La importància econòmica d'una minoria ètnica: el cas dels xuetes, segles XVI-XVIII

L’estudi de col·lectius minoritaris esdevé una de les peces importants de l’anàliside la història social, econòmica i cultural. El tema dels jueus acumula una amplabibliografia, atesa la rellevància d’aquesta minoria en el decurs de l’evolució històrica.Les connotacions de partida són, endemés, de caire bíblic; però els historiadors hantractat d’esbrinar, a banda d’aquestes perspectives que es relacionen de manera mésdirecta amb les confessions religioses, la funció d’un grup que tingué enormeimportància en camps diferents del coneixement, de la cultura (en el seu sentit més lax)i de l’economia.

Substance P-induced skin inflammation is not modulated by a single dose of sitagliptin in human volunteers.

Substance P (SP), an undecapeptide belonging to the tachykinin family, is released during the activation of sensory nerves, and causes vasodilation, edema and pain through activation of tissular Neurokinin 1 receptors. SP proinflammatory effects are terminated by angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), while the aminopeptidase dipeptidylpeptidase IV (DPPIV) can also play a role. The aim of this randomized, crossover, double-blind study was to assess the cutaneous vasoreactivity (flare and wheal reaction, burning pain sensation) to intradermal injection of ascending doses of SP in six volunteers receiving a single therapeutic dose of the DPPIV inhibitor sitagliptin or a matching placebo. Cutaneous SP challenges produced the expected, dose-dependent flare and wheal response, while eliciting mild to moderate local pain sensation with little dose dependency. However, no differences were shown in the responses observed under sitagliptin compared with placebo, while the study would have been sufficiently powered to detect a clinically relevant increase in sensitivity to SP. The results of this pilot study are in line with proteolytic cleavage of SP by ACE and NEP compensating the blockade of DPPIV to prevent an augmentation of its proinflammatory action.

The ADVANCE trial: clarifying the role of perindopril/indapamide fixed-dose combination in the reduction of cardiovascular and renal events in patients with diabetes mellitus.

Patients with type 2 diabetes mellitus exhibit a marked increase in cardiovascular and renal risk. A number of interventional trials have shown that these patients benefit greatly from aggressive BP lowering, especially when the drug regimen comprises an inhibitor of the renin-angiotensin system. The results of the placebo-controlled ADVANCE (Action in Diabetes and Vascular disease: PreterAx and DiamicroN MR Controlled Evaluation) trial, conducted in patients with type 2 diabetes, are exemplary in this respect. The systematic use of a fixed-dose combination containing the ACE inhibitor perindopril and the diuretic indapamide afforded substantial protection against cardiovascular mortality and myocardial infarction, while providing important renoprotection, reducing the development of micro- and macroalbuminuria, and allowing regression of nephropathy. The beneficial effects were obtained regardless of baseline BP and whether or not the patients were receiving antihypertensive therapy.

Antigen affinity and antigen dose exert distinct influences on CD4 T-cell differentiation.

Cumulative T-cell receptor signal strength and ensuing T-cell responses are affected by both antigen affinity and antigen dose. Here we examined the distinct contributions of these parameters to CD4 T-cell differentiation during infection. We found that high antigen affinity positively correlates with T helper (Th)1 differentiation at both high and low doses of antigen. In contrast, follicular helper T cell (TFH) effectors are generated after priming with high, intermediate, and low affinity ligand. Unexpectedly, memory T cells generated after priming with very low affinity antigen remain impaired in their ability to generate secondary Th1 effectors, despite being recalled with high affinity antigen. These data challenge the view that only strongly stimulated CD4 T cells are capable of differentiating into the TFH and memory T-cell compartments and reveal that differential strength of stimulation during primary T-cell activation imprints unique and long lasting T-cell differentiation programs.

A critical evaluation of secondary cancer risk models applied to Monte Carlo dose distributions of 2-dimensional, 3-dimensional conformal and hybrid intensity-modulated radiation therapy for breast cancer.

The comparison of radiotherapy techniques regarding secondary cancer risk has yielded contradictory results possibly stemming from the many different approaches used to estimate risk. The purpose of this study was to make a comprehensive evaluation of different available risk models applied to detailed whole-body dose distributions computed by Monte Carlo for various breast radiotherapy techniques including conventional open tangents, 3D conformal wedged tangents and hybrid intensity modulated radiation therapy (IMRT). First, organ-specific linear risk models developed by the International Commission on Radiological Protection (ICRP) and the Biological Effects of Ionizing Radiation (BEIR) VII committee were applied to mean doses for remote organs only and all solid organs. Then, different general non-linear risk models were applied to the whole body dose distribution. Finally, organ-specific non-linear risk models for the lung and breast were used to assess the secondary cancer risk for these two specific organs. A total of 32 different calculated absolute risks resulted in a broad range of values (between 0.1% and 48.5%) underlying the large uncertainties in absolute risk calculation. The ratio of risk between two techniques has often been proposed as a more robust assessment of risk than the absolute risk. We found that the ratio of risk between two techniques could also vary substantially considering the different approaches to risk estimation. Sometimes the ratio of risk between two techniques would range between values smaller and larger than one, which then translates into inconsistent results on the potential higher risk of one technique compared to another. We found however that the hybrid IMRT technique resulted in a systematic reduction of risk compared to the other techniques investigated even though the magnitude of this reduction varied substantially with the different approaches investigated. Based on the epidemiological data available, a reasonable approach to risk estimation would be to use organ-specific non-linear risk models applied to the dose distributions of organs within or near the treatment fields (lungs and contralateral breast in the case of breast radiotherapy) as the majority of radiation-induced secondary cancers are found in the beam-bordering regions.

Long-term follow-up of high-dose chemotherapy with autologous stem-cell transplantation and response-adapted whole-brain radiotherapy for newly diagnosed primary CNS lymphoma: results of the multicenter Ostdeutsche Studiengruppe Hamatologie und Onkologie OSHO-53 phase II study.

Background We previously reported the results of a phase II study for patients with newly diagnosed primary central nervous system lymphoma treated with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiotherapy (WBRT). Now, we update the initial results. Patients and methods From 1999 to 2004, 23 patients received high-dose methotrexate. In case of at least partial remission, high-dose busulfan/thiotepa (HD-BuTT) followed by aPBSCT was carried out. Patients refractory to induction or without complete remission after HD-BuTT received WBRT. Eight patients still alive in 2011 were contacted and Mini-Mental State Examination (MMSE) and the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (QLQ)-C30 were carried out. Results Of eight patients still alive, median follow-up is 116.9 months. Only one of nine irradiated patients is still alive with a severe neurologic deficit. In seven of eight patients treated with HD-BuTT, health condition and quality of life are excellent. MMSE and QLQ-C30 showed remarkably good results in patients who did not receive WBRT. All of them have a Karnofsky score of 90%-100%. Conclusions Follow-up shows an overall survival of 35%. In six of seven patients where WBRT could be avoided, no long-term neurotoxicity has been observed and all patients have an excellent quality of life.

Evaluación económica de los impactos del cambio climático sobre la salud

El Informe Stern, realizado a instancias del Gobierno Británico, se ha convertido en el documento paradigmático de la economía del cambio climático. No solo proporciona una estimación de los costes del cambio climático, sino que resulta ser una aportación fundamental a la evaluación de los datos existentes y al fomento de un mayor conocimiento de los aspectos económicos del cambio climático. El informe tiene una perspectiva internacional, por cuanto el cambio climático es un problema mundial, tanto en sus causas como en sus consecuencias. La adopción de medidas colectivas a nivel internacional es crucial para conseguir una respuesta eficaz, eficiente y equitativa. Así, se insta a la comunidad internacional a actuar con fuerza y de forma inmediata en la toma de decisiones que permitan reducir las emisiones (de CO2) para que los efectos del cambio climático no comiencen a ser irremediables. De hecho, la principal conclusión del informe es que los beneficios de la adopción de medidas prontas y firmes sobre el cambio climático superarán con creces los costes

Mobilization of hemopoietic stem cells with high-dose methotrexate plus granulocyte-colony-stimulating factor in patients with primary central nervous system lymphoma.

BACKGROUND: High-dose therapy with autologous stem cell support after standard dose induction is a promising approach for therapy of primary central nervous system lymphoma (PCNSL). High-dose methotrexate (HD-MTX) is a standard drug for induction of PCNSL; however, data about the capacity of HD-MTX plus granulocyte-colony-stimulating factor (G-CSF) to mobilize hemopoietic progenitors are lacking. STUDY DESIGN AND METHODS: This investigation describes the data from stem cell mobilization and apheresis procedures after one or two cycles of HD-MTX for induction of PCNSL within the East German Study Group for Haematology and Oncology 053 trial. Eligible patients proceeded to high-dose busulfan/thiotepa after induction therapy and mobilization. RESULTS: Data were available from nine patients with a median age of 58 years. The maximal CD34+ cell count per microL of blood after the first course of HD-MTX was 13.89 (median). Determination was repeated in six patients after the second course with a significantly higher median CD34+ cell count of 33.69 per microL. Five patients required two apheresis procedures and in four patients a single procedure was sufficient. The total yield of CD34+ cells per kg of body weight harvested by one or two leukapheresis procedures was 6.60 x 10(6) (median; range, 2.68 x 10(6)-15.80 x 10(6)). The yield of CD34+ cells exceeded the commonly accepted lower threshold of 3 x 10(6) cells per kg of body weight in eight of nine cases. Even in the ninth, hemopoietic recovery after stem cell reinfusion was rapid and safe. CONCLUSION: HD-MTX plus G-CSF is a powerful combination for stem cell mobilization in patients with PCNSL and permits safe conduction of time-condensed and dose-intense protocols with high-dose therapy followed by stem cell reinfusion after HD-MTX induction.

Simulação e análise econômica da produção in vivo e in vitro de embriões em bovinos

O objetivo deste trabalho foi avaliar o efeito das variáveis número de receptoras, protocolo de sincronização, indicadores de eficiência reprodutiva e custo da prenhez na eficiência econômica da produção in vivo e in vitro de embriões, em bovinos. Elaborou-se um aplicativo de simulação que permite ao usuário inserir os parâmetros das variáveis de entrada. Um cenário base, originado a partir de taxas tradicionais de eficiência das técnicas de produção in vivo (TE) e in vitro (PIVE) de embriões bovinos, foi introduzido no aplicativo de simulação como critério para comparação dos resultados. O aplicativo desenvolvido foi capaz de reproduzir os cenários de TE e PIVE. A produção de embriões foi simulada com o uso de simulação estocástica. Posteriormente determinou-se o número ótimo de receptoras por análise de sensibilidade. O valor presente líquido e o custo por prenhez foram utilizados como parâmetros de decisão. A sincronização para inovulação em tempo fixo reduziu a ociosidade de receptoras e, consequentemente, o custo final da prenhez em comparação à metodologia tradicional. A sexagem fetal deve estar associada à produção in vivo de embriões bovinos. Além disso, o número ótimo de receptoras por doadora é variável e dependente dos parâmetros de entrada do sistema.

La gobernanza económica de la Zona Euro

La Unión Europea se encuentra actualmente inmersa en un proceso de cambio de su sistema de gobernanza económica. Este artículo analiza por qué los Estados miembros están siendo capaces de cooperar en temas que en los años 1990s eran tabú en la arena comunitaria. En base a una metodología cualitativa y un marco teórico nutrido por los enfoques neofuncionalista e intergubernamental, concluimos que los acuerdos sobre gobernanza económica a los que se está llegando en la actualidad responden más a la necesidad que a la voluntad de hacer avanzar la integración.

La gobernanza económica de la Zona Euro

[spa] La Unión Europea se encuentra actualmente inmersa en un proceso de cambio de su sistema de gobernanza económica. Este artículo analiza por qué los Estados miembros están siendo capaces de cooperar en temas que en los años 1990s eran tabú en la arena comunitaria. En base a una metodología cualitativa y un marco teórico nutrido por los enfoques neofuncionalista e intergubernamental, concluimos que los acuerdos sobre gobernanza económica a los que se está llegando en la actualidad responden más a la necesidad que a la voluntad de hacer avanzar la integración.

Cell-permeable peptides induce dose- and length-dependent cytotoxic effects.

We have explored the threshold of tolerance of three unrelated cell types to treatments with potential cytoprotective peptides bound to Tat(48-57) and Antp(43-58) cell-permeable peptide carriers. Both Tat(48-57) and Antp(43-58) are well known for their good efficacy at crossing membranes of different cell types, their overall low toxicity, and their absence of leakage once internalised. Here, we show that concentrations of up to 100 microM of Tat(48-57) were essentially harmless in all cells tested, whereas Antp(43-58) was significantly more toxic. Moreover, all peptides bound to Tat(48-57) and Antp(43-58) triggered significant and length-dependent cytotoxicity when used at concentrations above 10 microM in all but one cell types (208F rat fibroblasts), irrespective of the sequence of the cargo. Absence of cytotoxicity in 208F fibroblasts correlated with poor intracellular peptide uptake, as monitored by confocal laser scanning fluorescence microscopy. Our data further suggest that the onset of cytotoxicity correlates with the activation of two intracellular stress signalling pathways, namely those involving JNK, and to a lesser extent p38 mitogen-activated protein kinases. These responses are of particular concern for cells that are especially sensitive to the activation of stress kinases. Collectively, these results indicate that in order to avoid unwanted and unspecific cytotoxicity, effector molecules bound to Tat(48-57) should be designed with the shortest possible sequence and the highest possible affinity for their binding partners or targets, so that concentrations below 10 microM can be successfully applied to cells without harm. Considering that cytotoxicity associated to Tat(48-57)- and Antp(43-58) bound peptide conjugates was not restricted to a particular type of cells, our data provide a general framework for the design of cell-penetrating peptides that may apply to broader uses of intracellular peptide and drug delivery.

Dimensão econômica de sistemas de integração lavoura-pecuária

Os sistemas de integração lavoura-pecuária (ILP) têm sido propostos como solução tecnológica para atender critérios de sustentabilidade, mas tal assertiva tem-se baseado principalmente em indicadores agronômicos e ambientais. Neste trabalho, explorou-se a perspectiva econômica da ILP. Os benefícios econômicos potenciais desses sistemas podem refletir-se em economia de escopo (diminuição do custo, em razão da produção de múltiplos produtos) ou nos efeitos de redução de risco pela diversificação. Além disso, eles podem envolver menor variabilidade produtiva e maior produtividade. A mensuração acurada das interações entre os componentes lavoura e animal (pastagem) é etapa-chave a ser perseguida. A tomada de decisão em prol de sistemas diversificados vis-à-vis sistemas especializados deve ser feita de acordo com os preços relativos. A ILP compete com sistemas especializados de pecuária, mas não apresenta taxas de retorno competitivas em comparação a sistemas especializados com soja. A elevada demanda por capital da ILP, particularmente para a aquisição de animais em recria para a engorda, explica as menores taxas de retorno da ILP e é vista como uma das principais restrições para a ampla adoção de sistemas mistos. O desenho de mecanismos de financiamento inovadores será essencial para promover e acelerar a adoção em larga escala da tecnologia.

La viabilidad económica de una Cataluña independiente

El objetivo del presente artículo es demostrar la viabilidad económica de Cataluña como Estado independiente, analizando en particular los aspectos comerciales y hacendísticos. Los datos demuestran que Cataluña tiene un nivel de PIB per cápita por encima de la media UE-15, y a pesar de ser un país de pequeña dimensión cuenta con una economía muy abierta que le permite obtener efectos de escala en el crecimiento y ser un país competitivo. Asimismo, en términos hacendísticos, se estima que una Cataluña independiente tendría una ganancia fiscal de alrededor del 7% del PIB, lo que le permitiría no sólo mantener el actual Estado del Bienestar sino incluso incrementarlo.