Reference intervals for deconjugated urine metanephrines by Bhattacharya analysis.

BACKGROUND: Urine metanephrines are used to screen for phaeochromocytoma or paraganglioma (PPGL). Current reference intervals (RI) derived in healthy individuals are not age or sex-stratified, and lower than in hypertensive patients, leading to high false positive rates. This study aims to determine age and sex-stratified RI from a contingent screening population. METHODS: Patients with 24-h deconjugated urine metanephrines from 3/6/2010 to 27/8/2022 were included (2936 males, 5285 females), initially by liquid chromatography-electrochemical detection (LC-ECD) then liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bhattacharya analysis was used after log transformation to determine age and sex-stratified RI for metanephrine excretion, normetanephrine excretion, metanephrine/creatinine and normetanephrine/creatinine ratios. RESULTS: Normetanephrine excretion increases with age (RI: males: 18-<30 years: <3.4 µmol/24 h, 30-<40 years: <3.7 µmol/24 h, 40+ years: <5.3 µmol/24 h; females: 18-<30 years: <2.7 µmol/24 h, 30-<40 years: <3.1 µmol/24 h, 40+ years: <3.7 µmol/24 h), while metanephrine excretion was consistent across adulthood (RI: males: 18+ years: <1.8 µmol/24 h; females: 18+ years: <1.2 µmol/24 h). However, normetanephrine/creatinine and metanephrine/creatinine increase steadily with age after early adulthood, likely due to a decrease in muscle mass, with females having higher normetanephrine/creatinine and metanephrine/creatinine ratios. CONCLUSIONS: Age and sex-stratified RI were derived for metanephrine excretion, normetanephrine excretion, metanephrine/creatinine and normetanephrine/creatinine ratios. This is expected to reduce false positives while flagging most PPGL.

Source apportionment of polychlorinated dibenzo-p-dioxins and dibenzofurans in the sediments of an urban estuary.

Polychlorinated dibenzo-p-dioxins and dibenzofurans in the sediments of aquatic systems are a persistent global problem that poses serious health risks. Identifying the sources of dioxins in natural water systems and the extent of their contributions to observed sediment concentrations is important from a health advisory and mitigation perspective. This paper proposes novel distribution-based qualitative and quantitative methods as source apportionment techniques and alternatives to conventional source attribution methods. Using sampled data, air, runoff, industrial effluent, and industrial paper and pulp wastes were identified as four distinct dioxin contributors to concentrations found in the sediments of the test bed region: the Houston Ship Channel-San Jacinto River-Galveston Bay (HSC-SJR-GB) estuarine system that also includes 2 Superfund sites with dioxin contamination. Two qualitative methods, the Kullback-Leibler divergence (K-L divergence) and the Bhattacharya measure (BM), and a quantitative method, the L2 norm, were used to investigate the spatial and temporal sourcing patterns of dioxins in the system sediments. The results indicated a global contribution from air and runoff sources across the estuarine system and over time with more localized impacts of the Superfund sites and the industrial sources. The results using the developed methodologies were compared with the output from the more conventional positive matrix factorization (PMF) method. Statistically significant correlations were observed among source contributions from the proposed methods and the PMF method, with Spearman's ρ ranging between - 0.596 to - 0.963 and 0.652 to 0.719, demonstrating the utility of the sourcing approaches used in the study. Additionally, the proposed methods were found to be rigorous in terms of elucidating spatial and temporal changes in the sourcing of dioxin to the estuary, indicating their suitability for use for other contaminants and other estuarine systems.

Harmonization of indirect reference intervals calculation by the Bhattacharya method.

OBJECTIVES: The aim of this study was to harmonize the criteria for the Bhattacharya indirect method Microsoft Excel Spreadsheet for reference intervals calculation to reduce between-user variability and use these criteria to calculate and evaluate reference intervals for eight analytes in two different years. METHODS: Anonymized laboratory test results from outpatients were extracted from January 1st 2018 to December 31st 2019. To assure data quality, we examined the monthly results from an external quality control program. Reference intervals were determined by the Bhattacharya method with the St Vincent's hospital Spreadsheet firstly using original criteria and then using additional harmonized criteria defined in this study. Consensus reference intervals using the additional harmonized criteria were calculated as the mean of four users' lower and upper reference interval results. To further test the operation criteria and robustness of the obtained reference intervals, an external user validated the Spreadsheet procedure. RESULTS: The extracted test results for all selected laboratory tests fulfilled the quality criteria and were included in the present study. Differences between users in calculated reference intervals were frequent when using the Spreadsheet. Therefore, additional criteria for the Spreadsheet were proposed and applied by independent users, such as: to set central bin as the mean of all the data, bin size as small as possible, at least three consecutive bins and a high proportion of bins within the curve. CONCLUSIONS: The proposed criteria contributed to the harmonization of reference interval calculation between users of the Bhattacharya indirect method Spreadsheet.

Intervalos de referencia en pediatría. Una guía de sus formas de cálculo ordenadas según su fortaleza metodológica / Pediatrics reference intervals. A guide of its calculation forms ordered according to their methodological strength

Resumen El objetivo de esta comunicación es proponer una guía de las formas decálculo de los intervalos de referencia (IR) en la población pediátrica ordenándolassegún su fortaleza metodológica. En primer lugar, el proceso recomendadopara definir un IR es el enfoque "directo", en el que se evalúanmuestras de sujetos considerados sanos. En segundo lugar, la convocatoria"indirecta", en la que a los resultados de las muestras de una base dedatos, se aplican criterios de exclusión y procesamientos estadísticos (métodosde Hoffmann y de Bhattacharya). Estos IR presentan poca diferenciacon los obtenidos por datos directos y se pueden considerar equivalentes,con la ventaja de su facilidad y sus costos más bajos. En tercer lugar, estánlos IR obtenidos de la bibliografía. La validación de los datos informadospor el fabricante es la última opción a tener en cuenta. Se reafirma laimportancia de contar con IR adecuados por sus aspectos clínicos y por laseguridad de los pacientes.

Abstract The aim of this communication is to propose a guide on the ways of calculating reference intervals (RI) in the pediatric population, ordering them according to their methodological strength. First, the recommended process to define an RI is the "direct" approach, in which samples of subjects considered healthy are evaluated. Secondly, the "indirect" approach, in which exclusion criteria and statistical processing are applied to the results ofthe samples in a database (Hoffmann and Bhattacharya methods). These RIs show little differences with those obtained by direct data and they can be considered equivalent, with the advantage of their ease and with lower costs. Thirdly, there are RIs that can be obtained from the bibliography. The validation of the data reported by the manufacturer is the last option to consider. The importance of having adequate RIs for their clinical aspects and for the safety of patients is reaffirmed.

Resumo O objetivo desta comunicação é propor um guia sobre as formas de cálculo dos intervalos de referência (IR) na população pediátrica, ordenando os mesmos de acordo com sua fortaleza metodológica. Emprimeiro lugar, o processo recomendado para definir um IR é a abordagem "direta", na qual sãoavaliadas amostras de indivíduos considerados saudáveis. Em segundo lugar, a abordagem "indireta",na qual critérios de exclusão e processamento estatístico (métodos de Hoffmann e Bhattacharya)são aplicados aos resultados das amostras em um banco de dados. Esses IR apresentam poucadiferença com os obtidos por dados diretos, podendo ser considerados equivalentes, com a vantagem de apresentarem facilidade e menor custo. Em terceiro lugar, os IR obtidos da bibliografia. A validadedos dados informados pelo fabricante é a última opção a ser considerada. A importância de termos IRadequados pelos seus aspectos clínicos e pela segurança dos pacientes é reafirmada.

Comparison of reference intervals derived by direct and indirect methods based on compatible datasets obtained in Turkey.

BACKGROUND: Indirect derivation of reference intervals (RIs) from the laboratory information system (LIS) has been recently pursued. We aimed at evaluating the accuracy of indirectly predicted RIs compared to the RIs established directly from healthy subjects in the nationwide RI study in Turkey, targeting 25 major chemistry analytes. METHODS: LIS data were retrieved from the laboratory that performed measurements for the direct study. They were cleaned by limiting to outpatients with age 18-65 years, and by allowing only one record per year per patient. Evaluated were four indirect methods of univariate approach: Hoffmann, Bhattacharya, Arzideh, and Wosniok methods. Power transformation of the LIS dataset was performed either using the power (λ) reported by the IFCC global RI study (the first two methods) or using a λ predicted (the last two). RESULTS: Compared to the direct study dataset, the LIS dataset showed a variable degree of alterations in peak location and shape. Consequently, lower-side peak-shifts observed in sodium, albumin, etc. led to lowered RI limits, whereas higher-side peak-shift observed in triglyceride, low-density lipoprotein cholesterol, etc. led to raised RI limits. Overall, 72% (62-81) of the RI limits predicted by indirect methods showed significant biases from direct RIs. However, the biases observed in total cholesterol, lactic dehydrogenase, etc. were attributed to a higher-side age-bias in LIS dataset. After excluding them, the overall proportion of biased RIs was reduced to 47% (38-54). CONCLUSION: To reduce prediction biases that remained after age adjustment, it is necessary to apply more rigorous data-cleaning before applying indirect methods.

TSH continuous reference intervals by indirect methods: A Comparisons to Partitioned Reference Intervals.

OBJECTIVE: To establish continuous reference intervals for TSH by data mining, using quantile regression with restricted cubic splines model. DESIGN AND METHOD: TSH results (n=13,333) were collected for a four years period (between March 2015 and February 2020). After an exclusion step, TSH results (n=8838) were used to derive continuous reference intervals (i.e. 2.5th and 97.5th percentiles) spanning 18-90 years of age, using quantile regression with restricted cubic splines (RCS) model, then compared to age-partitioned reference intervals generated by Bhattacharya analysis. RESULTS: Despite similar reference intervals to the Bhattacharya analysis, continuous reference intervals appeared to give a more accurate and consistent estimation of the upper reference limits (i.e.97.5thpercentiles) with complex age-related variations in serum TSH concentrations. CONCLUSION: Our results suggest that quantile regression with RCS model appears to be a very useful tool available for clinical laboratories to establish local continuous TSH reference intervals.

Optimal Shrinkage of Eigenvalues in the Spiked Covariance Model.

We show that in a common high-dimensional covariance model, the choice of loss function has a profound effect on optimal estimation. In an asymptotic framework based on the Spiked Covariance model and use of orthogonally invariant estimators, we show that optimal estimation of the population covariance matrix boils down to design of an optimal shrinker η that acts elementwise on the sample eigenvalues. Indeed, to each loss function there corresponds a unique admissible eigenvalue shrinker η* dominating all other shrinkers. The shape of the optimal shrinker is determined by the choice of loss function and, crucially, by inconsistency of both eigenvalues and eigenvectors of the sample covariance matrix. Details of these phenomena and closed form formulas for the optimal eigenvalue shrinkers are worked out for a menagerie of 26 loss functions for covariance estimation found in the literature, including the Stein, Entropy, Divergence, Fréchet, Bhattacharya/Matusita, Frobenius Norm, Operator Norm, Nuclear Norm and Condition Number losses.

Parathyroid hormone: Data mining for age-related reference intervals in adults.

OBJECTIVE: Age-related changes in parathyroid hormone (PTH) have been previously documented in adults. However, because of the limitations of traditional approaches to establishing reference intervals, age-related reference intervals have not been defined. We sought to use a data mining approach to derive age-related PTH reference intervals. DESIGN AND PARTICIPANTS: Results from patients undergoing PTH testing over a 4-year period were extracted from the database of a private pathology laboratory in New South Wales, Australia. Patients were included in the study if they were 18 years or older and had simultaneous determination of PTH, serum calcium, estimated glomerular filtration rate and 25-hydroxyvitamin D (25-OHD). Patients with abnormalities of serum calcium or renal function were excluded. MEASUREMENTS: Bhattacharya analysis of log-transformed data was used to derive age-related PTH reference intervals across adulthood. RESULTS: Results were available for 33 652 subjects. Among patients with optimal 25-OHD status, older age was associated with higher PTH concentrations. Age-related reference intervals were derived and showed a 63% increase in the upper and lower reference limits between the youngest (18-29 years of age) and the oldest (80 years of age or older) age partitions. The appropriateness of using a single reference interval for patients of all ages was evaluated against objective criteria and was found to be unsatisfactory. CONCLUSIONS: Data mining was demonstrated to be a useful tool for establishing age-related PTH reference intervals. The technique demonstrated that increasing age is associated with higher PTH concentrations and that age-related reference intervals are important for accurate result interpretation.

A reference interval study for common biochemical analytes in Eastern Turkey: a comparison of a reference population with laboratory data mining.

INTRODUCTION: The aim of this study was to define the reference intervals (RIs) in a Turkish population living in Northeast Turkey (Erzurum) for 34 analytes using direct and indirect methods. In the present study, the regional RIs obtained were compared with other RI studies, primarily the nationwide study performed in Turkey. MATERIALS AND METHODS: For the direct method, 435 blood samples were collected from a healthy group of females (N = 218) and males (N = 217) aged between 18 and 65 years. The sera were analysed in Ataturk University hospital laboratory using Roche reagents and analysers for 34 analytes. The data from 1,366,948 records were used to calculate the indirect RIs using a modified Bhattacharya method. RESULTS: Significant gender-related differences were observed for 17 analytes. There were also some apparent differences between RIs derived from indirect and direct methods particularly in some analytes (e.g. gamma-glutamyltransferase, creatine kinase, LDL-cholesterol and iron). The RIs derived with the direct method for some, but not all, of the analytes were generally comparable with the RIs reported in the nationwide study and other previous studies in Turkey.There were large differences between RIs derived by the direct method and the expected values shown in the kit insert (e.g. aspartate aminotransferase, total-cholesterol, HDL-cholesterol, and vitamin B12). CONCLUSIONS: These data provide region-specific RIs for 34 analytes determined by the direct and indirect methods. The observed differences in RIs between previous studies could be related to nutritional status and environmental factors.

Rotinas de tratamento digital de imagem Landsat 5/TM para a identificação de queimadas em lavouras canavieiras / Handling Landsat 5/TM digital image to identify burned in sugarcane plantations

O presente estudo teve como objetivo avaliar o desempenho de classificadores supervisionados e não-supervisionados para detecção automática de queimadas em canaviais utilizando imagens de satélite Landsat-5/TM. A área de estudo localiza-se na porção noroeste do município de Maracaju, MS, Brasil. Diferentes métodos de classificação e tratamento de imagem foram testados para mapear a colheita de cana com queima prévia de palha. As imagens foram tratadas com reamostragem para 15m, correção radiométrica e NDVI. Nas classificações, foram utilizados os algoritmos Maxver-ICM, Bhattacharya e ISOSEG. Os diferentes pré-processamentos e classificadores aplicados foram submetidos à validação estatística por meio dos parâmetros Kappa e exatidão global. Os resultados indicaram um expressivo potencial de classificadores supervisionados na identificação de queimadas de cana. Concluiu-se que é possível obter exatidões qualificadas como excelente quando empregado o classificador de Máxima Verossimilhança-ICM.

The present study aimed to evaluate the performance of supervised classifiers and unsupervised for automatic detection of fires in cane fields using satellite images Landsat-5/TM. The study area is located in the northwest from the town of Maracaju, state of Mato Grosso do Sul, Brazil. Different methods of classification and image processing were tested to map the cane harvesting prior to straw burning. The images were treated with resampling to 15m, radiometric correction and NDVI. The classifications were used algorithms Maxver-ICM, Bhattacharya and ISOSEG. The different pre-processing and applied classifiers were submitted to statistical validation through the parameters Kappa and overall accuracy. The results indicated a significant potential for supervised classifiers in identifying burnt cane. It was concluded that it is possible to obtain accuracies classified as excellent when used the Maximum Likelihood Classifier-ICM.