Testing the altitude attribution and vertical resolution of AirCore measurements with a new spiking method

AirCore samplers have been increasingly used to capture vertical profiles of trace gases reaching from the ground up to about 30 km, in order to validate remote sensing instruments and to investigate transport processes in the stratosphere. When deployed to a weather balloon, accurately attributing the trace gas measurements to the sampling altitudes is nontrivial, especially in the stratosphere. In this paper we present the CO-spiking experiment, which can be deployed to any AirCore on any platform in order to evaluate different computational altitude attribution processes and to experimentally derive the vertical resolution of the profile by injecting small volumes of signal gas at predefined GPS altitudes during sampling. We performed two CO-spiking flights with an AirCore from the Goethe University Frankfurt (GUF) deployed to a weather balloon in Traînou, France, in June 2019. The altitude retrieval based on an instantaneous pressure equilibrium assumption slightly overestimates the sampling altitudes, especially at the top of the profiles. For these two flights our altitude attribution is accurate within 250 m below 20 km. Above 20 km the positive bias becomes larger and reaches up to 1.2 km at 27 km altitude. Differences in descent velocities are shown to have a major impact on the altitude attribution bias. We parameterize the time lag between the theoretically attributed altitude and the actual CO-spike release altitude for both flights together and use it to empirically correct our AirCore altitude retrieval. Regarding the corrected profiles, the altitude attribution is accurate within ±120 m throughout the profile. Further investigations are needed in order to test for the scope of validity of this correction parameter regarding different ambient conditions and maximum flight altitudes. We derive the vertical resolution from the CO spikes of both flights and compare it to the modeled vertical resolution. The modeled vertical resolution is too optimistic compared to the experimentally derived resolution throughout the profile, albeit agreeing within 220 m. All our findings derived from the two CO-spiking flights are strictly bound to the GUF AirCore dimensions. The newly introduced CO-spiking experiment can be used to test different combinations of AirCore configurations and platforms in future studies.

Testing the altitude attribution and vertical resolution of AirCore measurements with a new spiking method

AirCores have been increasingly used to capture vertical profiles of trace gases reaching from the ground up to about 30 km, in order to validate remote sensing instruments and to investigate transport processes in the stratosphere. When deployed to a weather balloon, accurately attributing the trace gas measurements to the sampling altitudes is non-trivial especially in the stratosphere. In this paper we present the CO-spiking experiment, which can be deployed to any AirCore on any platform in order to evaluate different computational altitude attribution processes and to experimentally derive the vertical resolution of the profile by injecting small volumes of signal gas at predefined GPS-altitudes during sampling. We performed two CO-spiking flights with an AirCore from the Goethe-University of Frankfurt (GUF) deployed to a weather balloon in Traînou, France in June 2019. The altitude retrieval based on an instantaneous pressure equilibrium assumption slightly overestimates the sampling altitudes, especially at the top of the profiles. For these two flights our altitude attribution is accurate within 250 m below 20 km. Above 20 km the bias becomes larger and reaches up to 1.2 km at 27 km altitude. Differences in descent velocities are uncovered to have a major impact on the altitude attribution bias. We identified the time lag between the theoretically attributed altitude and the actual CO-spike release altitude to be a possible empirical correction parameter for our AirCore altitude retrieval across different flights. Regarding the corrected profiles, the altitude attribution is accurate within 120 m throughout the profile. Further investigations are needed in order to test for the scope of validity of this correction parameter regarding different ambient conditions and maximum flight altitudes. We derive the vertical resolution from the CO-spikes of both flights and compare it to the modelled vertical resolution. The modelled vertical resolution is better than the experimentally derived resolution throughout the profile, albeit agrees within 220 m. All our findings derived from the two CO-spiking flights are strictly bound to the GUF AirCore dimensions. The newly introduced CO-spiking experiment can be used to test different combinations of AirCore configurations and platforms in future studies.

Cefoxitin-Serum Creatinine Interference in a Patient With Nontuberculous Mycobacteria Ventriculomeningitis

Cefoxitin is a second-generation cephamycin antibiotic, which at concentrations ≥100 µg/mL is known to modestly interfere, for up to 2 hours post-infusion, with serum creatinine measurement via the traditional Jaffe-based assay. We report a case of a severe serum creatinine elevation while utilizing cefoxitin as a component of an antimicrobial regimen in a critically ill patient with Mycobacterium abscessus ventriculomeningitis. Our results, both via patient serum analysis and a cefoxitin spiking experiment, demonstrate interference despite the utilization of improved modern Jaffe-based assays. In fact, the cefoxitin-creatinine interference may be clinically relevant at concentrations 3 times lower than that listed in the package insert and may display more than a modest interference at typical therapeutic concentrations.

Mean Age from in situ observations with AirCore: Accuracy of altitude attribution investigated with the CO-spiking experiment

<p>In order to monitor possible changes of the mean age of air in the stratosphere, in situ high altitude observations of suitable tracers are required. The AirCore is a simple sampling technique, which can be deployed to weather balloons in order to capture a continuous vertical profile of atmospheric trace gases up to 30 km. During ascent it empties due to the decreasing ambient pressure with height. During descent the AirCore fills with ambient air due to the positive change in ambient pressure. The analysis results from a continuous gas analyzer are merged with the recorded in-flight information to obtain the vertical distribution of the target trace gases mole fractions.</p><p>In context of the Goethe-University data processing procedure, an instantaneous pressure equilibrium is assumed across the whole AirCore. Since the amount of collected air sample is especially low at high altitudes, the assumptions made for data processing affect the accuracy of the altitude attribution primarily in the stratosphere. In order to evaluate the sample-to-altitude attribution procedure, the setup for an altitude dependent CO-spiking experiment was developed, tested and deployed to an AirCore that was flown and analyzed in Traînou, France, in June 2019. This setup allows for releasing small spikes of high CO signal gas in the inlet of the AirCore during descent at predefined GPS altitudes. By assigning the associated mole fraction measurements to the sampling altitude, the spiking signals are assigned to a modelled altitude as well. The quality of the altitude retrieval can be evaluated by comparing the assigned signal altitudes to the GPS release altitudes. In principle, every laboratory can deploy this experiment to its respective AirCores in order to evaluate its altitude attribution quality. Here we present the experimental details and the results of the evaluation to show the accuracy of the altitude registration of Goethe-University AirCore profiles. In addition, the long-term time series of mid-latitude stratospheric mean age observations from Engel et al 2017 is extended with mean age calculated from CO<sub>2</sub>-profiles obtained from recent AirCore observations.</p>

ITIH5 and ECRG4 DNA Methylation Biomarker Test (EI-BLA) for Urine-Based Non-Invasive Detection of Bladder Cancer

Bladder cancer is one of the more common malignancies in humans and the most expensive tumor for treating in the Unites States (US) and Europe due to the need for lifelong surveillance. Non-invasive tests approved by the FDA have not been widely adopted in routine diagnosis so far. Therefore, we aimed to characterize the two putative tumor suppressor genes ECRG4 and ITIH5 as novel urinary DNA methylation biomarkers that are suitable for non-invasive detection of bladder cancer. While assessing the analytical performance, a spiking experiment was performed by determining the limit of RT112 tumor cell detection (range: 100–10,000 cells) in the urine of healthy donors in dependency of the processing protocols of the RWTH cBMB. Clinically, urine sediments of 474 patients were analyzed by using quantitative methylation-specific PCR (qMSP) and Methylation Sensitive Restriction Enzyme (MSRE) qPCR techniques. Overall, ECRG4-ITIH5 showed a sensitivity of 64% to 70% with a specificity ranging between 80% and 92%, i.e., discriminating healthy, benign lesions, and/or inflammatory diseases from bladder tumors. When comparing single biomarkers, ECRG4 achieved a sensitivity of 73%, which was increased by combination with the known biomarker candidate NID2 up to 76% at a specificity of 97%. Hence, ITIH5 and, in particular, ECRG4 might be promising candidates for further optimizing current bladder cancer biomarker panels and platforms.

Effects of Enoxaparin on Intravascular Sclerostin Release in Healthy Men

Sclerostin (Scl) is implicated in vascular calcification and angiogenesis and localizes within vasculature. Its molecule incorporates a heparin-binding site that implies also binding to endothelial glycocalyx. We preliminary tested whether intravenous (IV) low-molecular-weight heparin enoxaparin can stimulate intravascular release of this calcification inhibitor in humans. Sixteen male volunteers were injected with a bolus of 1 mg/kg body weight of enoxaparin. After 10 minutes, plasma immunoreactive Scl levels increased uniformly by a mean of 184% versus baseline level of 0.56 ± 0.17 ng/mL ( P = .0004). Plasma Scl levels were found still elevated after 2 and 6 hours (with a median of 20.9% and 8.69%, respectively) and became normal after 24 hours. The percentage of increase (Δ) in plasma Scl after 10 minutes was directly correlated with enoxaparin dose per kg/m2 of body mass index (ρ = 0.587, P = .017) and strongly inversely correlated with the preinjection Scl levels (ρ = −0.747, P = .0008). A robust negative association between the ΔScl increase after 10 minutes and the ΔScl decrease after 2 hours versus 10 minutes was observed (ρ = −0.835, P < .0001). Complementary in vitro spiking experiment showed no effects of enoxaparin addition and whole blood incubation on plasma Scl levels when measured with the immunoassay. This study shows that enoxaparin has a stimulating effect on the intravascular release of calcification inhibitor Scl in healthy men. This novel pharmacological action of the popular anticoagulant drug seems important in cardiovascular medicine.

Simultaneous Determination of Sildenafil and Tadalafil in Legal Drugs, Illicit/Counterfeit Drugs, and Wastewater Samples by High-Performance Liquid Chromatography

A sensitive analytical method was developed for the simultaneous determination of sildenafil and tadalafil in legal drugs, illicit/counterfeit drugs, and wastewater samples. Chromatographic separation of two analytes was achieved on a C18 column with a mobile phase including 50 mM phosphate buffer at pH 6.0 and acetonitrile (35 + 65, v/v) at the flow rate of 1.0 mL/min. Analytes were separated from each other in 6 min with high resolution. LOD/LOQ values were calculated as 28/92 ng/mL for sildenafil citrate and 39/129 ng/mL for tadalafil. Calibration plots for both analytes were linear with correlation coefficients &gt;0.9993. A validated method was successfully applied to legal and illicit erectile-dysfunction drug samples consumed in Istanbul, Turkey, and to wastewater samples. Nine different samples were analyzed for qualitative and quantitative measurement of their ingredients, and the results were compared with the values written on the labels of the drugs. The wastewater sample was also analyzed for its sildenafil and tadalafil content. To calculate the recoveries, a spiking experiment was performed and recovery rates for sildenafil and tadalafil were calculated as 101.30 ± 3.43 and 102.68 ± 1.59, respectively.

Significance of Serum 24,25-Dihydroxyvitamin D in the Assessment of Vitamin D Status: A Double-edged Sword?

BACKGROUND 24,25-Dihydroxyvitamin D [24,25(OH)2D] in serum may be both a nuisance and nutritionally valuable. METHODS We investigated the impact of 24,25(OH)2D3 on the performance of commercially available immunoassays for serum total 25-hydroxyvitamin D [25(OH)D] using (a) serum from a nationally representative sample of adults, (b) serum from a spiking experiment, and (c) data from the UK Vitamin D External Quality Assurance Scheme (DEQAS). We also investigated the utility of the serum ratio of 24,25(OH)2D3 to 25(OH)D as an index of inactivation and of response to vitamin D supplementation using randomized controlled trial (RCT) data. Measurement of 24,25(OH)2D in sera by a LC-MS/MS method allowed for an investigation of its impact on immunoassay-derived serum 25(OH)D values as well as its clinical utility. We report data from a nationally representative sample of adults, a recent vitamin D RCT in older adults, and DEQAS. RESULTS 24,25(OH)2D3 contributed to the positive bias observed in some immunoassays relative to LC-MS/MS-derived estimates for total 25(OH)D. A spiking experiment showed that the degree of cross-reactivity with 24,25(OH)2D was high and may underpin this positive bias. Adjustment for 24,25(OH)2D3 concentration brought estimates closer to true values. Data from the vitamin D RCT showed that the ratio of 24,25(OH)2D3 to 25(OH)D was associated with serum 25(OH)D3 and with response of serum 25(OH)D to vitamin D supplementation. CONCLUSIONS Our findings highlight that the effect of 24,25(OH)2D3 in serum is a double-edged sword—an interferent for some immunoassays, yet potentially informative of nutritional status.

Influence of Extraction Methodologies on the Analysis of Five Major Volatile Aromatic Compounds of Citronella Grass (Cymbopogon nardus) and Lemongrass (Cymbopogon citratus) Grown in Thailand

This paper deals with the systematic comparison of extraction of major volatile aromatic compounds (VACs) of citronella grass and lemongrass by classical microhydrodistillation (MHD), as well as modern accelerated solvent extraction (ASE). Sixteen VACs were identified by GC/MS. GC-flame ionization detection was used for the quantification of five VACs (citronellal, citronellol, geraniol, citral, and eugenol) to compare the extraction efficiency of the two different methods. Linear range, LOD, and LOQ were calculated for the five VACs. Intraday and interday precisions for the analysis of VACs were determined for each sample. The extraction recovery, as calculated by a spiking experiment with known standards of VACs, by ASE and MHD ranged from 64.9 to 91.2% and 74.3 to 95.2%, respectively. The extraction efficiency of the VACs was compared for three solvents of varying polarities (hexane, dichloromethane, and methanol), seven different temperatures (ranging from 40 to 160°C, with a gradual increment of 20°C), five time periods (from 1 to 10 min), and three cycles (1, 2, and 3 repeated extractions). Optimum extraction yields of VACs were obtained when extractions were carried out for 7 min with dichloromethane and two extraction cycles at 120°C. The results showed that the ASE technique is more efficient than MHD, as it results in improved yields and significant reduction in extraction time with automated extraction capabilities.