Endogenous topoisomerase II-mediated DNA breaks drive thymic cancer predisposition linked to ATM deficiency

The ATM kinase is a master regulator of the DNA damage response to double-strand breaks (DSBs) and a well-established tumour suppressor whose loss is the cause of the neurodegenerative and cancer-prone syndrome Ataxia-Telangiectasia (A-T). A-T patients and Atm−/− mouse models are particularly predisposed to develop lymphoid cancers derived from deficient repair of RAG-induced DSBs during V(D)J recombination. Here, we unexpectedly find that specifically disturbing the repair of DSBs produced by DNA topoisomerase II (TOP2) by genetically removing the highly specialised repair enzyme TDP2 increases the incidence of thymic tumours in Atm−/− mice. Furthermore, we find that TOP2 strongly colocalizes with RAG, both genome-wide and at V(D)J recombination sites, resulting in an increased endogenous chromosomal fragility of these regions. Thus, our findings demonstrate a strong causal relationship between endogenous TOP2-induced DSBs and cancer development, confirming these lesions as major drivers of ATM-deficient lymphoid malignancies, and potentially other conditions and cancer types.Junta de Andalucía SAF2010-21017, SAF2013-47343-P, SAF2014-55532-R, SAF2017-89619-R, CVI-7948European Research Council ERC-CoG-2014-64735

Transvaginal Ultrasound Accuracy in the Hydrosalpinx Diagnosis: A Systematic Review and Meta-Analysis

Hydrosalpinx is a condition with a crucial prognostic role in reproduction, and its diagnosis by a non-invasive technique such as ultrasound is key in achieving an adequate reproductive assessment while avoiding unnecessary laparoscopies. The aim of the present systematic review and meta-analysis is to synthetize and report the current evidence on transvaginal sonography (TVS) accuracy to diagnose hydrosalpinx. Articles on the topic published between January 1990 and December 2022 were searched in five electronic databases. Data from the six selected studies, comprising 4144 adnexal masses in 3974 women, 118 of which were hydrosalpinxes, were analyzed as follows: overall, TVS had a pooled estimated sensitivity for hydrosalpinx of 84% (95% confidence interval (CI) = 76-89%), specificity of 99% (95% CI = 98-100%), positive likelihood ratio of 80.7 (95% CI = 33.7-193.0), and negative likelihood ratio of 0.16 (95% CI = 0.11-0.25) and DOR of 496 (95% CI = 178-1381). The mean prevalence of hydrosalpinx was 4%. The quality of the studies and their risk of bias were assessed using QUADAS-2, evidencing an overall acceptable quality of the selected articles. We concluded that TVS has a good specificity and sensitivity for diagnosing hydrosalpinx

First sexual intercourse and subsequent regret in three developing countries

Purpose: Adolescents who engage in sex can be affected by a range of negative physical and psychological consequences. We intend to analyze the reasons behind first sex, regret, and the association between reasons and regret. Methods: A questionnaire was implemented to 8495 high schools students, aged 14-18, in the Philippines, El Salvador and Peru. Sexually active participants responded whether several circumstances were reasons involved in their first sexual relationship. They also responded whether they regretted having already had sexual relationships. Results: More than a third of respondents reported at least one external pressure leading to first sex, and about half reported at least one reason implying getting carried away by sexual arousal. More females affirmed they regret having already had sex. Logistic regression shows that reasons for first sex associated with regret were partner insistence, "uncontrolled situations" and seeing sexual images. These reasons were associated with regret even when love was also reported as related to first sex. Conclusions: Adolescent sexual experience is often motivated by pressure and circumstances that lower the control over their decisions concerning sex, such as external pressure (because most friends already had sex or because of partner insistence) or getting carried away by sexual arousal (through an "uncontrolled situation" or viewing sexual images) rather than by mature decisions, and this may result in later regret. Adolescents should be helped by parents, educators and policy makers to be aware of these characteristics of adolescent sex and empowered to make assertive and informed decisions concerning their sexuality

Evaluación del sistema de admisión a las carreras de Ingeniería Agronómica, Ingeniería Zootecnista y Medicina Veterinaria de la FAZ – UNT por los alumnos ingresantes : Año 2012

El ingreso a la FAZ - UNT adquirió distintas modalidades a través de los años. Actualmente, el Sistema de Admisión se aplica a las tres carreras de grado evaluando: Matemática, Física, Química y Biología. Los alumnos ingresadosdeben realizar un trabajo monográfico a cargo de un docente - tutor. El objetivo fue analizar y evaluar el Sistema de Admisión a las Carreras de Ingeniero Agrónomo, Zootecnista y Medicina Veterinaria por parte de los alumnos ingresantes – año 2012. Para la realización del presente trabajo se utilizaron los datos de una encuesta evaluativa confeccionada por la Comisión de Ingreso y se trabajó con una población de 250 ingresantes. Se obtuvo que al 73,6% de los alumnos encuestados le pareció adecuada la duración y los horarios del curso; el 68,8% opinó que las instalaciones son adecuadas y el 59,6% obtuvo un buen aprovechamiento de las clases presenciales, entre otros ítems. Se concluye que: duración, horarios y espacios destinados a las actividades del curso son adecuados para la implementación del mismo; Química fue la asignatura mejor aprovechada y los alumnos consideraron de gran utilidad la propuesta del trabajo monográfico. Esta encuesta permitirá mejorar condiciones de los ingresantes y contribuir a procesos de enseñanza - aprendizajeEje temático 1: Problemáticas y alternativas de mejora de la enseñanza b - Las estrategias de admisión e inclusión en el ingreso y los primeros añosFacultad de Ciencias Agrarias y Forestale

Large-Scale Temperature Changes across the Southern Andes: 20th-Century Variations in the Context of the Past 400 Years

Long-term trends of temperature variations across the southern Andes (37–55° S) are examined using a combination of instrumental and tree-ring records. A critical appraisal of surface air temperature from station records is presented for southern South America during the 20th century. For the interval 1930–1990, three major patterns in temperature trends are identified. Stations along the Pacific coast between 37 and 43° S are characterized by negative trends in mean annual temperature with a marked cooling period from 1950 to the mid-1970s. A clear warming trend is observed in the southern stations (south of 46°S), which intensifies at higher latitudes. No temperature trends are detected for the stations on the Atlantic coast north of 45° S. In contrast to higher latitudes in the Northern Hemisphere where annual changes in temperature are dominated by winter trends, both positive and negative trends in southern South America are due to mostly changes in summer (December to February) temperatures. Changes in the Pacific Decadal Oscillation (PDO) around 1976 are felt in summer temperatures at most stations in the Pacific domain, starting a period with increased temperature across the southern Andes and at higher latitudes.Tree-ring records from upper-treeline were used to reconstruct past temperature fluctuations for the two dominant patterns over the southern Andes. These reconstructions extend back to 1640 and are based on composite tree-ring chronologies that were processed to retain as much low-frequency variance as possible. The resulting reconstructions for the northern and southern sectors of the southern Andes explain 55% and 45% ofthe temperature variance over the interval 1930–1989, respectively. Cross-spectral analysis of actual and reconstructed temperatures over the common interval 1930–1989, indicates that most of the explained varianceis at periods >10 years in length. At periods >15 years, the squaredcoherency between actual and reconstructed temperatures ranges between 0.6 and 0.95 for both reconstructions. Consequently, these reconstructions are especially useful for studying multi-decennial temperature variations in the South American sector of the Southern Hemisphere over the past 360 years. As a result, it is possible to show that the temperatures during the 20thcentury have been anomalously warm across the southern Andes. The mean annual temperatures for the northern and southern sectors during the interval 1900–1990 are 0.53 °C and 0.86 °C above the1640–1899 means, respectively. These findings placed the current warming in a longer historical perspective, and add new support for the existence of unprecedented 20th century warming over much of the globe. The rate of temperature increase from 1850 to 1920 was the highest over the past 360 years, a common feature observed in several proxy records from higher latitudes in the Northern Hemisphere.Local temperature regimes are affected by changes in planetary circulation, with in turn are linked to global sea surface temperature (SST) anomalies. Therefore, we explored how temperature variations in the southern Andes since 1856 are related to large-scale SSTs on the South Pacific and South Atlantic Oceans. Spatial correlation patterns between the reconstructions and SSTs show that temperature variations in the northern sector of the southern Andes are strongly connected with SST anomalies in the tropical and subtropical Pacific. This spatial correlation pattern resembles the spatial signature of the PDO mode of SST variability over the South Pacific and is connected with the Pacific-South American (PSA) atmospheric pattern in the Southern Hemisphere. In contrast, temperature variations in the southern sector of the southern Andes are significantly correlated with SST anomalies over most of the South Atlantic, and in less degree, over the subtropical Pacific. This spatial correlation field regressed against SST resembles the `Global Warming' mode of SST variability, which in turn, is linked to the leading mode of circulation in the Southern Hemisphere. Certainly, part of the temperature signal present in the reconstructions can be expressed as a linear combination of four orthogonal modes of SST variability. Rotated empirical orthogonal function analysis, performed on SST across the South Pacific and South Atlantic Oceans, indicate that four discrete modes of SST variability explain a third, approximately, of total variance in temperature fluctuations across the southern Andes.Fil: Villalba, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Lara, Antonio. Universidad Austral de Chile; ChileFil: Boninsegna, Jose Armando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Masiokas, Mariano Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Delgado, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Aravena, Juan C.. Universidad de Chile; ChileFil: Roig Junent, Fidel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Schmelter, Andrea. Universitaet Bonn; AlemaniaFil: Wolodarsky, Alexia. Universidad Austral de Chile; ChileFil: Ripalta, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; Argentin

First-Trimester Sequential Screening for Preeclampsia Using Angiogenic Factors : Study Protocol for a Prospective, Multicenter, Real Clinical Setting Study

The incidence of preeclampsia (PE) is about 2-8%, making it one of the leading causes of perinatal morbidity and maternal mortality in the world. Early prophylactic low dose administration (150 mg) of acetylsalicylic acid is associated with a significant reduction in the incidence of early-onset PE, intrauterine growth restriction (IUGR), and neonatal mean stay in the intensive care unit (ICU). Universal implementation of a first-trimester screening system including angiogenic and antiangiogenic markers [the Placental Growth Factor (PlGF) and/or soluble fms-like Tyrosine Kinase-1 (sFlt-1)] has shown a prediction rate of 90% for early-onset PE but entails a high financial cost. The aim of this study is to determine the predictive and preventive capacity of a universal PE first-trimester two-step sequential screening model, determining the PlGF only in patients previously classified as intermediate risk by means of a multivariate model based on resources already used in the standard pregnancy control, in a real clinical setting. We hypothesize that this screening model will achieve similar diagnostic performance as the universal determination of PlGF but at a lower economic cost. This is a prospective, multicentric, cohort study in a real-world clinical setting. Every singleton pregnancy will be recruited at the routine first pregnancy visit. In a first step, the first-trimester risk of PE will be calculated using a multivariate Gaussian distribution model, based on medical history, mean blood pressure, Pregnancy-Associated Plasma Protein A (PAPP-A), and Uterine Artery Doppler Pulsatility Index (UTPI). Patients will be classified into three risk groups for PE: (1) risk ≥ 1/50, high-risk with no further testing (blinded PlGF); (2) risk between 1/51 and 1/500, medium-risk requiring further testing; and (3) risk ≤ 1/501, low-risk with no further testing. In a second step, the PlGF will only be determined in those patients classified as intermediate risk after this first step, and then reclassified into high- or low-risk groups. Prophylactic administration of aspirin (150 mg/day) will be prescribed only in high risk patients. As a secondary objective, sFlt-1 values will be blindly determined in patients with high and intermediate risk to assess its potential performance in the screening for PE. The study will be conducted in accordance with the principles of Good Clinical Practice. This study is approved by the Aragon Research Ethics Committee (CEICA) on 3 July 2020 (15/2020). , identifier: NCT04767438

Homérica: estudiar y vivir el mundo griego

Depto. de Filología ClásicaFac. de FilologíaFALSEsubmitte

Methodological approximation to an articulation between risk management, environmental management and land regulation

El nuevo escenario territorial generado por el cambio climático y la globalización económica ha aumentado la vulnerabilidad de la población a sufrir eventos asociados a riesgos naturales. El Ordenamiento Territorial surge como una herramienta para disminuir la vulnerabilidad, en forma planificada y sustentable con el ambiente. Sin embargo, para que dicha herramienta sea realmente eficaz, es necesario que integre la Gestión del Riesgo y la Gestión Ambiental, definiéndose de esa manera una metodología integradora. Con este fin, se presentan en este artículo dos aproximaciones metodológicas surgidas de la discusión de una comunidad de práctica integrada por académicos de universidades latinoamericanas que han unido sus esfuerzos y experiencias para solucionar un problema común, y que pretende disminuir el riesgo de sus poblaciones a sufrir desastres naturales.The new territorial scenario produced by climate change and economic globalization has made the population more vulnerable to suffer events associated to natural risks. Land Regulation is born as a tool to reduce vulnerability in a planned and environmentally sustainable way. However, in order for this tool to be truly efficient, it is necessary for it to be a part of both Risk Management and Environmental Management, thus defining an integrated methodology. With this aim in mind, this paper presents two methodological approaches born from the discussions of a practical community formed by Latin American university professors who have joined efforts and experiences to solve a common problem and which tries to reduce the risk that their populations run of suffering natural disasters.Departamento de Geografí

Methodological approximation to an articulation between risk management, environmental management and land regulation

El nuevo escenario territorial generado por el cambio climático y la globalización económica ha aumentado la vulnerabilidad de la población a sufrir eventos asociados a riesgos naturales. El Ordenamiento Territorial surge como una herramienta para disminuir la vulnerabilidad, en forma planificada y sustentable con el ambiente. Sin embargo, para que dicha herramienta sea realmente eficaz, es necesario que integre la Gestión del Riesgo y la Gestión Ambiental, definiéndose de esa manera una metodología integradora. Con este fin, se presentan en este artículo dos aproximaciones metodológicas surgidas de la discusión de una comunidad de práctica integrada por académicos de universidades latinoamericanas que han unido sus esfuerzos y experiencias para solucionar un problema común, y que pretende disminuir el riesgo de sus poblaciones a sufrir desastres naturales.The new territorial scenario produced by climate change and economic globalization has made the population more vulnerable to suffer events associated to natural risks. Land Regulation is born as a tool to reduce vulnerability in a planned and environmentally sustainable way. However, in order for this tool to be truly efficient, it is necessary for it to be a part of both Risk Management and Environmental Management, thus defining an integrated methodology. With this aim in mind, this paper presents two methodological approaches born from the discussions of a practical community formed by Latin American university professors who have joined efforts and experiences to solve a common problem and which tries to reduce the risk that their populations run of suffering natural disasters.Departamento de Geografí