Search Results (34)

Background/Objectives: Children with acute lymphoblastic leukemia (ALL) often experience treatment-related side effects. Physical therapy (PT) surveillance programs are helpful in identifying impairments; however, they do not typically incorporate assessments for peripheral neuropathy, motor proficiency, and foot drop. Our aim is to explore the feasibility of conducting additional functional tests to an existing surveillance program to improve the identification of impairments and characterize the prevalence of treatment-related deficits in children with ALL. Methods: A prospective, longitudinal descriptive study, embedded into a quality improvement initiative, was conducted. The surveillance program included standard assessments for ankle range of motion, activity level, balance, functional capacity, pain, gait, and kneeling to standing. Additional tests included motor and sensory function, foot posture, motor performance, quality of life, feasibility (recruitment and completion rates), service provision, and self-reported symptoms. Data were collected over 3 months. Results: Twenty children completed the study and 19 completed all assessments. Nineteen children presented deficits in at least two physical function tests. The most prevalent deficit identified from standard PT tests included decreased ankle range of motion (n = 19; 95%), and the most common deficit seen in the additional tests was impaired motor and sensory function (n = 14/19; 74%). Pain was the most common self-reported symptom in the checklist and the second worst subscale score in the pain dimension of the quality of life questionnaire (p < 0.001). Conclusions: Several treatment-related deficits were identified in children with ALL. Further research is warranted to explore the use of a standardized symptom checklist for the timely identification of functional limitations and impairments. Full article

Accredited laboratories participating in Proficiency Testing (PT) and Interlaboratory Comparison (ILC) typically submit measurement results (and associated uncertainties) to an organizer for performance evaluation using statistics such as the z-score and the En value. This requirement can undermine confidentiality when the disclosed plaintext values reveal commercially sensitive methods or client-related information. This paper proposes a secure-by-design PT/ILC workflow based on fully homomorphic encryption (FHE), enabling the required scoring computations to be executed directly on ciphertexts. Using the CKKS scheme (Microsoft SEAL), the organizer distributes encrypted assigned values and a public/evaluation key set; each participant locally encrypts pre-processed measurement data, evaluates encrypted z-score and En value, and returns only encrypted performance metrics. The organizer decrypts the metrics without receiving the ciphertexts of participants’ raw measurement values. We quantify feasibility via execution time, run-to-run variability across fresh key generations (coefficient of variation), and relative calculation error versus plaintext scoring. On commodity hardware, end-to-end score computation takes 1 to 8 s, the coefficient of variation can be reduced below 1e⁻¹⁰, and the relative error remains below 1e⁻⁶, indicating practical deployability and numerical stability for PT/ILC decision-making. Given that PT/ILC reporting cycles are typically on the order of days to weeks, a per-participant computation time of seconds is operationally negligible, while the observed coefficient of variation and relative error indicate that the CKKS approximation and key-dependent variability are far below typical decision thresholds used for pass/fail classification. Full article

Background: The clinical research laboratory plays a pivotal role in the execution of clinical studies. The accurate and consistent registration of patients is dependent on the competent use of laboratory equipment and manual techniques by technicians, ensuring the reliability of the data collected. To support these activities, the Groupe de Recherche Action en Santé (GRAS) has been registered with the College of American Pathologists (CAP) and the Clinical Laboratories Services (CLS) in Johannesburg, South Africa, for external proficiency testing (EPT) of its laboratory, as part of our commitment to quality assurance. The following report details the performance achievements over the past five years. Methods: Proficiency testing (PT) samples are dispatched to GRAS Lab three times a year (quarterly) and the results are generally returned within two to three weeks. In the field of parasitology, challenge specimens were prepared as follows: thick and thin blood films were stained with Giemsa and mounted with strips to protect them for multiple uses. Photographs, also known as whole slide images (WSIs), were also taken. For the biochemistry and haematology tests, a set of five samples were received for processing. All evaluations were carried out in accordance with the GRAS laboratory’s internal procedures. Results: The CAP laboratory’s performance in terms of the diagnosis of malaria and other blood parasites from 2020 to 2024 was 97.3% accurate (ranging from 93.33% to 100%), with 93.33%, 100%, 100%, 93.33% and 100% achieved in 2020, 2021, 2022, 2023 and 2024, respectively. The number of microscopists evaluated annually has been subject to variation according to operational staff at the time of evaluation. A total of 31 microscopists were enrolled in the CLS PT scheme, of which 73.9% were classified as ‘experts’ and 19.2% as ‘reference’ microscopists. In the field of haematology, the PT demonstrated 100% accuracy over the four-year study period. This outcome is indicative of the high-performance levels exhibited by the automated systems under scrutiny and the comparable nature of the data produced by these systems. The same trend was observed in the biochemistry PT results, with an overall score of 92.12%, ranging from 78% to 100%. Conclusions: Proficiency testing has been shown to be an effective tool for quality assurance in laboratories, helping to ensure the accuracy of malaria and other blood parasite diagnoses made by microscopists, as well as the results generated by automated systems. It has been instrumental in assisting laboratories in identifying issues related to test design and performance. Full article

The accurate quantification of food allergens is crucial for ensuring consumer safety and compliance with regulatory requirements. A proficiency test (PT) was organised to evaluate the performance of laboratories in quantifying total egg and total milk protein in cookies. The PT involved 20 laboratories, which reported results using mainly commercial ELISA kits and liquid chromatography–tandem mass spectrometry (LC-MS/MS). The findings indicate a satisfactory performance for milk protein determination among the majority of participant laboratories. However, the quantification of egg proteins in heated products remains a challenge, with most laboratories reporting results significantly below the reference value. Several potential factors contributing to this challenge are discussed, including the denaturation of egg proteins during heat treatment, differences in extraction strategies and the antibodies used in ELISA kits, and the lack of standardised methods and conversion factors for LC-MS/MS analysis. These findings underscore the importance of regular PT exercises to evaluate laboratory performance and ensure compliance with WHO/FAO recommendations. The results of this study aim to guide the development of improved analytical methods and strategies for ensuring the accurate quantification of food allergens. Full article

The water content in milk powder must be controlled to ensure its stability. The analytical methods used for its determination can be verified through proficiency testing (PT). This study evaluated the reference values, their uncertainty, and the implications for nine PT rounds on moisture determination in milk powder conducted between 2017 and 2021 by a Chilean PT provider. An independent laboratory assigned the reference values, considering the analysis session as a source of uncertainty. Results showed that in 77.8% of the rounds, uncertainty did not meet the ISO 13528:2022 criterion, requiring the use of z′-score, which increased the risk of erroneous evaluations in 5.8% of cases, particularly near threshold values (z′ ≈ 2.0 or 3.0). The robust standard deviation from participants’ results exceeded 0.14 g water/100 g milk powder in 63.0% of PT items, suggesting that future evaluations should consider modifying the standard deviation for proficiency assessment. Reference values were found to be compatible with participants’ consensus values, though their use affected 19.3% of performance classifications, reinforcing the need for independent reference values in PT schemes with a small number of laboratories. These findings highlight the importance of evaluating the dispersion trends in proficiency assessment and adapting standard deviation criteria for more accurate performance evaluation. Full article

Pseudocereals have gained attention due to their adaptability to different climates, high nutritional value, and suitability for gluten-free and plant-based diets. However, a challenge lies in the necessary adaptations in the diet pathways, mainly due to the lack of matrix-matching metrological tools. To address this problem, we developed a classification system to support laboratory decisions without shaped Proficiency Testing (PT) or Certified/Standard References Material. This system evaluates method performance through limit of detection (LOD), maximum uncertainty, and statistical comparison. For that matter, the mineral contents (Cu, Mn, Fe, Zn, Mg, P, Ca, K, and Na) of quinoa (Chenopodium quinoa), amaranth (Amaranthus caudatus), and buckwheat (Fagopyrum esculentum) were determined, using three different digestion methods, including dry-ashing, microwave, and graphite block acid digestion. A decision was reached concerning the optimal digestion method to be employed, with the results classified into three categories: (i) “rejected if results failed in two categories; (ii) “use with caution” if results were not satisfactory in one category; or (iii) “accepted”, if the results passed in all the categories. The system efficacy was exemplified by the effectiveness of dry-ashing and graphite block acid digestion by comparison with microwave digestion. Neither dry-ashing nor graphite block acid digestion can be recommended as an alternative method to the microwave digestion method when all the prioritized nutrient minerals are understudied. Although the microwave method is preferable for multi-elemental analysis, it is possible to obtain, with caution, comparable results from all the digestion methods if a higher relative combined uncertainty is defined (target uncertainty < 11%) under the assumption that this is suitable for the study. Full article

Milk adulteration may cause losses or quality problems in the dairy industry, with implications regarding consumers’ health. The addition of water is one of the most common adulterations, which can be detected by determining the freezing point of milk. A proficiency testing (PT) program is in place in Chile concerning the determination of the freezing point of raw milk. A limited number of laboratories participate regularly to assure the validity of their measurements. The reference values were obtained independently through a calibration test, as recommended by ISO 13528:2022 in those cases where a small number of participants are evaluated. The uncertainty of the reference values assigned to nine PT rounds that included three PT items was investigated. A modification has been proposed for their calculations, which consists of the incorporation of the CRM uncertainty. This involves assessing the participants’ performance using the z’-score across all laboratories utilizing the thermistor method, which presents a slightly higher likelihood of inaccurate evaluation (2.9% of total participations). The assigned values demonstrated compatibility with the participants’ results. It is recommended that the same standard deviation for proficiency assessment be utilized for evaluating the performance of participants. Full article

Background: The joint College of American Pathologists/American College of Medical Genetics and Genomics Cytogenetics Committee works to ensure the competency and proficiency of clinical cytogenetic testing laboratories through proficiency testing (PT) programs for various clinical tests offered by such laboratories, including the evaluation of cytogenetic abnormalities in solid tumors. Methods: Review and analyze 25 years (1999–2023) of solid tumor chromosome analysis PT results, utilizing G-banded karyograms. A retrospective review of results from 1999 to 2023 was performed, identifying the challenges addressing solid tumors. The chromosomal abnormalities and overall performance were evaluated. Results: A total of 21 solid tumor challenges were administered during the period 1999–2018. No solid tumor challenges were administered during the period 2019–2023. Challenges consisted of metaphase images and accompanying clinical history for the evaluation of numerical and/or structural abnormalities. All 21 cases reached 80% grading consensus for abnormality recognition. However, five cases (24%) failed to reach consensus for nomenclature reporting by participating laboratories. These cases illustrate errors in reporting chromosomal abnormalities, including whole-arm translocations and those involving sex chromosomes. In addition, they highlight the challenges with differentiation of terminal and interstitial deletions, difficulties in identifying correct breakpoints, and omission of brackets in neoplastic cases. Conclusions: This comprehensive 25-year review demonstrates the exceptional proficiency of cytogenetic laboratories in accurately identifying chromosome abnormalities in solid tumors, while also highlighting the challenges of reporting specific types of chromosomal abnormalities. Full article

In the Global Poliovirus Laboratory Network (GPLN), participation and successful completion in annual proficiency test (PT) panels has been a part of the WHO accreditation process for decades. The PT panel is a molecular external quality assessment (mEQA) that evaluates laboratory preparedness, technical proficiency, the accuracy of data interpretation, and result reporting. Using the Intratypic Differentiation (ITD) real-time RT-PCR kits from CDC, laboratories run screening assays and report results in accordance with the ITD algorithm to identify and type polioviruses. The mEQA panels consisted of 10 blinded, non-infectious lyophilized RNA transcripts, including programmatically relevant viruses and targets contained in the real-time PCR assays. Sample identities included wildtype, vaccine-derived (VDPV), Sabin-like polioviruses, enterovirus, and negatives, as well as categories of invalid and indeterminate. The performance of individual laboratories was assessed based on the laboratory’s ability to correctly detect and characterize the serotype/genotype identities of each sample. The scoring scheme assessed the laboratory readiness following GPLN guidelines. Laboratories receiving mEQA scores of 90 or higher passed the assessment, scores of less than 90 failed and required remedial actions and re-evaluation. In 2021 and 2022, 123 and 129 GPLN laboratories were invited to request the annual PT panel, and 118 and 127 laboratories submitted results, respectively. The overall results were good, with 86% and 91.5% of laboratories passing the PT panel on their first attempt in 2021 and 2022, respectively. Most labs scored the highest score of 100, and less than one quarter scored between 90 and 95. Less than 10% of submitting laboratories failed the PT, resulting in in-depth troubleshooting to identify root causes and remediations. Most of these laboratories were issued a second PT panel for repeat testing, and almost all laboratories passed the repeat PT panel. The results of the 2021 and 2022 annual mEQA PTs showed that, despite the COVID-19 pandemic, the performance remained high in the GPLN, with most labs achieving the highest score. For these labs, the real-time PCR assay updates that were implemented during 2021–2022 were carried out with full adherence to procedures and algorithms. Even initially failing labs achieved passing scores after remediation. Full article

Detection of botulinum neurotoxins (BoNTs) involves a combination of technical challenges that call for the execution of inter-laboratory proficiency tests (PTs) to define the performance and ease of implementation of existing diagnostic methods regarding representative BoNT toxin-types spiked in clinical, food, or environmental matrices. In the framework of the EU project EuroBioTox, we organized an international proficiency test for the detection and quantification of the clinically relevant BoNT/A, B, E, and F sero- and subtypes including concentrations as low as 0.5 ng/mL. BoNTs were spiked in serum, milk, and soil matrices. Here, we evaluate the results of 18 laboratories participating in this PT. Participants have implemented a wide array of detection methods based on functional, immunological, and mass spectrometric principles. Methods implemented in this proficiency test notably included endopeptidase assays either coupled to mass spectrometry (Endopep-MS) or enzyme-linked immunosorbent assays (Endopep-ELISA). This interlaboratory exercise pinpoints the most effective and complementary methods shared by the greatest number of participants, also highlighting the importance of combining the training of selected methods and of distributing toxin reference material to reduce the variability of quantitative data. Full article

Proficiency testing (PT) allows food laboratories to endorse their competency to provide food safety guarantees to producers and consumers. One of the recommended methods for assigning reference values in PT with a small number of participants consists in considering the results that a laboratory obtains by means of a calibration test based on certified reference material (CRM). The present study delves into the results from eight PT rounds on the determination of fat and crude protein from raw milk, with modifications in the number of samples and the analysis sessions from that required by the ISO 13528:2022. The uncertainty criterion of the assigned value established by the ISO 13528:2022 standard was met by 93% of the participating laboratories, which allowed most participants to be evaluated through z-score. The assigned values were generally compatible with the results obtained by the participants. Thus, it can be concluded that the design for the assignment of the reference value is appropriate for PT with a limited number of participants. It is recommended for future PT to limit the uncertainty of the CRM according to their availability and to update the standard deviation of the proficiency assessment for the Mid-Infrared Spectroscopy method (MIR). Full article

The primary challenge in unsupervised learning is training unnormalized density models and then generating similar samples. Few traditional unnormalized models know what the quality of the trained model is, as most models are evaluated by downstream tasks and often involve complex sampling processes. Kernel Stein Discrepancy (KSD), a goodness-of-fit test method, can measure the discrepancy between the generated samples and the theoretical distribution; therefore, it can be employed to measure the quality of trained models. We first demonstrate that, under certain constraints, KSD is equal to Maximum Mean Discrepancy (MMD), a two-sample test method. PT KSD GAN (Kernel Stein Discrepancy Generative Adversarial Network with a Pulling-Away Term) is produced to compel generated samples to approximate the theoretical distribution. The generator, functioning as an implicit generative model, employs KSD as loss to avoid tedious sampling processes. In contrast, the discriminator is trained to identify the data manifold, also known as an explicit energy-based model. To demonstrate the effectiveness of our approach, we undertook experiments on two-dimensional toy datasets. Our results highlight that our generator adeptly captures the accurate density distribution, while the discriminator proficiently recognizes the unnormalized approximate distribution shape. When applied to linear Independent Component Analysis datasets, the log likelihoods of PT KSD GAN improve by about 5‰ over existing methods when the data dimension is less than 30. Furthermore, our tests on image datasets reveal that the PT KSD GAN excels in navigating high-dimensional challenges, yielding authentically genuine samples. Full article

This study investigates the effectiveness of robust estimators of location and dispersion, used in proficiency testing and listed in ISO 13528:2015, in outlier detection. The models utilize (a) kernel density plots, (b) Z-factors, (c) Monte Carlo simulations, and (d) distributions derived from at most two contaminating distributions and one main Gaussian. The simulation parameters cover a wide range of those commonly encountered in proficiency testing (PT) schemes, so the results presented are of fairly general application. We chose a functional sub-optimal solution by grouping and classifying the model settings, resulting in five matrices readily usable for selecting the best robust estimator. Whenever at most half of the distribution of each contaminating population is outside the central distribution, there is only one optimal estimator. For all other cases, the five matrices provide the appropriate robust statistic. The proposed method applies to 95.1% of 144 results for an existing PT for cement. These actual datasets indicate that the Hampel estimator for the mean and the Q-method for the standard deviation provide the most appropriate performance statistic in 86.1% of the cases. Full article

For the early detection of avian influenza virus (AIV), molecular diagnostic methods such as real-time RT-PCR (rRT-PCR) are the first choice in terms of accuracy and speed in many countries. A laboratory’s capability to perform this diagnostic method needs to be measured through external and independent assessment to ensure that the method is validated within the laboratory and in interlaboratory comparison. The Animal and Plant Quarantine Agency of Korea has implemented five rounds of proficiency testing (PT) for rRT-PCR targeting local veterinary service laboratories involved in the AIV national surveillance program from 2020 to 2022. In each round, a portion composed of six or more samples was selected from the entire PT panel consisting of H5, H7, and H9 viruses isolated in Korea and distributed to each participant, and at least one pair of samples was commonly included in each panel for interlaboratory comparison. During the five rounds of PT, a few incorrect and outlying results were detected that required immediate inspection or corrective actions. However, in the quantitative measurement of Ct values, the average standard deviation or coefficient of variation decreased as multiple PT rounds progressed, and a positive correlation between consecutive rounds of PT was observed since 2021. The better consistency or stability in the experimental performance appeared to contribute to the more harmonized results in the latest PTs, and it is assumed that the positive reaction of participants to the challenges of quantitative assessment reports showing their status intuitively might work. We need to continue operating the PT program for local laboratories because they play crucial roles at the front line of the national avian influenza surveillance program, and frequent changes in the human resources or environment for diagnosis in those laboratories are inevitable. Full article

Although placing students in the appropriate proficiency levels of post-secondary English programs is crucial for optimal learning, the evaluation of placement tests (PTs) in terms of establishing their reliability and validity is relatively under-researched. This study assesses the validity, reliability, and effectiveness of an in-house online PT. The content validity was established through the internal and external moderation of the question papers and answer keys while criterion-related concurrent validity was established via IELTS benchmarking. New Student Survey was used to investigate the face validity. The internal consistency and reliability of the reading test items were measured using Cronbach’s alpha while descriptive statistics were calculated for the listening test. Paired sample t-test (dependent t-test) was used to assess the inter-rater reliability of the speaking and writing tests which were double-marked. The data analysis revealed that the PT was effective in placing students at different levels of the foundation program (FP) and the statistical analyses conducted to test the reliability and validity showed positive results for most of the test versions. The study offers useful insights to test developers and policymakers regarding the authentication of in-house tests and the creation of guidelines for PT design and evaluation. Full article