In-house Quality Control Research Articles

A-067 Simultaneous Measurement of Aldosterone and Plasma Renin Activity in Human Serum Using Liquid Chromatography Coupled to Tandem Mass Spectrometry for Clinical Research

Abstract Background The combination of primary aldosteronism (PA) and alterations in plasma renin activity (PRA) is a leading cause of secondary hypertension. An accurate measurement of Renin Angiotensin-Aldosterone System (RAAS) pathway improves the recognition of symptoms related to stroke, coronary disease, heart failure and metabolic syndrome. Methods Previously, surrogate matrices have been used when demonstrating the analytical performance of LC-MS/MS clinical research methods for the measurement of aldosterone and angiotensin I. Here, we have developed an analytically sensitive and reliable analytical strategy for simultaneous measurement of Aldosterone and Angiotensin I in human matrices. In-house calibrators and quality control samples were prepared, containing varying ranges of both aldosterone (20-2000pg/mL; 55-5548pmol/L) and angiotensin 1 (0.6-240ng/mL; 0.46-185nmol/L). The samples were extracted using the Oasis™ MAX 96-well µElution plate and then separated through the ACQUITY™ UPLC™ I-Class FL System using a XBridge™ Premier Peptide BEH™ C18 Column, over a run time of 3 minutes. Samples were then injected to Xevo™ TQ Absolute Mass Spectrometer, using both positive and negative acquisition modes. The downstream LC-MS/MS data analysis was performed using MassLynx™ MS Software. The analytical performance was demonstrated by extracting and quantifying two replicates of samples on two occasions per day over five separate days. Additionally, the stability of aldosterone and angiotensin I over the period of incubation (3-5hr) was evaluated, which is necessary when investigating the plasma renin activity in human Serum/Plasma samples. Results High reproducibility and repeatability were both determined, indicating total precision and repeatability (<15%CV) for both analytes and no significant changes were found in Aldosterone and Angiotensin I concentrations over 3-5hr of incubation. No significant system carryover (<10% of the lowest calibrator) from high concentration samples into subsequent blank injections was observed. In addition, calibration lines in human serum/plasma were linear, with coefficient of determinations (r2) >0.992 for all analyses at different incubation times. The analytical sensitivity of the clinical research method allows for precise quantification at 55 pmol/L for aldosterone and 0.46 nmol/L/hr for angiotensin I, with both analytes providing S/N (PtP) ≥10:1 and %RSD of <15% at these concentrations. Conclusions An analytically sensitive and selective clinical research method has been developed for the analysis of aldosterone and angiotensin I, using the Xevo TQ Absolute Mass Spectrometer. The Xevo TQ Absolute Mass Spectrometer enables the simultaneous analysis of physiologically low levels of aldosterone and plasma renin activity in human samples, (20pg/mL; 55pmol/L), (0.6ng/mL; 0.46nmol/h/L). A single test that improves instrument utilization, reduces cost, and allows the user to expand their existing test menu on the same platform has been established.

Solid Phase Extraction Methodology for Robust Isotope Analysis of Atmospheric Ammonium.

The stable nitrogen isotope composition (δ15N) of atmospheric ammonia (NH3) and ammonium (NH4+) has emerged as a potent tool for improving our understanding of the atmospheric burden of reduced nitrogen. However, current chemical oxidation methodologies commonly utilized for characterizing δ15N values of NH4+ samples have been found to lead to low precision for low concentration (i.e., < 5 μmol L-1) samples and often suffer from matrix interferences. Here, we present an analytical methodology to extract and concentrate NH4+ from samples through use of a sample pretreatment step using a solid phase extraction technique involving cation exchange resins. Laboratory control tests indicated that 0.4 g of cation exchange resin (Biorad AG-50W) and 10 mL of 4 M sodium chloride extraction solution enabled the complete capture and removal of NH4+. Using this sample pretreatment methodology, we obtained accurate and precise δ15N values for NH4+ reference materials and an in-house quality control sample at concentrations as low as 1.0 μM. Additionally, the sample pretreatment methodology was evaluated using atmospheric aerosol samples previously measured for δ15N-NH4+ (from Changdao Island, China), which indicated an excellent δ15N-NH4+ match between sample pretreatment and no treatment (y = (0.98 ± 0.05)x + (0.11 ± 0.6), R2 = 0.99). Further, this methodology successfully extracted NH4+ from aerosol samples and separated it from present matrix effects (samples collected from Oahu, Hawaii; pooled standard deviation δ15N-NH4+ = ± 0.5‰,n = 16 paired samples) that without pretreatment originally failed to quantitatively oxidize to nitrite for subsequent δ15N isotope analysis. Thus, we recommend applying this sample pretreatment step for all environmental NH4+ samples to ensure accurate and precise δ15N measurement.

Validation of the efficacy of pooled serum for serum glucose inhouse quality control material in comparison with commercial internal quality control in clinical chemistry laboratory

BackgroundThis study aimed to create an in-house glucose quality control material for humans, addressing the challenge of obtaining high-cost commercially prepared quality control materials in developing countries. MethodsAn in-house quality control material for glucose was prepared using a pooled serum sample and analyzed using a fully automated chemistry analyzer following the ISO 80 guidelines. The mean, standard deviation (SD), and coefficient of variance were calculated from the first 30 days of measurement, and the variability was checked over eight months using SPSS software. The study used Pearson's correlation with a 95% confidence interval and a P-value less than 0.05, which was statistically significant. ResultsThe average mean ± SD of human serum glucose was 185.2 ± 8.4 mg/dL, indicating that the precision between each measurement was better. The prepared in-house quality control material was stable for approximately five months without any significant change in the serum glucose concentration (mg/dl) (p-value<0.05). ConclusionsThe study suggests that room-temperature, 2–8 °C, and −20 °C to −30 °C storage of human serum samples for glucose analysis is a viable option, with stable glucose concentrations for up to 30 days. Pooled serum is a cost-effective method for in-house quality control, especially in resource-limited laboratories.

Accuracy and Sterilizability of In-House Printed Patient-Specific Aortic Model for Surgeon-Modified Stent Grafts-A Workflow Description for Emergency Aortic Endovascular Procedures.

Introduction: The use of 3D-printed aortic models for the creation of surgeon-modified endoprostheses represents a promising avenue in aortic surgery. By focusing on the potential impact of sterilization on model integrity and geometry, this report sheds light on the suitability of these models for creating customized endoprostheses. The study presented here aimed to investigate the safety and viability of 3D-printed aortic models in the context of sterilization processes and subsequent remodeling. Methods: The study involved the fabrication of 3D-printed aortic models using patient-specific imaging data and established additive manufacturing techniques. Five identical aortic models of the same patient were printed. Two models were subjected to sterilization and two to disinfection using commonly employed methods, and one model remained untreated. The models were checked by in-house quality control for deformation (heat map analyses) after the sterilization and disinfection processes. Three models (sterilized, disinfected, and untreated) were sent for ex-house (Lufthansa Technik, AG, Materials Technologies and Central Laboratory Services, Hamburg, Germany) evaluation and subsequent quantification of possible structural changes using advanced imaging and measurement technologies (macroscopic and SEM/EDX examinations). After sterilization and disinfection, each aortic model underwent sterility checks. Results: Based on macroscopic and SEM/EDX examinations, distinct evidence of material alterations attributed to a treatment process, such as a cleaning procedure, was not identified on the three implants. Comparative material analyses conducted via the EDX technique yield consistent results for all three implants. Disinfected and sterilized models tested negative for common pathogens. Conclusions: The evaluation of 3D-printed aortic models' safety after sterilization as well as their suitability for surgeon-modified endoprostheses is a critical step toward their clinical integration. By comprehensively assessing changes in model integrity and geometry after sterilization, this research has contributed to the broader understanding of the use of 3D-printed models for tailor-made endovascular solutions. As medical technologies continue to evolve, research endeavors such as this one can serve as a foundation for harnessing the full potential of 3D printing to advance patient-centered care in aortic surgery.

Determination of trace elements in ibuprofen drug products using microwave-assisted acid digestion and inductively coupled plasma-mass spectrometry

Trace elements are found in most drugs as a result of the drug formulation and drug production methods. An inductively coupled plasma-mass spectrometry method for the determination of 24 trace elements (Mg, Ti, V, Cr, Mn, Cu, Fe, Co, Ni, Zn, As, Se, Mo, Ru, Rh, Pd, Ag, Cd, Sb, Ba, Ir, Pt, Au, and Pb) in solid ibuprofen tablets was established in relation to the ICH Q3D(R1) guideline, to evaluate the possibility of linking trace elemental profiles to drug formulation strategies, and to differentiate between drug products based on the trace elemental profiles. Ten European ibuprofen drug products were evaluated (n=3). The sample preparation was performed by microwave-assisted acid digestion using only 10 mg of homogenized sample and 900 μL of a mix of 65% HNO3, 37% HCl, and 30% H2O2. Solid residuals primarily composed of insoluble SiO2 excipients were removed by centrifugation. Only concentrations of Mg, Fe, Ti, Mn, Cr, and Ni were detected above the limits of detection and did not exceed the ICH Q3D(R1) guideline permitted daily exposure limits. The trace elemental profiles were evaluated through principal component analysis. Three principal components describing 96% of the variance were useful in grouping the ibuprofen drug products, and the detected trace elemental remnants could be related to drug formulation and drug production strategies. An in-house quality control material was used in lack of certified reference materials and was in combination with spike recoveries used for method validation. Good spike recoveries (94–119%) were obtained for all measured trace elements except Mg. Mg showed acceptable spike recoveries (75–155%) for mid and high-spike concentrations, but poor recoveries (30–223%) were detected with low spike concentrations in spike matrices containing high amounts of Mg. Overall, the method is suggested applicable for solid drugs containing insoluble SiO2 excipients and drugs comparable to ibuprofen.

Diagnostic Efficacy of Photostimulated Chemiluminescence Assay for Detecting Anti-HIV Antibodies: A Retrospective Study.

The transmission of human immunodeficiency virus (HIV) through blood poses a slightly increased risk. As a result, patients requiring blood transfusions should be screened for HIV antibodies. This study examined the diagnostic effectiveness of the photostimulated chemiluminescence assay in detecting anti-HIV antibodies and determined the cut-off value for this method. The performance of the fully automated photostimulated chemiluminescence assay system was validated according to CNAS-GL038:2019 (2020) and CNAS-GL037:2019 (2019) guidelines. A retrospective study was conducted at the Department of Medical Laboratory, Nanjing Tongren Hospital, affiliated with Southeast University, from January 2020 to December 2022. A total of 77,386 cases were tested for anti-HIV antibodies using the photostimulated chemiluminescence assay, with 79 cases initially testing positive. The method's performance in detecting anti-HIV antibodies was evaluated using the Receiver Operating Characteristic (ROC) curve and the average Coefficient of Variation (CV) value of 3-year in-house quality control. The precision, detection limit, coincidence rate, and critical value of the performance verification results met the requirements. Using Western blotting (WB) as the reference method, positive cases were initially screened using the light-induced chemiluminescence method to determine the cut-off index (COI) value and draw the ROC curve. The maximum area under the ROC curve using the chemiluminescence method was 0.997, with a cutoff value of < 28.56, sensitivity of 98%, specificity of 100%, Jordan index of 0.98, and an average CV value of 3.55%. In conclusion, the photostimulated chemiluminescence assay has good diagnostic efficacy in detecting anti-HIV antibodies and is suitable for rapid screening before blood transfusion and surgery.

147 Determining Status of Five Genetic Conditions in U.S. Sheep with a Medium-Density Ovine Bead Array

Abstract Using molecular information in genetic evaluation has become routine in most livestock species. Small ruminants, however, are lagging in use of this technology, partly due to the higher cost of genotyping versus the value of the individual animal. Using a single genotyping platform to simultaneously obtain information for making genomic predictions, identifying genetic condition status, and verifying parentage avoids costs of running multiple DNA tests. Our objective was to develop and validate a process to obtain accurate genotypes for genetic conditions using a medium-density array, and to estimate their frequencies in U.S. sheep breeds. Samples (DNA) from 10,569 sheep from 9 breeds in the National Sheep Improvement Program, primarily Katahdin (8,657), Rambouillet (886), and Polypay (584), were genotyped with a commercial 50k single nucleotide polymorphism (SNP) bead chip. Genotypes for 5 genetic conditions, ovine progressive pneumonia (OPP) susceptibility (TMEM154), scrapie susceptibility (PRNP), double muscle (MSTN), callipyge (CLPG), and booroola FecB (BMPR1B), were determined using 66 SNP genotypes extracted from the bead chip. Targeted SNP markers were replicated 2 to 8 times on the array. The TMEM154 diplotypes were obtained by combining genotypes at 10 SNP markers. Variants for PRNP codon 136 and 171 were determined using 6 markers. The accuracy of assigning genetic status was validated using 15 reference DNA with known genotypes submitted blindly to the commercial laboratory. Consistency of replicated calls for an SNP was also evaluated. Following in-house laboratory-based quality control of the assay, acceptance of a genotype involved two steps. First, at least 60% of the replicated SNP on an animal needed to be assigned a genotype. Second, amongst those SNP genotyped, at least 60% needed to detect the same nucleotide. This strategy resulted in 98.4% and 90.9% of the animals having genetic status scored for PRNP and TMEM154, respectively. Where genotypes were accepted, OPP and scrapie susceptibility was assigned based on TMEM154 diplotypes and PRNP codons 136 and 171 genotypes, respectively. As shown in Table 1, genetic condition status differed appreciably among Katahdin, Polypay, and Rambouillet. Nearly 60% of Katahdins were characterized as highly susceptible to OPP while such was so in less than 15% Polypay and Rambouillet. Most (93.3%) Polypay were deemed scrapie resistant, with a majority of Katahdin (93.1%) and Rambouillet (80.6%) either resistant or rarely susceptible to this disease. However, 18.6% of Rambouillet were characterized as highly susceptible to scrapie. No animals carried the callipyge or FecB mutation. The double muscle mutation also was rare; in Katahdins, 2.7 and 0.2% of animals carried one or two copies, respectively. The approach developed accounted for genotyping inaccuracies, with full validation of genetic status. Furthermore, considerable variation in susceptibilities to OPP and scrapie was detected among breeds, which can be used in defining breeding objectives.

2-fluoro-1-methylpyridinium p-toluene sulfonate: a new LC-MS/MS derivatization reagent for vitamin D metabolites

Vitamin D analysis by MS faces several analytical challenges, including inefficient ionization, nonspecific fragmentation, interferences from epimers, isomers, and isobars, as well as very low concentration levels. In this study, we used 2-fluoro-1-methylpyridinium (FMP) p-toluene sulfonate for derivatization of vitamin D3 metabolites to increase detection sensitivity and allow for full chromatographic separation of vitamin D isomers and epimers. UHPLC-MS/MS was used for measurement of five vitamin D3 metabolites in human serum. Compared with Amplifex and 4-phenyl-1,2,4-triazolin-3,5-dion, the FMP p-toluene sulfonate reaction required less time to be performed. The method was optimized and validated to ensure accuracy, precision, and reliability. In-house and commercial quality control samples were used to assure the quality of the results for 25-hydroxyvitamin D3. The method showed very good linearity and intraday and interday accuracy and precision; coefficients of determination (r2) ranged between 0.9977 and 0.9992, relative recovery from 95 to 111%, and coefficient of variation from 0.9 to 11.3. Stability tests showed that the extracted derivatized serum samples were stable for 24 h after storage at −20°C; 24,25-dihydroxyvitamin D3 and 1,25-dihydroxyvitamin D3-FMP derivatives were stable for 1 week at −80°C. The method was applied to samples of healthy individuals for quantitative determination of vitamin D3, the two epimers of 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3.

Development of in-House Synthesis and Quality Control of [99mTc]Tc-PSMA-I&S.

Many radioactive PSMA inhibitory substances have already been developed for PET diagnostics and therapy of prostate cancer. Because PET radionuclides and instrumentation may not be available, technetium-99 m labelled tracers can be considered as a diagnostic alternative. A suitable tracer is [99mTc]Tc-PSMA-I&S, primarily developed for radio-guided surgery, which has been identified for diagnostics of prostate cancer. However, there is no commercial kit approved for the preparation of [99mTc]Tc-PSMA-I&S on the market. This work presents an automated process for the synthesis of [99mTc]Tc-PSMA-I&S concerning good manufacturing practice (GMP). We used a Scintomics GRP 4 V module, with the SCC software package for programming sequences for this development. The optimum reaction conditions were evaluated in preliminary experiments. The pH of the reaction solution was found to be crucial for the radiochemical yield and radiochemical purity. The validation of [99mTc]Tc-PSMA-I&S (n = 3) achieved a stable radiochemical yield of 58.7 ± 1.5% and stable radiochemical purities of 93.0 ± 0.3%. The amount of free [99mTc]TcO4- in the solution and reduced hydrolysed [99mTc]TcO2 was &lt;2%. Our automated preparation of [99mTc]Tc-PSMA-I&S has shown reliability and applicability in the clinical setting.

Inverted genomic regions between reference genome builds in humans impact imputation accuracy and decrease the power of association testing.

Over the last two decades, the human reference genome has undergone multiple updates as we complete a linear representation of our genome. Two versions of human references are currently used in the biomedical literature, GRCh37/hg19 and GRCh38. Conversions between these versions are critical for quality control, imputation, and association analysis. In the present study, we show that single-nucleotide variants (SNVs) in regions inverted between different builds of the reference genome are often mishandled bioinformatically. Depending on the array type, SNVs are found in approximately 2-5 Mb of the genome that are inverted between reference builds. Coordinate conversions of these variants are mishandled by both the TOPMed imputation server as well as routine in-house quality control pipelines, leading to underrecognized downstream analytical consequences. Specifically, we observe that undetected allelic conversion errors for palindromic (i.e., A/T or C/G) variants in these inverted regions would destabilize the local haplotype structure, leading to loss of imputation accuracy and power in association analyses. Though only a small proportion of the genome is affected, these regions include important disease susceptibility variants that would be affected. For example, the p value of a known locus associated with prostate cancer on chromosome 10 (chr10) would drop from 2.86×10-7 to 0.0011 in a case-control analysis of 20,286 Africans and African Americans (10,643 cases and 9,643 controls). We devise a straight-forward heuristic based on the popular tool, liftOver, that can easily detect and correct these variants in the inverted regions between genome builds to locally improve imputation accuracy.

Advances in imaging technologies for soybean seed analysis

Abstract: Among grain-producing species, soybean is one of the most important commodities, with increasing demand for production in coming years. Evaluation of soybean seed quality is fundamental for ensuring maximum germination and yield potential. Therefore, effective methods are necessary for examining different properties associated with physical-chemical, physiological, and seed-health changes that affect seed quality. This review focuses on the fundamental principles and on the application of techniques of radiographic imaging, magnetic resonance imaging, multispectral imagining, chlorophyll fluorescence imaging, and infrared thermography to evaluate changes related to loss of soybean seed quality, such as mechanical injury, injury caused by insects, embryonic malformation, and incomplete maturation. Computerized seedling image analysis is also presented for evaluation of seed lot vigor. The examples presented here show the potential of these image analysis techniques for identifying different types of injuries and increasing the efficiency of in-house quality control programs in soybean seed production companies.

Efficacy of In-House Quality Control Material Compared to Commercially Available Quality Control for Thyroid Hormone

Laboratory results in clinical laboratories are being generated by automated analyzers. The constant use of commercialcontrol materials is not economically feasible for many countries because of the non-availability or high cost of those materials.Therefore, the preparation of in-house quality control serum will be cost-effective for use in the laboratory. The commercialquality control for immunoassay is costlier and as per NABL 112 criteria, at least two levels of quality control should be run everyday for a laboratory with a large sample load. To overcome this problem our study aims to evaluate the efficacy of in-housepooled serum quality control in comparison with commercial internal quality control samples in thyroid hormone tests. Weprepared in-house quality control from leftover samples of subjects tested for thyroid profile after being screened for HIV, HCV,and HBsAg by pooling them together in a glass jar serum and kept in a deep freezer at -20ºC. Pooled serum was aliquot into 20vials each containing 500 μl. Every day along with commercial internal QC, one aliquot of pooled serum was analyzed for thirtydays for the following parameters: TSH, FT3, FT4. After getting thirty values for each parameter, mean, standard deviation, andcoefficient of variation were calculated for both IQC commercial sample and pooled serum sample.: In-house prepared qualitycontrol material performed as well as commercial quality control for thyroid profile. Therefore, prepared in-house quality controlcan be a good substitute for commercial quality control for thyroid profile.

Guide for starting or optimizing a 3D printing clinical service.

Three-dimensional (3D) printing has applications in many fields and has gained substantial traction in medicine as a modality to transform two-dimensional scans into three-dimensional renderings. Patient-specific 3D printed models have direct patient care uses in surgical and procedural specialties, allowing for increased precision and accuracy in developing treatment plans and guiding surgeries. Medical applications include surgical planning, surgical guides, patient and trainee education, and implant fabrication. 3D printing workflow for a laboratory or clinical service that produces anatomic models and guides includes optimizing imaging acquisition and post-processing, segmenting the imaging, and printing the model. Quality assurance considerations include supervising medical imaging expert radiologists' guidance and self-implementing in-house quality control programs. The purpose of this review is to provide a workflow and guide for starting or optimizing laboratories and clinical services that 3D-print anatomic models or guides for clinical use.

Opinion: Multi-Mycotoxin Reference Materials.

The analysis of mycotoxins in food and feed using liquid chromatography coupled with mass spectrometry is considered advantageous because the hyphenated technology enables simultaneous determination of multiple mycotoxins. Multi-mycotoxin analysis requires special consideration of quality control parameters to ensure proper evaluation of data quality for all target mycotoxins in method development and routine sample analysis. Mycotoxin matrix reference materials, especially certified reference materials, are stable and homogeneous matrices with certified traceability, concentrations, and uncertainty for mycotoxin(s) of interest. The use of these reference materials for single mycotoxin analysis has been a well-accepted practice and should be extended to multi-mycotoxin analysis. This opinion piece discusses the following essential metrological and operational components to improve data quality: (1) purposes of multi-mycotoxin reference materials; (2) comparison of reference materials, certified reference materials, and in-house quality control materials; (3) advantages of using reference materials for multi-mycotoxin analysis; (4) current trends and challenges of multi-mycotoxin reference materials. Potential applications of reference materials discussed here can improve routine mycotoxin determination and will lead to better accuracy and consistency of results. Quality control processes that incorporate reference materials in the field of mycotoxin analysis ensure successful development and implementation of liquid chromatography mass spectrometry-based multi-mycotoxin methods.

Automated radiosynthesis of [11 C]MTP38-a phosphodiesterase 7 imaging tracer-using [11 C]hydrogen cyanide for clinical applications.

We have developed 8-amino-3-(2S,5R-dimethyl-1-piperidyl)-[1,2,4]triazolo[4,3-a]pyrazine-5-[11 C]carbonitrile ([11 C]MTP38) as a positron emission tomography (PET) tracer for the imaging of phosphodiesterase 7. For the fully automated production of [11 C]MTP38 routinely and efficiently for clinical applications, we determined the radiosynthesis procedure of [11 C]MTP38 using [11 C]hydrogen cyanide ([11 C]HCN) as a PET radiopharmaceutical. Radiosynthesis of [11 C]MTP38 was performed using an automated 11 C-labeling synthesizer developed in-house within 40 min after the end of irradiation. [11 C]MTP38 was obtained with a relatively high radiochemical yield (33 ± 5.5% based on [11 C]CO2 at the end of irradiation, decay-corrected, n = 15), radiochemical purity (>97%, n = 15), and molar activity (47 ± 12 GBq/μmol at the end of synthesis, n = 15). All the results of the quality control (QC) testing for the [11 C]MTP38 injection complied with our in-house QC and quality assurance specifications. We successfully automated the radiosynthesis of [11 C]MTP38 for clinical applications using an 11 C-labeling synthesizer and sterile isolator. Taken together, this protocol provides a new radiopharmaceutical [11 C]MTP38 suitable for clinical applications.

Method for Reproducible Shipboard Segmented Flow Analysis Ammonium Measurement Using an In-House Reference Material for Quality Control

Ammonium is a fundamental nutrient for phytoplankton growth in seawater and is a key component of the microbial loop. Ammonium measured in parallel with other nutrients is crucial in understanding the small temporal scale changes in oceanographic ecology. Despite the importance of measuring ammonium at sea, owing to its lability, there is no consensus on the best method. The lack of availability of certified reference materials for ammonium in seawater also makes it difficult to assess the accuracy and reproducibility of ammonium measurements. In this study we present a modified segmented flow analysis method using ortho-phthaldialdehyde (OPA) with fluorescence detection to measure ammonium at sea together with four other macro-nutrients (nitrate, nitrite, silicate and phosphate) in near real time. An in-house ammonium quality control (QC) material was produced to improve the accuracy and repeatability of the measurement at sea. The QC was prepared following two different methods and stored in two types of containers. The suitability of the in-house QC’s as a reference material were assessed onboard the RV Investigator in 2018 during two oceanographic voyages, including one on the repeat SR03 CLIVAR transect. This paper describes the production and assessment of the in-house QC for ammonium in seawater, providing groundwork for creating a short-term stable ammonium reference material for sea going voyages. The uncertainty of this method of ammonium measurement was found to be 0.10 μmol/L at ammonium concentration of 1.0 μmol/L. Results show that preparation of the QC inside a laminar flow cabinet and directly into 10 mL polypropylene sample tubes just prior to the commencement of the voyage improved its stability.

In-House Preparation and Quality Control of Ac-225 Prostate-Specific Membrane Antigen-617 for the Targeted Alpha Therapy of Castration-Resistant Prostate Carcinoma.

Purpose:Ac-225 labeled with prostate-specific membrane antigen (PSMA-617), a transmembrane glycoprotein which is highly expressed in prostate carcinoma cells, is presently being considered a promising agent of targeted alpha therapy for the treatment of patients suffering from metastatic castration-resistant prostate cancer. In the present study, we report an optimized protocol for the preparation of therapeutic dose of Ac-225 PSMA-617 with high yield and radiochemical purity (RCP).Methods:Ac-225 PSMA-617 was prepared by adding the peptidic precursor-PSMA-617 (molar ratios, Ac-225: PSMA-617 = 30:1) in 1 ml ascorbate buffer to Ac-225 and heating the reaction mixture at 90°C for 25 min to obtain the radiopeptide with high RCP and yield. The radiolabeled peptide was administered in patients who met the eligibility criteria and posttherapy assessment was done.Results:Ten batches of Ac-225 PSMA-617 were prepared following this protocol. The radiopeptide was obtained with an adequate yield of 85%–87% and RCP of 97%–99%.Conclusion:The current protocol allows single-step, successful, routine inhouse radiolabeling of Ac-225 with PSMA-617 with high yield and RCP.

Intra-Laboratory Validation of Alpha-Galactosidase Activity Measurement in Dietary Supplements.

Introduction: Alpha-galactosidase (α-Gal) is an enzyme responsible for the hydrolyzation of glycolipids and glycoprotein commonly found in dietary sources. More than 20% of the general population suffers from abdominal pain or discomfort caused by intestinal gas and by indigested or partially digested food residuals. Therefore, α-Gal is used in dietary supplements to reduce intestinal gases and help complex food digestion. Marketed enzyme-containing dietary supplements must be produced in accordance with the Food and Drug Administration (FDA) regulations for Current Good Manufacturing Practice (cGMPs). Aim: in this work we illustrated the process used to develop and validate a spectrophotometric enzymatic assay for α-Gal activity quantification in dietary supplements. Methods: The validation workflow included an initial statistical-phase optimization of materials, reagents, and conditions, and subsequently a comparative study with another fluorimetric assay. A final validation of method performance in terms of specificity, linearity, accuracy, intermediate-precision repeatability, and system precision was then executed. Results and conclusions: The proven method achieved good performance in the quantitative determination of α-Gal activity in commercial food supplements in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals (ICH) guidelines and is suitable as a rapid in-house quality control test.

Improving quality of transcutaneous bilirubin measurements: Value of in-house developed quality control

ObjectivesQuality assurance (QA) plays an integral role in Point of Care Testing (POCT) programs. Quality control (QC) is an important QA program component to ensure high quality results and enhanced patient care. The measurement of transcutaneous bilirubin (TcB) in the POCT setting is an essential part of newborn care in Alberta, Canada. However, there is currently no available commercial QC material for TcB meters. An in-house developed QC material has been in use within a single TcB POCT program within Alberta. The objective of this study was to determine the performance of this QC material by other POCT staff and clinical end-users to assess whether its use could be expanded. Design and methodsTwo levels of QC material were measured by POCT staff and clinical end-users across 12 different sites using the Dräger Jaundice Meter JM-103® and JM-105® meters. ResultsThe performance of the QC material was acceptable when tested by POCT staff, was stable and reliable over time, and had an acceptable CV (≤8%). However, the data does not support use of the QC material by clinical end-users. ConclusionsThe use of the QC material could be expanded into other TcB settings for use by POCT staff. Additional training and experience with the QC material by end-users is needed to facilitate QC use in the clinical setting.

Do You Second That Emotion?

This paper discusses the emotions experienced by subtitlers who subtitle sensitive audiovisual material. “Sensitive audiovisual material” refers to audiovisual texts which deal with controversial and emotive topics, such as abuse, war, torture. This topic has remained under-researched in subtitling, despite having been sporadically explored in other fields of translation (Hubscher-Davidson, 2017; Rojo and Ramos Caro, 2016; Tabakowska, 2016).&#x0D; The data presented in this paper expand upon and complement the findings discussed in Perdikaki and Georgiou (2020) based on an online survey completed by 170 subtitlers. For the current paper, the data discussed come from an online focus group with three professional subtitlers and face-to-face interviews with one freelance subtitler as well as a team interview with two in-house quality control editors. Having confirmed in our previous study that many subtitlers are affected by the sensitive AV material they subtitle, this paper aims at a more nuanced exploration of how subtitlers regulate emotions elicited on-the-job, offering specific examples as well as emotion management techniques. Finally, the perspective of emotional responsiveness, depending on socio-economic contexts as well as the linguistic arsenal of the subtitler, is briefly discussed.