Use of a tyrosine kinase inhibitor as neoadjuvant therapy for non-small cell lung cancer: A case report

We report here a 66-year-old woman diagnosed with bronchioloalveolar carcinoma of the right lung cT4N2M0. The patient was from the Philippines, had never smoked, and tested positive for an EGFR mutation. She received gefitinib as neoadjuvant therapy for two months and displayed a partial response. The tumour was resected by performing a right pneumonectomy. The residual viable tumour accounted for less than 10%. Adjuvant chemotherapy with carboplatin-taxol was administered for four cycles. Fifteen months post-surgery, two brain metastases were found. Gefitinib was prescribed, and one month later complete radiological response was assessed. The patient remains asymptomatic and without visible disease four months later. Controlled randomised trials are needed to clarify the role of these target therapies in the neoadjuvant settin

Implementing the livelihood resilience framework: an indicator-based model for assessing mountain pastoral farming systems

CONTEXT: Ongoing decreases in family farms and livestock numbers in European mountain areas are linked to multiple interconnected challenges. The continuity of such farms concerns society at large since they also act as landscape stewards, and their management influences the provision of ecosystem services. The livelihood resilience lens provides a means of examining how farm households respond and build their capacity to persist, to adapt to changes and shocks, and eventually transform what is understood as farming. While an increasing number of studies address livelihood resilience in different parts of the world, its link with livelihood strategies and how these enhance or erode livelihood resilience dimensions is still missing. OBJECTIVE: We built and applied an indicator-based framework to characterize the livelihood strategies of mountain livestock farming households in the Catalan Pyrenees (Spain) considering local historical trends, to assess how these strategies contribute to their adaptive capacity. METHODS: We combined sustainable rural livelihoods and livelihood resilience frameworks and operationalized them to: group farm households with similar livelihood strategies based on their income-generating activities; asses the influence of capital assets and context on the adoption of strategies; and relate these strategies with their performance in three dimensions of adaptive capacity, namely capacity for learning and adaptation, self-organization, and diversity. Information was gathered surveying a sample of 103 farm households. RESULTS AND CONCLUSIONS: We identified five livelihood strategies showing different degrees of adaptive capacity. Farm households either intensified production (21.3% of the sample) or pursued various diversification pathways based on additional off-farm work (28.6%), rural-tourism activities (22.7%), or added-value production (13.3%). Pensioners (11.8%) had a low endowment of assets and presented the lowest estimates in several dimensions of adaptive capacity. In contrast, diversification into rural tourism scored higher in adaptive capacity, showing greater proactive capacity, farmer organization, and multiple income sources. SIGNIFICANCE: We explored the multidimensional issues that influence and are influenced by the livelihood strategies and their adaptive capacity at the farm household level. Our work highlights the relevance of including income-generating activities in addition to structural, technical, and socioeconomic variables in characterizing farming systems. It demonstrates the role of farmer involvement in formal and informal social cooperation networks in the sustainability and adaptive capacity of their households. To be successful, diversification strategies may require certain prerequisites in the farms, while strategies based on off-farm activities, although they support improved financial performance of the farm household, could also contribute to the displacement of agriculture from mountain areas

Inhibition of granulomatous inflammation and prophylactic treatment of schistosomiasis with a combination of edelfosine and Praziquantel

This is an open access article distributed under the terms of the Creative Commons Attribution License.[Background]: Schistosomiasis is the third most devastating tropical disease worldwide caused by blood flukes of the genus Schistosoma. This parasitic disease is due to immunologic reactions to Schistosoma eggs trapped in tissues. Egg-released antigens stimulate tissue-destructive inflammatory and granulomatous reactions, involving different immune cell populations, including T cells and granulocytes. Granulomas lead to collagen fibers deposition and fibrosis, resulting in organ damage. Praziquantel (PZQ) is the drug of choice for treating all species of schistosomes. However, PZQ kills only adult Schistosoma worms, not immature stages. The inability of PZQ to abort early infection or prevent re-infection, and the lack of prophylactic effect prompt the need for novel drugs and strategies for the prevention of schistosomiasis. [Methodology/Principal Findings]: Using in vitro and in vivo approaches, we have found that the alkylphospholipid analog edelfosine kills schistosomula, and displays anti-inflammatory activity. The combined treatment of PZQ and edelfosine during a few days before and after cercariae infection in a schistosomiasis mouse model, simulating a prophylactic treatment, led to seven major effects: a) killing of Schistosoma parasites at early and late development stages; b) reduction of hepatomegaly; c) granuloma size reduction; d) down-regulation of Th1, Th2 and Th17 responses at late post-infection times, thus inhibiting granuloma formation; e) upregulation of IL-10 at early post-infection times, thus potentiating anti-inflammatory actions; f) down-regulation of IL-10 at late post-infection times, thus favoring resistance to re-infection; g) reduction in the number of blood granulocytes in late post-infection times as compared to infected untreated animals. [Conclusions/Significance]: Taken together, these data suggest that the combined treatment of PZQ and edelfosine promotes a high decrease in granuloma formation, as well as in the cellular immune response that underlies granuloma development, with changes in the cytokine patterns, and may provide a promising and effective strategy for a prophylactic treatment of schistosomiasis.This work was supported by grants from the Junta de Castilla y León (SA342U13, CSI052A11-2, and CSI221A12-2), Real Federación Española de Fútbol-Sociedad Española de Medicina Tropical y Salud Internacional (RFEF-SEMTSI 2013), Spanish Ministerio de Economía y Competitividad (SAF2011-30518, SAF2014-59716-R, and RD12/0036/0065 from Red Temática de Investigación Cooperativa en Cáncer, Instituto de Salud Carlos III, cofunded by the Fondo Europeo de Desarrollo Regional of the European Union), and European Community’s Seventh Framework Programme FP7-2007-2013 (grant HEALTH-F2-2011-256986, PANACREAS).Peer Reviewe

In vitro and in vivo anti-schistosomal activity of the alkylphospholipid analog edelfosine

This is an open-access article distributed under the terms of the Creative Commons Attribution License.[Background]: Schistosomiasis is a parasitic disease caused by trematodes of the genus Schistosoma. Five species of Schistosoma are known to infect humans, out of which S. haematobium is the most prevalent, causing the chronic parasitic disease schistosomiasis that still represents a major problem of public health in many regions of the world and especially in tropical areas, leading to serious manifestations and mortality in developing countries. Since the 1970s, praziquantel (PZQ) is the drug of choice for the treatment of schistosomiasis, but concerns about relying on a single drug to treat millions of people, and the potential appearance of drug resistance, make identification of alternative schistosomiasis chemotherapies a high priority. Alkylphospholipid analogs (APLs), together with their prototypic molecule edelfosine (EDLF), are a family of synthetic antineoplastic compounds that show additional pharmacological actions, including antiparasitic activities against several protozoan parasites. [Methodology/Principal Findings]: We found APLs ranked edelfosine> perifosine> erucylphosphocholine> miltefosine for their in vitro schistosomicidal activity against adult S. mansoni worms. Edelfosine accumulated mainly in the worm tegument, and led to tegumental alterations, membrane permeabilization, motility impairment, blockade of male-female pairing as well as induction of apoptosis-like processes in cells in the close vicinity to the tegument. Edelfosine oral treatment also showed in vivo schistosomicidal activity and decreased significantly the egg burden in the liver, a key event in schistosomiasis. [Conclusions/Significance]: Our data show that edelfosine is the most potent APL in killing S. mansoni adult worms in vitro. Edelfosine schistosomicidal activity seems to depend on its action on the tegumental structure, leading to tegumental damage, membrane permeabilization and apoptosis-like cell death. Oral administration of edelfosine diminished worm and egg burdens in S. mansoni -infected CD1 mice. Here we report that edelfosine showed promising antischistosomal properties in vitro and in vivo.This work was supported by the Spanish Ministerio de Ciencia e Innovación (SAF2011-30518, and RD12/0036/0065 from Red Temática de Investigación Cooperativa en Cáncer, Instituto de Salud Carlos III, cofunded by the Fondo Europeo de Desarrollo Regional of the European Union), European Community's Seventh Framework Programme FP7-2007-2013 (grant HEALTH-F2-2011-256986, PANACREAS), Junta de Castilla y León (CSI052A11-2and SA342U13), Sociedad Española de Medicina Tropical y Salud Internacional (RFEF-SEMTSI 2013) and the Universidad de Salamanca (USAL17008).Peer Reviewe

Interface barriers for flux motion in high-temperature superconducting superlattices

We study angular dependent magnetoresistance in the vortex-liquid phase of epitaxial YBa2Cu3O7 thin films and YBa_2Cu_3O_7/PrBa_2Cu_3O_7 superlattices. Superlattices were grown with different PrBa_2Cu_3O_7 thickness in order to tune coupling between YBa_2Cu_3O_7 layers. While dissipation of single film and coupled superlattices is scaled with the anisotropic three-dimensional model in the whole angular range, decoupling through PrBa_2Cu_3O_7 spacer breaks down the scaling and yields strong reduction of the dissipation when the magnetic fields are applied up to ±20degrees around the interface direction. Bean-Livingston barriers at the interface are the mechanism which governs this behavior

Insights in the Stock Mixing Dynamics of Atlantic Bluefin Tuna in the North Atlantic

Effective fisheries management requires accurate stock identification, which can be challenging in mixed stock fisheries such as the Atlantic bluefin tuna (Thunnus thynnus). This species is currently managed considering two stocks known to spawn in the Mediterranean Sea and Gulf of Mexico, respectively. However, recent studies have shown that individuals from both spawning components can interbreed at a recently discovered spawning ground, located in the Slope Sea. A better understanding of the mixing patterns, as well as the proportion in which both stocks interbreed in the Slope Sea are valuable for a reliable Atlantic bluefin tuna stock assessment. With this aim, we assigned genetic origin of 2000 individuals captured at feeding aggregates across the North Atlantic using a 96 SNP panel and analyzed the genetic profile of 500 individuals including 200 potential Slope Sea spawners (i.e., spawning capable individuals captured in this area at the spawning season), using a 8000 SNP array. We confirmed that stock mixing occurs across different feeding aggregates in the North Atlantic, being stronger in the Northwest Atlantic, where the Mediterranean component was a majority at some locations within and near the Slope Sea spawning ground. The analysis of Slope Sea spawner candidate individuals showed nearly equal representation from both Mediterranean and Gulf of Mexico genetic origin individuals, suggesting similar contribution to the Slope Sea origin offspring. Our findings constitute an important progress towards the understanding of the Atlantic bluefin tuna stock mixing dynamics and the relevance of the recently discovered Slope Sea spawning ground for the conservation of the species.En prens

A global customer experience management architecture

Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works. A. Cuadra-Sanchez, M. Cutanda-Rodriguez, I. Perez-Mateos, A. Aurelius, K. Brunnstrom, J. Laulajainen, M. Varela, and J. E. López de Vergara, "A global customer experience management architecture", in Future Network and Mobile Summit, 2012, 1-8The quality of experience (QoE) is one of the main research lines in ITC industry, which seeks to manage quality as perceived by users. This document analyzes and describes requirements of a QoE driven management system architecture, which has been designed in the Celtic IPNQSIS project. The architecture is grouped into different levels: Data acquisition level, Monitoring level and Control Level. Each level comprises a specific set of capacities, such as Data collector, or Traffic Monitor amongst others. The architecture described in this paper constitutes the guidelines of the IPNQSIS project in terms of a QoE ecosystem that will settle the basis of global customer experience management architecture.This work is carried out in the framework of the Celtic and EUREKA initiative IPNQSIS (IP Network Monitoring for Quality of Service Intelligent Support) and has been partially funded by CDTI under Spanish PRINCE (PRoducto INdustrial para la gestión de la Calidad de Experiencia) project, meanwhile the Swedish part of the project is co funded by VINNOVA and the work of Finnish partners has been partially funded by Tekes

Artificially induced reduction of the dissipation anisotropy in high-temperature superconductors

Bi_2Sr_2CaCu_2O_8, RBa_2Cu_3O_7 (R=Y, Eu) thin films and RBa_2Cu_3O_7/PrBa_2Cu_3O_7 superlattices have been fabricated by sputtering technique. The anisotropic dissipation was measured close to the critical temperatures with high applied magnetic fields rotating from parallel to perpendicular to the substrate. In multilayers, in a large magnetic field interval, the dissipation anisotropy is reduced as much as 60% in comparison with the most anisotropic system (Bi_2Sr_2CaCu_2O_8) and at least 50% at 30 kOe in comparison with 123 films. This strong anisotropy reduction is discussed taking into account the role played by the superlattice modulation lengths on magnetic matching effects and coupling between the superconducting layers