Review of magnetic nanostructures grown by focused electron beam induced deposition (FEBID)

We review the current status of the use of focused electron beam induced deposition (FEBID) for the growth of magnetic nanostructures. This technique relies on the local dissociation of a precursor gas by means of an electron beam. The most promising results have been obtained using the Co₂(CO)₈ precursor, where the Co content in the grown nanodeposited material can be tailored up to more than 95%. Functional behaviour of these Co nanodeposits has been observed in applications such as arrays of magnetic dots for information storage and catalytic growth, magnetic tips for scanning probe microscopes, nano-Hall sensors for bead detection, nano-actuated magnetomechanical systems and nanowires for domain-wall manipulation. The review also covers interesting results observed in Fe-based and alloyed nanodeposits. Advantages and disadvantages of FEBID for the growth of magnetic nanostructures are discussed in the article as well as possible future directions in this field.Financial support by several projects is acknowledged: MAT2014-51982-C2-1-R, MAT2014-51982-C2-2-R and MAT2015-69725-REDT from MINECO (including FEDER funding), CELINA COST Action CM1301, Aragón Regional Government through project E26, FP7 Marie Curie Fellowship 3DMAGNANOW, EPSRC Early Career Fellowship EP/M008517/1 and Winton Fellowship

Health economics: identifying leading producers, countries relative specialization and themes

El área de investigación en economía de la salud tuvo una gran evolución a partir de la década de 1960 y está en constante crecimiento. Actualmente, el gasto en salud es un tema clave en todo el mundo. La bibliometría proporciona varios métodos para explorar el impacto y la evolución de la investigación. Así pues, el principal objetivo del presente estudio es comprender la situación actual de la investigación en materia de economía de la salud para el período 2010-2019. Se analizaron tres aspectos diferentes: la producción de los países, el índice de prioridad relativa y los temas principales. El conjunto de datos se obtuvo a partir de los documentos indizados en la base de datos Web of Science de 2010 a 2019. Se utilizó el software SciMAT para obtener el análisis temático mediante el análisis de mapas de la ciencia. Las revistas Health economics, Value in Health, Journal of Health Economics y European Journal of Health Economics son los principales productoras. Estados Unidos, Inglaterra y Alemania son los que tienen una mayor producción; los Países Bajos, Inglaterra y Australia son los que tienen el índice de prioridad relativa más alto. Los años de vida ajustados en función de la calidad y la desigualdad en materia de salud son los temas con mayor número de documentos y medidas de impacto. Este estudio es un marco útil basado en ciencia que servirá de base para futuras acciones de investigación.Health economics research area was a high evolution from the 1960s and it is constantly growing. Currently, the health expenditure is a key issue worldwide. Bibliometrics provides several methods to explore the impact and evolution of the research. Thus, the main aim of the present study is to understand the current status of the research in health economics for the period 2010-2019. Three different aspects were analyzed: countries production, relative priority index and main themes. The dataset was obtained from the documents indexed in the Web of Science database from 2010 to 2019. SciMAT software was used to obtain the thematic analysis by means of science mapping analysis. The journals Health economics, Value in Health, Journal of Health Economics, and European Journal of Health Economics are the main producers. USA, England and Germany are those with highest production; Netherlands, England and Australia are those with the highest relative priority index. Quality adjusted life years and Health inequality are the themes with the highest number of documents and impact measures. This study is a useful evidence-based framework on which to base future research actions

Fractional-order projection of a chaotic system with hidden attractors and its passivity-based synchronization

This paper presents the fractional-order projection of a chaotic system, which delivers a collection of self-excited and hidden chaotic attractors as a function of a single system parameter. Based on an integer-order chaotic system and the proposed transformation, the fractional-order chaotic system obtains when the divergence of integer and fractional vector fields flows in the same direction. Phase portraits, bifurcation diagrams, and Lyapunov exponents validate the chaos generation. Apart from these results, two passivity-based fractional control laws are designed effectively for the integer and fractional-order chaotic systems. In both cases, the synchronization schemes depend on suitable storage functions given by the fractional Lyapunov theory. Several numerical experiments confirm the proposed approach and agree well with the mathematical deductions

Subsidized pharmacological treatment for smoking cessation by the Spanish public health system

INTRODUCTION Research has shown that financing drug therapy increases smoking abstinence rates, although most of these studies have been carried out in the private healthcare setting. The aim of this work is to assess the effect of subsidized pharmacological treatment on smoking cessation rates by the Spanish public healthcare system. METHODS A pragmatic, randomized, clinical trial was performed by clusters. Randomization unit was the primary healthcare center and the analysis unit was the patient. Smokers consuming ≥10 cigarettes/day were randomly assigned to an intervention group that received financed pharmacological treatment or to a control group that followed usual care. The main outcome was self-reported or CO-confirmed continuous abstinence at 12 months. The main outcome, continuous abstinence rates (%), were compared between groups at 12 months post-intervention. A model was adjusted using mixedeffect logistic regression. RESULTS A total of 1154 patients were included from 23 healthcare centers. In the intention-to-treat analysis, selfreported abstinence after 12 months in the control and intervention groups, respectively, was 9.6% (37/387) and 15.4% (118/767) (gender-adjusted OR=1.75; 95% CI: 1.1– 2.8); for CO-confirmed abstinence the corresponding values were 3.1% (12/387) and 6.4% (49/767) (gender-adjusted OR=1.72; 95% CI: 0.7–4.0). Pharmacological treatment use was 35.1% (136/387) in the control group, and 58.3% (447/767) in the intervention group (adjusted OR=4.25; 95% CI: 1.8–9.9) CONCLUSIONS Subsidizing pharmacological treatment for smoking cessation increases self-reported or CO-confirmed abstinence rates under realistic conditions in the primary care setting of the Spanish public health systemThis trial was funded by the Fondo de Investigaciones Sanitarias (FIS) del Instituto de Salud Carlos III (ISCIII), the European Regional Development Fund (ERDF) under registration number 07528, as well as the 2016 and 2017 calls for grants for translations and publishing by the Fundación para la Investigación e Innovación Biosanitaria en Atención Primaria (FIIBA

Bright Field Microscopy as an Alternative to Whole Cell Fluorescence in Automated Analysis of Macrophage Images

Fluorescence microscopy is the standard tool for detection and analysis of cellular phenomena. This technique, however, has a number of drawbacks such as the limited number of available fluorescent channels in microscopes, overlapping excitation and emission spectra of the stains, and phototoxicity.We here present and validate a method to automatically detect cell population outlines directly from bright field images. By imaging samples with several focus levels forming a bright field -stack, and by measuring the intensity variations of this stack over the -dimension, we construct a new two dimensional projection image of increased contrast. With additional information for locations of each cell, such as stained nuclei, this bright field projection image can be used instead of whole cell fluorescence to locate borders of individual cells, separating touching cells, and enabling single cell analysis. Using the popular CellProfiler freeware cell image analysis software mainly targeted for fluorescence microscopy, we validate our method by automatically segmenting low contrast and rather complex shaped murine macrophage cells.The proposed approach frees up a fluorescence channel, which can be used for subcellular studies. It also facilitates cell shape measurement in experiments where whole cell fluorescent staining is either not available, or is dependent on a particular experimental condition. We show that whole cell area detection results using our projected bright field images match closely to the standard approach where cell areas are localized using fluorescence, and conclude that the high contrast bright field projection image can directly replace one fluorescent channel in whole cell quantification. Matlab code for calculating the projections can be downloaded from the supplementary site: http://sites.google.com/site/brightfieldorstaining

Regulation of cell death receptor S-nitrosylation and apoptotic signaling by Sorafenib in hepatoblastoma cells

Nitric oxide (NO) plays a relevant role during cell death regulation in tumor cells. The overexpression of nitric oxide synthase type III (NOS-3) induces oxidative and nitrosative stress, p53 and cell death receptor expression and apoptosis in hepatoblastoma cells. S-nitrosylation of cell death receptor modulates apoptosis. Sorafenib is the unique recommended molecular-targeted drug for the treatment of patients with advanced hepatocellular carcinoma. The present study was addressed to elucidate the potential role of NO during Sorafenib-induced cell death in HepG2 cells. We determined the intra- and extracellular NO concentration, cell death receptor expression and their S-nitrosylation modifications, and apoptotic signaling in Sorafenib-treated HepG2 cells. The effect of NO donors on above parameters has also been determined. Sorafenib induced apoptosis in HepG2 cells. However, low concentration of the drug (10nM) increased cell death receptor expression, as well as caspase-8 and -9 activation, but without activation of downstream apoptotic markers. In contrast, Sorafenib (10 µM) reduced upstream apoptotic parameters but increased caspase-3 activation and DNA fragmentation in HepG2 cells. The shift of cell death signaling pathway was associated with a reduction of S-nitrosylation of cell death receptors in Sorafenib-treated cells. The administration of NO donors increased S-nitrosylation of cell death receptors and overall induction of cell death markers in control and Sorafenib-treated cells. In conclusion, Sorafenib induced alteration of cell death receptor S-nitrosylation status which may have a relevant repercussion on cell death signaling in hepatoblastoma cells.Instituto de Salud Carlos III PI13/00021Ministerio de Economía y Competitividad BFU2012-32056Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía BIO-0216Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía CTS-6264Consejería de Salud, Junta de Andalucía PI13/ 0002

Identification of a biomarker panel for improvement of prostate cancer diagnosis by volatile metabolic profiling of urine

Background: The lack of sensitive and specific biomarkers for the early detection of prostate cancer (PCa) is a major hurdle to improve patient management. Methods: A metabolomics approach based on GC-MS was used to investigate the performance of volatile organic compounds (VOCs) in general and, more specifically, volatile carbonyl compounds (VCCs) present in urine as potential markers for PCa detection. Results: Results showed that PCa patients (n = 40) can be differentiated from cancer-free subjects (n = 42) based on their urinary volatile profile in both VOCs and VCCs models, unveiling significant differences in the levels of several metabolites. The models constructed were further validated using an external validation set (n = 18 PCa and n = 18 controls) to evaluate sensitivity, specificity and accuracy of the urinary volatile profile to discriminate PCa from controls. The VOCs model disclosed 78% sensitivity, 94% specificity and 86% accuracy, whereas the VCCs model achieved the same sensitivity, a specificity of 100% and an accuracy of 89%. Our findings unveil a panel of 6 volatile compounds significantly altered in PCa patients' urine samples that was able to identify PCa, with a sensitivity of 89%, specificity of 83%, and accuracy of 86%. Conclusions: It is disclosed a biomarker panel with potential to be used as a non-invasive diagnostic tool for PCa.info:eu-repo/semantics/publishedVersio

X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients

Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern

Transcriptional and genomic parallels between the monoxenous parasite Herpetomonas muscarum and Leishmania

Trypanosomatid parasites are causative agents of important human and animal diseases such as sleeping sickness and leishmaniasis. Most trypanosomatids are transmitted to their mammalian hosts by insects, often belonging to Diptera (or true flies). These are called dixenous trypanosomatids since they infect two different hosts, in contrast to those that infect just insects (monoxenous). However, it is still unclear whether dixenous and monoxenous trypanosomatids interact similarly with their insect host, as fly-monoxenous trypanosomatid interaction systems are rarely reported and under-studied–despite being common in nature. Here we present the genome of monoxenous trypanosomatid Herpetomonas muscarum and discuss its transcriptome during in vitro culture and during infection of its natural insect host Drosophila melanogaster. The H. muscarum genome is broadly syntenic with that of human parasite Leishmania major. We also found strong similarities between the H. muscarum transcriptome during fruit fly infection, and those of Leishmania during sand fly infections. Overall this suggests Drosophila-Herpetomonas is a suitable model for less accessible insect-trypanosomatid host-parasite systems such as sand fly-Leishmania

Thermal Stability of the Human Immunodeficiency Virus Type 1 (HIV-1) Receptors, CD4 and CXCR4, Reconstituted in Proteoliposomes

BACKGROUND: The entry of human immunodeficiency virus (HIV-1) into host cells involves the interaction of the viral exterior envelope glycoprotein, gp120, and receptors on the target cell. The HIV-1 receptors are CD4 and one of two chemokine receptors, CCR5 or CXCR4. METHODOLOGY/PRINCIPAL FINDINGS: We created proteoliposomes that contain CD4, the primary HIV-1 receptor, and one of the coreceptors, CXCR4. Antibodies against CD4 and CXCR4 specifically bound the proteoliposomes. CXCL12, the natural ligand for CXCR4, and the small-molecule CXCR4 antagonist, AMD3100, bound the proteoliposomes with affinities close to those associated with the binding of these molecules to cells expressing CXCR4 and CD4. The HIV-1 gp120 exterior envelope glycoprotein bound tightly to proteoliposomes expressing only CD4 and, in the presence of soluble CD4, bound weakly to proteoliposomes expressing only CXCR4. The thermal stability of CD4 and CXCR4 inserted into liposomes was examined. Thermal denaturation of CXCR4 followed second-order kinetics, with an activation energy (E(a)) of 269 kJ/mol (64.3 kcal/mol) and an inactivation temperature (T(i)) of 56°C. Thermal inactivation of CD4 exhibited a reaction order of 1.3, an E(a) of 278 kJ/mol (66.5 kcal/mol), and a T(i) of 52.2°C. The second-order denaturation kinetics of CXCR4 is unusual among G protein-coupled receptors, and may result from dimeric interactions between CXCR4 molecules. CONCLUSIONS/SIGNIFICANCE: Our studies with proteoliposomes containing the native HIV-1 receptors allowed an examination of the binding of biologically important ligands and revealed the higher-order denaturation kinetics of these receptors. CD4/CXCR4-proteoliposomes may be useful for the study of virus-target cell interactions and for the identification of inhibitors