A Practical Approach for Determination of Thermal Stress and Temperature-Dependent Material Properties in Multilayered Thin Films.

Multilayered thin films are essential to most microelectro-mechanical systems (MEMSs). The reliability and predictability of the behavior of such systems, especially when intended for usage at high temperatures or in harsh environments, demand the consideration of thermo-mechanical properties of the individual films of the multilayer arrangement during the design stage. This paper introduces a newly derived analytical model for the convenient indirect determination of the temperature-dependent Young's modulus and the thermally induced stress of individual layers within a multilayered thin film system, i.e., a multilayer-adapted Stoney equation. It is based on sample curvature measurement and requires data from only a single experiment. Experimental and numerical investigations of the new models are carried out using a five-layered sample of a RuAl metallization system developed for wireless high-temperature acoustic sensing. The results highlight the usability of the new model in practical MEMS analysis, enabling insights into complex layer stacks by overcoming current experimental limitations.

A preliminary study on the reference intervals of serum tumor marker in apparently healthy elderly population in southwestern China using real-world data.

BACKGROUND: The aim is to establish and verify reference intervals (RIs) for serum tumor markers for an apparently healthy elderly population in Southwestern China using an indirect method. METHODS: Data from 35,635 apparently healthy elderly individuals aged 60 years and above were obtained in West China Hospital from April 2020 to December 2021. We utilized the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate outliers. Subgroups are divided according to gender and age to examine the division of RIs. The Z-test was used to compare differences between groups, and 95% distribution RIs were calculated using a nonparametric method. RESULTS: In the study, we observed that the RIs for serum ferritin and Des-γ-carboxy prothrombin (DCP) were wider for men, ranging from 64.18 to 865.80 ng/ml and 14.00 to 33.00 mAU/ml, respectively, compared to women, whose ranges were 52.58 to 585.88 ng/ml and 13.00 to 29.00 mAU/ml. For other biomarkers, the overall RIs were established as follows: alpha-fetoprotein (AFP) 0-6.75 ng/ml, carcinoembryonic antigen (CEA) 0-4.85 ng/ml, carbohydrate antigen15-3 (CA15-3) for females 0-22.00 U/ml, carbohydrate antigen19-9 (CA19-9) 0-28.10 U/ml, carbohydrate antigen125 (CA125) 0-20.96 U/ml, cytokeratin 19 fragment (CYFRA21-1) 0-4.66 U/ml, neuron-specific enolase (NSE) 0-19.41 ng/ml, total and free prostate-specific antigens (tPSA and fPSA) for males 0-5.26 ng/ml and 0-1.09 ng/ml. The RIs for all these biomarkers have been validated through our rigorous processes. CONCLUSION: This study preliminarily established 95% RIs for an apparently healthy elderly population in Southwestern China. Using real-world data and an indirect method, simple and reliable RIs for an elderly population can be both established and verified, which are suitable for application in various clinical laboratories.

Supported Immunohistochemical Staining of Mucins.

Immunohistochemistry (IHC) staining is the most common method to detect the distribution and localization of biomarkers in different parts of a tissue. Antibodies for tandem repeat peptide of mucins are very popular, but antibodies for glycosylation or others are also used. IHC for mucin is the same protocol as IHC for others. This description includes IHC according to ABC method for processed formalin-fixed paraffin-embedded (FFPE) tissues. Protocol of in situ hybridization is also shown.

Should we depend on reference intervals from manufacturer package inserts? Comparing TSH and FT4 reference intervals from four manufacturers with results from modern indirect methods and the direct method.

OBJECTIVES: Correct interpretation of thyroid function tests relies on correct reference intervals (RIs) for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). ISO15189 mandates periodic verification of RIs, but laboratories struggle with cost-effective approaches. We investigated whether indirect methods (utilizing historical laboratory data) could replace the direct approach (utilizing healthy reference individuals) and compared results with manufacturer-provided RIs for TSH and FT4. METHODS: We collected historical data (2008-2022) from 13 Dutch laboratories to re-establish RIs by employing indirect methods, TMC (for TSH) and refineR (for FT4). Laboratories used common automated platforms (Roche, Abbott, Beckman or Siemens). Indirect RIs (IRIs) were determined per laboratory per year and clustered per manufacturer (>1.000.000 data points per manufacturer). Direct RIs (DRIs) were established in 125 healthy individuals per platform. RESULTS: TSH IRIs remained robust over the years for all manufacturers. FT4 IRIs proved robust for three manufacturers (Roche, Beckman and Siemens), but the IRI upper reference limit (URL) of Abbott showed a decrease of 2 pmol/L from 2015. Comparison of the IRIs and DRIs for TSH and FT4 showed close agreement using adequate age-stratification. Manufacturer-provided RIs, notably Abbott, Roche and Beckman exhibited inappropriate URLs (overall difference of 0.5-1.0 µIU/mL) for TSH. For FT4, the URLs provided by Roche, Abbott and Siemens were overestimated by 1.5-3.5 pmol/L. CONCLUSIONS: These results underscore the importance of RI verification as manufacturer-provided RIs are often incorrect and RIs may not be robust. Indirect methods offer cost-effective alternatives for laboratory-specific or platform-specific verification of RIs.

Description of 3 failed attempts to estimate the calcium equivalency of phytase for growth performance and tibia ash of broiler chickens when using graded dietary levels of limestone.

Three broiler experiments were conducted to estimate the Ca equivalency of a novel phytase using direct and indirect methods. All 3 experiments employed 4 concentrations of limestone to create 4 reference diets, deficient in nonphytate P, with increasing dietary Ca. Phytase was supplemented to the lowest Ca reference diet at 350, 700, 1,400, or 2,800 FYT/kg in experiment (Exp.) 1 and Exp. 2 and at 500, 1,000, 2,000, or 4,000 FYT/kg in Exp. 3. Broilers were fed from d 8 to 10 and 20 to 24, 19 to 21, or 7 to 10 and 7 to 21 posthatching in Exp. 1, 2, or 3, respectively. Diet did not affect growth performance or tibia ash in Exp. 1. Reducing the dietary Ca linearly (P < 0.05) increased body weight gain (BWG) and feed intake (FI) in Exp. 2 or Exp. 3. Feed conversion ratio (FCR) was decreased (linear or quadratic, P < 0.05) as dietary Ca was reduced in Exp. 2 or Exp. 3 (d 7-21). Tibia ash percent linearly (P < 0.05) decreased as dietary Ca decreased in Exp. 3 but only from d 7 to 21 and phytase increased (linear or quadratic, P < 0.05) FI and BWG, and decreased FCR. In Exp. 1 (d 8-10) and Exp. 2, apparent ileal digestibility (AID), total tract retention, and apparent digested and retained Ca or P increased (linear or quadratic, P < 0.05) as dietary Ca decreased. Phytase increased (linear or quadratic, P < 0.05) AID and apparent digested and retained Ca or P in Exp. 1 or Exp. 2. Due to the nature of the effect of dietary Ca on performance or tibia ash, it was not possible to use the indirect method to estimate the Ca equivalence of phytase in the current experiments. The total and digestible Ca equivalence of phytase could be estimated using the direct method. These experiments highlight challenges to consider when designing experiments to estimate the Ca equivalency for phytase in the future.

Establishment of a reference interval for total carbon dioxide using indirect methods in Chinese populations living in high-altitude areas: A retrospective real-world analysis.

BACKGROUND: Hypoxia leads to different concentrations of the bicarbonate buffer system in Tibetan people. Indirect methods were used to establish the reference interval (RI) for total carbon dioxide (tCO2) based on big data from the adult population of Tibet, a high-altitude area in Western China. METHODS: Anonymous tCO2 test data (n = 442,714) were collected from the People's Hospital of the Tibet Autonomous Region from January 2018, to December 2021. Multiple linear regression and variance component analyses were performed to assess the effects of sex, age, and race on tCO2 levels. Indirect methods, including Hoffmann, Bhattacharya, expectation maximization (EM), kosmic and refineR, were used to calculate the total RI and ethnicity-partitioned RI. RESULTS: A total of 230,821 real-world tCO2 test results were eligible. Sex, age, and race were significantly associated with the tCO2 levels. The total and ethnically-partitioned RIs estimated using the five indirect methods were comparable. The total RI of tCO2 was 14-24 mmol/L (calculated using Hoffmann and refineR) and 15-24 mmol/L (Bhattacharya, EM and kosmic). For Han nationality, the RIs were 14-25 mmol/L (calculated using Hoffmann and Bhattacharya), 16-23 mmol/L (EM), 15-24 mmol/L (kosmic), and 14.2-24.5 mmol/L (refineR). For the Tibetan population, the RIs were 14-24 mmol/L (calculated using Hoffmann and refineR), 15-24 mmol/L (Bhattacharya and kosmic), and 15-23 mmol/L (EM). The established RIs were significantly lower than those living at lower altitudes area (22-29 mmol/L) that was provided by the manufacturer. CONCLUSION: The tCO2 RI of the populations living on the Tibetan Plateau was significantly lower than those at the lower altitudes. The RIs established using indirect methods are suitable for clinical applications in Tibet.

Effects of Using Different Indirect Techniques on the Calculation of Reference Intervals: Observational Study.

BACKGROUND: Reference intervals (RIs) play an important role in clinical decision-making. However, due to the time, labor, and financial costs involved in establishing RIs using direct means, the use of indirect methods, based on big data previously obtained from clinical laboratories, is getting increasing attention. Different indirect techniques combined with different data transformation methods and outlier removal might cause differences in the calculation of RIs. However, there are few systematic evaluations of this. OBJECTIVE: This study used data derived from direct methods as reference standards and evaluated the accuracy of combinations of different data transformation, outlier removal, and indirect techniques in establishing complete blood count (CBC) RIs for large-scale data. METHODS: The CBC data of populations aged ≥18 years undergoing physical examination from January 2010 to December 2011 were retrieved from the First Affiliated Hospital of China Medical University in northern China. After exclusion of repeated individuals, we performed parametric, nonparametric, Hoffmann, Bhattacharya, and truncation points and Kolmogorov-Smirnov distance (kosmic) indirect methods, combined with log or BoxCox transformation, and Reed-Dixon, Tukey, and iterative mean (3SD) outlier removal methods in order to derive the RIs of 8 CBC parameters and compared the results with those directly and previously established. Furthermore, bias ratios (BRs) were calculated to assess which combination of indirect technique, data transformation pattern, and outlier removal method is preferrable. RESULTS: Raw data showed that the degrees of skewness of the white blood cell (WBC) count, platelet (PLT) count, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and mean corpuscular volume (MCV) were much more obvious than those of other CBC parameters. After log or BoxCox transformation combined with Tukey or iterative mean (3SD) processing, the distribution types of these data were close to Gaussian distribution. Tukey-based outlier removal yielded the maximum number of outliers. The lower-limit bias of WBC (male), PLT (male), hemoglobin (HGB; male), MCH (male/female), and MCV (female) was greater than that of the corresponding upper limit for more than half of 30 indirect methods. Computational indirect choices of CBC parameters for males and females were inconsistent. The RIs of MCHC established by the direct method for females were narrow. For this, the kosmic method was markedly superior, which contrasted with the RI calculation of CBC parameters with high |BR| qualification rates for males. Among the top 10 methodologies for the WBC count, PLT count, HGB, MCV, and MCHC with a high-BR qualification rate among males, the Bhattacharya, Hoffmann, and parametric methods were superior to the other 2 indirect methods. CONCLUSIONS: Compared to results derived by the direct method, outlier removal methods and indirect techniques markedly influence the final RIs, whereas data transformation has negligible effects, except for obviously skewed data. Specifically, the outlier removal efficiency of Tukey and iterative mean (3SD) methods is almost equivalent. Furthermore, the choice of indirect techniques depends more on the characteristics of the studied analyte itself. This study provides scientific evidence for clinical laboratories to use their previous data sets to establish RIs.

Comparative Analysis of Methods for Somatic Cell Counting in Cow's Milk and Relationship between Somatic Cell Count and Occurrence of Intramammary Bacteria.

The aim of this study was to compare three on-farm commercial methods for the indirect detection of subclinical mastitis in dairy cows: the California mastitis test (CMT), the Porta side somatic cell count milk test (Porta SCC), and the DeLaval cell counter (DCC), with the Fossomatic cell count (FSCC), and to evaluate the relationship between the determined somatic cell count SCC and the occurrence of intramammary pathogens in the milk of dairy cows. A total of 284 sensory unchanged mixed milk samples, collected during the milking on a dairy farm, were analyzed in this study for somatic cell counts by the mentioned on-farm tests. Quarter milk samples (n = 583) from all the selected cows were cultured. The agreement, sensitivity, and specificity of the three indirect commercial diagnostic tests (the CMT, the Porta SCC, and the DeLaval cell counter) were calculated, and the FSCC was used as the gold standard. The results were analyzed statistically using the Pearson correlation test and the paired t-test. The CMT matched with the FSCC in 83.1% of the samples, with the Porta SCC in 80.6%, and with the DCC in 80.3% of the samples. The sensitivity and specificity reached 81.0% and 92.9% for the CMT, 79.4% and 90.7% for the Porta SCC, and 75.8% and 97.5% for the DCC, respectively. The correlation between the FSCC and the Porta SCC was 0.86 (p < 0.0001), and between the FSCC and the DCC, it was 0.92 (p < 0.0001). The differences between them were insignificant. Bacteria were detected in 130 (22.3%) quarter milk samples. The most prevalent bacteria were Enterococcus spp. (36.2%), followed by E. coli (20%), coagulase-negative staphylococci (13.1%), A. viridans (9.2%), Streptococcus spp. (9.2%), Proteus spp. (6.2%), and S. intermedius (3.9%). Contagious isolates (S. aureus) were detected in 3 quarter milk samples (2.3%). The agreement between the individual tests and the microbiological culture was as follows: 69.2% for the CMT; 73.7% for the Porta SCC; 71.6% for the DCC; and 76.5% for the FSCC. Higher SCCs were detected in the milk samples contaminated with bacteria than in the healthy milk (p < 0.001). No significance was found between the presence of individual species of intramammary pathogens and the different levels of SCCs. Based on the results, bacteria are the predominant cause of subclinical mastitis. The increased SCC of some milk samples with no presence of bacteria meant that the increase could have been caused by numerous other agents (viruses, fungi, or algae) or factors for mastitis in the dairy industry.

Fat Hounsfield Unit Reference Interval Derived through an Indirect Method.

BACKGROUND: In vivo Hounsfield Unit (HU) values have traditionally been determined using direct CT image measurements. These measurements are dependent on the window/level used to examine the CT image and the individual conducting the fat tissue tracing. METHODS: Using an indirect method, a new reference interval (RI) is proposed. A total of 4000 samples of fat tissues were collected from routine abdominal CT examinations. A linear regression equation was then calculated using the linear part of the cumulative frequency plot of their average values. RESULTS: The regression function for total abdominal fat was determined to be y = 35.376*x - 123.48, and a 95% confidence RI of -123 to -89 was computed. A significant difference of 3.82 was observed between the average fat HU values of visceral and subcutaneous areas. CONCLUSIONS: Using statistical methods and the in vivo measurements of patient data, a series of RIs were determined for fat HU that is consistent with theoretical values.

Laboratorio de función tiroidea en pediatría. Ventajas y limitaciones de los métodos indirectos para la obtención de intervalos de referencia / Thyroid function laboratory in pediatrics. Advantages and limitations of indirect methods to obtain reference intervals

Obtener intervalos de referencia (IRs) confiables para pruebas de laboratorio en pediatría es particularmente complejo y costoso. Una alternativa a este problema es el uso de métodos indirectos, donde se usan grandes bases de datos preexistentes de pacientes. Nuestros objetivos fueron: calcular IR para TSH y hormonas tiroideas (Perfil tiroideo, PT) en población pediátrica que asiste al Hospital de Pediatría Juan P. Garrahan, por método indirecto y verificar la confiabilidad de los mismos para su aplicación. Se recolectaron datos de 19.842 pacientes entre enero de 2020 y diciembre de 2021. Se aplicaron filtros para eliminar los pacientes que pudieran tener afectado el PT. Los 4.861 pacientes incorporados al análisis fueron divididos en 3 grupos: G1: 0-12 meses (n: 551), G2:13 meses- 7 años (n: 1347) y G3: 8 -18 años (n: 2963). Los IR fueron calculados por 2 métodos: el de Hoffman adaptado y el de CLSI EP28A3, para cada grupo de edad. TSH, TT3 y T4L se analizaron con Architect i4000-Abbott y TT4 con Immulite 2000XPi-Siemens. Para la primera etapa de verificación se utilizaron 20 sueros de pacientes provenientes de análisis prequirúrgicos. Los outliers se detectaron aplicando el método de Tukey. Los datos fueron procesados según CLSI EP28A3c. Los IR obtenidos fueron similares a los previamente publicados obtenidos por método directo. Los resultados de la verificación fueron en su mayoría aceptados. Por lo tanto, los métodos indirectos son una buena alternativa de cálculo de IR en pediatría (AU)

Obtaining reliable reference ranges (RRs) for laboratory tests in pediatrics is particularly complex and costly. An alternative to this problem is to use of indirect methods, where large pre-existing patient databases are used. Our aims were to calculate RRs for TSH and thyroid hormones (thyroid profile, PT) in children seen at Hospital de Pediatría Juan P. Garrahan by indirect methods and to verify their reliability for their application. Data were collected from 19,842 patients seen between January 2020 and December 2021. Filters were applied to eliminate patients in whom the PT was potentially affected. The remaining 4,861 patients included in the analysis were divided into 3 groups: G1: 0-12 months (n: 551), G2: 13 months-7 years (n: 1347) and G3: 8-18 years (n: 2963). RRs were calculated by 2 methods: the adapted Hoffman method and the CLSI EP28A3 method, for each age group. TSH, TT3, and FT4 were analyzed with Architect i4000-Abbott and TT4 with Immulite 2000XPi-Siemens. For the first stage of verification, 20 patient sera from pre-surgical analysis were used. Outliers were detected by applying the Tukey method. The data were processed according to CLSI EP28A3c. The RRs obtained were similar to those previously published using the direct method. The verification results were mostly acceptable. Therefore, indirect methods are a good option for calculating RRs in children (AU)

Current status and challenges in establishing reference intervals based on real-world data.

Reference intervals (RIs) are the cornerstone for evaluation of test results in clinical practice and are invaluable in judging patient health and making clinical decisions. Establishing RIs based on clinical laboratory data is a branch of real-world data mining research. Compared to the traditional direct method, this indirect approach is highly practical, widely applicable, and low-cost. Improving the accuracy of RIs requires not only the collection of sufficient data and the use of correct statistical methods, but also proper stratification of heterogeneous subpopulations. This includes the establishment of age-specific RIs and taking into account other characteristics of reference individuals. Although there are many studies on establishing RIs by indirect methods, it is still very difficult for laboratories to select appropriate statistical methods due to the lack of formal guidelines. This review describes the application of real-world data and an approach for establishing indirect reference intervals (iRIs). We summarize the processes for establishing iRIs using real-world data and analyze the principle and applicable scope of the indirect method model in detail. Moreover, we compare different methods for constructing growth curves to establish age-specific RIs, in hopes of providing laboratories with a reference for establishing specific iRIs and giving new insight into clinical laboratory RI research. (201 words).

Investigation of Frequency-Domain Dimension Reduction for A2M-Based Bridge Damage Detection Using Accelerations of Moving Vehicles.

Recent decades have witnessed a rise in interest in bridge health monitoring utilizing the vibrations of passing vehicles. However, existing studies commonly rely on constant speeds or tuning vehicular parameters, making their methods challenging to be used in practical engineering applications. Additionally, recent studies on the data-driven approach usually need labeled data for damage scenarios. Still, getting these labels in engineering is difficult or even impractical because the bridge is typically in a healthy state. This paper proposes a novel, damaged-label-free, machine-learning-based, indirect bridge-health monitoring method named the assumption accuracy method (A2M). Initially, the raw frequency responses of the vehicle are employed to train a classifier, and K-folder cross-validation accuracy scores are then used to calculate a threshold to specify the bridge's health state. Compared to merely focusing on low-band frequency responses (0-50 Hz), utilizing full-band vehicle responses can significantly improve the accuracy, meaning that the bridge's dynamic information exists in the higher frequency ranges and can contribute to detecting bridge damage. However, raw frequency responses are generally in a high-dimensional space, and the number of features is much greater than that of samples. To represent the frequency responses via latent representations in a low-dimension space, appropriate dimension-reduction techniques are therefore, needed. It was found that principal component analysis (PCA) and Mel-frequency cepstral coefficients (MFCCs) are suitable for the aforementioned issue, and MFCCs are more damage-sensitive. When the bridge is in a healthy condition, the accuracy values obtained using MFCCs are primarily dispersed around 0.5, but following the occurrence of damage, they increased significantly to 0.89-1.0 in this study.

Reference intervals for thyroid disorders calculated by indirect method and comparison with reference change values.

Introduction: The aim of the study was to calculate reference intervals (RIs) for thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) and evaluate the clinical significance of these intervals by use of reference change values (RCV) of the analytes. Materials and methods: Laboratory patient data between August and December 2021 were evaluated for the study. A total of 188,912 patients with TSH, fT4, fT3, anti-thyroid peroxidase antibodies (Anti-TPO) and anti-thyroglobulin antibodies (Anti-Tg) results were evaluated. All measurements were performed on Cobas c801 (Roche Diagnostics, Penzberg, Germany) using electrochemiluminescence immunoassay technology. Estimated RIs were compared with manufacturer's by means of RCVs of analytes. Results: Thyroid stimulating hormone values didn't differ significantly by gender and age. The combined RIs for whole group (N = 28,437) was found as 0.41-4.37 mIU/mL. Free T4 values (11.6-20.1 pmol/L, N = 13,479 in male; 10.5-19.5 pmol/L, N = 17,634 female) and fT3 values (3.38-6.35 pmol/L, N = 2,516 in male; 3.39-5.99 pmol/L, N = 3,348 pmol/L in female) significantly differed by gender (P < 0.050). Both fT4 and fT3 values also showed significant differences in age subgroups comparisons. So, male and female RIs were represented separately for age subgroups. When compared with manufacturer's RIs, TSH whole group and fT4 subgroups RIs didn't exceed the analytes' RCVs, but this difference was greater for fT3. Conclusions: Reference interval estimation by use of indirect method out of laboratory data may be more accurate than manufacturer provided RIs. This population based RIs evaluated using RCV of analytes may provide useful information in clinical interpretation of laboratory results.

Within-subject biological variation estimates using an indirect data mining strategy. Spanish multicenter pilot study (BiVaBiDa).

OBJECTIVES: The estimates of biological variation (BV) have traditionally been determined using direct methods, which present limitations. In response to this issue, two papers have been published addressing these limitations by employing indirect methods. Here, we present a new procedure, based on indirect methods that analyses data collected within a multicenter pilot study. Using this method, we obtain CVI estimates and calculate confidence intervals (CI), using the EFLM-BVD CVI estimates as gold standard for comparison. METHODS: Data were collected over a 18-month period for 7 measurands, from 3 Spanish hospitals; inclusion criteria: patients 18-75 years with more than two determinations. For each measurand, four different strategies were carried out based on the coefficient of variation ratio (rCoeV) and based on the use of the bootstrap method (OS1, RS2 and RS3). RS2 and RS3 use symmetry reference change value (RCV) to clean database. RESULTS: RS2 and RS3 had the best correlation for the CVI estimates with respect to EFLM-BVD. RS2 used the symmetric RCV value without eliminating outliers, while RS3 combined RCV and outliers. When using the rCoeV and OS1 strategies, an overestimation of the CVI value was obtained. CONCLUSIONS: Our study presents a new strategy for obtaining robust CVI estimates using an indirect method together with the value of symmetric RCV to select the target population. The CVI estimates obtained show a good correlation with those published in the EFLM-BVD database. Furthermore, our strategy can resolve some of the limitations encountered when using direct methods such as calculating confidence intervals.

Changing Immunochemistry Platforms: Thyroid Function Test Comparison and Reference Intervals Based on Clinical Needs.

BACKGROUND: Diagnosis of thyroid dysfunction relies on thyroid stimulating hormone (TSH), free thyroxine (FT4), and free tri-iodothyronine (FT3) tests against valid reference intervals (RIs). We changed the immunoassay platform from Abbott Architect to Siemens Atellica and aimed to establish Atellica RIs based on laboratory information system (LIS) patient data. METHODS: Atellica thyroid hormone immunoassays were verified against those of Architect. Real-life patient results were retrieved from LIS. A single result per patient dataset was used to establish the RIs by the indirect method. RESULTS: Atellica and Architect assays correlated well but Atellica showed a positive bias between 13% and 53%, the largest for FT4. Variations of the Atellica assays were ≤4%. The 95% Atellica RIs were 0.4-3.8 mU/L for TSH, 0.9-1.6 ng/dL for FT4, and 227-416 pg/dL for FT3. Considering the accumulating clinical experience with Atellica, the RIs for clinical use were adjusted as 0.5-4.0 mU/L, 0.9-1.8 ng/dL, and 169-409 pg/dL, respectively. CONCLUSIONS: We verified thyroid hormone RIs for Atellica by the indirect method for the first time. Our model proved reliable for selecting results of presumably healthy individuals from LIS data. Critical review of the RIs with local endocrinologists is essential.

Comparative study on direct and indirect methods for wet desulphurisation and denitrification based on micro-nano bubbles.

The wet desulphurisation and denitrification technique based on micro-nano bubbles, which is available by either D-method or I-method, is a promising novel process. By employing piped water, Na2SO3 aqueous solution and HA-Na aqueous solution as the absorption liquids, a comparative study was conducted in this article on D-method and I-method to analyze their performance, advantages and disadvantages. It was accompanied by an investigation of how initial pH and initial temperature values of the absorption liquids affected the removal efficiency. The results suggested a positive correlation between NO/SO2 removal efficiencies and pH values but a little improvement in the removal efficiency under alkaline conditions. Furthermore, heating the absorption liquids inhibited the removal of NO and SO2. When manipulated in the same experimental environment, D-method and I-method did not present a significant difference in the SO2 removal efficiency, while the former was remarkably more effective than the latter in removing NO. To put together, D-method had higher removal efficiency, but required a large-scale micro-nano bubble generator to process a large quantity of flue gas as the micro-nano bubble generator was subject to a limited inlet flow rate. Consequently, an increase in investment and operating costs was incurred, while this issue could be avoided by I-method.

An indirect approach for reference intervals establishment of immunoglobulin A, G and M: the combination of laboratory database and statistics.

Immunoglobulins are affected by sex, age and region, so it is necessary to establish suitable reference intervals (RIs) for clinical diagnosis. Various statistical methods were used to calculate RIs, but there has been a lack of comparison among the methods. Research based on immunoglobulin RIs establishment with various methods would provide a methodological basis for further research. A total of 16,525 individuals were enrolled in the study. Individuals were selected in the medical examination center of First Hospital of Jilin University from 2014 to 2020. The lambda-mu-sigma (LMS) method was performed to evaluate the dynamic changes in analytes. RIs were calculated by parametric, non-parametric, Hoffman method and Bhattacharya method. Sex and age partitions were found for immunoglobulins G and immunoglobulin M. The levels of IgM showed no difference with age in males, but showed differences after 50 years of age in females. Circulating immunoglobulin A concentrations showed an increasing trend with age, and immunoglobulin M showed a fluctuating trend with age. Obvious difference (>5%) was commonly found among the four methods, however, the RIs established by the four methods all passed the verification with a high passing rate. Sex and age differences should be considered for immunoglobulins G and immunoglobulin M in clinical practice. The feasibility of the four indirect methods was proven, which would provides a methodological reference for further studies and benefit the application of clinical data.

The indirect method in the establishment of reference intervals for complement 3 and complement 4: A retrospective study.

Objective: The establishment of reference intervals (RIs) for complement 3 (C3) and complement 4 (C4) is rare, especially by indirect methods. Therefore, this study aims to establish regional RIs for C3 and C4 by an indirect method, using relevant statistical methods. Methods: Total of 12,313 data points for C3 and 12,125 data points for C4 were obtained from the First Hospital of Jilin University's database in China and standardised using the Tukey and Box-Cox statistical methods. The coefficients of the skewness-median-coefficient of variation curves (LMS) were used to determine the critical value for age, and a subsequent z test used to compare the differences. A non-parametric method was used to establish the RIs. Results: The C3 and C4 concentrations showed no significant differences by sex, and a weak correlation with age. No significant difference was found after calculating the z value for the age points on the LMS curves. The RIs for C3 and C4 were 0.83-1.58 g/L and 0.15-0.40 g/L, respectively. The RIs all passed verification. Conclusion: Suitable RIs for C3 and C4 were established for the local population, and will benefit clinical diagnosis. The feasibility and practicability of the indirect method were demonstrated.

Indirect Methods To Measure Unfolded Proteins In Living Cells Using Fluorescent Proteins.

In the study of the unfolded protein response pathway, it is essential to determine the amount of unfolded proteins that the cell is accumulating. Besides being essential it is one of the most challenging technique because of the difficulty to detect unfolded proteins without producing protein denaturation with the method itself. Thus, indirect methods became very useful as the use of fluorescent proteins. In this chapter, we present some of the most used methods to indirectly measure protein folding in living cells using fluorescent proteins.

Big data and reference intervals.

Although reference intervals (RIs) play an important role in clinical diagnosis, there remain significant differences with respect to race, gender, age and geographic location. Accordingly, the Clinical Laboratory Standards Institute (CLSI) EP28-A3c has recommended that clinical laboratories establish RIs appropriate to their subject population. Unfortunately, the traditional and direct approach to establish RIs relies on the recruitment of a sufficient number of healthy individuals of various age groups, collection and testing of large numbers of specimens and accurate data interpretation. The advent of the big data era has, however, created a unique opportunity to "mine" laboratory information. Unfortunately, this indirect method lacks standardization, consensus support and CLSI guidance. In this review we provide a historical perspective, comprehensively assess data processing and statistical methods, and post-verification analysis to validate this big data approach in establishing laboratory specific RIs.