47 research outputs found

    Sigma metrics for assessing the analytical quality of clinical chemistry assays: a comparison of two approaches

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    Introduction: Two approaches were compared for the calculation of coefficient of variation (CV) and bias, and their effect on sigma calculation, when different allowable total error (TEa) values were used to determine the optimal method for Six Sigma quality management in the clinical laboratory. Materials and methods: Sigma metrics for routine clinical chemistry tests using three systems (Beckman AU5800, Roche C8000, Siemens Dimension) were determined in June 2017 in the laboratory of Peking Union Medical College Hospital. Imprecision (CV%) and bias (bias%) were calculated for ten routine clinical chemistry tests using a proficiency testing (PT)- or an internal quality control (IQC)-based approach. Allowable total error from the Clinical Laboratory Improvement Amendments of 1988 and the Chinese Ministry of Health Clinical Laboratory Center Industry Standard (WS/ T403-2012) were used with the formula: Sigma = (TEa − bias) / CV to calculate the Sigma metrics (σCLIA, σWS/T) for each assay for comparative analysis. Results: For the PT-based approach, eight assays on the Beckman AU5800 system, seven assays on the Roche C8000 system and six assays on the Siemens Dimension system showed σCLIA > 3. For the IQC-based approach, ten, nine and seven assays, respectively, showed σCLIA > 3. Some differences in σ were therefore observed between the two calculation methods and the different TEa values. Conclusions: Both methods of calculating σ can be used for Six Sigma quality management. In practice, laboratories should evaluate Sigma multiple times when optimizing a quality control schedule

    EVNet: An Explainable Deep Network for Dimension Reduction

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    Dimension reduction (DR) is commonly utilized to capture the intrinsic structure and transform high-dimensional data into low-dimensional space while retaining meaningful properties of the original data. It is used in various applications, such as image recognition, single-cell sequencing analysis, and biomarker discovery. However, contemporary parametric-free and parametric DR techniques suffer from several significant shortcomings, such as the inability to preserve global and local features and the pool generalization performance. On the other hand, regarding explainability, it is crucial to comprehend the embedding process, especially the contribution of each part to the embedding process, while understanding how each feature affects the embedding results that identify critical components and help diagnose the embedding process. To address these problems, we have developed a deep neural network method called EVNet, which provides not only excellent performance in structural maintainability but also explainability to the DR therein. EVNet starts with data augmentation and a manifold-based loss function to improve embedding performance. The explanation is based on saliency maps and aims to examine the trained EVNet parameters and contributions of components during the embedding process. The proposed techniques are integrated with a visual interface to help the user to adjust EVNet to achieve better DR performance and explainability. The interactive visual interface makes it easier to illustrate the data features, compare different DR techniques, and investigate DR. An in-depth experimental comparison shows that EVNet consistently outperforms the state-of-the-art methods in both performance measures and explainability.Comment: 18 pages, 15 figures, accepted by TVC

    TP53-related signature for predicting prognosis and tumor microenvironment characteristics in bladder cancer: A multi-omics study

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    Background: The tumor suppressor gene TP53 is frequently mutated or inactivated in bladder cancer (BLCA), which is implicated in the pathogenesis of tumor. However, the cellular mechanisms of TP53 mutations are complicated, yet well-defined, but their clinical prognostic value in the management of BLCA remains controversial. This study aimed to explore the role of TP53 mutation in regulating the tumor microenvironment (TME), elucidate the effects of TP53 activity on BLCA prognosis and immunotherapy response.Methods: A TP53-related signature based on TP53-induced and TP53-repressed genes was used to construct a TP53 activity-related score and classifier. The abundance of different immune cell types was determined using CIBERSORT to estimate immune cell infiltration. Moreover, the heterogeneity of the tumor immune microenvironment between the high and low TP53 score groups was further evaluated using single-cell mass cytometry (CyTOF) and imaging mass cytometry (IMC). Moreover, pathway enrichment analysis was performed to explore the differential biological functions between tumor epithelial cells with high and low TP53 activity scores. Finally, the receptor–ligand interactions between immune cells and tumor epithelial cells harboring distinct TP53 activity were analyzed by single-cell RNA-sequencing.Results: The TP53 activity-related gene signature differentiated well between TP53 functional retention and inactivation in BLCA. BLCA patients with low TP53 scores had worse survival prognosis, more TP53 mutations, higher grade, and stronger lymph node metastasis than those with high TP53 scores. Additionally, CyTOF and IMC analyses revealed that BLCA patients with low TP53 scores exhibited a potent immunosuppressive TME. Consistently, single-cell sequencing results showed that tumor epithelial cells with low TP53 scores were significantly associated with high cell proliferation and stemness abilities and strongly interacted with immunosuppressive receptor–ligand pairs.Conclusion: BLCA patients with low TP53 scores have a worse prognosis and a more immunosuppressive TME. This TP53 activity-related signature can serve as a potential prognostic signature for predicting the immune response, which may facilitate the development of new strategies for immunotherapy in BLCA

    A global multicenter study on reference values: 2. Exploration of sources of variation across the countries.

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    This global multicenter study on reference values (RVs) allowed us to explore biological sources of variation (SVs) of RVs across the world.As described in the first part of this paper, RVs of 50 major analytes from 13,396 healthy individuals living in 12 countries were obtained. Analyzed in this study were 23 clinical chemistry analytes and 8 analytes measured by immunoturbidimetry. Multiple regression analysis was performed for each gender, country by country, analyte by analyte, by setting four major SVs (age, BMI, and levels of drinking and smoking) as a fixed set of explanatory variables. For analytes with skewed distributions, log-transformation was applied. The association of each source of variation with RVs was expressed as partial correlation coefficient (rp).Obvious gender and age-related changes in the RVs were observed in many analytes, almost consistently between countries. Compilation of age-related change profiles of RVs after adjusting for between-country differences revealed peculiar patterns specific to each analyte. Judged fromrp, BMI related changes were observed in many nutritional and inflammatory markers in almost all countries. However, the slope of linear BMI vs. RV relationship differed greatly among countries for some analytes. Alcohol and smoking-related changes were observed less conspicuously in a limited number of analytes.Features of sex, age, alcohol, and smoking-related changes in RVs of major analytes were almost comparable worldwide. The finding of differences in BMI-related changes among countries in some analytes is quite relevant to understanding ethnic differences in susceptibility to nutritionally related diseases

    Robust estimation of bacterial cell count from optical density

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    Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

    An approach to grading coalbed methane resources in China for the purpose of implementing a differential production subsidy

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    Abstract The heterogeneity of coalbed methane (CBM) resources was not taken into account when the current indiscriminate subsidy policy was developed. In it, limited subsidy funds are given first to high-quality resources and even to subsidize profitable projects. Thus, the policy has had less than the intended effect in improving CBM production. To implement a new type of differential subsidy, it is necessary to grade the CBM resources, as will be discussed in this paper. After the factors affecting the resources value are systemically examined, sorted and merged, the relationship between the key factors and economic value is analyzed by an engineering economics method, and the production profile type, peak production (or stable production) and buried depth are used as grading factors. The production profile type is used to categorize, and peak production and buried depth are used to grade resources within the same category. The grading method is as follows: use subsidy levels at the economic critical point (NPV = 0) to identify the grades of resources, and determine the combination of peak production and buried depth for different resources grades base on indifference curves drawn according to the relationship between the economic value and peak production and buried depth

    A CBM development well type optimization method based on the long-run marginal cost

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    Reasonable optimization of development well type is the prerequisite to realize the economic and effective development of coalbed methane (CBM). However, the existing CBM development well type optimization methods are disadvantageous in many aspects. CBM is a kind of typical unconventional natural gas resource, and its study focuses on single-well evaluation. In this paper, the assessment method and the evaluation index (EI) for CBM development well type optimization based on the long-run marginal cost (LRMC) were constructed on the basis of CBM characteristics from the perspective of economic feasibility. Then, the corresponding decision making criteria were established. Finally, this newly developed method was applied to the well-type optimization of different development blocks in two important CBM development basins in China. And the following research and application results were obtained. First, under the current technical and economic conditions, both directional well and horizontal well are economically feasible to the development of Block A in the Qinshui Basin and Block B in eastern margin of the Ordos Basin, and the economically optimal well type is a horizontal well in Block A and a directional well in Block B. Second, compared with single-well steady daily gas production and single-well investment, the evaluation results on the schemes of different well types present critical value, above which the economic benefit of different schemes are equivalent. Third, EI of different well types is affected by many factors, e.g. geological characteristic of gas reservoirs, single-well production profile, CBM selling price, investment and cost. Therefore, it is necessary to carry out dynamic analysis and update in time based on the change of various influential factors so as to ensure the rationality of decision-making. In conclusion, this newly developed method is intrinsically consistent with traditional evaluation methods, and it is more advantageous with strong operability, intuitive evaluation results and quick and accurate optimization of CBM development well types. Keywords: Coalbed methane (CBM), Long-run marginal cost (LRMC), Development well, Well-type optimization, Directional wells, Horizontal wells, Surface development, Decision making criteria, Critical poin

    Low appendicular skeletal muscle index increases the risk of carotid artery plaque in postmenopausal women with and without hypertension/hyperglycemia: a retrospective study

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    Abstract Background This study aimed to evaluate whether the low appendicular skeletal muscle index (ASMI) is closely associated with the risk of carotid artery plaque (CAP) in postmenopausal women with and without hypertension/hyperglycemia stratified by body mass index (BMI) categories. Methods A total of 2048 Chinese postmenopausal women aged 40–88 years were eventually enrolled in this retrospective study. Skeletal muscle mass was estimated by using segmental multifrequency bioelectrical impedance analysis. ASMI was defined as follows: appendicular skeletal muscle mass(kg)/[height(m)]2. CAP was assessed by B-mode ultrasound. We explored the association between ASMI quartiles or low skeletal muscle mass and the risk of CAP by using multivariate-adjusted logistic regression models. A potential nonlinear relationship was also tested using restricted cubic spline regression. Results CAP was observed in 289/1074 (26.9%) normal-weight and 319/974 (32.8%) overweight/obese postmenopausal women. Individuals with CAP had significantly lower ASMI values than those without (P  0.05). In comparison with the highest ASMI quartile, the lowest ASMI quartile was significantly associated with a high risk of CAP development in non-hypertensive individuals with normal weight (odds ratio [OR] = 2.43; 95% confidence interval [CI]: 1.44 ~ 4.12) or overweight/obesity (OR = 4.82, 95% CI: 2.79 ~ 8.33), hypertensive individuals with normal weight (OR = 5.90, 95% CI: 1.46 ~ 11.49) or overweight/obesity (OR = 7.63, 95% CI: 1.62 ~ 35.86), non-hyperglycemic individuals with normal weight (OR = 2.61, 95% CI: 1.54 ~ 4.43) or overweight/obesity (OR = 2.94, 95% CI: 1.84 ~ 4.70), and hyperglycemic individuals with normal weight (OR = 6.66, 95% CI: 1.08 ~ 41.10) or overweight/obesity (OR = 8.11, 95% CI: 2.69 ~ 24.49). Moreover, low skeletal muscle was independently associated with the risk of CAP in postmenopausal women, regardless of the BMI category. Conclusion ASMI was inversely associated with the risk of CAP development in postmenopausal women, especially in patients with high blood sugar and/or hypertension, indicating that skeletal muscle mass maintenance may contribute to prevention of CAP in postmenopausal women
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