Performance of QuantiFERON-TB Gold Plus assays in children and adolescents at risk of tuberculosis: a cross-sectional multicentre study

Introduction: The QuantiFERON-TB Gold Plus (QFT-Plus) assay, which features two antigen-stimulated tubes (TB1 and TB2) instead of a single tube used in previous-generation interferon-gamma release assays (IGRAs), was launched in 2016. Despite this, data regarding the assay’s performance in the paediatric setting remain scarce. This study aimed to determine the performance of QFT-Plus in a large cohort of children and adolescents at risk of tuberculosis (TB) in a low-burden setting. Methods: Cross-sectional, multicentre study at healthcare institutions participating in the Spanish Paediatric TB Research Network, including patients <18 years who had a QFT-Plus performed between September 2016 and June 2020. Results: Of 1726 patients (52.8% male, median age: 8.4 years), 260 (15.1%) underwent testing during contact tracing, 288 (16.7%) on clinical/radiological suspicion of tuberculosis disease (TBD), 649 (37.6%) during new-entrant migrant screening and 529 (30.6%) prior to initiation of immunosuppressive treatment. Overall, the sensitivity of QFT-Plus for TBD (n=189) and for latent tuberculosis infection (LTBI, n=195) was 83.6% and 68.2%, respectively. The agreement between QFT-Plus TB1 and TB2 antigen tubes was excellent (98.9%, κ=0.961). Only five (2.5%) patients with TBD had discordance between TB1 and TB2 results (TB1+/TB2−, n=2; TB1−/TB2+, n=3). Indeterminate assay results (n=54, 3.1%) were associated with young age, lymphopenia and elevated C reactive protein concentrations. Conclusions: Our non-comparative study indicates that QFT-Plus does not have greater sensitivity than previous-generation IGRAs in children in both TBD and LTBI. In TBD, the addition of the second antigen tube, TB2, does not enhance the assay’s performance substantially

Interferon-Gamma Release Assays Differentiate Between Mycobacterium avium Complex and Tuberculous Lymphadenitis in Children

OBJECTIVES: To assess the performance of interferon-gamma release assays (IGRAs) in the differential diagnosis between Mycobacterium avium complex (MAC) and tuberculosis (TB) in children affected with subacute/chronic submandibular/cervical lymphadenitis. STUDY DESIGN: Multicenter observational study comparing children with microbiologically-confirmed MAC lymphadenitis from the European NontuberculouS MycoBacterial Lymphadenitis in childrEn (ENSeMBLE) study with children with TB lymphadenitis from the Spanish Network for the Study of Pediatric TB (pTBred) database. RESULTS: Overall, 78 patients with MAC and 34 with TB lymphadenitis were included. Among MAC cases, 44/74 (59.5%) had positive tuberculin skin test (TST) results at the 5 mm cutoff, compared with 32/33 (97%) TB cases (p<0.001); at the 10 mm cutoff TST results were positive in 23/74 (31.1%) vs. 26/31 (83.9%), respectively (P < .001). IGRA results were positive in only 1/32 (3.1%) MAC cases who had undergone IGRA testing, compared with 21/23 (91.3%) TB cases (p<0.001). Agreement between TST and IGRA results was poor in MAC (23.3%;κ=0.017), but good in TB cases (95.6%;κ=0.646). IGRAs had a specificity of 96.9% (95%CI:84.3-99.8%), positive predictive value (PPV) of 95.4% (95%CI:78.2-99.8%), and negative predictive value (NPV) of 93.9% (95%CI:80.4-98.9%) for TB lymphadenitis. CONCLUSIONS: In contrast to TST, IGRAs have high specificity, NPV and PPV for TB lymphadenitis in children with subacute/chronic lymphadenopathy, and consequently can help to discriminate between TB and MAC disease. Therefore, IGRAs are useful tools in the diagnostic work-up of children with lymphadenopathy, particularly when culture- and PCR-results are negative

Docencia en Derecho y Proceso: hacia un aprendizaje de calidad en la Universidad

Presentación / Esther Pillado González (pp. 11-13). -- La adaptación de la asignatura derecho procesal penal al grado en la Universidad Carlos III de Madrid: un proceso aún inconcluso / Juan Manuel Alcoceba Gil (pp. 17-26). -- Role playing, cooperación competitiva y method case en la docencia-aprendizaje del Derecho Procesal / Cristina Alonso Salgado (pp. 27-35). -- Esquemas y materiales básicos para explicar en el grado en derecho el sistema de impugnación de actos jurídicos de las administraciones públicas en España / Roberto O. Bustillo Bolado (pp. 37-40). -- Nuevas herramientas y técnicas para la docencia del derecho / Juan Cámara Ruiz (pp. 41-51). -- Novas técnicas na docência em direito / Marco Carvalho Gonçalves (pp. 53-60). -- Experiência de lecionação em Direito em cursos não jurídicos – a lecionação da UC de Direito das Crianças e Jovens ao Mestrado em Intervenção Psicossocial com Crianças, Jovens e Famílias do Instituto de Educação / Cristina M. A. Dias (pp. 61-67). -- Los programas universitarios para mayores: la docencia en Derecho en la Universidad de Vigo / Teresa Estévez Abeleira (pp. 69-79). -- El aprendizaje activo del Derecho Procesal / María Dolores Fernández Fustes (81-92). -- El aprendizaje como método de adquirir los conocimientos / Raquel López Jiménez (pp. 93-101). -- Alumnado con necesidades especiales en el grado en derecho: el reto de la normalización e inclusión / Ángel M. Mariño de Andrés y M. Teresa Martínez Táboas (pp. 103-110). -- Docencia y proceso penal: intentando experimentar el proceso / Sabela Oubiña Barbolla (pp. 111-127). -- La integración de las redes sociales en la enseñanza del Derecho Penal / Natalia Pérez Rivas (pp. 129-135). -- Análisis y prospectiva de una plataforma e-learning en ciencias jurídicas / Amparo Rodríguez Damián, Margarita Pino Juste, Arturo Casar Sarasola y Manuel Pérez Cota (pp. 137-149). -- La evaluación de competencias en las materias “prácticas externas” del Máster Universitario en Abogacía: problemas y retos / Mónica Siota Álvarez (pp. 151-164). -- La enseñanza del derecho procesal a través del método del caso / Helena Soleto Muñoz (pp. 165-178). -- A aprendizagem activa do Direito Processual – reflexão sobre velhos hábitos e novas práticas / Lurdes Varregoso Mesquita (pp. 179-189). -- Acão executiva e metodologia aplicada – demonstração de caso / Lurdes Varregoso Mesquita, Diana Leiras (pp. 191-201). -- Derecho Constitucional y género / Almudena Bergareche Gros (pp. 205-216). -- Aproximación al fenómeno de la violencia de género a través de las novelas como recurso didáctico / María Castro Corredoira (pp. 217-227). -- La formación en género en derecho penal: el cine como recurso didáctico / Natalia Pérez Rivas, Fernando Vázquez-Portomeñe Seijas (pp. 229-240). -- Cuestiones controvertidas de la docencia en el ámbito del derecho constitucional: la perspectiva de género y el principio de transversalidad / Pablo Riquelme Vázquez (pp. 241-253). -- Storytelling y cine extranjero en la explicación del sistema de justicia penal español / Cristina Alonso Salgado (pp. 257-263). -- Direito e Cinema. Breve reflexão a partir da experiência da docência ao 1.º ano do curso de Direito / Maria Clara Calheiros (pp. 265-273). -- El cine como opción pedagógica en la enseñanza del derecho penal / Fernando Vázquez-Portomeñe Seijas y María Castro Corredoira (pp. 275-286). -- El jurista del siglo XXI y la Universidad del siglo pasado: ¿realidades irreconciliables? / Amaya Arnáiz Serrano (pp. 289-307). -- La formación del abogado del siglo XXI / Emiliano Carretero Morales (pp. 309-321). -- El cambio del perfil del alumno y su influencia a la enseñanza superior / Anna Fiodorova (pp. 323-335). -- La enseñanza del derecho en el marco Bolonia: reflexiones en base a las distintas tradiciones jurídicas / Mercedes Llorente Sánchez-Arjona (pp. 337-355)

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

N&#243;dulos opalinos en facies marginales del salar Olaroz (Puna Argentina)

This article reports the results of a petrological and geochemical study of silica nodules from Quaternary alluvial fallS of the Olaroz Salar. The nodules are mainly constituted by C-T opal, d. (101) spacing to 4,11 A, implying a high-disorder; this is commonly observed in opa! rocks formed in near surface environments, without burial and heating. The chemical composition of the nodules is anomalous when compared with other typical silica-rocks formed in arid continental closed basin, without any eruptive environments (for instance the Cuenca del Tajo in Spain). The siliceous nodules do not have the characteristics of the silcretes and are not associated to the evaporitic facies of the salar. Their genesis is probably related to contamination of groundwater of the alluvial fan with high-silica thermal water. The C-T opal would thus precipitate by either displacing tbe terrigenous host-rock or replacing previous ulexite nodules.<br><br>Se realiza un estudio petrol&#243;gico y geoqu&#237;mico de los n&#243;dulos sil&#237;ceos que se encuentran incluidos en sedimentos terr&#237;genos cuaternarios de la Cuenca de Olaroz (La Puna, Argentina). Estos n&#243;dulos se localizan en abanicos aluviales que aparecen encajados, debido a los cambios en el nivel de base que se produce desde el Pleistoceno a la actualidad, durante la evoluci&#243;n de los cuerpos lacustres a salares. Un estudio mediante DRX revela que son rocas constituidas por &#243;palo C-T, con un espaciado (101) a 4,11 A, que implica un grado de desorden alto, t&#237;pico de las rocas sil&#237;ceas formadas en superficie y que no han sufrido enterramiento ni influencia t&#233;rmica. Su composici&#243;n qu&#237;mica es an&#243;mala si se compara con rocas sil&#237;ceas continentales formadas en ambiente endorreico y fuera de un marco volc&#225;nico (Mioceno de la Cuenca del Tajo). No poseyendo caracter&#237;sticas de silcretas y no estando asociadas a la sedimentaci&#243;n evapor&#237;tica de los salares, se considera la influencia de aguas termales. La contaminaci&#243;n local y en un momento dado de las aguas fre&#225;ticas de los abanicos aluviales por aguas termales ricas en s&#237;lice, propiciar&#237;a junto con la evaporizaci&#243;n la precipitaci&#243;n de la sil&#237;ceo Los n&#243;dulos sil&#237;ceos crecer&#237;an desplazando el sedimento terr&#237;geno que constituye la roca caja o reemplazando n&#243;dulos previa de ulexita

Root calcretes and uranium-bearing silcretes at sedimentary discontinuities in the miocene of the Madrid Basin (Toledo, Spain)

This paper reports a detailed study of the calcrete and silcrete profiles in the Miocene detrital deposits in the western area of Madrid, at the boundary of two main sedimentary units. The aims of this work were to better understand the pedogenic and diagenetic environments in which these profiles formed and to determine the cause(s) of their enrichment in uranium. Calcrete and silcrete duricrusts are characteristic features of closed continental basins in semiarid climates; this paper discusses the significance of duricrusts as indicators of important change in such basins.The detailed macromorphological, micromorphological, and geochemical study of three duricrust profiles revealed the sequence of pedogenic, vadose, and groundwater processes responsible for their formation. During the first stage of their development, carbonate laminae formed a white “grill-like” structure within the detrital parent materials. The microstructure and macrostructure of the carbonate, which includes alveolar septal structures and needle-fiber calcite, indicates the important role of roots and their associated microorganisms in calcrete formation. Early silicification occurred in the pedogenic-vadose environment affecting the detrital parent material, roots, and calcretes, forming an early silcrete defined by opaline glaebules and silica rhizoliths. The detailed preservation of the cells in the silicified roots denotes the early replacement of root organic matter.The green or green-yellowish fluorescence of the silicified root structures under short-wavelength UV shows their preferential enrichment in uranium. Calcitization and silicification coexisted in the pedogenic vadose environment, leading to several reversible replacements of calcite and silica. Later, the rise of the water table promoted silicification under phreatic conditions, as indicated by the good preservation of the texture of the detrital host rocks and calcretes. Other silcrete textures, such as ovoidal opaline accumulations, intraclasts produced by autobrecchification, and vadose silica cements, indicate later vadose environments, and consequently variations in the water table.The geochemical features of the calcretes and silcretes (major, minor, and rare earth elements) were inherited from their parent materials. The rare-earth-element patterns of some silcretes show them to have a positive Ce anomaly, suggesting that oxidizing conditions reigned during their formation. The good correlation between silica and uranium suggests that the silica phases acquired uranium through the direct silicification of roots that had fixed uranium from organic matter.This study shows that calcrete–silcrete duricrusts provide detailed information regarding the processes occurring in semiarid continental basins. In the studied basin, roots played a key role in both the development of the duricrust profiles and their enrichment in uranium. These duricrusts provide important information for understanding the overall stratigraphy of the studied basin and its large-scale sequential evolution

Transformaciones edaficas y diageneticas de los depositos aluviales distales del mioceno de la cuenca de Madrid, area de Paracuellos de Jarama

The distal aluvial fan and the palustrine deposits of the Paracuellos de Jarama area display a variety of specific pedogenic and diagenetic features. The processes affecting these sediments were controlled by: the sedimentary environment, the lithology and initia1 texture of the sediments and by the pedogenic-diagenetic environment in which the transformations occurred. Thus, in the distal alluvial areas (PEL profile) the first processes were the formation of thin carbonate laminae and sepiolite, further, these deposits were silicified and later, a spheroidal dolomite is formed on the opaline chert. In lacustnne environments (UPC profile), drying and root activity led to the formation of palustrine carbonates that were silicified, and the initial texture and structure were preserved. The silicification consisted on a pseudomorphic replacement that produced mainly opal whereas quartz was formed mostly by cementation and ageing of previous opal. In both environments, when the silicification occurs on sepiolite, or micrite with sepiolite, atypical microfibrous opal is produced. This replacement can lead to the release of Mg, favounng a later formation of dolomite on the opaline chert, with evidence of bacteria1 activity. Al1 these processes occurred in a shallow phreatic or even vadose environment.<br><br>Los dep&#243;sitos distales de los abanicos aluviales arc&#243;sicos y tambi&#233;n los carbonatos palustres del &#225;rea de Paracuellos de Jarama presentan rasgos muy espec&#237;ficos debidos a los procesos ed&#225;ficos y diagen&#233;ticos que han sufrido. Los procesos que han afectado a estos sedimentos, y su intensidad, estuvieron controlados por: el ambiente sedimentario, la litolog&#237;a y textura/estructura inicial del material y tambi&#233;n por el ambiente pedog&#233;nico- diagen&#233;tico superficial en el que se han desarrollado las transformaciones. As&#237;, en las lutitas de las zonas distales de los abanicos (perfil PEL) se forman inicialmente l&#225;minas de carbonato ed&#225;fico y sepiolita, posteriormente tiene lugar la silicificaci&#243;n y, a continuaci&#243;n, la formaci&#243;n de dolom&#237;as esencialmente esferoidales. En ambientes lacustres (perfil UPC), la intensa desecaci&#243;n y la actividad biol&#243;gica conducen a la formaci&#243;n de calizas palustres que posteriormente se silicifican conservando la textura y estructura. La silicificaci&#243;n es, en gran parte, un reemplazamiento pseudom&#243;rfico que origina principalmente &#243;palo, mientras que el cuarzo se forma por cementaci&#243;n y tambi&#233;n por envejecimiento del &#243;palo. En ambos ambientes, cuando la silicificaci&#243;n se produce sobre arcillas, probablemente sepiol&#237;ticas, o sobre carbonatos muy ricos en sepiolita, se generan &#243;palos at&#237;picos de microestructura fibrosa. Este proceso puede liberar magnesio, que posteriormente puede ser utilizado para la formaci&#243;n de dolomita de posible origen bacteriano sobre el s&#237;lex opalino (perfil PEL). Todos estos procesos tuvieron lugar en ambiente fre&#225;tico somero o incluso vadoso