Clearance Measurements Research Articles

Accuracy of GFR Estimating Equations in Patients with Discordances between Creatinine and Cystatin C-Based Estimations.

Large discordances between eGFR on the basis of creatinine (eGFR cr ) or cystatin C (eGFR cys ) are common in clinical practice. However, which GFR estimating equation (eGFR cr , eGFR cys , or eGFR cr-cys ) is most accurate in these settings is not known. In this real-world study of 9404 concurrent measurements of creatinine, cystatin C, and iohexol clearance, all three equations performed similarly when eGFR cr and eGFR cys were similar (45% of cases). However, with large discordances (55% of cases), eGFR cr-cys was much more accurate than either alone. These findings were consistent among individuals with cardiovascular disease, heart failure, diabetes mellitus, liver disease, and cancer who have been underrepresented in research cohorts. Thus, when eGFR cr and eGFR cys are largely discordant in clinical practice, eGFR cr-cys is more accurate than eGFR cr or eGFR cys . Cystatin C is recommended as a confirmatory test to eGFR when more precise estimates are needed for clinical decision making. Although eGFR on the basis of both creatinine and cystatin (eGFR cr-cys ) is the most accurate estimate in research studies, it is uncertain whether this is true in real-world settings, particularly when there are large discordances between eGFR based on creatinine (eGFR cr ) and that based on cystatin C (eGFR cys ). We included 6185 adults referred for measured GFR (mGFR) using plasma clearance of iohexol in Stockholm, Sweden, who had 9404 concurrent measurements of creatinine, cystatin C, and iohexol clearance. The performance of eGFR cr , eGFR cys , and eGFR cr-cys was assessed against mGFR with median bias, P30 , and correct classification of GFR categories. We stratified analyses within three categories: eGFR cys at least 20% lower than eGFR cr (eGFR cys <eGFR cr ), eGFR cys within 20% of eGFR cr (eGFR cys ≈eGFR cr ), and eGFR cys at least 20% higher than eGFR cr (eGFR cys >eGFR cr ). eGFR cr and eGFR cys were similar in 4226 (45%) samples, and among these samples all three estimating equations performed similarly. By contrast, eGFR cr-cys was much more accurate in cases of discordance. For example, when eGFR cys <eGFR cr (47% of samples), the median biases were 15.0 (overestimation), -8.5 (underestimation), and 0.8 ml/min per 1.73 m 2 for eGFR cr , eGFR cys , and eGFR cr-cys , respectively; P30 was 50%, 73%, and 84%, respectively; and correct classification was 38%, 45%, and 62%, respectively. When eGFR cys >eGFR cr (8% of samples), the median biases were -4.5, 8.4, and 1.4 ml/min per 1.73m 2 . The findings were consistent among individuals with cardiovascular disease, heart failure, diabetes mellitus, liver disease, and cancer. When eGFR cr and eGFR cys are highly discordant in clinical practice, eGFR cr-cys is more accurate than either eGFR cr or eGFR cys .

Influence of surgical masks on the avoidance of virtual pedestrians

To combat the COVID-19 pandemic, governments around the world have proposed a series of mitigation strategies. While responses varied across different governing bodies, recommendations such as social distancing and the use of surgical masks were nearly universal. These recommendations, as well as the social anxiety that emerged during the pandemic, are likely to have influenced pedestrian interactions. In this study, we have examined the effect of surgical masks on locomotor circumvention strategies in response to virtual pedestrians. We further explored the relationship between measures of obstacle clearance and feelings of anxiety related to community ambulation in the context of the pandemic. Using virtual reality, locomotor circumvention strategies in response to approaching pedestrians with and without surgical masks were measured in a sample of 11 healthy young individuals. Additionally, a questionnaire was developed and used to gain insights into participants’ behaviours during and after a strict period of restrictions that were in effect before the summer of 2020. Results showed that participants maintained a larger clearance when virtual pedestrians wore a surgical mask. Furthermore, clearance was positively associated with anxiety toward community ambulation in the context of the pandemic. Our findings provide evidence that mask-wearing elicits an increase in physical distancing during pedestrian interactions. Furthermore, results indicate that social context and mental health status influence locomotor outcomes measured in the context of a pedestrian interaction task and highlight the potential of virtual reality simulations to study locomotion in the community setting.

Sex and strain differences in renal hemodynamics in mice.

The present study was to examine sex and strain differences in glomerular filtration rate (GFR) and renal blood flow (RBF) in C57BL6, 129/Sv, and C57BLKS/J mice, three commonly used mouse strains in renal research. GFR was measured by transdermal measurement of FITC-sinitrin clearance in conscious mice. RBF was measured by a flow probe placed in the renal artery under an anesthetic state. In C57BL6 mice, there were no sex differences in both GFR and RBF. In 129/Sv mice, females had significantly greater GFR than males at age of 24 weeks, but not at 8 weeks. However, males had higher RBF and lower renal vascular resistance (RVR). Similar to 129/Sv, female C57BLKS/J had significantly greater GFR at both 8 and 24 weeks, lower RBF, and higher RVR than males. Across strains, male 129/Sv had lower GFR and higher RBF than male C57BL6, but no significant difference in GFR and greater RBF than male C57BLKS/J. No significant difference in GFR or RBF was observed between C57BL6 and C57BLKS/J mice. Deletion of eNOS in C57BLKS/J mice reduced GFR in both sexes, but decreased RBF in males. Furthermore, there were no sex differences in the severity of renal injury in eNOS-/- dbdb mice. Taken together, our study suggests that sex differences in renal hemodynamics in mice are strain and age dependent. eNOS was not involved in the sex differences in GFR, but in RBF. Furthermore, the sexual dimorphism did not impact the severity of renal injury in diabetic nephropathy.

Design of a Shield Tail Clearance Measuring Sensor for a Shield Machine

To improve the measurement accuracy and judge the distance between shield segments and shield tail accurately, the online monitoring technology of shield tail clearance was studied. Firstly, a sensor that can be used for shield tail clearance measurement was designed, and its key parts were selected. Secondly, the characteristics of the key parts were simulated to verify their feasibility. Finally, the monitoring principle was analyzed

Frequency-scanning interferometry for axial clearance of rotating machinery based on speed synchronization and extended Kalman filter

Rotor-stator axial clearance is a crucial design parameter affecting rotating machines' efficiency and safety. To realize accurate dynamic axial clearance measurement in high-speed rotating machinery with frequency-scanning interferometry (FSI), this paper proposes a novel algorithm of Doppler error suppression. By introducing rotor speed simultaneously as a Kalman filter parameter, the extended Kalman filter model is constructed by combining the a-priori information of rotating machinery. The feasibility is tested and verified by both simulation and experiment. This algorithm can suppress the Doppler error in FSI measurement and separate the axial movement and end face runout in real-time. Under laboratory conditions, a position measurement precision of ±3.5μm was achieved for rotation speed changing around 2400rpm.

Research on Tip Clearance Measurement Technology of Aero-engine Blade Based on Optical Fiber Sensing System

A novel non-contact detecting method of aero-engine blade tip clearance based on an optical fiber sensing system is presented. To eliminate the sensor measurement error caused by the slight change of the reflectivity value of the mechanical end face when the light source angle fluctuates and rotates, a three-coil coaxial fiber bundle sensor is proposed. Relevant experimental results show that the system has the advantages of high measurement sensitivity, small sensing probe volume, strong electromagnetic interference resistance, and high reliability. The application of this technology provides an effective method for dynamic radial gap detection of high-speed rotating machinery.

Fast algorithm of single frequency-swept interferometry for the dynamic axial clearance measurement of high-speed rotating machinery.

Utilizing the periodicity of the rotating machinery, dynamic clearance measurement can be achieved with a single swept light source without any additional auxiliary devices, which has the advantages of simplicity and reliability. However, there is a shortcoming that previous algorithm is not fast enough to achieve real-time measurement when the machinery rotates at high speed. Aiming at this shortcoming, utilizing the correlation between mimic signal and measurement signal, combined with information for multiple periods, the fast algorithms and dynamic clearance corrected model were proposed. And the relationship between demodulation speed and cycle numbers was also discussed. Simulation was carried out to discuss the influence of different algorithm on the demodulation speed and accuracy. A test system was set up in the simulated environment for clearance measurement, and the results show that, the demodulation time of the proposed algorithm costs decreased dramatically, the speed has increased by about ten times, and the dynamic clearance measurement error is less than 2 µm.

Estimated GFR With Cystatin C and Creatinine in Clinical Practice: A Retrospective Cohort Study

Estimation of glomerular filtration rate (eGFR) and staging of chronic kidney disease (CKD) are essential to guide management. Although creatinine is routinely used, a recent national task force recommended the use of cystatin C for confirmation. The objective of this study was to examine the following parameters: (1) how cystatin C correlates with creatinine eGFR; (2) how it indicates differences in CKD staging; and (3) how it may affect kidney care delivery. Retrospective observational cohort study. 1,783 inpatients and outpatients who had cystatin C and creatinine levels drawn within 24 hours at Brigham Health-affiliated clinical laboratories. Serum creatinine levels, basic clinical/sociodemographic variables, and reasons for ordering cystatin C from a structured partial chart review. Univariate and multivariable linear and logistic regression. Cystatin C-based eGFR was very strongly correlated with creatinine-based eGFR (Spearman correlation ρ=0.83). Cystatin C eGFR resulted in a change to a later CKD stage in 27%, an earlier stage in 7%, and no change in 66% of patients. Black race was associated with a lower likelihood of change to a later stage (OR, 0.53; 95% CI [0.36, 0.75]; P<0.001), whereas age (OR per year OR, 1.03; 95% CI [1.02, 1.04]; P<0.001) and Elixhauser score (OR per point OR, 1.22; 95% CI [1.10, 1.36]; P<0.001) were associated with a higher likelihood of change to a later stage. Single center, no direct measurement of clearance for comparison, and inconsistent self-identification of race/ethnicity. Cystatin C eGFR correlates strongly with creatinine eGFR but can have a substantial effect on CKD staging. As cystatin C is adopted, clinicians must be informed on this impact.

Challenges faced by mango exporters

The mango is one of the most ancient and important Asian fruit. India is the world’s largest mango producer, accounting for 45 per cent of global mango production. Despite being the world’s largest producer of mangoes, India only exports a very small amount of its produce owing to several constraints. The study revealed major challenges faced by mango exporters in Gujarat state. Major challenges were found to be high international freight charges, difficulties in custom clearance, sanitary and phytosanitary (SPS) measures, unavailability of quality mangoes in sufficient quantity, difficulties in certification, high local transportation charges, lack of standardization on post harvest handling, poor infrastructure facilities like cold storage, pack house, etc., competition from other exporting countries, lack of institutional support with respect to credit, problem finding reliable foreign distributor, Unavailability of market information, Price fluctuation of the commodity supply at home country, Problems in quoting price with fluctuating exchange rates, Labelling and packaging requirement, Confusing foreign import regulations and Unavailability or untimely export incentive.

Dynamic and high-speed measurement system for blade tip clearance of engine with optical comb

For blade tip clearance measurement, the optical measurement method has the characteristics of high precision, anti-electromagnetic interference, and non-contact measurement. A dynamic and high-speed blade tip clearance measurement system based on time stretch dispersive Fourier transform with the optical comb is proposed and demonstrated. The dynamic experiments are designed to verify the accuracy of the system. The results show that the measuring speed is up to 17.6 MHz and the measurement errors are less than 1 μm under dynamic conditions. The experiments prove that the system has the advantages of high measurement accuracy, high speed, and good repeatability. It can provide a new tool for engine health monitoring.

675. Sulbactam-durlobactam (SUL-DUR) versus colistin therapy in patients with Acinetobacter baumannii-calcoaceticus complex (ABC) infections: A detailed safety review from the pivotal phase 3, global, randomized, active-controlled trial (ATTACK)

Abstract Background SUL-DUR is a β-lactam/β-lactamase inhibitor combination in development for the treatment of ABC, which is a cause of severe infections with substantial mortality. ATTACK evaluated the efficacy and safety of SUL-DUR versus colistin (COL) in patients with serious ABC infections. The primary efficacy endpoint, 28-day all-cause mortality, was achieved. The safety profile of SUL-DUR versus colistin is presented here. Methods ATTACK consisted of two parts. Part A was the randomized, non-inferiority portion in ABC hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, ventilated pneumonia, or bacteremia; patients were randomized 1:1 to SUL-DUR or colistin for 7 to 14 days. Part B provided open label SUL-DUR for patients intolerant of colistin or with colistin-resistant ABC. Safety data presented here include both Part A and Part B. All patients received imipenem/cilastatin as background therapy. The primary safety objective was nephrotoxicity (RIFLE classification); other safety endpoints included treatment-emergent adverse events (TEAEs) and assessments of laboratory parameters. Results The safety population includes 203 unique patients. TEAEs were common reflecting the critical level of illness. More frequently reported with colistin treatment are severe, serious, and drug-related TEAEs (infections, renal and urinary disorders, and gastrointestinal) (Table 1). Nervous system, infections and renal disorders leading to discontinuation of study drug were more common in the colistin arm (Table 2). During treatment, liver-associated enzymes were similar between arms. Creatinine clearance measures of central tendency showed reduction during the trial in the colistin arm. Nephrotoxicity (RIFLE classification) occurred significantly less often with SUL-DUR: 13.2% (12/91) and 37.6% (32/85), difference -24.4% [p=0.0002]. Conclusion SUL-DUR treated patients had reduced nephrotoxicity, fewer drug-related TEAEs, no safety signals, and fewer TEAEs leading to discontinuation of study drug. If approved, SUL-DUR could be an important therapeutic option for Acinetobacter infections including carbapenem-resistant and multidrug-resistant strains. Disclosures Drew Lewis, MD, MTM&amp;H, Entasis Therapeutics: employee|Entasis Therapeutics: employee|Entasis Therapeutics: Stocks/Bonds|Entasis Therapeutics: Stocks/Bonds Khurram Rana, PharmD, Entasis Therapeutics: Employee|Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds Gabrielle Poirier, BS, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds David Altarac, MD, MPA, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds.

From environmental exploration to clearance measurement – developing mobile robot systems for decommissioning of nuclear power plants

Abstract The number of decommissioning projects related to nuclear power plants is increasing and has been regarded as a challenging task for many nations. For example, Germany has decided to phase out nuclear power plants by the year 2022. To reduce the hazardous potential and the personal radiation exposure of the employees, robotic support in the decommissioning process is needed. In this contribution, a robot-based closed chain is presented as an important component for an automation and digitalization of the dismantling process of a nuclear power plant. The focus of the chain is on the investigation and decontamination of flat wall areas in nuclear facilities. First, geometric and radiation data are collected autonomously with a mobile, agile robot. The collected data is processed by using Building Information Modelling (BIM) methods to support the following steps. A second, industrial platform is modified to enable the positioning of two developed tools, a milling tool, and a contamination array, which will be used for decontamination and clearance measurement of concrete surfaces.

Umbilical Cord Blood Cell Clearance Post-Infusion in Immune-Competent Children with Cerebral Palsy

Umbilical cord blood cells have therapeutic potential for neurological disorders, through a paracrine mechanism of action. A greater understanding of the safety and immunological effects of allogeneic donor cord blood cells in the context of a healthy recipient immune system, such as in cerebral palsy, is needed. This study aimed to determine how quickly donor cord blood cells were cleared from the circulation in children with cerebral palsy who received a single intravenous infusion of 12/12 human leucocyte antigen (HLA)-matched sibling cord blood cells. Twelve participants with cerebral palsy aged 2–12 years received cord blood cell infusions as part of a phase I trial of umbilical blood infusion for cerebral palsy. Digital droplet PCR analysis of DNA copy number variants specific to donor and recipient was used to assess donor DNA clearance at five timepoints post-infusion, a surrogate measure of cell clearance. Donor cells were cleared by 3 months post-infusion in 11/12 participants. When detected, donor DNA was at a fraction of 0.01–0.31% of total DNA with no signs of graft-versus-host disease in any participant. The donor DNA clearance times provided by this study have important implications for understanding the safety of allogeneic cord blood cell infusion for cerebral palsy and translational tissue engineering or regenerative medicine research in other disorders.

157 A randomized controlled trial to determine the most sensitive outcome measure of airway clearance in cystic fibrosis

157 A randomized controlled trial to determine the most sensitive outcome measure of airway clearance in cystic fibrosis

Nasal epithelial cell culture fluorescence recovery after photobleaching predicts cystic fibrosis therapeutic response.

Human nasal epithelial (HNE) cells can be sampled noninvasively and cultured to provide a model of the airway epithelium that reflects cystic fibrosis (CF) pathophysiology. We hypothesised that in vitro measures of HNE cell physiology would correlate directly with in vivo measures of lung physiology and therapeutic response, providing a framework for using HNE cells for therapeutic development and precision medicine. We sampled nasal cells from participants with CF (CF group, n=26), healthy controls (HC group, n=14) and single CF transmembrane conductance regulator (CFTR) mutation carrier parents of the CF group (CR group, n=16). Participants underwent lung physiology and sweat chloride testing, and nuclear imaging-based measurement of mucociliary clearance (MCC) and small-molecule absorption (ABS). CF participants completed a second imaging day that included hypertonic saline (HS) inhalation to assess therapeutic response in terms of MCC. HNE measurements included Ussing chamber electrophysiology, small-molecule and liquid absorption rates, and particle diffusion rates through the HNE airway surface liquid (ASL) measured using fluorescence recovery after photobleaching (FRAP). Long FRAP diffusion times were associated with increased MCC response to HS in CF. This implies a strong relationship between inherent factors affecting ASL mucin concentration and therapeutic response to a hydrating therapy. MCC decreased with age in the CR group, which had a larger range of ages than the other two groups. Likely this indicates a general age-related effect that may be accentuated in this group. Measures of lung ABS correlated with sweat chloride in both the HC and CF groups, indicating that CFTR function drives this measure of paracellular small-molecule probe absorption. Our results demonstrate the utility of HNE cultures for assessing therapeutic response for hydrating therapies. In vitro measurements of FRAP were particularly useful for predicting response and for characterising important properties of ASL mucus that were ultimately reflected in lung physiology.

New model-based method for aero-engine turbine blade tip clearance measurement

Active control of aero-engine turbine tip clearance is one of the best chances for engine performance uplift currently. To do that, the first requirement is real-time measurement of tip clearance in aero-engine working environment. However, turbine complexity makes it unlikely for tip clearance sensors to be loaded. In recognition of that, this paper proposed a model-based method for tip clearance measurement. Firstly, by considering previously wrongly neglected factors such as load deformation, a mathematical model to monitor dynamic tip clearance changes is built to improve calculation accuracy. Then, after clarifying the coupling relationship between engine models and tip clearance models, this paper builds a component-level mathematical model integrating dynamic characteristics of turbine tip clearance, which helps realize accurate measurement of tip clearance in working environment. How tip clearance affects turbine efficiency is studied afterwards and reported to aero-engine model, so as to mitigate performance difference between aero-engine model and real engines caused by turbine tip clearance. Lastly, by hardware-in-the-loop simulation, tip clearance model demonstrates 15.9% better accuracy than previously built models in terms of turbine centrifugal deformation calculation. As tip clearance measurement model takes averagely 0.34 ms in calculation, meeting the operation requirement, it proves to be an effective new way.

In vitro electrochemical detection of the degradation of amyloid-β oligomers

The clearance of overloaded amyloid β (Aβ) oligomers is thought to be an attractive and potential strategy for the therapy of Alzheimer’s disease (AD). A variety of strategies have already been utilized to study Aβ degradation in vitro. Here, the electrochemical detection based on direct electrooxidation of specific Tyr residues within Aβ peptide has been developed as a simple and robust approach for monitoring the oligomers’ degradation. C60 was employed for photodegrading Aβ oligomers due to the generated ROS under light irradiation. The oxidation current of Tyr residues by square wave voltammetry (SWV) increased upon the Aβ degradation, confirming that the structure variation of Aβ peptide indeed influenced the exposure of those redox species to the electrode surface and final signal output. Chronoamperometric assay also found the electrooxidation of Tyr undergone an irreversible process. Additionally, the direct electrochemistry was capable of detecting the aggregation with rapid test and better sensitivity in compared with dynamic light scattering (DLS), atomic force microscopy (AFM) and thioflavin T (ThT) based fluorescence assay. Thus, this work indicated the potential application of direct electrochemistry in the in vitro measurement of Aβ degradation and clearance, providing new insights and a complementary means into the AD theranostics.

An Endorsement of the Removal of Race From GFR Estimation Equations: A Position Statement From the National Kidney Foundation Kidney Disease Outcomes Quality Initiative

An Endorsement of the Removal of Race From GFR Estimation Equations: A Position Statement From the National Kidney Foundation Kidney Disease Outcomes Quality Initiative

Validation of Methods for in Vitro-in Vivo Extrapolation Using Hepatic Clearance Measurements in Isolated Perfused Fish Livers.

In vitro biotransformation assays using hepatocytes or liver subcellular fractions, combined with in vitro-in vivo extrapolation (IVIVE) models, have been proposed as an alternative to live fish bioconcentration studies. The uncertainty associated with IVIVE approaches to date has been attributed to assay protocols, model assumptions, or variability of in vivo data. An isolated perfused trout liver model that measures hepatic clearance has been proposed for validating IVIVE predictions in the absence of other confounding factors. Here, we investigated the hepatic clearances of five chemicals (pyrene, phenanthrene, 4-n-nonlyphenol, deltamethrin, and methoxychlor) in this model and compared measured rates to values predicted from published in vitro intrinsic clearances for validation of IVIVE models. Additionally, we varied protein concentrations in perfusates to test binding assumptions of these models. We found that measured and predicted hepatic clearances were in very good agreement (root mean squared error 16.8 mL h-1 g-1) across three levels of protein binding and across a more diverse chemical space than previously studied within this system. Our results show that current IVIVE methods can reliably predict in vivo clearance rates and indicate that discrepancies from measured bioconcentration factors might be driven by other processes, such as extrahepatic biotransformation, etc., and help streamline optimization efforts to the processes that truly matter.

Dual-View Stereovision-Guided Automatic Inspection System for Overhead Transmission Line Corridor

Overhead transmission line corridor detection is important to ensure the safety of power facilities. Frequent and uncertain changes in the transmission line corridor environment requires an efficient and autonomous UAV inspection system, whereas the existing UAV-based inspection systems has some shortcomings in control model and ground clearance measurement. For one thing, the existing manual control model has the risk of striking power lines because it is difficult for manipulators to judge the distance between the UAV fuselage and power lines accurately. For another, the ground clearance methods based on UAV usually depend on LiDAR (Light Detection and Ranging) or single-view visual repeat scanning, with which it is difficult to balance efficiency and accuracy. Aiming at addressing the challenging issues above, a novel UAV inspection system is developed, which can sense 3D information of transmission line corridor by the cooperation of the dual-view stereovision module and an advanced embedded NVIDIA platform. In addition, a series of advanced algorithms are embedded in the system to realize autonomous control of UAVs and ground clearance measurement. Firstly, an edge-assisted power line detection method is proposed to locate the power line accurately. Then, 3D reconstruction of the power line is achieved based on binocular vision, and the target flight points are generated in the world coordinate system one-by-one to guide the UAVs movement along power lines autonomously. In order to correctly detect whether the ground clearances are in the range of safety, we propose an aerial image classification based on a light-weight semantic segmentation network to provide auxiliary information categories of ground objects. Then, the 3D points of ground objects are reconstructed according to the matching points set obtained by an efficient feature matching method, and concatenated with 3D points of power lines. Finally, the ground clearance can be measured and detected according to the generated 3D points of the transmission line corridor. Tests on both corresponding datasets and practical 220-kV transmission line corridors are conducted. The experimental results of different modules reveal that our proposed system can be applied in practical inspection environments and has good performance.