Standard Liquid Research Articles

Abstract 689: A randomized phase III study assessing the efficacy of liquid biopsy in early diagnosis of recurrence and second malignancies in lung cancer survivors

Abstract We designed a 6,000-patient prospective, multi-institutional randomized clinical trial to assess the efficacy of liquid biopsy in early diagnosis of recurrence and second malignancies in lung cancer survivors. To ensure over 25% of participants are of disadvantaged or minority status, we have recruited multiple community hospitals (Jamaica, Flushing, Wyckoff, and Staten Island/Bronx satellites of Northwell hospitals) to the study in partnership with Memorial Sloan Kettering Cancer Center. Patients included in this study are survivors of non-metastatic non-small cell lung cancer, status-post definitive treatment (surgery or radiation) with no evidence of disease for at least one year. These patients may be on maintenance therapy for their prior lung cancer but may not have any other active malignancy at the time of enrollment. Participants will be randomized 1:1 to standard surveillance at the discretion of the treating physician or standard surveillance plus six-monthly methylation-based liquid biopsy tests over a two-year study period, and strict guidelines on follow-up of positive liquid biopsy testing will be provided to reduce harms from false positives or overdiagnosis. The primary endpoint of this study is the incidence of late stage cancer (distant recurrence or new primary cancer of stage III/IV). Secondary endpoints include incidence of early cancers (locoregional recurrence or new primary cancer of stage I/II), metastasis-free survival, and utilization of liquid biopsy versus standard of care scans. We will stratify our results by minority and socioeconomic status to specifically ascertain the effect of this intervention on populations of need. This is the first randomized controlled trial of liquid biopsy in a survivor population and the first trial utilizing liquid biopsy in a large minority population. We will have preliminary experiences to report in April 2022. Citation Format: Sana Raoof. A randomized phase III study assessing the efficacy of liquid biopsy in early diagnosis of recurrence and second malignancies in lung cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 689.

NLDFT adsorption models for zeolite porosity analysis with particular focus on ultra-microporous zeolites using O2 and H2

The most often used gases for the PSD characterization of zeolites are N2 and Ar. According to the IUPAC Technical Report (2015), Ar is recommended as more reliable than N2, which molecules possess a significant quadrupole moment that may influence the adsorption isotherms on polar surfaces. In practice, however, using Ar as a cryogen for Ar adsorption measurements is not preferred due to its higher cost than liquid N2.We propose using O2 which has a much lower quadrupole moment than N2, and its adsorption can be measured using standard liquid N2 as a coolant. To support using O2, we demonstrate good agreement between the PSDs calculated from O2 and Ar adsorption.In the present work, we develop several semiempirical models based on nonlocald density functional theory (NLDFT) for the PSD characterization of several types of zeolites.We discuss the underlying difficulties in modeling gas adsorption on zeolites which adsorption potential field depends on both the pore width and the chemical structure of the zeolite.For the analysis of ultra microporous zeolites such as Chabazite and molecular sieve 5A, we apply H2 in combination with O2 at 77 K. H2 molecule has a smaller diameter than O2 and diffuses faster into ultra micropores, reducing the time of isotherm measurement. Moreover, we show that the dual gas analysis method can be used with O2 isotherms measurements omitting low-pressure points, making the analysis faster.

A randomized phase III study assessing the efficacy of liquid biopsy in early diagnosis of recurrence and second malignancies in lung cancer survivors.

TPS10617 Background: Lung cancer survivors are highly enriched for extensive smoking histories and have an increased risk of subsequent primary cancers, including those of the larynx, mouth and throat, esophagus, pancreas, bladder, thyroid, stomach, small intestine, colon, rectum, and kidney. Guideline-concordant surveillance after definitive treatment for lung cancer consists of periodic chest CT scans, which do not visualize the majority of second malignancies that this population ultimately develops. Disadvantaged and minority patients are diagnosed with recurrence and second primary cancers at later stages due to reduced compliance with survivorship surveillance. To address these issues, we propose utilizing multi-cancer early detection (MCED) liquid biopsies. MCED liquid biopsies are part of a rapidly growing field of research that assesses parallel cancer screening for multiple cancer types with point of care blood, urine, or saliva sampling. We selected a methylation-based screening liquid biopsy for multiple reasons: 1) it has the highest PPV and specificity of any test clinically validated in the multi-cancer detection setting thus far, 2) it produces a tissue of origin, allowing for targeted workup of positive findings, and 3) it requires only a single test, which we believe will minimize attrition among vulnerable populations with decreased access to healthcare. We designed a 9,000-patient prospective, multi-institutional randomized clinical trial to assess the efficacy of liquid biopsy in early diagnosis of recurrence and second malignancies in lung cancer survivors. To ensure over 25% of participants are of minority status, we have recruited multiple community hospitals to the study in partnership with Memorial Sloan Kettering Cancer Center. Patients included in this study are survivors of non-metastatic non- small cell lung cancer, status-post definitive treatment (surgery or radiation) with no evidence of disease for at least one year. Participants will be randomized 1:1 to standard surveillance or standard surveillance plus six-monthly methylation-based liquid biopsy tests over a two-year study period, and strict guidelines on follow-up of positive liquid biopsy testing will be provided to reduce harms from false positives or over-diagnosis. Methods: The primary endpoint of this study is the incidence of late stage cancer (distant recurrence or new primary cancer of stage III/IV). Secondary endpoints include cancer-specific mortality, eligibility for definitive interventions once cancer is diagnosed, and utilization of liquid biopsy versus standard of care scans. This is the first randomized controlled trial of screening liquid biopsy in a survivorship population and the first trial utilizing liquid biopsy in a large minority population.

Online measurement of syrup brix with microwave open coaxial resonator sensor

Aiming at the shortcomings of the existing online measurement methods of syrup brix, a microwave open coaxial resonator sensor with an improved structure was developed, which can be used in the automatic sugar production process. When the syrup mixture comes into contact with the opening of the resonant cavity, the resonant responses (resonant frequency and quality factor) are significantly changed by the material perturbation. By measuring a standard liquid sample with known permittivity, the electric permittivity could be accurately determined. For syrup of 55–90 °Bx, the resonance frequency increases with the increase in brix, and there is a highly reliable quadratic relationship between them. In addition, a quartic relationship exists between the quality factor and the brix; a quadratic relationship between the real part of permittivity and the brix; and a quartic relationship between the imaginary part of the permittivity and the brix. Hence, both the resonant responses of the resonator and the permittivity obtained can be used to evaluate the brix of syrup. Further, the resonant frequency, which had the best correlation, was selected as the index for syrup brix measurement, and standard syrup samples from 60 to 90 °Bx were measured online. The errors between the predicted and measured values were less than 2%, which indicates that the resonant frequency can be used as a reliable index for syrup brix measurement. The syrup brix sensor has the advantages of high accuracy and stability, and can be applied to online measurement of syrup brix in sucrose production to improve the quality of sucrose products. • A microwave method using an open coaxial resonator is proposed for the measurement of the brix of syrup for the first time. • The structure of the sensor has been improved, which makes it have higher measurement accuracy and stability. • Electromagnetic simulation was carried out to reveal the resonant fields.

Dietary Lysine Requirement of Women Over 60 Years Estimated Using Indicator Amino Acid Oxidation (IAAO) Technique, Is Not Different From Current Recommendations

ObjectivesThe goals of the current study were to 1) define the lysine requirement in female adults >60years using the indicator amino acid oxidation method (IAAO) method with L-[1–13C]phenylalanine as the indicator and to 2) compare the derived estimate to our previous estimates in young women done in both luteal and follicular phase of the mensural cycle. MethodsSixteen healthy women (>60 years) were randomly assigned to receive 3 to 7 lysine intakes from 10 to 80 mg. kg–1. d–1. Subjects were adapted to a standard liquid diet providing 1.0 g. kg–1.d–1protein and adequate energy, for 2 days, with indicator oxidation measurements on day 3. The rate of release of13CO2 from the oxidation of L-[1–13C]phenylalanine was measured in breath. A two-phase linear mixed effect model, and parametric bootstrap was used to determine the mean and 95% confidence interval (CI) of the lysine requirement. The overlap of the 95% CI between the older and younger women were used to compare the requirement estimates. The null hypothesis was accepted if the interval contained zero. ResultsThe mean and upper 95% CI of the lysine requirement of older women was 29 and 33 mg.kg–1.d–1respectively. This was not different from our previous estimate of 30.9 mg.kg–1.d–1for young women in the follicular phase of the mensural cycle. However, it was lower than our previous estimate of 37.7 mg.kg–1.d–1derived during the luteal phase of the mensural cycle. ConclusionsThis is the first study to report on the lysine requirement in older women >60 years. Although the estimate in older women is not different from current recommendations derived in young men, the results suggest that lysine requirement in young and older women may differ based on mensural cycle phase. Funding SourcesCIHR.

Quality of Oral Drug Formulations of Artemisinin-Based Combination Therapy Sold in Katsina State, Nigeria

There are increasing reports of substandard antimalarial drugs, and these have been a severe under-recognised public health problem especially in developing countries. For this reason, 21 samples of different brands of artemisinin-based combination therapies (ACTs) comprising of artemether/lumefantrine and artesunate/amodiaquine oral drug formulations that are available on sale in different hospital pharmacies and patent medicine stores in Katsina State, Nigeria were evaluated for microbial and chemical qualities. Microbial limit test (MLT) and assay for the content of the active pharmaceutical ingredients (APIs) using standard high performance liquid chromatography (HPLC) procedures were carried out as described in the official monograph of the United States Pharmacopoeia (USP) and the International Pharmacopoeia (IP). The results obtained had indicated that all the ACTs oral drug preparations were free from microbial contamination except one sample of artesunate-amodiaquine showing viable total combined yeasts/moulds count (TYMC) of 1.0 x 101 colony forming units (CFU)/g. All the samples complied with the USP and IP criteria for the microbiological quality of non-sterile oral dosage forms. On the other hand, 10 (47.6%) out of the 21 samples met the specific chemical quality standards. Moreover, 8 (57.1%) and 3 (42.9%) of the artemether/lumefantrine and artesunate/amodiaquine had active ingredient outside the set pharmacopoeial limit and, therefore, were none compliant to the IP specifications for percentage content. The presence of substandard ACTs may lead to possible therapeutic failure from the use of such kind of formulations, facilitate the development and spread of drug-resistance. There is the need for effective government regulation and adequate enforcement on the production, distribution and sales of good quality medicines.

MP48-05 CHANGES IN PITUITARY–GONADAL HORMONES AFTER ENZALUTAMIDE OR ABIRATERONE PLUS PREDNISONE IN MEN WITH CASTRATION-RESISTANT PROSTATE CANCER (HEAT): RESULTS FROM A RANDOMISED CLINICAL TRIAL

You have accessJournal of UrologyCME1 May 2022MP48-05 CHANGES IN PITUITARY–GONADAL HORMONES AFTER ENZALUTAMIDE OR ABIRATERONE PLUS PREDNISONE IN MEN WITH CASTRATION-RESISTANT PROSTATE CANCER (HEAT): RESULTS FROM A RANDOMISED CLINICAL TRIAL Klara Ternov, Jens Sønksen, Mikkel Fode, Henriette Lindberg, Caroline Kistorp, Rasmus Bisbjerg, Jens Faber, Ganesh Palapattu, and Peter Busch Østergren Klara TernovKlara Ternov More articles by this author , Jens SønksenJens Sønksen More articles by this author , Mikkel FodeMikkel Fode More articles by this author , Henriette LindbergHenriette Lindberg More articles by this author , Caroline KistorpCaroline Kistorp More articles by this author , Rasmus BisbjergRasmus Bisbjerg More articles by this author , Jens FaberJens Faber More articles by this author , Ganesh PalapattuGanesh Palapattu More articles by this author , and Peter Busch ØstergrenPeter Busch Østergren More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002619.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Enzalutamide (ENZ) and abiraterone acetate plus prednisone (AAP) are both androgen receptor targeting treatments for metastatic castration-resistant prostate cancer (mCRPC). AAP inhibits the androgen production, whereas ENZ blocks the androgen receptor signalling. Herein, we compare treatment changes between ENZ and AAP in hormones of the pituitary–gonadal axis. METHODS: First-line ENZ (160 mg/day) and AAP (1000 mg abiraterone acetate and 10 mg prednisone/day) for mCRPC were compared in this randomised (1:1) phase IV trial. Eligible patients had progressive metastatic prostate cancer castrate levels of testosterone (<1.7 nmol/L). Fasting serum hormones, including testosterone, free-testosterone, sexual hormone binding globulin (SHGB), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), were measured by the gold standard assay liquid chromatography – tandem mass spectrometry before 11 am at baseline and at 12-week post-intervention. The treatment difference in changed hormones was compared with logarithmic mixed models analysis, and the within-subject change for each treatment group was analysed with logarithmic paired samples t-test. RESULTS: From June 2017 to September 2019, 170 participants were randomized to receive ENZ (n=84 analysed) or AAP (n=85 analysed). A 19.9% higher increase in FSH was found for ENZ than AAP. A larger decline in testosterone and SHGB was found for AAP than ENZ. More patients had lower than detectable levels of free-testosterone in the AAP group (83/85) than the ENZ group (6/84) (chi-square test p <0.001). CONCLUSIONS: In men with castrate-levels of testosterone, ENZ and AAP both inhibit the androgen stimulation of prostate cancer, but by different mechanism of action resulting in different pituitary–gonadal hormonal profiles. Source of Funding: Herlev and Gentofte University Hospital © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e821 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Klara Ternov More articles by this author Jens Sønksen More articles by this author Mikkel Fode More articles by this author Henriette Lindberg More articles by this author Caroline Kistorp More articles by this author Rasmus Bisbjerg More articles by this author Jens Faber More articles by this author Ganesh Palapattu More articles by this author Peter Busch Østergren More articles by this author Expand All Advertisement PDF DownloadLoading ...

Physical exercise positively modulates nonalcoholic steatohepatitis-related hepatic endoplasmic reticulum stress.

Obesity is a predictive factor for the development of nonalcoholic steatohepatitis (NASH). Although some of the mechanisms associated with NASH development are still elusive, its pathogenesis relies on a complex broad spectrum of (interconnected) metabolic-based disorders. We analyzed the effects of voluntary physical activity (VPA) and endurance training (ET), as preventive and therapeutic nonpharmacological strategies, respectively, against hepatic endoplasmic reticulum (ER) stress, ER-related proapoptotic signaling, and oxidative stress in an animal model of high-fat diet (HFD)-induced NASH. Adult male Sprague-Dawley rats were divided into standard control liquid diet (SCLD) or HFD groups, with sedentary, VPA, and ET subgroups in both (sedentary animals with access to SCLD[SS], voluntarily physically active animals with access to SCLD[SV], and endurance-trained animals with access to SCLD[ST] in the former and sedentary animals with access to liquid HFD[HS], voluntarily physically active animals with access to liquid HFD[HV], and endurance-trained animals with access to liquid HFD[HT] in the latter, respectively). Hepatic ER stress and ER-related proapoptotic signaling were evaluated by Western blot and reverse transcriptase-polymerase chain reaction; redox status was evaluated through quantification of lipid peroxidation, protein carbonyls groups, and glutathione levels as well as antioxidant enzymes activity. In SCLD-treated animals, VPA significantly decreased eukaryotic initiation factor-2 alpha (eIF2α). In HFD-treated animals, VPA significantly decreased eIF2α and phospho-inositol requiring enzyme-1 alpha(IRE1α) but ET significantly decreased eIF2α and significantly increased both spliced X-box binding protein 1 (sXBP1) and unspliced X-box binding protein 1; a significant increase of phosphorylated-eIF2α(p-eIF2α) to eIF2α ratio occurred in ET versus VPA. HS compared to SS disclosed a significant increase of total and reduced glutathione, HV compared to SV a significant increase of oxidized glutathione, HT compared to ST a significant increase of p-eIF2α to eIF2α ratio and sXBP1. Physical exercise counteracts NASH-related ER stress and its associated deleterious consequences through a positive and dynamical modulation of the hepatic IRE1α-X-box binding protein 1 pathway.

The dimensional evolution of structure and dynamics in hard sphere liquids.

The formulation of the mean-field infinite-dimensional solution of hard sphere glasses is a significant milestone for theoretical physics. How relevant this description might be for understanding low-dimensional glass-forming liquids, however, remains unclear. These liquids indeed exhibit a complex interplay between structure and dynamics, and the importance of this interplay might only slowly diminish as dimension d increases. A careful numerical assessment of the matter has long been hindered by the exponential increase in computational costs with d. By revisiting a once common simulation technique involving the use of periodic boundary conditions modeled on Dd lattices, we here partly sidestep this difficulty, thus allowing the study of hard sphere liquids up to d = 13. Parallel efforts by Mangeat and Zamponi [Phys. Rev. E 93, 012609 (2016)] have expanded the mean-field description of glasses to finite d by leveraging the standard liquid-state theory and, thus, help bridge the gap from the other direction. The relatively smooth evolution of both the structure and dynamics across the d gap allows us to relate the two approaches and to identify some of the missing features that a finite-d theory of glasses might hope to include to achieve near quantitative agreement.

Compact Multifunctional Five-Wire Line-Based Microwave Sensor for Volumetric Characterization of Liquids

A new microwave sensor system with a five-wire line configuration is developed for volumetric characterization of liquids. Compared with the existing permittivity-based evaluation methods, the sensor is low profile, low-cost, submersible, easy to fabricate and implement (can be inserted into a container through a small access). An analytical model is proposed for accurate permittivity determination, and the effects of the line length and frequency range on the signals are thoroughly studied for optimal setting. The accuracy of the sensor is verified with standard liquids of known permittivity. From the measurement of honey and alcoholic drinks, explicit relationships are found between the permittivity and the constituent content, thereby facilitating liquid discrimination. The potential for the detection of liquid stacking and level change is well demonstrated in the evaluation of oil samples. The sensor offers an alternative solution to assessment of a wide range of liquids in food, oil, agricultural and bio-sensing applications.

A Study of Controlled Release of Nano Particle Liquid Medicated Formulation using the RP-HPLC Method for Determination of Norethindrone into Dissolution Media

The determination of norethindrone can be done using a variety of approaches. Both sophisticated and validation strategies are included in this technique. The purpose of this research was to improve and test a smooth overturned segment-excessive standard performance liquid chromatographic technique for assessing norethindrone in dissolution media. The column is a C18 column from Thermo Scientific (250 mm x 4.6mm ID, 5m length). Deionized water, acetonitrile (50:50, v/v), and 5 ml/l acetic acid was made up with the cellular phase. The detecting wavelength was changed to 245 nm and the glide rate was changed to 1.3 ml/minute. The basic approach that was utilised was to investigate norethindrone release from a nanoparticle liquid medication device (LMF). The results showed that the procedure has become easy, precise, and particular.

High-precision vapor pressure measurement apparatus with facile and inexpensive construction

This study describes an apparatus for high-precision variable temperature measurement of liquid vapor pressure. The apparatus can be used to measure the vapor pressure using only 0.5 ml of the liquid sample. To evaluate the accuracy of the device measurement, water and 2-propanol are utilized as standard liquids, and their vapor pressure is measured with a maximum uncertainty of ∼1%. This apparatus can be replicated using inexpensive and commonly used laboratory fittings and fixtures, making it an indispensable tool for synthetic chemists and chemical engineers involved in the iterative synthesis of compounds, targeting different vapor–liquid equilibrium regimes.

Reliability in viscosity measurement of thickening agents for dysphagia management: Are results obtained by cone-and-plate rheometers reproducible between laboratories?

Viscosity measurement using a cone-and-plate rheometer is considered to provide an objective and reliable evaluation of thickening agents for dysphagia management. Here, we showed its measurement uncertainty in the context of an inter-laboratory study. Eight test samples (i.e., four viscosity standard liquids, one xanthan gum reagent powder, and three commercial thickening agent powders) were distributed to 10 laboratories in a blinded manner. According to the same standard operating procedure, each laboratory dissolved the xanthan gum or thickening agents at four concentrations (0.5-4.0 g/100 g) and then measured their viscosity (35-803 mPa∙s). As for the viscosity of the standard liquids, the grand means were 98-100% of the certified values, and the relative standard deviations for repeatability (RSDr ) and reproducibility (RSDR ) were ca. 1% and ca. 5%, respectively, suggesting good accuracy in the measurement process. On the other hand, as for the viscosity of the thickening agents, RSDr and RSDR were ca. 2-6% and ca. 5-8%, respectively; however, heterogeneity in the preparation process comprising a manual dissolving step may increase these to near 60%. Furthermore, RSDr and RSDR of estimated additive concentrations to achieve targeted viscosities (50-500 mPa∙s) based on concentration-viscosity curves were ca. 1-3% and ca. 3-5%, respectively, with a few exceptions. These findings suggest that a strictly standardized procedure provides reliable data on the viscosity measurements for thickening agents.

Detection of insulin analogues and large peptides >2kDa in urine.

Insulin analogues and large bioactive peptides may be used by athletes to enhance performance and are banned by the World Anti-Doping Agency (WADA). In addition to insulin analogues, the large peptides include a structurally diverse set of peptides including analogues of growth hormone releasing hormone (GHRH), insulin-like growth factor-1 (IGF-1), and mechano-growth factor (MGF). Detection of this class of peptides is difficult due to their absorptive losses and presence at very low concentrations in urine. In this report, a high throughput method is described that allows sensitive detection of four classes of large peptides in one assay. Sample extraction is performed by ultrafiltration to concentrate the urine followed by solid phase extraction in a 96-well micro-elution plate. Peptides in the urine samples are detected on a triple quadrupole mass spectrometer coupled to standard flow liquid chromatography. The method was validated and evaluated for limit of detection, limit of identification, specificity, precision, carryover, recovery, matrix interference, and post-extraction stability. The limit of detection for insulin analogues is between 5 and 25 pg/ml and between 5 and 50 pg/ml for the other peptide classes. Specificity was good with no detection of interfering peaks in blank urine samples. Carryover from a high concentration sample was not observed and the post-extraction stability was between 77% and 107%. The method was able to detect insulin analogues in three diabetic urine samples. Increased screening for this class of peptides will improve detection and deterrence.

A Nonintrusive Flow Rate Sensor Based on Microwave Split-Ring Resonators and Thermal Modulation

Microwave sensors offer noncontact solutions for flow rate measurements, central to various applications in pharmaceutics, chemical analysis, and biomedicine. The challenge, however, remains for microwave flow rate sensing of uniform liquids, where different flow rates do not lead to any permittivity or conductivity variations. In this work, we propose a noncontact, nonintrusive microwave sensor, capable of measuring the flow rate of uniform liquids. This sensor comprises a microwave split-ring resonator (SRR) integrated with a temperature modulation technique. The sensor operates based on the change in the dielectric properties of the liquid inside the channel, induced by local delivery of thermal energy. Different flow rates affect the exposure time of the liquid to thermal energy, which alters its permittivity and loss tangent, consequently changing the response of the SRR. The SRR with the integrated fluidic channel is designed to operate at 4.6 GHz with a resonant amplitude of &#x2212;6.8 dB and a <inline-formula> <tex-math notation="LaTeX">$Q$ </tex-math></inline-formula>-factor (&#x2212;3 dB) of 98. By monitoring the <inline-formula> <tex-math notation="LaTeX">$S_{21}$ </tex-math></inline-formula> (dB) response, flow rates ranging from 1 to 40 mL/h are differentiated. The <inline-formula> <tex-math notation="LaTeX">$S_{21}$ </tex-math></inline-formula> (dB) response&#x2019;s achieved sensitivity to different flow rates is <inline-formula> <tex-math notation="LaTeX">$\vert 0.02\vert $ </tex-math></inline-formula> dB/mL/h. The proof of concept is successfully evaluated using water and isopropanol as two standard liquids. The results indicate the potential of the proposed nonintrusive flow rate sensing method in various applications, such as drug delivery and chemical sample preparation.

In vitro characterization of S-23 metabolites produced by human liver microsomes, and subsequent application to urine after a controlled oral administration

The selective androgen receptor modulators are a recent class of anabolic agents, used to improve athletic performance. Among these molecules, there is (2 S)-N-(4-cyano-3-trifluoromethylphenyl)− 3-(3-fluoro-4-chlorophenoxyl)2-hydroxy-2-methyl-propanamide, commonly known as S-23. This molecule appeared very recently on the doping market. As a result, very few data are available in the literature, and nothing has been published about long-term effects of S-23. The authors focused on the detection of S-23 and its metabolites in human urine, following a single oral administration of approx. 8 mg to a volunteer, using standard ultra-performance liquid chromatography-triple quadrupole-mass spectrometry (UPLC-MS/MS), and ultra-performance liquid chromatography-quadrupole time of flight-mass spectrometry (UPLC-Q-TOF-MS). To the best of the authors knowledge, this seems to be the first study ever achieved on S-23. In vitro experiment was performed, using human liver microsomes, in order to investigate the potential CYP- and UGT-dependent S-23 metabolites. Four metabolites were produced, which were identified as hydroxy-S-23 (C18H12O4N2ClF4: m/z [M-H-] 431.0423); O-dephenylate-S-23 (C12H10O3N2F3: m/z [M-H-] 287.0647); S-23-glucuronide (C24H20O9N2ClF4: m/z [M-H-] 591.0794) and hydroxy-S-23-glucuronide (C24H20O10N2ClF4: m/z [M-H-] 607.0743). After consumption of S-23, the parent drug was detectable in hydrolyzed urine from 2 h post administration up to 28 days, with concentrations ranging between 0.5 and 93 ng/mL. In the urine, only one of the four metabolites identified in vitro was detected, hydroxy-S-23. This metabolite was detected up to 28 days. It does not seem to increase the window of detection of S-23 as the ratio between hydroxy-S-23 and the parent drug was always lower than 1. Another metabolite, dihydroxy-S-23, not identified in vitro, was identified in the urine of the volunteer. Hair sample, collected one month after the consumption of a single tablet, was negative for S-23 and hydroxy-S-23, with a LOQ at 0.1 pg/mg.

Comparison of capillary and venous blood sampling for routine coagulation assays

ObjectivesCapillary blood samples are generally assumed as unsuitable for coagulation testing since it is recognized that contamination with tissue factor and dilution with tissue fluid affects the coagulation assay. However, limited data is available about coagulations assays in which capillary blood sampling is compared to the standard venous blood withdrawal method. The aim of this study was to perform a method comparison between capillary and venous blood sampling for routine coagulation assays. MethodsBoth venous and capillary (finger stick) blood samples were collected from 188 healthy volunteers and patients. In citrate plasma, International Normalized Ratio (INR), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, and D-dimer were measured according to routine protocols using the ACL-TOP 750 LAS (Werfen) coagulation analyzer. Regression analysis was performed and the mean relative difference between capillary and venous sampling was reflected to the total allowable error (TEa). ResultsStrong correlations and acceptable variations, using the TEa as decision limit, were found for INR, PT, TT, fibrinogen, and D-dimer between capillary and venous sampling. However, capillary sampling resulted in significant shorter APTT values when using the standard APTT-SP Liquid reagent with a mean bias of −10.4% [95% CI −12.4 to −8.4]. ConclusionBased on these results, capillary blood sampling proved to be an alternative blood withdrawal method for routine coagulation assays, with the exception of APTT, if a venipuncture is unavailable or undesired.

Radiofrequency dielectric properties of standard liquids: water, methanol and ethanol

Knowledge of the dielectric properties of materials in the radiofrequencies is essential in understanding the nature and composition of these materials. These properties also provide information on the purity and quality of the materials. We studied the dielectric properties of three standard liquids namely, water, methanol and ethanol using measured data and computer simulations Measurements were made using a Hewlett Packard Network Analyzer in the frequency range between 10 MHz and 3.0 GHz. We also developed and utilized a MATLAB software to simulate electromagnetic waves propagation in the radiofrequency range between 10 Hz and 3 GHz frequencies, at room temperature of about 21.0 degrees Celsius.

NANOENERGY AND NANOTECHNOLOGY OF THE NEW TECHNOLOGICAL PARADIGMSAVING HUMANITY FROM POISONING THE PLANET EARTH.

When using existing industrial technologies, a very high price of energy resources remains, due to their imperfection and the need to heat almost all fixed assets, as well as a lack of resources to restore the disturbed balance between the biosphere and the technosphere, caused by the lack of highly efficient cycle technologies: mining, production of useful products from them, rational use of these products and, finally, its utilization. Of what is extracted from the land, 95% goes either to intermediate consumption or buried. The world is in a state where the environmental damage of technology has exceeded the capabilities of the Earth. With the preservation of existing industrial technologies, resources in the world are becoming less and less, humanity has nothing to pay for cleaning and restoring the environment. Only new technologies and new resources will save humanity from collapse. The solution lies in finding a new alternative, renewable, harmless and sustainable source of energy, the very use of which is an industry for the processing and destruction of created waste - recycling, comparable in volume with the entire transport and energy complex. In this case, it is possible to stabilize the world at the current level of consumption and implement the idea of sustainable development. &#x0D; This article, based on the results of fifty years of work of author on development of breakthrough energy technologies in theory and practice of a non-ideal, close to non- degenerate plasma, started with PhD in Physics &amp; Mathematics A.A. Rumiantsev who, unfortunately, passed away in 1990. Author predicted and confirmed the existence of a fundamentally new state of physical matter - quantum plasma nanocondensate - liquefied plasma, combining the properties inherent in standard liquid and ionized plasma - a fundamentally new, effective, and harmless energy source, the use of which helps reduce the pollution caused by waste. Purification of planet Earth, which has been contaminated to the limit, in some areas of which gas contamination, slagging, and municipal waste exceed all permissible norms, will lead to a boost in the immune system of the population, which will make it possible for humans to exist safely.

Microwave Dielectric Property Retrieval From Open-Ended Coaxial Probe Response With Deep Learning

This work presents a technique for dielectric property retrieval through Debye parameter reconstruction from open-ended coaxial probe (OECP) response. Debye parameters were obtained with the application of a deep learning (DL) model to the reflection coefficient response of the OECP when terminated with a material under test. The OECP was modelled with the well-known admittance technique from 0.5 to 6 GHz with 20 MHz resolution. A dataset was generated using the admittance technique and obtained data was utilized to design the DL model. As part of the standard procedure, the dataset was separated to train, validate, and test parts by allocating the 80%, 10%, and 10% of the dataset to each section, respectively. Obtained percent relative error for Debye parameters were 1.86±3.01%, 3.33±9.52%, and 2.07±7.42% for <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\epsilon _{s}$ </tex-math></inline-formula> , <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\epsilon _\infty $ </tex-math></inline-formula> and <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\tau $ </tex-math></inline-formula> , respectively. To further test the constructed DL model, OECP responses were measured at the same frequency band when it was terminated with five different standard liquids, four mixtures, and a gel-like material. Reconstructed Debye parameters from the DL model were used to retrieve the complex dielectric properties and obtained results were compared with the literature data. Obtained mean percent relative error was ranging from 1.21±0.06 to 10.89±0.08 within the frequency band of interest.