Assignment Of Values Research Articles

Approaches for the production of reference materials with qualitative properties—The new International Standard ISO 33406

The number of reference materials (RMs), including certified reference materials (CRMs) characterized for qualitative properties, has steadily increased in recent years. In response, the Technical Committee for Reference Materials of the International Organization for Standardization, ISO/TC 334, developed ISO 33406 to provide guidance to reference material producers (RMPs) on producing qualitative RMs. ISO 33406 builds on the general requirements in ISO 17034:2016 for RMP competence and offers specific guidance on value assignment, assessment of homogeneity and stability, statement of metrological traceability, and measurement uncertainty evaluation for RMs with qualitative property values.

Linac- and CyberKnife-based MRI-only treatment planning of prostate SBRT using an optimized synthetic CT calibration curve.

CT Hounsfield Units (HUs) are converted to electron density using a calibration curve obtained from physical measurements of an electron density phantom. HU values assigned to an MRI-derived synthetic computed tomography (sCT) may present a different relationship with electron density compared to CT HU. Correct assignment of sCT HU values is critical for accurate dose calculation and delivery. The goals of this work were to develop a sCT calibration curve using patient data acquired on a clinically commissioned CT scanner and assess for CyberKnife- and volumetric modulated arc therapy (VMAT)-based MR-only treatment planning of prostate SBRT. Same-day CT and MRI simulation in the treatment position were performed on 10 patients treated with SBRT to the prostate. Dixon in-phase and out-of-phase MRIs were acquired on a 3T scanner using a 3D T1-weighted gradient-echo sequence to generate sCTs using a commercial sCT algorithm. CT and sCT datasets were co-registered and HU values compared using mean absolute error (MAE). An optimized HU-to-density calibration curve was created based on average HU values across an institutional patient database for each of the four sCT tissue types. Clinical CyberKnife and VMAT treatment plans were generated on each patient CT and recomputed onto corresponding sCTs. Dose distributions computed using CT and sCT were compared using gamma criteria and dose-volume-histograms. For the optimized calibration curve, HU values were -96, 37, 204, and 1170 and relative electron densities were 0.95, 1.04, 1.1, and 1.7 for adipose, soft tissue, inner bone, and outer bone, respectively. The proposed sCT protocol produced total MAE of 94±20HU. Gamma values mean±std (min-max) were 98.9%±0.9% (97.1%-100%) and 97.7%±1.3% (95.3%-99.3%) for VMAT and CyberKnife plans, respectively. MRI-derived sCT using the proposed approach shows excellent dosimetric agreement with conventional CT simulation, demonstrating the feasibility of MRI-derived sCT for prostate SBRT treatment planning.

Stepping-up accurate quantification of chlorinated paraffins: Successful certification of the first matrix reference material

BackgroundChlorinated paraffins (CPs) are industrial chemicals categorised as persistent organic pollutants because of their toxicity, persistency and tendency to long-range transport, bioaccumulation and biomagnification. Despite having been the subject of environmental attention for decades, analytical methods for CPs still struggle reaching a sufficient degree of accuracy. Among the issues negatively impacting the quantification of CPs, the unavailability of well-characterised standards, both as pure substances and as matrix (certified) reference materials (CRMs), has played a major role. The focus of this study was to provide a matrix CRM as quality control tool to improve the comparability of CPs measurement results. ResultsWe present the process of certification of ERM®-CE100, the first fish reference material assigned with certified values for the mass fraction of short-chain and medium-chain chlorinated paraffins (SCCPs and MCCPs, respectively). The certification was performed in accordance with ISO 17034:2016 and ISO Guide 35:2017, with the value assignment step carried out via an intercomparison of laboratories of demonstrated competence in CPs analysis and applying procedures based on different analytical principles. After confirmation of the homogeneity and stability of the CRM, two certified values were assigned for SCCPs, depending on the calibrants used: 31 ± 9 μg kg−1 and 23 ± 7 μg kg−1. The MCCPs certified value was established as 44 ± 17 μg kg−1. All assigned values are relative to wet weight in the CRM that was produced as a fish paste to enhance similarity to routine biota samples. Significance and noveltyThe fish tissue ERM-CE100 is the first matrix CRM commercially available for the analysis of CPs, enabling analytical laboratories to improve the accuracy and the metrological traceability of their measurements. The certified CPs values are based on results obtained by both gas and liquid chromatography coupled with various mass spectrometric techniques, offering thus a broad validity to laboratories employing different analytical methods and equipment.

Development of an SI-traceable N-terminal pro-B-type natriuretic peptide certified reference material using structure-based impurity-corrected isotope dilution mass spectrometry approaches.

N-Terminal pro-B-type natriuretic peptide (NT-proBNP) is a pivotal biomarker for the diagnosis and prognosis of heart failure (HF). However, no SI-traceable certified reference material (CRM) or reference measurement procedure (RMP) is available for this biomarker, and so clinical testing results obtained in different laboratories cannot be traced to a higher-order standard, leading to incomparable measurements. Protein hydrolysis and protein cleavage isotope dilution mass spectrometry (AAA-IDMS and PepA-IDMS) were used to develop a CRM. Structurally related impurities were identified by high-resolution mass spectrometry. The quantitative AAA-IDMS results were corrected according to the amino acid compositions of the impurities. Using PepA-IDMS, two peptides from the proteolyzed product were confirmed as signature peptides. To obtain traceable and accurate results, the signature peptides were quantified using impurity-corrected AAA-IDMS. The candidate NT-proBNP solution was denatured and enzymatically digested using the Glu-C endoproteinase. The released signature peptides were measured using an isotopic dilution approach. The homogeneity and stability of the candidate CRM were characterized, and their uncertainties were combined with the value assignment process. The developed CRM can be considered a unique SI-traceable NT-proBNP reference material and is expected to be used as a primary calibrator for matrix NT-proBNP CRM development.

Development and Standardization of an Adaptation Index to Assess the Climate Resilient Practices by Paddy Growers

India is prominently recognized as the foremost producer of paddy, cultivating this crop over 47.83 million hectares and generating 135.75 million tonnes of paddy, thus playing a substantial role in the worldwide paddy output. However, there is an anticipated decline in paddy production yields due to the projected effects of climate change, estimated to range from 10% to 30% by 2030. In recent times, adaptation to climate change has become a major concern to farmers, policy makers and researchers. Climate resilient rice production practices need to be enhanced at the farm level in order to aid rural residents in improving their household food security. Against this backdrop, the proposed research seeks to fill this crucial knowledge gap by developing and constructing adaptation index tailored specifically for paddy growers in India. Through a literature review and discussions with experts, we have identified indicators and sub-indicators using the indicator approach method. These indicators will help us understand how paddy growers are adapting to climate change and implementing climate resilient practices. The relevancy rating score was obtained from 30 experts in the concerned area. Based on the relevancy score, 8 indicators and 23 sub-indicators of 0.80 and above were considered for inclusion in the adaptation index. To compute the index values for each of the identified indicators, their relative importance in the adaptation practices was worked out by assignment of index values to indicators through Principal component analysis (PCA) based on the high factor loadings exceeded 0.5 of sub-indicators were considered and the findings revealed that disease and management had highest index value of 3.461, followed by methods of paddy establishment (2.195), crop rejuvenation techniques (2.10), altered planting dates (2.049), water saving and management techniques (1.987), nursery management (1.562), paddy varieties (1.342) and spacing (1.214).

Model Counting and Sampling via Semiring Extensions

Many decision and optimization problems have natural extensions as counting problems. The best known example is the Boolean satisfiability problem (SAT), where we want to count the satisfying assignments of truth values to the variables, which is known as the #SAT problem. Likewise, for discrete optimization problems, we want to count the states on which the objective function attains the optimal value. Both SAT and discrete optimization can be formulated as selective marginalize a product function (MPF) queries. Here, we show how general selective MPF queries can be extended for model counting. MPF queries are encoded as tensor hypernetworks over suitable semirings that can be solved by generic tensor hypernetwork contraction algorithms. Our model counting extension is again an MPF query, on an extended semiring, that can be solved by the same contraction algorithms. Model counting is required for uniform model sampling. We show how the counting extension can be further extended for model sampling by constructing yet another semiring. We have implemented the model counting and sampling extensions. Experiments show that our generic approach is competitive with the state of the art in model counting and model sampling.

Reply to “Comment on Comparison of direct and indirect measures of transport efficiency in single particle inductively coupled plasma mass spectrometry” by H. Goenaga-Infante

This paper provides a rebuttal to the comments on our original research article entitled “Comparison of Direct and Indirect Measures of Transport Efficiency in Single Particle ICP-MS” recently published by Goenaga-Infante in Spectrochimica Acta Part B: Atomic Spectroscopy.The intent of our study is not to condemn the dynamic mass flow (DMF) method but rather to explore the use parameters under which it can and cannot be applied. As explained in the original paper, the goal of this study is to evaluate the ranges of use conditions under which measures of transport efficiency (TE) yield accurate and reproducible results for spICP-MS measurements of particle number concentration (PNC) and particle size (diameter, PS) of various gold nanoparticle (AuNP) suspensions. The evaluation was performed through a systematic comparison of three methods for the measurement of TE: the particle frequency (TEF), particle size (TES), and DMF methods using three types of spray chambers operated at cooled and ambient temperature conditions and employing different ICP-MS platforms. While we appreciate thorough critical and constructive comments on our paper, we strongly disagree that the conclusions and highlights are not supported by the content and findings about the features and benefits of the DMF method.The discussion of three additional independent studies in this field by other spICP-MS expert groups that have been published after the submission of our manuscript is included in this paper. While the DMF approach has been used in two interlaboratory comparisons for TE determination in spICP-MS measurements of PNC, only one laboratory, namely the laboratory led by Goenaga-Infante, provided results using the DMF method in both projects. A method cannot be considered validated if successful results have only been demonstrated within one laboratory.The paper by Goenaga-Infante claims that the main use of DMF, the assignment of a SI traceable PNC value to new commercial nanomaterials (NMs), has not been highlighted explicitly in our original paper. The advantages and disadvantages of the DMF, TES, and TEF methods to measure TE were presented throughout the manuscript and are clearly summarized in the conclusion. The assignment of PNC that is metrologically traceable to the SI implies that all known or suspected uncertainty components including bias are taken into account. Our research shows that under some use conditions, the biases inherent to the DMF method are not yet fully understood and cannot be accounted for. While Cuello-Nuñez et al. Journal of Analytical Atomic Spectrometry, 2020, DOI: https://doi.org/10.1039/c9ja00415g state that cooled conditions (2 °C) were used in their work, they do not define the level of bias that can be expected if different spray chamber temperatures are used, and they do not provide recommendations on the optimal use conditions that define the field of applicability of the DMF method. Furthermore, besides the use of a Scott-type spray chamber cooled to 2 °C, neither the composition material of the spray chamber nor the volume of the Scott-type spray chamber were specified. It is important to note that in our original research, fifteen of the nineteen experiments were conducted using a cooled spray chamber. Also, the four different ICP-MS platforms were used in the standard configuration and with additional spray chamber options encountered in common ICP-MS usage. The value of our work is that it extends the study of Cuello-Nuñez et al. to a wide variety of use conditions routinely encountered in spICP-MS analysis.

U.S. Healthcare Provider Views and Practices Regarding Planned Birth Setting.

We conducted 19 in-depth, semistructured, qualitative interviews of eight obstetricians, eight midwives, and three pediatricians from across the United States. Interviews explored healthcare providers' interpretation of the current evidence and their personal and professional experiences with childbirth within the existing medical, ethical, and legal context in the United States. Themes emerged concerning risks and benefits, decision-making, and patient-provider power dynamics. Collectively, the narratives illuminated fundamental ideological tensions between in- and out-of-hospital providers arising from divergent assignment of value to described risks and benefits. The majority of physicians focused on U.S.-specific data demonstrating increased neonatal morbidity and mortality associated with delayed access to hospital-based interventions, thereby justifying hospital birth as the standard of care. By contrast, midwives emphasized data demonstrating fewer interventions and superior maternal and neonatal outcomes in high-income European countries, where out-of-hospital birth is more common for low-risk birthing people. A key gap in counseling was revealed, as no interviewees offered anticipatory counseling regarding birth setting options. Providers directly and indirectly illustrated the propensity for asymmetric power relations between birth providers and pregnant people, especially in hospital settings. The narratives highlight the common goal of optimizing maternal and neonatal outcomes despite tensions arising from divergent prioritization of specific maternal and neonatal risks. Our findings suggest opportunities to foster collaboration and optimize outcomes via mutual respect and improved integration of care.

Learning-augmented maximum flow

We propose a framework for speeding up maximum flow computation by using predictions. A prediction is a flow, i.e., an assignment of non-negative flow values to edges, which satisfies the flow conservation property, but does not necessarily respect the edge capacities of the actual instance (since these were unknown at the time of learning). We present an algorithm that, given an m-edge flow network and a predicted flow, computes a maximum flow in O(mη) time, where η is the ℓ1 error of the prediction, i.e., the sum over the edges of the absolute difference between the predicted and optimal flow values. Moreover, we prove that, given an oracle access to a distribution over flow networks, it is possible to efficiently PAC-learn a prediction minimizing the expected ℓ1 error over that distribution. Our results fit into the recent line of research on learning-augmented algorithms, which aims to improve over worst-case bounds of classical algorithms by using predictions, e.g., machine-learned from previous similar instances. So far, the main focus in this area was on improving competitive ratios for online problems. Following Dinitz et al. (2021) [6], our results are among the firsts to improve the running time of an offline problem.

An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) for the quantification of phenobarbital in human serum and plasma.

Phenobarbital serves as an antiepileptic drug (AED) and finds application in the treatment of epilepsy either as monotherapy or adjunctive therapy. This drug exhibits various pharmacodynamic properties that account for its beneficial effects as well as potential side effects. Accurate measurement of its concentration is critical for optimizing AED therapy through appropriate dose adjustments. Therefore, our objective was to develop and validate a new reference measurement procedure (RMP) for the accurate quantification of phenobarbital levels in human serum and plasma. A sample preparation protocol based on protein precipitation followed by a high dilution step was established in combination with a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using a C8 column to separate target analytes from known and unknown interferences. Assay validation and determination of measurement uncertainty were performed based on current guidelines. Selectivity and Specificity were assessed using spiked serum and plasma samples; to investigate possible matrix effects (MEs) a post-column infusion experiment and a comparison of standard line slopes was performed. Precision and accuracy were determined within a multiday precision experiment. The RMP was shown to be highly selective and specific, with no evidence of matrix interferences. It can be used to quantify phenobarbital in the range of 1.92 to 72.0 μg/mL. Intermediate precision was less than 3.2 %, and repeatability coefficient of variation (CV) ranged from 1.3 to 2.0 % across all concentration levels. The relative mean bias ranged from -3.0 to -0.7 % for native serum levels, and from -2.8 to 0.8 % for Li-heparin plasma levels. The measurement uncertainties (k=1) for single measurements and target value assignment were 1.9 to 3.3 % and 0.9 to 1.6 %, respectively. A novel LC-MS/MS-based candidate RMP for the quantification of phenobarbital in human serum and plasma is presented which can be used for the standardization of routine assays and the evaluation of clinically relevant samples.

Development of an insulin-like growth factor-1 certified reference material by SI-traceable isotope-dilution mass spectrometry

In this study, an insulin-like growth factor-1 (IGF-1) certified reference material (CRM) was developed by the National Institute of Metrology (NIM), and two different principles for evaluating the IGF-1 CRM were established. After optimisation of the acid hydrolysis conditions (110 °C, 36 h), quantitative determination of peptide purity, and chromatographic separation and mass spectrometric detection, amino acid analysis-based high-performance liquid chromatography combined with isotope-dilution tandem mass spectrometry (AAA-HPLC-IDMS/MS) and peptide analysis-based HPLC-IDMS/MS (Peptide-HPLC-IDMS/MS) were used for certified value assignment; the results obtained were 136.28 and 135.01 μg/g, respectively, which were in good agreement. These results were subjected to the normal distribution test, outlier test, and method consistency test. The homogeneity and stability of the reference materials were also examined, and the uncertainty introduced in the experimental process was calculated. The final certified value was (136 ± 15) μg g−1 (k = 2). The CRM was found to be stable for at least six months when stored at −70 °C and for 7 d when stored at higher temperatures (−20 °C, 4 °C, 25 °C, or 40 °C). The CRM is expected to be used as a primary calibrator for quality control in biopharmaceutical production and clinical diagnostics.

Accuracy of quantitative viral secondary standards: a re-examination.

Interlaboratory agreement of viral load assays depends on accuracy and uniformity of quantitative calibrators. Previous work, published in JCM several years ago, demonstrated poor agreement of secondary cytomegalovirus (CMV) standards with nominal values. This study re-evaluated this issue among commercially produced secondary standards for both BK virus (BKV) and CMV, using digital polymerase chain reaction (dPCR) to compare the materials from three different manufacturers. Overall, standards showed an improved agreement compared to prior work, against nominal values, indicating a substantial improvement in the production of accurate secondary viral standards, while supporting the need for further work in this area and for the broad adaption of international unit (IU) as a reporting standard for quantitative viral load results.

Addressing the Binning Problem in Calibration Assessment through Scalar Annotations

Abstract Computational linguistics models commonly target the prediction of discrete—categorical—labels. When assessing how well-calibrated these model predictions are, popular evaluation schemes require practitioners to manually determine a binning scheme: grouping labels into bins to approximate true label posterior. The problem is that these metrics are sensitive to binning decisions. We consider two solutions to the binning problem that apply at the stage of data annotation: collecting either distributed (redundant) labels or direct scalar value assignment. In this paper, we show that although both approaches address the binning problem by evaluating instance-level calibration, direct scalar assignment is significantly more cost-effective. We provide theoretical analysis and empirical evidence to support our proposal for dataset creators to adopt scalar annotation protocols to enable a higher-quality assessment of model calibration.

Evolution and impact of Standard Reference Materials (SRMs) for determining vitamin D metabolites.

The National Institute of Standards and Technology (NIST), in collaboration with the National Institutes of Health, Office of Dietary Supplements (NIH ODS), introduced the first Standard Reference Material® (SRM) for determining vitamin D metabolites in 2009 motivated by significant concerns about the comparability and accuracy of different assays to assess vitamin D status. After 14years, a suite of five serum matrix SRMs and three calibration solution SRMs are available. Values were also assigned for vitamin D metabolites in five additional SRMs intended primarily to support measurements of other clinical diagnostic markers. Both the SRMs and the certification approach have evolved from significant exogenous serum content to primarily endogenous content and from value assignment by combining the results of multiple analytical methods to the use of measurements exclusively from reference measurement procedures (RMPs). The impact of the availability of these SRMs can be assessed by both the distribution information (sales) and by reports in the scientific literature describing their use for method validation, quality control, and research. In this review, we describe the development of these SRMs, the evolution in design and value assignment, the expansion of information reported, and SRM use in validating analytical methods and providing quality assurance within the vitamin D measurement community.

Subsequent bilateral key comparison study - organic solvent calibration solution - gravimetric preparation and value assignment of aflatoxin B1 (AfB1) in acetonitrile (ACN)

Main textThe original CCQM-K154.b comparison was coordinated by the Bureau International des Poids et Mesures (BIPM) and the Chinese National Institute of Metrology (NIM) on behalf of the Organic Analysis Working Group (OAWG) of the Comité Consultatif pour la Quantité de Matière (CCQM) for National Measurement Institutes (NMIs) and Designated Institutes (DIs) which provide measurement services in organic analysis under the 'Comité International des Poids et Mesures' Mutual Recognition Arrangement (CIPM MRA) and/or have participated in the BIPM's Mycotoxin Metrology Capacity Building and Knowledge Transfer (MMCBKT) project as part of its "Metrology for Safe Food and Feed in Developing Economies" Capacity Building Programme.Gravimetrically-prepared solutions having an assigned mass fraction of specified organic analytes are routinely used to calibrate measurement processes for the quantification of the same analytes in matrix samples. Appropriate assignments of the property value and associated uncertainty of calibration solutions thus underpin the traceability of routine analysis and are critical for accurate measurements. Evidence of successful participation in relevant international comparisons is needed to document calibration and measurement capability claims (CMCs) made by national metrology institutes and designated institutes. In total, eleven NMIs/DIs participated in the Track C, Model II, Key Comparison CCQM-K154.b [Gravimetric preparation and value assignment of aflatoxin B1 (AfB1) in acetonitrile (ACN)] for emerging areas of global interest and innovation. Participants were requested to gravimetrically prepare calibration solutions and value assign the mass fractions, expressed in mg/kg, of aflatoxin B1 (AfB1) in the acetonitrile (ACN) solution. Study samples, with assigned values and associated uncertainties were prepared by the comparison participants and sent to the coordinating laboratory for comparison. The Key Comparison Reference Values (KCRVs), calculated form values measured by the coordinating laboratory based on calibrations obtained from independent gravimetrically prepared calibrant solutions, agreed with participants reported values, within their stated uncertainties.AfB1 was selected to be representative of polar aflatoxins. Aflatoxins are a class of mycotoxins generally produced by fungi of the genus Aspergillus. It was anticipated to provide a challenge representative for the gravimetrical preparation and value assignment of calibration solutions in the mass fraction range of 2 mg/kg to 50 mg/kg of mycotoxins with broadly similar structural characteristics.In the original study CCQM-K154.b, nine participants of the MMCBKT programme were provided with a stock solution having a known AfB1 mass fraction and expanded uncertainty to use to gravimetrically prepare and value assign a calibration solution. Three NMIs/DIs also participated using their own calibration solutions. The use of in-house solutions required anadditional capacity to undertake a fit-for-purpose purity assessment. NIM was the only NMI participating using both the MMCBKT based and their own in-house assigned solutions in order to connect the two different groups.It was decided to propose separate KCRVs for each of the two ampoules provided by the participating NMIs/DIs based on the AfB1 mass fraction. This allowed participants to demonstrate the efficacy of their implementation of the approaches used to gravimetrically prepare calibrations solutions and to assess the AfB1 mass fraction.The majority of the AfB1 mass fraction KCRVs (wKCRV) for CCQM-K154.b spanned a mass fraction range of 2.02 mg/kg to 31.57 mg/kg. The relative expanded uncertainties U(wKCRV) ranged from 0.69 % to 2.93 %. Inspection of the degree of equivalence plots for the AfB1 mass fraction assignments in CCQM-K154.b indicated that there was an excellent agreement of results. Solely, the AfB1 mass fraction assignments of the INRAP (Institut National de Recherche et d'Analyse Physico-Chimique, Tunisia) did not agree with the KCRVs. It was found that the samples were altered as a result of an acid contamination.The INRAP has produced a new batch of AfB1 calibration solution using the AfB1 stock solution originally provided to MMCBKT participants to be able to demonstrate the efficacy of their implementation of the approaches used to gravimetrically prepare calibrations solutions and to assess the AfB1 mass fraction. The BIPM organized the present subsequent bilateral comparison CCQM-K154.b.1 to assess the new batch of AfB1 calibration solution of the INRAP. Inspection of the degree of equivalence plots for the AfB1 mass fraction assignments indicated that there is an excellent agreement of the INRAP results for CCQM-K154.b.1.To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database https://www.bipm.org/kcdb/.The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

A candidate reference measurement procedure for the quantification of α-synuclein in cerebrospinal fluid using an SI traceable primary calibrator and multiple reaction monitoring.

α-synuclein aggregation is an important hallmark of neurodegenerative diseases such as Parkinson's disease (PD) and Lewy body dementia. α-synuclein has been increasingly used as a diagnostic biomarker in PD and other synucleinopathies. Current clinical assays rely on antibody-based immunoassays to detect α-synuclein, which possess high sensitivity, afford high throughput and require small sample volumes. The utility of these assays, however, may be compounded by the specificity, selectivity and batch-to-batch heterogeneity of the antibody used, which can lead to deviations in the total amount of the protein measured when comparing results among different laboratories. Similarly, current mass spectrometry-based quantification methods for α-synuclein lack well-defined, value assigned calibrators to ensure comparability of measurements. Therefore, there is still an unmet need for the standardisation of clinical measurements for α-synuclein that can be achieved by the development of reference measurement procedures (RMPs) utilising calibrators traceable to the SI (International System of Units). Here, we report a candidate RMP for α-synuclein, using an SI traceable primary calibrator and an isotope dilution mass spectrometry (IDMS) approach to address this need. The gravimetrically prepared primary calibrator was traceably quantified utilising a combination of amino acid analysis (AAA) and quantitative nuclear magnetic resonance (qNMR) for value assignment. An optimised targeted sample clean-up procedure involving a non-denaturing Lys-C digestion and solid-phase extraction strategy was devised, followed by the development of a targeted multiple reaction monitoring (MRM) method for the quantification of α-synuclein in cerebrospinal fluid (CSF). This candidate RMP was then deployed for the sensitive detection and accurate quantification of multiple proteotypic α-synuclein peptides in patient derived CSF samples. The LC-MS based results were subsequently compared to immunoassay data to assess the overall performance of our approach. The development and adoption of this candidate RMP, along with the availability of the SI traceable primary calibrator will allow for reliable quantifications of α-synuclein in CSF by an LC-MS based assay. The RMP will potentially contribute towards the standardisation of this important biomarker and may lead to future interlaboratory comparisons.

Online and offline mixed teaching quality assessment method for physical education class based on value assignment method

Abstract The blended teaching mode combines the advantages of online and offline teaching, which can improve the effect of university physical education teaching. The article takes the acquisition path of students’ multidimensional learning behavior data as the entry point, introduces the data preprocessing method after acquiring online learning behavior, and then establishes the online-offline blended teaching quality evaluation index system for physical education classes based on the CIPP model. The subjective and objective weights of the evaluation indexes are solved by using the AHP method and the improved pull-apart grade method, and the comprehensive, integrated assignment method is introduced to weigh the subjective and objective weights in order to obtain the comprehensive weights. Based on the weights of the indicators obtained by AHP-ISD, a teaching quality assessment model for physical education courses was established by combining the SVM model, and the SMO algorithm was selected to optimize the training of the model. To assess the application effectiveness of the model, a comprehensive assessment of its teaching quality was carried out, and the teaching effect of the blended teaching mode was also explored. The weight of the learning outcome evaluation index is 0.438 at most, the accuracy of the SMO algorithm training model is up to 99.99%, and the range of error scores between the model evaluation value and the actual value is between [0.01,0.03] points. The teaching quality assessment model based on the assignment method can obtain more accurate teaching quality assessment results for physical education courses and provide a new direction for optimizing the hybrid teaching assessment method of physical education courses.

Continuous Value Assignment: A Doubly Robust Data Augmentation for Off-Policy Learning.

Deep reinforcement learning (RL) has witnessed remarkable success in a wide range of control tasks. To overcome RL's notorious sample inefficiency, prior studies have explored data augmentation techniques leveraging collected transition data. However, these methods face challenges in synthesizing transitions adhering to the authentic environment dynamics, especially when the transition is high-dimensional and includes many redundant/irrelevant features to the task. In this article, we introduce continuous value assignment (CVA), an innovative optimization-level data augmentation approach that directly synthesizes novel training data in the state-action value space, effectively bypassing the need for explicit transition modeling. The key intuition of our method is that the transition plays an intermediate role in calculating the state-action value during optimization, and therefore directly augmenting the state-action value is more causally related to the optimization process. Specifically, our CVA combines parameterized value prediction and nonparametric value interpolation from neighboring states, resulting in doubly robust target values w.r.t. novel states and actions. Extensive experiments demonstrate CVA's substantial improvements in sample efficiency across complex continuous control tasks, surpassing several advanced baselines.

Assignment of the biological value of solid breast masses based on quantitative evaluations of spectral CT examinations using electron density mapping, Zeffective mapping and iodine mapping

ObjectiveWe aimed to asses, in a clinical setting, whether the newly available quantitative evaluation of electron density (ED) in spectral CT examinations of the breast provide information on the biological identity of solid breast masses and whether ED maps yield added value to the diagnostic information of iodine maps and Zeff maps calculated from the same CT image datasets. MethodsAll patients at the University Breast Cancer Center who underwent a clinically indicated Dual Layer Computed Tomography (DLCT) examination for staging of invasive breast cancer from 2018 to 2020 were prospectively included. Iodine concentration maps, Zeff maps and ED maps were automatically reconstructed from the DLCT datasets. Region of interest (ROI) based evaluations in the breast target lesions and in the aorta were performed semi-automatically in identical anatomical positions using dedicated evaluation software. Case-by-case evaluations were carried independently by 2 of 4 radiologists for each examination, respectively. Statistical analysis derived from the ROIs was done by calculating ROC/AUC curves and Youden indices. ResultsThe evaluations comprised 166 DLCT examinations. In the ED maps the measurements in the breast target lesions yielded Youden cutpoints of 104.0% (reader 1) and 103.8% (reader 2) resulting in AUCs of 0.63 and 0.67 at the empirical cutpoints. The variables “Zeff” and “iodine content” derived from the target lesions showed superior diagnostical results, with a Youden cutpoint of 8.0 mg/ml in the iodine maps and cutpoints of 1.1/1.2 in the Zeff maps the AUCs ranging from 0.84 to 0.85 (p = 0.023 to <0.000). The computational combination of Zeff and ED measurements in the target lesions yielded a slight AUC increase (readers 1: 0.85–0.87; readers 2: 0.84–0.94). The ratios of the measured values in the target lesions normalized to the values measured in the aorta showed comparable results. The AUCs of ED derived from the cutpoints showed inferior results to those derived from the Zeff maps and iodine maps (ED: 0.64 and 0.66 for reader 1 and 2; Zeff: 0.86 for both readers; iodine content: 0.89 and 0.86 for reader 1 and 2, respectively). The computational combination of the ED results and the Zeff measurements did not lead to a clinically relevant diagnostic gain with AUCs ranging from 0.86 to 0.88. ConclusionsQuantitative assessments of Zeff, iodine content and ED all targeting the physical and chemical aspects of iodine uptake in solid breast masses confirmed diagnostically robust cutpoints for the differentiation of benign and malignant findings (Zeff < 7.7, iodine content of <0.8 mg/ml). The evaluations of the ED did not indicate any added diagnostic value beyond the quantitative assessments of Zeff and iodine content. Further research is warranted to develop suitable clinical indications for the use of ED maps.

An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure for the quantification of zonisamide in human serum and plasma.

To describe and validate an isotope dilution-liquid chromatograph-tandem mass spectrometry (ID-LC-MS/MS) based reference measurement procedure (RMP) for zonisamide to accurately measure serum and plasma concentrations. Quantitative nuclear magnetic resonance (qNMR) spectroscopy was employed to determine the absolute content of the reference material used in order to establish traceability to SI units. Separation of zonisamide from known or unknown interferences was performed on a C8 column. For sample preparation a protocol based on protein precipitation in combination with a high dilution step was established. Assay validation and determination of measurement uncertainty were performed based on guidelines from the Clinical and Laboratory Standards Institute, the International Conference on Harmonization, and the Guide to the expression of uncertainty in measurement. The RMP was proven to be highly selective and specific with no evidence of a matrix effect, allowing for quantification of zonisamide within the range of 1.50-60.0 μg/mL. Intermediate precision was <1.4 % and repeatability CV ranged from 0.7 to 1.2 % over all concentration levels. The relative mean bias ranged from 0.0 to 0.8 % for native serum levels and from 0.2 to 2.0 % for Li-heparin plasma levels. The measurement uncertainties for single measurements and target value assignment ranged from 1.1 to 1.4 % and 0.8-1.0 %, respectively. We present a novel LC-MS/MS-based candidate RMP for zonisamide in human serum and plasma which provides a traceable and reliable platform for the standardization of routine assays and evaluation of clinically relevant samples.