Lower Limit Research Articles

Biological Reference Ranges for Healthy Indian Blood Donors: Experience of a Tertiary Care Center Vis-à-Vis International Literature.

Complete blood count is the most common, basic test requisitioned in hematology. The normal reference ranges of hematological parameters are required owing to variable socioeconomic, environmental, and genetic factors in populations. The current study determines the reference ranges of the healthy Indian donor population of a high socioeconomic group. The study was conducted in the Department of Transfusion Medicine at a tertiary care hospital in India and included 4098 individuals, aged 18-65 years coming for voluntary blood donation from July 2021 to October 2022. Blood samples were collected in K2EDTA, analyzed on the Sysmex XN-31 hematology analyzer, and using statistical tools, the normal reference ranges were calculated. The reference ranges for hemoglobin (HB) (137-185 g/L), WBC (5.1-1.7 × 109/L), platelet count (115.6-370.0 × 109/L) were noted. No statistically significant changes were observed in different age groups. There were gender-wise differences noted in nearly all parameters. The HB and hematocrit (HCT) range was slightly higher in other Indian and other Asian populations with comparable values with the Chinese, Korean populations, and Western populations; RBC parameters were overall comparable with minor differences; the WBC count was higher than the other Indian and Asian populations particularly the upper limit of lymphocyte and monocyte; and the range of platelet counts had a comparable upper limit with all populations and had the lowest lower value in males in our study, which was comparable to only the Chinese population. It is concluded that reference ranges of common parameters were calculated with minor changes noted in all hematological parameters on comparing with other Indian, Asian population, and Western data.

Spectrofluorimetric determination of acetone in water samples with solid-phase extraction and a new benzaldehyde derivative

A new method is described for acetone (C(CH3)2O) determination in water samples. The method is based on the reaction with 4-(dimethylamino)benzaldehyde (DMAB) in dimethyl sulfoxide (DMSO) in slightly basic medium, resulting in a highly fluorescent compound with fluorescent wavelengths undisturbed by other common fluorescent compounds. Experimental conditions were optimized (reagents concentrations, reaction time) to reach optimal sensitivity. For the analysis of aqueous samples, a preconcentration step of acetone by solid-phase extraction (SPE) followed by an elution step in DMSO was optimized using Isolute ENV + columns. A highly satisfactory low detection limit of 0.014 μM (0.8 μg L−1) was achieved by combining these two steps, with a linear range from 0.048 to 5 μM and relative standard deviations between 5.7 % and 6.9 %. The protocol was validated on complex real water samples such as river water and wastewater, and our fluorimetric method with DMAB was in good agreement with the reference LC-UV method with DNPH.

Nitrogen-Doped Carbon Quantum Dots Activated Dandelion-Like Hierarchical WO3 for Highly Sensitive and Selective MEMS Sensors in Diabetes Detection.

High sensitivity, low concentration, and excellent selectivity are pronounced primary challenges for semiconductor gas sensors to monitor acetone from exhaled breath. In this study, nitrogen-doped carbon quantum dots (N-CQDs) with high reactivity were used to activate dandelion-like hierarchical tungsten oxide (WO3) microspheres to construct an efficient and stable acetone gas sensor. Benefiting from the synergistic effect of both the abundant active sites provided by the unique dandelion-like hierarchical structure and the high reaction potential generated by the sensitization of the N-CQDs, the resulting 16 wt % N-CQDs/WO3 sensor shows an ultrahigh response value (Ra/Rg = 74@1 ppm acetone), low detection limit (0.05 ppm), outstanding selectivity, and reliable stability to acetone at the optimum working temperature of 210 °C. Noteworthy that the N-CQDs facilitate the carrier migration and intensify the reaction between acetone and WO3 during the sensing process. Considering the above advantages, N-CQDs as a sensitizer to achieve excellent gas-sensitive properties of WO3 are a promising new strategy for achieving accurate acetone detection in real time and facilitating the development of portable human-exhaled gas sensors.

Clinical Pharmacokinetics of Atropine Administered Ocularly Using an Ultrasensitive Bioanalytical Assay.

Purpose: Previous pharmacokinetic studies conducted on atropine sulfate ophthalmical solution have utilized bioanalytical assays that lacked sufficient sensitivity to fully characterize the complete pharmacokinetic profile. To address these limitations, Pharma Medica Research Inc. has developed and validated an ultrasensitive bioanalytical method capable of accurately quantifying the active enantiomer, L-hyoscyamine, with a very low limit of quantitation of 0.500 pg/mL. The objective of this study was to evaluate the pharmacokinetics of L-hyoscyamine in healthy subjects using a highly sensitive bioanalytical assay. Methods: Ten subjects were administered 0.3 mg of Isopto Atropine solution into the conjunctival sac of the eye. Blood samples were taken as early as 2 min and up to 24 h following administration. The plasma samples were assayed for L-hyoscyamine using a chiral method with an analytical range of 0.500-500 pg/mL. The pharmacokinetic parameters were estimated using both a noncompartmental and compartmental approach. Results: The pharmacokinetics of L-hyoscyamine were fully characterized as there were no samples that were below the limit of quantitation following dosing. Using noncompartmental analysis, the mean Cmax was 467.9 ± 159.4 pg/mL with a median (range) Tmax of 0.5 (0.08-1) h. The mean area under the concentration-time curve was 1668.96 ± 436.02 h·pg/mL and the mean half-life was 3.91 ± 1.16 h. Overall, the study drug was well tolerated and no serious adverse events were reported. Conclusion: Through the utilization of a proprietary ultrasensitive bioanalytical method, a comprehensive investigation into the pharmacokinetics of L-hyoscyamine has been successfully conducted. This advanced method offers significant potential for optimizing study designs and facilitating in-depth examinations of the pharmacokinetics of ocularly administered atropine formulations.

Investigation into the linearity of the Roche c 702 carbamazepine assay.

Carbamazepine is an anticonvulsant drug which is monitored in patients due to toxic side effects. At Manchester University NHS Foundation Trust (MFT) carbamazepine is measured using Roche's Kinetic Interaction of Microparticles in Solution (KIMS) method on the c 702 platform. The assay has an upper limit of linearity of 20 mg/L. Samples with concentrations above this limit should be identified and manually diluted. However, a poor EQA return from UK NEQAS for Tox and TDM Distribution 456 has highlighted an issue with the Roche KIMS assay. Sample A of the distribution had a carbamazepine concentration of 36 mg/L but was underreported by several Roche users. This indicated that the assay was not consistently identifying high concentration samples which required a dilution. In this investigation, fresh frozen plasma was spiked with carbamazepine concentrations ranging from 15 to 40 mg/L. The spiked samples and EQA material were analysed at two clinical laboratories using the Roche KIMS assay. Samples spiked with concentrations 20-30 mg/L were not consistently identified for dilution by the analyser. This was observed at both hospital sites. Spike samples and EQA with concentrations >30 mg/l were correctly identified at both sites. The manual dilution policy has been changed at MFT so all samples with a carbamazepine level ≥15 mg/L will be manually diluted. The problem was reported to Roche who are investigating the issue further. We would suggest that other laboratories look at validating their dilution protocols.

Fabrication of natural enzyme-covered / amino-modified Pd-Pt bimetallic-doped zeolitic imidazolate framework for ultrasensitive detection of metabolites.

The present article introduced an natural enzyme-covered/amino-modified Pd-Pt bimetallic-doped zeolitic imidazolate framework (NAPPZ) for ultrasensitive and specific detection of glucose. The dodecahedral nanomaterial zeolitic imidazolate framework (ZIF-8)-loaded Pd-Pt bimetallic nanoparticles endowed the composite with peroxidase-like activity. The modification with glucose oxidase (GOx) facilitated the rapid access of H2O2 produced through glucose oxidation to the Pd-Pt nanoparticles vicinity reducing diffusion. GOx specifically catalyzes the transformation of glucose into H2O2, which then H2O2 rapidly migrates to the Pd-Pt nanoparticles, catalyzing the oxidation of colorless o-phenylenediamine into the orange-yellow product 2,3-diaminophenazine. Based on the aforementioned cascade reaction, the NAPPZ and NAPPZ based on ChOx were utilized for detecting glucose in human urine samples and cholesterol in milk, respectively. The NAPPZ strategy presented a broad detection range (20-1100μmol L-1) and a low detection limit (15.9μmol L-1) for glucose, and the NAPPZ based on ChOx strategy approach offered a broad detection range (10-500μmol L-1) and low detection limit (6.4μmol L-1) for cholesterol. Therefore, this novel method holds significant potential in the areas of clinical diagnostics and food safety.

Fe(OH)3/Ti3C2Tx nanocomposites for enhanced ammonia gas sensor at room temperature.

Two-dimensional material (2D material) MXene has great application potential in gas sensors because of its excellent controllable performance and vast specific surface area. In this study, we used a straightforward in-situ electrostatic self-assembly technique to create Fe(OH)3/Ti3C2Tx nanocomposites, which were then used to fabricate gas sensors for ammonia detection at room temperature (25 ℃). Several characterization methods were performed aimed at determining the surface appearance and construction of the nanocomposites, and the sensing characteristics and mechanism were also systematically examined. The findings demonstrate the effective incorporation of amorphous Fe(OH)3 nanoparticles on the surface of Ti3C2Tx. Additionally the nanocomposites of Fe(OH)3/Ti3C2Tx have considerably higher specific surface area than pure Ti3C2Tx, hence offering more active NH3 adsorption sites. The response of the sensor to 100 ppm NH3 was 48.6% at room temperature, which was 9.3 times more higher than that of pure Ti3C2Tx. The sensors also have the advantages of long-term stability (33 days), low NH3 detection limit (500 ppb), and rapid recovery time (85 s) and response times (78 s). It is anticipated that this work will be helpful for developing the new generation of wearable ammonia sensors at room temperature.

A Portable Electrochemical Biosensor Based on an Amino-Modified Ionic Metal-Organic Framework for the One-Site Detection of Multiple Organophosphorus Pesticides.

Constructing stable, portable sensors and revealing their mechanisms is challenging. Ion metal-organic frameworks (IMOFs) are poised to serve as highly effective electrochemical sensors for detecting organophosphorus pesticides (OPs), leveraging their unique charge properties. In this work, an amino-modified IMOF was constructed and combined with near-field communication (NFC) technology to develop a portable, touchless, and battery-free electrochemical biosensor NH2-IMOF@CS@AChE. -NH2 in NH2-IMOF gives the framework a higher electropositivity compared to IMOF, enhancing the electrostatic attraction with acetylcholinesterase (AChE), which is beneficial for immobilizing AChE. Furthermore, the uncoordinated O atoms and the (CH3)2NH2+ groups in NH2-IMOF help to form stronger bonds with AChE through hydrogen bonds. The results showed a wide linear response range of 1 × 10-15 to 1 × 10-9 M and a low detection limit of 1.24 × 10-13 M for glyphosate (Gly) in the practical detection of OPs. Additionally, electrochemical biosensor arrays were constructed to effectively identify and distinguish multiple OPs on the basis of their unique differential pulse voltammetry (DPV) electrochemical signals. This work provides a simple and effective solution for on-site OP analysis and can be widely applied in food safety and water quality monitoring.

Highly Efficient Manganese Bromides with Reversible Luminescence Switching through Amorphous-Crystalline Transition.

While luminescent stimuli-responsive materials (LSRMs) have become one of the most sought-after materials owing to their potential in optoelectronic applications, the use of earth-scarce lanthanides remains a crucial problem to be solved for further development. In this work, two manganese-based LSRMs, (R)-(+)-1-phenylethylammonium manganese bromide, (R-PEA)2MnBr4, and (S)-(-)-1-phenylethylammonium manganese bromide, (S-PEA)2MnBr4, are successfully demonstrated. Both (R-PEA)2MnBr4 and (S-PEA)2MnBr4 show a kinetically stable red-emissive amorphous state and a thermodynamically stable green-emissive crystalline state at room temperature, where the fully reversible transition can be done through melt-quenching and annealing processes. Based on this property, a reusable manganese-halide-based time-temperature indicator is demonstrated for the first time. Furthermore, an X-ray scintillator with a low limit of detection (18.1 nGy/s) and a high spatial resolution limit (30.0 lp/mm) are achieved by exploiting the high transparency of amorphous states. These results uncover the multifunctionality of manganese halides and pave the way for upcoming research.

Distinguishing Surface and Bulk Reactivity: Concentration-Dependent Kinetics of Iodide Oxidation by Ozone in Microdroplets.

Iodine oxidation reactions play an important role in environmental, biological, and industrial contexts. The multiphase reaction between aqueous iodide and ozone is of particular interest due to its prevalence in the marine atmosphere and unique reactivity at the air-water interface. Here, we explore the concentration dependence of the I- + O3 reaction in levitated microdroplets under both acidic and basic conditions. To interpret the experimental kinetics, molecular simulations are used to benchmark a kinetic model, which enables insight into the reactivity of the interface, the nanometer-scale subsurface region, and the bulk interior of the droplet. For all experiments, a kinetic description of gas- and liquid-phase diffusion is critical to interpreting the results. We find that the surface dominates the iodide oxidation kinetics under concentrated and acidic conditions, with the reactive uptake coefficient approaching an upper limit of 10-2 at pH 3. In contrast, reactions in the subsurface dominate under more dilute and alkaline conditions, with inhibition of the surface reaction at pH 12 and an uptake coefficient that is 10× smaller. The origin of a changing surface mechanism with pH is explored and compared to previous ozone-dependent measurements.

Tissue transglutaminase immunoglobulin A exceeds endomysial antibody in specificity of celiac diagnosis at ≥10 times the upper limit of normal.

Serologic diagnosis using tissue transglutaminase immunoglobulin A (TTG-IgA) and endomysial antibody (EMA) is being integrated into the care of pediatric patients with positive screening for celiac disease. The purpose of this study was to assess the utility of EMA in pediatric patients being considered for serologic diagnosis. Patients with TTG-IgA testing performed between May 1, 2022 and April 30, 2023 and with subsequent duodenal biopsy within 6 months were included. TTG-IgA serum samples were frozen and sent for EMA testing and titer. EMA was evaluated for positivity and TTG-IgA (normal <15 u/mL) for elevation <10 times (10x) the upper limit of normal (ULN) and ≥10x ULN (≥150 u/mL). Sensitivity and specificity of EMA and TTG-IgA were calculated using biopsy histology as the gold standard. Four hundred and eighty-six patients were included. The sensitivity and specificity of TTG-IgA ≥15 u/mL was 87.5% and 95.4% while EMA was 77.5% and 97.3%. For patients with TTG-IgA ≥10x ULN the specificity was 99.3%. The positive predictive value of TTG-IgA at ≥10x ULN was 91.4% and for EMA was 83.6%. All three patients with false positive TTG-IgA ≥10x ULN also had false positive EMA, and two of these patients had type 1 diabetes mellitus. TTG-IgA has greater sensitivity at the screening threshold of ≥15 u/mL and greater specificity and positive predictive value at ≥10x ULN than EMA. TTG-IgA at ≥10x ULN is superior to EMA for the serologic diagnosis of celiac disease.

A-093 Assessing Alkaline Phosphatase Reference Intervals Using Gamma-Glutamyl Transferase as a Surrogate for Normal Liver Function

Abstract Background There are limited published studies assessing reference intervals (RIs) for hepatic enzymes, particularly for alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT). In the US, ALP and GGT RIs were established on Roche assays using a European cohort of ≤ 450 patients that may not reflect population variance across practice settings. Further, age- and sex-specific variation in ALP and GGT may warrant tiered RIs, but evidence to justify this approach is limited. We aimed to evaluate the manufacturer’s RIs by comparing them to indirectly estimated RIs (IRIs) from routine clinical data. Methods 217,333 AST, ALT, ALP, and GGT results (Roche c702) performed between 1/1/2019-12/31/2022 on outpatients ≥21 years were extracted from the laboratory information system. The first ALP for each patient was identified, and the earliest AST, ALT, and GGT drawn within 7 days was included. This approach was repeated for GGT. Concordance and correlation were calculated using Weighted Cohen’s Kappa and Spearman’s rank correlation coefficient respectively. {refineR}, an algorithm for calculating IRIs, was applied to patients with “normal” liver function (defined as normal AST, ALT for all IRIs, plus normal GGT for ALP IRIs, and ALP for GGT IRIs). IRIs were estimated for all males, all females, females ≤50, and females &amp;gt;50 years and compared to the method specific manufacturer RI (ALP: 40-129 Units/L for males and 35-104 Units/L for females; GGT: 8-61 Units/L for males and 5-36 Units/L for females). Results Of the 71,783 outpatients, 54.9% were female, 74% self-identified as white and 19% as black. The median age was 58 (IQR: 43-68 years), the median ALP concentration was 77 (62-97 Units/L), and the median GGT concentration was 28 (17-57 Units/L). A moderate agreement between ALP and GGT was observed (Kappa = 0.48, 95% confidence interval: 0.46-0.51). A positive correlation between ALP and GGT was observed r = 0.51 (p&amp;lt;0.0001). For ALP, no significant differences were observed between the lower limit of the IRIs and the current RI. The upper limit of estimated IRIs was 132 [95% confidence interval: 117-147 Units/L] for patients with normal AST/ALT/GGT (n = 1596). For males, the sex-specific upper limit was 120 [101-140 Units/L] and for females, was 123 [110-136 Units/L]. Age stratified upper limits for females were 120 [101-140 Units/L], and 109 [97-121 Units/L] for ≤50 and &amp;gt;50 years, respectively. For GGT, no significant differences were observed for the lower limits. The upper limit for all patients with normal AST/ALT/ALP (n = 2,446) was 62 [55-70 Units/L]. For males, all females, females ≤50 and &amp;gt;50 years was 58 [46-69 Units/L], 40 [39-51 Units/L], 31 [23-39 Units/L], and 56 [41-71 Units/L]. Conclusions For the majority of patient subsets, the manufacturer RI agreed well with the IRIs. However, significant differences in IRIs were observed for the upper limit of ALP IRIs of all females with normal hepatobilliary function and in GGT for all females and females &amp;gt;50 years. Further investigation of the impact of preselecting patient populations on IRI estimation and a direct RI study on select patient subsets is worth investigation.

B-310 Freezing and thawing serum without mixing prior to analysis causes false low Thyroglobulin results

Abstract Background Thyroglobulin (Tg), a glycoprotein that is synthesized in follicular cells of the thyroid gland, is the precursor of Thyroxin (T4) and Triiodothyronine (T3). Tg is a biomarker used for many clinical conditions, including monitoring for recurrence in patients with differentiated thyroid carcinoma. Typically, Tg levels drop to very low or undetectable levels after surgical excision and/or radioiodine ablation of the thyroid, with post-operative levels greater than 1-2 ng/ml indicating potential disease recurrence. Discordant Tg results in a patient sample were identified during a quality check of Tg results. This study investigates the root of cause of the discrepant Tg results. Given that: 1) Tg analyses were performed twice a week at our laboratory due to low daily test volume and patients’ samples received on an unanalytical day were stored at -20°C until analysis; 2) Tg analyses were performed by various medical technologists; 3) sample mixation prior to analysis was not routine practice for our automated laboratory, we hypothesized that the discrepancy was due to inconsistent sample handling, e.g., mixation vs unmixation prior to analysis. Methods Analysis of the daily QC and PT results in the period of the incident occurence ruled out causes in analytical phase. We split 52 de-identified patient serum samples into two equal aliquots and subsequently stored both aliquots at -20°C for 48 hours. Both aliquots of each sample were thawed at room temperature for 1 hour. One of the aliquots was analyzed for Tg without mixing, and the other was analyzed after mixing using a Vortexer for 4 seconds at 250 xg. To investigate if Tg concentrations form a gradient from the top to the bottom of a red-top vacutainer tube, five patient samples with Tg at 2.59, 2.79, 2.92, 52.37 and 144.12 ng/mL were thawed without mixing following storage at -20°C for 48 hours. Five layer (600 μl/layer) aliquots were carefully and sequentially taken from top to bottom for each specimen, and the Tg concentration in the aliquot of each layer was determined using the Beckman Coulter Access-2 Immunoassay. Results Of the 52 patients samples, 14 Tg results were excluded from statistical analysis due to exceeding the assay dynamic range (2 above and 12 below the upper and low limits, respectively). Analysis of the remaining 38 patient samples showed the mean of Tg concentrations was 22.8% (SD 18%) higher in mixed samples than the un-mixed samples. Regression analysis showed an R2 = 0.9976 (Mixed Tg = 1.1523 x Un-mixed + 0.4174, range 0.1 - 275.7 ng/mL, intercept 95%CI -0.721 to 1.556, slop 95%CI 1.1331 to 1.1715, p-value &amp;lt;0.001). Results of Tg gradient analysis showed significant higher Tg values in the 2nd, 3rd, 4th and 5th than the 1st layer by 26% (SD 11%), 63% (26%), 112% (57%), and 160% (76%), respectively. Conclusions False Tg values were found in samples without mixing before analysis after thawing from frozen state, due to formation of Tg concentration gradient in test tube. For obtaining reliable results, samples must be mixed before analysis when thawed from frozen storage.

A-315 Cardiac Troponin Concentrations in Pediatric Patients Infected with Respiratory Syncytial Virus

Abstract Background Respiratory syncytial virus (RSV) is associated with considerable morbidity and mortality in pediatric patients. Cardiac troponin I (TnI) has been shown to increase in patients with acute respiratory illness, including COVID-19. The impact of RSV infection on circulating TnI has been formally demonstrated in the literature. The goal of this study was to assess the relationship between TnI and respiratory syncytial virus (RSV) in pediatric patients. Methods A prospective study was conducted at St. Louis Children’s Hospital from October 2023 to February 2024. Patients older than 6 months who presented to the ED and had a CBC ordered within 6 hours of testing positive for RSV on the Biofire® FilmArray® Respiratory Panel were enrolled. Patients with Rhinovirus, Enterovirus, Streptococcus pneumoniae, or Adenovirus infections were included as controls. Remnant EDTA specimens were tested on an Abbott ARCHITECT i2000 for high sensitivity TnI (hs-TnI) with a limit of detection of 1.4 ng/L and a limit of quantitation of 3.5 ng/L. 99% upper reference limits from the CALIPER database on the Abbott of &amp;lt;7 ng/L were used as a threshold for positive results. The electronic medical record (EPIC) was assessed for demographic information and outcomes including length of stay (LOS), intensive care unit (ICU) length of stay, requirement of supplemental oxygen, white blood cell count (WBC), and creatinine. Results A total of 103 patients had RSV and 35 had other respiratory infections (ORI). The average age for the RSV positive group was 2.3 and for the ORI group was 2.4. Males made up 61% of the RSV+ group and 51% of the ORIs. 93 patients in the RSV group were admitted. The median TnI for RSV patients was 1.4 (IQR, 1.2-2.9) and for ORIs was 1.4 (IQR, 1.4-6.8). TnI was measurable in 58% of those with RSV and 54% in ORIs. We next assessed the correlation between hospital LOS and TnI in RSV+ patients, with a Pearson r of 0.42 (95% CI= 0.23-0.58). There was no correlation between WBC and LOS (r=-0.04, 95% CI=-0.25-0.17). There was also no correlation between TnI and WBCs or creatinine. Of admitted patients, 44 (47%) in the RSV group were in the ICU compared to 18 (51.4%) in those with ORIs. RSV+ patients that required ICU treatment had comparable TnI (1.4, IQR, 0.9-3.5) to those that didn’t require ICU stay (1.4, IQR, 0.75-1.5). There was no correlation between ICU LOS and TnI in RSV+ patients (r=-0.08, 95% CI=-0.39-0.24). There was a significant difference in mean TnI concentrations in RSV+ patients that required supplemental oxygen (8.7, 95% CI: 0-19) versus those that did not (1.7, 95% CI: 1.1-2.4). Conclusions There was no difference in TnI in patients hospitalized for RSV relative to ORIs. While TnI concentration was associated with LOS, there were minimally other associations between TnI and outcomes in patients hospitalized with RSV. While TnI elevations are associated with acute respiratory infections in adults, the impact on pediatric patients is not as clear. Future investigation is needed to understand how severe respiratory infections impact pediatric cardiac function.

B-313 Assessment of β2-microglobulin concentration in pleural effusions

Abstract Background β2-microglobulin (β2-m) is a biomarker used in serum for different types of pathologies. It has been described that lymphocyte activation processes us tuberculosis infections, AIDS virus or cytomegalovirus infections, can produce an increase in the concentration of this marker. As a tumor marker is useful in lymphomas diagnosis. In the bibliography has reported that processes involving renal failure lead to a significant increase in its concentration. In patients with renal failure and treated with hemodialysis, have been described medians twenty times the upper reference limit. The objective is to assess whether the concentration of (β2-m) in pleural fluid is affected by the same factors as in serum. Methods We analyzed 303 pleural effusions (PE) samples from undiagnosed patients with pleural effusion. β2-microglobulin levels were prospectively measured by electrochemiluminescence (ECLIA) assays (Cobas c702, Roche Diagnostics®). Glomerular filtration rate (GFR) was calculated by CKD-EPI equation. The diagnostic performance of β2-microglobulin was evaluated by receiver operating characteristic (ROC) curve analysis. Statistical analyses were performed using SPSS software. Results Pleural fluid of 303 patients (104 female, 204 male) were collected. The median age was 72 ± 10,6 years. For all samples β2-m median concentration was 5,85 mg/L (IQR:3.4 -6.45).When we compared all results according to kidney failure values; GFR &amp;gt;60mL/min β2-m median concentration was 4,12mg/L and if GFR &amp;lt;60 mL/min, β2-m was 8,62g/L significant difference have found (p&amp;lt;0,001). Comparing results between malignant pleural effusions (MPE) (n=96) and benign pleural effusions (BPE) (n=207), MPE median concentration was 5.38 mg/L and 6.07mg/L significant difference (p&amp;lt;0,001). Benign pathologies associated with pleural effusions, tuberculosis samples had the highest concentration of β2-m. Tuberculosis samples (n=6) had a normal distribution, obtaining a value [mean (SD)] of 7.28 mg/mL (2,13) mg/mL. For tuberculosis samples and patients without renal failure (n=5) (GFR&amp;gt;60 mL/min), the area under the ROC curve was 0.98 (95% CI: 0.88-0.98) (p&amp;lt;0.005). For β2-m cut-off point was 5.150 mg/L, a sensitivity of 100%, specificity of 16%, positive predictive value (PPV) of 14% and negative predictive value (NPV) of 100% were obtained. Patients with lymphomas present the highest concentration in the group of malignant pleural effusions, but further investigations could not be performed due to the small sample size. Conclusions Based on the results obtained from our present study, it can be concluded that β2-microglobulin marker in pleural effusions has significant association with glomerular filtration rate, as well as occurs in serum. Higher concentrations were found in patients with GFR&amp;gt;60 mL/min and tuberculosis. Using 5,15 mg/L cut-off point, 100% of NPV was obtained.

B-159 Fast Cleanup for 19 Steroid Analytes in Serum Using Supported Liquid Extraction (SLE)

Abstract Background Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a powerful tool that holds promise in designing the future of steroid analysis in the clinical laboratory. It is already widely used in steroid analysis in endocrinology and is being utilized increasingly in newer applications for individual steroids and panels relevant in clinical research. LC-MS/MS is gaining user base owing to greater sensitivity and specificity and gradually even replacing some of the legacy test methods. Improved sample preparation, modern chromatography methods, and sensitive, faster scanning mass spectrometers have all played a role in improving LC-MS/MS. Steroid analysis for clinical research can require very low limits of detection which demand high recoveries and very clean extracted samples. Supported Liquid Extraction (SLE) can provide very clean extracted samples with less method development and a streamlined workflow compared to solid phase extraction (SPE). Laboratories desire high-throughput methods which consolidate analytes into one panel with fast chromatographic run times. Chromatographic separation of steroid isomers with the same m/z is necessary for accurate quantitation by LCMS/MS. Meeting these criteria can be challenging in a single LC-MS/MS method. Methods Each 200 µL serum sample was pretreated with 200 µL of pH 6 Ammonium Acetate buffer (aq) before being loaded onto a Novum™ PRO SLE, MAX 96-well plate, following the standard SLE protocol. Samples were eluted using 2 × 900 µL of Dichloromethane or Ethyl Acetate. After evaporation of the elution solvent, samples were reconstituted in 100 µL of 0.5 mM Ammonium Fluoride / Methanol (60:40, v/v). A Kinetex™ 2.6 μm C18, 50 x 3.0 mm column using a gradient of 0.5 mM Ammonium Fluoride (aq) and Methanol on an Agilent® 1290 Infinity UHPLC and SCIEX® 7500 Triple Quad™ were used for quantitation. Results Here, we present an effective sample extraction method and LC-MS/MS analysis method for the quantitation of a 19-analyte steroid panel from serum. The Kinetex 2.6 μm C18 column provided a fast 8-minute chromatographic separation and good selectivity for steroid analytes in both positive ion mode and negative ion mode. Calibration curves with a linear fit and 1/x weighting, showed good linearity with R2 of &amp;gt;0.99 for all analytes except 17-OH-Pregnenolone and DHEAS when using Dichloromethane as the elution solvent, and R2 of &amp;gt;0.980 for all analytes when using Ethyl Acetate as the elution the solvent. Accuracy of samples using Dichloromethane as the elution solvent were 80-112 %, except for 17-OH-Pregnenolone and DHEAS. Accuracy of all samples using the Ethyl Acetate elution solvent were 91-118 %. Conclusions The-96 well plate extraction method was robust, reproducible, and can be automated. SLE using Novum Pro MAX combined with a fast LC method provides a simple, rapid, high-throughput workflow for identification and quantitation of 19 steroids from serum.

Room-Temperature Flexible CNT/Fe2O3 Film Sensor for ppb-Level H2S Detection.

Carbon nanotubes (CNTs) had room temperature response, large surface area, and excellent mechanical properties, making them favorable for the design of flexible, wearable, and portable gas sensors. However, CNTs were lacking in response and selective response to different gases, such as H2S. Here, we demonstrated a flexible H2S ppb-level gas sensor based on a carbon nanotube/amorphous Fe2O3 (CNT/Fe2O3) film at room temperature, which was fabricated via a simple one-step solvent-thermal method. The CNT/Fe2O3 film gas sensor exhibited a high selective response to H2S (with a response of 55.1% to 100 ppb H2S), rapid reversible response at room temperature (with a response time of ∼127 s to 100 ppb H2S), and low limit of detection to about 2 ppb. Additionally, the CNT/Fe2O3 film maintained good sensing performance under various bending conditions and could be further fabricated into the fiber gas sensor device via wet stretching, retaining response at the ppb level (with a response of 18.6% to 100 ppb H2S). This research on a flexible gas sensor device based on the CNT film/fiber opened up new possibilities for wearable portable electronic device applications.

Magnesium geochemistry of authigenic carbonate at marine cold seep

Cold seeps, featured by their extremely methane-rich sedimentary environments, play a significant role in the geological history and are common in marine sediments across the seafloor. Primary dolomite, possibly mediated by microorganisms, can be widely discovered in methane-rich environments. Hence, cold seeps may provide new insights into the ‘dolomite problem’, which has confused geologists for decades. Magnesium isotope geochemistry of seep carbonates contributes to the understanding of the dolomite formation mechanism in marine environments. In this paper, magnesium geochemical characteristics of carbonates in modern sediments are summarized, along with rare researches on magnesium isotopes of seep carbonates. Methane vigorously interacts with sulfate by anaerobic oxidation of methane at cold seeps, producing vast amounts of dissolved sulfide which can significantly promote dolomitization of seep carbonates. Compared with temperature, alkalinity, mineralogy, etc., the competition between rapid carbonate precipitation rates and aqueous ligands may be the main factor of the magnesium fractionation at cold seeps, which is controlled by the kinetic effect. The range of magnesium isotopes of seep carbonates is narrow (from -3.46‰ to -2.36‰), and an upper limit of magnesium content seems to exist. This characteristic may be a good indicator for identifying dolomitization related to anaerobic oxidation of methane. Whereas, mechanisms of magnesium isotope fractionation and dolomitization at cold seeps remain unclear, necessitating more natural samples tested, stimulated calculation and laboratory experiment.

Determination of the Relative Sign of the Higgs Boson Couplings to W and Z Bosons Using WH Production via Vector-Boson Fusion with the ATLAS Detector

The associated production of Higgs and W bosons via vector-boson fusion is highly sensitive to the relative sign of the Higgs boson couplings to W and Z bosons. In this Letter, two searches for this process are presented, using 140 fb−1 of proton-proton collision data at s=13 TeV recorded by the ATLAS detector at the LHC. The first search targets scenarios with opposite-sign couplings of the W and Z bosons to the Higgs boson, while the second targets standard model-like scenarios with same-sign couplings. Both analyses consider Higgs boson decays into a pair of b quarks and W boson decays with an electron or muon. The data exclude the opposite-sign coupling hypothesis with a significance beyond 5σ, and the observed (expected) upper limit set on the cross section for vector-boson fusion WH production is 9.0 (8.7) times the standard model value at 95% confidence level. © 2024 CERN, for the ATLAS Collaboration 2024 CERN

Forecasting Population in an Uncertain World: Approaches, New Uses, and Troubling Limitations

AbstractThe long human lifespan enables long run forecasts of population size and age distribution. New methods include biodemographic research on upper limits to life expectancy and incorporation of early experiences affecting later life mortality such as smoking, obesity, and childhood health shocks. Some fertility forecasts incorporate education and quantum‐tempo insights. Statistical time series and Bayesian methods generate probabilistic forecasts. Yet recent decades have brought surprising changes in the economy, natural environment, and vital rates. In these changing circumstances we need new methods and the increasing use of probabilistic models and Bayesian methods incorporating outside information. The increasing use of microsimulation combined with aggregate forecasting methods is a very promising development enabling more detailed and heterogeneous forecasts. Some new uses of stochastic forecasts are interesting in themselves. Probabilistic mortality forecasts are used in finance and insurance, and a new Longevity Swap industry has been built on them. Random sample paths used to generate stochastic population forecasts can stress‐test public pension designs for fiscal stability and intergenerational equity. Population forecasting a few decades ago was a dull backwater of demographic research, but now it is increasingly important and is full of intellectual and technical challenges.