Marcadores tumorales en neuroblastoma: un análisis retrospectivo

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Pediatria. Fecha de Lectura: 25-11-2021El cáncer pediátrico es, en su conjunto, una patología infrecuente que cumple criterios de enfermedad rara, y sin embargo es la primera causa de muerte por enfermedad en niños excluida la patología perinatal. El neuroblastoma es el tumor sólido extracraneal más frecuente en pediatría. Las formas de riesgo alto, que se dan en niños mayores de 18 meses, y que son habitualmente metastásicas (estadio M) y con genética desfavorable (principalmente amplificación del oncogen NMYC) presentan una elevada tasa de recaídas (mayor del 40%) y una supervivencia que apenas supera el 50% a pesar de tratamiento agresivo multimodal incluyendo inmunoterapia. El desarrollo de nuevas terapias dirigidas contra alteraciones específicas del neuroblastoma podía incrementar la supervivencia de pacientes de mal pronóstico. Las dos alteraciones más relevantes son la mutación de Kinasa de Linfoma Anaplásico (ALK), responsable de las formas familiares, y presente en aproximadamente el 10% de los neuroblastomas esporádicos, y la sobreexpresión de Aurora Kinasa A, proteína que estabiliza NMYC. Se ha realizado una revisión retrospectiva de los neuroblastomas diagnosticados y/o tratados en nuestro centro desde la implantación de protocolos estandarizados (1990-2016). Se ha comparado las características con las principales series internacionales, en particular con la base de datos del International Neuroblastoma Risk Group (INRG). Se ha estudiado asimismo la mutación de ALK (mediante secuenciación Sanger) y la sobreexpresión de AURKA (mediante PCR cuantitativa e inmunohistoquímica) en muestras parafinadas de pacientes estadio M. Nuestros pacientes son comparables, en características y supervivencia, a las series nacionales e internacionales publicadas. Hemos encontrado correlación entre inmunohistoquímica positiva para AURKA y amplificación de NMYC. Consideramos que los pacientes con amplificación de NMYC se podrían beneficiar de tratamiento dirigido con inhibidores de AURK

Meta-Revisiones: Concepto y Desarrollo

Background: In the last years, overviews of systematic reviews, or umbrella reviews, have seen a dramatic increase in their use. An overview aims to provide a summary of the included reviews and will often examine research questions beyond those addressed in the systematic reviews being synthesised. The purpose of this article is to provide some recommendations on how overviews should be conducted and reported. Method: A literature review was performed to identify relevant papers on both methodological and applied overviews. Results: The current literature recommends carrying out overviews by following similar steps to those of systematic reviews: (a) Defining the overview research question; (b) inclusion and exclusion criteria; (c) literature search; (d) data extraction; (e) assessment of risk of bias and reporting quality; (f) overview results; and (g) reporting the overview. Of special interest is how to address dependencies between the systematic reviews. Conclusions: Overviews allow evidence to be efficiently combined from multiple systematic reviews. This offers the possibility of translating and summarizing large amounts of information. As in primary studies and systematic reviews, conducting and reporting of overviews must meet appropriate quality standards.Antecedentes: en los últimos años, las meta-revisiones, o revisiones paraguas, han incrementado exponencialmente su uso. Una meta-revisión proporciona un resumen de las revisiones incluidas y, a menudo, aborda preguntas más allá de las planteadas en las revisiones sistemáticas sintetizadas. El propósito de este artículo fue proporcionar recomendaciones sobre cómo deben hacerse y reportarse las meta-revisiones. Método: se llevó a cabo una revisión de la literatura para identificar artículos relevantes sobre meta-revisiones, tanto metodológicos como aplicados. Resultados: a día de hoy la literatura sobre meta-revisiones recomienda seguir los mismos pasos que en las revisiones sistemáticas: (a) definición de la pregunta de investigación; (b) criterios de inclusión y exclusión; (c) búsqueda de la literatura; (d) extracción de datos; (e) valoración del riesgo de sesgo y de la calidad del reporte; (f) presentación de resultados; y (g) reporte de la meta-revisión. De especial interés es cómo abordar los problemas de dependencia entre las revisiones sistemáticas sintetizadas. Conclusiones: las meta-revisiones permiten combinar evidencia de múltiples revisiones sistemáticas de una forma eficiente. Esto permite transformar y resumir grandes cantidades de información. Al igual que en los estudios primarios y las revisiones sistemáticas, las meta-revisiones deben realizarse y reportarse cumpliendo con estándares mínimos de calidad.This study was funded by Agencia Estatal de Investigación (Government of Spain) and by FEDER Funds, AEI/10.13039/501100011033, grants no. PID2019-104033GA-I00 and PID2019-104080GB-I00

Meta-análisis de Generalización de la Fiabilidad de la Dimensional Obssesive-Compulsive Scale

Background: The Dimensional Obsessive-Compulsive Scale (DOCS) is a well-established tool for assessing obsessive-compulsive symptomatology. A reliability generalization meta-analysis was conducted to estimate the average reliability of DOCS scores and how reliability estimates vary according to the composition and variability of samples, to identify study characteristics that can explain its variability, and to estimate the reliability induction rate. Method: A literature search produced 86 studies that met the inclusion criteria. Results: For the DOCS total scores, an average alpha coefficient of .925 was found (95% CI [.920,.931]), as well as mean alphas of .881, .905, .913, and .914 for Contamination, Responsibility, Unacceptable Thoughts, and Symmetry subscales, respectively. Moderator analysis showed that internal consistency fell significantly the more clinical and subclinical participants there were in the sample, and the larger the mean score in the sample for the total scores. The most important moderator variables for the subscales were the standard deviation and the mean of the scores. Conclusions: The DOCS scores exhibited excellent internal consistency reliability for both total score and subscale scores and DOCS is suitable both for research and clinical purposes.Antecedentes: la Dimensional Obsessive-Compulsive Scale (DOCS) (Abramowitz, 2010) es un instrumento para la evaluación del TOC. En este estudio se llevó a cabo un estudio de generalización de la fiabilidad de la DOCS para estimar un coeficiente alfa medio y analizar la heterogeneidad de estos y el influjo de distintas variables moderadores. Método: se realizó una búsqueda bibliográfica de 86 estudios incluibles. Resultados: para la escala total, se estimó un coeficiente alfa medio de .925, así como para sus subescalas: Contaminación .881, Responsabilidad con respecto al daño .905, Pensamientos inaceptables .913 y Simetría .913. Los análisis de moderadores revelaron que la consistencia interna disminuyó significativamente a mayor porcentaje de participantes clínicos o subclínicos en la muestra, así como a mayor puntuación media de la muestra para las puntuaciones totales; para las subescalas la desviación típica y la media de las puntuaciones fueron los moderadores más relevantes. Conclusiones: las puntuaciones de la DOCS muestran una excelente fiabilidad por consistencia interna, tanto para la escala global como para las subescalas, pudiendo usarse tanto para fines clínicos como de investigación.This research was funded with a grant from the Spanish Government, Ministerio de Economía, Industria y Competitividad, and FEDER funds (project n. PSI2016-77676-P)

A meta-review of transparency and reproducibility-related reporting practices in published meta-analyses on clinical psychological interventions (2000–2020)

Meta-analysis is a powerful and important tool to synthesize the literature about a research topic. Like other kinds of research, meta-analyses must be reproducible to be compliant with the principles of the scientific method. Furthermore, reproducible meta-analyses can be easily updated with new data and reanalysed applying new and more refined analysis techniques. We attempted to empirically assess the prevalence of transparency and reproducibility-related reporting practices in published meta-analyses from clinical psychology by examining a random sample of 100 meta-analyses. Our purpose was to identify the key points that could be improved, with the aim of providing some recommendations for carrying out reproducible meta-analyses. We conducted a meta-review of meta-analyses of psychological interventions published between 2000 and 2020. We searched PubMed, PsycInfo and Web of Science databases. A structured coding form to assess transparency indicators was created based on previous studies and existing meta-analysis guidelines. We found major issues concerning: completely reproducible search procedures report, specification of the exact method to compute effect sizes, choice of weighting factors and estimators, lack of availability of the raw statistics used to compute the effect size and of interoperability of available data, and practically total absence of analysis script code sharing. Based on our findings, we conclude with recommendations intended to improve the transparency, openness, and reproducibility-related reporting practices of meta-analyses in clinical psychology and related areas.This research has been funded with a grant from the Ministerio de Ciencia e Innovación and by FEDER funds (Project n° PID2019-104080GB-I00)

A reliability generalization meta-analysis of the child and adolescent perfectionism scale

Background: Perfectionism is a prevalent disposition of personality involved in the development and maintenance of a wide range of psychological disorders. The Child and Adolescent Perfectionism Scale (CAPS) is the most usually applied test to assess perfectionism in children and adolescents. This study aimed: (a) to conduct a reliability generalization meta-analysis to estimate the average reliability of the CAPS scores and to search for characteristics of the studies that may explain the variability among reliability estimates, and (b) to estimate the reliability induction rate of the CAPS. Method: An exhaustive search allowed to select 56 studies that reported alpha coefficients with the data at hand for the CAPS. Results: The average alpha coefficients were 0.87, 0.84 and 0.83, respectively for the CAPS total score and its two subscales, Socially Prescribed Perfectionism (SPP) and Self-Oriented Perfectionism (SOP). Regarding O'Connor's version, the average reliability coefficients were 0.82, 0.74 and 0.73, respectively, for SPP, SOP-Critical and SOP-Strivings. Some study characteristics (ethnicity, language, mean age and standard deviation of the scores, psychometric vs applied) showed a statistical association with the reliability coefficients of SPP and SOP. The reliability induction rate was 29.8%. Limitations: Due to the scarcity of studies, we could not examine the reliability scores of other versions of the CAPS and test-retest reliability. Conclusions: In terms of reliability, the original version of the CAPS present better results than O'Connor's version. The original version of the CAPS is a reliable instrument to be employed with general research purposes, but not for clinical practice.Ministerio de Economía y Competitividad of the Spanish Government; Fondo Europeo de Desarrollo Regional (FEDER) Project no. PSI2016-77676‐P

A Meta-analysis of Gut Microbiota in Children with Autism

Previous studies have reported dysbiosis in the gut microbiota (GM) of children with autism spectrum disorders (ASD), which may be a determining factor on child development through the microbiota-gut-brain axis. However, it is not clear if there is a specific group of dysbiotic bacteria in ASD. The aim of this study was to carry out a meta-analysis on the studies that analyze GM in children with ASD. 18 studies fulfilled our selection criteria. Our results showed a lower relative abundance of Streptococcus (SMD+ = − 0.999; 95% CI − 1.549, − 0.449) and Bifidobacterium genera (SMD+ = − 0.513; 95% CI − 0.953, − 0.073) in children with ASD. Overall, the Bifidobacterium genera is involved. However, differences found between studies are attributed to factors such as reporting bias

Health-Related Quality of Life in People with Advanced HIV Disease, from 1996 to 2021: Systematic Review and Meta-analysis

The purpose of the study was to assess the effects of advanced HIV disease (AHD) on health-related quality of life (HRQoL) in PLHIV, the changes in HRQoL outcomes over the last 25 years, and the differences between countries according to level of economic development. We conducted a systematic review and meta-analysis. The search was conducted in PubMed and Web of Science using the terms: “health-related quality of life”, “HQRoL”, “HIV”, “AIDS”, “advanced HIV disease” and “low CD4 cells”. Studies inclusion criteria were: adult population; initiated after 1996 and published before July 2021; clinical trials, cross-sectional, cohort, and case–control studies; studies analyzing the relationship between AHD and HRQoL; English or Spanish language. Standardized mean differences (d+) were calculated to estimate the effect size for the meta-analyses. Summary statistics were calculated using a random-effects model, and analyses of effect moderators, using mixed-effects models. The meta-analysis included 38 studies. The results indicated that HRQoL is worse in patients with AHD compared to those without. The main HRQoL domains affected were overall health perception and concern and physical and functional health and symptoms. We found a moderate impact for age and gender on some HRQoL domains. There were no differences in relation to socioeconomic inequities, country of residence, or time period analyzed. In conclusion, advanced HIV disease has a negative impact on health and well-being in PLHIV. Our results show that despite all the advances in antiretroviral treatments over the last 25 years, AHD persists as a source of extreme vulnerability, regardless of where PLHIV live.El objetivo del estudio fue evaluar los efectos de la enfermedad avanzada de sida (EAS) en la calidad de vida relacionada con la salud (CVRS) en personas que viven con el VIH (PVVIH), los cambios experimentados en la CVRS en los últimos 25 años y las diferencias entre países. Realizamos una revisión sistemática y metaanálisis. La búsqueda se llevó a cabo en PubMed y Web of Science utilizando los términos: “calidad de vida relacionada con la salud”, “CVRS”, “VIH”, “SIDA”, “enfermedad avanzada por VIH” y “células CD4 bajas”. Los criterios de inclusión de los estudios fueron: población adulta; iniciado después de 1996 y publicado antes de julio de 2021; ensayos clínicos, estudios transversales, de cohorte y de casos y controles; estudios que analizan la relación entre EAS y CVRS; idioma inglés o español. Se calcularon diferencias de medias estandarizadas (d+) para estimar el tamaño del efecto para los metaanálisis. Los efectos promedios se calcularon utilizando un modelo de efectos aleatorios, y el análisis de moderadores utilizando modelos de efectos mixtos. El metaanálisis incluyó 38 estudios. Los resultados indicaron que la CVRS es peor en pacientes con EAS en comparación con aquellos sin EAS. Los principales dominios de CVRS afectados son la percepción de salud general y su preocupación, y la función física y de salud y los síntomas asociados. Encontramos un impacto moderado por edad y género en algunos dominios de CVRS. No encontramos diferencias en cuanto a las desigualdades socioeconómicas, país de residencia o período de tiempo analizado. En conclusión, la enfermedad avanzada por VIH tiene un impacto negativo en la salud y el bienestar en las personas con VIH. Nuestros resultados muestran que, a pesar de todos los avances en los tratamientos antirretrovirales en los últimos 25 años, el EAS persiste como una fuente de extrema vulnerabilidad, independientemente de dónde vivan las personas con VIH.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature

Maximize Resolution or Minimize Error? Using Genotyping-By-Sequencing to Investigate the Recent Diversification of Helianthemum (Cistaceae)

A robust phylogenetic framework, in terms of extensive geographical and taxonomic sampling, well-resolved species relationships and high certainty of tree topologies and branch length estimations, is critical in the study of macroevolutionary patterns. Whereas Sanger sequencing-based methods usually recover insufficient phylogenetic signal, especially in recently diversified lineages, reduced-representation sequencing methods tend to provide well-supported phylogenetic relationships, but usually entail remarkable bioinformatic challenges due to the inherent trade-off between the number of SNPs and the magnitude of associated error rates. The genus Helianthemum (Cistaceae) is a species-rich and taxonomically complex Palearctic group of plants that diversified mainly since the Upper Miocene. It is a challenging case study since previous attempts using Sanger sequencing were unable to resolve the intrageneric phylogenetic relationships. Aiming to obtain a robust phylogenetic reconstruction based on genotyping-by-sequencing (GBS), we established a rigorous methodological workflow in which we i) explored how variable settings during dataset assembly have an impact on error rates and on the degree of resolution under concatenation and coalescent approaches, ii) assessed the effect of two extreme parameter configurations (minimizing error rates vs. maximizing phylogenetic resolution) on tree topology and branch lengths, and iii) evaluated the effects of these two configurations on estimates of divergence times and diversification rates. Our analyses produced highly supported topologically congruent phylogenetic trees for both configurations. However, minimizing error rates did produce more reliable branch lengths, critically affecting the accuracy of downstream analyses (i.e. divergence times and diversification rates). In addition to recommending a revision of intrageneric systematics, our results enabled us to identify three highly diversified lineages in Helianthemum in contrasting geographical areas and ecological conditions, which started radiating in the Upper Miocene.España, MINECO grants CGL2014- 52459-P and CGL2017-82465-PEspaña, Ministerio de Economía, Industria y Competitividad, reference IJCI-2015-2345

Twin studies of subjective sleep quality and sleep duration, and their behavioral correlates: Systematic review and meta-analysis of heritability estimates

Twin studies have shown that a substantial proportion of the variance for sleep variables is due to genetic factors. However, there is still considerable heterogeneity among research reports. Our main objectives were to: 1) Review the twin literature regarding sleep quality and duration, as well as their behavioural correlates; 2) Estimate the mean heritability of subjective sleep quality and sleep duration; 3) Assess heterogeneity among studies on these topics; and 4) Search for moderator variables. Two parallel meta-analyses were carried out for sleep quality and sleep duration. Seventeen articles were included in the meta-analysis. Mean MZ correlations were consistently higher than DZ correlations. A mean heritability of 0.31 (95% CI: 0.20, 0.41) was found for subjective sleep quality (range: 0-0.43) and 0.38 (95% CI: 0.16, 0.56) for sleep duration (range: 0-1). Heterogeneity indexes were significant for both sleep quality (I2 = 98.77, p < .001) and sleep duration (I2 = 99.73, p < .001). The high heterogeneity warrants further research considering possible moderators that may affect heritability

Fixed-point Processing for an IR Positioning System based on QADA Receivers

2022 IEEE 12th International Conference on Indoor Positioning and Indoor Navigation (IPIN), 5-8 September, 2022, Beijing, China.Indoor optical positioning systems have increased in popularity in recent years because they can provide centimeter accuracy in three dimensions (3D) utilizing light-emitting diodes (LEDs) and photoreceptors. This work presents the design of a positioning system, which is based on a set of four photoreceptors functioning as beacons at known places for a single LED to be positioned. However, it might be extended to additional emitters with some medium access control. The associated processing is explained, as well as the basic assumptions to be addressed when approaching its hardware implementation, such as the preliminary partitioning of tasks between hardware and software, and the fixed-point representation of the processing to be implemented in hardware. The system has been validated by simulation in a 2 × 2 × 3.4 m3 volume, yielding mean absolute errors around 0.004 m for the X and Y axes, and around 0.01 m for the Z-axis, as well as lower standard deviations than 0.004 m for the X and Y axes and 0.01 m for the Z-axis.Agencia Estatal de InvestigaciónUniversidad de Alcal