Macrophage migration inhibitory factor downregulation: a novel mechanism of resistance to anti-angiogenic therapy.

Anti-angiogenic therapies for cancer such as VEGF neutralizing antibody bevacizumab have limited durability. While mechanisms of resistance remain undefined, it is likely that acquired resistance to anti-angiogenic therapy will involve alterations of the tumor microenvironment. We confirmed increased tumor-associated macrophages in bevacizumab-resistant glioblastoma patient specimens and two novel glioblastoma xenograft models of bevacizumab resistance. Microarray analysis suggested downregulated macrophage migration inhibitory factor (MIF) to be the most pertinent mediator of increased macrophages. Bevacizumab-resistant patient glioblastomas and both novel xenograft models of resistance had less MIF than bevacizumab-naive tumors, and harbored more M2/protumoral macrophages that specifically localized to the tumor edge. Xenografts expressing MIF-shRNA grew more rapidly with greater angiogenesis and had macrophages localizing to the tumor edge which were more prevalent and proliferative, and displayed M2 polarization, whereas bevacizumab-resistant xenografts transduced to upregulate MIF exhibited the opposite changes. Bone marrow-derived macrophage were polarized to an M2 phenotype in the presence of condition-media derived from bevacizumab-resistant xenograft-derived cells, while recombinant MIF drove M1 polarization. Media from macrophages exposed to bevacizumab-resistant tumor cell conditioned media increased glioma cell proliferation compared with media from macrophages exposed to bevacizumab-responsive tumor cell media, suggesting that macrophage polarization in bevacizumab-resistant xenografts is the source of their aggressive biology and results from a secreted factor. Two mechanisms of bevacizumab-induced MIF reduction were identified: (1) bevacizumab bound MIF and blocked MIF-induced M1 polarization of macrophages; and (2) VEGF increased glioma MIF production in a VEGFR2-dependent manner, suggesting that bevacizumab-induced VEGF depletion would downregulate MIF. Site-directed biopsies revealed enriched MIF and VEGF at the enhancing edge in bevacizumab-naive patients. This MIF enrichment was lost in bevacizumab-resistant glioblastomas, driving a tumor edge M1-to-M2 transition. Thus, bevacizumab resistance is driven by reduced MIF at the tumor edge causing proliferative expansion of M2 macrophages, which in turn promotes tumor growth

Is hazard perception ability culturally specific? A cross-cultural comparison between China, Spain and the UK

Hazard perception refers to a driver’s ability to spot hazards on the road in time to make a safe manoeuvre to avoid collision. Such a test is now part of the formal licencing procedure in the UK and in parts of Australia. But can such tests be successfully exported to other countries to reduce traffic fatalities? The aim of this project is to study whether hazard perception skill is culturally specific by comparing UK, Spanish and Chinese drivers across clips filmed in all three countries. Data collection was set-up in the respective countries in collaboration with the University of Granada (Spain) and Tsinghua University (China). Participants had to watch 30 video clips filmed from the driver’s perspective (10 filmed in each of the three countries). Two variants of the test were created: a typical hazard perception test (with full clips requiring speeded responses to hazards), and a hazard prediction task (or 'What Happens Next?' task), where the film ends immediately prior to the hazard onset. This latter test removes the confound of individual hazard thresholds, as participants could successfully report 'what happens next' without judging whether it posed a hazard to them. All videos contained a variety of hazardous situations (or precursors to hazards) reflecting the particular driving environment of each country. Three hundred participants across the 3 countries were tested, evenly divided between learner and experienced drivers. The differences between the culturally-specific tests in their ability to discriminate between driver groups will be discussed in regards to the potential for employing hazard perception testing in diverse geographical locations and cultures

Los conocimientos profesionales en la atención primaria de la salud de la persona/familia en la angustia mental: perspectiva Le Boterf

O objetivo deste trabalho foi identificar os saberes e fazeres constituídos na prática da Saúde da Família (SF), na visão dos enfermeiros, no que se refere ao atendimento à pessoa e família em sofrimento mental na perspectiva dos saberes profissionais de Le Boterf. Método: Foi feito uma pesquisa descritiva exploratória de abordagem qualitativa, delineada para apresentar e aprofundar a construção de competências dos profissionais enfermeiros, foi aplicada em 3 Unidades da SF. Resultados: fazendo uma análise temática, chegou-se às seguintes categorias: “Saber agir com pertinência”; “Saber mobilizar saberes e conhecimentos em um contexto profissional”; “Saber interagir saberes múltiplos”; “Saber transpor”; “Saber aprender e saber aprender a aprender”; “Saber envolver-se”. Considerações finais: verificou-se que entre os saberes a maior dificuldade é a de “saber transpor”, e que o cotidiano das equipes de SF exige muito desse saber. Foi verificado pouca transposição de saberes/fazeres em situações reais.El objetivo del estudio fue identificar los conocimientos y acciones en la práctica de la Salud de la Familia (SF), a la vista de las enfermeras en relación con la persona y la familia en el cuidado angustia mental en términos de conocimientos profesionales de Le Boterf. Método: Un estudio cualitativo exploratorio descriptivo, se indica para introducir y profundizar en el desarrollo de habilidades de las enfermeras, aplicado a 3 unidades SF. Resultados: hacer un análisis temático, llegó a las siguientes categorías: “Saber actuar correctamente”; “Conociendo a movilizar conocimientos y experiencia en el ámbito profesional”; “Sabiendo que interactúan múltiples saberes”; “Sabiendo transponer”; “El saber aprender y saber cómo aprender a aprender”; “Sabiendo participar”. Consideraciones finales: se encontró el conocimiento de la mayor dificultad es la de "ser capaz de incorporar", y que los equipos diarias SF requiere mucho este conocimiento. Poco transposición del saber/hacer en situaciones reales ha sido verificada.Aim of this study was to identify knowing-doing actions constituted the practice of Family Health (FH), in view of nurses in relation to the person and family care in mental distress in terms of professional knowledge of Le Boterf. Method: Descriptive exploratory qualitative study, to deepen contruction of nurse in FH. The survey was conducted in 3 Units FH. Result: Doing a thematic analysis, came to the following categories: “Knowing how to act and react with relevance”; “Knowing how to combine resources and mobilize them in a professional context”; “Knowing how to interact with multiple knowledges”; “Knowing how to transpose”; “Knowing how to learn and knowing how to learn to learn”; “Knowing how to engage”. Final considerations: the greatest difficulty was "be able to transpose," and that the daily demand of the FH teams requires a lot of this knowledge. Little transposition of knowing-doing in real situations has been verified

Single valley Dirac fermions in zero-gap HgTe quantum wells

Dirac fermions have been studied intensively in condensed matter physics in recent years. Many theoretical predictions critically depend on the number of valleys where the Dirac fermions are realized. In this work, we report the discovery of a two dimensional system with a single valley Dirac cone. We study the transport properties of HgTe quantum wells grown at the critical thickness separating between the topologically trivial and the quantum spin Hall phases. At high magnetic fields, the quantized Hall plateaus demonstrate the presence of a single valley Dirac point in this system. In addition, we clearly observe the linear dispersion of the zero mode spin levels. Also the conductivity at the Dirac point and its temperature dependence can be understood from single valley Dirac fermion physics.Comment: version 2: supplementary material adde

Gate-tuned normal and superconducting transport at the surface of a topological insulator

Three-dimensional topological insulators are characterized by the presence of a bandgap in their bulk and gapless Dirac fermions at their surfaces. New physical phenomena originating from the presence of the Dirac fermions are predicted to occur, and to be experimentally accessible via transport measurements in suitably designed electronic devices. Here we study transport through superconducting junctions fabricated on thin Bi2Se3 single crystals, equipped with a gate electrode. In the presence of perpendicular magnetic field B, sweeping the gate voltage enables us to observe the filling of the Dirac fermion Landau levels, whose character evolves continuously from electron- to hole-like. When B=0, a supercurrent appears, whose magnitude can be gate tuned, and is minimum at the charge neutrality point determined from the Landau level filling. Our results demonstrate how gated nano-electronic devices give control over normal and superconducting transport of Dirac fermions at an individual surface of a three-dimensional topological insulator.Comment: 28 pages, 5 figure

Socio-professional profile of the foreign teacher in Brazilian public university

Este trabajo, fruto de una tesis de doctorado en educación, tuvo como objetivo comprender la figura del profesor extranjero, su perfil, dificultades, retos y contribución a la permanencia en la reconstrucción de las prácticas didáctico-pedagógicas y su actuación como profesional docente en las universidades públicas brasileñas. El estudio se justifica debido a su número creciente, particularmente durante en los últimos diez años y que, por lo tanto, no ha sido objeto de investigación sistemática. Nuestro universo de investigación ha sido la UNB, Universidad pública federal de Brasilia, que concentra el mayor número de estos profesores. Utilizamos los datos del INEP (microdatos del censo de la educación superior, 2011) como base para localizar a estos docentes. Se aplicaron cuestionarios a más de 37,3% de las nacionalidades presentes (19 de 51 nacionalidades) que corresponde al 7,6% de una población estimada de 250 docentes, como documentos de consulta (sitios web de la escuela, sitio web personal, servicios de fotocopia). El análisis cualitativo y el tratamiento estadístico de los datos nos permitió obtener los siguientes Resultados: los profesores extranjeros que se encuentran en UNB son originarios, en su mayoría, de los países de América Latina y de Europa, son blancos o de color, son doctores y están contratados a tiempo completo y dedicación exclusiva. También intervienen en tareas de investigación y extensión. Estos docentes encuentran grandes dificultades de adaptación a sus lugares de trabajo debido a la falta de mecanismos de socialización y de ayuda en sus prácticas pedagógicas. A la luz de la complejidad del paradigma de Edgar Morin, se puede afirmar que el profesor extranjero sobrevive en la Universidad Pública Brasileña en medio de dilemas y contradicciones tales como problemas culturales, de alteridad y de aceptación por parte de los estudiantes, su inserción en la propia universidad es la busca permanente de medios para poder conectar. Sin embargo, debemos destacar la gran contribución de estos profesores a la calidad de los programas de grado y la inserción internacional de las universidades.This paper fruit of a doctorate thesis in education aimed to understand the foreign teacher, its profile, difficulties, contributions permanence challenges and reconstruction of didactic-pedagogical practices and for its professional exercise in the brazilian public universities. The study was justified because of their increasing number particularly during the last decade and also the lack of systematic research of the thematic. Our universe was the UnB, federal public university of Brasilia where we found the bigger number of these teachers. Using the INEP data (micro data of census of higher education, 2011) we could localize those ones. Questionnaires were applied to more than 37,3% of the nationalities present (19 of 51 nationalities) corresponding to 7,6% of the population estimated to 250 teachers, documents consulting (school websites, personnel website, photocopy services). The qualitative analysis and the statistical data treatment allowed us to obtain the following results: the teachers met at UnB are from Latin America and Europe, are white or brunet, are doctors and are contracted full time. They also act in teaching, research and extension. These teachers met many adaptation difficulties in their workplace due to a lack of socialization and help mechanisms in their teaching practices. By means of the complexity paradigm of Edgar Morin, we could confirm that the foreign teacher survive in the Brazilian public university within dilemmas and contradictions like cultural problems, alterity and acceptation by the students, its insertion in the own university and is always in search for means to connect the parts. Although, we could note the big contributions of these teachers in the quality of the graduate programs and the international insertion of their universities.Esse trabalho, fruto de uma tese de doutorado em educação buscou apreender o professor estrangeiro, no seu perfil, suas dificuldades, suas contribuições e desafios para a permanência e reconstrução das práticas didático-pedagógicas e para a atuação como profissional docente nas universidades públicas brasileiras. O estudo se justificou pelo fato de termos um grande número desses sujeitos nas universidades públicas brasileiras principalmente nos últimos dez anos e que, portanto, nunca foi ainda objeto de um estudo sistemático. Nosso universo de pesquisa foi a UnB, instituição pública federal que concentra o maior número desses professores. Dados do INEP (microdados do censo do ensino superior do ano de 2011) nos serviram de base para localizar esses docentes. Foram aplicados questionários a mais de 37,3% das nacionalidades presentes (19 das 51 nacionalidades) correspondendo a 7,6% de uma população de 250 professores além de entrevistas semiestruturadas, consulta a documentos disponibilizados nas IES e em outros locais (sites web das faculdades, sites pessoais e copiadoras). A análise qualitativa e o tratamento estatístico dos dados nos permitiram chegar as seguintes conclusões: os professores estrangeiros que se encontram na UNB são originários na sua maioria dos países da América Latina e da Europa, se declaram brancos ou pardos, têm títulos de doutores, trabalham em regime de dedicação exclusiva e atuam no ensino, pesquisa e extensão. Esses docentes encontram grandes dificuldades de adaptação em seus locais de trabalho devido à falta de mecanismos de socialização e de auxílio em suas práticas pedagógicas. À luz do paradigma da complexidade de Edgar Morin, pôde se afirmar que o professor estrangeiro sobrevive na universidade pública brasileira em meio a dilemas e contradições que vão desde inquietações culturais, alteridade e aceitação pelos alunos até sua própria integração na universidade e a busca permanente da união dessas partes. No entanto, há de se notar a grande contribuição desses professores no que tange à inserção dos programas de pós-graduação onde atua em altos patamares de qualidade além da além da inserção internacional.peerReviewe

Assimilation of healthy and indulgent impressions from labelling influences fullness but not intake or sensory experience

Background: Recent evidence suggests that products believed to be healthy may be over-consumed relative to believed indulgent or highly caloric products. The extent to which these effects relate to expectations from labelling, oral experience or assimilation of expectations is unclear. Over two experiments, we tested the hypotheses that healthy and indulgent information could be assimilated by oral experience of beverages and influence sensory evaluation, expected satiety, satiation and subsequent appetite. Additionally, we explored how expectation-experience congruency influenced these factors. Results: Results supported some assimilation of healthiness and indulgent ratings—study 1 showed that indulgent ratings enhanced by the indulgent label persisted post-tasting, and this resulted in increased fullness ratings. In study 2, congruency of healthy labels and oral experience promoted enhanced healthiness ratings. These healthiness and indulgent beliefs did not influence sensory analysis or intake—these were dictated by the products themselves. Healthy labels, but not experience, were associated with decreased expected satiety. Conclusions: Overall labels generated expectations, and some assimilation where there were congruencies between expectation and experience, but oral experience tended to override initial expectations to determine ultimate sensory evaluations and intake. Familiarity with the sensory properties of the test beverages may have resulted in the use of prior knowledge, rather than the label information, to guide evaluations and behaviour

Spin-related tunneling through a nanostructured electric-magnetic barrier on the surface of a topological insulator

We investigate quantum tunneling through a single electric and/or magnetic barrier on the surface of a three-dimensional topological insulator. We found that (1) the propagating behavior of electrons in such system exhibits a strong dependence on the direction of the incident electron wavevector and incident energy, giving the possibility to construct a wave vector and/or energy filter; (2) the spin orientation can be tuned by changing the magnetic barrier structure as well as the incident angles and energies

The history and evolution of the clinical effectiveness of haemophilia type a treatment: a systematic review.

First evidence of cases of haemophilia dates from ancient Egypt, but it was when Queen Victoria from England in the 19th century transmitted this illness to her descendants, when it became known as the "royal disease". Last decades of the 20th century account for major discoveries that improved the life expectancy and quality of life of these patients. The history and evolution of haemophilia healthcare counts ups and downs. The introduction of prophylactic schemes during the 1970s have proved to be more effective that the classic on-demand replacement of clotting factors, nevertheless many patients managed with frequent plasma transfusions or derived products became infected with the Human Immunodeficiency Virus (HIV) and Hepatitis C virus during the 1980s and 1990s. Recombinant factor VIII inception has decreased the risk of blood borne infections and restored back longer life expectancies. Main concerns for haemophilia healthcare are shifting from the pure clinical aspects to the economic considerations of long-term replacement therapy. Nowadays researchers' attention has been placed on the future costs and cost-effectiveness of costly long-term treatment. Equity considerations are relevant as well, and alternative options for less affluent countries are under the scope of further research. The aim of this review was to assess the evidence of different treatment options for haemophilia type A over the past four decades, focusing on the most important technological advances that have influenced the natural course of this "royal disease"