Stereocontrolled Synthesis of α-3-Deoxy-d-manno-oct-2-ulosonic Acid (α-Kdo) Glycosides Using C3-p-Tolylthio-Substituted Kdo Donors: Access to Highly Branched Kdo Oligosaccharides.

3-Deoxy-d-manno-oct-2-ulosonic acid (Kdo) is an eight-carbon monosaccharide found widely in bacterial lipopolysaccharides (LPSs) and capsule polysaccharides (CPSs). We developed an indirect method for the stereoselective synthesis of α-Kdo glycosides with a C3-p-tolylthio-substituted Kdo phosphite donor. The presence of the p-tolylthio group enhanced the reactivity, suppressed the formation of elimination by-products (2,3-enes), and provided complete α-stereocontrol. A variety of Kdo α-glycosides were synthesized by our method in excellent yields (up to 98 %). After glycosylation, the p-tolylthio group can be efficiently removed by free-radical reduction. Subsequently, the orthogonality of the phosphite donor and thioglycoside donor was demonstrated by the one-pot synthesis of a trisaccharide in Helicobacter pylori and Neisseria meningitidis LPS. Moreover, an efficient total synthesis route to the challenging 4,5-branched Kdo trisaccharide in LPSs from several A. baumannii strains was highlighted. To demonstrate the high reactivity of our approach further, the highly crowded 4,5,7,8-branched Kdo pentasaccharide was synthesized as a model molecule for the first time. Additionally, the reaction mechanism was investigated by DFT calculations.

Retrospective study to identify homocysteine reference intervals in healthy Chinese 60 years of age and above.

Background: Homocysteine (Hcy) are associated with many age-related diseases. Heterogeneous physiology with aging combined with unresolved assays standardization necessitates the establishment of specific Hcy reference intervals (RIs) applicable to the elderly. This retrospective study aimed to identify Hcy RIs in the elderly aged 60 years and older from a hospital in Jiangsu Province, China. Methods: Data from individuals undergoing routine physical examinations were collected. Hcy were measured on Hitachi 7600 analyzer using hydrolase-based enzymatic cycling method. Outliers were identified by Dixon methods. Age- and gender-specific differences were estimated by nonparametric tests. Factors affected Hcy were assessed using multivariate linear regression. RIs with 90% confidence intervals were determined by nonparametric method. Results: A total of 2594 individuals were included. Hcy levels increased with age (r=0.248, p<0.001). Males have consistently higher Hcy levels (median (interquartile range): 11.95 (8.89-15.30) mmol/L) than females (9.65 (7.05-12.69) mmol/L; p<0.001). Multivariate adjustment analysis showed correlations between Hcy and gender (b=0.188, p<0.001), age (b=0.427, p<0.001) were significant. The Hcy RIs were 5.10-25.46 mmol/L for males, and 4.14-18.91 mmol/L for females, respectively. Conclusions: This study identified ageand gender-specific Hcy RIs in the elderly, which may guide clinicians in interpreting laboratory findings and clinical management.

Lyme borreliosis diagnosis: state of the art of improvements and innovations.

With almost 700 000 estimated cases each year in the United States and Europe, Lyme borreliosis (LB), also called Lyme disease, is the most common tick-borne illness in the world. Transmitted by ticks of the genus Ixodes and caused by bacteria Borrelia burgdorferi sensu lato, LB occurs with various symptoms, such as erythema migrans, which is characteristic, whereas others involve blurred clinical features such as fatigue, headaches, arthralgia, and myalgia. The diagnosis of Lyme borreliosis, based on a standard two-tiered serology, is the subject of many debates and controversies, since it relies on an indirect approach which suffers from a low sensitivity depending on the stage of the disease. Above all, early detection of the disease raises some issues. Inappropriate diagnosis of Lyme borreliosis leads to therapeutic wandering, inducing potential chronic infection with a strong antibody response that fails to clear the infection. Early and proper detection of Lyme disease is essential to propose an adequate treatment to patients and avoid the persistence of the pathogen. This review presents the available tests, with an emphasis on the improvements of the current diagnosis, the innovative methods and ideas which, ultimately, will allow more precise detection of LB.

Verification of Reference Interval of Thyroid Hormones With Manual and Automated Indirect Approaches: Comparison of Hoffman, KOSMIC and refineR Methods.

INTRODUCTION: The interpretation of quantitative test results requires the availability of appropriate reference intervals (RIs). Every laboratory has been advised by scientific literature and reagent manufacturers to establish RIs for all analytes. Measuring RIs using direct methods is very costly, and it poses ethical and practical challenges. To overcome these challenges, indirect methods, such as Hoffman, and newer automated approaches, such as KOSMIC and refineR, are used to verify RIs for thyroid hormones. OBJECTIVE: To verify RIs for thyroid hormones in adult patients using Hoffman, KOSMIC and refineR methods and to compare these with reference ranges given in kit literature or standard textbooks. MATERIALS AND METHODS: The observed values (results) of thyroid hormone were collected from the LIS (Laboratory Information System) of the Biochemistry Department at the B. J. Medical College and Civil Hospital in Ahmedabad between 1 January 2021 and 31 May 2022. Hoffman, KOSMIC and refineR methods were used to verify the RIs. The computerised Hoffman approach, which Katayev et al. describe, is a simple method for determining RI from hospital data. Zierk et al. pre-validated and suggested the KOSMIC method based on Python programming, whereas refineR was proposed by Tatjana et al. based on R programming language. RESULTS: Hoffman, KOSMIC and refineR's indirect RI techniques revealed comparable results with kit literature in free T3 and T4, whereas higher upper reference limits of thyroid-stimulating hormone (TSH) compared to kit literature were observed with KOSMIC and refineR methods. However, the computerised Hoffman method revealed comparable results with TSH also. CONCLUSION: Indirect approaches, such as Hoffman, KOSMIC and refineR, provide reliable RI verification for free T3 and T4 utilising patient samples obtained from LIS. However, the manual Hoffman method provides reliable RI verification for TSH data derived from the hospital population as compared to automated approaches, such as KOSMIC and refineR.

Prevalence of opioid dependence in New South Wales, Australia, 2014-16: Indirect estimation from multiple data sources using a Bayesian approach.

AIMS: To estimate the prevalence of, and number of unobserved people with opioid dependence by sex and age group in New South Wales (NSW), Australia. DESIGN: We applied a Bayesian statistical modelling approach to opioid agonist treatment records linked to adverse event rate data. We estimated prevalence from three types of adverse event separately: opioid mortality, opioid-poisoning hospitalizations and opioid-related charges. We extended the model and produced prevalence estimates from a 'multi-source' model based on all three types of adverse event data. SETTING, PARTICIPANTS AND MEASUREMENTS: This study was conducted in NSW, Australia, 2014-16 using data from the Opioid Agonist Treatment and Safety (OATS) study, which included all people who had received treatment for opioid dependence in NSW. Aggregate data were obtained on numbers of adverse events in NSW. Rates of each adverse event type within the OATS cohort were modelled. Population data were provided by State and Commonwealth agencies. FINDINGS: Prevalence of opioid dependence among those aged 15-64 years in 2016 was estimated to be 0.96% (95% credible interval [CrI] = 0.82%, 1.12%) from the mortality model, 0.75% (95% CrI = 0.70%, 0.83%) from hospitalizations, 0.95% (95% CrI = 0.90%, 0.99%) from charges and 0.92% (95% CrI = 0.88%, 0.96%) from the multi-source model. Of the estimated 46 460 (95% CrI = 44 680, 48 410) people with opioid dependence in 2016 from the multi-source model, approximately one-third (16 750, 95% CrI = 14 960, 18 690) had no record of opioid agonist treatment within the last 4 years. From the multi-source model, prevalence in 2016 was estimated to be 1.24% (95% CrI = 1.18%, 1.31%) in men aged 15-44, 1.22% (95% CrI = 1.14%, 1.31%) in men 45-64, 0.63% (95% CrI = 0.59%, 0.68%) in women aged 15-44 and 0.56% (95% CrI = 0.50%, 0.63%) in women aged 45-64. CONCLUSIONS: A Bayesian statistical approach to estimate prevalence from multiple adverse event types simultaneously calculates that the estimated prevalence of opioid dependence in NSW, Australia in 2016 was 0.92%, higher than previous estimates.

A innovative wavelet transformation method optimization in the noise-canceling application within intelligent building occupancy detection monitoring.

The study deals with detection of the occupation of Intelligent Building (IB) using data obtained from indirect methods with Big Data Analysis within IoT. In the area of daily living activity monitoring, one of the most challenging tasks is occupancy prediction, giving us information about people's mobility in the building. This task can be done via monitoring of CO2 as a reliable method, which has the ambition to predict the presence of the people in specific areas. In this paper, we propose a novel hybrid system, which is based on the Support Vector Machine (SVM) prediction of the CO2 waveform with the use of sensors that measure indoor/outdoor temperature and relative humidity. For each such prediction, we also record the gold standard CO2 signal to objectively compare and evaluate the quality of the proposed system. Unfortunately, this prediction is often linked with a presence of predicted signal activities in the form of glitches, often having an oscillating character, which inaccurately approximates the real CO2 signals. Thus, the difference between the gold standard and the prediction results from SVM is increasing. Therefore, we employed as the second part of the proposed system a smoothing procedure based on Wavelet transformation, which has ambitions to reduce inaccuracies in predicted signal via smoothing and increase the accuracy of the whole prediction system. The whole system is completed with an optimization procedure based on the Artificial Bee Colony (ABC) algorithm, which finally classifies the wavelet's response to recommend the most suitable wavelet settings to be used for data smoothing.

Comparison of reference intervals for biochemical and hematology markers derived by direct and indirect procedures based on the Isfahan cohort study.

INTRODUCTION: Indirect methods for reference interval (RI) establishment apply statistical techniques to generate RIs for test result interpretation using stored laboratory data. They present unique advantages relative to traditional direct approaches such as fewer resource requirements; however, there is debate regarding their performance. Herein, we aimed to compare indirect and direct approaches for RI establishment by harnessing data from the Isfahan Cohort Study (ICS). This cohort includes both healthy individuals and those with a history of disease, enabling a direct comparison. METHODS: Participants were recruited as part of ICS, including 6504 adults aged 34 years and older. Sociodemographic characteristics, anthropometry, blood pressure, various biochemical indices, and hematology parameters were collected. The refineR method was used to establish indirect RIs (before applying exclusion criteria). Direct RIs were calculated using nonparametric methods per CLSI EP28-A3 guidelines (after applying exclusion criteria). Bias ratios were calculated for each parameter to assess significant differences in estimations. RESULTS: Direct and indirect RI estimations for most hematological and biochemical parameters were comparable. Statistically significant bias ratios between methods were observed for the upper limits of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), hemoglobin (female), and platelet count as well as the lower limits of mean corpuscular hemoglobin (female), mean corpuscular volume, hemoglobin, and hematocrit (female). CONCLUSION: Data presented indicate RIs derived from direct and indirect approaches are similar, but not identical. Further work should focus on the clinical significance of such differences as well as the investigation of necessary data-cleaning criteria before indirect method application.

Application of the Hoffmann, Bhattacharya, nonparametric test, and Q-Q plot methods for establishing reference intervals from laboratory databases.

BACKGROUND: Reference intervals (RIs) are vital for interpreting laboratory biomarkers and enabling clinical decision-making. Among various RI-estimation methods, we explored the application value of Hoffmann, Bhattacharya, nonparametric test, and Q-Q plot methods for estimating the RI of urea, creatinine, and uric acid (UA). METHOD: This cross-sectional study collected patient data recorded between January 2020 and April 2022 at the Chongqing University Central Hospital Laboratory Information System. The RIs of urea, creatinine, and UA levels were established using the Hoffmann, Bhattacharya, nonparametric, and Q-Q plot methods, and RI differences with different computational methods were verified using the reference change value (RCV%) of biological variability. RESULTS: We included 16,474 and 123,570 patients in the physical examination and clinical groups, respectively. In the clinical group, differences in the RI upper limit of analytes with the four methods (excluding the Q-Q plot method) were within the permissible RCV% range; only the nonparametric test produced an RI of urea with the lower limit within the permissible RCV% range. In the physical examination group, the relative RI differences among the four methods (excluding the lower limit of RI obtained using the Q-Q plot) were all within the acceptable RCV% range; the relative deviation of the RI of UA with the four methods was within the acceptable RCV% range (excluding the lower RI limit obtained using the Q-Q plot and nonparametric test). CONCLUSION: The Hoffmann and Bhattacharya methods may provide reliable RIs for indirect estimations of urea, creatinine, and UA based on laboratory datasets.

Agreement and validity between body fat estimated by skinfold measurement and air displacement plethysmography in adolescents / Concordância e validade entre a gordura corporal estimada por medidas de dobras cutâneas e pletismografia por deslocamento de ar em adolescentes

ABSTRACT Objective: Assess the agreement and validity between relative body fat percentages estimated using anthropometric measurements and air displacement plethysmography (ADP). Methods: A cross-sectional study was conducted on 118 adolescents (60 females) aged 10 to 14 years (x̄=12.19, sd=1.18). Adolescents were classified as eutrophic or with overweight according to body mass index (body weight/height2) (x̄=20,12, sd=3,56). Measurements of skinfold thickness (triceps and medial calf) were collected and used to estimate relative body fat by the Slaughter equation. ADP was used as a reference method for the estimation of relative body fat. Agreement between body fat measurement methods (anthropometry × ADP) was analyzed by the Bland-Altman method. The mean error (ME) was calculated by subtracting the body fat percentage estimated by the Slaughter equation from the body fat percentage estimated by ADP. Validity was tested with the concordance correlation coefficient (CCC). Results: There was no agreement between the methods, regardless of sex and weight status. For boys with overweight (ME = 4.52; p = 0.007), eutrophic girls (ME = 6.37; p < 0.001), and girls with overweight (ME = 5.55; p < 0.001), the Slaughter equation resulted in overestimation of body fat compared with ADP. Skinfold equations did not demonstrate validity when compared with ADP. Conclusion: Slaughter's skinfold equations did not demonstrate agreement and validity compared with ADP in either sex or weight status. Skinfold equations should be used with caution and, whenever possible, in combination with other body composition indicators.

RESUMO Objetivo: Avaliar a concordância e validade entre os percentuais de gordura corporal estimados usando medidas antropométricas e pletismografia por deslocamento de ar (PDA). Métodos: Um estudo transversal foi conduzido em 118 adolescentes (60 meninas) com idade entre 10 e 14 anos (x̄=12,19, dp=1,18). Os adolescentes foram classificados como eutróficos ou com sobrepeso de acordo com o índice de massa corporal (peso/altura2) (x̄=20,12, dp=3,56). Medidas de dobras cutâneas (tríceps e panturrilha medial) foram coletadas e utilizadas para estimar a gordura corporal relativa pela equação de Slaughter. A PDA foi utilizada como método de referência para a estimativa da gordura corporal relativa. A concordância entre os métodos de medida de gordura corporal (antropometria × PDA) foi analisada pelo método de Bland-Altman. O erro médio (EM) foi calculado subtraindo o percentual de gordura corporal estimado pela equação de Slaughter do percentual de gordura corporal estimado pela PDA. A validade foi testada com o coeficiente de correlação de concordância (CCC). Resultados: Não houve concordância entre os métodos, independente do sexo e status de peso. Para meninos com excesso de peso (EM = 4,52; p = 0,007), meninas eutróficas (EM = 6,37; p < 0,001) e meninas com excesso de peso (EM = 5,55; p < 0,001), a equação de Slaughter resultou em superestimação da gordura corporal comparada com PDA. As equações de dobras cutâneas não demonstraram validade quando comparadas ao PDA. Conclusão: As equações de dobras cutâneas de Slaughter não demonstraram concordância e validade em comparação com PDA em ambos os sexos ou status de peso. As equações de dobras cutâneas devem ser utilizadas com cautela e, sempre que possível, acompanhada de outros indicadores de composição corporal.

Indirect estimation of reference intervals for thyroid parameters using advia centaur XP analyzer.

Background: The aim of this study was to determine the reference intervals (RIs) for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and FT3/FT4 ratio using indirect methods. Methods: We analyzed 1256 results TSH, FT4 and FT3 collected from a laboratory information system between 2017 and 2021. All measurements were performed on a Siemens ADVIA Centaur XP analyzer using the chemiluminescent immunoassay. We calculated the values of the 2.5th and 97.5th percentiles as recommended by the IFCC (CLSI C28-A3). Results: The RIs derived for TSH, FT4, FT3 and FT3/FT4 ratio were 0.34-4.10 mIU/L, 11.3-20.6 pmol/L, 3.5-6.32 pmol/L and 0.21-0.47, respectively. We found a significant difference between calculated RIs for the TSH and FT4 and those recommended by the manufacturer. Also, FT3 values were significantly higher in the group younger than 30 years relative to the fourth decade (5.26 vs. 5.02, p=0.005), the fifth decade (5.26 vs. 4.94, p=0.001), the sixth decade (5.26 vs. 4.87, p<0.001), the seventh decade (5.26 vs. 4.79, p<0.001) and the group older than 70 years old (5.26 vs. 4.55, p<0.001). Likewise, we found for TSH values and FT3/FT4 ratio a significant difference (p <0.001) between different age groups. Conclusions: The establishing RIs for the population of the Republic of Srpska were significantly differed from the recommended RIs by the manufacturer for TSH and FT4. Our results encourage other laboratories to develop their own RIs for thyroid parameters by applying CLSI recommendations.

Modeling Age Patterns of Under-5 Mortality: Results From a Log-Quadratic Model Applied to High-Quality Vital Registration Data.

Information about how the risk of death varies with age within the 0-5 age range represents critical evidence for guiding health policy. This study proposes a new model for summarizing regularities about how under-5 mortality is distributed by detailed age. The model is based on a newly compiled database that contains under-5 mortality information by detailed age in countries with high-quality vital registration systems, covering a wide array of mortality levels and patterns. It uses a log-quadratic approach in predicting a full mortality schedule between ages 0 and 5 on the basis of only one or two parameters. With its larger number of age-groups, the proposed model offers greater flexibility than existing models in terms of both entry parameters and model outcomes. We present applications of this model for evaluating and correcting under-5 mortality information by detailed age in countries with problematic mortality data.

Comparação entre métodos de estimativa de evapotranspiração de referência no município de São José dos Ausentes (RS), Brasil / Comparison between methods of estimation of reference evapotranspiration in the municipality of São José dos Ausentes (RS), Brazil

RESUMO A evapotranspiração de referência é uma componente muito importante do balanço hídrico e sua estimativa é essencial para execução de projetos agrícolas e ambientais, estudos de balanço hídrico, projetos e manejo de irrigação, modelagem de processos climatológicos e planejamento do gerenciamento dos recursos hídricos. O método de Penman-Monteith é considerado pela Food and Agriculture Organization of the United Nations como padrão para estimar a evapotranspiração de referência, contudo, dada a dificuldade de se obter um número grande de variáveis meteorológicas que são empregadas nesse método, tem-se utilizado vários outros métodos para estimar a evapotranspiração de referência. O presente trabalho teve como objetivo comparar, por meio de valores diários e mensais estimados pelo método de Penman-Monteith, o desempenho dos métodos de Thornthwaite, Hargraves-Samani, Makkink, Blaney-Criddle, Camargo e Jensen-Haise para o município de São José dos Ausentes, no Rio Grande do Sul. Os dados utilizados para estimar a evapotranspiração de referência foram obtidos pelo sistema Agritempo, que armazena e disponibiliza os dados da estação meteorológica automática do Instituto Nacional de Meteorologia. Os resultados apontam que o método de Blaney-Criddle foi o que apresentou os melhores resultados nas escalas tanto diária quanto mensal, seguido pelo método de Jensen-Haise, na escala mensal. Já os métodos que apresentaram os piores desempenhos foram o de Thorntwaite e Camargo, sendo classificados com desempenho "sofrível" na escala mensal e como "péssimo" e "mau", respectivamente, na escala diária.

ABSTRACT Reference evapotranspiration is a very important component of the water balance and its estimation is essential for the execution of agricultural and environmental projects, for studies of water balance, irrigation projects and management, modeling of climatological processes and planning of water resources management. The Penman-Monteith method is considered by the Food and Agriculture Organization of the United Nations as a standard for estimating reference evapotranspiration; however, due to the difficulty of obtaining a large number of meteorological variables that are employed in this method, several other methods have been used to estimate the reference evapotranspiration. The present coursework had the objective to compare the performance of the Thornthwaite, Hargraves-Samani, Makkink, Blaney-Criddle, Camargo, and Jensen-Haise methods for the municipality of São José dos Ausentes, using daily and monthly values estimated by the Penman-Monteith method. The data used to estimate the reference evapotranspiration were obtained through the Agritempo system, which stores and makes available the data of the automatic meteorological station of the National Meteorological Institute. The results show that the Blaney-Criddle method presented the best results, both daily and monthly, followed by the Jensen-Haise method in the monthly scale. On the other hand, the methods that presented the worst performances were those of Thorntwaite and Camargo, classified as "poor" on the monthly scale, and as "terrible" and "bad", respectively, on the daily one.

[International Consensus on Antinuclear Antibody Patterns in Portugal]. / International Consensus on Antinuclear Antibody em Portugal.

INTRODUCTION: Screening for autoantibodies in HEp-2 cells by indirect immunofluorescence is currently accepted as the gold-standard test for the diagnosis of systemic autoimmune diseases. The main objective of the International Consensus on ANA Patterns is to achieve a consensus on the nomenclature and description of antinuclear antibody morphological patterns. This work aims to build on the International Consensus on ANA Patterns project to establish a nomenclature consensus in Portugal, thus contributing to harmonization in autoimmune diagnosis and promoting diagnostic quality in autoimmune systemic rheumatic diseases. MATERIAL AND METHODS: Participating laboratories identified all the nuclear and cytoplasmic pattern designations in the International Consensus on ANA Patterns (including the anti-cell pattern code), and matched them with the corresponding Portuguese nomenclature in use. The results were aggregated and used as a foundation for nomenclature harmonization work. Consensus meetings followed an iterative process, until a final consensual proposal was drafted. RESULTS: Prior agreement between laboratories was over 75% for 23 of the total 29 anti-cell patterns. The degree to which each laboratory is aligned with the International Consensus on ANA Patterns international reference ranges from 22.1% to 100%. It was possible to write a consensual version of the International Consensus on ANA Patterns nomenclature for Portugal. DISCUSSION: There was a good consensus basis for the nomenclature in the International Consensus on ANA Patterns, despite relevant differences with some translations. The study highlights the need for collaboration among laboratories towards an unambiguous description of laboratory results. CONCLUSION: This study shows that there is good potential for collaboration between laboratories in order to produce the consensus needed to improve diagnosis and patient follow-up.

Introdução: A pesquisa de autoanticorpos em células HEp-2 através de imunofluorescência indireta é o teste padrão atualmente aceite como a ferramenta central para o diagnóstico das doenças autoimunes sistémicas. O International Consensus on Antinuclear Antibody (ANA) Patterns tem como objetivo principal alcançar um consenso na nomenclatura e na descrição dos diferentes padrões morfológicos de anticorpos antinucleares. Este trabalho tem como objetivo ampliar o projeto do International Consensus on ANA Patterns de forma a estabelecer um consenso em Portugal para a sua nomenclatura, procurando contribuir para a harmonização no diagnóstico autoimune e promover a qualidade diagnóstica nas doenças reumáticas sistémicas autoimunes.Material e Métodos: Os laboratórios participantes identificaram cada designação de padrão citoplasmático e nuclear do International Consensus on ANA Patterns (incluindo o código padrão anti-célula), e fizeram corresponder a cada uma a respetiva nomenclatura portuguesa em uso. Os resultados foram agregados e serviram de base ao trabalho de harmonização da nomenclatura. Seguiram-se reuniões de consenso, num processo iterativo até à redação de uma proposta final consensualizada.Resultados: A concordância prévia entre laboratórios era superior a 75% para 23 do total de 29 padrões anti-célula. O grau em que cada laboratório está alinhado com a referência internacional do International Consensus on ANA Patterns varia entre 22,1% e 100%. Foi possível elaborar uma versão consensualizada da nomenclatura do International Consensus on ANA Patterns para Portugal.Discussão: Existia uma boa base de consenso para a nomenclatura do International Consensus on ANA Patterns, mas com diferenças importantes em algumas das traduções da terminologia. O estudo realça a necessidade de colaboração entre laboratórios para uma descrição inequívoca dos resultados laboratoriais.Conclusão: Este trabalho mostra o potencial positivo da colaboração entre laboratórios para gerar consensos que contribuam para a melhoria do diagnóstico e acompanhamento dos doentes.

Determination and Environmental Implications of Aqueous-Phase Rate Constants in Radical Reactions.

Interests in the kinetics of radical-induced reactions in aqueous solution have grown remarkably due to their water engineering significance (e.g., advanced oxidation processes). Although compilations of the rate constants (k) for various radicals have been documented, surprisingly a systematic review has yet to be reported on the development of reliable methods for determining k values. A knowledge gap exists to critically evaluate and screen the various methods to measure them. In this review, we summarize the direct and indirect methods under steady-state and non-steady-state conditions, followed by critical evaluations on their advantages and disadvantages. The radicals of ·OH, [Formula: see text] , [Formula: see text] , and Cl· were chosen based on their significant aquatic environmental relevance. MS excel spreadsheets that demonstrate the determination processes were provided allowing one to reproduce the data and/or to analyze the unprocessed raw data as a "template". We formulated a standard operation procedure for the k determination, although there is simply no "versatile" method fitting for all radical reactions. Finally, existing challenges and future research focus are discussed. This is the first review covering methodological approaches and considerations, aiming to provide a holistic and fundamental basis to choose an appropriate method for determining the k values for bimolecular reactions between target compounds and radicals in the aqueous phase.

Big data and reference intervals: rationale, current practices, harmonization and standardization prerequisites and future perspectives of indirect determination of reference intervals using routine data.

Reference intervals are commonly used as a decision-making tool. In this review, we provide an overview on "big data" and reference intervals, describing the rationale, current practices including statistical methods, essential prerequisites concerning data quality, including harmonization and standardization, and future perspectives of the indirect determination of reference intervals using routine laboratory data.

Validity of Field Methods to Estimate Fat-Free Mass Changes Throughout the Season in Elite Youth Soccer Players.

The aim of this study was to determine the most effective anthropometric equations or bioelectrical impedance analysis (BIA) devices for quantifying the sensitivity to change in fat-free mass (FFM) in elite young soccer players, in comparison with measurements using dual-energy X-ray absorptiometry (DXA), between the pre- and mid-season. A total of 40 elite youth soccer players participated in this study. DXA values provided a criterion measure of FFM. Correlation coefficients, biases, limits of agreement, and differences were used as measures of sensitivity to change. All body density, skinfold, and anthropometric equations and BIA devices used to obtain FFM data showed positive and very large correlations (r from 0.70 to 0.89) with DXA. A significant increase in FFM was shown between time points using DXA, BIA, and all anthropometric equations (p < 0.01). The magnitudes of differences were small for DXA, BIA inbody and all anthropometric equations except those of Faulkner (1966), Durnin and Rahaman (1967), Brook (1971), and Sarría et al. (1998). Six anthropometric equations [Faulkner (1966), Durnin and Womersley (1974), Carter (1982), Slaughter et al. (1988), Reilly et al. (2009), and Munguia-Izquierdo et al. (2018)] and BIA Tanita showed no statistical differences compared to DXA, with a low bias. We concluded that the equations developed by Durnin and Womersley (1974), Carter (1982), Slaughter et al. (1988), Reilly et al. (2009), and Munguia-Izquierdo et al. (2018) showed the best sensitivity in assessing FFM changes between pre- and mid-season in elite youth soccer players.

Measuring and correcting bias in indirect estimates of under-5 mortality in populations affected by HIV/AIDS: a simulation study.

BACKGROUND: In populations that lack vital registration systems, under-5 mortality (U5M) is commonly estimated using survey-based approaches, including indirect methods. One assumption of indirect methods is that a mother's survival and her children's survival are not correlated, but in populations affected by HIV/AIDS this assumption is violated, and thus indirect estimates are biased. Our goal was to estimate the magnitude of the bias, and to create a predictive model to correct it. METHODS: We used an individual-level, discrete time-step simulation model to measure how the bias in indirect estimates of U5M changes under various fertility rates, mortality rates, HIV/AIDS rates, and levels of antiretroviral therapy. We simulated 4480 populations in total and measured the amount of bias in U5M due to HIV/AIDS. We also developed a generalized linear model via penalized maximum likelihood to correct this bias. RESULTS: We found that indirect methods can underestimate U5M by 0-41% in populations with HIV prevalence of 0-40%. Applying our model to 2010 survey data from Malawi and Tanzania, we show that indirect methods would underestimate U5M by up to 7.7% in those countries at that time. Our best fitting model to correct bias in U5M had a root median square error of 0.0012. CONCLUSIONS: Indirect estimates of U5M can be significantly biased in populations affected by HIV/AIDS. Our predictive model allows scholars and practitioners to correct that bias using commonly measured population characteristics. Policies and programs based on indirect estimates of U5M in populations with generalized HIV epidemics may need to be reevaluated after accounting for estimation bias.

Indirect estimation of infant mortality in small areas* / Estimação indireta da mortalidade infantil em pequenas áreas / Estimación indirecta de la mortalidad infantil en pequeñas áreas

The Brass-type indirect methods of early-age mortality estimation have been used for more than four decades, providing very robust estimates for countries without reliable vital registration systems. However, when estimation areas become smaller, the number of dead children could be very small, especially among those born to young women, who provide essential information to estimate recent mortality. In these cases, estimates could be affected by random errors and unexpected annual fluctuations. At the same time, although it is very unlikely that demographic trends in a small area would follow patterns very different from those prevailing in the broader environment they belong to, it is possible that some local events may become relevant to small areas, causing some deviations from the assumptions that may hold true to the larger area. The objective of this paper is to propose an adaptation of the indirect estimation approach, which would allow obtaining infant and child mortality estimates for small areas. As such, this proposal belongs to the realm of indirect estimation methods, sharing the limitations and advantages that characterize this type of estimation procedures. The method is illustrated with data from the 2014 Population and Housing Census of Myanmar. The results indicate that the method proposed here provides reliable and consistent infant mortality estimates, compared to the original Brass' method, even in very small areas.

Métodos indiretos do tipo Brass para estimar a mortalidade nas primeiras idades da vida têm sido usados por mais de quatro décadas, fornecendo estimativas muito robustas para países que não possuem sistemas confiáveis de estatísticas vitais. No entanto, quando as áreas de estimativa são pequenas, o número de crianças mortas pode ser muito baixo, especialmente entre os nascidos de mulheres jovens, que fornecem informações essenciais para estimar a mortalidade recente. Nestes casos, as estimativas podem ser afetadas por erros aleatórios e flutuações anuais inesperadas. Ao mesmo tempo, embora seja muito improvável que as tendências demográficas em uma área pequena sigam padrões muito diferentes daqueles prevalecentes no ambiente mais amplo ao qual pertencem, é possível que certos eventos locais se tornem relevantes em pequenas áreas, causando alguns desvios de padrões que na área maior são válidos. O objetivo deste trabalho é propor uma adaptação da abordagem de estimativa indireta, que permita obter estimativas de mortalidade infantil e das crianças em pequenas áreas. Dessa forma, tal proposta pertence ao escopo dos métodos de estimativa indireta, compartilhando as limitações e vantagens que caracterizam essa metodologia de estimativa. O método é ilustrado com dados do Censo de População e Habitação de Myanmar, 2014. Os resultados indicam que o método proposto aqui fornece estimativas confiáveis e consistentes de mortalidade infantil, em comparação com os resultados do método original de Brass, mesmo em áreas muito pequenas.

Los métodos indirectos del tipo Brass para estimar la mortalidad en las edades tempranas se han utilizado durante más de cuatro décadas y han proporcionado estimaciones muy robustas para países que no cuentan con sistemas de estadísticas vitales fiables. Sin embargo, cuando las áreas de estimación son pequeñas, el número de niños muertos podría ser muy reducido, especialmente entre los nacidos de mujeres jóvenes, quienes proporcionan información esencial para estimar la mortalidad reciente. En estos casos, las estimaciones podrían verse afectadas por errores aleatorios y fluctuaciones anuales inesperadas. Al mismo tiempo, aunque es muy poco probable que las tendencias demográficas en un área pequeña sigan patrones muy diferentes de los que prevalecen en el entorno más amplio al cual pertenecen, es posible que ciertos eventos locales se tornen relevantes en áreas pequeñas, causando algunas desviaciones de los supuestos que para el área más grande pueden ser válidos. El objetivo de este trabajo es proponer una adaptación del enfoque de estimación indirecta que permita obtener estimaciones de mortalidad infantil y en la niñez para áreas pequeñas. Como tal, esta propuesta pertenece al ámbito de los métodos de estimación indirecta, por lo que comparte las limitaciones y ventajas que caracterizan a esta metodología de estimación. El método se ilustra con datos del censo de población y vivienda de Myanmar de 2014. Los resultados obtenidos indican que el método aquí propuesto brinda estimaciones de mortalidad infantil confiables y consistentes, en comparación con los resultados del método original de Brass, incluso en áreas muy pequeñas.

Indirect methods for reference interval determination - review and recommendations.

Reference intervals are a vital part of the information supplied by clinical laboratories to support interpretation of numerical pathology results such as are produced in clinical chemistry and hematology laboratories. The traditional method for establishing reference intervals, known as the direct approach, is based on collecting samples from members of a preselected reference population, making the measurements and then determining the intervals. An alternative approach is to perform analysis of results generated as part of routine pathology testing and using appropriate statistical techniques to determine reference intervals. This is known as the indirect approach. This paper from a working group of the International Federation of Clinical Chemistry (IFCC) Committee on Reference Intervals and Decision Limits (C-RIDL) aims to summarize current thinking on indirect approaches to reference intervals. The indirect approach has some major potential advantages compared with direct methods. The processes are faster, cheaper and do not involve patient inconvenience, discomfort or the risks associated with generating new patient health information. Indirect methods also use the same preanalytical and analytical techniques used for patient management and can provide very large numbers for assessment. Limitations to the indirect methods include possible effects of diseased subpopulations on the derived interval. The IFCC C-RIDL aims to encourage the use of indirect methods to establish and verify reference intervals, to promote publication of such intervals with clear explanation of the process used and also to support the development of improved statistical techniques for these studies.

Different methods to determine the encapsulation efficiency of protein in PLGA nanoparticles.

BACKGROUND: Effective encapsulation of drugs into the delivery systems could increase the efficiency of nanoparticles in prevention and treatment of diseases. OBJECTIVE: The purpose of this study was to compare the different methods for determination of encapsulation efficiency of a model protein in the PLGA nanoparticles. METHODS: The various direct methods include dichloromethane, acetonitrile, modified acetonitrile and NaOH based extraction and radioactive methods were used to directly calculate the encapsulation efficiency of the loaded protein in the PLGA nanoparticles. Furthermore, indirect methods include BCA, Fluorescent and radioactive methods were compared. RESULTS: The encapsulation efficiencies determined by indirect methods include dichloromethane, acetonitrile, modified acetonitrile, NaOH based extraction and radioactive methods were 12.62% ± 1.97, 17.43% ± 2.51, 64.69% ± 4.31, 86.36% ± 2.25 and 90.15% ± 1.78, respectively. Moreover, the encapsulation efficiencies determined by indirect methods include BCA, fluorescent and radioactive methods were 81.46% ± 1.92, 88.23% ± 1.15 and 89.6% ± 1.9, respectively. CONCLUSIONS: Among the results obtained by indirect methods, radioactive and fluorescent methods showed more reliable. Moreover, NaOH and radioactive methods were the most reliable methods among the direct methods.