On the Accurate Estimation of Information-Theoretic Quantities from Multi-Dimensional Sample Data.

Using information-theoretic quantities in practical applications with continuous data is often hindered by the fact that probability density functions need to be estimated in higher dimensions, which can become unreliable or even computationally unfeasible. To make these useful quantities more accessible, alternative approaches such as binned frequencies using histograms and k-nearest neighbors (k-NN) have been proposed. However, a systematic comparison of the applicability of these methods has been lacking. We wish to fill this gap by comparing kernel-density-based estimation (KDE) with these two alternatives in carefully designed synthetic test cases. Specifically, we wish to estimate the information-theoretic quantities: entropy, Kullback-Leibler divergence, and mutual information, from sample data. As a reference, the results are compared to closed-form solutions or numerical integrals. We generate samples from distributions of various shapes in dimensions ranging from one to ten. We evaluate the estimators' performance as a function of sample size, distribution characteristics, and chosen hyperparameters. We further compare the required computation time and specific implementation challenges. Notably, k-NN estimation tends to outperform other methods, considering algorithmic implementation, computational efficiency, and estimation accuracy, especially with sufficient data. This study provides valuable insights into the strengths and limitations of the different estimation methods for information-theoretic quantities. It also highlights the significance of considering the characteristics of the data, as well as the targeted information-theoretic quantity when selecting an appropriate estimation technique. These findings will assist scientists and practitioners in choosing the most suitable method, considering their specific application and available data. We have collected the compared estimation methods in a ready-to-use open-source Python 3 toolbox and, thereby, hope to promote the use of information-theoretic quantities by researchers and practitioners to evaluate the information in data and models in various disciplines.

Análise de particularidades da participação lusófona em uma Rede de Conhecimentos em Enfermagem / Análisis de las particularidades de la participación lusófona en una Red de Conocimientos de Enfermería / Analysis of the particularities of Lusophone participation in a Nursing Knowledge Network

Resumo Objetivo Descrever o exercício conceitual de reflexão sobre as possibilidades e particularidades da participação das Escolas de Enfermagem e Faculdades de Enfermagem lusófonas na Rede de Conhecimentos em Enfermagem. Método Análise das informações obtidas em um levantamento de recursos institucionais de acordo com o marco conceitual proposto por Prug e Prusak sobre rede de conhecimentos. A ponderação de aspectos positivos e negativos - analisando o aprendizado com as informações - levou em consideração as possíveis soluções para um plano de ação. Resultados Tanto nas ações institucionais para suportar a pesquisa em Enfermagem como nos benefícios almejados com a participação na Rede existe o interesse na internacionalização da pesquisa e no trabalho colaborativo. Com a ampliação dos horizontes da ciência da Enfermagem lusófona, este trabalho visa aumentar o impacto da pesquisa e agilizar a divulgação e a utilização dos resultados, tanto na educação como na clínica. Conclusão e Implicações para a prática A participação das referidas instituições oferece inúmeras possibilidades de demonstrar originalidade, criatividade e perícia de sua prática docente e de pesquisa, favorecendo o compartilhamento de ideias e práticas. A prática de produção científica, por docentes e discentes, pode ser aprimorada pelo refinamento de modos de pensar, criar, produzir e disseminar.

Resumen Objetivo Describir el ejercicio conceptual de reflexión de las posibilidades y particularidades de la participación de facultades de Enfermería de lengua portuguesa en la Red de Conocimientos de Enfermería. Método Análisis de datos obtenidos de un sondeo de recursos institucionales bajo el marco conceptual de Prug y Prusak sobre la red de conocimiento. El planteamiento de aspectos positivos y negativos del aprendizaje abarcó soluciones para elaborar un plan de acción. Resultados En las acciones institucionales de apoyo a la investigación en Enfermería y los beneficios aspirados con la participación en la Red, existe un interés por la internacionalización de la investigación y el trabajo colaborativo -que tiene como objetivo aumentar el impacto de la investigación, estimular la divulgación y el aprovechamiento de los resultados en la enseñanza y la clínica, con la ampliación de los horizontes de la Enfermería de instituciones de habla portuguesa. Conclusión e Implicaciones en la práctica La Red ofrece numerosas posibilidades para las instituciones participantes respecto a la demostración de originalidad, creatividad y experiencia en la práctica docente y de investigación, fomentando el intercambio de ideas y prácticas. La práctica de la producción científica por profesores y estudiantes puede verse mejorada por la reflexión, creación, producción y difusión de conocimientos.

Abstract Objective To describe the conceptual exercise of reflecting on the possibilities and particularities of the participation of Lusophone schools of nursing in the Nursing Knowledge Network. Method An analysis was conducted using information obtained from an environmental scan of institutional resources following the conceptual framework by Prug and Prusak on the knowledge networks. The learnings reported in the analysis are based on the collected information and reflections on the positive and negative aspects of participation, while proposing possible solutions for an action plan. Results There is interest in the internationalization of research and collaborative work both as institutional actions to support nursing research and potential benefits due to participation in the Network. The collaborative work has potential to increase the impact of research, expedite dissemination and use of results both in education and in clinical practice, broadening the horizons of Lusophone nursing science. Conclusion and Implications for practice Participation of these institutions in the Network offers numerous possibilities to demonstrate the originality, creativity and expertise of their teaching and research practice, encouraging the sharing of ideas and practices. The practice of scientific production in all its scenarios by educators and students can be improved through refined ways of thinking, creating, producing, and disseminating knowledge.

Internacionalização para o incremento da produção de conhecimentos em enfermagem: estudo de reflexão / Internationalization to increase the production of knowledge in nursing: a reflection study

Objetivo: refletir sobre oportunidades para a internacionalização da Enfermagem em países lusófonos proporcionadas por uma rede internacional de conhecimentos em Enfermagem. Método: método reflexivo que conduz à percepção modificada de uma dada situação levando a novas ideias, revelando temas de análise e propostas de possíveis soluções através de um plano de ação. A reflexão concentrou-se em diálogos interdisciplinares, inovação conceitual-metodológica e fortalecimento da liderança em Enfermagem. Resultados: a reflexão focalizou: (a) o diálogo além do contexto cultural e científico lusófono para a Rede ser reconhecida como parceiro intelectual substancial; (b) a incorporação de abordagens, referenciais e desenhos de pesquisa multidisciplinares; e (c) a mobilização de conhecimento sobre causas sociais para o fortalecimento da liderança da Enfermagem global nas questões de justiça social e equidade em saúde. Considerações finais: a Enfermagem lusófona possui expertise para inovar com estratégias para reforçar a internacionalização.

Objective: reflect on opportunities for the internationalization of nursing in Lusophone countries provided by an international network of nursing knowledge. Method: a reflexive method leading to the modified perception of a given situation leading to new ideas, revealing themes of analysis and proposals for possible solutions through an action plan. This reflection focused on interdisciplinary dialogues, methodological-conceptual innovation, and strengthening of leadership in nursing. Results: the reflection focused on: 1) the dialogue beyond the Lusophone cultural and scientific context for the network to be recognized as a substantial intellectual partner; 2) the incorporation of multidisciplinary approaches, references, and research designs; and 3) the mobilization of knowledge about social causes to strengthen global nursing leadership in issues of social justice and health equity. Final considerations: Lusophone nursing has expertise to innovate with strategies to strengthen internationalization.

Objetivo: reflexionar sobre las oportunidades de internacionalización de la Enfermería en los países de lengua portuguesa proporcionadas por una red internacional de conocimiento en Enfermería. Método: método reflexivo que conduce a una percepción modificada de una situación que lleva a nuevas ideas, revelando temas de análisis y propuestas de posibles soluciones por medio de un plan de acción. La reflexión se centró en los diálogos interdisciplinarios, la innovación conceptual-metodológica y el fortalecimiento del liderazgo en enfermería. Resultados: la reflexión tuvo como foco: (a) el diálogo más allá del contexto cultural y científico de la lengua portuguesa para que la Red sea reconocida como un socio intelectual sustancial; (b) la incorporación de enfoques, referencias y diseños de investigación multidisciplinarios; y (c) la movilización de conocimiento sobre las causas sociales para fortalecer el liderazgo mundial de enfermería en temas de justicia social y equidad en salud. Consideraciones finales: La Enfermería em países de lengua portuguesa tiene el expertise para innovar con estrategias para reforzar la internacionalización.

Training-professional profile of nurses teaching at the Technical Schools of the Unified Health System / Perfil formación-profesional del enfermero docente en las Escuelas Técnicas del Sistema Único de Salud / Perfil formativo-profissional dos enfermeiros docentes das Escolas Técnicas do Sistema Único de Saúde

ABSTRACT Objective: to describe the training-professional profile of nursing professors in the vocational course in nursing at the Technical Schools of the Unified Health System. Methods: a quantitative descriptive research, carried out with 61 nurses who are professors of technical courses in nursing at five technical schools in three Brazilian regions. Data were collected through an online questionnaire and submitted to descriptive analysis. Results: only 36% of teaching nurses were licensed and 80% had a specialization in nursing or health. Although 95.1% of participants considered training for teaching necessary, 44.2% did not have qualifications for this job. The average length of work in care was 8 years, focusing on the hospital network. Conclusion: the need for professor training and investment in it is evidenced, as the training of essential workers for nursing care and consolidation of the Unified Health System is on the agenda.

RESUMEN Objetivo: describir el perfil formativo-profesional de los profesores de enfermería en el curso técnico en enfermería de las Escuelas Técnicas del Sistema Único de Salud. Métodos: investigación cuantitativa, descriptiva, realizada con 61 enfermeras que son profesoras de cursos técnicos en enfermería en cinco escuelas técnicas en tres regiones brasileñas. Los datos se recopilaron a través de un cuestionario en línea y se sometieron a análisis descriptivo. Resultados: se destaca que solo el 36% de los profesores de enfermería tenía licencia y el 80% tenía especialización en el campo de la enfermería o la salud. Si bien el 95,1% de los participantes consideró necesaria la formación para la docencia, el 44,2% no tenía la calificación para este puesto. El tiempo promedio de experiencia en la atención fue de 8 años, con foco en la red hospitalaria. Conclusión: se evidencia la necesidad de formación e inversión docente en la misma, ya que la formación de los trabajadores esenciales para la atención de enfermería y la consolidación del Sistema Único de Salud está en la agenda.

RESUMO Objetivo: descrever o perfil formativo-profissional dos enfermeiros docentes do curso técnico em enfermagem das Escolas Técnicas do Sistema Único de Saúde. Métodos: pesquisa quantitativa, do tipo descritiva, realizada com 61 enfermeiros professores de cursos técnicos em enfermagem de cinco escolas técnicas de três regiões brasileiras. Os dados foram coletados por questionário online e submetidos à análise descritiva. Resultados: destaca-se que apenas 36% dos enfermeiros docentes eram licenciados e 80% tinham especialização na área de enfermagem ou saúde. Apesar de 95,1% dos participantes considerar necessária a formação para o ensino, 44,2% não tinha qualificação para este trabalho. O tempo médio de atuação na assistência foi de 8 anos, concentrando-se na rede hospitalar. Conclusão: evidencia-se a necessidade de formação docente e o investimento nesta, pois está em pauta a formação de trabalhadores essenciais para o cuidado em enfermagem e consolidação do Sistema Único de Saúde.

Training-professional profile of nurses teaching at the Technical Schools of the Unified Health System.

OBJECTIVE: to describe the training-professional profile of nursing professors in the vocational course in nursing at the Technical Schools of the Unified Health System. METHODS: a quantitative descriptive research, carried out with 61 nurses who are professors of technical courses in nursing at five technical schools in three Brazilian regions. Data were collected through an online questionnaire and submitted to descriptive analysis. RESULTS: only 36% of teaching nurses were licensed and 80% had a specialization in nursing or health. Although 95.1% of participants considered training for teaching necessary, 44.2% did not have qualifications for this job. The average length of work in care was 8 years, focusing on the hospital network. CONCLUSION: the need for professor training and investment in it is evidenced, as the training of essential workers for nursing care and consolidation of the Unified Health System is on the agenda.

Enfermeiros e escolas de enfermagem nos anuários da Universidade de Coimbra, de 1866 a 1956 / Nurses and nursing schools in the yearbooks of the University of Coimbra, from 1866 to 1956 / Enfermeros y escuelas de enfermería en los anuarios de la Universidad de Coímbra, de 1866 a 1956

Contexto: O final do século XIX e o início do século XX é um período de profundas transformações nas instituições de assistência e nos seus profissionais. Objetivo: Conhecer este período da história da enfermagem em Portugal. Analisar os anuários da Universidade de Coimbra, considerando-os como fonte primária. Metodologia: Análise descritiva histórica de 73 anuários, com levantamento de fontes e construção de síntese descritiva e interpretativa. Resultados: Verificámos a concentração de material nos anos 1896 a 1927. A análise, sintetizou 4 tópicos: 1) nomes e funções dos enfermeiros; 2) os enfermeiros, no decreto de reforma dos Hospitais da Universidade de Coimbra, em 1911, o quadro e os vencimentos em 1915-16; 3) enfermeiros hípicos e militares em 1915-16 e 1917-18; 4) a escola de enfermagem de 1919-20 a 1926-27 e os professores universitários. Conclusão: Encontrámos 104 nomes de enfermeiros, com funções definidas, considerados pessoal auxiliar e não pessoal clínico. O enfermeiro chefe surge com destaque. Aparece a escola de enfermagem dos hospitais da universidade, com a identificação dos professores universitários regentes.

Background: The end of the 19th century and the beginning of the 20th century combine a period of profound transformations in care institutions and their professionals. Objective: To know this period of nursing history in Portugal, analyze the yearbooks of the University of Coimbra, considering them as the primary source. Methodology: Descriptive historical analysis of 73 yearbooks, with a survey of sources and construction of descriptive and interpretative synthesis. Results: The available material was centered on the years 1896 to 1927. The analysis synthesized 4 topics: 1) names and functions of nurses; 2) nurses, in the decree of the reform of the Hospitals of the University of Coimbra, in 1911, the staff and salaries in 1915-16; 3) equine veterinary nurses and military nurses in 1915-16 and 1917-18; 4) the nursing school from 1919-20 to 1926-27 and university professors. Conclusion: We found 104 names with defined functions, considered as auxiliary staff and non-clinical personnel. The head nurse comes out prominently. The nursing school of the university hospitals appears, with the identification of the university head teachers.

Contexto: El final del siglo XIX y el comienzo del siglo XX es un período de profundas transformaciones en las instituciones de asistencia y en sus profesionales. Objetivo: Conocer este período de la historia de la enfermería en Portugal. Analizar los anuarios de la Universidad de Coímbra, considerándolos como una fuente primaria. Metodología: Análisis descriptivo histórico de 73 anuarios, con estudio de las fuentes y construcción de síntesis descriptivas e interpretativas. Resultados: Comprobamos la concentración de material de los años comprendidos entre 1896 y 1927. El análisis resumió 4 temas: 1) nombres y funciones de los enfermeros; 2) los enfermeros en el decreto de reforma de los Hospitales Universitarios de Coímbra en 1911, el equipo y los sueldos en 1915-16; 3) los enfermeros ecuestres y militares en 1915-16 y 1917-18; 4) la escuela de enfermería de 1919-20 a 1926-27 y los profesores universitarios. Conclusión: Encontramos 104 nombres de enfermeros, con funciones definidas, considerados personal auxiliar y no personal clínico. El enfermero jefe aparece destacado. Aparece la escuela de enfermería de los hospitales universitarios, con la identificación de los profesores universitarios a cargo.

Enfermería durante la guerra civil española y su posguerra (1936-1949): olvido e inhabilitación / Nursing during the Spanish Civil War and its post-war period (1936-1949): forgetting and disabling / Enfermagem durante a Guerra Civil Espanhola e seu período pós-guerra (1936-1949): esquecendo e incapacitando

Marco contextual: El modelo de salud en la Segunda República española (1931-1939) y las prácticas asistenciales desarrolladas por el personal enfermero transformaron las condiciones sanitarias del país. Sin embargo, durante la Guerra Civil (1936-1939), los cuidados sociosanitarios fueron desiguales. Objetivo: Analizar la influencia sanitaria durante la Guerra Civil y la posguerra española. Metodología: Investigación histórico-descriptiva, relacionada con la sanidad durante la guerra civil española y la posguerra. Recopilación de información: documentos enfermeros; análisis: periódicos, libros, leyes. Se realizó un análisis interpretativo por fechas y acontecimientos del periodo de estudio. Resultados: Entre 1939 y 1949, las leyes promulgadas revisaron el trabajo realizado por los sanitarios, lo que llevó a la represión y eliminación de funcionaros sanitarios ajenos a las ideas políticas imperantes, y supuso un proceso de purificación y descalificación. Conclusión: El Gobierno de la Segunda República española atribuyó importancia a la higiene en el ámbito sanitario y doméstico. Llegada la Guerra Civil, España sufrió carencias de cuidados sanitarios a nivel civil y militar. Durante la posguerra, la identidad de parte de la enfermería fue omitida y olvidada.

Background: The health model during the Second Spanish Republic (1931-1939) and the care practices developed by the nursing staff transformed the health conditions of the country. During the civil war (1936-1939), social and health care was unequal. Objective: Analyse the influence of health care during and after the Spanish Civil War. Methodology: Historical-descriptive research related to health care during the Civil War. Compilation of information: nursing documents, newspapers, books, laws. Interpretative analysis by dates and events of the period of study. Results: Between 1939 and 1949, the laws enacted revised the work carried out by the health workers, leading to the repression and elimination of the health workers who were alien to the prevailing political ideas, which meant a process of purification. Conclusion: The government of the Second Republic attributed importance to hygiene in the sanitary and domestic field. After the Civil War, Spain suffered from a lack of health care at both civil and military levels. During the post-war the identity of part of the nursing profession was forgotten.

Enquadramento: O modelo de saúde durante a Segunda República Espanhola (1931-1939) e as práticas assistenciais desenvolvidas pelos enfermeiros transformaram as condições de saúde do país.Durante a Guerra Civil (1936-1939), a assistência social e sanitária foi desigual. Objetivo: Analisar a influência dos cuidados de saúde durante a Guerra Civil Espanhola e período pós-guerra. Metodologia: Investigação histórico-descritiva sobre os cuidados de saúde durante a Guerra Civil. Compilação de informação: documentos de enfermagem, jornais, livros, leis. Análise interpretativa por datas e eventos do período em estudo. Resultados: Entre 1939 y 1949, as leis promulgadas reviram o trabalho realizado pelos trabalhadores da saúde, levando à repressão e eliminação de muitos que eram alheios às idéias políticas predominantes, o que implicava um processo de purificação e desqualificação. Conclusão: O Governo da Segunda República atribuiu importância à higiene no campo sanitário e doméstico. Após a Guerra Civil, a Espanha sofreu com a falta de cuidados de saúde. Durante o período pós-guerra, a identidade de parte da profissão de enfermagem foi omitida e esquecida.

Ensino clínico de fundamentos de enfermagem na comunidade / Clinical teaching of nursing fundamentals in the community

Objetivo: descrever a metodologia e as estratégias do plano educacional do ensino clínico de Fundamentos de Enfermagem na comunidade que, por meio do estudo de determinantes de saúde com pessoas idosas, tem como meta a formação de competências e capacidades dos estudantes do curso de Licenciatura em Enfermagem. Método: trata-se de um estudo qualitativo, descritivo, do tipo relato de experiência, desenvolvido com estudantes de Enfermagem. Apresentam-se os resultados em forma de figuras. Resultados: conduziu-se os estudantes a desenvolver as competências definidas pelas diferentes capacidades e critérios vivenciados pelos estudantes, neste ensino clínico, durante as experiências de aprendizagem sugeridas, assim como outras que foram implementadas. Conclusão: permitiu-se, ao estudante de Enfermagem, pela integração de atividades de Enfermagem compartilhadas entre equipes e subequipes, construir seu próprio conhecimento e acrescentar qualidade técnica e científica à sua formação. Tornou-se o estudo de determinantes de saúde com pessoas idosas fundamental para a formação de competências dos estudantes do curso de Licenciatura em Enfermagem. Pode-se disponibilizar, por esta experiência, com propostas baseadas no olhar do continente europeu, uma nova dimensão de aprendizagem no ensino clínico da Licenciatura de Enfermagem para outros continentes.(AU)

Objective: to describe the methodology and strategies of the educational plan of the clinical teaching of Nursing Fundamentals in the community that, through the study of health determinants with elderly people, has the goal of training the skills and abilities of undergraduate students in Nursing. Method: this is a qualitative, descriptive, experience-type study developed with Nursing students. The results are presented in figures. Results: the students were led to develop the competencies defined by the different capacities and criteria experienced by the students, in this clinical teaching, during the suggested learning experiences, as well as others that were implemented. Conclusion: the Nursing student was allowed to integrate nursing activities shared between teams and subteams, to build their own knowledge and to add technical and scientific quality to their training. It has become the study of health determinants with older people key to the training of students' undergraduate nursing course. Through this experience, it is possible to offer, based on the perspective of the European continent, a new dimension of learning in the clinical teaching of the Nursing Degree to other continents.(AU)

Objetivo: describir la metodología y las estrategias del plan educativo de la enseñanza clínica de Fundamentos de Enfermería en la comunidad que, a través del estudio de determinantes de salud con personas mayores, tiene como meta la formación de competencias y capacidades de los estudiantes del curso de Licenciatura en Enfermería. Método: se trata de un estudio cualitativo, descriptivo, del tipo relato de experiencia, desarrollado con estudiantes de Enfermería. Se presentan los resultados en forma de figuras. Resultados: se llevó a los estudiantes a desarrollar las competencias definidas por las diferentes capacidades y criterios vivenciados por los estudiantes, en esta enseñanza clínica, durante las experiencias de aprendizaje sugeridas, así como otras que se implementaron. Conclusión: se permitió al estudiante de Enfermería, por la integración de actividades de Enfermería compartidas entre equipos y subequipos, construir su propio conocimiento y añadir calidad técnica y científica a su formación. Se ha convertido el estudio de determinantes de salud con personas de edad avanzada para la formación de competencias de los estudiantes del curso de Licenciatura en Enfermería. Se puede disponer, por esta experiencia, con propuestas basadas en la mirada del continente europeo, una nueva dimensión de aprendizaje en la enseñanza clínica de la Licenciatura de Enfermería para otros continentes.

Capecitabine and irinotecan with bevacizumab 2-weekly for metastatic colorectal cancer: the phase II AVAXIRI study.

BACKGROUND: The optimal sequence of chemotherapeutic agents is not firmly established for the treatment of metastatic colorectal cancer (mCRC). This phase II multi-centre study investigated the efficacy and tolerability of a standard capecitabine plus irinotecan (XELIRI) regimen with bevacizumab in previously untreated patients with mCRC. METHODS: Patients received intravenous irinotecan 175 mg/m(2) on day 1 and oral capecitabine 1000 mg/m(2) (800 mg/m(2) for patients >65 years of age) twice daily on days 2-8, followed by a 1-week rest, and bevacizumab 5 mg/kg as an intravenous infusion on day 1 every 2 weeks. RESULTS: Seventy-seven patients were included in the intention-to-treat and safety populations. Progression-free survival at 9 months was 61%. The overall response and disease control rates were 51% and 84%, respectively. Median progression-free and overall survival times were 11.9 and 24.8 months, respectively. 48 patients (62%) had at least one grade 3/4 adverse event, the most common being asthenia, diarrhoea and neutropenia. Quality of life varied little over the study period with mean visual analogue scale general health scores ranging from 71 to 76 over cycles 1-11. CONCLUSION: Our study found irinotecan and capecitabine administered fortnightly with bevacizumab in patients with mCRC to be an effective and tolerable regimen. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT00875771. Trial registration date: 04/02/2009.

Prognostic relevance of estrogen receptor-α Ser167 phosphorylation in stage II-III colon cancer patients.

Preclinical and clinical data suggest a protective role for estrogens on colon cancer (CRC) risk. estrogen receptor (ER) ß is the prevalent ER in normal colonic mucosa, whereas its expression is significantly reduced in CRC. An increased ERα/ß ratio has been documented in colon carcinomas and is associated with increased proliferation and decreased apoptosis. The aim of our study was to evaluate the expression of activated ERα and its prognostic implications in patients with stage II-III CRC. Phospho-ERα(Ser167) (pERα(Ser167)) expression was assessed by immunohistochemistry in 218 CRC paraffin-embedded tumor samples. A high pERα(Ser167) expression was more commonly observed in women, older patients, and patients with high baseline glucose levels. This higher pERα(Ser167) expression was associated with decreased 5-year disease-free interval (DFI; 66% versus 78%, P = .07) and overall survival (65% versus 73%, P = .46). The negative impact of high pERα(Ser167) expression on DFI was particularly significant (P < .05) in women (85% versus 60%), young (82% versus 61%), nondiabetic (85% versus 66%), and stage II patients (86% versus 72% and low versus high pERα(Ser167), respectively). Multivariate analysis confirmed that pERα(Ser167) score was a significant prognostic factor for both DFI and overall survival, independent of sex, age, glucose levels, tumor stage, bowel obstruction/perforation, or adjuvant chemotherapy. These findings illustrate the relevance of estrogen pathways in colon cancer biology and may provide novel therapeutic avenues to be explored in this context.

MiR-107 and miR-99a-3p predict chemotherapy response in patients with advanced colorectal cancer.

BACKGROUND: MicroRNAs (miRNAs) are involved in numerous biological and pathological processes including colorectal cancer (CRC). The aim of our study was to evaluate the ability of miRNA expression patterns to predict chemotherapy response in a cohort of 78 patients with metastatic CRC (mCRC). METHODS: We examined expression levels of 667 miRNAs in the training cohort and evaluated their potential association with relevant clinical endpoints. We identified a miRNA profile that was analysed by RT-qPCR in an independent cohort. For a set of selected miRNAs, bioinformatic target predictions and pathway analysis were also performed. RESULTS: Eight miRNAs (let-7 g*, miR-107, miR-299-5p, miR-337-5p, miR-370, miR-505*, miR-889 and miR-99a-3p) were significant predictors of response to chemotherapy in the training cohort. In addition, overexpression of miR-107, miR-337-5p and miR-99a-3p, and underexpression of miR-889, were also significantly associated with improved progression-free and/or overall survival. MicroRNA-107 and miR-99a-3p were further validated in an independent cohort as predictive markers for chemotherapy response. In addition, an inverse correlation was confirmed in our study population between miR-107 levels and mRNA expression of several potential target genes (CCND1, DICER1, DROSHA and NFKB1). CONCLUSIONS: MiR-107 and miR-99a-3p were validated as predictors of response to standard fluoropyrimidine-based chemotherapy in patients with mCRC.

Amphiphilic polymers bearing gluconolactone moieties: synthesis and long side-chain crystalline behavior.

The synthesis and characterization of amphiphilic polymers bearing gluconolactone moieties has been described. In a first step, an unprotected glycomonomer 2-[({[4-(d-gluconamid-N-yl)butyl]amino}carbonyl)oxy]ethyl acrylate, HEAG, has been synthesized. Posterior, this glycomonomer has been copolymerized with methyl methacrylate at different compositions and the kinetic behavior has been also studied calculating the monomer reactivity ratios by Kelen-Tüdös extended equation. In addition, the long side-chain crystalline behavior of these carbohydrate-based copolymers with high composition of glycomonomer has been examined by using conventional and modulated differential scanning calorimetry and X-ray diffraction measurements. At the same time, the phase separation behavior of carbohydrate-based copolymers with lower HEAG content has been determined by their glass transition temperature measurements. Finally, the thermal stability of all these amphiphilic copolymers has been evaluated by thermogravimetric analysis.

Biocidal capability optimization in organic-inorganic nanocomposites based on titania.

Optimization of the interfacial agent content in biocidal titania-isotactic polypropylene nanocomposites is performed by evaluating their structural, thermal, optical, and biocidal properties. The balance between the photochemistry (photokilling) behavior and the thermal properties is achieved in the nanocomposites with an incorporation of 2 wt.% in inorganic nanoparticles (Tio2) using a compatibilizer content ranging from 50 to 80 wt.% with respect to the titania amount

Elderly patients with advanced colorectal cancer derive similar benefit without excessive toxicity after first-line chemotherapy with oxaliplatin-based combinations: comparative outcomes from the 03-TTD-01 phase III study.

PURPOSE: Healthy elderly patients with metastatic colorectal cancer may benefit from chemotherapy as much as the younger population. This analysis compares the outcomes of first-line oxaliplatin plus fluoropyrimidines in elderly versus young patients. PATIENTS AND METHODS: 348 patients were randomized to capecitabine 1000 mg/(m2 12 h), days 1-14 plus oxaliplatin 130 mg/m2 day 1, every 3 weeks or weekly infusional 5-FU 2250 mg/m2 over 48 h plus bimonthly oxaliplatin 85 mg/m2. We evaluated response rate, time to progression, overall survival and toxicity according to age. RESULTS: ORR for elderly and young patients were 34.9% and 44.7%, respectively (p=0.081). Median TTP did not differ between the two groups: 8.3 months for patients > or =70 years and 9.6 months for those <70 years (p=0.114). Median OS was 16.8 months and 20.5 months for the > or =70 and <70 years groups, respectively (p=0.74). With XELOX, mild paresthesia and an increase in transaminase levels were more frequent for young patients, whereas grade 3/4 diarrhea was higher in those > or =70 years (25% vs. 8%, p=0.005). For FUOX, only paresthesia was significantly lower in patients > or =70 years (53% vs. 71%, p=0.032). CONCLUSION: Elderly patients with MCRC benefit from first-line oxaliplatin-fluoropyrimidine combinations as much as younger patients, without increased toxicity.

Phase III study of capecitabine plus oxaliplatin compared with continuous-infusion fluorouracil plus oxaliplatin as first-line therapy in metastatic colorectal cancer: final report of the Spanish Cooperative Group for the Treatment of Digestive Tumors Trial.

PURPOSE: The aim of this phase III trial was to compare the efficacy and safety of capecitabine plus oxaliplatin (XELOX) versus Spanish-based continuous-infusion high-dose fluorouracil (FU) plus oxaliplatin (FUOX) regimens as first-line therapy for metastatic colorectal cancer (MCRC). PATIENTS AND METHODS: A total of 348 patients were randomly assigned to receive XELOX (oral capecitabine 1,000 mg/m2 bid for 14 days plus oxaliplatin 130 mg/m2 on day 1 every 3 weeks) or FUOX (continuous-infusion FU 2,250 mg/m2 during 48 hours on days 1, 8, 15, 22, 29, and 36 plus oxaliplatin 85 mg/m2 on days 1, 15, and 29 every 6 weeks). RESULTS: There were no significant differences in efficacy between XELOX and FUOX arms, which showed, respectively, median time to tumor progression (TTP; 8.9 v 9.5 months; P = .153); median overall survival (18.1 v 20.8 months; P = .145); and confirmed response rate (RR; 37% v 46%; P = .539). The safety profile of the two regimens was similar, although there were lower rates of grade 3/4 diarrhea (14% v 24%) and grade 1/2 stomatitis (28% v 43%), and higher rates of grade 1/2 hyperbilirubinemia (37% v 21%) and grade 1/2 hand-foot syndrome (14% v 5%) with XELOX versus FUOX, respectively. CONCLUSION: This randomized study shows a similar TTP of XELOX compared with FUOX in the first-line treatment of MCRC, although there was a trend for slightly lower RR and survival. XELOX can be considered as an alternative to FUOX.

Phase II trial of vinorelbine and estramustine in the treatment of metastatic hormone-resistant prostate cancer.

The purpose of this study was to investigate the efficacy and safety of combination chemotherapy using estramustine and vinorelbine in chemotherapy-naïve patients with hormone-resistant prostate cancer (HRPC). The patients (n = 54) received oral estramustine 840 mg/day on Days 1 to 14 and IV vinorelbine 25 mg/m(2) on Days 1 and 8 of every 3 wk cycle. The median number of cycles per patient was 9 (range, 1 to 27). Fifty-three patients were evaluable for toxicity and survival and 52 for prostate specific antigen (PSA) response. Median age was 68 (range, 46-80). PSA sustained decrease >50% was seen in 52% of patients (95% CI: 38-66%). A complete response was seen in 3 and a partial response in 12 of 25 patients with measurable disease, for an overall objective response of 60% (95% CI: 41-79%). Improvement in performance status was observed in 30 out of 43 evaluable for clinical benefit response. The median duration of response was 7 mo and median time to progression was 6 mo. The median survival time was 15 mo. The most common adverse event was mild gastrointestinal toxicity. In general, toxicity G3-4 was low: granulocytopenia Grade 3-4 (8%), thrombocytopenia Grade 3 (6%), and anemia Grade 3 (13%). Other Grade 3 toxicities included deep vein thrombosis (4%), hepatic (2%), cardiac ischemia (2%), fatigue (6%), and sensory neuropathy (2%). There were 2 treatment-related deaths (4%). We conclude that vinorelbine and estramustine as used in this trial is an efficacious and well-tolerated therapeutic regimen in the management of HRPC.

Estesioneuroblastoma: diagnóstico, prognóstico e tratamento / Esthesioneuroblastoma: diagnosis, prognosis and treatment

Estesioneuroblastoma é uma neoplasia rara, com origem nas células neurais do epitélio olfatório, responsável por 2 por cento dos tumores da cavidade nasal. Histologicamente se caracteriza pela presença de rosetas ou pseudo-rosetas, que säo estromas organizadas circularmente, compostas por núcleos diferenciados e cordas fibrilares, microvascularidade com células neuroepiteliais ao redor dos vasos sanguíneos. Apresentamos um caso, de difícil diagnóstico inicial, revelando patologia em estágio avançado, com mau prognóstico. O diagnóstico precoce com estadiamento apropriado e o tratamento adequado säo fatores importantes para a obtençäo de melhores índices de sobrevivência.