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Impacto de las variantes genéticas de susceptibilidad a leucemia linfocítica crónica y de la vía de la autofagia sobre la supervivencia y la progresión de la enfermedad
No full textLa leucemia linfocítica crónica (LLC) es la forma más común de leucemia en adultos en
los países occidentales. Aunque esta enfermedad puede seguir un curso indolente, en otros
casos progresa rápidamente, se vuelve resistente al tratamiento y puede transformarse en
un linfoma de células B más agresivo. Aunque los estudios de asociación del genoma
completo (GWAS, por sus siglas en inglés) han identificado parte del componente
genético de la línea germinal que subyace a la susceptibilidad a la LLC, el uso potencial
de estas variantes para predecir la progresión de la enfermedad y la supervivencia del
paciente sigue siendo una incógnita. Así mismo, aún desconocemos la importancia que
las variantes genéticas en la ruta de la autofagia tienen sobre la etiología de la enfermedad,
su progresión y supervivencia de los pacientes. En esta tesis, nuestro objetivo fue
dilucidar los determinantes genéticos asociados con la progresión de la enfermedad y la
supervivencia de los pacientes, y profundizar en el papel que la autofagia tiene en el
desarrollo de la LLC. Por último, trabajamos en la caracterización funcional de las
variantes genéticas consideradas de interés.
En el primer estudio, incluido en esta tesis, se evaluó si la presencia de 41 variantes
genéticas de susceptibilidad para la LLC identificadas previamente en estudios de GWAS
nos podían ayudar a predecir la supervivencia global (SG) y el tiempo hasta el primer
tratamiento (THPT) en 1.039 pacientes con LLC. Nuestros resultados mostraron que,a
pesar de que algunos polimorfismos genéticos de un solo nucleótido (SNPs) asociaban
débilmente con la SG y el THPT de los pacientes, estas asociaciones no eran significativas
tras la correcciones por comparaciones múltiples. Además, los puntajes de riesgo
poligénico (PRSs) generados con estos SNPs mostraron una baja capacidad para predecir
la SG de los pacientes y el THPT, con áreas bajo la curva ROC (AUROC, por sus siglas
en inglés) de 0,57 y 0,62 respectivamente. Este ha sido el mayor estudio realizado hasta
la fecha para evaluar el efecto que las variantes genéticas de susceptibilidad para la LLC
tienen sobre la SG de los pacientes y el THPT y nos ha permitido comprobar de forma
inequívoca que las variantes genéticas de susceptibilidad para la LLC no afectan
sustancialmente a la SG de los pacientes con LLC y confirmar resultados previos que
sugerían un efecto nulo de estas variantes genéticas en la determinación del THPT.
En el segundo estudio, que forma parte de esta tesis, se analizaron más de 55.000 SNPs
relacionados con la autofagia en cuatro poblaciones independientes, incluyendo un total de 5.472 casos de LLC y 726.465 controles. Esta investigación identificó asociaciones
significativas con los genes CDKN2A y BCL2, que se correlacionaron con un mayor
riesgo de desarrollar LLC. La variante más significativa fue la asociada a CDKN2A (p =
1.57×10⁻¹²). También se validaron asociaciones previamente conocidas para los genes
FAS, BCL2 y BAK1, que están implicados en la regulación de la autofagia y la apoptosis
celular. A nivel molecular, los SNPs en los genes CDKN2A y FAS se correlacionaron con
niveles elevados de expresión de CDKN2A y ACTA2 en sangre y linfocitos, lo que sugiere
que estas variantes pueden afectar la respuesta inmune y los procesos celulares clave. No
obstante, el estudio no encontró una asociación significativa entre estas variantes y el
flujo de autofagia, ni con la progresión de la enfermedad o la supervivencia de los
pacientes, lo que indica que estas variantes podrían ser más relevantes para la iniciación
de la LLC que para su evolución posterior.Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in
Western countries. Although this disease may follow an indolent course, in some cases it
progresses rapidly, becomes resistant to treatment and/or transforms into a more
aggressive B-cell lymphoma. Although genome-wide association studies (GWAS) have
uncovered part of the germline genetic component underlying CLL susceptibility, the
potential use of these variants to predict disease progression and patient survival remains
unknown, as does the role of the autophagy-related genetic variants in disease etiology,
progression and survival. In this thesis, we aimed to elucidate the genomic determinants
associated with disease progression and survival, further investigate the role of autophagy
in CLL, and functionally characterize the most promising genetic variants.
In the first study, 41 variants previously identified in GWAS studies were evaluated to
determine whether they could predict overall survival (OS) and time to first treatment in
1,039 patients with CLL. Although some SNPs showed weak associations with OS and
THPT, these were not significant after applying corrections for multiple testing.
Furthermore, the polygenic risk scores (PRSs) generated with these SNPs show a low
ability to predict survival and disease progression, with areas under the ROC curve
(AUROC) of 0.57 for OS and 0.62 for THPT. Although this is the largest study evaluating
the effect of GWAS-identified susceptibility variants for CLL on OS, the results suggest
that CLL susceptibility variants do not substantially affect overall survival in CLL patients
and confirm previous results suggesting no effect of these variants on THPT.
In the second study, more than 55,000 autophagy-related SNPs were analyzed in four
independent populations, including a total of 5,472 CLL cases and 726,465 controls. This
research identified significant associations with the genes CDKN2A and BCL2, which
were correlated with an increased risk of developing CLL. The most significant variant
was the one associated with CDKN2A (p=1.57×10⁻¹²). Previously known associations
were also validated for the genes FAS, BCL2, and BAK1, which are involved in the
regulation of autophagy and cell apoptosis. At the molecular level, SNPs in the CDKN2A
and FAS genes were correlated with elevated expression levels of CDKN2A and ACTA2
in blood and lymphocytes, suggesting that these variants may affect immune response
and key cellular processes. However, the study found no significant association between these variants and autophagic flux, disease progression or survival, indicating that these
variants might be more relevant to the initiation of CLL than to its subsequent evolution.Tesis Univ. Granada.European Union’s Horizon 2020 research and innovation program, Nº 856620the Instituto de Salud Carlos III and FEDER (Madrid, Spain; PI17/02256 and PI20/01845)Consejería de Transformación Económica, Industria, Conocimiento y Universidades y FEDER (PY20/01282)US National Cancer Institute grants P50 CA97274 and R01 CA9215
Medical Examination Before Marriage -A Comparative Study
No full textThe topic of medical examination before marriage is a contemporary issue that
emerged in the 1980s. Given the recent health and social challenges, along with
the significant advancements in the field of genomics, this topic has resurfaced
and has been adopted in many Arab countries as a prerequisite for marriage
contracts. There is a debate regarding its obligatory nature, with some viewing it
as a requirement and others as a preventive measure. Among scholars, opinions
vary, with some permitting it, others mandating it, and some opposing it. This
disagreement arises from the evidence presented by each side and the pros and
cons associated with these medical examinations. It should be noted that the
requirement for medical examination before marriage is not intended to impose
restrictions or hardships; rather, it aims to positively impact the preservation of
people’s interests at various levels. One of its primary objectives is the
protection of life and lineage, alongside the objective of preserving wealth
Unraveling the lab-scaling up production of activated carbon from plastic-enriched waste
No full textThis work explores the preparation of activated carbon from the pyrolysis char residues in two different scale scenarios, i.e. a laboratory furnace and a scaled-up version in a lab-pilot plant rotatory furnace. As the activating method, K2CO3 was added to the carbonaceous precursor. The activation temperature (700-800ºC) and the impregnation char: K2CO3 ratio (1:0.25-1:2) were modified in both setups, comparing the attained results of textural development and chemical composition by elemental analysis and XPS. The effect of the agitation during the activation process was also evaluated at the lab-pilot plant scale. The results pointed out a better definition of the textural properties at the lab-pilot plant scale, with an important influence on the agitation in the process. Thus, the optimum temperature was set as 750 ºC, and the char: K2CO3 ratio as 1:0.5, leading to a material with an area of ~1100 m2 g-1, and a pore volume of ~0.8 cm3 g-1. The resulting activated carbon could adsorb up to 270 mg CO2 g-1. Dynamic tests of CO2-CH4 mixtures (from 20:80 to 40:60) were carried out with the optimized material prepared at the lab-pilot plant scale, demonstrating the suitability of the valorized residue as activated carbon for biogas upgrading, with high stability in sequential reusing assays
Exploring consumer behaviour on carbon labelled food products: Evidence from a survey on the case of sandwich production and consumption in UK
No full textGrant ‘Marie Skłodowska-Curie Actions (MSCA) Postdoctoral Fellowship’ with Grant agreement ID: 101052284By assessing carbon footprints and raising awareness of carbon labelling, the food sector is setting long-term targets to reduce carbon emissions and accelerate the transition to low-carbon food production. Carbon labelling, also known as carbon labelling, informs customers about a product's production, distribution, and disposal carbon emissions. This study examines how customers view carbon labelling and how it affects their purchases. The study also examines the complex food industry, identifying the biggest carbon emitters and proposing sustainable alternatives. The study collects qualitative and quantitative data using mixed methodologies. An overview of the literature shows how carbon labelling promotes sustainable consumption. Life Cycle Assessment (LCA) is used to evaluate two sandwich recipes' carbon footprints, focusing on emissions per item. LCA results indicated that carbon footprint of a cheese and mayonnaise sandwich ranged between 700 and 750 g CO2 eq, while a ham and cheese sandwich ranged between 1053 and 1070 g CO2 eq., and the primary contributors for these emissions were ingredient production, packaging and energy consumption. A sandwich maker partnership simplifies case study data collection, providing a complete carbon footprint analysis throughout production. This study suggests ways to minimise food industry carbon emissions for a sustainable future. Consumer knowledge and relevance of carbon labelling vary, according to our results. Survey findings revealed that 68.6 % of respondents recognise the significance of carbon labelling, however, only 26.9 % reported that their purchasing decisions are influenced by carbon labelling. This indicated a gap between consumer awareness and behavioural change. Consumers are concerned about carbon footprints; thus, carbon labels affect shopping decisions differently. This study suggests that consumer education, standardisation of carbon labelling and recipe modifications could increase effectiveness of carbon labelling in the food industry and its potential to change consumer behaviour towards greener choices and lower carbon footprints.Marie Skłodowska-Curie Actions (MSCA) 10105228
‘With music somewhere else’. The phenomenon of macrofestivals in Spain as a reflection of the new paradigms of leisure and cultural consumption
No full textLos macrofestivales de música han experimentado una expansión significativa durante la última década, consolidándose como uno de los principales motores económicos de la industria cultural en España. Cada año, cerca de mil eventos de este tipo movilizan a grandes multitudes por todo el país, generando ingresos multimillonarios y reuniendo en varios días a las principales figuras de la música a nivel nacional e internacional. Sin embargo, detrás de este exitoso modelo se ocultan una serie de problemáticas relacionadas con la precariedad, la desigualdad y la falta de regulación que ameritan una profunda reflexión dada su supremacía en los nuevos modelos de ocio y consumo cultural. El presente artículo tiene como objetivo, tras la recopilación de la bibliografía mediática y académica disponible, profundizar en las dimensiones que intervienen en el desarrollo de los macrofestivales de música en España. En el plano analítico, estos aspectos se explican a través del capital humano involucrado (trabajadores, artistas y público), el impacto ambiental que generan así como las diversas implicaciones políticas y económicas que subyacen de todo lo anterior. Por último, se pretende aportar pistas y experiencias para repensar el binomio ocio-cultura desde un compromiso hacia modelos más inclusivos, sostenibles y democráticos.Macro music festivals have experienced a significant expansion over the last decade, consolidating themselves as one of the main economic engines of the cultural industry in Spain. Each year, nearly a thousand events mobilize huge crowds all over the country, generating multi-million-dollar revenues and bringing together during several days the main national and international music stars. However, behind this successful model are hidden a series of issues related to instability, inequality and lack of regulation that merit a profound reflection given these events’ supremacy in the new models of leisure and cultural consumption. This article aims, after a revision of the media and academic literature, to examine the dimensions involved in the development of these macro music festivals in Spain. On an analytical level, these aspects are explained by the human capital involved (workers, artists and public), the environmental impact they generate, as well as the various political and economic implications that underline all the above. Finally, the aim is also to provide clues and experiences to rethink this leisure-culture binomial from a commitment towards more inclusive, sustainable and democratic models.Grupo de investigación Antropología y Filosofía (SEJ-126). Universidad de Granada.
Departamento de Antropología, Geografía e Historia. Universidad de Jaén.
Departamento de Filosofía II. Universidad de Granada
Transmission of Knowledge and Mobility of Scholars in the Ṭabaqāt ʽulamāʼ Ifrīqiya of Abū l-ʽArab al-Tamīmī
No full textEsta publicación es resultado del proyecto PID2021-122872NB-C22. Tránsitos y migraciones en el norte de África: análisis diacrónico de la población y su entorno (DIANA), el cual, junto con el proyecto PID2021-122872NB-C21. Transformaciones del espacio magrebí en perspectiva histórica (TRAMAGHIS), se integra en el proyecto coordinado de investigación Tránsitos y transformaciones en el espacio y la población magrebíes (MAGNA II). Ambos han sido financiados por MICIN/AEI/10.13039/501100011033 y FEDER Una manera de hacer Europa.La presente aportación estudia la circulación de ulemas en la región de Ifrīqiya anterior al s. IV H./s. X d. C., atendiendo a los lugares a los que acudieron para formarse y, a la vez, en qué medida Ifrīqiya fue foco de atracción para sabios foráneos. Para ello, se analiza la relación maestro-discípulo de los ulemas recogidos en las Ṭabaqāt ʽulamāʼ Ifrīqiya de Abū l-ʽArab al-Tamīmī (m. 945/333), la obra más antigua acerca de los sabios de la región anteriores al s. X, junto con el Kitāb ṭabaqāt ʽulamāʼ Ifrīqiya de Ibn Hāriṯ al-Jušanī (m. 971/361). De este modo es posible establecer los destinos más relevantes en lo que se refiere a la movilidad hacia el exterior, así como describir la transmisión del conocimiento que depende de un dinamismo interno, dentro de la propia región, siendo Qayrawān en todo caso el centro aglutinador de la actividad intelectual. El presente análisis no puede dejar de considerar el hecho de que algunos de estos sabios desempeñaron ciertas actividades comerciales o económicas, que con frecuencia aparecen vinculadas en la propia obra a sus tareas religiosas. Del mismo modo, los datos indican que el comercio pudo ser una vía de acceso en la región al ámbito intelectual.The present contribution studies the circulation of ulema in the Ifrīqiya region before the 4th-century H./10th-century a. C., taking into account the places to which they went to train and, at the same time, to what extent Ifrīqiya was a focus of attraction for foreign scholars. To do this, the teacher-disciple relationship of the ulema is analyzed as stated in the Ṭabaqāt ʽulamāʼ Ifrīqiya of Abū l-ʽArab al-Tamīmī (d. 945/333), the oldest work about the wise men of the region before the 10th-century, together with the Kitāb ṭabaqāt ʽulamāʼ Ifrīqiya of Ibn Hārith al-Jushanī (d. 971/361). Data are provided on the most relevant destinations in terms of mobility to the outside, as well as the transmission of knowledge that depends on internal dynamism, within the region itself, Qayrawān being in any case the unifying center of intellectual activity. The present analysis cannot fail to consider the fact that some of these wise men carried out certain comercial or economic activities, which often appear linked in the work itself to their religious tasks. Likewise, the data indicate that trade may have been a gateway to the intelectual sphere in the region.MICIN/AEI/10.13039/501100011033 PID2021-122872NB-C22, PID2021-122872NB-C21FEDER Una manera de hacer Europ
Validation of the computerised battery for neuropsychological evaluation of children (BENCI) in a Cuban sample
No full textAndalusian agency for international developmental cooperation of the regional government of AndalusiaThe aim of this research was to analyse the reliability and validity of the Computerised Battery for Neuropsychological Evaluation of Children (BENCI) in a Cuban population of children and adolescents. The study involved 1714 Cuban students between the ages of 6 and 18 who were divided into three groups according to their level of education (Elementary: 6–11 years old; High School: 12–14 years old; and Pre-University: 15–18 years old). All participants were evaluated using the BENCI with some also undergoing additional neuropsychological testing. The BENCI evaluates the following cognitive domains: processing speed, visuomotor coordination, attention, memory, language, and executive functions. The results showed that the BENCI has good test–retest reliability indices and high internal consistency values in Reasoning, Reaction Time, and Working Memory. In terms of validity, the data revealed significant correlations between the BENCI tests and other neuropsychological tests assessing similar cognitive functions. The BENCI also has discriminative validity, as it was found that performance on the tests varies according to the level of education of those being evaluated. In terms of construct validity, confirmatory factor analysis showed that the fit indices for the executive functions dimension of the BENCI are adequate. The data show that the BENCI is a reliable and valid instrument for assessing neurodevelopment in Cuban children and adolescents. Since this is the first neuropsychological test of its kind to be validated in the Cuban population, this finding is of particular importance.Regional government of Andalusi
Análisis de Riesgos - Introducción a la Teoría de Decisión Estadística (Tema 2)
No full textEste material aborda los principios fundamentales de la teoría de decisión estadística, un marco esencial para enfrentar problemas en los que la incertidumbre influye de manera significativa. Se analizan los elementos básicos de un problema de decisión: el decisor, los estados de la naturaleza, las alternativas posibles y las funciones de utilidad, pérdida y riesgo.
Se justifica cómo estas funciones permiten modelar matemáticamente las consecuencias de cada decisión, proporcionando herramientas para cuantificar beneficios, costes y probabilidades de distintos escenarios. Asimismo, se describe la adaptación de los criterios de decisión en función del nivel de información disponible: certeza, incertidumbre o riesgo.
Mediante ejemplos prácticos y casos reales, se ilustra el uso de tablas y árboles de decisión, junto con técnicas de optimización basadas en programación lineal. Finalmente, se destaca la relevancia de esta teoría para la toma de decisiones estratégicas en áreas como la economía, la salud o la gestión de riesgos.
El objetivo de este material es ofrecer una visión clara y aplicada de la teoría de decisión estadística, brindando herramientas útiles para fortalecer la capacidad de tomar decisiones fundamentadas en datos.This material addresses the fundamental principles of statistical decision theory, an essential framework for tackling problems where uncertainty plays a significant role.
The basic elements of a decision problem are analyzed: the decision-maker, states of nature, possible alternatives, and utility, loss, and risk functions. It is explained how these functions enable the mathematical modeling of decision consequences, providing tools to quantify benefits, costs, and probabilities of different scenarios.
The adaptation of decision criteria is described according to the level of available information: certainty, uncertainty, or risk. Through practical examples and real-world cases, the use of decision tables and trees is illustrated, along with optimization techniques based on linear programming.
Finally, the relevance of this theory for strategic decision-making in fields such as economics, healthcare, or risk management is highlighted. The objective of this material is to provide a clear and applied overview of statistical decision theory, offering useful tools to strengthen the ability to make informed, data-driven decisions
Child and Adolescent Health Programs in Obesity and Depression: A Systematic Review and Meta-Analysis
No full textObesity and depression are public health issues of increasing concern worldwide.
This study aims to evaluate programs that address obesity and their impact on depressive
symptoms in children and adolescents. Obesity and depression share a bidirectional
relationship, where each can serve as both a cause and a consequence of the other. Methods:
A systematic review and meta-analysis were conducted following PRISMA criteria,
with the registration recorded under PROSPERO code (CRD42024550644). The selected
publications report on intervention programs for obesity and depression in children and
adolescents aged 6 to 18 years. The selection was from databases including PUBMED,
SCOPUS, LILACS, COCHRANE, WOS, SciELO, and ScienceDirect, using PICOS criteria
to define inclusion. ROB-2 and ROBINS-1 were applied to assess bias. Results: Out of
3376 articles reviewed, eight met the inclusion criteria, some including several programs.
These programs varied in duration and type, demonstrating changes in reducing Body
Mass Index (BMI) and depressive symptoms. However, evidence supporting the effectiveness
of programs that address both conditions is limited, particularly in developing
countries. Additionally, the results exhibit high heterogeneity due to the diversity of evaluation
criteria and methodological approaches, highlighting considerable risks of bias.
Conclusions: Intervention programs for obesity management show statistically significant
effects on depressive symptoms, although there is heterogeneity in the designs for their
standardization and long-term follow-up strategies; however, the evaluations consider
DSM-5 and ICD-11 criteria, which contributes to homogeneity. It is vital to address these
closely related issues from a multidimensional perspective, considering socio-emotional
and psychological factors, and to promote early intervention to maximize effectiveness and
enhance quality of life at various stages of development.Code 11340012 of
Universidad Santo Tomás, Chile (Proyectos de Agencia Nacional de Investigación y Desarrollo, ANID,
grant: SA77210016FONIS SA24I0065, NAM22I0009 and FOVI220134Universidad de
Granad
Sfruttamento economico e sfruttamento culturale nel mercato di lavoro (presentación de Power-Point)
No full textLa “Cátedra Extraordinaria de Filosofía Social de la Discriminación Corporal” se crea el 1 de junio de 2023 por convenio entre la Universidad de Granada y el Instituto de las Mujeres (BOE núm. 139, de 12 de junio de 2023). El acuerdo entre ambas entidades estará vigente hasta el 31 de octubre de 2025, si bien el proyecto de la Cátedra nace con la vocación de consolidarse y estabilizarse como espacio de estudio, reflexión e intervención social.José Luis Moreno Pestaña y Pablo Beas Marín presentan la Cátedra Extraordinaria de Filosofía Social de la Discriminación Corporal en la Università degli Studi di Milano-Bicocca en el marco de los Seminarios de Teoría Crítica organizados por Vittorio Morfino el próximo 7 de mayo de 2025. Además, imparten la conferencia titulada «Sfruttamento economico e sfruttamento culturale nel mercato del lavoro». Este power-point contiene su intervención.José Luis Moreno Pestaña and Pablo Beas Marín present the Extraordinary Chair of Social Philosophy of Corporal Discrimination at the Università degli Studi di Milano-Bicocca within the framework of the Critical Theory Seminars organized by Vittorio Morfino on May 7, 2025. In addition, they will give a lecture entitled “Sfruttamento economico e sfruttamento culturale nel mercato del lavoro”. This power-point contains their intervention.Cátedra Extraordinaria Filosofía Social de la Discriminación Corporal (Inmujeres-UGR