Prognostic and Clinicopathological Significance of CCND1/Cyclin D1 Upregulation in Melanomas: A Systematic Review and Comprehensive Meta-Analysis

We would like to thank the research group CTS-392 (Plan Andaluz de Investigación, Junta de Andalucía, Spain).Simple Summary The incidence of cutaneous melanoma is increasing worldwide, currently responsible for 287,723 new cases and 60,712 deaths per year (GLOBOCAN, IARC, WHO). It should be also highlighted that some less frequent subtypes of melanomas-i.e., acral, uveal, and mucous melanoma-are responsible for significant morbidity associated with metastasis, responding typically worse to newer therapies. Therefore, new biomarkers are needed to improve the prognosis in individual patients. In this sense, the present study showed that CCND1/cyclin D1 upregulation is a common molecular oncogenic alteration in melanomas that probably favors the growth and expansion on cutaneous primary melanomas. Furthermore, immunohistochemical cyclin D1 overexpression strongly predicted a higher Breslow thickness, currently considered the most relevant prognostic factor in individual patients with melanomas. Finally, special attention should be paid to the CCND1/cyclin D1 complex in mucosal melanomas, whose upregulation was strikingly altered. Our objective was to evaluate the prognostic and clinicopathological significance of cyclin D1 (CD1) overexpression/CCND1 amplification in melanomas. We searched studies published before September 2019 (PubMed, Embase, Web of Science, Scopus). We evaluated the quality of the studies included (QUIPS tool). The impact of CD1 overexpression/CCND1 amplification on overall survival and relevant clinicopathological characteristic were meta-analyzed. We performed heterogeneity, sensitivity, small-study effects, and subgroup analyses. Forty-one studies and 3451 patients met inclusion criteria. Qualitative evaluation demonstrated that not all studies were performed with the same rigor, finding the greatest risk of bias in the study confounding domain. Quantitative evaluation showed that immunohistochemical CD1 overexpression had a statistical association with Breslow thickness (p = 0.007; OR = 2.09,95% CI = 1.23-3.57), significantly higher frequency of CCND1/cyclin D1 abnormalities has been observed in the primary tumor compared to distant metastases (p = 0.004), revealed also by immunohistochemical overexpression of the protein (p < 0.001; OR = 0.53,95% CI = 0.40-0.71), while the CCND1 gene amplification does not show association (p = 0.43); while gene amplification, on the contrary, appeared more frequently in distant metastases (p = 0.04; OR = 1.70,95% CI = 1.01-2.85) and not in the primary tumor. In conclusion, CCND1/cyclin D1 upregulation is a common molecular oncogenic alteration in melanomas that probably favors the growth and expansion of the primary tumor. This upregulation is mainly consequence to the overexpression of the cyclin D1 protein, and not to gene amplification

Early Diagnosis of Oral Cancer: A Complex Polyhedral Problem with a Difficult Solution

Oral and oropharyngeal cancers are a growing problem, accounting for 377,713 and 98,412 new cases per year all over the world and 177,757 and 48,143 deaths annually, respectively. Despite the substantial improvement in diagnostic procedures and treatment techniques in recent years, the mortality rate has not decreased substantially in the last 40 years, which is still close to 50% of cases. The major cause responsible for this high mortality is associated with the high percentage of oral cancers diagnosed in advanced stages (stages III and IV) where the treatment harbors poor efficacy, resulting in challenges, mutilations, or disability. The main reason for cancer to be diagnosed at an advanced stage is a diagnostic delay, so it is critical to reduce this delay in order to improve the prognosis of patients suffering from oral cancer. The causes of oral cancer diagnostic delay are complex and concern patients, healthcare professionals, and healthcare services. In this manuscript, oral cancer diagnostic delay is critically reviewed based on current evidence, as well as their major causes, main problems, and potential improvement strategiesResearch group CTS-392 (Plan Andaluz de Investigación, Junta de Andalucía, Spain

Dysplasia in oral lichen planus: relevance, controversies and challenges. A position paper

Background: Patients with oral lichen planus (OLP) have an increased risk of oral cancer. For this reason, OLP is classified as an oral potentially malignant disorder. However, the precise personal (or individual) risk is unknown. Recent meta-analytical studies have reported that dysplastic OLP may transform to cancer in around 6% of cases, while the rate of transformation is lower (<1.5%) in non-dysplastic cases. The presence of epithelial dysplasia has emerged as the most powerful indicator for assessing cancer risk in oral potentially malignant disorders in routine practice. However, the general acceptance of epithelial dysplasia as an accompanying histologic feature in OLP is subject to great controversy. Many pathologists consider the presence of dysplasia as a criterion to exclude OLP when routinely reporting on this disease. This practice, widespread among oral pathology professionals, has resulted in the underestimation of the potential for malignancy of OLP. Material and Methods: A review of the literature was carried out in order to critically analyze the relevance, controversies and challenges encountered across the diagnosis of epithelial dysplasia in OLP. Results: 12 studies have been published examining dysplastic changes in OLP, reporting figures ranging from 0.54% to 25% of cases with dysplasia in the first diagnostic biopsy. The diagnosis of dysplasia in the OLP poses an additional difficulty due to the fact that the affected oral epithelium per se develops changes related to autoimmune aggression. Among the most frequent histological features of OLP that develops dysplasia are basal cell hyperplasia with basaloid appearance, loss of basal cells polarity, cellular and nuclear pleomorphism and irregular stratification. Conclusions: Epithelial dysplasia should not be considered an exclusion criterion for OLP; its evaluation requires experienced pathologists in this field

Influence of an insulating megaregolith on heat flow and crustal temperature structure of Mercury

Mercury is covered by a megaregolith layer, which constitutes a poor thermally conducting layer that must have an influence on the thermal state and evolution of the planet, although most thermal modeling or heat flow studies have overlooked it. In this work we have calculated surface heat flows and subsurface temperatures from the depth of thrust faults associated with several prominent lobate scarps on Mercury, valid for the time of the formation of these scarps, by solving the heat equation and taking into account the insulating effects of a megaregolith layer. We conclude that megaregolith insulation could have been an important factor limiting heat loss and therefore interior cooling and contraction of Mercury. As mercurian megaregolith properties are not very well known, we also analyze the influence of these properties on the results, and discuss the consequences of imposing the condition that the total radioactive heat production must be lower than the total surface heat loss (this is, the Urey ratio, Ur, must be lower than 1) in a cooling and thermally contracting planet such as Mercury at the time of scarp emplacement. Our results show that satisfying the condition of Ur < 1 implies that the average abundances of heat producing elements silicate layer is 0.4 times or less the average surface value, placing an upper bound on the bulk content of heat producing elements in Mercury’s interior

Valores de éxito y emprendimiento

El entorno mundial de crisis económica y financiera en el que nos encontramos desde hace años ha dificultado la incorporación de jóvenes al mercado laboral, si a esto le sumamos el crecimiento de la tasa de paro y las cualificaciones exigidas por las empresas en el primer empleo las opciones de conseguir un puesto de trabajo se vislumbran, a priori, complicadas. Ante estos hechos muchos jóvenes, movidos por la desesperación, terminan buscando una oportunidad de trabajo fuera de nuestras fronteras. Alternativas como el emprendimiento o el autoempleo podrían ser una opción para la juventud de optar al mercado laboral. Ante el paradigma actual de la duda que pueda plantearse cualquier persona joven sobre la idea de emprender o no, el conocer que valores que pueden determinar el éxito de dicho emprendimiento podría ser un vehículo que le facilitase la consecución de los objetivos marcados. El presente trabajo busca conocer que valores han determinado el éxito de personas relevantes en su profesión y cuáles de esos valores coinciden con las características del emprendedor.The global environment of economic and financial crisis in which we find for years has hampered the incorporation of youth into the labor market. If we add the growth of the unemployment rate and the qualifications required by companies in the first job the chances of getting a job become complicated. Given these facts many young people out of desperation they end up looking for a job opportunity outside our borders. Alternatives such as entrepreneurship or self-employment may be an option for young people to get into the labor market as long as they were accompanied by support from governments, administrations, organizations and institutions to help them on the path of entrepreneurship. Given the current paradigm of doubt that may arise any young person on the idea of undertaking or not, knowing that values that can determine the success of this venture could be a vehicle that will facilitate the achievement of the objectives. The present work seeks to understand which values have determined the success of relevant people in your profession and which of these values match the characteristics of the entrepreneur.peerReviewe

Moviendo la mirada: narrando con fotogramas

This Degree Dissertation (TFG) grew from my interest in cinema, more specifically from the interest in the narrative techniques that the film language uses to tell stories since the early days of the moving image. After studying various subjects related to film analysis, the static image (picture techniques) and graphic expression, I chose to use charcoal and pencil as graphical techniques for the drawings I present here. The project is involved in the creation of a narrative story, departing from cinematographic elements - the shot and the frame-, and translating them into a graphical language. Then, this TFG presents five drawings that have as departing point stills captured from different films; These drawings, decontextualized from their original environment ,have the ability to create a new narrative. The structure of the FG is divided in two main sections: a theoretical section that reflects on the relationship between cinema and painting and explores the different types of shot and the importance of the ellipsis. And another section focused on the development of the practical project and the process of it.El presente Trabajo Final de Grado (TFG) parte de mi interés por el cine, y más concretamente, por las técnicas narrativas que el lenguaje cinematográfico utiliza para contar historias desde los inicios de la imagen en movimiento. Tras cursar diferentes asignaturas relacionadas con el análisis cinematográfico, la imagen estática (fotografía/técnicas fotográficas) y la expresión gráfica, opté por utilizar el carboncillo y el lápiz conté como técnica gráfica para los dibujos realizados. El proyecto se mueve en la creación de una historia narrativa de ámbito cinematográfico, desde un lenguaje gráfico e incluyendo elementos propios del cine: el plano y el encuadre. Así pues, el TFG presenta una serie de dibujos que como base referencial toman fotogramas de diferentes películas ; descontextualizados de su entorno original y puestos en relación entre sí, obteniendo la capacidad de crear una nueva narración. La estructura del TFG se divide en dos apartados principales: un apartado teórico que reflexiona acerca de las relaciones entre cine y pintura e indaga en los diferentes tipos de plano y en la importancia de la elipsis. Y otro apartado centrado en el desarrollo del proyecto práctico y en los antecedentes previos a éste.Ruiz González, I. (2014). Moviendo la mirada: narrando con fotogramas. http://hdl.handle.net/10251/49175.Archivo delegad

From Bismarck to Beveridge : the other pension reform in Spain

El envejecimiento de la población es un proceso imparable que continúa suponiendo un reto para la sostenibilidad del sistema de reparto de pensiones en la mayoría de los países desarrollados, incluida España. Gran parte de estos países necesitan llevar a cabo reformas en sus sistemas de pensiones para controlar su gasto y, en algunos casos, ya han empezado. Sin embargo, existen otros mecanismos que suponen cambios en parámetros del sistema, que al ser percibidos como secundarios por los ciudadanos no son apreciados como tal reforma. Este es el caso de modificaciones en los topes de las pensiones y de las bases de cotización y que en España se ha denominado, por parte de los expertos en pensiones, como la «Reforma silenciosa». El objetivo de este documento es analizar las implicaciones que este tipo de reforma tendría en el caso de España, siendo el primer trabajo que cuantifi ca y evalúa su potencial impacto en dicho país. Con este fin se ha empleado un modelo de proyección contable, con generaciones solapadas y agentes heterogéneos, de gastos del sistema de pensiones español hasta el año 2070. Los resultados obtenidos muestran que este tipo de reforma no solo tendría potencial para contener el gasto futuro, sino que también podría suponer un cambio en la naturaleza del sistema al ser capaz de convertir un sistema contributivo (o Bismarckiano) en otro de tipo asistencial (o Beveridge). Esto último podría tener importantes consecuencias, pues ambos sistemas persiguen objetivos distintos. En el documento también se pone de relieve que las características institucionales que hacen posible este tipo de reforma en España existen al mismo tiempo en la mayoría de los países desarrollados con sistemas de pensiones tipo Bismarckiano. Y por lo tanto, creemos que las lecciones aprendidas en este documento para el caso español podrían ser de utilidad para otros paísesAging is an unstoppable process and it remains a major challenge for the sustainability of the PAYG pension system in most developed countries, including in Spain. Many countries need to introduce reforms of their pension systems in order to control their expenditure, and in some cases this has already begun. However, there are other sorts of changes to certain parameters that are perceived as secondary, e.g. the different path of minimum and maximum pensions, and the upper and lower caps on contributions. This has signifi cant implications for the distributive structure of the social security system that cannot be readily perceived by the population. That is why some economists in Spain refer to it as the “Silent Reform”. The aim of this paper is to analyse the consequences this type of reform would have in Spainindeed, it is the fi rst paper to actually quantify and evaluate the potential impact it would have on the country. We have used an accounting model with heterogeneous agents and overlapping generations in order to project pension expenditures up until 2070. The results show that this kind of reform could potentially contain future expenditure and could also change the nature of the pension system from a contributory or Bismarckian-type system into an assistential or Beveridgean-type one. This change could have signifi cant consequences as both systems have different objectives. The paper also shows that the institutional characteristics that make this kind of reform in Spain feasible are also present in most developed countries with Bismarckian pension systems. Therefore, we believe that the lessons learned in this paper on this kind of reform could well prove useful to other countrie

Actitudes hacia las pruebas de ingreso a la función pública docente de los/as maestros/as de educación infantil y primaria de la Región de Murcia

La presente tesis doctoral tuvo por objetivo analizar las actitudes de los maestros y maestras de infantil, primaria y las distintas especialidades, de la Región de Murcia, hacia las pruebas de acceso a la función docente. Desde un enfoque de investigación mixta, mediante un diseño secuencial explicativo, se realizó una primera recogida de datos cuantitativa y, posteriormente, una fase de recolección cualitativa. Se parte de la Teoría de la Conducta Planificada (en adelante, TCP), desarrollada por Ajzen y Fishbein (1980), para construir la escala de valoración de actitudes del opositor docente (EAOD). En una primera fase, el instrumento EAOD se aplicó a 399 participantes, recogiendo las creencias de los opositores a las pruebas de ingreso en torno a los constructos Actitud, Norma Subjetiva, Control Percibido e Intención. El contenido de la EAOD fue validado a través de jueces expertos y sus características técnicas examinadas a través del análisis factorial de componentes principales y un modelo de ecuaciones múltiples que confirmó la estructura interna de las dimensiones y los ítems, así como un óptimo ajuste al modelo TCP. La segunda fase de recogida de información se llevó a cabo a través del guion de entrevista de creencias del opositor docente (ECOD) y permitió recoger historias y relatos del opositor docente que fueron analizados cualitativamente a través del programa ATLAS.ti. Mediante la utilización de instrumentos de recogida de datos cuantitativos y cualitativos, los resultados obtenidos revelaron la fuerza del Control Percibido que mostró capacidad predictiva frente a la Intención del opositor. Como conclusiones, los opositores mostraron actitudes positivas hacia la profesión docente, entre las que destacó la vocación por la docencia, y que refuerzan su intención de participar en los procesos selectivos hacia los que se detectaron actitudes más negativas, basadas en las experiencias en torno a las pruebas, que el opositor valoró como evaluaciones subjetivas y, por tanto, injustas. La preparación y afrontamiento de las pruebas de ingreso se configura como un evento de gran trascendencia en la vida de los maestros y sobre cuyo procedimiento cabe reflexionar en pro de formulaciones más objetivas que garanticen que el sistema cumple la función de seleccionar a los candidatos más idóneos para ejercer la labor docente.This doctoral thesis is aimed to analyze the attitudes of nursery and primary school teachers towards the access exams to the public teaching function, in Región de Murcia. Relying on a mixed-method approach, through an Explanatory Sequential Design, we collected and analyzed quantitative and then qualitative data in two consecutive phases. First, based on the Theory of Planned Behaviour (hereinafter, TBP), developed by Ajzen and Fishbein (1980), a TPB questionnaire (EAOD) was designed and implemented on 399 applicants to the entry exams to collect their beliefs on Attitude, Subjective Norms, Perceived behavioral Control and Intention. The EAOD content was validated by experts’ judgements and its technical features were explored by factorial analysis of principal components. Through a Structural Equation Model (SEM), the structural relationships of dimensions and items were examined showing optimal results as well as optimal measures of global fit of TPB model. The second phase of qualitative data collection consisted of an interview protocol (ECOD) that allowed gathering life stories of teachers’ experiences on competitive exams, which were analyzed by ATLAS.ti. program. Therefore, using quantitative and qualitative data collection instruments, results showed the predictive power of Perceived Control through teachers’ Intention. In conclusion, candidates held positive attitudes to education (highlighting vocation) that reinforced a stronger intention to take part in the selection processes which were described negatively based on the experiences that surround them and that caused teachers to consider them as subjective exams and, thus, unfair. Taking part in the teachers’ entry exams become of great significance for teachers’ lives. Consideration should be given to teacher recruitment processes in pursuit of more objective evaluations so as to ensure the system fulfills its role in selecting the most suitable candidates for teaching profession

Dilation-free graphs in the l1 metric

The dilation-free graph of a planar point set S is a graph that spans S in such a way that the distance between two points in the graph is no longer than their planar distance. Metrically speaking, those graphs are equivalent to complete graphs; however they have far fewer edges when considering the Manhattan distance (we give here an upper bound on the number of saved edges). This article provides several theoretical, algorithmic, and complexity features of dilation-free graphs in the l1-metric, giving several construction algorithms and proving some of their properties. Moreover, special attention is paid to the planar case due to its applications in the design of printed circuit boards

Reuse of Spanish civil war air-raid shelters in Alicante: the R46 Balmis and R31 Seneca shelter

More than a hundred public air-raid shelters were constructed beneath Alicante during the Spanish Civil war. Their architectural uniqueness and humanitarian purpose render these shelters a tangible testament to our recent history. The Alicante Municipal Archives hold reports written by technicians who inspected the shelters in the 1940s, which were subsequently included in the Special Plan for public shelters in 1953. Half a century later, in 2003, information on the air-raid shelters was included in another Special Plan aimed at protecting Alicante’s archaeological heritage. Thanks to the work of the Municipal Heritage Conservation unit (COPHIAM) and the Special Protection Plan for Urban Archaeology (PEPA), the exact or approximate locations were identified for almost 90% of the shelters known to have existed. This paper describes interventions in two of these architectural spaces using advanced museology techniques. The first concerns air-raid shelter R46, located in the Plaza del Dr. Balmis in the city centre. This was built in 1938, and is rectangular with two entrances. The second is air-raid shelter R31, located in the Plaza Séneca