal impact, as they are typically inactive during the winter months throughout D. merriami’s range . Additional research could tease apart the interactive influence of temperature, predation, and seasonality on kangaroo rat activity patterns.Our study also provides new insight into the nocturnal activity patterns of Merriam’s kangaroo rat as other studies have shown that r months , and nocr months . In contA critical step in using animal-borne accelerometry to quantify difficult-to-observe behaviors is to validate with time-matched and paired datasets of behavioral observations and acceleration data. Many methods have been developed to conduct validation studies, including independent captive studies , 79, obsDipodomys merriami). We provide a proof-of-concept approach using combined accelerometry/telemetry devices to record validation videos and assemble large acceleration datasets that allowed us to quantify behavioral patterns across the summer active period. Our study represents one of the most robust behavioral datasets of a keystone species that is estimated to be the most abundant vertebrate in many habitats across southwestern North America [next generation natural history biologging technique continues to be further developed and improved.Here, we present the first study using accelerometry to quantify behavior on a free-ranging population of a heteromyid rodent, a keystone species in desert areas across North America (Meriam’s kangaroo rat,  America . We founBelow is the link to the electronic supplementary material.Supplementary Material 1


In previous papers, it has been shown how Schrödinger’s equation which includes an electromagnetic field interaction can be deduced from a fluid dynamical Lagrangian of a charged potential flow that interacts with an electromagnetic field. The quantum behaviour is derived from Fisher information terms added to the classical Lagrangian, showing that a quantum mechanical system is driven by information and not only electromagnetic fields. This program was applied to Pauli’s equations by removing the restriction of potential flow and using the Clebsch formalism. Although the analysis was quite successful, there were terms that did not admit interpretation, a number of which can be easily traced to the relativistic Dirac theory. Here, this analysis is repeated for a relativistic flow, pointing to a new approach for deriving relativistic quantum mechanics. A comprehensive introduction to the subject of the variational formalism of non-relativistic fluid dynamics and quantum mechanics and their deep interconnections is provided in ,2, and wc. This is of course to be expected, as the work of Clebsch preceded Einstein’s work on special relativity by 48 years. There is a practical basis as well, as relativistic flows are hardly encountered on earth.The original work of Clebsch and all the following publications assume a non-relativistic fluid in which the velocity of the flow is much slower than the speed of light in a vacuum The standard approach to relativistic flows is based on the energy–momentum tensor ,4,5; howWe begin by introducing a variational principle for a relativistic charged classical particle with a vector potential interaction and a system of the same. This is followed by the Eckart  Lagrangim denotes the particle’s mass, e denotes the particle’s charge, and We study a particle travelling in a constant metric spacetime. The action c to convert between the two system of units For a spacetime with a Lorentz–Minkowski metric, the partition into spatial and temporal coordinates is easy. The spatial coordinates are →=x1,x2,x Δ1γow) that∂ε0∂s0=T0l form,2ΔdMα→=ΔdQEquation  is Lorenows that:ΔdEinα→0=; hence,dV0dt0=dV follows:dWα→0=dEit at t=0:d3xl form,2ΔdMα→=ΔdQquation (ΔdEinα→=ΔΔ1γow) thEquation , we obtam and charge e. It follows that the mass and charge densities are proportional to the number density n:We can now combine the internal and kinetic parts of the varied Lagrangian, taking into account the specific enthalpy definition in Equation :(55)ΔdLkEquation  we may wing form:d(λv→)dt=m and charge e; thus, it follows from Equation , we hav4A≡∫Ld3xd example , p. 248)e obtain:dνdt=∂ν∂ting form:λv→=α∇→β+We now show that a velocity field provided by Equation  such thaquations , 79) an anα,β,ν quations  must satown that:d∇→νdt=∇→ons (λv→:d(λv→)dt=Equation . FurtherEquation ):(98)∇→wing form:d(λv→)dt=Equation ; thus, iEquation , meaningEquation  using arIt may be claimed the previous approach introduces unnecessary complications to the theory of relativistic fluid dynamics by adding three additional scalar fields Equation  in the pquations , 85) an anα,β,ν quations  that:, a, aα,β,ν tions in ; after tEquation  to obtaiquation c2=γEquation  it folloEquation  of [1] (m is the particle’s mass and ℏ is Planck’s constant divided by While the analogies between spin fluid dynamics and classical Clebsch fluid dynamics are quite convincing ,2, thereA side benefit of the above work is the ability to canonically derive the momentum energy tensor of a relativistic fluid.c, we may writeAs the current paper is of limited scope, we have not been able to compare the above Lagrangian with its low-speed limit and derive the relevant quantum equation; hopefully, this will be done in a subsequent more expanded paper. However, it is easy to see even here that Schrödinger’s theory is the limit of the theory described by the Lagrangian density of Equation . We writEquation  can be cEquation , in whic14ℏ22m∂μaEquation .We conclude by acknowledging the importance of the comparison between the fluid route to relativistic quantum mechanics and the more established route laid out by Dirac; this certainly deserves an additional paper, which I hope to compose in the near future.


Ensuring wellbore stability is of utmost importance for safety when drilling in deep formations. However, high temperatures severely disrupt the drilling fluid gel system, leading to severe stability issues within ultra-deep formations containing micropores. This study focused on the development of a polymer-based plugging material capable of withstanding high temperatures up to 200 °C. A kind of microsphere, referred to as SST (styrene–sodium styrene sulfonate copolymer), was synthesized with a particle size of 322 nm. Compared to polystyrene, the thermal stability of SST is greatly improved, with a thermal decomposition temperature of 362 °C. Even after subjecting SST to hot rolling at 200 °C for 16 h, the particle size, elemental composition, and zeta potential remained stable within an aqueous dispersion system. The results of core displacement and NMR tests demonstrate that SST considerably reduces the pore diameter with a remarkable plugging efficiency of 78.9%. Additionally, when drilling fluids reach 200 °C, SST still enhances drilling fluid suspension and dispersion, and reduces fluid loss by over 36% by facilitating the dispersion of clay particles, improving the gel structure of the drilling fluid, resisting clay dehydration, and promoting plugging. The development of SST provides valuable insights into the preparation of high-temperature-resistant microspheres and the formulation of effective plugging agents for deep-well drilling fluids. Wellbore stability is a critical technical challenge that is commonly encountered in drilling engineering ,2,3,4,5.Currently, the existing plugging materials can be categorized into two types: rigid and flexible materials. Rigid plugging materials are typically inorganic, mainly ultrafine calcium carbonate, silicon dioxide, and graphene ,20,21,22In order to enhance the adaptability of inorganic plugging materials to the formation, many scholars have carried out the study of graft modification of inorganic materials. For example, microspheres of polymer-coated modified silica and microspheres of silane-graft-modified silica have dramatically improved the plugging efficiency of inorganic materials and have other additional effects such as lowering the filtration loss of drilling fluids and inhibiting shale swelling ,28. It iIn recent years, there has been a growing interest in polymeric plugging agents as potential materials for drilling fluid plugging ,30. PolyIn this study, a new method for the preparation of microspheres by the copolymerization of styrene with sulfonated styrene was proposed to address the issue of high-temperature instability at 200 °C and provide new perspectives on the preparation of high-temperature resistance microspheres. The proposed plugging agent (SST) not only can plug formation micropores and reduce fluid loss but also significantly promotes the high-temperature stability of the drilling fluid gel system. The development of this plugging agent is expected to contribute to resolving the challenge of high-temperature resistance in drilling fluids and provide insights for preparing new microspheres with high-temperature stability.−1, 3061 cm−1, and 3028 cm−1 correspond to the benzene ring–CH stretching vibration absorption peaks [−1 and 2582 cm−1 represent the methylene-asymmetric and para-stretching vibration absorption peaks, indicating the polymerization of C=C double bonds. The peaks at 1601 cm−1, 1493 cm−1, and 1450 cm−1 are C–C stretching vibration absorption peaks in the benzene ring. Furthermore, the characteristic peaks of sodium styrene sulfonate are located at 1184 cm−1 and 1128 cm−1 [In on peaks . AdditioIn order to compare the thermal stability of SST, polystyrene microspheres (PS) without sodium p-styrene sulfonate were prepared using the same method, and the thermal stability of the two materials is shown in The thermal properties of SST were investigated through thermal gravimetric analysis. v/v).Since SST is stored in aqueous dispersion systems and primarily used in such environments, it is important to study its thermal stability in an aqueous dispersion system at a concentration of 2%  of SST changes minimally, from 322 nm to 314 nm, following the high-temperature treatment. This indicates that its particle size remains highly stable at 200 °C. However, there is a reduction in particle size uniformity, leading to a wider particle size distribution as depicted in The shape evolution of SST before and after hot rolling was observed by SEM, and the microscopic morphology of SST is illustrated in The morphology of the original SST is shown in To study the dispersion properties and structural stability of SST, the zeta potential of SST dispersions was measured after hot rolling at different temperatures to evaluate the stability of SST in high-temperature aqueous dispersion systems. Moreover, the impact of high temperature on the composition of SST was analyzed by freeze-drying the dispersions and determining their elemental contents.SST demonstrates excellent thermal stability in aqueous dispersion systems. Plugging micropores is a severe challenge in drilling engineering as it is essential to maintaining the stability of the borehole wall and drilling safety. Excellent plugging performance prevents the drilling fluid from invading the formation, avoids the shale’s hydration, and contributes to the wellbore stability. Therefore, the performance of SST in plugging was evaluated using NMR technology.The morphology and NMR T2 curves of the artificial core before and after SST flooding are shown in The T2 relaxation time is positively correlated with the volume of the pores. Thus, the small T2 relaxation time corresponds to the small volume of pores in the core and vice versa . The verThe addition of SST slightly decreases the G′ and G″ of the drilling fluid before and after the hot rolling. The negative charge on the surface of SST and the electrostatic repulsion reduce the electrostatic attraction of the inter-clay structure and strengthen the mesh gel structure. However, adding SST has a minimal effect on the rheological properties of the drilling fluid, which can be seen in The filtration performance of drilling fluids is critical for maintaining borehole wall safety. Generally, the plugging effect of the plugging agent can be evaluated by the reduction in drilling fluid filtration loss in combination with clay. SST was added to the drilling fluid, and the fluid loss of each drilling fluid before and after hot rolling at 200 °C was evaluated; the results are shown in After drying the filter cake of the drilling fluid following hot rolling at 200 °C, the microstructure was investigated using SEM, and the images are shown in The drilling fluid filter cake after hot rolling shows apparent agglomerated clay and crevices, and the surface of the filter cake is rough, as shown in The stability of drilling fluids, including suspension stability and dispersion stability, is the basis for the comprehensive performance of drilling fluids. Therefore, the stability of the drilling fluid was evaluated through experiments regarding colloidal stability and suspension stability, and the contribution of SST to the stability of the drilling fluid was analyzed through the experimental results.The drilling fluid is an opaque dispersion gel system; the higher the transmissivity, the greater the system deposition. The left, middle, and right sides of the curves in The addition of SST entirely changes the shape of the curve and improves its stability dozens of times due to the negatively charged nature of both SST and clay particles. Adding SST increases the electrostatic repulsion between the clay particles, thus improving the dispersion and suspension stability. The zeta potential measurements further confirm these stability improvements.As shown in The impact of 2% SST on the zeta potential of the drilling fluid at different temperatures is shown in The mechanism of SST in the drilling fluid was analyzed through particle size testing, and the results are presented in The median particle size of the clay, as shown in The application of the plugging agent SST in drilling fluids at 200 °C significantly improved the stability of the ultra-high temperature drilling fluids. The styrene-based microspheres can be highly stable by copolymerizing with sodium styrene sulfonate. It shows the feasibility of the microspheres copolymerized with styrene and sodium styrene sulfonate as ultra-high-temperature agents for drilling fluids.In this study, high-temperature-resistant styrene-based microspheres were prepared, and their characteristics and effects on drilling fluids were investigated. The key findings are listed as follows.A kind of monodisperse hydrophilic microsphere with a particle size of 322 nm was prepared by the copolymerization of sodium styrene sulfonate and styrene, which exhibited a significant core-plugging efficiency of 78.9% and effectively reduced the rock pores.Unlike general polystyrene-based microspheres, SST has excellent thermal stability, and it can maintain its stability of particle size, morphology, elemental composition, and zeta potential in an aqueous solution at 200 °C.For drilling fluids under 200 °C, SST still improved the filter cake quality, enhanced suspension and dispersion stability, and reduced fluid loss by more than 36%.It was found that in drilling fluids, SST achieved improvement in drilling fluid performance in multi-functional ways such as by plugging the micropores of the filter cake, improving the dispersion of the clay, and promoting the particle size grading of the drilling fluids.4)2S2O8, AR) were purchased from Sinopharm Reagent Co. Sodium p-styrene sulfonate  and sodium carbonate (99.8%) were provided by Shanghai Maclean Biochemical Technology Co., Shanghai, China. Polyethylene glycol octylphenyl ether  was obtained from Beijing J&K Science Co., Beijing, China. Bentonite is an industrial product from Huaian County Tengfei Bentonite Development Company, Ltd., Zhangjiakou, China. The based bentonite fluid (DF) was made by adding 4 wt% bentonite and 0.3 wt% sodium carbonate to water and stirring for 24 h [Styrene St, 99%) and ammonium persulfate  at 40–800 °C with a heating rate of 10 K/min. The composition of SST was derived from the elemental analyzer .SST was characterized by Fourier Transform Infrared Spectroscopy  with a scanning frequency of 400 cmSST with a concentration of 0.25 wt% was dropped on the silicon wafer and dried, and then the microscopic morphology of the microspheres SST was observed using scanning electron microscopy at 10,000×. Additionally, the microscopic morphology of the filter cake was observed at 3000×. The sample preparation procedure followed: we dried the filter cake and glued it on the carrier table using conductive adhesive before gold spraying.The particle size of SST and the drilling fluids was determined using dynamic light scattering (DLS) by a particle sizer  at 10–12% shading. Zeta potential was measured using a potential analyzer  with a 1000 dilution of the sample. The zeta potential value of each sample was achieved by averaging three test results to minimize instrumental measurement errors.The synthetic sandstone core made by the Key Laboratory of Unconventional Oil and Gas Resources Development of China University of Petroleum (East China) was utilized to evaluate the plugging performance of SST. The core was mounted into a core-flooding apparatus  and entirely saturated with water. Water flooding was conducted with an injection rate of 5 mL/min for 48 h. The confining pressure of the flooding experiments was 5 MPa, and the maximum injection pressure was kept below 5 MPa. After completing water flooding, the core was dried using a vacuum oven at 105 °C for 48 h. Following the above experimental procedure, the core-flooding was performed for the flooding experiment using SST with a 2% (volumetric) concentration. The water saturation of the synthetic core after water and SST flooding was tested by NMR  to determine the initial porosity of the core and evaluate the plugging effect of SST, respectively.The elastic modulus (G′) and viscous modulus (G″) of the drilling fluid at different shear frequencies, as well as the viscosity at different shear rates, were measured by a Harker rheometer . The shear frequency ranged from 0.013 Hz, while the shear rate ranged from 0.1–1000 1/s.The fluid loss was measured based on API standards. Specifically, filtration loss or fluid loss is the volume of water lost by drilling fluid through a 75 mm diameter filter area (filter paper) within 30 min at room temperature and 100 psi differential pressure ,24,28. TThe drilling fluid was diluted 10 times and tested for suspension stability using an emulsion stability analyzer  with a scanning interval of 5 min for 2 h ,40. The