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This letter addresses the problem of trajectory planning in a marsupial robotic system consisting of an unmanned aerial vehicle (UAV) linked to an unmanned ground vehicle (UGV) through a non-taut tether with controllable length. To the best of our knowledge, this is the first method that addresses the trajectory planning of a marsupial UGV-UAV with a non-taut tether. The objective is to determine a synchronized collision-free trajectory for the three marsupial system agents: UAV, UGV, and tether. First, we present a path planning solution based on optimal Rapidly-exploring Random Trees (RRT*) with novel sampling and steering techniques to speed-up the computation. This algorithm is able to obtain collision-free paths for the UAV and the UGV, taking into account the 3D environment and the tether. Then, the letter presents a trajectory planner based on non-linear least squares. The optimizer takes into account aspects not considered in the path planning, like temporal constraints of the motion imposed by limits on the velocities and accelerations of the robots, or raising the tether's clearance. Simulated and field test results demonstrate that the approach generates obstacle-free, smooth, and feasible trajectories for the marsupial system., 8 pages, 4 figures, 3 tables

El cáncer de mama (CM) es la primera causa de muerte por cáncer en mujeres tanto a nivel mundial como en Chile. Basados en características clínicas, histológicas y moleculares, múltiples estudios han identificado cuatro subtipos básicos de CM, los cuales están asociados a estrategias de tratamiento específicas y diferenciadas. El CM HER2-positivo representa un 15-25% de todas las neoplasias mamarias y se caracteriza por su agresividad, recurrencia temprana y mayor tendencia a presentar compromiso del sistema nervioso central. En las últimas décadas, nuevas terapias dirigidas se han posicionado como el estándar de tratamiento y han cambiado la historia natural de esta enfermedad, transformándola en una enfermedad potencialmente curable incluso en etapas avanzadas. Esta revisión busca entregar un resumen de las bases biológicas de esta enfermedad. Por otro lado, dada la aparición de un creciente número de nuevas estrategias de manejo sistémico, nos proponemos revisar sus mecanismos de acción analizando reportes de datos clínicos publicados y la experiencia de nuestro grupo.

This study focuses on the relationship between the starch de-structuring process and its shear-induced rheological properties. Waxy potato starch underwent a de-structuring process (120–150 °C for 30 min under continuous stirring) where the starch granules were completely gelatinised and subsequently reduced into fragments and polymer chains. A significant increase in the degree of branching was noted in 140 and 150 °C de-structured waxy potato starch (DWPS) samples as compared to its native form. However, no significant change in the side-chain profile of DWPS samples was detected. Laser diffraction measurements revealed the presence of large particles in DWPS samples, which indicated that the starch de-structuring process into its macromolecules was incomplete even at 150 °C for 30 min. Complex shear-induced behaviours (shear-thickening, shear-induced gelation and/or anti-thixotropy) were noted in 120 and 140 °C DWPS samples. Such behaviours were attributed to the reduction in size and increased number of fragments, together with interactions among fragments and amylopectin chains in these DWPS samples when subjected to shear.

This study investigated the effect of puka gum (PG) (crude and purified) concentration on its emulsification properties in terms of droplet size distribution, zeta potential, rheological and microstructural properties of the emulsions and their visual phase separation. Different concentrations of PG (1–10% w/w) were used to stabilize 15% w/w soybean oil-in-water emulsions. The effect of constant shear rate and time on the apparent viscosity of PG solutions was also tested. PG stabilised-oil-in-water emulsions exhibited monomodal size distributions with average droplet sizes (d32) below 2 μm at 4% w/w PG. The apparent viscosity of these emulsions was dependent on gum concentration exhibiting a Newtonian behaviour at low PG concentrations (≤4% w/w), with shear-thinning at higher concentrations, becoming slightly more pronounced above 100s−1 and especially at 10% w/w gum. The loss modulus (G”) was higher than the storage modulus (G’) at all concentrations indicating that the liquid-like behaviour dominated at all frequencies. The apparent viscosity of PG solutions, showed an irreversible loss of viscosity after shearing over a period of time, presumably resulting from chain breakage and molecular weight reduction. PG droplets were negatively charge with zeta-potential values in the range of −30 – (−45) mV. Furthermore, PG-stabilised emulsions remained stable against phase separation for at least 30 days. Crude and purified PG exhibited no major differences in terms of their emulsifying properties at 4% w/w suggesting that a purification process may not be required for food formulations. Overall, PG can be considered as a promising natural emulsifier for emulsion-based foods and beverage products.

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BackgroundInformation on tuberculosis (TB) and coronavirus disease 2019 (COVID-19) is still limited. The aim of this study was to describe the features of the TB/COVID-19 co-infected individuals from a prospective, anonymised, multicountry register-based cohort with special focus on the determinants of mortality and other outcomes.MethodsWe enrolled all patients of any age with either active TB or previous TB and COVID-19. 172 centres from 34 countries provided individual data on 767 TB-COVID-19 co-infected patients, (>50% population-based).ResultsOf 767 patients, 553 (74.0%) out of 747 had TB before COVID-19 (including 234 out of 747 with previous TB), 71 (9.5%) out of 747 had COVID-19 first and 123 (16.5%) out of 747 had both diseases diagnosed within the same week (n=35 (4.6%) on the same day). 85 (11.08%) out of 767 patients died (41 (14.2%) out of 289 in Europe and 44 (9.2%) out of 478 outside Europe; p=0.03): 42 (49.4%) from COVID-19, 31 (36.5%) from COVID-19 and TB, one (1.2%) from TB and 11 from other causes. In the univariate analysis on mortality the following variables reached statistical significance: age, male gender, having more than one comorbidity, diabetes mellitus, cardiovascular disease, chronic respiratory disease, chronic renal disease, presence of key symptoms, invasive ventilation and hospitalisation due to COVID-19. The final multivariable logistic regression model included age, male gender and invasive ventilation as independent contributors to mortality.ConclusionThe data suggest that TB and COVID-19 are a “cursed duet” and need immediate attention. TB should be considered a risk factor for severe COVID disease and patients with TB should be prioritised for COVID-19 preventative efforts, including vaccination.

Introducci��n: actualmente existe un debate sobre si la ���Dependencia Emocional��� constituye un trastorno real, el aumento de las publicaciones sobre este tema en los ��ltimos a��os parece reflejar el inter��s por este problema. El objetivo de esta revisi��n es proporcionar una visi��n general completa de los estudios emp��ricos actuales sobre la dependencia emocional desde una perspectiva integradora. M��todo: se llev�� a cabo una revisi��n de la literatura para (i) identificar estudios emp��ricos que eval��en la dependencia emocional en mujeres (ii) revisar el concepto, su definici��n, identificaci��n y aspectos asociados y (iii) presentar, relacionar y discutir los resultados. Resultados: la revisi��n sistem��tica de la literatura identific�� 19 estudios relevantes. Los estudios incluidos utilizaron muestras cl��nicas y de poblaci��n general (menores, adolescentes y adultos) y se centraron en las caracter��sticas de las personas afectadas por el problema. Los trabajos se focalizaron en (1) la validaci��n de instrumentos de medida; y (2) estudios descriptivos o correlacionales. Discusi��n: es necesario un consenso con respecto a la definici��n y al diagn��stico de la dependencia emocional. Existe una necesidad de mayor consistencia y estandarizaci��n en esta ��rea. Es vital un esfuerzo internacional para comprender la psicopatolog��a del problema y desarrollar mejores pr��cticas en el tratamiento., Psicosom��tica y Psiquiatr��a, N��m. 5 (2018): abril-mayo-junio

A comprehensive view of cell metabolism provides a new vision of cancer, conceptualized as tissue with cellular-altered metabolism and energetic dysfunction, which can shed light on pathophysiological mechanisms. Cancer is now considered a heterogeneous ecosystem, formed by tumor cells and the microenvironment, which is molecularly, phenotypically, and metabolically reprogrammable. A wealth of evidence confirms metabolic reprogramming activity as the minimum common denominator of cancer, grouping together a wide variety of aberrations that can affect any of the different metabolic pathways involved in cell physiology. This forms the basis for a new proposed classification of cancer according to the altered metabolic pathway(s) and degree of energy dysfunction. Enhanced understanding of the metabolic reprogramming pathways of fatty acids, amino acids, carbohydrates, hypoxia, and acidosis can bring about new therapeutic intervention possibilities from a metabolic perspective of cancer.

This paper describes the development of a reactive behavioral response framework for the tabletop robot Haru. The framework enables the robot to react to external stimuli through a repertoire of expressive routines. The behavioral response framework is inspired by the simple reactive behaviors of organisms (e.g. reflexes) based on a bottom-up attention model. First, a participatory study for behavior elicitation was conducted. We explored the possible expressive behaviors of the robot and the possible stimuli trigger. These stimuli-response (S-R) pairs are designed befitting the robot's characteristics. Then, we developed a perception and a reactive behavior module that automatically translates any perceived stimulus into expressive behavioral responses. We evaluated the proposed S-R framework using Haru in an interaction setting and our results show an increase in human attention activity indicative of its positive impact to conveying the robot's sense of agency.

Item does not contain fulltext This paper describes the development of a reactive behavioral response framework for the tabletop robot Haru. The framework enables the robot to react to external stimuli through a repertoire of expressive routines. The behavioral response framework is inspired by the simple reactive behaviors of organisms (e.g. reflexes) based on a bottom-up attention model. First, a participatory study for behavior elicitation was conducted. We explored the possible expressive behaviors of the robot and the possible stimuli trigger. These stimuli-response (S-R) pairs are designed befitting the robot's characteristics. Then, we developed a perception and a reactive behavior module that automatically translates any perceived stimulus into expressive behavioral responses. We evaluated the proposed S-R framework using Haru in an interaction setting and our results show an increase in human attention activity indicative of its positive impact to conveying the robot's sense of agency. ICSR 2021: 13th International Conference on Social Robotics (Singapore, November 10-13, 2021)

Background The search for immunological markers with ability of predicting clinical outcome is a priority in lymphomas, and in cancer in general. It is well known that some immunomodulatory cells, such as myeloid derived suppressor cells (MDSCs) or regulatory T cells (Tregs), are recruited by tumors, jeopardizing antitumor immunosurveillance. In this work, we have studied blood levels of these immunosuppressive cells in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), prior to and along the course of the experimental rituximab, gemcitabine, dexamethasone, and cisplatin (R2-GDP) schedule, as a translational substudy of the R2-GDP-GOTEL trial (EudraCT Number: 2014-001620-29), which included lenalidomide as an immunomodulator. Methods Blood samples were taken before treatment, at cycle 3 and end of induction. Samples were analyzed by flow cytometry. Non-parametric tests were used. Mann-Whitney U test was used to compare basal cells distributions, and Wilcoxon test was considered to compare cells distribution at different times. Spearman test was performed to measure the degree of association between cell populations. Results In this study, MDSC and Treg circulating concentration was found increased in all patients compared with a healthy control group and decreased after treatment only in patients with longest overall survival (>24 months), reaching the levels of the healthy group. Likewise, the number of inhibited T lymphocytes expressing Programmed Death-1 (PD-1) were increased in peripheral blood from patients and decreased on the treatment, whereas activated T lymphocytes increased after therapy in those with better overall survival. Conclusions In conclusion, blood concentration of MDSCs and Treg cells may be good prognostic markers for overall survival after 2 years in R/R DLBCL. These results point to a possible role of these elements in the immunosuppression of these patients, as assessed by the circulating activated and inhibited T lymphocytes, and therefore, they may be considered as therapeutic targets in DLBCL.

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Background Several therapeutic options are now available in the adjuvant melanoma setting, mandating an understanding of their benefit €'risk profiles in order to make informed treatment decisions. Herein we characterize adjuvant nivolumab select (immune-related) treatment-related adverse events (TRAEs) and evaluate possible associations between safety and recurrence-free survival (RFS) in the phase III CheckMate 238 trial. Methods Patients with resected stage IIIB-C or IV melanoma received nivolumab 3 mg/kg every 2 weeks (n=452) or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks (n=453) for up to 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. First-occurrence and all-occurrence select TRAEs were analyzed within discrete time intervals: from 0 to 3 months of treatment, from >3-12 months of treatment, and from the last dose (regardless of early or per-protocol treatment discontinuation) to 100 days after the last dose. Possible associations between select TRAEs and RFS were investigated post randomization in 3-month landmark analyses and in Cox model analyses (including a time-varying covariate of select TRAE), within and between treatment groups. Results From the first nivolumab dose to 100 days after the last dose, first-occurrence select TRAEs were reported in 67.7% (306/452) of patients. First-occurrence select TRAEs were reported most frequently from 0 to 3 months (48.0%), during which the most common were pruritus (15.5%) and diarrhea (15.3%). Most select TRAEs resolved within 6 months. There was no clear association between the occurrence (or not) of select TRAEs and RFS by landmark analysis or by Cox model analysis within treatment arms or comparing nivolumab to the ipilimumab comparator arm. Conclusion Results of this safety analysis of nivolumab in adjuvant melanoma were consistent with its established safety profile. In the discrete time intervals evaluated, most first-occurrence TRAEs occurred early during treatment and resolved. No association between RFS and select TRAEs was evident. Trial registration number NCT02388906. ©

New treatment strategies such as immune checkpoint inhibitors and oncolytic viruses are opening new possibilities in cancer therapy. Preliminary results in melanoma and other tumors showed that the combination of talimogene laherparepvec with an anti-PD-1/PD-L1 or anti-CTLA4 has greater efficacy than either therapy alone, without additional safety concerns beyond those expected for each agent. The presence of residual cancer after neoadjuvant chemotherapy in early breast cancer patients is an unmet medical need. SOLTI-1503 PROMETEO is a window of opportunity trial, which evaluates the combination of talimogene laherparepvec in combination with atezolizumab in women with operable HER2-negative breast cancer who present residual disease after neoadjuvant chemotherapy. The primary end point is therate of residual cancer burden0/1. Clinical Trial Registration: NCT03802604 (ClinicalTrials.gov).

Tumor progression is mediated by reciprocal interaction between tumor cells and their surrounding tumor microenvironment (TME), which among other factors encompasses the extracellular milieu, immune cells, fibroblasts, and the vascular system. However, the complexity of cancer goes beyond the local interaction of tumor cells with their microenvironment. We are on the path to understanding cancer from a systemic viewpoint where the host macroenvironment also plays a crucial role in determining tumor progression. Indeed, growing evidence is emerging on the impact of the gut microbiota, metabolism, biomechanics, and the neuroimmunological axis on cancer. Thus, external factors capable of influencing the entire body system, such as emotional stress, surgery, or psychosocial factors, must be taken into consideration for enhanced management and treatment of cancer patients. In this article, we review prognostic and predictive biomarkers, as well as their potential evaluation and quantitative analysis. Our overarching aim is to open up new fields of study and intervention possibilities, within the framework of an integral vision of cancer as a functional tissue with the capacity to respond to different non-cytotoxic factors, hormonal, immunological, and mechanical forces, and others inducing stroma and tumor reprogramming.

International audience; We here report the detection of extended He ii λ4686 nebular emission in the central region of NGC 1569 using the integral field spectrograph MEGARA at the 10.4-m Gran Telescopio Canarias. The observations cover a Field of View (FoV) of 12.5 arcsec×11.3 arcsec at seeing-limited spatial resolution of ∼15 pc and at a spectral resolution of R=6000 in the wavelength range 4330-5200Å. The emission extends over a semi-circular arc of ∼40 pc width and ∼150 pc diameter around the super star cluster A (SSC-A). The A V derived using Balmer decrement varies from the Galactic value of 1.6 mag to a maximum of ∼4.5 mag, with a mean value of 2.65±0.60 mag. We infer 124±11 Wolf-Rayet (WR) stars in SSC-A using the He ii λ4686 broad feature and A V =2.3 mag. The He + ionizing photon rate from these WR stars is sufficient to explain the luminosity of the He ii nebula. The observationally-determined total He + and H 0 ionizing photon rates, their ratio, and the observed number of WR stars in SSC-A are all consistent with the predictions of simple stellar population models at an age of 4.0±0.5 Myr, and mass of (5.5±0.5)×10 5 M. Our observations reinforce the absence of WR stars in SSC-B, the second most massive cluster in the FoV. None of the other locations in our FoV where He ii λ4686 emission has been reported from narrow-band imaging observations contain WR stars.

© 2013 IEEE. We present a novel implementation of a Rock-Paper-Scissors (RPS) game interaction with a social robot. The framework is tailored to be computationally lightweight, as well as entertaining and visually appealing through collaboration with designers and animators. The fundamental gesture recognition pipeline employs a Leap motion device and two separate machine learning architectures to evaluate kinematic hand data on-the-fly. The first architecture is used to recognize and segment human motion activity in order to initialize the RPS play, and the second architecture is used to classify hand gestures into rock, paper or scissors. The employed tabletop robot interacts in the RPS play through unique animated gestural movements and vocalizations designed by animators which communicate the robot's choices as well as cognitive reflection on winning, losing and draw states. Performance of both learning architectures is carefully evaluated with respect to accuracy, reliability and run time performance under different feature and classifier types. Moreover, we assess our system during an interactive RPS play between robot and human. Experimental results show that the proposed system is robust to user variations and play style in real environment conditions. As such, it offers a powerful application for the subsequent exploration of social human-machine interaction.

Background: Previously, findings from CheckMate 238, a double-blind, phase 3 adjuvant trial in patients with resected stage IIIB–C or stage IV melanoma, showed significant improvements in recurrence-free survival and distant metastasis-free survival with nivolumab versus ipilimumab. This report provides updated 4-year efficacy, initial overall survival, and late-emergent safety results. Methods: This multicentre, double-blind, randomised, controlled, phase 3 trial was done in 130 academic centres, community hospitals, and cancer centres across 25 countries. Patients aged 15 years or older with resected stage IIIB–C or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) to receive nivolumab or ipilimumab via an interactive voice response system and stratified according to disease stage and baseline PD-L1 status of tumour cells. Patients received intravenous nivolumab 3 mg/kg every 2 weeks or intravenous ipilimumab 10 mg/kg every 3 weeks for four doses, and then every 12 weeks until 1 year of treatment, disease recurrence, unacceptable toxicity, or withdrawal of consent. The primary endpoint was recurrence-free survival by investigator assessment, and overall survival was a key secondary endpoint. Efficacy analyses were done in the intention-to-treat population (all randomly assigned patients). All patients who received at least one dose of study treatment were included in the safety analysis. The results presented in this report reflect the 4-year update of the ongoing study with a database lock date of Jan 30, 2020. This study is registered with ClinicalTrials.gov, NCT02388906. Findings: Between March 30 and Nov 30, 2015, 906 patients were assigned to nivolumab (n=453) or ipilimumab (n=453). Median follow-up was 51·1 months (IQR 41·6–52·7) with nivolumab and 50·9 months (36·2–52·3) with ipilimumab; 4-year recurrence-free survival was 51·7% (95% CI 46·8–56·3) in the nivolumab group and 41·2% (36·4–45·9) in the ipilimumab group (hazard ratio [HR] 0·71 [95% CI 0·60–0·86]; p=0·0003). With 211 (100 [22%] of 453 patients in the nivolumab group and 111 [25%] of 453 patients in the ipilimumab group) of 302 anticipated deaths observed (about 73% of the originally planned 88% power needed for significance), 4-year overall survival was 77·9% (95% CI 73·7–81·5) with nivolumab and 76·6% (72·2–80·3) with ipilimumab (HR 0·87 [95% CI 0·66–1·14]; p=0·31). Late-emergent grade 3–4 treatment-related adverse events were reported in three (1%) of 452 and seven (2%) of 453 patients. The most common late-emergent treatment-related grade 3 or 4 adverse events reported were diarrhoea, diabetic ketoacidosis, and pneumonitis (one patient each) in the nivolumab group, and colitis (two patients) in the ipilimumab group. Two previously reported treatment-related deaths in the ipilimumab group were attributed to study drug toxicity (marrow aplasia in one patient and colitis in one patient); no further treatment-related deaths were reported. Interpretation: At a minimum of 4 years' follow-up, nivolumab demonstrated sustained recurrence-free survival benefit versus ipilimumab in resected stage IIIB–C or IV melanoma indicating a long-term treatment benefit with nivolumab. With fewer deaths than anticipated, overall survival was similar in both groups. Nivolumab remains an efficacious adjuvant treatment for patients with resected high-risk melanoma, with a safety profile that is more tolerable than that of ipilimumab. Funding: Bristol Myers Squibb and Ono Pharmaceutical. © 2020 Elsevier Ltd

We propose a comprehensive approach to oncological disease, based on a systemic consideration of biology, health and disease. Our two previous review articles focused on tumour microenvironment and the discovery of new biomarkers; here we discuss the practical application of these principles to pathology, through the identification, evaluation and quantitative analysis of new prognostic and predictive factors (Immunoscore, TIME). We also consider the clinical use of promising, better tolerated treatments, such as immunotherapy. The integrative pathologist now has access to the latest improved oncology stratification tools designed to identify effective treatment strategies, based on the natural evolution of clinical and scientific knowledge that transcend the gene-centric theory of cancer. Copyright © 2019 Sociedad Espanola de Anatomia Patologica. Publicado por Elsevier Espana, S.L.U. All rights reserved.

We report the detection of 7 new Wolf-Rayet (WR) star locations in M81 using the Multi-Object Spectrograph of the OSIRIS instrument at Gran Telescopio Canarias. These detections are the result of a follow-up of an earlier study using the same instrumental set-up that resulted in the detection of 14 WR locations. We analyse the entire sample of 21 spectra to classify them to one of the known WR sub-types using template spectra of WR stars in the Large Magellanic Cloud (LMC), with similar metallicity to M81. Taking into consideration the dispersion in the strengths of the bumps for a given WR sub-type, we found that 19 of the 21 locations correspond to individual stars, including all the 7 new detections, of sub-types: WNL, WNE, WCE and the transitional WN/C. None of the detections correspond to WCL or WO types. The positions of these stars in the red bump vs blue bump luminosity diagram agrees well with an evolutionary path according to the Conti scenario. Based on this, we propose this diagram as a straightforward tool for spectral classification of extragalactic WR sources. The detection of individual WR stars in M81, which is at a distance of 3.6 Mpc, opens up a new environment for testing the massive star evolutionary models., Comment: 15 pages, 7 figures, 6 tables; accepted to MNRAS

© 2020, Springer Nature Switzerland AG. In this paper, we present a method of communicating affects from a remote user through the telepresence robot Haru. In this preliminary work, we transform the traditional mode of communicating text messages with emojis in the smartphone domain to the robot domain through robomojis- a hardware rendition of emojis. First we analyze human affects and expressions and synthesized these through the design of robomojis. Based on the telepresence robot Haru platform, we built a communication module that enables a remote user with a smartphone to send text and emoji messages to the robot. The robot then communicates these affectively through the rendition of robomojis. By exploiting the robot’s rich modality and through design, our preliminary results show that robomojis deliver better rendition than emojis. Although participants prefer the use of smartphones over telepresence robot due to convenience, our findings also show that they are willing to use the robomoji features in a telepresence robot such as Haru. This could enhance further the role of social robots as telepresence robots and open the possibility of integrating them to the traditional communication ecosystem.

[Introduction] Leptomeningeal dissemination due to HER2-overexpressing breast cancer is a rare and hard to treat complication with short-term dismal prognosis., [Patient concerns] A 34-year-old female previously treated because of HER2+ breast cancer is admitted to the Neurology Department in December 2016 due to sensory-motor neurological semiology., [Diagnosis] A wide set of diagnostic tests is performed and finally cytologic findings after repeated CSF confirm leptomeningeal infiltration by breast carcinoma (panCK+, GATA3+)., [Interventions] Weekly intrathecal triple therapy with methotrexate, cytarabine and hydrocortisone plus trastuzumab is carried out during 4 months., [Outcomes] Clinical and pathological response that lasts more than 24 months., [Conclusion] Leptomeningeal carcinomatosis is an oncological situation where conventional therapies have limited activity. In HER2+ advanced breast cancer patients, intrathecal therapy with anti-HER2 therapy (trastuzumab) is feasible and may reach long-term disease control, especially in cases of low-tumor burden.

Background Metastatic triple-negative breast cancer (mTNBC) has a poor prognosis and aggressive clinical course. tnAcity evaluated the efficacy and safety of first-line nab-paclitaxel plus carboplatin (nab-P/C), nab-paclitaxel plus gemcitabine (nab-P/G), and gemcitabine plus carboplatin (G/C) in patients with mTNBC. Patients and methods Patients with pathologically confirmed mTNBC and no prior chemotherapy for metastatic BC received (1 : 1 : 1) nab-P 125 mg/m2 plus C AUC 2, nab-P 125 mg/m2 plus G 1000 mg/m2, or G 1000 mg/m2 plus C AUC 2, all on days 1, 8 q3w. Phase II primary end point: investigator-assessed progression-free survival (PFS); secondary end points included overall response rate (ORR), overall survival (OS), percentage of patients initiating cycle 6 with doublet therapy, and safety. Results In total, 191 patients were enrolled (nab-P/C, n = 64; nab-P/G, n = 61; G/C, n = 66). PFS was significantly longer with nab-P/C versus nab-P/G [median, 8.3 versus 5.5 months; hazard ratio (HR), 0.59 [95% CI, 0.38–0.92]; P = 0.02] or G/C (median, 8.3 versus 6.0 months; HR, 0.58 [95% CI, 0.37–0.90]; P = 0.02). OS was numerically longer with nab-P/C versus nab-P/G (median, 16.8 versus 12.1 months; HR, 0.73 [95% CI, 0.47–1.13]; P = 0.16) or G/C (median, 16.8 versus 12.6 months; HR, 0.80 [95% CI, 0.52–1.22]; P = 0.29). ORR was 73%, 39%, and 44%, respectively. In the nab-P/C, nab-P/G, and G/C groups, 64%, 56%, and 50% of patients initiated cycle 6 with a doublet. Grade ≥3 adverse events were mainly hematologic. Conclusions First-line nab-P/C was active in mTNBC and resulted in a significantly longer PFS and improved risk/benefit profile versus nab-P/G or G/C.

Aims and objectives: \ud The aim of the 2018 EAHP Survey on Medicines Shortages was to provide a clearer picture on the issue of medicines shortages, including the impact on hospital pharmacists' time, budgets and the effect on patient care. Methods: A survey was conducted by the EAHP, collecting information from European hospital pharmacists on the shortage situation in their respective countries. The survey ran from 19 March 2018 to 11 June 2018. Keele University, UK analysed and compared the results to those of the 2014 survey. \ud \ud Results: \ud There were 1666 responses to the 2018 survey, which represented a threefold increase from the 2014 survey which received 607 responses. Ninety per cent of respondents answered 'Yes' when asked if shortages of medicines are a current problem in delivering the best care to patients, while only 7% of respondents answered 'No', and 3% 'Unsure'.Problems with shortages of antimicrobials were most commonly reported (77% of respondents reporting this as an issue in 2018 vs 57% in 2014), followed by preventative medicines (43% in 2018 vs 20% in 2014) and anaesthetics (39% in 2018 vs 27% in 2014). Fifty-nine per cent of respondents have seen care delayed as a consequence of medication shortages, with cancellations of care (31% of respondents), medication errors (25% of respondents) and suboptimal treatment for patients (25% of respondents) also being frequently reported.Sixty-three per cent of respondents reported having had to pay a higher price to procure from alternate sources most of the time or always when there was a shortage of a medicine. \ud \ud Conclusions: \ud Medicines shortages is an increasing problem across Europe and is having an adverse impact on patient care. Medicines shortages are adding to hospital pharmacists' time pressures and have an adverse budgetary impact. More timely information about impending shortages and how long they will last is seen as necessary to help manage the problem.

ilustraciones, fotografías, mapas Los resultados de la caracterización biofísica que se publican en este volumen (Rangel et al., 2019) indican que la Serranía de Manacacías presenta una alta importancia ecológica con muestras represen- tativas de ecosistemas que se encuentran con una baja representatividad en el SINAP. Adicionalmente, estos ecosistemas presentan altos valores de biodiversidad y mantienen las condiciones ideales para el mantenimiento, reproducción y cría de especies de flora y fauna, en los grupos de mamíferos, rep- tiles, aves, anfibios, mariposas y crustáceos. Varias especies registradas en el área se encuentran bajo categorías de amenaza según la Unión Internacional para la Conservación de la Naturaleza (UICN), o se mencionan en los apéndices I y II de la Convención sobre el Comercio Internacional de Especies Amenazadas de Fauna y Flora Silvestres (CITES). Para la región se obtuvieron nuevos registros de flora y fauna a nivel local y regional. (texto tomado de la fuente) GEOLOGÍA Y GEOMORFOLOGÍA DE LA SERRANÍA DE MANACACÍAS (META) ORINOQUÍA COLOMBIANA / Geology and geomorphology of the “serranía” of Manacacías (Meta, Colombian Orinoquian region) -- SUELOS DE LA SERRANÍA DE MANACACÍAS (META) ORINOQUÍA COLOMBIANA / Soils of the “serranía” of Manacacías (Meta, Colombian Orinoquian region) -- EL CLIMA DE LA REGIÓN DE LA SERRANÍA DE MANACACÍAS, (META) ORINOQUÍA COLOMBIANA / The climate of the region the “serranía” of Manacacías (Meta, Colombian Orinoquian region) -- APROXIMACIÓN BIOCLIMÁTICA DE LA SERRANÍA DE MANACACÍAS (META) ORINOQUÍA COLOMBIANA / Bioclimatic approximation of the “serranía” of Manacacías (Meta, Colombian Orinoquian region) -- LA VEGETACIÓN DE LA SERRANÍA DE MANACACÍAS (META) ORINOQUÍA COLOMBIANA / The vegetation of the “serranía” of Manacacías (Meta, Colombian Orinoquian region) -- FLORA Y VEGETACIÓN ACUÁTICA DE LA SERRANÍA DE MANACACÍAS (META) ORINOQUÍA COLOMBIANA / Aquatic vegetation of the “serranía” of Manacacías (Meta, Colombian Orinoquian region) -- PATRONES DE RIQUEZA Y DIVERSIDAD DE LAS PLANTAS CON FLORES DE LA SERRANÍA DE MANACACÍAS (META)ORINOQUÍA COLOMBIANA / Richness and diversity patterns of the flowering plants of the “serranía” of Manacacías (Meta, Colombian Orinoquian region) -- PATRONES DE USO Y AMENAZAS A LA FLORA Y LA VEGETACIÓN DE LA SERRANÍA DE MANACACÍAS (META) ORINOQUÍA COLOMBIANA / Patterns of use and threats to the flora and vegetation of the “serranía” of Manacacías (Meta, Colombian Orinoquian region) -- CRUSTÁCEOS, DECÁPODOS DE LA SERRANÍA DE MANACACÍAS, (META) ORINOQUÍA COLOMBIANA / Crustaceans, Decapods of the “serranía” of Manacacías (Meta, Colombian Orinoquian region) -- LOMBRICES DEL SUELO DE LA SERRANÍA DE MANACACÍAS (META) ORINOQUÍA COLOMBIANA / Earthworms of the soil from “serranía” of Manacacías (Meta, Colombian Orinoquian region) -- MaRiposas diuRnas (papilionidae-HespeRioidae) de dos sectoRes de la SERRANÍA DE MANACACÍAS (meta) oRinoQuía colombiana / Butterflies (Papilionidae-Hesperioidae) of two sectors of the region the “serranía” of Manacacías (Meta, Colombian Orinoquian region) -- DIVERSIDAD DE ANFIBIOS Y REPTILES EN LA REGIÓN DE LA SERRANÍA DE MANACACÍAS, MUNICIPIO DE SAN MARTÍN, (META) ORINOQUÍA COLOMBIANA / Diversity of amphibians and reptiles of the “serranía” of Manacacías, San Martín (Meta, Colombian Orinoquian region) -- RIQUEZA Y DIVERSIDAD DE LA COMUNIDAD DE AVES EN ÁREAS DE LA SERRANÍA DE MANACACÍAS (META) ORINOQUÍA COLOMBIANA / Richness and diversity pattern of the bird community in areas of the “serranía” of Manacacías (Meta, Colombian Orinoquian region) -- MAMÍFEROS DE LA REGIÓN DE LA SERRANÍA DE MANACACÍAS (META) ORINOQUÍA COLOMBIANA / Mammals of the “serranía” of Manacacías (Meta, Colombian Orinoquian region) Diego Casallas-Pabón, Nathaly Calvo-Roa -- PECES DE LA SERRANÍA DE MANACACÍAS (META) ORINOQUÍA COLOMBIANA / Fishes of the “serranía” of Manacacías (Meta, Colombian Orinoquian region) -- ECOSISTEMAS DE LA SERRANÍA DE MANACACÍAS (META) ORINOQUÍA COLOMBIANA / Ecosystems of the “serranía” of Manacacías (Meta, Colombian orinoquian region) -- ASPECTOS CARTOGRÁFICOS DE LA VEGETACIÓN, LOS ECOSISTEMAS Y LAS AMENAZAS EN LA SERRANÍA DE MANACACÍAS (META) ORINOQUÍA COLOMBIANA / Cartographic aspects of vegetation, ecosystems and threats in the “serranía” of Manacacías (Meta, Colombian Orinoquian region) -- APROXIMACIÓN SOCIOECONÓMICA SOBRE LA SERRANÍA DE MANACACÍAS (META) ORINOQUÍA COLOMBIANA / Socioeconomic approach on the “serranía” of Manacacías (Meta, Colombian Orinoquian region) -- LA BIODIVERSIDAD Y LOS SERVICIOS ECOSISTÉMICOS EN LA SERRANÍA DE MANACACÍAS (META) ORINOQUÍA COLOMBIANA / Biodiversity and ecosystem services in the area of the “serranía” of Manacacías (Meta, Colombian Orinoquian region) primera edición

ilustraciones, fotografías, mapas Esta obra presenta una antología científica de información física y natural de este sector de los Llanos Colombianos, en la cual el lector encontrará información en detalle de la temática enumerada. La segunda parte de la obra, es una excelente presentación fotográfica de las especies, sus hábitats, paisajes, lo que valoriza aún más la calidad y la eficacia del texto. El libro ofrece también una base de referencia para estudios en el área de la biodiversidad de los humedales y sabanas de Arauca, de sus principales componentes y de sus posibles desarrollos y aplicaciones. Finalmente, se espera que la presente contribución aumenté los niveles de conocimientos de la región en la población, haciendo de las ciencias básicas un herramienta para el análisis de la realidad ambiental actual. De esta manera, se contribuirá en la conservación de este importante sector de los llanos colombianos, región cuyos ecosistemas ha sido drásticamente transformados en los últimos 60 años. (texto tomado de la fuente) UNIDADES GEOMORFÓLOGICAS AL NORESTE DEL RÍO CRAVO NORTE, COLOMBIA / Geomorphological units northeast of the Cravo Norte river, Colombia --GEOLOGÍA Y GEOMORFOLOGÍA DEL TERRITORIO SABANAS Y HUMEDALES DE ARAUCA, COLOMBIA /Geology and geomorphology of the savannas and wetlands territory of Arauca, Colombia -- SUELOS DEL TERRITORIO SABANAS Y HUMEDALES DE ARAUCA, COLOMBIA / Soils of the savannas and wetlands territory of Arauca, Colombia -- BIOCLIMA DEL TERRITORIO SABANAS Y HUMEDALES DE ARAUCA, COLOMBIA / Bioclimate of the savannas and wetlands territory of Arauca, Colombia -- VEGETACIÓN ACUÁTICA DEL TERRITORIO SABANAS Y HUMEDALES DE ARAUCA, COLOMBIA / Aquatic vegetation of the savannas and wetlands territory of Arauca, Colombia -- USOS Y AMENAZAS PARA LA CONSERVACIÓN DE LAS PLANTAS CON FLORES DEL TERRITORIO SABANAS Y HUMEDALES DE ARAUCA, COLOMBIA / Uses and threats for the conservation of flowering plants of the savannas and wetlands territory of Arauca, Colombia -- GEOLOGÍA DEL NORESTE DEL RÍO CRAVO NORTE (MARGEN IZQUIERDA), COLOMBIA / Northeast geology of the Cravo Norte river (Left margin), Colombia --HIDROLOGÍA DE LAS CUENCAS DEL TERRITORIO SABANAS Y HUMEDALES DE ARAUCA, COLOMBIA / Hydrology of the basins of the savannas and wetlands territory of Arauca, Colombia -- CARACTERIZACIÓN CLIMÁTICA DEL TERRITORIO SABANAS Y HUMEDALES DE ARAUCA, COLOMBIA / Climate characterization of the savannas and wetlands territory of Arauca, Colombia -- LA VEGETACIÓN DEL TERRITORIO SABANAS Y HUMEDALES DE ARAUCA (COLOMBIA) /The vegetation of the savannas and wetlands territory of Arauca (Colombia) -- RIQUEZA Y DIVERSIDAD DE LAS PLANTAS CON FLORES EN EL TERRITORIO SABANAS Y HUMEDALES DE ARAUCA, COLOMBIA / Richness and diversity of flowering plants of the savannas and wetlands territory of Arauca, Colombia -- CRUSTÁCEOS DECÁPODOS DEL TERRITORIO SABANAS Y HUMEDALES DE ARAUCA, COLOMBIA / Decapods Crustaceans of the savannas and wetlands territory of Arauca, Colombia -- LOMBRICES DEL SUELO DEL TERRITORIO SABANAS Y HUMEDALES DE ARAUCA,COLOMBIA / Earthworms of the savannas and wetlands territory of Arauca, Colombia -- MARIPOSAS DIURNAS (PAPILIONIDAE-HESPERIOIDAE) EN TERRITORIOS AL NORESTE DEL RÍO CRAVO NORTE, ARAUCA (COLOMBIA) /Butterfly (Papilionidae-Hesperioidae) in territories northeast of the Cravo Norte river, Arauca (Colombia) / RIQUEZA Y DIVERSIDAD DE LAS AVES DEL TERRITORIO SABANAS Y HUMEDALES DE ARAUCA, COLOMBIA / Bird community richness and composition of the savannas and wetlands territory of Arauca, Colombia -- CARACTERIZACIÓN DE LA COMUNIDAD ÍCTICA DEL TERRITORIO SABANAS Y HUMEDALES DE ARAUCA, COLOMBIA /Characterization of the fish community of the savannas and wetlands territory of Arauca, Colombia -- SERVICIOS ECOSISTÉMICOS DEL TERRITORIO SABANAS Y HUMEDALES DE ARAUCA, COLOMBIA / Ecosystem services of the savannas and wetlands territory of Arauca, Colombia -- APROXIMACIONES CARTOGRÁFICAS A LA VEGETACIÓN, LOS ECOSISTEMAS Y LAS AMENAZAS EN EL TERRITORIO SABANAS Y HUMEDALES DE ARAUCA, COLOMBIA / Cartographic approaches to vegetation, ecosystems and threats of the savannas and wetlands territory of Arauca, Colombia -- ÍNDICE DE FLORA Y FAUNA -- ANEXO FOTOGRÁFICO -- ANEXO CARTOGRÁFICO primera edición

Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) subtype. The histological transformation (HT) of FL is an event considered frequent in the natural history of this tumor. We studied the transformation rates, predictive factors, and treatment characteristics that may impact in the survival of patients with FL and HT. A total of 1074 patients diagnosed with FL were prospectively enrolled from 1990 to 2016 in a Spanish registry. Sixty-four HTs were recorded based on clinical criteria (55%) or histological confirmation (45%). The cumulative incidence rate of transformation at 5 years is 7.3%. The 5-year overall survival (OS) without HT was 85% (95% confidence interval [CI], 70%-90%) vs 66% (95% CI, 51%-76%; P = 0.0012) with HT. Factors associated with HT were elevated lactate dehydrogenase (LDH) (odds ratio [OR] 1.83), intermediate-high Follicular lymphoma international prognostic index (FLIPI) (OR 2.16-OR 3.21), B symptoms (OR 2.46), or Eastern Cooperative Oncology Group (ECOG) 1 (OR 2.35). Treatment options related to HT were "watch and wait" or no rituximab or anthracyclines initially. A 5-year OS for patients treated with chemotherapy before HT was 55% (95% CI, 38%-69%) versus 81% (95% CI, 53%-93%; P = 0.009) for those who had not received it. The HT rate has decreased after the introduction of rituximab, as has been previously described. The timing of this treatment had an impact on the survival of these patients.

Although the metastasic breast cancer is still an incurable disease, recent advances have increased significantly the time to progression and the overall survival. However, too much information has been produced in the last 2 years, so a well-based guideline is a valuable document in treatment decision making. The SEOM guidelines are intended to make evidence-based recommendations on how to manage patients with advanced and recurrent breast cancer to achieve the best patient outcomes based on a rational use of the currently available therapies. To assign a level of certainty and a grade of recommendation the United States Preventive Services Task Force guidelines methodology was selected as reference.

Objective: To determine the proportion of people infected by HIV or AIDS under follow-up in the VACH Cohort in 2012 who were lost to follow-up from 2013 to 2014, and to establish the sociodemographic features relating to this loss. Methods: We considered subjects with less than one recorded consultation per year studied to be lost to follow-up. We built logistic regression models to calculate the odds ratios (OR) and their 95% confidence intervals (95% CI), of the variables relating to loss to follow-up. Results: The overall percentage of losses to follow-up was 15.5% (95% CI 14.9-16-1). The variables associated with loss to follow up were: not receiving antiretroviral treatment (ART) (OR: 1.948, 95% CI: 1.651-2.298), being an immigrant (OR: 1.746; 95%Cl: 1.494-2.040), intravenous drug consumption being the mechanism for HIV transmission (OR: 1.498, 95% CI: 1.312-1.711), being unemployed (OR: 1.331; 95% CI: 1.179-1.503), being without a partner (OR: 1.948, 95% CI: 1.651-1.298), belonging to a low socioeconomic class (OR: 1.279; 95% Cl: 1.143-1.431), and being attended in a hospital with fewer than 1000 patients under follow-up (OR: 1.257, 95% CI: 1.121-1.457), as well as being under age and having spent less time under follow-up in the Cohort. Conclusions: 15.5% of the patients were lost to follow-up over a period of 2 years in the VACH Cohort. This was associated with a series of sociodemographic and epidemiological variables that it might be useful to identify to design initiatives targeting the populations most likely to abandon the circuits of care, and guide strategies towards achieving Objective 90-90-90. (C) 2018 Published by Elsevier Espana, S.L.U.

El presente artículo pretende abordar la historia de la restauración arquitectónica cordobesa, con especial atención al concepto de “falso histórico”. La “Unidad de estilo” marcará el siglo XIX hasta que la nueva centuria traiga consigo el triunfo de la tendencia conservadora, matizada en lo sucesivo hasta llegar a un equilibrio estético-histórico. El panorama español sigue esta evolución hasta que la Dictadura Franquista impone de nuevo los valores historicistas, postura que cambiará en los albores de la democracia. Córdoba es testigo de esta evolución y sus restauraciones reflejan las distintas caras de las tendencias patrimoniales europeas, con actuaciones que deberían ser revisadas. This article aims to address the history of Cordoba’s architectural restoration, with special attention to the concept of “false history”. The “Unity of style” will mark the nineteenth century until the new century brings with it the triumph of the conservative tendency, nuanced in the future until reaching an aesthetic-historical balance. The Spanish panorama follows this evolution until the Franco dictatorship again imposes historicist values, a position that will change at the dawn of democracy. Cordoba is witness this evolution and its restorations reflect the different faces of European heritage trends, with actions that should be reviewed.

Internet Gaming Disorder is an increasingly prevalent disorder, which can have severe consequences in affected young people and in their families. There is an urgent need to improve existing treatment programs; these are currently hampered by the lack of research in this area. It is necessary to more carefully define the symptomatic, psychosocial and personality characterization of these patients and the interaction between treatment and relevant variables. The objectives of this study were three: (1) to analyze the symptomatic and personality profiles of young patients with Internet Gaming Disorder in comparison with healthy controls; (2) to analyze the effectiveness of a cognitive behavioral treatment on reducing symptomatology; and (3) to compare the results of that treatment with or without the addition of a psychoeducational group offered to the parents. The final sample consisted of 30 patients consecutively admitted to a specialized mental health unit in Spain, and 30 healthy controls. The experimental group received individual cognitive-behavioral therapy. The experimental group was divided into two subgroups (N = 15), depending on the addition or not of a psychoeducational group for their parents (consecutively admitted). Scores on the Millon Adolescent Personality Inventory (MACI), the Symptom Checklist-Revised (SCL-90-R), the State-Trait Anxiety Index (STAI), and other clinical and psychopathological measures were recorded. The patients were re-assessed post treatment (except for the MACI questionnaire). Compared with healthy controls, patients did not differ in symptomatology at baseline, but scored significantly higher in the personality scales: Introversive and Inhibited, and in the expressed concerns scales: Identity Confusion, Self-Devaluation, and Peer Insecurity and scored significantly lower in the Histrionic and Egotistic scale. In the experimental group, pre-post changes differed statistically on SCL-90-R scales Hostility, Psychoticism, and Global Severity Index and on the diagnostic criteria for Internet Gaming Disorder, regardless of the addition of a psychoeducational group for parents. Pre-post changes did not differ between experimental subgroups. However, the subgroup without psychoeducation for parents presented statistically higher drop-out rates during treatment. The results of this study are based on a sample of patients seeking treatment related to problems with online gaming, therefore, they may be of value for similar patients.

According to data from recent studies from Europe, a large percentage of patients have restricted access to innovative medicines for metastatic melanoma. Melanoma World Society and European Association of Dermato-oncology conducted a Web-based survey on access to first-line recommended treatments for metastatic melanoma by current guidelines (National Comprehensive Center Network, European Society for Medical Oncology [ESMO] and European Organization for Research and Treatment of Cancer/European Association of Dermato-oncology/European dermatology Forum) among melanoma experts from 27 European countries, USA, China, Australia, Argentina, Brazil, Chile and Mexico from September 1st, 2017 to July 1st, 2018. Data on licencing and reimbursement of medicines and the number of patient treated were correlated with the data on health expenditure per capita (HEPC), Mackenbach score of health policy performance, health technology assessment (HTA), ASCO and ESMO Magnitude of clinical benefit scale (ESMO MCBS) scores of clinical benefit and market price of medicines. Regression analysis for evaluation of correlation between the parameters was carried out using SPSS software. The estimated number of patients without access in surveyed countries was 13768. The recommended BRAFi + MEKi combination and anti-PD1 immunotherapy were fully reimbursed/covered in 19 of 34 (55.8%) and 17 of 34 (50%) countries, and combination anti-CTLA4+anti-PD1 in was fully covered in 6 of 34 (17.6%) countries. Median delay in reimbursement was 991 days, and it was in significant correlation with ESMO MCBS (p = 0.02), median market price (p = 0.001), HEPC and Mackenbach scores (p < 0.01). Price negotiations or managed entry agreements (MEAs) with national authorities were necessary for reimbursement. In conclusion, great discrepancy exists in metastatic melanoma treatment globally. Access to innovative medicines is in correlation with economic parameters as well as with healthcare system performance parameters. Patient-oriented drug development, market access and reimbursement pathways must be urgently found. © 2018 Elsevier Ltd

Resumen de los autores Grado en Ingeniería en Diseño Industrial y Desarrollo de Productos (Universidad Politécnica de Valencia) Por tercer año consecutivo se ha trabajado con la metodología de la clase inversa en la docencia de la asignatura de 4º curso “Diseño de Detalle en Elementos de Mobiliario Urbano” del Grado de Ingeniería en Diseño Industrial y Desarrollo de Productos. En este curso se ha dejado abierto el objeto del proyecto y únicamente se ha concretado el escenario o contexto del mismo. Este entorno ha sido el Jardín del Turia de Valencia, un lugar caracterizado por la variedad de actividades y la concentración de usuarios que se dan cita diariamente en este enclave. El núcleo de la investigación previa se ha fundamentado en el trabajo de campo del grupo en distintas áreas de este entorno y el desarrollo y puesta en común de una encuesta que se ha pasado personalmente “in situ” y a través de Google. A continuación, se ha realizado una aproximación individual desde el “design thinking” al concepto de la “smartcity” y su posible aplicación en este contexto para resolver o mejorar aspectos concretos. A partir del análisis de los datos obtenidos y de los intereses propios, el estudiante ha realizado el planteamiento de su proyecto enfrentándose a cuestiones diversas y obteniendo interesantes resultados. ESP

The addictive use of video games is recognized as a problem with clinical relevance and is included in international diagnostic manuals and classifications of diseases. The association between "Internet addiction" and mental health has been well documented across a range of investigations. However, a major drawback of these studies is that no controls have been placed on the type of Internet use investigated. The aim of this study is to review systematically the current literature in order to explore the association between Internet Gaming Disorder (IGD) and psychopathology. An electronic literature search was conducted using PubMed, PsychINFO, ScienceDirect, Web of Science and Google Scholar (r.n. CRD42018082398). The effect sizes for the observed correlations were identified or computed. Twenty-four articles met the eligibility criteria. The studies included comprised 21 cross-sectional and three prospective designs. Most of the research was conducted in Europe. The significant correlations reported comprised: 92% between IGD and anxiety, 89% with depression, 85% with symptoms of attention deficit hyperactivity disorder (ADHD), and 75% with social phobia/anxiety and obsessive-compulsive symptoms. Most of the studies reported higher rates of IGD in males. The lack of longitudinal studies and the contradictory results obtained prevent detection of the directionality of the associations and, furthermore, show the complex relationship between both phenomena.

Background Despite the efficacy of innovative treatments for metastatic melanoma, their high costs has led to disparities in cancer care among different European countries. We analysed the availability of these innovative therapies in Europe and estimated the number of patients without access to first-line recommended treatment per current guidelines of professional entities such as the European Society for Medical Oncology (ESMO), the European Organisation for Research and Treatment of Cancer (EORTC), the European Association of Dermato-Oncology (EADO), and European Dermatology Forum (EDF). Materials and methods Web-based online survey was conducted in 30 European countries with questions about the treatment schedules from 1st May 2015 to 1st May 2016: number of metastatic melanoma patients, registration and reimbursement of innovative medicines (updated data, as of 1st October 2016), percentage of patients treated and availability of clinical studies and compassionate-use programmes. Results The recommended BRAF inhibitor (BRAFi) + MEK inhibitor (MEKi) combination was both registered and fully reimbursed in 9/30 (30%) countries, and in 13/30 (43%) (all from Eastern Europe) not reimbursed. First-line immunotherapy with anti-PD1 antibodies was registered and fully reimbursed in 14/30 (47%) countries, while in 13/30 (43%) (all from Eastern Europe) not reimbursed. It was estimated that in Europe 19,600 patients with metastatic melanoma are treated, and 5238 (27%) do not have access to recommended first-line therapy. Significant correlation was found between human development index (HDI, UNDP report 2015), (r = 0.662; p < 0.001), health expenditure per capita (r = 0.695; p < 0.001) and the Mackenbach score of health policy performance (r = 0.765; p < 0.001) with the percentage of patients treated with innovative medicines and a number of reimbursed medicines. Conclusions Great discrepancy exists in metastatic melanoma treatment across Europe. It is crucial to increase the awareness of national and European policymakers, oncological societies, melanoma patients' associations and pharma industry. © 2017 Elsevier Ltd

Contiene 1 tabla, 7 figuras, 1. The Mediterranean seagrass Posidonia oceanica maintains a biodiverse ecosystem and it is a worldwide important carbon sink. It grows for millennia, accumulating organic-rich soils (mats) beneath the meadows. This marine habitat is protected by the European Union; however, it is declining rapidly due to coastal development. Understanding its response to disturbances could inform habitat restoration, but many environmental impacts predate monitoring programs (, L.L.-M. is funded by The Leverhulme Trust towards an Early Career Fellowship (ECF- 2013-530, Posidonia as environmental archive: long-term ecology and conservation views). The study was also supported by the Spanish Ministry of Economy and Competitiveness, SUMILEN project (CTM2013-47728-R, Advances in sampling techniques, biogeochemical characterization, and quantification of the millenary deposits of seagrasses), and the Spanish Autonomous Organism of National Parks, PALEOPARK project (ref. 1104, Millenary changes in the ecosystems of insular National Parks: perturbations, resilience, and trends after the seagrass archives).

Addiction to technologies has been a widely debated scientific and clinically, being a condition for further study as potential psychiatric disorder. Some Spanish scales measure Internet addiction, but no one has been validated clinically. The aims were to describe a clinical sample of patients in treatment for a technology addiction, and to validate clinically the “Problematic Internet Entertainment Use Scale for Adults” (PIEUSAd). Little-scale clinical adult sample (N=31; 71 % men, and an age mean of 33.31) was selected, collecting socio-demographic and clinical data, technological usages, and the PIEUSAd and Compulsive Internet Use Scale in a survey. The setting was a public health center in Barcelona (Spain). The patients in treatment for a technological addiction as primary diagnosis were usually young males, which suffer from a genuine e-addiction (above all, internet addiction, gaming and cybersex); only the middle seems to have a dual pathology (usually another addiction). They are usually referred by other clinician and the majority don’t have previous psychiatric care. The PIEUSAd showed large variability in item scored, and high factor and construct validity, and excellent reliability (a=0.98). In conclusion, the heterogeneity in the characteristics of patients is evidenced. Moreover, the PIEUSAd has been clinical validated to do a better screen in technological addictions, where “loss of control” and “evasion” seems to be the prevalent addictive symptoms in these types of patients.\ud Spanish abstract: La adicción a las tecnologías ha sido debatida ampliamente tanto científica como clínicamente, siendo una condición a estudiar como potencial trastorno psiquiátrico. Algunas escalas españolas miden la adicción al internet, pero ninguna ha sido validada clínicamente. Los objetivos son describir la muestra clínica de pacientes en tratamiento por una adicción tecnológica, así como validar clínicamente la “Problematic Internet Entertainment Use Scale for Adults” (PIEUSAd). Una muestra clínica a pequeña escala (N=31; 71 % hombres, con una edad media de 33,31) fue seleccionada, se recogieron datos socio-demográficos, clínicos y de uso de tecnologías, así como la PIEUSAd y la “Compulsive Internet Use Scale” a través de una encuesta. El contexto fue un centro de salud pública de Barcelona (España). Los pacientes en tratamiento por una adicción tecnológica como primer diagnóstico eran usualmente hombres jóvenes que sufrían de una e-adicción genuina (sobre todo, adicción a internet, videojuegos o cibersexo); solo la mitad parecía sufrir una patología dual (normalmente otra adicción). Eran normalmente derivados por otros profesionales de la salud y la mayor parte no habían sido tratados psiquiá- tricamente con anterioridad. La PIEUSAd mostró gran variabilidad en sus puntuaciones, alta validez factorial y de constructo, y excelente fiabilidad (a=0,98). En conclusión, la heterogeneidad de las características de los pacientes fue evidenciada. Además, la PIEUSAd ha sido validada clínicamente para poder hacer un mejor cribado en las adicciones tecnológicas, donde la “pérdida de control” y la “evasión” parecen ser los síntomas prevalentes en estos tipos de pacientes.

En este artículo se presenta un análisis clínico de las diferencias psicopatológicas entre dos grupos de pacientes, mujeres, con problemas de Dependencia Emocional con y sin consumo de sustancias ilegales comórbido. Las pacientes fueron evaluadas mediante los cuestionarios TDS100, SCL-90-R, BIS-11 y una entrevista semiestructurada adaptada de la entrevista SCID-I. Los grupos se formaron en función de si existía consumo de drogas o no en el momento de la evaluación. \ud A través de los resultados hallados, se puede concluir que el grupo de mujeres con un consumo ocasional de drogas presenta una mayor gravedad en la escala de Acomodación medida a través del TDS-100, así como puntuaciones más altas en psicopatología comórbida (Sensibilidad Interpersonal, Ansiedad, Hostilidad, Ideación paranoide, Psicoticismo y GSI) medida por el SCL-90-R. Finalmente, el grupo con uso de drogas obtuvo puntuaciones significativamente más altas en la subescala Impulsividad Motora medida por el BIS-11.\ud English abstract: In this article we present a clinical analysis of the psychopathological differences between women patients with Affective Dependence problems with and without comorbid substance use. The patients were assessed trough the TDS-100, SCL-90-R, BIS-11 questionnaires and a semi-structured interview adapted from the SCID-I interview. The groups were created based on the substance use at the moment of the assessment.\ud The results reveal that the group of women with occasional use of drugs shows higher severity in the Accommodation scale measured trough the TDS-100 and in the comorbid psychopathology measured by the SCL-90R (Interpersonal Sensitivity, Anxiety, Hostility, Paranoid ideation, Psychoticism y GSI). Finally, the group with drug use obtained significantly higher scores in the Motor Impulsiveness subscale measured by the BIS-11.

A. Gil de Paz... et al. "MEGARA, the new intermediate-resolution optical IFU and MOS for GTC: getting ready for the telescope". Ground-based and Airborne Instrumentation for Astronomy VI, Proc.SPIE 9908 ( (4 August 2016); doi: 10.1117/12.2231988. Copyright 2016 Society of Photo‑Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited., Proceedings of the VI Ground-based and Airborne Instrumentation for Astronomy Conference (Edinburgh, United Kingdom), MEGARA (Multi-Espectrógrafo en GTC de Alta Resolución para Astronomía) is an optical Integral-Field Unit (IFU) and Multi-Object Spectrograph (MOS) designed for the GTC 10.4m telescope in La Palma that is being built by a Consortium led by UCM (Spain) that also includes INAOE (Mexico), IAA-CSIC (Spain), and UPM (Spain). The instrument is currently finishing AIV and will be sent to GTC on November 2016 for its on-sky commissioning on April 2017. The MEGARA IFU fiber bundle (LCB) covers 12.5x11.3 arcsec2 with a spaxel size of 0.62 arcsec while the MEGARA MOS mode allows observing up to 92 objects in a region of 3.5x3.5 arcmin 2 around the IFU. The IFU and MOS modes of MEGARA will provide identical intermediate-to-high spectral resolutions (RFWHM∼6,000, 12,000 and 18,700, respectively for the low-, mid- and high-resolution Volume Phase Holographic gratings) in the range 3700-9800 ÄA. An x-y mechanism placed at the pseudo-slit position allows (1) exchanging between the two observing modes and (2) focusing the spectrograph for each VPH setup. The spectrograph is a collimator-camera system that has a total of 11 VPHs simultaneously available (out of the 18 VPHs designed and being built) that are placed in the pupil by means of a wheel and an insertion mechanism. The custom-made cryostat hosts a 4kx4k 15-μm CCD. The unique characteristics of MEGARA in terms of throughput and versatility and the unsurpassed collecting are of GTC make of this instrument the most efficient tool to date to analyze astrophysical objects at intermediate spectral resolutions. In these proceedings we present a summary of the instrument characteristics and the results from the AIV phase. All subsystems have been successfully integrated and the system-level AIV phase is progressing as expected

Adjuvant interferon-alpha 2b (IFN-alpha 2b) has been studied extensively in clinical trials, but there have been few studies of real-world use. The aim of this study is to describe the IFN-alpha 2b real-world patterns in patients with high-risk melanoma in Spain. This was a retrospective and multicentre chart review study of an unselected cohort of patients with melanoma at high risk for relapse (stage IIB/IIC/III) treated with IFN-alpha 2b. Patterns were assessed in terms of dose and compliance to planned treatment. A survival analysis was carried out for the full population and according to Kirkwood scheme compliance and the presence of ulceration. Of 327 patients treated with IFN-alpha 2b, 318 received a high-dose regimen following the standard Kirkwood scheme; thus, patterns are described for this regimen. A total of 121 (38%) and 88 (28%) patients had at least one dose reduction during the induction and maintenance phases, respectively. Dose delay was required in fewer than 10% of patients. A total of 78, 40 and 38% of the patients completed the induction phase, maintenance phase and completed treatment, respectively. The median progression-free and overall survival for the full population were 3.2 and 10.5 years, respectively. There were no differences in progression-free survival and overall survival according to Kirkwood scheme compliance and the presence of ulceration. The most frequent adverse events were neutropenia (31%) and fatigue (30%). High-dose IFN alpha 2b is the most frequently used regimen in Spain as an adjuvant systemic treatment for high-risk melanoma. Despite poor compliance, in this retrospective study, IFN alpha 2b treatment provided a benefit consistent with that described previously. (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

The crystalline fraction of enamel, dentin and metapodial bone of modern and fossil mammals were studied by X-ray diffraction analysis. The powdered samples were collected from several equids, giraffids, rhinocerotids and proboscideans of Spanish Neogene deposits. Changes in the crystallinity index (CI) of apatite are particularly useful to estimate later diagenetic changes in the fossil material. The enamel displays larger CI than dentine and metapodial bone since they have a more dense structure; furthermore there is not a clear relationship between the CI enlargement and the geological age of samples. In addition, the fluorine content increases during the fossilization process and accordingly the parameter CI increases in fossil samples. The carbonate enrichment is not linked to the age of the deposits; however this carbonate increase in enamel, dentine and metapodial bone reduces the CI parameter. The host sediments play an essential role in the crystallinity changes observed in fossil bones; e.g., in the silica sands case, samples display a high CI while in the claystone and chalks case, they display a lower crystallinity index.Se ha determinado el índice de cristalinidad (IC) mediante difracción de rayos X de muestras actuales y fósiles pertenecientes a esmalte, dentina y hueso de metápodo de équidos, jiráfidos, rinocerótidos y proboscídeos de diferentes yacimientos neógenos españoles. Con estos valores de la cristalinidad del apatito se estima semicuantitativamente la evolución de los cambios diagenéticos ocurridos en el material óseo fósil. Se ha observado que el esmalte presenta un IC mayor que la dentina y hueso de metápodo, debido a su estructura más compacta. Sin embargo, no hay una correlación clara entre el incremento de la cristalinidad y la edad de las muestras. Además, el contenido de flúor aumenta durante los procesos de fosilización y como consecuencia aumenta el IC en las muestras fósiles. Por otro lado, el enriquecimiento diagenético de carbonato no está relacionado con la edad de los yacimientos, pero al aumentar su contenido en el esmalte, dentina y hueso de metápodo, disminuye en ellos su IC. Los sedimentos adyacentes juegan un papel clave en los cambios de cristalinidad de los huesos fósiles, como es el caso de los yacimientos con arenas, donde las muestras tienen un IC alto, por el contrario los yacimientos de margas y arcillas tienen un IC más bajo.

Diversos autores defienden la Dependencia Emocional como una categoría diagnóstica propia. El perfil psicopatológico de las personas afectadas por este trastorno ha sido expuesto a nivel teórico o basado en observaciones clínicas. Con este estudio se pretende determinar el perfil psicopatológico de una muestra de pacientes que presentaban problemas de Dependencia Emocional, desadaptativa, así como estudiar la relación entre autoestima y síntomas psicopatológicos. Se analiza el perfil sintomático a través de los resultados del Symptom CheckList-90 items-Revised (SCL-90-R) y el nivel de autoestima medido a través del Rosenberg Self-Esteem Scale (RSES) de una muestra de 33 pacientes de género femenino admitidos consecutivamente, que consultaron por problemas de dependencia emocional. Las pacientes presentaban elevada puntuación en las escalas obsesión-compulsión, sensibilidad interpersonal, depresión, ansiedad, hostilidad, ideación paranoide, psicoticismo (medidas a través del SCL-90-R) comparados con baremos normativos de población psiquiátrica española y una autoestima baja (medida a través del RSES). En la muestra la autoestima correlaciona de manera negativa con somatización, obsesión-compulsión, depresión y hostilidad. Se discuten las características y perfiles de esta muestra clínica.\ud English abstract: Several authors defend that Affective Dependence is a diagnostic category. The psychopathological profile of these patients has been explained from a theoretical point of view or based on clinical observations. In that study we want to determinate the pathological profile of a sample of patients with problems of affective dependence, and to study the relationship between their self-esteem and their psychopathological symptoms. We analyzed the symptomatic profile of a sample of 33 female consecutive patients consulting for affective dependence, measured trough the Symptom CheckList-90 items-Revised (SCL-90-R) and the Rosenberg Self-Esteem Scale (RSES). Patients present high obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, paranoid ideation, psychoticism (measured by the SCL- 90-R) compared with compared with normative scores of Spanish psychiatric population, and low self-esteem (measured by the RSES). In these subjects the self- esteem showed negative correlation with somatization, obsessive-compulsive, depression and hostility. These characteristics and profiles are discussed.

The efficiency of combustion in furnaces is the measure of heat released in the flame absorbed by the fluid to be heated and is considered one of the most important variables when conducting studies on processes that occur in continuous process industries. The furnace efficiency is calculated using various mathematical models proposed in the literature; these models vary in complexity depending on the analyzed variables. The models I and II are based on the amount of energy absorbed by the furnace using the heating value, the model III contains variables such as air excess, stack gas temperature and adiabatic flame temperature, meanwhile the model IV contains heating losses in furnace's wall (2%), the stack gas temperature and excess air. In this paper was used computer simulation to evaluate fuel gas mixtures with Lower Heating Values (LHV) between 800 to 2500 Btu/ft³, and they were compared with natural gas and data process; the results show that the combustion characteristics might change by varying the fuel composition. It was also found decreased combustion efficiency due to high hydrogen concentration; on the other hand the adiabatic flame temperature was increased in function of gas composition. Model IV presented in this research allowed evaluating combustion process efficiency using only two variables: stack gas temperature and the excess air. La eficiencia de combustión en hornos es la medida del calor liberado en la llama que es absorbido por el fluido a calentar y es considerada una de las variables más importantes en la realización de estudios de los procesos que ocurren en una planta de proceso continuo. La eficiencia de un horno es calculada usando diferentes modelos matemáticos propuestos en la literatura, los cuales varían en su complejidad dependiendo de las variables analizadas. Los modelos I y II se basan en la cantidad de calor que es absorbida por el equipo fundamentados en el poder calorífico, el modelo III incluye variables como el exceso de aire, temperatura de chimenea y la temperatura adiabática de llama, mientras el modelo IV incluye pérdidas con las paredes del horno del 2%, la temperatura de chimenea y el exceso de aire. Mediante simulación computacional fueron simuladas mezclas de gas combustible con poder calorífico inferior (LHV por sus siglas en inglés) entre 800-2500 BTU/pie³, y se compararon con el gas natural y con datos de proceso; encontrando que las características de la combustión cambian debido a la variación en la composición del combustible. Se presentó baja eficiencia debido a la alta concentración de hidrógeno y un aumento en la temperatura adiabática de llama en función de la composición del gas. Finalmente el modelo IV permitió evaluar la eficiencia del proceso de combustión de forma efectiva, pues solamente utiliza la temperatura de chimenea y el exceso de aire.