Chronodisruption and Ambulatory Circadian Monitoring in Cancer Patients: Beyond the Body Clock

Purpose of Review: Circadian rhythms impose daily rhythms a remarkable variety of metabolic and physiological functions, such as cell proliferation, inflammation, and DNA damage response. Accumulating epidemiological and genetic evidence indicates that circadian rhythms’ disruption may be linked to cancer. The integration of circadian biology into cancer research may offer new options for increasing cancer treatment effectiveness and would encompass the prevention, diagnosis, and treatment of this disease. Recent Findings: In recent years, there has been a significant development and use of multi-modal sensors to monitor physical activity, sleep, and circadian rhythms, allowing, for the very first time, scaling accurate sleep monitoring to epidemiological research linking sleep patterns to disease, and wellness applications providing new potential applications. Summary: This review highlights the role of circadian clock in tumorigenesis, cancer hallmarks and introduces the state-of-the-art in sleep-monitoring technologies, discussing the eventual application of insights in clinical settings and cancer researchThis work was supported in part by CLARIFY project, within European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 875160, Instituto de Fomento de la Región de Murcia (INFO) and the European Regional Development Fund (FEDER

Unraveling the effect of silent, intronic and missense mutations on VWF splicing: contribution of next generation sequencing in the study of mRNA

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. clinicaltrials.gov identifier:02869074

Cuentos del Olivar

En este apasionante viaje tenemos las puertas abiertas para todo aquel que se quiera sumar, ya sea trabajando en pos de la difusión de la cultura ligada al olivo o disfrutando de lecturas como las que se recogen en este libro, que seguro les depara un sabroso disfrute y les descubre una cultura del olivar que tiene a sus espaldas varios milenios de historia. Les deseo que paladeen cada uno de estos relatos, que conforman un excelente aperitivo literario.Área de Historia del Art

Pasados y presente. Estudios para el profesor Ricardo García Cárcel

Ricardo García Cárcel (Requena, 1948) estudió Historia en Valencia bajo el magisterio de Joan Reglà, con quien formó parte del primer profesorado de historia moderna en la Universidad Autónoma de Barcelona. En esta universidad, desde hace prácticamente cincuenta años, ha desarrollado una extraordinaria labor docente y de investigación marcada por un sagaz instinto histórico, que le ha convertido en pionero de casi todo lo que ha estudiado: las Germanías, la historia de la Cataluña moderna, la Inquisición, las culturas del Siglo de Oro, la Leyenda Negra, Felipe II, Felipe V, Austrias y Borbones, la guerra de la Independencia, la historia cultural, los mitos de la historia de España... Muy pocos tienen su capacidad para reflexionar, ordenar, analizar, conceptualizar y proponer una visión amplia y llena de matices sobre el pasado y las interpretaciones historiográficas. A su laboriosidad inimitable se añade una dedicación sin límites en el asesoramiento de alumnos e investigadores e impulsando revistas, dosieres, seminarios o publicaciones colectivas. Una mínima correspondencia a su generosidad lo constituye este volumen a manera de ineludible agradecimiento

Tensor Renormalization Group en teoría de campos bosónica

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Física Teórica. Fecha de Lectura: 25-04-2023We present a study of scalar boson theory in discretized 2D space-time. We explore its real space renormalization group and its integrability properties using tools from tensor network theory and exactly solvable models. One main feature of the work is that we do not discretize the fields at any point in the process, thus preserving its interpretation as a field theory. The present work compiles a series of three articles written in collaboration with my thesis director, Esperanza López, and Germán Sierra. In two of them we adapt well-known tensor network procedures to a boson in two dimensions, firstly to the free model and then we include interactions. Specifically, we present a singular value decomposition for continuous matrices and use it to adapt the Tensor Renormalization Group (TRG) protocol. We show that in this way our new algorithm implements the renormalization group based on entanglement properties of the field theory. Later on we explore the interacting case in the framework of perturbation theory. We highlight the similarities of our real space renormalization procedure with the Wilsonian renormalization techniques in momentum space. In both cases we apply the new algorithms to obtain numerical results. Our basic benchmark is the computation of the partition function with periodic boundary conditions. This quantity is exactly obtainable by straightforward computations in momentum space. Therefore it is possible to estimate the precision of our algorithm in a reliable way. In the free massless limit, we are able to compute the central charge of the corresponding conformal field theory with high precision. We also show that, as happens with the original TRG algorithm, a non-physical IR fixed point with corner double line structure appears along the renormalization flow generated by our algorithm. In the studied models, the partition function is computed starting from local statistical weights. We also explore the properties of the free boson model using the tools of exactly solvable models, both in the massless and massive regime. We show that the statistical weights satisfy the Yang-Baxter equation. We find the eigenvalues and eigenvectors of the row-to-row transfer matrix, obtain the conserved charges and implement the quantum inverse scattering method. It is known that some statistical weights of other integrable models have a dual interpretation: they can be also understood as the 2-particle scattering S-matrices of a model with factorizable global S-matrix. We show that this is also the case of the statistical weights of the free boson on a 2D latticePresentamos un estudio de la teoría del bosón escalar en un espacio-tiempo discretizado de dos dimensiones. En él exploramos su grupo de renormalización en espacio real y sus propiedades de integrabilidad, empleando para ello herramientas de la teoría de redes tensoriales y modelos exactamente solubles. Una de las principales características del trabajo es que no discretizamos los campos en ningún momento, preservando así su interpretación como teoría de campos. El presente trabajo compila tres artículos escritos en colaboración con mi directora de tesis, Esperanza López, y Germán Sierra. En dos de ellos adaptamos procedimientos conocidos de redes tensoriales a un bosón en dos dimensiones, primero al modelo libre y después incluyendo interacciones. En concreto proponemos una descomposición en valores singulares (singular value decomposition) para matrices continuas y la usamos para adaptar el protocolo conocido como Tensor Renormalization Group (TRG). El nuevo algoritmo que obtenemos implementa el grupo de renormalización basándose en las propiedades de entrelazamiento del modelo. Más adelante exploramos el caso con interacción en el marco de teoría de perturbaciones, destacando las similitudes de nuestro procedimiento de renormalización en espacio real con las técnicas de renormalización wilsoniana en espacio de momentos. En ambos casos aplicamos los nuevos algoritmos para obtener resultados numéricos. Nuestra referencia principal para ello es el cálculo de la función de partición con condiciones de contorno periódicas. Como esta es una cantidad que se puede obtener de forma exacta mediante cálculos simples en espacio de momentos, nos es posible estimar la precisión de nuestro algoritmo de manera fiable. En el límite de la teoría libre y sin masa, podemos calcular la carga central de la teoría conforme correspondiente con gran precisión. También mostramos que, al igual que sucede con el algoritmo TRG original, aparece un punto fijo infrarrojo no físico con estructura de corner double line al avanzar en el flujo de renormalización generado por nuestro algoritmo. En los modelos estudiados, la función de partición se calcula a partir de pesos estadísticos locales. También exploramos las propiedades del bosón libre utilizando las herramientas de modelos exactamente solubles, tanto en el régimen sin masa como en el masivo. Hallamos que los pesos estadísticos satisfacen la ecuación de Yang-Baxter. Encontramos los autovalores y autovectores de la matriz de transferencia fila-a-fila, obtenemos las cargas conservadas e implementamos el quantum inverse scattering method. Se sabe que algunos pesos estadísticos de otros modelos integrables admiten una doble interpretación: también pueden entenderse como matrices S asociadas a la dispersión de 2 partículas en un modelo con matriz S global factorizable. Mostramos que este es el caso para los pesos estadísticos del bosón libre en una retícula bidimensiona

Un brocense de cine

El trabajo obtuvo un Premio Tomás García Verdejo a las buenas prácticas educativas en la Comunidad Autónoma de Extremadura para el curso 2018/2019, Modalidad B.Se describe una experiencia llevada a cabo en el IES El Brocense (Cáceres) que consistió en desarrollar distintas acciones utilizando como recurso el cine. Además de aprender contenidos de las asignaturas impartidas a través del cine, se perseguía fomentar la convivencia escolar y promover la igualdad entre hombres y mujeres. Algunas de las actividades realizadas fueron: jornadas sobre el cine, elaboración y grabación de cortos cinematográficos, asistencia a un musical, participación en conferencias y jornadas sobre cine, elaboración de carteles, etc.ExtremaduraES

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p<0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p<0·0001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status