Accessibility and local development: interaction between cross-border accessibility and local development in Portugal and Spain

The main objective in this work is to understand road infrastructure’s impact on development, especially in the EU-context and in the border areas between Portugal and Spain. In these areas, a new road infrastructure was built in the last decades, changing completely the accessibility panorama, while the development variables seem to get worst in most of the cross border regions. Some links are still missing, but some already exist and are not having the expected development impact. The analysis is to be done at the municipality level in order to evaluate the regional differences within the cross border area, which is not possible at the higher NUTIII level.Peer Reviewe

Impact Of A Biomarker-based Strategy On Oncology Drug Development: A Meta-analysis Of Clinical Trials Leading To Fda Approval

Background: In order to ascertain the impact of a biomarker-based (personalized) strategy, we compared outcomes between US Food and Drug Administration (FDA)-approved cancer treatments that were studied with and without such a selection rationale. Methods: Anticancer agents newly approved (September 1998 to June 2013) were identified at the Drugs@FDA website. Efficacy, treatment-related mortality, and hazard ratios (HRs) for time-to-event endpoints were analyzed and compared in registration trials for these agents. All statistical tests were two-sided. Results: Fifty-eight drugs were included (leading to 57 randomized [32% personalized] and 55 nonrandomized trials [47% personalized], n = 38 104 patients). Trials adopting a personalized strategy more often included targeted (100% vs 65%, P < .001), oral (68% vs 35%, P = .001), and single agents (89% vs 71%, P = .04) and more frequently permitted crossover to experimental treatment (67% vs 28%, P = .009). In randomized registration trials (using a random-effects meta-analysis), personalized therapy arms were associated with higher relative response rate ratios (RRRs, compared with their corresponding control arms) (RRRs = 3.82, 95% confidence interval [CI] = 2.51 to 5.82, vs RRRs = 2.08, 95% CI = 1.76 to 2.47, adjusted P = .03), longer PFS (hazard ratio [HR] = 0.41, 95% CI = 0.33 to 0.51, vs HR = 0.59, 95% CI = 0.53 to 0.65, adjusted P < .001) and a non-statistically significantly longer OS (HR = 0.71, 95% CI = 0.61 to 0.83, vs HR = 0.81, 95% CI = 0.77 to 0.85, adjusted P = .07) compared with nonpersonalized trials. Analysis of experimental arms in all 112 registration trials (randomized and nonrandomized) demonstrated that personalized therapy was associated with higher response rate (48%, 95% CI = 42% to 55%, vs 23%, 95% CI = 20% to 27%, P < .001) and longer PFS (median = 8.3, interquartile range [IQR] = 5 vs 5.5 months, IQR = 5, adjusted P = .002) and OS (median = 19.3, IQR = 17 vs 13.5 months, IQR = 8, Adjusted P = .04). A personalized strategy was an independent predictor of better RR, PFS, and OS, as demonstrated by multilinear regression analysis. Treatment-related mortality rate was similar for personalized and nonpersonalized trials. Conclusions: A biomarker-based approach was safe and associated with improved efficacy outcomes in FDA-approved anticancer agents.10711Joan and Irwin Jacobs FundMy Answer To Cancer philanthropic fundFoundation Medicin

O Trabalho Reestruturado: Mudanças nos Rituais dos Bancários

Esta comunicação é o fruto de uma investigação sobre a “preparação” dos bancários. O referencial teórico resgata os temas “competências” e “habilidades”. O estudo de caso ocorreu numa “agência” de médio porte. Pesquisa qualitativa, configurada como exploratória. Utilizaram-se um roteiro de entrevistas semi-estruturado e um questionário como técnicas de coleta de dados. Trabalhou-se com a análise de conteúdos. Os resultados revelaram uma dualidade na formação profissional. As tarefas efetuam-se pela qualificação tradicional, atuação mais eficiente, prática tecnicista; do outro lado, a dimensão do modelo de competência, quando o colaborador decide em situações não previstas nos regulamentos, e trabalha em várias atividades, um polivalente. Observou-se que as ferramentas de qualificação (programas de estímulo à educação formal e empresarial) são disponibilizadas pela organização. Os empregados estão a praticar ações que elevem sua capacitação profissional, incentivados pelo plano de carreira que está na meta da empresa, também já assimilaram a noção de autodesenvolvimento

Bacterioplankton dynamics within a large anthropogenically impacted urban estuary

© 2016 Jeffries, Schmitz Fontes, Harrison, Van-Dongen-Vogels, Eyre, Ralph and Seymour. The abundant and diverse microorganisms that inhabit aquatic systems are both determinants and indicators of aquatic health, providing essential ecosystem services such as nutrient cycling but also causing harmful blooms and disease in impacted habitats. Estuaries are among the most urbanized coastal ecosystems and as a consequence experience substantial environmental pressures, providing ideal systems to study the influence of anthropogenic inputs on microbial ecology. Here we use the highly urbanized Sydney Harbor, Australia, as a model system to investigate shifts in microbial community composition and function along natural and anthopogenic physicochemical gradients, driven by stormwater inflows, tidal flushing and the input of contaminants and both naturally and anthropogenically derived nutrients. Using a combination of amplicon sequencing of the 16S rRNA gene and shotgun metagenomics, we observed strong patterns in microbial biogeography across the estuary during two periods: one of high and another of low rainfall. These patterns were driven by shifts in nutrient concentration and dissolved oxygen leading to a partitioning of microbial community composition in different areas of the harbor with different nutrient regimes. Patterns in bacterial composition were related to shifts in the abundance of Rhodobacteraceae, Flavobacteriaceae, Microbacteriaceae, Halomonadaceae, Acidomicrobiales, and Synechococcus, coupled to an enrichment of total microbial metabolic pathways including phosphorus and nitrogen metabolism, sulfate reduction, virulence, and the degradation of hydrocarbons. Additionally, community beta-diversity was partitioned between the two sampling periods. This potentially reflected the influence of shifting allochtonous nutrient inputs on microbial communities and highlighted the temporally dynamic nature of the system. Combined, our results provide insights into the simultaneous influence of natural and anthropogenic drivers on the structure and function of microbial communities within a highly urbanized aquatic ecosystem

The Brazilian Tunable Filter Imager for the SOAR telescope

This paper presents a new Tunable Filter Instrument for the SOAR telescope. The Brazilian Tunable Filter Imager (BTFI) is a versatile, new technology, tunable optical imager to be used in seeing-limited mode and at higher spatial fidelity using the SAM Ground-Layer Adaptive Optics facility at the SOAR telescope. The instrument opens important new science capabilities for the SOAR community, from studies of the centers of nearby galaxies and the insterstellar medium to statistical cosmological investigations. The BTFI takes advantage of three new technologies. The imaging Bragg Tunable Filter concept utilizes Volume Phase Holographic Gratings in a double-pass configuration, as a tunable filter, while a new Fabry-Perot (FP) concept involves technologies which allow a single FP etalon to act over a large range of interference orders and spectral resolutions. Both technologies will be in the same instrument. Spectral resolutions spanning the range between 25 and 30,000 can be achieved through the use of iBTF at low resolution and scanning FPs beyond R ~2,000. The third new technologies in BTFI is the use of EMCCDs for rapid and cyclically wavelength scanning thus mitigating the damaging effect of atmospheric variability through data acquisition. An additional important feature of the instrument is that it has two optical channels which allow for the simultaneous recording of the narrow-band, filtered image with the remaining (complementary) broad-band light. This avoids the uncertainties inherent in tunable filter imaging using a single detector. The system was designed to supply tunable filter imaging with a field-of-view of 3 arcmin on a side, sampled at 0.12" for direct Nasmyth seeing-limited area spectroscopy and for SAM's visitor instrument port for GLAO-fed area spectroscopy. The instrument has seen first light, as a SOAR visitor instrument. It is now in comissioning phase.Comment: accepted in PAS

Mitochondrial and sarcoplasmic reticulum abnormalities in cancer cachexia: Altered energetic efficiency?

Background Cachexia is a wasting condition that manifests in several types of cancer, and the main characteristic is the profound loss of muscle mass. Methods The Yoshida AH-130 tumor model has been used and the samples have been analyzed using transmission electronic microscopy, real-time PCR and Western blot techniques. Results Using in vivo cancer cachectic model in rats, here we show that skeletal muscle loss is accompanied by fiber morphologic alterations such as mitochondrial disruption, dilatation of sarcoplasmic reticulum and apoptotic nuclei. Analyzing the expression of some factors related to proteolytic and thermogenic processes, we observed in tumor-bearing animals an increased expression of genes involved in proteolysis such as ubiquitin ligases Muscle Ring Finger 1 (MuRF-1) and Muscle Atrophy F-box protein (MAFBx). Moreover, an overexpression of both sarco/endoplasmic Ca2 +-ATPase (SERCA1) and adenine nucleotide translocator (ANT1), both factors related to cellular energetic efficiency, was observed. Tumor burden also leads to a marked decreased in muscle ATP content. Conclusions In addition to muscle proteolysis, other ATP-related pathways may have a key role in muscle wasting, both directly by increasing energetic inefficiency, and indirectly, by affecting the sarcoplasmic reticulum-mitochondrial assembly that is essential for muscle function and homeostasis. General significance The present study reports profound morphological changes in cancer cachectic muscle, which are visualized mainly in alterations in sarcoplasmic reticulum and mitochondria. These alterations are linked to pathways that can account for energy inefficiency associated with cancer cachexia. Highlights ► Skeletal muscle from cachectic animals showed fiber morphologic alterations. ► These alterations are mitochondrial disruption and dilatation of sarcoplasmic reticulum. ► An overexpression of both sarco/endoplasmic Ca2 +-ATPase (SERCA1) and adenine nucleotide translocator (ANT1) was reported. ► Tumor burden also leads to a marked decreased in muscle ATP content. Previous article in issu

Active regulatory T-cells contribute to broadened T-cell repertoire diversity in ivIg-treated SLE patients

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Myocardial infarction with non-obstructive coronary arteries: A comprehensive review and future research directions

Acute coronary syndromes constitute a variety of myocardial injury presentations that include a subset of patients presenting with myocardial infarction with non-obstructive coronary arteries (MINOCA). This acute coronary syndrome differs from type 1 myocardial infarction (MI) regarding patient characteristics, presentation, physiopathology, management, treatment, and prognosis. Two-thirds of MINOCA subjects present ST-segment elevation; MINOCA patients are younger, are more often female and tend to have fewer cardiovascular risk factors. Moreover, MINOCA is a working diagnosis, and defining the aetiologic mechanism is relevant because it affects patient care and prognosis. In the absence of relevant coronary artery disease, myocardial ischaemia might be triggered by an acute event in epicardial coronary arteries, coronary microcirculation, or both. Epicardial causes of MINOCA include coronary plaque disruption, coronary dissection, and coronary spasm. Microvascular MINOCA mechanisms involve microvascular coronary spasm, takotsubo syndrome (TTS), myocarditis, and coronary thromboembolism. Coronary angiography with non-significant coronary stenosis and left ventriculography are first-line tests in the differential study of MINOCA patients. The diagnostic arsenal includes invasive and non-invasive techniques. Medical history and echocardiography can help indicate vasospasm or thrombosis, if one finite coronary territory is affected, or specify TTS if apical ballooning is present. Intravascular ultrasound, optical coherence tomography, and provocative testing are encouraged. Cardiac magnetic resonance is a cornerstone in myocarditis diagnosis. MINOCA is not a benign diagnosis, and its polymorphic forms differ in prognosis. MINOCA care varies across centres, and future multi-centre clinical trials with standardized criteria may have a positive impact on defining optimal cardiovascular care for MINOCA patients

Diverse specificity of cellulosome attachment to the bacterial cell surface

This work was supported by the EU FP7 programme under the WallTraC project (grant No. 263916) and by projects PTDC/BIA-MIC/5947/2014, RECI/BBB-BEP/0124/2012 and EXPL/BIA-MIC/1176/2012 supported by Fundacao para a Ciencia e Tecnologia (FCT-MCTES). The Research Unit UCIBIO (Unidade de Ciencias Biomoleculares Aplicadas) is financed by national funds from FCT/MCTES EC (UID/Multi/04378/2013) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007728). We thank the European Synchrotron Radiation Facility (Grenoble, France), Soleil (Saint-Aubin, France) and Diamond Light Source (Harwell, UK) for data collection and the European Community's Seventh Framework Programme (FP7/2007-2013) under BioStruct-X (grant agreement No. 283570, proposal number: Biostruct-X_ 4399) for funding.During the course of evolution, the cellulosome, one of Nature's most intricate multi-enzyme complexes, has been continuously fine-tuned to efficiently deconstruct recalcitrant carbohydrates. To facilitate the uptake of released sugars, anaerobic bacteria use highly ordered protein-protein interactions to recruit these nanomachines to the cell surface. Dockerin modules located within a non-catalytic macromolecular scaffold, whose primary role is to assemble cellulosomal enzymatic subunits, bind cohesin modules of cell envelope proteins, thereby anchoring the cellulosome onto the bacterial cell. Here we have elucidated the unique molecular mechanisms used by anaerobic bacteria for cellulosome cellular attachment. The structure and biochemical analysis of five cohesin-dockerin complexes revealed that cell surface dockerins contain two cohesin-binding interfaces, which can present different or identical specificities. In contrast to the current static model, we propose that dockerins utilize multivalent modes of cohesin recognition to recruit cellulosomes to the cell surface, a mechanism that maximises substrate access while facilitating complex assembly.publishersversionpublishe