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Purpose Panitumumab plus FOLFOX (P-FOLFOX) is standard first-line treatment for RAS wild-type (WT) metastatic colorectal cancer. The value of panitumumab rechallenge is currently unknown. We assessed addition of panitumumab to FOLFIRI (P-FOLFIRI) beyond progression to P-FOLFOX in patients with no RAS mutations in liquid biopsy (LB). Methods In this randomized phase II trial, patients were assigned (3:2 ratio) to second-line P-FOLFIRI (arm A) or FOLFIRI alone (arm B). LB for circulating tumor DNA analysis was collected at study entry and at disease progression. Primary endpoint was 6-month progression-free survival. Two-stage Simon design required 85 patients to be included (EudraCT 2017-004519-38). Results Between February 2019 and November 2020, 49 patients were screened (16 RAS mutations in LB detected) and 31 included (18 assigned to arm A and 13 to arm B). The study was prematurely closed due to inadequate recruitment. Serious adverse events were more frequent in arm A (44% vs. 23%). Overall response rate was 33% (arm A) vs. 7.7% (arm B). Six-month progression-free survival rate was 66.7% (arm A) and 38.5% (arm B). Median progression-free survival was 11.0 months (arm A) and 4.0 months (arm B) (hazard ratio, 0.58). At disease progression, RAS or BRAF mutations in LB were found in 4/11 patients (36%) in arm A and 2/10 (20%) in arm B. Conclusions The BEYOND study suggests a meaningful benefit of P-FOLFIRI beyond progression to P-FOLFOX in metastatic colorectal cancer patients with WT RAS status selected by LB. This strategy deserves further investigation.

Awarding joint or sole custody is of crucial importance for the lives of both the child and the parents. This paper first models the factors explaining a court’s decision to grant child custody and later tests the predictive capacity of the proposed model. We conducted an empirical study using data from 1,884 court rulings, identifying and labeling factual elements, legal principles, and other relevant information. We developed a neural network model that includes eight factual findings, such as the relationship between the parents and their economic resources, the child’s opinion, and the psychological report on the type of custody. We performed a temporal validation using cases later in time than those in the training sample for prediction. Our system predicted the court’s decisions with an accuracy exceeding 85%. We obtained easy-to-apply decision rules with the decision tree technique. The paper contributes by identifying the factors that best predict joint custody, which is useful for parents, lawyers, and prosecutors. Parents would do well to know these findings before venturing into a courtroom.

Liquid biopsy has improved significantly over the last decade and is attracting attention as a tool that can complement tissue biopsy to evaluate the genetic landscape of solid tumors. In the present study, we evaluated the usefulness of liquid biopsy in daily oncology practice in different clinical contexts. We studied ctDNA and tissue biopsy to investigate EGFR, KRAS, NRAS, and BRAF mutations from 199 cancer patients between January 2016 and March 2021. The study included 114 male and 85 female patients with a median age of 68 years. A total of 122 cases were lung carcinoma, 53 were colorectal carcinoma, and 24 were melanoma. Liquid biopsy was positive for a potentially druggable driver mutation in 14 lung and colorectal carcinoma where tissue biopsy was not performed, and in two (3%) lung carcinoma patients whose tissue biopsy was negative. Liquid biopsy identified nine (45%) de novo EGFR-T790M mutations during TKI-treatment follow-up in lung carcinoma. BRAF-V600 mutation resurgence was detected in three (12.5%) melanoma patients during follow-up. Our results confirm the value of liquid biopsy in routine clinical oncologic practice for targeted therapy, diagnosis of resistance to treatment, and cancer follow-up.

Resumen Introduccion La aplasia cutis congenita (ACC) es un padecimiento dermico de presentacion poco frecuente que se caracteriza por la ausencia de piel al nacimiento y se asocia a malformaciones craneales, faciales, dermicas y oseas. El diagnostico es fundamentalmente clinico. Caso clinico Masculino de 5 dias de vida extrauterina, producto unico de madre primigesta y sin antecedentes familiares de relevancia. La exploracion fisica revelo defectos simetricos y bilaterales en la piel de ambas extremidades inferiores caracterizados por fragilidad cutanea, costras y ulceras recubiertas de pseudomembranas, asociados a una disminucion del espacio interdigital de ortejos de pie izquierdo, retraccion del pie y genu varum . Se manejo con aloinjertos de epidermis cultivado in vitro , cuidados generales de las heridas y seguimiento clinico posterior. Discusion La ACC asociada a epidermolisis ampollosa es una de las formas de presentacion menos frecuente. Es necesario descartar otro tipo de patologias dermicas. Se recomienda manejo clinico con cubierta cutanea biologica o sintetica, prevencion de infecciones, tratamiento oportuno de las complicaciones y seguimiento clinico.

The airborne spectroradiometers AHS and CASI were used as a source of hyperspectral and thermal remote sensing data during the REFLEX campaign. Data geolocation and a first simple atmospheric correction was performed by INTA in near-real time with a specific on-site setup and distributed to all campaign participants. In this paper we present briefly the AHS and CASI REFLEX flight campaign followed by a detailed description of the methodology used for image processing and finally the results obtained in terms of image quality. As a conclusion, near-real time processing for AHS and CASI level 1 geolocated products was successful as most of CASI level 2 results but further work is needed for achieving accurate AHS level 2 products.

El cambio a la utilización del expediente electrónico en la Administración de Justicia está suponiendo notables dificultades debido al enorme volumen de expedientes abiertos los cuales están exclusivamente en soporte papel o combinando elementos tanto en papel como electrónicos. Este artículo propone la adopción de una medida práctica para la sustitución progresiva del soporte papel: la digitalización, en el momento de su desglose, de los documentos aportados por las partes y su posterior conservación en formato electrónico en los archivos de la Administración.

This paper investigates the signalling role of tax policy in promoting, or hindering, the ability of a monopolist to practise entry deterrence. We show that environmental policy can facilitate the incumbent firm's concealment of information from potential entrants, thus deterring entry, and yet entail welfare improvements. Furthermore, we demonstrate that entry deterrence is more likely to arise when environmental regulation cannot be rapidly revised across time if market conditions change (inflexible regimes) than when regulatory agencies can adjust environmental policy over time.

La naturaleza jurídica de la custodia documental cambia al pasar de realizarse con documentos en soporte papel a hacerlo con documentos electrónicos. Con la regulación actual, deja de constituir un contrato de depósito, aunque siguen resultando aplicables muchas de las obligaciones del depositario. Sí que puede considerarse como un servicio de la sociedad de la información, por lo que es aplicable lo establecido para estos en la Ley 34/2002, de 11 de julio, de Servicios de la Sociedad de la Información, y, cuando los documentos contengan datos personales, también como un tratamiento de datos por cuenta de terceros. Pero, los cambios más importantes se deben a la constitución, por parte del Reglamento eIDAS, de la preservación de firmas y sellos electrónicos como un servicio de confianza. La aparición de esta nueva figura plantea numerosos interrogantes sobre quiénes son los agentes indicados para realizar cada una de las funciones asociadas a la conservación de los documentos electrónicos auténticos durante periodos prolongados de tiempo. The legal nature of document custody changes when it moves from paper documents to electronic ones. With the current Spanish regulation, it no longer constitutes a deposit agreement, although many of the depositary's obligations continue to be applicable. On the other hand, it can be considered as a service of the information society and therefore is applicable the liability regime established for them in the Spanish Law of Services for the Information Society, and also as a processing of data on behalf of third party, when documents contain personal data. However, the most important changes are due to the constitution by the eIDAS European Union Regulation of the preservation of electronic signatures and electronic stamps as a trust service. The emergence of this new figure raises numerous questions about who are the agents indicated to carry out each of the functions associated with the preservation of authentic electronic records for extended periods of time.

Contribution to the vascular plants flora of San Ignacio de Huinay natural reserve, Comau fiord, Región de los Lagos, Chile. To date, 262 species with their herbaria sheets stored in 5 different American and European herbaria (CONC, M, MA, and SGO) and that of Huinay, are known in the territory. In this work some first new records for the South Cone are included, such as Potentilla anglica, Plantago media, and Mentha x rotundifolia. Furthermore, some of the records are new for the Flora of Chile, such as Juncus burkartii, only known from Argentina). Other species very scarcely cited in Chile, such as Solanum nigrum and Bromus squarrosus, are also included. Contribución a la flora de plantas vasculares de la reserva biológica de San Ignacio de Huinay, situada en el fiordo de Comau, Región de los Lagos, Chile. Hasta ahora se tiene testimonio de herbario de 262 especies, con los pliegos depositados en herbarios de instituciones científicas americanas y europeas (CONC, M, MA y SGO), además del propio del centro científico. En este trabajo se incluyen primeras citas para el Cono Sur de las especies naturalizadas Potentilla anglica, Plantago media y Mentha x rotundifolia, y primeros registros para la flora de Chile de Juncus burkartii, conocido de Argentina. También se han encontrado otras plantas introducidas poco citadas en Chile como Solanum nigrum y Bromus squarrosus.

Aplasia cutis congenita (ACC) is a skin condition of rare presentation, this disease is characterized by absence of skin at birth and associated with facial, skin and bone skull deformities. The diagnosis is mainly clinical.Male 5 days after birth, unique product of primigravida mother and no family history of relevance. Physical examination revealed bilateral and symmetrical skin defects of both lower extremities, the disease is characterized by skin fragility, scabs, and coated pseudomembrane ulcers, decreased interdigital space between toes of the left foot, retraction of the foot and genu varum. It was handled with allograft of epidermis cultured in vitro, general wound care and clinical follow-up.ACC associated with epidermolysis bullosa is one of the rarer forms of presentation. It is necessary to rule out other skin diseases. Clinical management is recommended with biological or synthetic skin cover, infection prevention, early treatment of complications and clinical follow.

Resumen Objetivo Evaluar el impacto de una actividad formativa en la calidad de la realizacion de la tecnica espirometrica entre las enfermeras de un area de salud Diseno Estudio cuasiexperimental antes-despues Emplazamiento Diez equipos de atencion primaria Participantes Veinte enfermeras del equipo de atencion primaria (EAP) Intervencion Realizacion de una actividad de formacion de 5 h de duracion basada en los principios del aprendizaje de adultos. Mediciones principales. Se evaluo la fiabilidad de las medidas de 2 observadores sobre el mismo paciente para la capacidad vital forzada (CVF), el flujo espiratorio maximo en el primer segundo (FEV1), el flujo espiratorio maximo o peak expiratory flow (FEM o PEF) y la calidad de la curva espirometrica Resultados El coeficiente de correlacion intraclase (CCI) entre las medidas de los observadores aumento de manera significativa para el PEF: preformacion, 0,941; intervalo de confianza (IC) del 95%, 0,897-0,967; posformacion, 0,993; IC del 95%, 0,987-0,997. El CCI no se modifico para la CVF y elFEV1. La calidad de la curva de flujo espiratorio seconsidero buena en el 32,0% de los casos antes de la formacion y en el 88,9% tras ella (p Conclusiones La formacion continuada realizada sobre actividades que ya estan implantadas en los equipos y que permite la participacion activa puede ser util para mejorar la calidad de determinados procesos asistenciales

Internal medicine, art and science in the third millennium is a statement that Medicine is not only science. It acts on the sick individual to reestablish a natural state as a curative art. Medical art, commissioned by an individual or a society, is service. It requires vocation to obtain satisfaction. However due to the incidence of value changes, market globalization, technological and industrial development, the patient/physician relationship is becoming a user/provider relationship. Physician-related factors such as a higher health care demand, resource shortage and a progressive specialization have also influenced this change of paradigm. This is causing dissatisfaction, loss of self-esteem and a lower ethical commitment among professionals. We need to recover a professional repertoire of ideas in the context of a global ethics. Responsibility and co-responsibility are ethical principles addressed to technological civilizations and their collateral effects on people and environment that lead to a "responsible globalization". We also need a scientific futurology to define risks and avoid errors. In this era of progressive specialization, Internal Medicine, with its holistic vision of mankind, may play a fundamental role in the field of bioethics.