Insulin reference intervals in Brazilian adolescents by direct and indirect approaches: validation of a data mining method from laboratory data

array:23 ["pii" => "S0021755724000421" "issn" => "00217557" "doi" => "10.1016/j.jped.2024.03.009" "estado" => "S300" "fechaPublicacion" => "2024-09-01" "aid" => "1278" "copyright" => "Sociedade Brasileira de Pediatria" "copyrightAnyo" => "2024" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "J Pediatr (Rio J). 2024;100:512-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:17 [ "pii" => "S0021755724000433" "issn" => "00217557" "doi" => "10.1016/j.jped.2024.03.010" "estado" => "S300" "fechaPublicacion" => "2024-09-01" "aid" => "1279" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "J Pediatr (Rio J). 2024;100:519-26" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Quality of life of families and siblings of children with cerebral palsy treated at a reference neurorehabilitation center in Brazil" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "519" "paginaFinal" => "526" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Bruno Leonardo Scofano Dias, Maura Calixto Cecherelli de Rodrigues, José Luiz Muniz Bandeira Duarte" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Bruno Leonardo Scofano" "apellidos" => "Dias" ] 1 => array:2 [ "nombre" => "Maura Calixto Cecherelli" "apellidos" => "de Rodrigues" ] 2 => array:2 [ "nombre" => "José Luiz Muniz Bandeira" "apellidos" => "Duarte" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755724000433?idApp=UINPBA000049" "url" => "/00217557/0000010000000005/v1_202408020453/S0021755724000433/v1_202408020453/en/main.assets" ] "itemAnterior" => array:17 [ "pii" => "S0021755724000366" "issn" => "00217557" "doi" => "10.1016/j.jped.2024.03.006" "estado" => "S300" "fechaPublicacion" => "2024-09-01" "aid" => "1273" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "J Pediatr (Rio J). 2024;100:505-11" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Clinical significance and different strategies for re-elevation of plasma EBV-DNA during treatment in pediatric EBV-associated hemophagocytic lymphohistiocytosis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "505" "paginaFinal" => "511" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0001" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2066 "Ancho" => 3175 "Tamanyo" => 382542 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Fig " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Different time points for monitoring EBV-DNA during treatment." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Wenzhi Zhang, Yun Peng, Yining Qiu, Li Cheng, Yuhong Yin, Ying Li, Lizhen Zhao, Xiaoyan Wu" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Wenzhi" "apellidos" => "Zhang" ] 1 => array:2 [ "nombre" => "Yun" "apellidos" => "Peng" ] 2 => array:2 [ "nombre" => "Yining" "apellidos" => "Qiu" ] 3 => array:2 [ "nombre" => "Li" "apellidos" => "Cheng" ] 4 => array:2 [ "nombre" => "Yuhong" "apellidos" => "Yin" ] 5 => array:2 [ "nombre" => "Ying" "apellidos" => "Li" ] 6 => array:2 [ "nombre" => "Lizhen" "apellidos" => "Zhao" ] 7 => array:2 [ "nombre" => "Xiaoyan" "apellidos" => "Wu" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755724000366?idApp=UINPBA000049" "url" => "/00217557/0000010000000005/v1_202408020453/S0021755724000366/v1_202408020453/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Insulin reference intervals in Brazilian adolescents by direct and indirect approaches: validation of a data mining method from laboratory data" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "512" "paginaFinal" => "518" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Monica D.C. Freire, Paulo R.T.P. Dias, Thiago S.P. Souza, Caio K. Hirose, Paula B.M.C. Araujo, Mario F.T. Neves" "autores" => array:6 [ 0 => array:4 [ "nombre" => "Monica D.C." "apellidos" => "Freire" "email" => array:1 [ 0 => "freire5@yahoo.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0001" ] ] ] 1 => array:3 [ "nombre" => "Paulo R.T.P." "apellidos" => "Dias" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0002" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0003" ] 2 => array:2 [ "etiqueta" => "d" "identificador" => "aff0004" ] ] ] 2 => array:3 [ "nombre" => "Thiago S.P." "apellidos" => "Souza" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Caio K." "apellidos" => "Hirose" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "f" "identificador" => "aff0006" ] ] ] 4 => array:3 [ "nombre" => "Paula B.M.C." "apellidos" => "Araujo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "g" "identificador" => "aff0007" ] ] ] 5 => array:3 [ "nombre" => "Mario F.T." "apellidos" => "Neves" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "h" "identificador" => "aff0008" ] ] ] ] "afiliaciones" => array:8 [ 0 => array:3 [ "entidad" => "Universidade do Estado do Rio de Janeiro, Pós Graduação em Ciências Médicas, Rio de Janeiro, RJ, Brazil" "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:3 [ "entidad" => "Universidade Federal Fluminense, Instituto de Saúde Coletiva, Departamento de Epidemiologia e Bioestatística, Niterói, RJ, Brazil" "etiqueta" => "b" "identificador" => "aff0002" ] 2 => array:3 [ "entidad" => "Instituto de Ensino e Pesquisa DASA, São Paulo, SP, Brazil" "etiqueta" => "c" "identificador" => "aff0003" ] 3 => array:3 [ "entidad" => "Universidade do Estado do Rio de Janeiro, Núcleo de Estudos e Pesquisas em Atenção ao Uso de Drogas, Rio de Janeiro, RJ, Brazil" "etiqueta" => "d" "identificador" => "aff0004" ] 4 => array:3 [ "entidad" => "Universidade do Estado do Rio de Janeiro, Instituto de Matemática e Estatística, Rio de Janeiro, RJ, Brazil" "etiqueta" => "e" "identificador" => "aff0005" ] 5 => array:3 [ "entidad" => "DASA, Analytics Department, São Paulo, SP, Brazil" "etiqueta" => "f" "identificador" => "aff0006" ] 6 => array:3 [ "entidad" => "Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Pós-graduação em Endocrinologia, Rio de Janeiro, RJ, Brazil" "etiqueta" => "g" "identificador" => "aff0007" ] 7 => array:3 [ "entidad" => "Universidade do Estado do Rio de Janeiro, Faculdade de Ciências Médicas, Rio de Janeiro, RJ, Brazil" "etiqueta" => "h" "identificador" => "aff0008" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0001" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0001" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 4417 "Ancho" => 3344 "Tamanyo" => 527479 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Fig " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Plot of the Bhattacharya method applied to data-mined LIS data base (DB2), per age and sex partition. A, Female 12 and 13 years-old; B, Female 14 years-old; C, Female 15 years-old; D, Female 16 and 17 years-old; E, Male 12 to 14 years-old; F, Male 15 years-old; G, Male 16 and 17 years-old. Linear region represents the distribution of “healthy” individuals and RI are determined by the extension of the linear region of the “healthy” group." ] ] ] "textoCompleto" => "IntroductionReference intervals (RI) for laboratory tests are fundamental tools in clinical practice as they provide a critical framework for assessing and interpreting laboratory results. By comparing a patient's values to these predefined intervals, healthcare professionals can detect abnormalities, diagnose diseases, and make informed decisions regarding treatment and patient care. Hence, appropriately defined reference values are of vital importance.<a class="elsevierStyleCrossRef" href="#bib0001">1</a>Every laboratory should establish RI suitable for its specific service populations, according to the International Federation of Clinical Chemistry (IFCC) Clinical Laboratory Standards Institute (CLSI), since RI might be affected by race, age, sex, region, and other factors.<a class="elsevierStyleCrossRef" href="#bib0002">2</a> This partitioning is of utmost importance in pediatrics, as physiological advances after birth and during adolescence result in changes in many laboratory analytes.<a class="elsevierStyleCrossRef" href="#bib0003">3</a> Therefore, the use of wide age groups or missing sex grouping in adolescence can be intrinsically associated with inaccuracy.<a class="elsevierStyleCrossRef" href="#bib0004">4</a>The determination of RI can be done through direct and indirect methods.<a class="elsevierStyleCrossRef" href="#bib0002">2</a> IFCC, to this day, considers the a priori direct method as the gold standard, but it has considerable drawbacks, such as difficulty in recruiting sufficient reference individuals; selection bias in small-sample data; and time, labor, and financial costs.<a class="elsevierStyleCrossRef" href="#bib0005">5</a> In addition, for special groups, such as in pediatric population, it is difficult to obtain a large number of apparently healthy individuals. Transference of RI from different populations – an alternative to the determination of one's laboratory own RI - may result in a marked variation of sample classification, affecting diagnosis and treatment.<a class="elsevierStyleCrossRef" href="#bib0006">6</a>As an alternative to clinical studies, the indirect approach, determines RI from data mined from existing laboratory datasets by calculation through various mathematical methods available.<a class="elsevierStyleCrossRef" href="#bib0007">7</a> Indirect methods may be more feasible to determine RI specific to local populations, especially appropriate in vulnerable populations, where ethical considerations and practical problems often hinder the recruiting of sufficient numbers of healthy volunteers.With the advent of medical big data, the use of indirect methods based on data sets previously obtained from clinical laboratories is promising. The establishment of RI using indirect methods roughly involves data acquisition, data cleaning, transformation of skewed data, elimination of outliers or error values, and selection of appropriate statistical methods to calculate the reference limits (RLs).<a class="elsevierStyleCrossRef" href="#bib0008">8</a>Nowadays, childhood obesity is an emerging problem.<a class="elsevierStyleCrossRef" href="#bib0009">9</a> The rising prevalence of obesity is causing an increase in obesity-related complications such as insulin resistance.<a class="elsevierStyleCrossRef" href="#bib0010">10</a> Hyperinsulinemia is a normal physiological state during puberty,<a class="elsevierStyleCrossRef" href="#bib0011">11</a> but children with obesity can have abnormally high fasting blood insulin (FBI) levels.<a class="elsevierStyleCrossRef" href="#bib0012">12</a>The gold standard for the assessment of IR is the hyperinsulinemic euglycemic clamp, which is invasive, expensive, and complex to use in the daily clinical practice.<a class="elsevierStyleCrossRef" href="#bib0011">11</a> Therefore, the most common surrogate markers of IR are the fasting plasma insulin and the homeostasis model assessment insulin resistance (HOMA-IR).<a class="elsevierStyleCrossRef" href="#bib0010">10</a>The aim of this study was to determine RI for FBI in Brazilian adolescents - by a posteriori direct approach using the ERICA Study database<a class="elsevierStyleCrossRef" href="#bib0013">13</a> and by an indirect approach, using LIS outpatient data mining and Bhattacharya method – and, by compare their results, evaluate the data mining indirectly determined RI.Materials and methodsStudy design and subjectsThe study determined RI for FBI from 2 different databases of Brazilian adolescents, from 12 years-old to 17 years, 11 months, and 30 days old (from now called 17 years-old), according to age and sex partitions. DB1 consists of a reference population of healthy individuals, from 124 Brazilian cities, recruited from January 2013 to November 2014,<a class="elsevierStyleCrossRef" href="#bib0002">2</a> as part of a large population study on cardiovascular risk in adolescence, the ERICA study.<a class="elsevierStyleCrossRef" href="#bib0013">13</a> DB2 was obtained by data mining the laboratory information system (LIS) of a large commercial laboratory, from outpatients whose samples were directly drawn by the laboratory, from four States and the Federal District of Brazil, from January 2011 to June 2015.Exclusion criteria for DB1 were fasting glucose equal or higher than 126 mg/dL, glycated hemoglobin equal or higher than 6.5%, self-reported pregnancy or suspicion of pregnancy, self-reported acute or chronic illness, and regular prescription drug use. DB2 included individuals only once,<a class="elsevierStyleCrossRef" href="#bib0014">14</a> based on the first FBI determination observed on the database timeline, and excluded females with a positive BHCG testing, anytime 9 months prior to the FBI test result observed.Outliers were removed from both data sets prior to partitioning, after data log transformation, by the Chauvenet criteria.Age and sex partitions were calculated on DB1 and used as partitions on DB2 as well.The authors used the RefVal software to perform a posteriori direct method calculation of RI for FBI for DB12, and Bhattacharya indirect method obtain RI from DB2.<a class="elsevierStyleCrossRef" href="#bib0015">15</a>,<a class="elsevierStyleCrossRef" href="#bib0016">16</a>Based on the direct and indirect RI obtained, the authors evaluated the rates of agreement of RI upper limits (URL) in diagnosing elevated FBI levels on individuals in DB1.FBI analyses were performed by the same commercial laboratory on both databases, on 5 laboratory sites throughout Brazil using standard operations, on Roche Diagnostics electrochemiluminescence platform. The laboratory is accredited by the Clinical Laboratories Accreditation Program of the Brazilian Society of Clinical Pathology and Laboratory Medicine. Standard pre-analytical methods and materials were determined and instructed by the same laboratory for the collection and sample handling on both databases.This study was approved by the Ethics Committee of the Pedro Ernesto University Hospital – Universidade do Estado do Rio de Janeiro, under the document number: 2.970.023. Data were analyzed using R software 4.2.3, RefVal software and Microsoft Excel - Office 365.FBI levels and RI were presented in µIU/mL. RI represents the values between the lower and upper reference limits. Standard deviations are also available per partition.Age and sex partitionsAfter data log-transformation, initial age and sex partitions were defined arbitrarily using DB1: males 12, 13, 14, 15, 16, and 17 years-old, and female 12, 13, 14, 15, 16, and 17 years-old. Then the authors used the Bartlett test to approach the homogeneity of variances for each group (transformed data). Since variance results were not homogeneous, the authors used the Kruskal-Wallis test to evaluate if there were significant differences in FBI DB1 measurements on age and sex groups. As they were present, the authors performed multiple pairwise paired t-tests between the levels of the within-subject groups. P-values are adjusted using the Bonferroni multiple-testing correction method. Groups with no statistically significant differences were merged into a single partition.The authors then applied the DB1 partitions, considered the reference sample obtained by individual interview and physical examination for the gold standard RI calculation method, at DB1, once DB1 is the data set with the highest percentage of “healthy” subjects. This allowed comparisons between DB1 and DB2 RI, per partition.Direct approach RIDB1 was used for the determination of RI by the a posteriori direct method, for each age and sex group, as described by IFCC C28-A3c Guidelines.<a class="elsevierStyleCrossRef" href="#bib0002">2</a> The authors performed RI direct estimates of log-transformed FBI levels, after outlier exclusion, per partition, by parametric and bootstrap methods. RI represents the central 95 % range. Lower and upper reference limits correspond to the 2.5th and 97.5th percentiles, respectively. The authors additionally determined their 90 % confidence intervals (90 % CI).Indirect approach RIAfter data log transformation, subsequent outlier removal and partitioning, DB2 was used for the indirect determination of RI, for each age and sex partition, by a mathematical mixture separation method, the Bhattacharya method, widely used and described on literature.<a class="elsevierStyleCrossRef" href="#bib0015">15</a> In brief, a graphical method is used to identify an underlying Gaussian distribution amongst other data, which may include an “unhealthy” dataset of individuals.Validation of the indirectly determined fasting blood insulin URLComparison of the diagnosis of elevated FBI of DB1 individualsThe authors identified the diagnosis of elevated FBI by the indirectly determined URL on every subject of DB1 and compared it to the diagnosis obtained when using the directly determined 90 % CI URL. The question addressed is if a subject's FBI measurement would have different clinical interpretations when compared to the highest probabilistic gold-standard URL - in this case, the higher limit of 90 % CI of the direct URL- and when compared to the indirectly determined URL.Four groups of results were determined according to the diagnostic agreement, for sex and age partitions: FBI below DB1 90 % CI URL and DB2 URL; B: FBI above DB1 90 % CI URL and below DB2 URL; C: FBI below DB1 90 % CI URL and above DB2 URL; D: FBI above DB1 90 % CI URL and DB2 URL. This analysis was used to evaluate the consistency of the decision impact caused by the indirectly determined URL, compared to the directly determined URL.ResultsDatabase population distribution and FBI level resultsDB1, derived from the ERICA Study, consisted of 29,200 individuals from 12 to 17 years old, after exclusion criteria application. Outliers removed represented 1.2 % (453) of the sample, therefore 28,747 individuals were selected for partitioning and subsequent RI determination. Most of the participants were female (n = 16,919; 58.85 %). Population distribution after removal of outliers, and before partitioning was not normal. Age and sex groups determined were: female 12 and 13 years-old (n = 4775); female 14 years-old (n = 3035); female 15 years-old (n = 3164); female 16 and 17 years-old (n = 5945); male 12 to 14 years-old (n = 5451); male 15 years-old (n = 2315); and, male 16 and 17 years-old (n = 4062).DB2 consisted of 5895 adolescents, after exclusion criteria. The distribution prior to the removal of outliers and partitioning was not normal. After log-transformation and removal of outliers (n = 532; 8.27 %), 3692 were female (62.6 %). Then, age and sex partitions from DB1 were used to group DB2 subjects.The mean FBI measurements – recalculated from the log-transformed results - were significantly higher in DB2, on all groups. <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a> shows the distribution characteristics and FBI measurements of both databases.<elsevierMultimedia ident="tbl0001"></elsevierMultimedia>Reference intervals for FBI in adolescentsURL determined by Bhattacharya method (<a class="elsevierStyleCrossRef" href="#fig0001">Figure 1</a>) were slightly lower than the 90 % CI URL directly obtained on DB1, except for group female 12 and 13 years-old. (24.27 µIU/mL versus 22.9 µIU/mL). <a class="elsevierStyleCrossRef" href="#tbl0002">Table 2</a> shows RI determined per age and sex group, by both methods.<elsevierMultimedia ident="fig0001"></elsevierMultimedia><elsevierMultimedia ident="tbl0002"></elsevierMultimedia>Diagnostic agreement of elevated FBI between direct and indirect URLThe directly determined 90 % CI URL, and the URL calculated by the Bhattacharya method were used to assess if the FBI level of each DB1 individual subject was considered elevated. The authors observed high agreement rates for elevated FBI levels, in all partitions (<a class="elsevierStyleCrossRef" href="#tbl0003">Table 3</a>).<elsevierMultimedia ident="tbl0003"></elsevierMultimedia>DiscussionFasting blood insulin level is an important biomarker for insulin resistance observed in overweight, obesity and metabolic syndrome, conditions related to cardiovascular risk.<a class="elsevierStyleCrossRef" href="#bib0017">17</a> Healthy adolescents respond to normal metabolic changes with increased insulin resistance. Therefore, FBI levels physiologically also increase in pubertal youngsters.<a class="elsevierStyleCrossRef" href="#bib0011">11</a> The present findings on the FBI RI in different groups of adolescents, regardless of the methodology used, corroborate this physiological knowledge. A systematic review conducted by Van der Aa et al. showed insulin resistance prevalence rates from 3.1% to 44%.<a class="elsevierStyleCrossRef" href="#bib0010">10</a> The authors used six different methods to define insulin resistance and a variety of cut-offs, leaving a gap of consensus regarding RI for FBI in pediatrics. This highlights the importance of understanding the URL of blood insulin levels in adolescents to properly address pathological insulin resistance in this population.In recent years, several studies on pediatric RI of multiple analytes using both direct and indirect approaches have been published.<a class="elsevierStyleCrossRefs" href="#bib0018">18-22</a> Large multicentric studies attempted to determine pediatric RI to several analytes. CALIPER Study by Colantonio et al. presented fasting insulin results from 190 individuals between 6 and under 19 years old, but not its RI.<a class="elsevierStyleCrossRef" href="#bib0022">22</a> Kelly et al. published a posteriori direct calculated RI for insulin from 240 subjects from 11 to 19 years-old, without further age or sex partitions, and observed extremely high URL obtained by Abbott Architect platform.<a class="elsevierStyleCrossRef" href="#bib0023">23</a> Later, Adeli et al. in a collaboration between The Canadian Health Measures Survey and CALIPER initiative, were able to use insulin measurements processed on Centaur XP and Immulite 2000 platforms from 1700 adolescents from 11 to 19 years-old and proposed the same lower (2.1 µIU/mL) and upper (21.8 µIU/mL) limits for both boys and girls without additional age partitions.<a class="elsevierStyleCrossRef" href="#bib0004">4</a> However, age and sex partitions are key to pubertal adolescents since insulin resistance varies according to Tanner stages in males and females.<a class="elsevierStyleCrossRef" href="#bib0011">11</a> The present study, on the other hand, brings the novelty of establishing insulin RI addressing this issue.It is known that uncertainties and differences between a reference population-derived RI and the local population served by a specific laboratory can affect the diagnostic accuracy if the laboratory simply verifies or transfers these RI to apply in other populations than the original one.<a class="elsevierStyleCrossRef" href="#bib0024">24</a> Additionally, accurate determination of RI, directly or indirectly calculated, and comparison between methods, can be affected by biological variables that influence and demand appropriate group separation (homogeneity, age, sex, nutritional state, ethnicity).<a class="elsevierStyleCrossRef" href="#bib0025">25</a>,<a class="elsevierStyleCrossRef" href="#bib0026">26</a> Both RI estimation methods can lead to erroneous RI if stratification for variables is not performed properly. Despite the Brazilian geographical broadness, DB1 and DB2 samples in this study were analyzed on five sites of the same commercial laboratory, by the same analytical platform (Roche Diagnostics) in order to optimize quality control and the use of similar standard operational procedures. Also, since the unknown fraction of the pathological distribution can affect the capability of separation of groups from DB2, the authors calculated age and sex partitions from DB1, which enrolled only healthy subjects after individual interview and examination, and then applied them to DB2 calculations.<a class="elsevierStyleCrossRef" href="#bib0025">25</a> The large number of individuals enrolled in the ERICA Study not only allowed statistically calculated DB1 age and sex partitions but provided the highest number of adolescents for the direct calculation of FBI RI in the literature.<a class="elsevierStyleCrossRef" href="#bib0013">13</a>Mathematical indirect methods, such as Bhattacharya and others, can be calculated without the strict need to identify and exclude individuals according to signs of disease or to prefer individuals with signs of “good health”. It uses mixed data sets that are mainly composed of healthy persons, with some percentage of “diseased” ones (less than 20%).<a class="elsevierStyleCrossRef" href="#bib0008">8</a> The authors observed that mean FBI measurements were significantly higher on DB2 than DB1, as it represents the expected mixture of “healthy” and “unhealthy” subjects. Still, efforts to exclude known potential “non-healthy” individuals can improve the quality of the indirect RI obtained and can be achieved by exclusion criteria, such as: eliminating inpatients and pregnant women; using selected health records such as clinical history or laboratory findings; eliminating subjects with more than one analyte measurement as an indication of ongoing disease investigation; and by removal of outliers.<a class="elsevierStyleCrossRef" href="#bib0014">14</a> However, filtering algorithms may not be enough to accurately determine indirect RI.<a class="elsevierStyleCrossRef" href="#bib0025">25</a> Mathematical methods should be added to further separate and identify the subjacent unknown “non-diseased” population. With the development of informatics technology and the availability of real-world big data, various mathematical methods for RI determination were developed, became more feasible and accurate and were compared in performance.<a class="elsevierStyleCrossRef" href="#bib0007">7</a>,<a class="elsevierStyleCrossRef" href="#bib0027">27</a>,<a class="elsevierStyleCrossRef" href="#bib0028">28</a> Hoffmann, Bhattacharya, truncated minimum chi-square (TMC), and Kolmogorov-Smirnov distance (kosmic) indirect methods are the most widely used, and performed accordingly, in several studies.<a class="elsevierStyleCrossRef" href="#bib0007">7</a>,<a class="elsevierStyleCrossRef" href="#bib0028">28</a>,<a class="elsevierStyleCrossRef" href="#bib0029">29</a>In the present study, regardless of the mean difference in insulin measurements, the Bhattacharya method was able to separate the Gaussian distributed “healthy” individuals for the determination of accurate indirect RI. This statement is validated by the similarity between DB1 and DB2 derived RI and the elevated diagnostic agreement rates for high FBI in all partitions. The lowest diagnostic agreement for elevated FBI found was 97.56%. These findings also indicate the accuracy of the indirect method used in this study.To the best of our knowledge, this is a novel study to determine age and sex FBI RI through direct and indirect methods, for Brazilian adolescents, and to evaluate the indirect outcomes compared to the established standards of the direct method. These findings highlight the practicality, feasibility, cost-effectiveness, and accuracy of employing the Bhattacharya indirect method, facilitated by data mining of a large commercial LIS, in determining RI in adolescents. Significantly, this indirect method proves to be a reliable alternative, overcoming the inherent challenges associated with the conventional "gold standard" direct approach. Further studies using various indirect methods to determine RI in Brazilian pediatric populations should be encouraged, and further validations of the method in different analytes can be evaluated based on the large-scale ERICA study database. In the context of the prevailing big data era, Brazilian researchers are stimulated to contribute by presenting and publishing local RI through meticulous LIS data mining and indirect methodologies for local vulnerable populations, such as children and older adults.FundingThis research did not receive any funding from public, commercial, or not-for-profit organizations." "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:3 [ "identificador" => "xres2214786" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abss0001" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abss0002" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abss0003" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abss0004" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1856799" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0001" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "sec0002" "titulo" => "Materials and methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0003" "titulo" => "Study design and subjects" ] 1 => array:2 [ "identificador" => "sec0004" "titulo" => "Age and sex partitions" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Direct approach RI" ] 3 => array:2 [ "identificador" => "sec0006" "titulo" => "Indirect approach RI" ] 4 => array:3 [ "identificador" => "sec0007" "titulo" => "Validation of the indirectly determined fasting blood insulin URL" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0008" "titulo" => "Comparison of the diagnosis of elevated FBI of DB1 individuals" ] ] ] ] ] 4 => array:3 [ "identificador" => "sec0009" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Database population distribution and FBI level results" ] 1 => array:2 [ "identificador" => "sec0011" "titulo" => "Reference intervals for FBI in adolescents" ] 2 => array:2 [ "identificador" => "sec0012" "titulo" => "Diagnostic agreement of elevated FBI between direct and indirect URL" ] ] ] 5 => array:2 [ "identificador" => "sec0013" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "sec0014" "titulo" => "Funding" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-11-29" "fechaAceptado" => "2024-03-15" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1856799" "palabras" => array:4 [ 0 => "Data mining" 1 => "Insulin" 2 => "Reference interval" 3 => "Adolescent" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo determine reference intervals (RI) for fasting blood insulin (FBI) in Brazilian adolescents, 12 to 17 years old, by direct and indirect approaches, and to validate indirectly determined RI. MethodsTwo databases were used for RI determination. Database 1 (DB1), used to obtain RI through a posteriori direct method, consisted of prospectively selected healthy individuals. Database 2 (DB2) was retrospectively mined from an outpatient laboratory information system (LIS) used for the indirect method (Bhattacharya method). ResultsFrom DB1, 29345 individuals were enrolled (57.65 % female) and seven age ranges and sex partitions were statistically determined according to mean FBI values: females: 12 and 13 years-old, 14 years-old, 15 years-old, 16 and 17 years-old; and males: 12, 13 and 14 years-old, 15 years-old, 16 and 17 years-old. From DB2, 5465 adolescents (67.5 % female) were selected and grouped according to DB1 partitions. The mean FBI level was significantly higher in DB2, on all groups. The RI upper limit (URL) determined by Bhattacharya method was slightly lower than the 90 % CI URL directly obtained on DB1, except for group female 12 and 13 years old. High agreement rates for diagnosing elevated FBI in all groups on DB1 validated indirect RI presented. ConclusionThe present study demonstrates that Bhattacharya indirect method to determine FBI RI in adolescents can overcome some of the difficulties and challenges of the direct approach." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abss0001" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abss0002" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abss0003" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abss0004" "titulo" => "Conclusion" ] ] ] ] "NotaPie" => array:1 [ 0 => array:1 [ "nota" => "Institution or service with which the work is associated for indexing in Index Medicus/MEDLINE, City, Country: Universidade do Estado do Rio de Janeiro, Departamento de Pós Graduação em Ciências Médicas. Rio de Janeiro – Brazil." ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0001" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 4417 "Ancho" => 3344 "Tamanyo" => 527479 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Fig " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Plot of the Bhattacharya method applied to data-mined LIS data base (DB2), per age and sex partition. A, Female 12 and 13 years-old; B, Female 14 years-old; C, Female 15 years-old; D, Female 16 and 17 years-old; E, Male 12 to 14 years-old; F, Male 15 years-old; G, Male 16 and 17 years-old. Linear region represents the distribution of “healthy” individuals and RI are determined by the extension of the linear region of the “healthy” group." ] ] 1 => array:8 [ "identificador" => "tbl0001" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0002" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "FBI, fasting blood insulin." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0001"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0002"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">data base 1</th><a name="en0003"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">data base 2</th><a name="en0004"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="top" scope="col">p value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><a name="en0005"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0006"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">n \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0007"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">FBI mean (µIU/mL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0008"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">SD \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0009"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">n \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0010"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">FBI mean (µIU/mL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0011"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">SD \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0013"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Females \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0015"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0017"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0019"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0021"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">12–13 yo \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">4775 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0023"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10.2 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">4.85 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0025"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">928 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">15.8 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">8.23 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0029"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">14 yo \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">3035 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0031"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">9.45 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">4.68 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0033"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">478 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">13.6 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0035"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">7.48 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0036"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0037"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">15 yo \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">3164 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">8.97 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">4.46 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0041"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">532 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">13.9 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0043"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">8.20 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0045"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">16–17 yo \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0046"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">5945 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">8.59 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">4.35 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0049"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1754 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0050"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">12.8 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0051"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">7.78 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0053"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Males \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0055"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0057"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0061"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">12–14 yo \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">5451 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">8.43 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0064"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">4.76 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0065"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1187 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0066"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">14.0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0067"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">8.28 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0068"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0069"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">15 yo \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0070"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2315 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0071"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">7.98 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">4.51 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0073"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">320 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0074"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">13.1 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0075"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">8.53 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0076"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0077"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">16–17 yo \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0078"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">4062 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0079"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">7.33 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0080"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">4.32 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0081"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">696 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0082"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">12.1 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0083"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">8.21 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0084"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3612007.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Age and sex partitions, number of subjects and FBI central measures." ] ] 2 => array:8 [ "identificador" => "tbl0002" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0003" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "LRL, lower reference limit; URL, upper reference limit; LRL 90 %CI, lower reference limit 90 % confidence interval; URL 90 %CI, upper reference limit 90 % confidence interval; FBI, fasting blood insulin." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0085"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0086"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Data base 1 (Direct)</th><a name="en0087"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Data base 2 (Bhattacharya)</th></tr><tr title="table-row"><a name="en0088"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0089"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">LRL \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0090"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">LRL 90 %CI \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0091"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">URL \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0092"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">URL 90 %CI \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0093"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">LRL \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0094"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">URL \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0095"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Females \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0096"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0097"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0098"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0099"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0100"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0101"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0102"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">12–13 years-old \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0103"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2.6 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0104"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2.4–2.7 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0105"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">22.2 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0106"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">21.7–22.9 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0107"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.6 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0108"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">24.27 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0109"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">14 years-old \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0110"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2.2 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0111"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.9–2.5 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0112"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">21.4 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0113"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">20.6–22.9 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0114"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.2 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0115"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">22.33 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0116"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">15 years-old \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0117"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2.3 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0118"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2.1–2.5 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0119"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">20.9 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0120"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">19.9–21.5 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0121"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.36 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0122"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">19.62 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0123"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">16–17 years-old \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0124"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2.1 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0125"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.9–2.3 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0126"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">19.5 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0127"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">19.1–20.1 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0128"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.96 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0129"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">19.38 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0130"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Males \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0131"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0132"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0133"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0134"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0135"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0136"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0137"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">12–14 years-old \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0138"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0139"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.9–2.1 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0140"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">20.8 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0141"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">20.3–21.3 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0142"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.18 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0143"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">21.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0144"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">15 years-old \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0145"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.88 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0146"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.5–2.0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0147"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">20.2 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0148"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">19.9–21 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0149"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.57 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0150"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">19.24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0151"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">16–17 years-old \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0152"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.6 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0153"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.4–1.7 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0154"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">19.3 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0155"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">18.6–20.2 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0156"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0157"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">16.62 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3612005.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Reference intervals established by a posteriori direct method and indirect method (Bhattacharya method)." ] ] 3 => array:8 [ "identificador" => "tbl0003" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0004" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "A, FBI below DB1 URL (90 % CI) and DB2 URL; B, FBI above DB1 URL (90 % CI) and below DB2 URL; C, FBI below DB1 URL (90 % CI) and above DB2 URL; D, FBI above DB1 URL (90 % CI) and DB2 URL." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0158"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0159"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">A \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0160"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">B \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0161"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">C \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0162"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">D \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0163"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0164"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">diagnostic agreement (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0165"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Females \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0166"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0167"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0168"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0169"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0170"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0171"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0172"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">12–13 years-old \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0173"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">4675 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0174"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">34 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0175"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0176"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">66 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0177"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0178"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">99.29 % \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0179"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">14 years-old \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0180"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2972 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0181"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0182"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0183"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">61 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0184"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0185"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">99.93 % \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0186"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">15 years-old \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0187"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">3068 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0188"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0189"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">33 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0190"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">63 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0191"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0192"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">98.96 % \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0193"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">16–17 years-old \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0194"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">5787 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0195"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0196"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">29 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0197"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">129 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0198"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0199"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">99.51 % \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0200"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Males \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0201"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0202"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0203"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0204"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0205"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0206"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0207"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">12–14 years-old \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0208"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">5321 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0209"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0210"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0211"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">117 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0212"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0213"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">99.76 % \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0214"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">15 years-old \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0215"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2236 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0216"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0217"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">33 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0218"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">46 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0219"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0220"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">98.57 % \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0221"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">16–17 years-old \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0222"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">3880 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0223"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0224"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">99 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0225"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">83 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0226"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0227"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">97.56 % \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3612006.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Diagnostic agreement rates for elevated FBI per age and sex group, at DB1." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec1" "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib0001" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recommendation for the review of biological reference intervals in medical laboratories" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Henny" 1 => "A. Vassault" 2 => "G. Boursier" 3 => "I. Vukasovic" 4 => "P. Mesko Brguljan" 5 => "M. Lohmander" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Chem Lab Med" "fecha" => "2016" "volumen" => "54" "paginaInicial" => "1893" "paginaFinal" => "1900" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0002" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Wayne P.C. and LSI 2008. CLSI. Defining, establishing, and verifying reference intervals in the clinical laboratory; Approved Guideline—Third Edition. CLSI document C28-A3c." ] ] ] 2 => array:3 [ "identificador" => "bib0003" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Age- and sex-specific dynamics in 22 hematologic and biochemical analytes from birth to adolescence" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Zierk" 1 => "F. Arzideh" 2 => "T. Rechenauer" 3 => "R. Haeckel" 4 => "W. Rascher" 5 => "M. Metzler" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1373/clinchem.2015.239731" "Revista" => array:6 [ "tituloSerie" => "Clin Chem" "fecha" => "2015" "volumen" => "61" "paginaInicial" => "964" "paginaFinal" => "973" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25967371" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0004" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Complex reference values for endocrine and special chemistry biomarkers across pediatric, adult, and geriatric ages: establishment of robust pediatric and adult reference intervals on the basis of the Canadian health measures survey" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Adeli" 1 => "V. Higgins" 2 => "M. Nieuwesteeg" 3 => "J.E. Raizman" 4 => "Y. Chen" 5 => "S.L. Wong" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1373/clinchem.2015.240523" "Revista" => array:6 [ "tituloSerie" => "Clin Chem" "fecha" => "2015" "volumen" => "61" "paginaInicial" => "1063" "paginaFinal" => "1074" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26044507" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0005" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Critical comments to a recent EFLM recommendation for the review of reference intervals" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "R. Haeckel" 1 => "W. Wosniok" 2 => "F. Arzideh" 3 => "J. Zierk" 4 => "E. Gurr" 5 => "T. Streichert" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1515/cclm-2016-1112" "Revista" => array:6 [ "tituloSerie" => "Clin Chem Lab Med" "fecha" => "2017" "volumen" => "55" "paginaInicial" => "341" "paginaFinal" => "347" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28151722" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0006" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Paediatric reference intervals are heterogeneous and differ considerably in the classification of healthy paediatric blood samples" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.B. Alnor" 1 => "P.J. Vinholt" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00431-019-03377-w" "Revista" => array:6 [ "tituloSerie" => "Eur J Pediatr" "fecha" => "2019" "volumen" => "178" "paginaInicial" => "963" "paginaFinal" => "971" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30997593" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0007" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of using different indirect techniques on the calculation of reference intervals: observational study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Yang" 1 => "Z. Su" 2 => "R. Mu" 3 => "Y. Diao" 4 => "X. Zhang" 5 => "Y. Liu" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "J Med Internet Res" "fecha" => "2023" "paginaInicial" => "25" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0008" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Current status and challenges in establishing reference intervals based on real-world data" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S. Ma" 1 => "J. Yu" 2 => "X. Qin" 3 => "J Liu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/10408363.2023.2195496" "Revista" => array:6 [ "tituloSerie" => "Crit Rev Clin Lab Sci" "fecha" => "2023" "volumen" => "60" "paginaInicial" => "427" "paginaFinal" => "441" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/37038925" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0009" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ERICA: prevalences of hypertension and obesity in Brazilian adolescents" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.V. Bloch" 1 => "C.H. Klein" 2 => "M. Szklo" 3 => "M.C. Kuschnir" 4 => "A. Abreu G de" 5 => "L.A. Barufaldi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Rev Saude Publica" "fecha" => "2016" "volumen" => "50" "paginaInicial" => "S9" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0010" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Population-based studies on the epidemiology of insulin resistance in children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M.P. Van Der Aa" 1 => "S. Fazeli Farsani" 2 => "C.A. Knibbe" 3 => "A. De Boer" 4 => "M.M Van Der Vorst" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "J Diabetes Res" "fecha" => "2015" "volumen" => "2015" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0011" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Insulin resistance of puberty" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.M. Kelsey" 1 => "P.S. Zeitler" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s11892-016-0751-5" "Revista" => array:5 [ "tituloSerie" => "Curr Diab Rep" "fecha" => "2016" "volumen" => "16" "paginaInicial" => "64" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27179965" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0012" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Childhood and adolescent obesity: a review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A.R. Kansra" 1 => "S. Lakkunarajah" 2 => "M.S. Jay" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Front Pediatr" "fecha" => "2021" "volumen" => "8" ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0013" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The study of cardiovascular risk in adolescents - ERICA: rationale, design and sample characteristics of a national survey examining cardiovascular risk factor profile in Brazilian adolescents" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.V. Bloch" 1 => "M. Szklo" 2 => "M.C.C. Kuschnir" 3 => "G. De Azevedo Abreu" 4 => "L.A. Barufaldi" 5 => "C.H. Klein" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12889-015-1442-x" "Revista" => array:5 [ "tituloSerie" => "BMC Public Health" "fecha" => "2015" "volumen" => "15" "paginaInicial" => "94" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25880653" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0014" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Blood sampling frequency as a proxy for comorbidity indices when identifying patient samples for review of reference intervals" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S. Lykkeboe" 1 => "S.L. Andersen" 2 => "C.G. Nielsen" 3 => "P. Vestergaard" 4 => "P.A. Christensen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1515/cclm-2021-0987" "Revista" => array:6 [ "tituloSerie" => "Clin Chem Lab Med" "fecha" => "2022" "volumen" => "60" "paginaInicial" => "252" "paginaFinal" => "260" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34856091" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0015" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A simple method of resolution of a distribution into Gaussian components" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "C.G. Bhattacharya" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Biometrics" "fecha" => "1967" "volumen" => "23" "paginaInicial" => "115" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6050463" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0016" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The IFCC recommendation on estimation of reference intervals. The RefVal program" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "H.E. Solberg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1515/CCLM.2004.121" "Revista" => array:6 [ "tituloSerie" => "Clin Chem Lab Med" "fecha" => "2004" "volumen" => "42" "paginaInicial" => "710" "paginaFinal" => "714" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15327004" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0017" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiovascular actions of insulin" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R. Muniyappa" 1 => "M. Montagnani" 2 => "K.K. Koh" 3 => "M.J. Quon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/er.2007-0006" "Revista" => array:6 [ "tituloSerie" => "Endocr Rev" "fecha" => "2007" "volumen" => "28" "paginaInicial" => "463" "paginaFinal" => "491" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17525361" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0018" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Indirectly determined hematology reference intervals for pediatric patients in Berlin and Brandenburg" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I. Mrosewski" 1 => "T. Dähn" 2 => "J. Hehde" 3 => "E. Kalinowski" 4 => "I. Lindner" 5 => "T.M. Meyer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1515/cclm-2021-0853" "Revista" => array:6 [ "tituloSerie" => "Clin Chem Lab Med" "fecha" => "2022" "volumen" => "60" "paginaInicial" => "408" "paginaFinal" => "432" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34904427" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0019" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Paediatric reference intervals for ionised calcium – a data mining approach" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J.Z Yong Chung" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Chem Lab Med" "fecha" => "2021" "volumen" => "59" "paginaInicial" => "e271" "paginaFinal" => "e273" ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0020" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Indirectly determined reference intervals for automated white blood cell differentials of pediatric patients in Berlin and Brandenburg" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I. Mrosewski" 1 => "T. Dähn" 2 => "J. Hehde" 3 => "E. Kalinowski" 4 => "I. Lindner" 5 => "T.M. Meyer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1515/cclm-2022-1265" "Revista" => array:6 [ "tituloSerie" => "Clin Chem Lab Med" "fecha" => "2023" "volumen" => "61" "paginaInicial" => "1116" "paginaFinal" => "1122" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36669090" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0021" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An indirect data-mining approach to standardise paediatric serum phosphate reference intervals in Wales" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Rodham" 1 => "S. Zouwail" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Chem Lab Med" "fecha" => "2023" "volumen" => "62" "paginaInicial" => "e19" "paginaFinal" => "e21" ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0022" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Closing the gaps in pediatric laboratory reference intervals: a CALIPER database of 40 biochemical markers in a healthy and multiethnic population of children" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.A. Colantonio" 1 => "L. Kyriakopoulou" 2 => "M.K. Chan" 3 => "C.H. Daly" 4 => "D. Brinc" 5 => "A.A. Venner" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Chem" "fecha" => "2012" "volumen" => "58" "paginaInicial" => "854" "paginaFinal" => "868" ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0023" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Complex reference value distributions and partitioned reference intervals across the pediatric age range for 14 specialized biochemical markers in the CALIPER cohort of healthy community children and adolescents" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Kelly" 1 => "J.E. Raizman" 2 => "V. Bevilacqua" 3 => "M.K. Chan" 4 => "Y. Chen" 5 => "F. Quinn" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cca.2015.08.020" "Revista" => array:6 [ "tituloSerie" => "Clin Chim Acta" "fecha" => "2015" "volumen" => "450" "paginaInicial" => "196" "paginaFinal" => "202" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26310965" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0024" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "CLSI-based transference of the CALIPER database of pediatric reference intervals from Abbott to Beckman, Ortho, Roche and Siemens Clinical Chemistry Assays: direct validation using reference samples from the CALIPER cohort" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.P. Estey" 1 => "A.H. Cohen" 2 => "D.A. Colantonio" 3 => "M.K. Chan" 4 => "T.B. Marvasti" 5 => "E. Randell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clinbiochem.2013.04.001" "Revista" => array:6 [ "tituloSerie" => "Clin Biochem" "fecha" => "2013" "volumen" => "46" "paginaInicial" => "1197" "paginaFinal" => "1219" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23578738" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0025" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The importance of correct stratifications when comparing directly and indirectly estimated reference intervals" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R. Haeckel" 1 => "W. Wosniok" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Chem Lab Med" "fecha" => "2021" "volumen" => "59" "paginaInicial" => "1628" "paginaFinal" => "1633" ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0026" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biological variables influencing the estimation of reference limits" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.K. Özçürümez" 1 => "R. Haeckel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/00365513.2018.1471617" "Revista" => array:6 [ "tituloSerie" => "Scand J Clin Lab Invest" "fecha" => "2018" "volumen" => "78" "paginaInicial" => "337" "paginaFinal" => "345" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29764232" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0027" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Application of the Hoffmann, Bhattacharya, nonparametric test, and Q-Q plot methods for establishing reference intervals from laboratory databases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C. Yang" 1 => "L. Lang" 2 => "S. Wang" 3 => "H. Fang" 4 => "H. Chen" 5 => "Q. Xie" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clinbiochem.2022.12.016" "Revista" => array:6 [ "tituloSerie" => "Clin Biochem" "fecha" => "2023" "volumen" => "113" "paginaInicial" => "9" "paginaFinal" => "16" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36587756" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0028" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Utilization of five data mining algorithms combined with simplified preprocessing to establish reference intervals of thyroid-related hormones for non-elderly adults" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Zhong" 1 => "C. Ma" 2 => "L. Hou" 3 => "Y. Yin" 4 => "F. Zhao" 5 => "Y. Hu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12874-023-01898-5" "Revista" => array:5 [ "tituloSerie" => "BMC Med Res Methodol" "fecha" => "2023" "volumen" => "23" "paginaInicial" => "108" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/37131135" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0029" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Validation and comparison of five data mining algorithms using big data from clinical laboratories to establish reference intervals of thyroid hormones for older adults" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Ma" 1 => "Y. Zou" 2 => "L. Hou" 3 => "Y. Yin" 4 => "F. Zhao" 5 => "Y. Hu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clinbiochem.2022.05.008" "Revista" => array:6 [ "tituloSerie" => "Clin Biochem" "fecha" => "2022" "volumen" => "107" "paginaInicial" => "40" "paginaFinal" => "49" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35636495" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/00217557/0000010000000005/v1_202408020453/S0021755724000421/v1_202408020453/en/main.assets" "Apartado" => array:4 [ "identificador" => "10179" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/00217557/0000010000000005/v1_202408020453/S0021755724000421/v1_202408020453/en/main.pdf?idApp=UINPBA000049&text.app=https://jped.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755724000421?idApp=UINPBA000049"]

Statistics

Original article

Monica D.C. Freirea,

Corresponding author

freire5@yahoo.com

Corresponding author.

, Paulo R.T.P. Diasb,c,d, Thiago S.P. Souzae, Caio K. Hirosef, Paula B.M.C. Araujog, Mario F.T. Nevesh

a Universidade do Estado do Rio de Janeiro, Pós Graduação em Ciências Médicas, Rio de Janeiro, RJ, Brazil

b Universidade Federal Fluminense, Instituto de Saúde Coletiva, Departamento de Epidemiologia e Bioestatística, Niterói, RJ, Brazil

c Instituto de Ensino e Pesquisa DASA, São Paulo, SP, Brazil

d Universidade do Estado do Rio de Janeiro, Núcleo de Estudos e Pesquisas em Atenção ao Uso de Drogas, Rio de Janeiro, RJ, Brazil

e Universidade do Estado do Rio de Janeiro, Instituto de Matemática e Estatística, Rio de Janeiro, RJ, Brazil

f DASA, Analytics Department, São Paulo, SP, Brazil

g Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Pós-graduação em Endocrinologia, Rio de Janeiro, RJ, Brazil

h Universidade do Estado do Rio de Janeiro, Faculdade de Ciências Médicas, Rio de Janeiro, RJ, Brazil

Read

1024

Times
was read the article

376

Total PDF

648

Total HTML

Share statistics

 array:23 [
  "pii" => "S0021755724000421"
  "issn" => "00217557"
  "doi" => "10.1016/j.jped.2024.03.009"
  "estado" => "S300"
  "fechaPublicacion" => "2024-09-01"
  "aid" => "1278"
  "copyright" => "Sociedade Brasileira de Pediatria"
  "copyrightAnyo" => "2024"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "fla"
  "cita" => "J Pediatr &#40;Rio J&#41;. 2024;100:512-8"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:1 [
    "total" => 0
  ]
  "itemSiguiente" => array:17 [
    "pii" => "S0021755724000433"
    "issn" => "00217557"
    "doi" => "10.1016/j.jped.2024.03.010"
    "estado" => "S300"
    "fechaPublicacion" => "2024-09-01"
    "aid" => "1279"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "fla"
    "cita" => "J Pediatr &#40;Rio J&#41;. 2024;100:519-26"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:11 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Quality of life of families and siblings of children with cerebral palsy treated at a reference neurorehabilitation center in Brazil"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "519"
          "paginaFinal" => "526"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Bruno Leonardo Scofano Dias, Maura Calixto Cecherelli de Rodrigues, Jos&#233; Luiz Muniz Bandeira Duarte"
          "autores" => array:3 [
            0 => array:2 [
              "nombre" => "Bruno Leonardo Scofano"
              "apellidos" => "Dias"
            ]
            1 => array:2 [
              "nombre" => "Maura Calixto Cecherelli"
              "apellidos" => "de Rodrigues"
            ]
            2 => array:2 [
              "nombre" => "Jos&#233; Luiz Muniz Bandeira"
              "apellidos" => "Duarte"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755724000433?idApp=UINPBA000049"
    "url" => "/00217557/0000010000000005/v1_202408020453/S0021755724000433/v1_202408020453/en/main.assets"
  ]
  "itemAnterior" => array:17 [
    "pii" => "S0021755724000366"
    "issn" => "00217557"
    "doi" => "10.1016/j.jped.2024.03.006"
    "estado" => "S300"
    "fechaPublicacion" => "2024-09-01"
    "aid" => "1273"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "fla"
    "cita" => "J Pediatr &#40;Rio J&#41;. 2024;100:505-11"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Clinical significance and different strategies for re-elevation of plasma EBV-DNA during treatment in pediatric EBV-associated hemophagocytic lymphohistiocytosis"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "505"
          "paginaFinal" => "511"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "fig0001"
          "etiqueta" => "Figure 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 2066
              "Ancho" => 3175
              "Tamanyo" => 382542
            ]
          ]
          "detalles" => array:1 [
            0 => array:3 [
              "identificador" => "alt0001"
              "detalle" => "Fig "
              "rol" => "short"
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Different time points for monitoring EBV-DNA during treatment&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Wenzhi Zhang, Yun Peng, Yining Qiu, Li Cheng, Yuhong Yin, Ying Li, Lizhen Zhao, Xiaoyan Wu"
          "autores" => array:8 [
            0 => array:2 [
              "nombre" => "Wenzhi"
              "apellidos" => "Zhang"
            ]
            1 => array:2 [
              "nombre" => "Yun"
              "apellidos" => "Peng"
            ]
            2 => array:2 [
              "nombre" => "Yining"
              "apellidos" => "Qiu"
            ]
            3 => array:2 [
              "nombre" => "Li"
              "apellidos" => "Cheng"
            ]
            4 => array:2 [
              "nombre" => "Yuhong"
              "apellidos" => "Yin"
            ]
            5 => array:2 [
              "nombre" => "Ying"
              "apellidos" => "Li"
            ]
            6 => array:2 [
              "nombre" => "Lizhen"
              "apellidos" => "Zhao"
            ]
            7 => array:2 [
              "nombre" => "Xiaoyan"
              "apellidos" => "Wu"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755724000366?idApp=UINPBA000049"
    "url" => "/00217557/0000010000000005/v1_202408020453/S0021755724000366/v1_202408020453/en/main.assets"
  ]
  "en" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
    "titulo" => "Insulin reference intervals in Brazilian adolescents by direct and indirect approaches&#58; validation of a data mining method from laboratory data"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "512"
        "paginaFinal" => "518"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Monica D&#46;C&#46; Freire, Paulo R&#46;T&#46;P&#46; Dias, Thiago S&#46;P&#46; Souza, Caio K&#46; Hirose, Paula B&#46;M&#46;C&#46; Araujo, Mario F&#46;T&#46; Neves"
        "autores" => array:6 [
          0 => array:4 [
            "nombre" => "Monica D&#46;C&#46;"
            "apellidos" => "Freire"
            "email" => array:1 [
              0 => "freire5@yahoo.com"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0001"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0001"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Paulo R&#46;T&#46;P&#46;"
            "apellidos" => "Dias"
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0002"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0003"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0004"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Thiago S&#46;P&#46;"
            "apellidos" => "Souza"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">e</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Caio K&#46;"
            "apellidos" => "Hirose"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">f</span>"
                "identificador" => "aff0006"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Paula B&#46;M&#46;C&#46;"
            "apellidos" => "Araujo"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">g</span>"
                "identificador" => "aff0007"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "Mario F&#46;T&#46;"
            "apellidos" => "Neves"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">h</span>"
                "identificador" => "aff0008"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:8 [
          0 => array:3 [
            "entidad" => "Universidade do Estado do Rio de Janeiro&#44; P&#243;s Gradua&#231;&#227;o em Ci&#234;ncias M&#233;dicas&#44; Rio de Janeiro&#44; RJ&#44; Brazil"
            "etiqueta" => "a"
            "identificador" => "aff0001"
          ]
          1 => array:3 [
            "entidad" => "Universidade Federal Fluminense&#44; Instituto de Sa&#250;de Coletiva&#44; Departamento de Epidemiologia e Bioestat&#237;stica&#44; Niter&#243;i&#44; RJ&#44; Brazil"
            "etiqueta" => "b"
            "identificador" => "aff0002"
          ]
          2 => array:3 [
            "entidad" => "Instituto de Ensino e Pesquisa DASA&#44; S&#227;o Paulo&#44; SP&#44; Brazil"
            "etiqueta" => "c"
            "identificador" => "aff0003"
          ]
          3 => array:3 [
            "entidad" => "Universidade do Estado do Rio de Janeiro&#44; N&#250;cleo de Estudos e Pesquisas em Aten&#231;&#227;o ao Uso de Drogas&#44; Rio de Janeiro&#44; RJ&#44; Brazil"
            "etiqueta" => "d"
            "identificador" => "aff0004"
          ]
          4 => array:3 [
            "entidad" => "Universidade do Estado do Rio de Janeiro&#44; Instituto de Matem&#225;tica e Estat&#237;stica&#44; Rio de Janeiro&#44; RJ&#44; Brazil"
            "etiqueta" => "e"
            "identificador" => "aff0005"
          ]
          5 => array:3 [
            "entidad" => "DASA&#44; Analytics Department&#44; S&#227;o Paulo&#44; SP&#44; Brazil"
            "etiqueta" => "f"
            "identificador" => "aff0006"
          ]
          6 => array:3 [
            "entidad" => "Universidade Federal do Rio de Janeiro&#44; Faculdade de Medicina&#44; P&#243;s-gradua&#231;&#227;o em Endocrinologia&#44; Rio de Janeiro&#44; RJ&#44; Brazil"
            "etiqueta" => "g"
            "identificador" => "aff0007"
          ]
          7 => array:3 [
            "entidad" => "Universidade do Estado do Rio de Janeiro&#44; Faculdade de Ci&#234;ncias M&#233;dicas&#44; Rio de Janeiro&#44; RJ&#44; Brazil"
            "etiqueta" => "h"
            "identificador" => "aff0008"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0001"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:8 [
        "identificador" => "fig0001"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 4417
            "Ancho" => 3344
            "Tamanyo" => 527479
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0001"
            "detalle" => "Fig "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Plot of the Bhattacharya method applied to data-mined LIS data base &#40;DB2&#41;&#44; per age and sex partition&#46; A&#44; Female 12 and 13 years-old&#59; B&#44; Female 14 years-old&#59; C&#44; Female 15 years-old&#59; D&#44; Female 16 and 17 years-old&#59; E&#44; Male 12 to 14 years-old&#59; F&#44; Male 15 years-old&#59; G&#44; Male 16 and 17 years-old&#46; Linear region represents the distribution of &#8220;healthy&#8221; individuals and RI are determined by the extension of the linear region of the &#8220;healthy&#8221; group&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0007">Introduction</span><p id="para0006" class="elsevierStylePara elsevierViewall">Reference intervals &#40;RI&#41; for laboratory tests are fundamental tools in clinical practice as they provide a critical framework for assessing and interpreting laboratory results&#46; By comparing a patient&#39;s values to these predefined intervals&#44; healthcare professionals can detect abnormalities&#44; diagnose diseases&#44; and make informed decisions regarding treatment and patient care&#46; Hence&#44; appropriately defined reference values are of vital importance&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a></p><p id="para0007" class="elsevierStylePara elsevierViewall">Every laboratory should establish RI suitable for its specific service populations&#44; according to the International Federation of Clinical Chemistry &#40;IFCC&#41; Clinical Laboratory Standards Institute &#40;CLSI&#41;&#44; since RI might be affected by race&#44; age&#44; sex&#44; region&#44; and other factors&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a> This partitioning is of utmost importance in pediatrics&#44; as physiological advances after birth and during adolescence result in changes in many laboratory analytes&#46;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a> Therefore&#44; the use of wide age groups or missing sex grouping in adolescence can be intrinsically associated with inaccuracy&#46;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a></p><p id="para0008" class="elsevierStylePara elsevierViewall">The determination of RI can be done through direct and indirect methods&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a> IFCC&#44; to this day&#44; considers the <span class="elsevierStyleItalic">a priori</span> direct method as the gold standard&#44; but it has considerable drawbacks&#44; such as difficulty in recruiting sufficient reference individuals&#59; selection bias in small-sample data&#59; and time&#44; labor&#44; and financial costs&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> In addition&#44; for special groups&#44; such as in pediatric population&#44; it is difficult to obtain a large number of apparently healthy individuals&#46; Transference of RI from different populations &#8211; an alternative to the determination of one&#39;s laboratory own RI - may result in a marked variation of sample classification&#44; affecting diagnosis and treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a></p><p id="para0009" class="elsevierStylePara elsevierViewall">As an alternative to clinical studies&#44; the indirect approach&#44; determines RI from data mined from existing laboratory datasets by calculation through various mathematical methods available&#46;<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a> Indirect methods may be more feasible to determine RI specific to local populations&#44; especially appropriate in vulnerable populations&#44; where ethical considerations and practical problems often hinder the recruiting of sufficient numbers of healthy volunteers&#46;</p><p id="para0010" class="elsevierStylePara elsevierViewall">With the advent of medical big data&#44; the use of indirect methods based on data sets previously obtained from clinical laboratories is promising&#46; The establishment of RI using indirect methods roughly involves data acquisition&#44; data cleaning&#44; transformation of skewed data&#44; elimination of outliers or error values&#44; and selection of appropriate statistical methods to calculate the reference limits &#40;RLs&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a></p><p id="para0011" class="elsevierStylePara elsevierViewall">Nowadays&#44; childhood obesity is an emerging problem&#46;<a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a> The rising prevalence of obesity is causing an increase in obesity-related complications such as insulin resistance&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a> Hyperinsulinemia is a normal physiological state during puberty&#44;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a> but children with obesity can have abnormally high fasting blood insulin &#40;FBI&#41; levels&#46;<a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a></p><p id="para0012" class="elsevierStylePara elsevierViewall">The gold standard for the assessment of IR is the hyperinsulinemic euglycemic clamp&#44; which is invasive&#44; expensive&#44; and complex to use in the daily clinical practice&#46;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a> Therefore&#44; the most common surrogate markers of IR are the fasting plasma insulin and the homeostasis model assessment insulin resistance &#40;HOMA-IR&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a></p><p id="para0013" class="elsevierStylePara elsevierViewall">The aim of this study was to determine RI for FBI in Brazilian adolescents - by <span class="elsevierStyleItalic">a posteriori</span> direct approach using the ERICA Study database<a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a> and by an indirect approach&#44; using LIS outpatient data mining and Bhattacharya method &#8211; and&#44; by compare their results&#44; evaluate the data mining indirectly determined RI&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0008">Materials and methods</span><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0009"><span class="elsevierStyleItalic">Study design and subjects</span></span><p id="para0014" class="elsevierStylePara elsevierViewall">The study determined RI for FBI from 2 different databases of Brazilian adolescents&#44; from 12 years-old to 17 years&#44; 11 months&#44; and 30 days old &#40;from now called 17 years-old&#41;&#44; according to age and sex partitions&#46; DB1 consists of a reference population of healthy individuals&#44; from 124 Brazilian cities&#44; recruited from January 2013 to November 2014&#44;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a> as part of a large population study on cardiovascular risk in adolescence&#44; the ERICA study&#46;<a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a> DB2 was obtained by data mining the laboratory information system &#40;LIS&#41; of a large commercial laboratory&#44; from outpatients whose samples were directly drawn by the laboratory&#44; from four States and the Federal District of Brazil&#44; from January 2011 to June 2015&#46;</p><p id="para0015" class="elsevierStylePara elsevierViewall">Exclusion criteria for DB1 were fasting glucose equal or higher than 126 mg&#47;dL&#44; glycated hemoglobin equal or higher than 6&#46;5&#37;&#44; self-reported pregnancy or suspicion of pregnancy&#44; self-reported acute or chronic illness&#44; and regular prescription drug use&#46; DB2 included individuals only once&#44;<a class="elsevierStyleCrossRef" href="#bib0014"><span class="elsevierStyleSup">14</span></a> based on the first FBI determination observed on the database timeline&#44; and excluded females with a positive BHCG testing&#44; anytime 9 months prior to the FBI test result observed&#46;</p><p id="para0016" class="elsevierStylePara elsevierViewall">Outliers were removed from both data sets prior to partitioning&#44; after data log transformation&#44; by the Chauvenet criteria&#46;</p><p id="para0017" class="elsevierStylePara elsevierViewall">Age and sex partitions were calculated on DB1 and used as partitions on DB2 as well&#46;</p><p id="para0018" class="elsevierStylePara elsevierViewall">The authors used the RefVal software to perform <span class="elsevierStyleItalic">a posteriori</span> direct method calculation of RI for FBI for DB1<span class="elsevierStyleSup">2</span>&#44; and Bhattacharya indirect method obtain RI from DB2&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0016"><span class="elsevierStyleSup">16</span></a></p><p id="para0019" class="elsevierStylePara elsevierViewall">Based on the direct and indirect RI obtained&#44; the authors evaluated the rates of agreement of RI upper limits &#40;URL&#41; in diagnosing elevated FBI levels on individuals in DB1&#46;</p><p id="para0020" class="elsevierStylePara elsevierViewall">FBI analyses were performed by the same commercial laboratory on both databases&#44; on 5 laboratory sites throughout Brazil using standard operations&#44; on Roche Diagnostics electrochemiluminescence platform&#46; The laboratory is accredited by the Clinical Laboratories Accreditation Program of the Brazilian Society of Clinical Pathology and Laboratory Medicine&#46; Standard pre-analytical methods and materials were determined and instructed by the same laboratory for the collection and sample handling on both databases&#46;</p><p id="para0021" class="elsevierStylePara elsevierViewall">This study was approved by the Ethics Committee of the Pedro Ernesto University Hospital &#8211; Universidade do Estado do Rio de Janeiro&#44; under the document number&#58; 2&#46;970&#46;023&#46; Data were analyzed using R software 4&#46;2&#46;3&#44; RefVal software and Microsoft Excel - Office 365&#46;</p><p id="para0022" class="elsevierStylePara elsevierViewall">FBI levels and RI were presented in &#181;IU&#47;mL&#46; RI represents the values between the lower and upper reference limits&#46; Standard deviations are also available per partition&#46;</p></span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0010">Age and sex partitions</span><p id="para0023" class="elsevierStylePara elsevierViewall">After data log-transformation&#44; initial age and sex partitions were defined arbitrarily using DB1&#58; males 12&#44; 13&#44; 14&#44; 15&#44; 16&#44; and 17 years-old&#44; and female 12&#44; 13&#44; 14&#44; 15&#44; 16&#44; and 17 years-old&#46; Then the authors used the Bartlett test to approach the homogeneity of variances for each group &#40;transformed data&#41;&#46; Since variance results were not homogeneous&#44; the authors used the Kruskal-Wallis test to evaluate if there were significant differences in FBI DB1 measurements on age and sex groups&#46; As they were present&#44; the authors performed multiple pairwise paired <span class="elsevierStyleItalic">t</span>-tests between the levels of the within-subject groups&#46; P-values are adjusted using the Bonferroni multiple-testing correction method&#46; Groups with no statistically significant differences were merged into a single partition&#46;</p><p id="para0024" class="elsevierStylePara elsevierViewall">The authors then applied the DB1 partitions&#44; considered the reference sample obtained by individual interview and physical examination for the gold standard RI calculation method&#44; at DB1&#44; once DB1 is the data set with the highest percentage of &#8220;healthy&#8221; subjects&#46; This allowed comparisons between DB1 and DB2 RI&#44; per partition&#46;</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0011">Direct approach RI</span><p id="para0025" class="elsevierStylePara elsevierViewall">DB1 was used for the determination of RI by the <span class="elsevierStyleItalic">a posteriori</span> direct method&#44; for each age and sex group&#44; as described by IFCC C28-A3c Guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a> The authors performed RI direct estimates of log-transformed FBI levels&#44; after outlier exclusion&#44; per partition&#44; by parametric and bootstrap methods&#46; RI represents the central 95 &#37; range&#46; Lower and upper reference limits correspond to the 2&#46;5th and 97&#46;5th percentiles&#44; respectively&#46; The authors additionally determined their 90 &#37; confidence intervals &#40;90 &#37; CI&#41;&#46;</p></span><span id="sec0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0012">Indirect approach RI</span><p id="para0026" class="elsevierStylePara elsevierViewall">After data log transformation&#44; subsequent outlier removal and partitioning&#44; DB2 was used for the indirect determination of RI&#44; for each age and sex partition&#44; by a mathematical mixture separation method&#44; the Bhattacharya method&#44; widely used and described on literature&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a> In brief&#44; a graphical method is used to identify an underlying Gaussian distribution amongst other data&#44; which may include an &#8220;unhealthy&#8221; dataset of individuals&#46;</p></span><span id="sec0007" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0013"><span class="elsevierStyleItalic">Validation of the indirectly determined fasting blood insulin URL</span></span><span id="sec0008" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0014">Comparison of the diagnosis of elevated FBI of DB1 individuals</span><p id="para0027" class="elsevierStylePara elsevierViewall">The authors identified the diagnosis of elevated FBI by the indirectly determined URL on every subject of DB1 and compared it to the diagnosis obtained when using the directly determined 90 &#37; CI URL&#46; The question addressed is if a subject&#39;s FBI measurement would have different clinical interpretations when compared to the highest probabilistic gold-standard URL - in this case&#44; the higher limit of 90 &#37; CI of the direct URL- and when compared to the indirectly determined URL&#46;</p><p id="para0028" class="elsevierStylePara elsevierViewall">Four groups of results were determined according to the diagnostic agreement&#44; for sex and age partitions&#58; FBI below DB1 90 &#37; CI URL and DB2 URL&#59; B&#58; FBI above DB1 90 &#37; CI URL and below DB2 URL&#59; C&#58; FBI below DB1 90 &#37; CI URL and above DB2 URL&#59; D&#58; FBI above DB1 90 &#37; CI URL and DB2 URL&#46; This analysis was used to evaluate the consistency of the decision impact caused by the indirectly determined URL&#44; compared to the directly determined URL&#46;</p></span></span></span><span id="sec0009" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0015">Results</span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0016"><span class="elsevierStyleItalic">Database population distribution and FBI level results</span></span><p id="para0029" class="elsevierStylePara elsevierViewall">DB1&#44; derived from the ERICA Study&#44; consisted of 29&#44;200 individuals from 12 to 17 years old&#44; after exclusion criteria application&#46; Outliers removed represented 1&#46;2 &#37; &#40;453&#41; of the sample&#44; therefore 28&#44;747 individuals were selected for partitioning and subsequent RI determination&#46; Most of the participants were female &#40;<span class="elsevierStyleItalic">n</span> &#61; 16&#44;919&#59; 58&#46;85 &#37;&#41;&#46; Population distribution after removal of outliers&#44; and before partitioning was not normal&#46; Age and sex groups determined were&#58; female 12 and 13 years-old &#40;<span class="elsevierStyleItalic">n</span> &#61; 4775&#41;&#59; female 14 years-old &#40;<span class="elsevierStyleItalic">n</span> &#61; 3035&#41;&#59; female 15 years-old &#40;<span class="elsevierStyleItalic">n</span> &#61; 3164&#41;&#59; female 16 and 17 years-old &#40;<span class="elsevierStyleItalic">n</span> &#61; 5945&#41;&#59; male 12 to 14 years-old &#40;<span class="elsevierStyleItalic">n</span> &#61; 5451&#41;&#59; male 15 years-old &#40;<span class="elsevierStyleItalic">n</span> &#61; 2315&#41;&#59; and&#44; male 16 and 17 years-old &#40;<span class="elsevierStyleItalic">n</span> &#61; 4062&#41;&#46;</p><p id="para0030" class="elsevierStylePara elsevierViewall">DB2 consisted of 5895 adolescents&#44; after exclusion criteria&#46; The distribution prior to the removal of outliers and partitioning was not normal&#46; After log-transformation and removal of outliers &#40;<span class="elsevierStyleItalic">n</span> &#61; 532&#59; 8&#46;27 &#37;&#41;&#44; 3692 were female &#40;62&#46;6 &#37;&#41;&#46; Then&#44; age and sex partitions from DB1 were used to group DB2 subjects&#46;</p><p id="para0031" class="elsevierStylePara elsevierViewall">The mean FBI measurements &#8211; recalculated from the log-transformed results - were significantly higher in DB2&#44; on all groups&#46; <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a> shows the distribution characteristics and FBI measurements of both databases&#46;</p><elsevierMultimedia ident="tbl0001"></elsevierMultimedia></span><span id="sec0011" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0017"><span class="elsevierStyleItalic">Reference intervals for FBI in adolescents</span></span><p id="para0032" class="elsevierStylePara elsevierViewall">URL determined by Bhattacharya method &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Figure 1</a>&#41; were slightly lower than the 90 &#37; CI URL directly obtained on DB1&#44; except for group female 12 and 13 years-old&#46; &#40;24&#46;27 &#181;IU&#47;mL versus 22&#46;9 &#181;IU&#47;mL&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0002">Table 2</a> shows RI determined per age and sex group&#44; by both methods&#46;</p><elsevierMultimedia ident="fig0001"></elsevierMultimedia><elsevierMultimedia ident="tbl0002"></elsevierMultimedia></span><span id="sec0012" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0018"><span class="elsevierStyleItalic">Diagnostic agreement of elevated FBI between direct and indirect URL</span></span><p id="para0033" class="elsevierStylePara elsevierViewall">The directly determined 90 &#37; CI URL&#44; and the URL calculated by the Bhattacharya method were used to assess if the FBI level of each DB1 individual subject was considered elevated&#46; The authors observed high agreement rates for elevated FBI levels&#44; in all partitions &#40;<a class="elsevierStyleCrossRef" href="#tbl0003">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0003"></elsevierMultimedia></span></span><span id="sec0013" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0019">Discussion</span><p id="para0034" class="elsevierStylePara elsevierViewall">Fasting blood insulin level is an important biomarker for insulin resistance observed in overweight&#44; obesity and metabolic syndrome&#44; conditions related to cardiovascular risk&#46;<a class="elsevierStyleCrossRef" href="#bib0017"><span class="elsevierStyleSup">17</span></a> Healthy adolescents respond to normal metabolic changes with increased insulin resistance&#46; Therefore&#44; FBI levels physiologically also increase in pubertal youngsters&#46;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a> The present findings on the FBI RI in different groups of adolescents&#44; regardless of the methodology used&#44; corroborate this physiological knowledge&#46; A systematic review conducted by Van der Aa et al&#46; showed insulin resistance prevalence rates from 3&#46;1&#37; to 44&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a> The authors used six different methods to define insulin resistance and a variety of cut-offs&#44; leaving a gap of consensus regarding RI for FBI in pediatrics&#46; This highlights the importance of understanding the URL of blood insulin levels in adolescents to properly address pathological insulin resistance in this population&#46;</p><p id="para0035" class="elsevierStylePara elsevierViewall">In recent years&#44; several studies on pediatric RI of multiple analytes using both direct and indirect approaches have been published&#46;<a class="elsevierStyleCrossRefs" href="#bib0018"><span class="elsevierStyleSup">18-22</span></a> Large multicentric studies attempted to determine pediatric RI to several analytes&#46; CALIPER Study by Colantonio et al&#46; presented fasting insulin results from 190 individuals between 6 and under 19 years old&#44; but not its RI&#46;<a class="elsevierStyleCrossRef" href="#bib0022"><span class="elsevierStyleSup">22</span></a> Kelly et al&#46; published <span class="elsevierStyleItalic">a posteriori</span> direct calculated RI for insulin from 240 subjects from 11 to 19 years-old&#44; without further age or sex partitions&#44; and observed extremely high URL obtained by Abbott Architect platform&#46;<a class="elsevierStyleCrossRef" href="#bib0023"><span class="elsevierStyleSup">23</span></a> Later&#44; Adeli et al&#46; in a collaboration between The Canadian Health Measures Survey and CALIPER initiative&#44; were able to use insulin measurements processed on Centaur XP and Immulite 2000 platforms from 1700 adolescents from 11 to 19 years-old and proposed the same lower &#40;2&#46;1 &#181;IU&#47;mL&#41; and upper &#40;21&#46;8 &#181;IU&#47;mL&#41; limits for both boys and girls without additional age partitions&#46;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> However&#44; age and sex partitions are key to pubertal adolescents since insulin resistance varies according to Tanner stages in males and females&#46;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a> The present study&#44; on the other hand&#44; brings the novelty of establishing insulin RI addressing this issue&#46;</p><p id="para0036" class="elsevierStylePara elsevierViewall">It is known that uncertainties and differences between a reference population-derived RI and the local population served by a specific laboratory can affect the diagnostic accuracy if the laboratory simply verifies or transfers these RI to apply in other populations than the original one&#46;<a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a> Additionally&#44; accurate determination of RI&#44; directly or indirectly calculated&#44; and comparison between methods&#44; can be affected by biological variables that influence and demand appropriate group separation &#40;homogeneity&#44; age&#44; sex&#44; nutritional state&#44; ethnicity&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0026"><span class="elsevierStyleSup">26</span></a> Both RI estimation methods can lead to erroneous RI if stratification for variables is not performed properly&#46; Despite the Brazilian geographical broadness&#44; DB1 and DB2 samples in this study were analyzed on five sites of the same commercial laboratory&#44; by the same analytical platform &#40;Roche Diagnostics&#41; in order to optimize quality control and the use of similar standard operational procedures&#46; Also&#44; since the unknown fraction of the pathological distribution can affect the capability of separation of groups from DB2&#44; the authors calculated age and sex partitions from DB1&#44; which enrolled only healthy subjects after individual interview and examination&#44; and then applied them to DB2 calculations&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a> The large number of individuals enrolled in the ERICA Study not only allowed statistically calculated DB1 age and sex partitions but provided the highest number of adolescents for the direct calculation of FBI RI in the literature&#46;<a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a></p><p id="para0037" class="elsevierStylePara elsevierViewall">Mathematical indirect methods&#44; such as Bhattacharya and others&#44; can be calculated without the strict need to identify and exclude individuals according to signs of disease or to prefer individuals with signs of &#8220;good health&#8221;&#46; It uses mixed data sets that are mainly composed of healthy persons&#44; with some percentage of &#8220;diseased&#8221; ones &#40;less than 20&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a> The authors observed that mean FBI measurements were significantly higher on DB2 than DB1&#44; as it represents the expected mixture of &#8220;healthy&#8221; and &#8220;unhealthy&#8221; subjects&#46; Still&#44; efforts to exclude known potential &#8220;non-healthy&#8221; individuals can improve the quality of the indirect RI obtained and can be achieved by exclusion criteria&#44; such as&#58; eliminating inpatients and pregnant women&#59; using selected health records such as clinical history or laboratory findings&#59; eliminating subjects with more than one analyte measurement as an indication of ongoing disease investigation&#59; and by removal of outliers&#46;<a class="elsevierStyleCrossRef" href="#bib0014"><span class="elsevierStyleSup">14</span></a> However&#44; filtering algorithms may not be enough to accurately determine indirect RI&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a> Mathematical methods should be added to further separate and identify the subjacent unknown &#8220;non-diseased&#8221; population&#46; With the development of informatics technology and the availability of real-world big data&#44; various mathematical methods for RI determination were developed&#44; became more feasible and accurate and were compared in performance&#46;<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0027"><span class="elsevierStyleSup">27</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0028"><span class="elsevierStyleSup">28</span></a> Hoffmann&#44; Bhattacharya&#44; truncated minimum chi-square &#40;TMC&#41;&#44; and Kolmogorov-Smirnov distance &#40;kosmic&#41; indirect methods are the most widely used&#44; and performed accordingly&#44; in several studies&#46;<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0028"><span class="elsevierStyleSup">28</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0029"><span class="elsevierStyleSup">29</span></a></p><p id="para0038" class="elsevierStylePara elsevierViewall">In the present study&#44; regardless of the mean difference in insulin measurements&#44; the Bhattacharya method was able to separate the Gaussian distributed &#8220;healthy&#8221; individuals for the determination of accurate indirect RI&#46; This statement is validated by the similarity between DB1 and DB2 derived RI and the elevated diagnostic agreement rates for high FBI in all partitions&#46; The lowest diagnostic agreement for elevated FBI found was 97&#46;56&#37;&#46; These findings also indicate the accuracy of the indirect method used in this study&#46;</p><p id="para0039" class="elsevierStylePara elsevierViewall">To the best of our knowledge&#44; this is a novel study to determine age and sex FBI RI through direct and indirect methods&#44; for Brazilian adolescents&#44; and to evaluate the indirect outcomes compared to the established standards of the direct method&#46; These findings highlight the practicality&#44; feasibility&#44; cost-effectiveness&#44; and accuracy of employing the Bhattacharya indirect method&#44; facilitated by data mining of a large commercial LIS&#44; in determining RI in adolescents&#46; Significantly&#44; this indirect method proves to be a reliable alternative&#44; overcoming the inherent challenges associated with the conventional &#34;gold standard&#34; direct approach&#46; Further studies using various indirect methods to determine RI in Brazilian pediatric populations should be encouraged&#44; and further validations of the method in different analytes can be evaluated based on the large-scale ERICA study database&#46; In the context of the prevailing big data era&#44; Brazilian researchers are stimulated to contribute by presenting and publishing local RI through meticulous LIS data mining and indirect methodologies for local vulnerable populations&#44; such as children and older adults&#46;</p></span><span id="sec0014" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0020">Funding</span><p id="para0040" class="elsevierStylePara elsevierViewall">This research did not receive any funding from public&#44; commercial&#44; or not-for-profit organizations&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:8 [
        0 => array:3 [
          "identificador" => "xres2214786"
          "titulo" => "Abstract"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abss0001"
              "titulo" => "Objective"
            ]
            1 => array:2 [
              "identificador" => "abss0002"
              "titulo" => "Methods"
            ]
            2 => array:2 [
              "identificador" => "abss0003"
              "titulo" => "Results"
            ]
            3 => array:2 [
              "identificador" => "abss0004"
              "titulo" => "Conclusion"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1856799"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "sec0001"
          "titulo" => "Introduction"
        ]
        3 => array:3 [
          "identificador" => "sec0002"
          "titulo" => "Materials and methods"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0003"
              "titulo" => "Study design and subjects"
            ]
            1 => array:2 [
              "identificador" => "sec0004"
              "titulo" => "Age and sex partitions"
            ]
            2 => array:2 [
              "identificador" => "sec0005"
              "titulo" => "Direct approach RI"
            ]
            3 => array:2 [
              "identificador" => "sec0006"
              "titulo" => "Indirect approach RI"
            ]
            4 => array:3 [
              "identificador" => "sec0007"
              "titulo" => "Validation of the indirectly determined fasting blood insulin URL"
              "secciones" => array:1 [
                0 => array:2 [
                  "identificador" => "sec0008"
                  "titulo" => "Comparison of the diagnosis of elevated FBI of DB1 individuals"
                ]
              ]
            ]
          ]
        ]
        4 => array:3 [
          "identificador" => "sec0009"
          "titulo" => "Results"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0010"
              "titulo" => "Database population distribution and FBI level results"
            ]
            1 => array:2 [
              "identificador" => "sec0011"
              "titulo" => "Reference intervals for FBI in adolescents"
            ]
            2 => array:2 [
              "identificador" => "sec0012"
              "titulo" => "Diagnostic agreement of elevated FBI between direct and indirect URL"
            ]
          ]
        ]
        5 => array:2 [
          "identificador" => "sec0013"
          "titulo" => "Discussion"
        ]
        6 => array:2 [
          "identificador" => "sec0014"
          "titulo" => "Funding"
        ]
        7 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2023-11-29"
    "fechaAceptado" => "2024-03-15"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1856799"
          "palabras" => array:4 [
            0 => "Data mining"
            1 => "Insulin"
            2 => "Reference interval"
            3 => "Adolescent"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Objective</span><p id="spara008" class="elsevierStyleSimplePara elsevierViewall">To determine reference intervals &#40;RI&#41; for fasting blood insulin &#40;FBI&#41; in Brazilian adolescents&#44; 12 to 17 years old&#44; by direct and indirect approaches&#44; and to validate indirectly determined RI&#46;</p></span> <span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Methods</span><p id="spara009" class="elsevierStyleSimplePara elsevierViewall">Two databases were used for RI determination&#46; Database 1 &#40;DB1&#41;&#44; used to obtain RI through <span class="elsevierStyleItalic">a posteriori</span> direct method&#44; consisted of prospectively selected healthy individuals&#46; Database 2 &#40;DB2&#41; was retrospectively mined from an outpatient laboratory information system &#40;LIS&#41; used for the indirect method &#40;Bhattacharya method&#41;&#46;</p></span> <span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Results</span><p id="spara010" class="elsevierStyleSimplePara elsevierViewall">From DB1&#44; 29345 individuals were enrolled &#40;57&#46;65 &#37; female&#41; and seven age ranges and sex partitions were statistically determined according to mean FBI values&#58; females&#58; 12 and 13 years-old&#44; 14 years-old&#44; 15 years-old&#44; 16 and 17 years-old&#59; and males&#58; 12&#44; 13 and 14 years-old&#44; 15 years-old&#44; 16 and 17 years-old&#46; From DB2&#44; 5465 adolescents &#40;67&#46;5 &#37; female&#41; were selected and grouped according to DB1 partitions&#46; The mean FBI level was significantly higher in DB2&#44; on all groups&#46; The RI upper limit &#40;URL&#41; determined by Bhattacharya method was slightly lower than the 90 &#37; CI URL directly obtained on DB1&#44; except for group female 12 and 13 years old&#46; High agreement rates for diagnosing elevated FBI in all groups on DB1 validated indirect RI presented&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0005">Conclusion</span><p id="spara011" class="elsevierStyleSimplePara elsevierViewall">The present study demonstrates that Bhattacharya indirect method to determine FBI RI in adolescents can overcome some of the difficulties and challenges of the direct approach&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abss0001"
            "titulo" => "Objective"
          ]
          1 => array:2 [
            "identificador" => "abss0002"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abss0003"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abss0004"
            "titulo" => "Conclusion"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:1 [
        "nota" => "<p class="elsevierStyleNotepara" id="notep0001">Institution or service with which the work is associated for indexing in Index Medicus&#47;MEDLINE&#44; City&#44; Country&#58; Universidade do Estado do Rio de Janeiro&#44; Departamento de P&#243;s Gradua&#231;&#227;o em Ci&#234;ncias M&#233;dicas&#46; Rio de Janeiro &#8211; Brazil&#46;</p>"
      ]
    ]
    "multimedia" => array:4 [
      0 => array:8 [
        "identificador" => "fig0001"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 4417
            "Ancho" => 3344
            "Tamanyo" => 527479
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0001"
            "detalle" => "Fig "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Plot of the Bhattacharya method applied to data-mined LIS data base &#40;DB2&#41;&#44; per age and sex partition&#46; A&#44; Female 12 and 13 years-old&#59; B&#44; Female 14 years-old&#59; C&#44; Female 15 years-old&#59; D&#44; Female 16 and 17 years-old&#59; E&#44; Male 12 to 14 years-old&#59; F&#44; Male 15 years-old&#59; G&#44; Male 16 and 17 years-old&#46; Linear region represents the distribution of &#8220;healthy&#8221; individuals and RI are determined by the extension of the linear region of the &#8220;healthy&#8221; group&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0001"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0002"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spara003" class="elsevierStyleSimplePara elsevierViewall">FBI&#44; fasting blood insulin&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0001"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0002"></a><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">data base 1</th><a name="en0003"></a><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">data base 2</th><a name="en0004"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="top" scope="col">p value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><a name="en0005"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0006"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0007"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">FBI mean &#40;&#181;IU&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0008"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0009"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0010"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">FBI mean &#40;&#181;IU&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0011"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0013"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0015"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0017"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0019"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0021"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">12&#8211;13 yo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4775&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0023"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4&#46;85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0025"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">928&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8&#46;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0029"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">14 yo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3035&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0031"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">9&#46;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4&#46;68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0033"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">478&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0035"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">7&#46;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0036"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0037"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">15 yo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3164&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8&#46;97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0041"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">532&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0043"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8&#46;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0045"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">16&#8211;17 yo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0046"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5945&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8&#46;59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0049"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1754&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0050"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0051"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">7&#46;78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0053"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Males&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0055"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0057"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0061"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">12&#8211;14 yo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5451&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8&#46;43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0064"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4&#46;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0065"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1187&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0066"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0067"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0068"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0069"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">15 yo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0070"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2315&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0071"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">7&#46;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4&#46;51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0073"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">320&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0074"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0075"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8&#46;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0076"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0077"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">16&#8211;17 yo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0078"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4062&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0079"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">7&#46;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0080"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4&#46;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0081"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">696&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0082"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0083"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8&#46;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0084"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3612007.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara002" class="elsevierStyleSimplePara elsevierViewall">Age and sex partitions&#44; number of subjects and FBI central measures&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0002"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0003"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spara005" class="elsevierStyleSimplePara elsevierViewall">LRL&#44; lower reference limit&#59; URL&#44; upper reference limit&#59; LRL 90 &#37;CI&#44; lower reference limit 90 &#37; confidence interval&#59; URL 90 &#37;CI&#44; upper reference limit 90 &#37; confidence interval&#59; FBI&#44; fasting blood insulin&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0085"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0086"></a><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Data base 1 &#40;Direct&#41;</th><a name="en0087"></a><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Data base 2 &#40;Bhattacharya&#41;</th></tr><tr title="table-row"><a name="en0088"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0089"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">LRL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0090"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">LRL 90 &#37;CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0091"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">URL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0092"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">URL 90 &#37;CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0093"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">LRL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0094"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">URL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0095"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0096"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0097"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0098"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0099"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0100"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0101"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0102"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">12&#8211;13 years-old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0103"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0104"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2&#46;4&#8211;2&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0105"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">22&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0106"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">21&#46;7&#8211;22&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0107"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0108"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">24&#46;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0109"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">14 years-old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0110"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0111"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;9&#8211;2&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0112"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">21&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0113"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">20&#46;6&#8211;22&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0114"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0115"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">22&#46;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0116"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">15 years-old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0117"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0118"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2&#46;1&#8211;2&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0119"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">20&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0120"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">19&#46;9&#8211;21&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0121"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0122"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">19&#46;62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0123"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">16&#8211;17 years-old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0124"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0125"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;9&#8211;2&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0126"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">19&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0127"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">19&#46;1&#8211;20&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0128"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;96&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0129"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">19&#46;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0130"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Males&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0131"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0132"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0133"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0134"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0135"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0136"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0137"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">12&#8211;14 years-old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0138"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0139"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;9&#8211;2&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0140"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">20&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0141"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">20&#46;3&#8211;21&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0142"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0143"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">21&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0144"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">15 years-old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0145"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0146"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;5&#8211;2&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0147"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">20&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0148"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">19&#46;9&#8211;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0149"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0150"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">19&#46;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0151"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">16&#8211;17 years-old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0152"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0153"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;4&#8211;1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0154"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">19&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0155"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">18&#46;6&#8211;20&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0156"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0157"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16&#46;62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3612005.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara004" class="elsevierStyleSimplePara elsevierViewall">Reference intervals established by <span class="elsevierStyleItalic">a posteriori</span> direct method and indirect method &#40;Bhattacharya method&#41;&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0003"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0004"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spara007" class="elsevierStyleSimplePara elsevierViewall">A&#44; FBI below DB1 URL &#40;90 &#37; CI&#41; and DB2 URL&#59; B&#44; FBI above DB1 URL &#40;90 &#37; CI&#41; and below DB2 URL&#59; C&#44; FBI below DB1 URL &#40;90 &#37; CI&#41; and above DB2 URL&#59; D&#44; FBI above DB1 URL &#40;90 &#37; CI&#41; and DB2 URL&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0158"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0159"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0160"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0161"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0162"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0163"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0164"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">diagnostic agreement &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0165"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0166"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0167"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0168"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0169"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0170"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0171"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0172"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12&#8211;13 years-old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0173"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4675&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0174"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0175"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0176"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0177"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0178"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">99&#46;29 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0179"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14 years-old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0180"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2972&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0181"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0182"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0183"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0184"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0185"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">99&#46;93 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0186"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15 years-old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0187"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3068&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0188"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0189"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0190"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0191"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0192"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">98&#46;96 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0193"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16&#8211;17 years-old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0194"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5787&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0195"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0196"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0197"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">129&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0198"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0199"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">99&#46;51 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0200"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Males&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0201"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0202"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0203"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0204"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0205"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0206"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0207"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12&#8211;14 years-old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0208"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5321&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0209"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0210"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0211"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">117&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0212"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0213"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">99&#46;76 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0214"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15 years-old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0215"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2236&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0216"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0217"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0218"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0219"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0220"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">98&#46;57 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0221"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16&#8211;17 years-old&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0222"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3880&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0223"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0224"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0225"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0226"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0227"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">97&#46;56 &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3612006.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara006" class="elsevierStyleSimplePara elsevierViewall">Diagnostic agreement rates for elevated FBI per age and sex group&#44; at DB1&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "cebibsec1"
          "bibliografiaReferencia" => array:29 [
            0 => array:3 [
              "identificador" => "bib0001"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Recommendation for the review of biological reference intervals in medical laboratories"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Henny"
                            1 => "A&#46; Vassault"
                            2 => "G&#46; Boursier"
                            3 => "I&#46; Vukasovic"
                            4 => "P&#46; Mesko Brguljan"
                            5 => "M&#46; Lohmander"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Chem Lab Med"
                        "fecha" => "2016"
                        "volumen" => "54"
                        "paginaInicial" => "1893"
                        "paginaFinal" => "1900"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0002"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Wayne P&#46;C&#46; and LSI 2008&#46; CLSI&#46; Defining&#44; establishing&#44; and verifying reference intervals in the clinical laboratory&#59; Approved Guideline&#8212;Third Edition&#46; CLSI document C28-A3c&#46;"
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0003"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Age- and sex-specific dynamics in 22 hematologic and biochemical analytes from birth to adolescence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Zierk"
                            1 => "F&#46; Arzideh"
                            2 => "T&#46; Rechenauer"
                            3 => "R&#46; Haeckel"
                            4 => "W&#46; Rascher"
                            5 => "M&#46; Metzler"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1373/clinchem.2015.239731"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Chem"
                        "fecha" => "2015"
                        "volumen" => "61"
                        "paginaInicial" => "964"
                        "paginaFinal" => "973"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25967371"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0004"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Complex reference values for endocrine and special chemistry biomarkers across pediatric&#44; adult&#44; and geriatric ages&#58; establishment of robust pediatric and adult reference intervals on the basis of the Canadian health measures survey"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46; Adeli"
                            1 => "V&#46; Higgins"
                            2 => "M&#46; Nieuwesteeg"
                            3 => "J&#46;E&#46; Raizman"
                            4 => "Y&#46; Chen"
                            5 => "S&#46;L&#46; Wong"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1373/clinchem.2015.240523"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Chem"
                        "fecha" => "2015"
                        "volumen" => "61"
                        "paginaInicial" => "1063"
                        "paginaFinal" => "1074"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26044507"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Critical comments to a recent EFLM recommendation for the review of reference intervals"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "R&#46; Haeckel"
                            1 => "W&#46; Wosniok"
                            2 => "F&#46; Arzideh"
                            3 => "J&#46; Zierk"
                            4 => "E&#46; Gurr"
                            5 => "T&#46; Streichert"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1515/cclm-2016-1112"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Chem Lab Med"
                        "fecha" => "2017"
                        "volumen" => "55"
                        "paginaInicial" => "341"
                        "paginaFinal" => "347"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28151722"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0006"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Paediatric reference intervals are heterogeneous and differ considerably in the classification of healthy paediatric blood samples"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46;B&#46; Alnor"
                            1 => "P&#46;J&#46; Vinholt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00431-019-03377-w"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Pediatr"
                        "fecha" => "2019"
                        "volumen" => "178"
                        "paginaInicial" => "963"
                        "paginaFinal" => "971"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30997593"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0007"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of using different indirect techniques on the calculation of reference intervals&#58; observational study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Yang"
                            1 => "Z&#46; Su"
                            2 => "R&#46; Mu"
                            3 => "Y&#46; Diao"
                            4 => "X&#46; Zhang"
                            5 => "Y&#46; Liu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "J Med Internet Res"
                        "fecha" => "2023"
                        "paginaInicial" => "25"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0008"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current status and challenges in establishing reference intervals based on real-world data"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46; Ma"
                            1 => "J&#46; Yu"
                            2 => "X&#46; Qin"
                            3 => "J Liu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1080/10408363.2023.2195496"
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Rev Clin Lab Sci"
                        "fecha" => "2023"
                        "volumen" => "60"
                        "paginaInicial" => "427"
                        "paginaFinal" => "441"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/37038925"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0009"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "ERICA&#58; prevalences of hypertension and obesity in Brazilian adolescents"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;V&#46; Bloch"
                            1 => "C&#46;H&#46; Klein"
                            2 => "M&#46; Szklo"
                            3 => "M&#46;C&#46; Kuschnir"
                            4 => "A&#46; Abreu G de"
                            5 => "L&#46;A&#46; Barufaldi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Rev Saude Publica"
                        "fecha" => "2016"
                        "volumen" => "50"
                        "paginaInicial" => "S9"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Population-based studies on the epidemiology of insulin resistance in children"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46;P&#46; Van Der Aa"
                            1 => "S&#46; Fazeli Farsani"
                            2 => "C&#46;A&#46; Knibbe"
                            3 => "A&#46; De Boer"
                            4 => "M&#46;M Van Der Vorst"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "J Diabetes Res"
                        "fecha" => "2015"
                        "volumen" => "2015"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0011"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Insulin resistance of puberty"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;M&#46; Kelsey"
                            1 => "P&#46;S&#46; Zeitler"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s11892-016-0751-5"
                      "Revista" => array:5 [
                        "tituloSerie" => "Curr Diab Rep"
                        "fecha" => "2016"
                        "volumen" => "16"
                        "paginaInicial" => "64"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27179965"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0012"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Childhood and adolescent obesity&#58; a review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46;R&#46; Kansra"
                            1 => "S&#46; Lakkunarajah"
                            2 => "M&#46;S&#46; Jay"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Front Pediatr"
                        "fecha" => "2021"
                        "volumen" => "8"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0013"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The study of cardiovascular risk in adolescents - ERICA&#58; rationale&#44; design and sample characteristics of a national survey examining cardiovascular risk factor profile in Brazilian adolescents"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;V&#46; Bloch"
                            1 => "M&#46; Szklo"
                            2 => "M&#46;C&#46;C&#46; Kuschnir"
                            3 => "G&#46; De Azevedo Abreu"
                            4 => "L&#46;A&#46; Barufaldi"
                            5 => "C&#46;H&#46; Klein"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s12889-015-1442-x"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMC Public Health"
                        "fecha" => "2015"
                        "volumen" => "15"
                        "paginaInicial" => "94"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25880653"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0014"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Blood sampling frequency as a proxy for comorbidity indices when identifying patient samples for review of reference intervals"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S&#46; Lykkeboe"
                            1 => "S&#46;L&#46; Andersen"
                            2 => "C&#46;G&#46; Nielsen"
                            3 => "P&#46; Vestergaard"
                            4 => "P&#46;A&#46; Christensen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1515/cclm-2021-0987"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Chem Lab Med"
                        "fecha" => "2022"
                        "volumen" => "60"
                        "paginaInicial" => "252"
                        "paginaFinal" => "260"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34856091"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A simple method of resolution of a distribution into Gaussian components"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "C&#46;G&#46; Bhattacharya"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Biometrics"
                        "fecha" => "1967"
                        "volumen" => "23"
                        "paginaInicial" => "115"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6050463"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0016"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The IFCC recommendation on estimation of reference intervals&#46; The RefVal program"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "H&#46;E&#46; Solberg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1515/CCLM.2004.121"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Chem Lab Med"
                        "fecha" => "2004"
                        "volumen" => "42"
                        "paginaInicial" => "710"
                        "paginaFinal" => "714"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15327004"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0017"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cardiovascular actions of insulin"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "R&#46; Muniyappa"
                            1 => "M&#46; Montagnani"
                            2 => "K&#46;K&#46; Koh"
                            3 => "M&#46;J&#46; Quon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/er.2007-0006"
                      "Revista" => array:6 [
                        "tituloSerie" => "Endocr Rev"
                        "fecha" => "2007"
                        "volumen" => "28"
                        "paginaInicial" => "463"
                        "paginaFinal" => "491"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17525361"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0018"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Indirectly determined hematology reference intervals for pediatric patients in Berlin and Brandenburg"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "I&#46; Mrosewski"
                            1 => "T&#46; D&#228;hn"
                            2 => "J&#46; Hehde"
                            3 => "E&#46; Kalinowski"
                            4 => "I&#46; Lindner"
                            5 => "T&#46;M&#46; Meyer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1515/cclm-2021-0853"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Chem Lab Med"
                        "fecha" => "2022"
                        "volumen" => "60"
                        "paginaInicial" => "408"
                        "paginaFinal" => "432"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34904427"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0019"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Paediatric reference intervals for ionised calcium &#8211; a data mining approach"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46;Z Yong Chung"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Chem Lab Med"
                        "fecha" => "2021"
                        "volumen" => "59"
                        "paginaInicial" => "e271"
                        "paginaFinal" => "e273"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Indirectly determined reference intervals for automated white blood cell differentials of pediatric patients in Berlin and Brandenburg"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "I&#46; Mrosewski"
                            1 => "T&#46; D&#228;hn"
                            2 => "J&#46; Hehde"
                            3 => "E&#46; Kalinowski"
                            4 => "I&#46; Lindner"
                            5 => "T&#46;M&#46; Meyer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1515/cclm-2022-1265"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Chem Lab Med"
                        "fecha" => "2023"
                        "volumen" => "61"
                        "paginaInicial" => "1116"
                        "paginaFinal" => "1122"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36669090"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0021"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An indirect data-mining approach to standardise paediatric serum phosphate reference intervals in Wales"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Rodham"
                            1 => "S&#46; Zouwail"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Chem Lab Med"
                        "fecha" => "2023"
                        "volumen" => "62"
                        "paginaInicial" => "e19"
                        "paginaFinal" => "e21"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0022"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Closing the gaps in pediatric laboratory reference intervals&#58; a CALIPER database of 40 biochemical markers in a healthy and multiethnic population of children"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;A&#46; Colantonio"
                            1 => "L&#46; Kyriakopoulou"
                            2 => "M&#46;K&#46; Chan"
                            3 => "C&#46;H&#46; Daly"
                            4 => "D&#46; Brinc"
                            5 => "A&#46;A&#46; Venner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Chem"
                        "fecha" => "2012"
                        "volumen" => "58"
                        "paginaInicial" => "854"
                        "paginaFinal" => "868"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0023"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Complex reference value distributions and partitioned reference intervals across the pediatric age range for 14 specialized biochemical markers in the CALIPER cohort of healthy community children and adolescents"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Kelly"
                            1 => "J&#46;E&#46; Raizman"
                            2 => "V&#46; Bevilacqua"
                            3 => "M&#46;K&#46; Chan"
                            4 => "Y&#46; Chen"
                            5 => "F&#46; Quinn"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cca.2015.08.020"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Chim Acta"
                        "fecha" => "2015"
                        "volumen" => "450"
                        "paginaInicial" => "196"
                        "paginaFinal" => "202"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26310965"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0024"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "CLSI-based transference of the CALIPER database of pediatric reference intervals from Abbott to Beckman&#44; Ortho&#44; Roche and Siemens Clinical Chemistry Assays&#58; direct validation using reference samples from the CALIPER cohort"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;P&#46; Estey"
                            1 => "A&#46;H&#46; Cohen"
                            2 => "D&#46;A&#46; Colantonio"
                            3 => "M&#46;K&#46; Chan"
                            4 => "T&#46;B&#46; Marvasti"
                            5 => "E&#46; Randell"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.clinbiochem.2013.04.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Biochem"
                        "fecha" => "2013"
                        "volumen" => "46"
                        "paginaInicial" => "1197"
                        "paginaFinal" => "1219"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23578738"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The importance of correct stratifications when comparing directly and indirectly estimated reference intervals"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46; Haeckel"
                            1 => "W&#46; Wosniok"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Chem Lab Med"
                        "fecha" => "2021"
                        "volumen" => "59"
                        "paginaInicial" => "1628"
                        "paginaFinal" => "1633"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0026"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biological variables influencing the estimation of reference limits"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;K&#46; &#214;z&#231;&#252;r&#252;mez"
                            1 => "R&#46; Haeckel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1080/00365513.2018.1471617"
                      "Revista" => array:6 [
                        "tituloSerie" => "Scand J Clin Lab Invest"
                        "fecha" => "2018"
                        "volumen" => "78"
                        "paginaInicial" => "337"
                        "paginaFinal" => "345"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29764232"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0027"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Application of the Hoffmann&#44; Bhattacharya&#44; nonparametric test&#44; and Q-Q plot methods for establishing reference intervals from laboratory databases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "C&#46; Yang"
                            1 => "L&#46; Lang"
                            2 => "S&#46; Wang"
                            3 => "H&#46; Fang"
                            4 => "H&#46; Chen"
                            5 => "Q&#46; Xie"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.clinbiochem.2022.12.016"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Biochem"
                        "fecha" => "2023"
                        "volumen" => "113"
                        "paginaInicial" => "9"
                        "paginaFinal" => "16"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36587756"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0028"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Utilization of five data mining algorithms combined with simplified preprocessing to establish reference intervals of thyroid-related hormones for non-elderly adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Zhong"
                            1 => "C&#46; Ma"
                            2 => "L&#46; Hou"
                            3 => "Y&#46; Yin"
                            4 => "F&#46; Zhao"
                            5 => "Y&#46; Hu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s12874-023-01898-5"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMC Med Res Methodol"
                        "fecha" => "2023"
                        "volumen" => "23"
                        "paginaInicial" => "108"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/37131135"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0029"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Validation and comparison of five data mining algorithms using big data from clinical laboratories to establish reference intervals of thyroid hormones for older adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Ma"
                            1 => "Y&#46; Zou"
                            2 => "L&#46; Hou"
                            3 => "Y&#46; Yin"
                            4 => "F&#46; Zhao"
                            5 => "Y&#46; Hu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.clinbiochem.2022.05.008"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Biochem"
                        "fecha" => "2022"
                        "volumen" => "107"
                        "paginaInicial" => "40"
                        "paginaFinal" => "49"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35636495"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/00217557/0000010000000005/v1_202408020453/S0021755724000421/v1_202408020453/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "10179"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Original articles"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/00217557/0000010000000005/v1_202408020453/S0021755724000421/v1_202408020453/en/main.pdf?idApp=UINPBA000049&text.app=https://jped.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755724000421?idApp=UINPBA000049"
]

Article information

ISSN: 00217557
Original language: English

DOI:10.1016/j.jped.2024.03.009

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	6	6	12
2024 October	43	59	102
2024 September	191	68	259
2024 August	120	89	209
2024 July	90	56	146
2024 June	81	28	109
2024 May	88	43	131
2024 April	29	27	56

Indexed in:

Follow us:

Statistics

Indexed in:

Follow us:

Statistics

Subscribe to our newsletter