Search

We here present the results of an analysis of the optical spectroscopy of 42 globular cluster (GC) candidates in the nearby spiral galaxy M81 (3.61~Mpc). The spectra were obtained using the long-slit and MOS modes of the OSIRIS instrument at the 10.4~m Gran Telescopio Canarias (GTC) at a spectral resolution of $\sim$1000. We used the classical H$\beta$ vs [MgFe]$'$ index diagram to separate genuine old GCs from clusters younger than 3 Gyr. Of the 30 spectra with continuum signal-to-noise ratio $>10$, we confirm 17 objects to be classical GCs (age $>10$~Gyr, $-1.4<$[Fe/H]$<-$0.4), with the remaining 13 being intermediate-age clusters (1-7.5~Gyr). We combined age and metallicity data of other nearby spiral galaxies ($\lesssim18$~Mpc) obtained using similar methodology like the one we have used here to understand the origin of GCs in spiral galaxies in the cosmological context. We find that the metal-poor ([Fe/H]<$-$1) GCs continued to form up to 6~Gyr after the first GCs were formed, with all younger systems (age $<8$~Gyr) being metal-rich., Comment: 16 pages, 13 figures, 8 tables; Accepted for publication in MNRAS

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 withcontrollable 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 paper 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., Comment: This work has duplication, and in its case the article uploaded by my colleague David Alejo (arXiv:2204.01828) should be considered. In this way we only want to publish the article arXiv:2204.01828 for later updating

Triple-negative breast cancer (TNBC) is particularly challenging due to the weak or absent response to therapeutics and its poor prognosis. The effectiveness of neoadjuvant chemotherapy (NAC) response is strongly influenced by changes in elements of the tumor microenvironment (TME). This work aimed to characterize the residual TME composition in 96 TNBC patients using immunohistochemistry and in situ hybridization techniques and evaluate its prognostic implications for partial responders vs. non-responders. Compared with non-responders, partial responders containing higher levels of CD83+ mature dendritic cells, FOXP3+ regulatory T cells, and IL-15 expression but lower CD138+ cell concentration exhibited better OS and RFS. However, along with tumor diameter and positive nodal status at diagnosis, matrix metalloproteinase-9 (MMP-9) expression in the residual TME was identified as an independent factor associated with the impaired response to NAC. This study yields new insights into the key components of the residual tumor bed, such as MMP-9, which is strictly associated with the lack of a pathological response to NAC. This knowledge might help early identification of TNBC patients less likely to respond to NAC and allow the establishment of new therapeutic targets.

With a high risk of relapse and death, and a poor or absent response to therapeutics, the triple-negative breast cancer (TNBC) subtype is particularly challenging, especially in patients who cannot achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Although the tumor microenvironment (TME) is known to influence disease progression and the effectiveness of therapeutics, its predictive and prognostic potential remains uncertain. This work aimed to define the residual TME profile after NAC of a retrospective cohort with 96 TNBC patients by immunohistochemical staining (cell markers) and chromogenic in situ hybridization (genetic markers). Kaplan–Meier curves were used to estimate the influence of the selected TME markers on five-year overall survival (OS) and relapse-free survival (RFS) probabilities. The risks of each variable being associated with relapse and death were determined through univariate and multivariate Cox analyses. We describe a unique tumor-infiltrating immune profile with high levels of lymphocytes (CD4, FOXP3) and dendritic cells (CD21, CD1a and CD83) that are valuable prognostic factors in post-NAC TNBC patients. Our study also demonstrates the value of considering not only cellular but also genetic TME markers such as MUC-1 and CXCL13 in routine clinical diagnosis to refine prognosis modelling.

2022 International Conference on Robotics and Automation (ICRA) (Philadelphia, PA, USA , 23-27 May 2022), Item does not contain fulltext, This paper describes the development of a 3- stage signalling framework to trigger a social robot's bottom- up reactive behavior inspired by a biological model. In the first stage, low-level firing of stimuli due to external sources is constructed through perception grounding. This is followed by a saliency classifier which fires-up high level salient signals that require attention and are used to trigger the robot's reactive behavior. The whole framework evolves primarily on the knowledge ontology that defines the characteristics of the social robot and the querying mechanism that correlates the perceived stimuli with the ontology to trigger the reactive behavior. We evaluated the performance of our system with timing metrics and we achieved good results for our application.

2022 International Conference on Robotics and Automation (ICRA) (Philadelphia, PA, USA , 23-27 May 2022), Item does not contain fulltext, This paper describes the development of a 3- stage signalling framework to trigger a social robot's bottom- up reactive behavior inspired by a biological model. In the first stage, low-level firing of stimuli due to external sources is constructed through perception grounding. This is followed by a saliency classifier which fires-up high level salient signals that require attention and are used to trigger the robot's reactive behavior. The whole framework evolves primarily on the knowledge ontology that defines the characteristics of the social robot and the querying mechanism that correlates the perceived stimuli with the ontology to trigger the reactive behavior. We evaluated the performance of our system with timing metrics and we achieved good results for our application.

[Background] Breast cancer is the most common malignancy and the second leading cause of cancer-related mortality in Spanish women. Ribociclib in combination with endocrine therapy (ET) has shown superiority in prolonging survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) vs. ET alone., [Methods] CompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR+, HER2– ABC. The primary endpoints were safety and tolerability. Here we report data for Spanish patients enrolled in CompLEEment-1., [Results] A total of 526 patients were evaluated (median follow-up: 26.97 months). Baseline characteristics showed a diverse population with a median age of 54 years. At study entry, 56.5% of patients had visceral metastases and 8.7% had received prior chemotherapy for advanced disease. Rates of all-grade and Grade ≥3 adverse events (AEs) were 99.0% and 76.2%, respectively; 21.3% of patients experienced a serious AE, and 15.8% of AEs led to treatment discontinuation. AEs of special interest of neutropenia, increased alanine aminotransferase, increased aspartate aminotransferase and QTcF prolongation occurred in 77.8%, 14.8%, 11.4% and 4.0% of patients, respectively. Patients aged >70 years experienced increased rates of all-grade and Grade ≥3 neutropenia and anemia. Efficacy results were consistent with the global study., [Conclusions] Results from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR+, HER2− ABC, including populations of interest (NCT02941926)., [Trial registration] ClinicalTrials.gov NCT02941926.

Ewing Sarcoma (EWS) is an aggressive bone and soft tissue tumor that mainly affects children, adolescents, and young adults. The standard therapy, including chemotherapy, surgery, and radiotherapy, has substantially improved the survival of EWS patients with localized disease. Unfortunately, this multimodal treatment remains elusive in clinics for those patients with recurrent or metastatic disease who have an unfavorable prognosis. Consistently, there is an urgent need to find new strategies for patients that fail to respond to standard therapies. In this regard, in the last decade, treatments targeting epigenetic dependencies in tumor cells and the immune system have emerged into the clinical scenario. Additionally, recent advances in nanomedicine provide novel delivery drug systems, which may address challenges such as side effects and toxicity. Therefore, therapeutic strategies stemming from epigenetics, immunology, and nanomedicine yield promising alternatives for treating these patients. In this review, we highlight the most relevant EWS preclinical and clinical studies in epigenetics, immunotherapy, and nanotherapy conducted in the last five years.

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., Comment: 8 pages, 4 figures, 3 tables. Version accepted in IEEE-Robotics and Automation Letters. "Copyright 2023 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses..."

New therapeutic options are needed in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Lenalidomide-based schedules can reverse rituximab refractoriness in lymphoma.In the phase II R2-GDP trial, 78 patients unsuitable for autologous stem cell transplant received treatment with the following schedule: lenalidomide 10 mg Days (D)1-14, rituximab 375 mg/m2 D1, cisplatin 60 mg/m2 D1, gemcitabine 750 mg/m2 D1 and D8, and dexamethasone 20 mg D1-3, up to 6 cycles (induction phase), followed by lenalidomide 10 mg (or last lenalidomide dose received) D1-21 every 28 days (maintenance phase). Primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and monitorization of key circulating immune biomarkers (EU Clinical Trials Register number: EudraCT 2014-001620-29).After a median follow-up of 37 months, ORR was 60.2% [37.1% complete responses (CR) and 23.1% partial responses (PR)]. Median OS was 12 months (47 vs. 6 months in CR vs. no CR); median PFS was 9 months (34 vs. 5 months in CR vs. no CR). In the primary refractory population, ORR was 45.5% (21.2% CR and 24.3% PR). Most common grade 3-4 adverse events were thrombocytopenia (60.2%), neutropenia (60.2%), anemia (26.9%), infections (15.3%), and febrile neutropenia (14.1%). Complete responses were associated with a sharp decrease in circulating myeloid-derived suppressor cells and regulatory T cells.R2-GDP schedule is feasible and highly active in R/R DLBCL, including the primary refractory population. Immune biomarkers showed differences in responders versus progressors.©2022 The Authors; Published by the American Association for Cancer Research.

We here present the luminosity function (LF) of globular clusters (GCs) in five nearby spiral galaxies using the samples of GC candidates selected in Hubble Space Telescope mosaic images in F435W, F555W and F814W filters. Our search, which surpasses the fractional area covered by all previous searches in these galaxies, has resulted in the detection of 158 GC candidates in M81, 1123 in M101, 226 in NGC4258, 293 in M51 and 173 in NGC628. The LFs constructed from this dataset, after correcting for relatively small contamination from reddened young clusters, are log-normal in nature, which was hitherto established only for the Milky Way (MW) and Andromeda among spiral galaxies. The magnitude at the turn-over (TO) corresponds to Mv(TO)=-7.41+/-0.14 in four of the galaxies with Hubble types Sc or earlier, in excellent agreement with Mv(TO)=-7.40+/-0.10 for the MW. The TO magnitude is equivalent to a mass of ~3x10^5 Msun for an old, metal-poor population. Mv(TO) is fainter by ~1.16 magnitude for the fifth galaxy, M101, which is of Hubble type Scd. The TO dependence on Hubble type implies that the GCs in early-type spirals are classical GCs, which have a universal TO, whereas the GC population in late-type galaxies is dominated by old disk clusters, which are in general less massive. The radial density distribution of GCs in our sample galaxies follows the S\'ersic function with exponential power-law indices, and effective radii of 4.0-9.5 kpc. GCs in the sample galaxies have a mean specific frequency of 1.10+/-0.24, after correcting for magnitude and radial incompleteness factors., Comment: 24 pages. Accepted in MNRAS

ICSR 2021: 13th International Conference on Social Robotics (Singapore, November 10-13, 2021), 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.

PURPOSE: The randomized phase III coBRIM study (NCT01689519) demonstrated improved progression-free survival (PFS) and overall survival (OS) with addition of cobimetinib to vemurafenib compared with vemurafenib in patients with previously untreated BRAFV600 mutation-positive advanced melanoma. We report long-term follow-up of coBRIM, with at least 5 years since the last patient was randomized. PATIENTS AND METHODS: Eligible patients were randomized 1:1 to receive either oral cobimetinib (60 mg once daily on days 1-21 in each 28-day cycle) or placebo in combination with oral vemurafenib (960 mg twice daily). RESULTS: 495 patients were randomized to cobimetinib plus vemurafenib (n = 247) or placebo plus vemurafenib (n = 248). Median follow-up was 21.2 months for cobimetinib plus vemurafenib and 16.6 months for placebo plus vemurafenib. Median OS was 22.5 months (95% CI, 20.3-28.8) with cobimetinib plus vemurafenib and 17.4 months (95% CI, 15.0-19.8) with placebo plus vemurafenib; 5-year OS rates were 31% and 26%, respectively. Median PFS was 12.6 months (95% CI, 9.5-14.8) with cobimetinib plus vemurafenib and 7.2 months (95% CI, 5.6-7.5) with placebo plus vemurafenib; 5-year PFS rates were 14% and 10%, respectively. OS and PFS were longest in patients with normal baseline lactate dehydrogenase levels and low tumor burden, and in those achieving complete response. The safety profile remained consistent with previously published reports. CONCLUSIONS: Extended follow-up of coBRIM confirms the long-term clinical benefit and safety profile of cobimetinib plus vemurafenib compared with vemurafenib monotherapy in patients with BRAFV600 mutation-positive advanced melanoma.

ICSR 2021: 13th International Conference on Social Robotics (Singapore, November 10-13, 2021), 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), 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.

We here present the luminosity function (LF) of globular clusters (GCs) in five nearby spiral galaxies using the samples of GC candidates selected in Hubble Space Telescope mosaic images in F435W, F555W and F814W filters. Our search, which surpasses the fractional area covered by all previous searches in these galaxies, has resulted in the detection of 158 GC candidates in M81, 1123 in M101, 226 in NGC4258, 293 in M51 and 173 in NGC628. The LFs constructed from this dataset, after correcting for relatively small contamination from reddened young clusters, are log-normal in nature, which was hitherto established only for the Milky Way (MW) and Andromeda among spiral galaxies. The magnitude at the turn-over (TO) corresponds to Mv(TO)=-7.41+/-0.14 in four of the galaxies with Hubble types Sc or earlier, in excellent agreement with Mv(TO)=-7.40+/-0.10 for the MW. The TO magnitude is equivalent to a mass of ~3x10^5 Msun for an old, metal-poor population. Mv(TO) is fainter by ~1.16 magnitude for the fifth galaxy, M101, which is of Hubble type Scd. The TO dependence on Hubble type implies that the GCs in early-type spirals are classical GCs, which have a universal TO, whereas the GC population in late-type galaxies is dominated by old disk clusters, which are in general less massive. The radial density distribution of GCs in our sample galaxies follows the S\'ersic function with exponential power-law indices, and effective radii of 4.0-9.5 kpc. GCs in the sample galaxies have a mean specific frequency of 1.10+/-0.24, after correcting for magnitude and radial incompleteness factors., Comment: 24 pages. Accepted in MNRAS

In this paper, we explore the storytelling potential of a robot. We exploit the use of creative contents that maximize the embodied communication affordance of the empathic robot Haru. We identify the elements in storytelling such as narration, agency, engagement and education and synthesized these into the robot. Through effective design we investigated the possible answers that could leverage the limitations and the challenges in developing storytelling applications through a robotic medium. Our preliminary findings show that the use of an embodied agent such as a robot in storytelling only has meaning when its communicative affordance (i.e. embodiment, expressiveness, and other modalities) is tapped, adding new dimension to the experience. Otherwise, traditional storytelling delivery (e.g. tablet) without the use of embodiment will suffice. Hence, robots need to be performers rather than just mere props in storytelling.

In this paper, we explore the storytelling potential of a robot. We exploit the use of creative contents that maximize the embodied communication affordance of the empathic robot Haru. We identify the elements in storytelling such as narration, agency, engagement and education and synthesized these into the robot. Through effective design we investigated the possible answers that could leverage the limitations and the challenges in developing storytelling applications through a robotic medium. Our preliminary findings show that the use of an embodied agent such as a robot in storytelling only has meaning when its communicative affordance (i.e. embodiment, expressiveness, and other modalities) is tapped, adding new dimension to the experience. Otherwise, traditional storytelling delivery (e.g. tablet) without the use of embodiment will suffice. Hence, robots need to be performers rather than just mere props in storytelling.

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 ove

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

Posidonia oceanica (L.) Delile meadows are highly productive coastal marine ecosystems that provide multiple ecosystem services. The seagrass is not always the major contributor to total primary production, however, little is known about long-term changes in the composition of primary producers within seagrass meadows. Understanding compositional shifts within the community of primary producers is crucial to evaluate how climate and anthropogenic change affect the functioning of seagrass ecosystems. Here we analysed marker pigment composition in seagrass cores from two bays of the Cabrera Island (Balearic Islands, Spain) to asses long-term changes in phototrophic community composition and production in seagrass meadows, and identify the environmental factors triggering those changes. The proxy dataset was explored using principal component analyses (PCA): one including the pigment dataset to look for associations between producers' groups, and another one combining the pigment dataset with plausible local and global regulatory factors to assess the environmental drivers of change. Analyses of characteristic pigments and morphological fossils (cysts) showed that the abundance of dinoflagellates increased over the last 150–300 years, coeval with a rise in solar irradiance and air temperature. When compared among embayments, pigments from cyanobacteria predominated in seagrass meadows located at Es Port, a sheltered bay receiving higher terrestrial runoff; whereas pigments from diatoms, seagrasses and rodophytes were more common at Santa Maria, an exposed bay with clearer waters. Water depth also played a role in controlling the phototrophic community composition, with greater abundance of diatoms in the shallowest waters (<5 m). Overall, our results suggested that historical and spatial variation in seagrass meadows' phototrophic community composition was influenced by the interaction between local factors (catchment-bay characteristics) and global climate proc

Posidonia oceanica (L.) Delile meadows are highly productive coastal marine ecosystems that provide multiple ecosystem services. The seagrass is not always the major contributor to total primary production, however, little is known about long-term changes in the composition of primary producers within seagrass meadows. Understanding compositional shifts within the community of primary producers is crucial to evaluate how climate and anthropogenic change affect the functioning of seagrass ecosystems. Here we analysed marker pigment composition in seagrass cores from two bays of the Cabrera Island (Balearic Islands, Spain) to asses long-term changes in phototrophic community composition and production in seagrass meadows, and identify the environmental factors triggering those changes. The proxy dataset was explored using principal component analyses (PCA): one including the pigment dataset to look for associations between producers' groups, and another one combining the pigment dataset with plausible local and global regulatory factors to assess the environmental drivers of change. Analyses of characteristic pigments and morphological fossils (cysts) showed that the abundance of dinoflagellates increased over the last 150–300 years, coeval with a rise in solar irradiance and air temperature. When compared among embayments, pigments from cyanobacteria predominated in seagrass meadows located at Es Port, a sheltered bay receiving higher terrestrial runoff; whereas pigments from diatoms, seagrasses and rodophytes were more common at Santa Maria, an exposed bay with clearer waters. Water depth also played a role in controlling the phototrophic community composition, with greater abundance of diatoms in the shallowest waters (<5 m). Overall, our results suggested that historical and spatial variation in seagrass meadows' phototrophic community composition was influenced by the interaction between local factors (catchment-bay characteristics) and global climate proc

We here report the detection of extended HeII4686 nebular emission in the central region of NGC1569 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 x 11.3 arcsec at seeing-limited spatial resolution of ~15 pc and at a spectral resolution of R=6000 in the wavelength range 4330--5200 Angstrom. 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 Av 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 HeII4686 broad feature and Av=2.3 mag. The He+ ionizing photon rate from these WR stars is sufficient to explain the luminosity of the HeII4686 nebula. The observationally-determined total He+ and H0 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)x10^5 Msun. 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 HeII4686 emission has been reported from narrow-band imaging observations contain WR stars., Comment: 20 pages. Accepted in MNRAS

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

This paper presents a non-linear optimization method for trajectory planning of tethered aerial robots. Particularly, the paper addresses the planning problem of an unmanned aerial vehicle (UAV) linked to an unmanned ground vehicle (UGV) by means of a tether. The result is a collision-free trajectory for UAV and tether, assuming the UGV position is static. The optimizer takes into account constraints related to the UAV, UGV and tether positions, obstacles and temporal aspects of the motion such as limited robot velocities and accelerations, and finally the tether state, which is not required to be tense. The problem is formulated in a weighted multi-objective optimization framework. Results from simulated scenarios demonstrate that the approach is able to generate obstacle-free and smooth trajectories for the UAV and tether., Comment: 7 pages, 4 figures, 2 tables, accepted ICRA'21

Breast cancer (BC) is the most common cancer in women in Spain. During the COVID‐19 pandemic caused by the SARS‐CoV‐2 virus, patients with BC still require timely treatment and follow‐up; however, hospitals are overwhelmed with infected patients and, if exposed, patients with BC are at higher risk for infection and serious complications if infected. Thus, health care providers need to evaluate each BC treatment and in‐hospital visit to minimize pandemic‐associated risks while maintaining adequate treatment efficacy. Here we present a set of guidelines regarding available options for BC patient management and treatment by BC subtype in the context of the COVID‐19 pandemic. Owing to the lack of evidence about COVID‐19 infection, these recommendations are mainly based on expert opinion, medical organizations' and societies' recommendations, and some published evidence. We consider this a useful tool to facilitate medical decision making in this health crisis situation we are facing.

[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.

Defining a robot's expressivity is a difficult task that requires thoughtful consideration of the potential of various robot modalities and a model of communication that humans understand. Humanoid and zoomorphic-designed robots can easily take cues from human and animals, respectively when designing their expressivity. However, a robot design that is neither human nor animal-like does not have a clear model to follow in terms of designing expressivity. Animation presents a potential model in these circumstances as animated characters in movies take various forms, sizes, shapes and styles, and are successful in defining expressivity that is widely accepted across different languages and cultures. In this paper, we discuss the development and design of the expressivity of Haru, a table top robot that is neither human nor animal-like and the application of animation expertise to the holistic treatment of the different modalities. The method maximizes animation techniques and expertise normally applied to movies to generate expressivity that is then transferred to the robot hardware. Experimental results show that the robot's expressivity generated using our method is easily understood and are preferred to the conventional approach of generating expressions.

© 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.

© 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.

© 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.

© 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.

Defining a robot's expressivity is a difficult task that requires thoughtful consideration of the potential of various robot modalities and a model of communication that humans understand. Humanoid and zoomorphic-designed robots can easily take cues from human and animals, respectively when designing their expressivity. However, a robot design that is neither human nor animal-like does not have a clear model to follow in terms of designing expressivity. Animation presents a potential model in these circumstances as animated characters in movies take various forms, sizes, shapes and styles, and are successful in defining expressivity that is widely accepted across different languages and cultures. In this paper, we discuss the development and design of the expressivity of Haru, a table top robot that is neither human nor animal-like and the application of animation expertise to the holistic treatment of the different modalities. The method maximizes animation techniques and expertise normally applied to movies to generate expressivity that is then transferred to the robot hardware. Experimental results show that the robot's expressivity generated using our method is easily understood and are preferred to the conventional approach of generating expressions.

[Background] PD-L1 immunohistochemistry (IHC) has been traditionally used for predicting clinical responses to immune checkpoint inhibitors (ICIs). However, there are at least 4 different assays and antibodies used for PD-L1 IHC, each developed with a different ICI. We set to test if next generation RNA sequencing (RNA-seq) is a robust method to determine PD-L1 mRNA expression levels and furthermore, efficacy of predicting response to ICIs as compared to routinely used, standardized IHC procedures., [Methods] A total of 209 cancer patients treated on-label by FDA-approved ICIs, with evaluable responses were assessed for PD-L1 expression by RNA-seq and IHC, based on tumor proportion score (TPS) and immune cell staining (ICS). A subset of serially diluted cases was evaluated for RNA-seq assay performance across a broad range of PD-L1 expression levels., [Results] Assessment of PD-L1 mRNA levels by RNA-seq demonstrated robust linearity across high and low expression ranges. PD-L1 mRNA levels assessed by RNA-seq and IHC (TPS and ICS) were highly correlated (p < 2e-16). Sub-analyses showed sustained correlation when IHC results were classified as high or low by clinically accepted cut-offs (p < 0.01), and results did not differ by tumor type or anti-PD-L1 antibody used. Overall, a combined positive PD-L1 result (≥1% IHC TPS and high PD-L1 expression by RNA-Seq) was associated with a 2-to-5-fold higher overall response rate (ORR) compared to a double negative result. Standard assessments of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) showed that a PD-L1 positive assessment for melanoma samples by RNA-seq had the lowest sensitivity (25%) but the highest PPV (72.7%). Among the three tumor types analyzed in this study, the only non-overlapping confidence interval for predicting response was for “RNA-seq low vs high” in melanoma., [Conclusions] Measurement of PD-L1 mRNA expression by RNA-seq is comparable to PD-L1 expression by IHC both analytically and clinically in predicting ICI response. RNA-seq has the added advantages of being amenable to standardization and avoidance of interpretation bias. PD-L1 by RNA-seq needs to be validated in future prospective ICI clinical studies across multiple histologies.

Merkel cell carcinoma (MCC) is a rare, aggressive, primary cutaneous neuroendocrine tumor that typically presents as an indurated nodule on sun‐exposed areas of the head and neck in the white population. Major risk factors include immunosuppression, UV light exposure, and advanced age. Up to 80% of MCC are associated with Merkel cell polyomavirus. About 50% of patients present with localized disease, and surgical resection with or without adjuvant radiotherapy is generally indicated in this context. However, recurrence rates are high and overall prognosis rather poor, with mortality rates of 33%–46%. MCC is a chemosensitive disease, but responses in the advanced setting are seldom durable and not clearly associated with improved survival. Several recent trials with checkpoint inhibitors (pembrolizumab, avelumab, nivolumab) have shown very promising results with a favorable safety profile, in both chemonaïve and pretreated patients. In 2017, avelumab was approved by several regulatory agencies for the treatment of metastatic MCC, the first drug to be approved for this orphan disease. More recently, pembrolizumab has also been approved by the U.S. Food and Drug Administration in this setting. Immunotherapy has therefore become the new standard of care in advanced MCC. This article reviews current evidence and recommendations for the diagnosis and treatment of MCC and discusses recent therapeutic advances and their implications for care in patients with advanced disease. This consensus statement is the result of a collaboration between the Spanish Cooperative Group for Neuroendocrine Tumors, the Spanish Group of Treatment on Head and Neck Tumors, and the Spanish Melanoma Group.

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.

[Background] PD-L1 immunohistochemistry (IHC) has been traditionally used for predicting clinical responses to immune checkpoint inhibitors (ICIs). However, there are at least 4 different assays and antibodies used for PD-L1 IHC, each developed with a different ICI. We set to test if next generation RNA sequencing (RNA-seq) is a robust method to determine PD-L1 mRNA expression levels and furthermore, efficacy of predicting response to ICIs as compared to routinely used, standardized IHC procedures., [Methods] A total of 209 cancer patients treated on-label by FDA-approved ICIs, with evaluable responses were assessed for PD-L1 expression by RNA-seq and IHC, based on tumor proportion score (TPS) and immune cell staining (ICS). A subset of serially diluted cases was evaluated for RNA-seq assay performance across a broad range of PD-L1 expression levels., [Results] Assessment of PD-L1 mRNA levels by RNA-seq demonstrated robust linearity across high and low expression ranges. PD-L1 mRNA levels assessed by RNA-seq and IHC (TPS and ICS) were highly correlated (p < 2e-16). Sub-analyses showed sustained correlation when IHC results were classified as high or low by clinically accepted cut-offs (p < 0.01), and results did not differ by tumor type or anti-PD-L1 antibody used. Overall, a combined positive PD-L1 result (≥1% IHC TPS and high PD-L1 expression by RNA-Seq) was associated with a 2-to-5-fold higher overall response rate (ORR) compared to a double negative result. Standard assessments of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) showed that a PD-L1 positive assessment for melanoma samples by RNA-seq had the lowest sensitivity (25%) but the highest PPV (72.7%). Among the three tumor types analyzed in this study, the only non-overlapping confidence interval for predicting response was for “RNA-seq low vs high” in melanoma., [Conclusions] Measurement of PD-L1 mRNA expression by RNA-seq is comparable to PD-L1 expression by IHC both analytically and clinically in predicting ICI response. RNA-seq has the added advantages of being amenable to standardization and avoidance of interpretation bias. PD-L1 by RNA-seq needs to be validated in future prospective ICI clinical studies across multiple histologies.

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 p

MEGARA is the new generation IFU and MOS optical spectrograph built for the 10.4m Gran Telescopio CANARIAS (GTC). The project was developed by a consortium led by UCM (Spain) that also includes INAOE (Mexico), IAA-CSIC (Spain) and UPM (Spain). The instrument arrived to GTC on March 28th 2017 and was successfully integrated and commissioned at the telescope from May to August 2017. During the on-sky commissioning we demonstrated that MEGARA is a powerful and robust instrument that provides on-sky intermediate-to-high spectral resolutions RFWHM ~ 6,000, 12,000 and 20,000 at an unprecedented efficiency for these resolving powers in both its IFU and MOS modes. The IFU covers 12.5 x 11.3 arcsec 2 while the MOS mode allows observing up to 92 objects in a region of 3.5 x 3.5 arcmin 2 . In this paper we describe the instrument main subsystems, including the Folded-Cassegrain unit, the fiber link, the spectrograph, the cryostat, the detector and the control subsystems, and its performance numbers obtained during commissioning where the fulfillment of the instrument requirements is demonstrated. © 2018 SPIE.

On June 25th 2017, the new intermediate-resolution optical IFU and MOS of the 10.4-m GTC had its first light. As part of the tests carried out to verify the performance of the instrument in its two modes (IFU and MOS) and 18 spectral setups (identical number of VPHs with resolutions R=6000-20000 from 0.36 to 1 micron) a number of astronomical objects were observed. These observations show that MEGARA@GTC is called to fill a niche of high-throughput, intermediateresolution IFU and MOS observations of extremely-faint narrow-lined objects. Lyman-¿ absorbers, star-forming dwarfs or even weak absorptions in stellar spectra in our Galaxy or in the Local Group can now be explored to a new level. Thus, the versatility of MEGARA in terms of observing modes and spectral resolution and coverage will allow GTC to go beyond current observational limits in either depth or precision for all these objects. The results to be presented in this talk clearly demonstrate the potential of MEGARA in this regard. © 2018 SPIE.

The vast majority of patients treated with radiotherapy develop dermatological side effects. Acute radiation dermatitis or chronic skin fibrosis are well known sequels of radiation, but there are also other infrequent skin toxicities following external radiotherapy we should be aware of. We present a case of a rare form of delayed radiation dermatitis consisting of a localized acneiform eruption, confirmed by skin biopsy, in the irradiated fields in a woman with breast cancer. We review the clinical characteristics and risk factors available in the literature about this unusual adverse effect of radiotherapy. It is important for dermatologists to recognize this rare adverse effect, owing to the important impact on physical and psychosocial health of the patients and because it may delay the surgical reconstruction.

The vast majority of patients treated with radiotherapy develop dermatological side effects. Acute radiation dermatitis or chronic skin fibrosis are well known sequels of radiation, but there are also other infrequent skin toxicities following external radiotherapy we should be aware of. We present a case of a rare form of delayed radiation dermatitis consisting of a localized acneiform eruption, confirmed by skin biopsy, in the irradiated fields in a woman with breast cancer. We review the clinical characteristics and risk factors available in the literature about this unusual adverse effect of radiotherapy. It is important for dermatologists to recognize this rare adverse effect, owing to the important impact on physical and psychosocial health of the patients and because it may delay the surgical reconstruction.

Recent geophysical mapping of the Arctic seafloor has revealed extensive erosion caused by ice and glacial landforms on ridge crests and plateaus where present water depths are shallower than . Such erosion stems from thick outlet glaciers and massive ice shelf complexes. Cores and glacigenic landforms suggest that the largest ice shelf complex was confined to the Amerasian sector of the Arctic Ocean, roughly 135,000 years ago. We apply a peak over threshold approach to assess whether the calving fronts of this ice shelf complex comprise a likely source of the deep draft icebergs responsible for the mapped plow marks. This approach is novel to modeling Arctic paleoglacial configurations. Predicted extreme calving front drafts match observed deep-draft iceberg marks if the ice shelf complex is sufficiently large. We explain the methodology of Kirchner, Furrer, Jakobsson and coauthors [1] in a storyboard framework, i.e., with figures and sketches. Here, we extend their approach by using shelf specific threshold selection, an alternative estimate to scale ‘coastlines’, supervised pooling of estimates and uncertainty estimates based on parametric bootstrap. For theoretical details as well as details about the precise origin and preprocessing of the data we refer to [1], much of the statistical theory is covered in [2, 2].

BACKGROUND: Serous chorioretinopathy has been associated with MEK inhibitors, including cobimetinib. We describe the clinical features of serous retinopathy observed with cobimetinib in patients with BRAF V600-mutated melanoma treated in the Phase III coBRIM study. METHODS: In the coBRIM study, 493 patients were treated in two randomly assigned treatment groups: cobimetinib and vemurafenib (n = 247) or vemurafenib (n = 246). All patients underwent prospective ophthalmic examinations at screening, at regular intervals during the study, and whenever ocular symptoms developed. Patients with serous retinopathy were identified in the study database using a group of relevant and synonymous adverse event terms. RESULTS: Eighty-six serous retinopathy events were reported in 70 patients (79 events in 63 cobimetinib and vemurafenib-treated patients vs seven events in seven vemurafenib-treated patients). Most patients with serous retinopathy identified by ophthalmic examination had no symptoms or had mild symptoms, among them reduced visual acuity, blurred vision, dyschromatopsia, and photophobia. Serous retinopathy usually occurred early during cobimetinib and vemurafenib treatment; median time to onset was 1.0 month. Most events were managed by observation and continuation of cobimetinib without dose modification and resolved or were resolving by the data cutoff date (19 Sept 2014). CONCLUSIONS: Cobimetinib treatment was associated with serous retinopathy in patients with BRAF V600-mutated melanoma. Retinopathy was generally asymptomatic or mild. Periodic ophthalmologic evaluations at regular intervals and at the manifestation of any visual disturbance are recommended to facilitate early detection and resolution of serous retinopathy while patients are taking cobimetinib. Trial Registration Clinicaltrials.gov (NCT01689519). First received: September 18, 2012.

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

MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A. Davies K2 Non-mutational adaptive changes in melanoma cells exposed to BRAF and MEK inhibitors help the establishment of drug resistance Gennaro Ciliberto, Luigi Fattore, Debora Malpicci, Luigi Aurisicchio, Paolo Antonio Ascierto, Carlo M. Croce, Rita Mancini K3 Tumor-intrinsic beta-catenin signaling mediates tumor-immune avoidance Stefani Spranger, Thomas F. Gajewski K4 Intracellular tumor antigens as a source of targets of antibody-based immunotherapy of melanoma Yangyang Wang, Soldano Ferrone Combination therapies K5 Harnessing radiotherapy to improve responses to immunotherapy in cancer Claire Vanpouille-Box, Erik Wennerberg, Karsten A. Pilones, Silvia C. Formenti, Sandra Demaria K6 Creating a T cell-inflamed tumor microenvironment overcomes resistance to checkpoint blockade Haidong Tang, Yang Wang, Yang-Xin Fu K7 Biomarkers for treatment decisions? Reinhard Dummer K8 Combining oncolytic therapies in the era of checkpoint inhibitors Igor Puzanov K9 Immune checkpoint blockade for melanoma: should we combine or sequence ipilimumab and PD-1 antibody therapy? Michael A. Postow News in immunotherapy K10 An update on adjuvant and neoadjuvant therapy for melanom Ahmad Tarhini K11 Targeting multiple inhibitory receptors in melanoma Joe-Marc Chauvin, Ornella Pagliano, Julien Fourcade, Zhaojun Sun, Hong Wang, Cindy Sanders, John M. Kirkwood, Tseng-hui Timothy Chen, Mark Maurer, Alan J. Korman, Hassane M. Zarour K12 Improving adoptive immune therapy using genetically engineered T cells David F. Stroncek Tumor microenvironment and biomarkers K13 Myeloid cells and tumor exosomes: a crosstalk for assessing immunosuppression? Veronica Huber, Licia Rivoltini K14 Update on the SITC biomarker taskforce: progress and challenges Magdalena Thurin World-wide immunosc

RNAi screens are widely used in functional genomics. Although the screen data can be susceptible to a number of experimental biases, many of these can be corrected by computational analysis. For this purpose, here we have developed a web-based platform for integrated analysis and visualization of RNAi screen data named CARD (for Comprehensive Analysis of RNAi Data; available at https://card.niaid.nih.gov). CARD allows the user to seamlessly carry out sequential steps in a rigorous data analysis workflow, including normalization, off-target analysis, integration of gene expression data, optimal thresholds for hit selection and network/pathway analysis. To evaluate the utility of CARD, we describe analysis of three genome-scale siRNA screens and demonstrate: (i) a significant increase both in selection of subsequently validated hits and in rejection of false positives, (ii) an increased overlap of hits from independent screens of the same biology and (iii) insight to microRNA (miRNA) activity based on siRNA seed enrichment.

© 2015 Chartered Society of Physiotherapy. Objective: To determine whether dexketoprofen administered by phonophoresis or iontophoresis is more effective for the treatment of subacromial impingement syndrome (SIS) than conventional ultrasound therapy. Design: Randomised clinical trial. Setting: University hospital. Participants: Ninety-nine participants with SIS without a complete tear of the rotator cuff were assigned at random to three intervention groups. Intervention groups: Participants received ultrasound (n= 32), phonophoresis with dexketoprofen (50 mg/session) (n= 33) or iontophoresis with dexketoprofen (50 mg/session) (n= 34). All participants completed 20 treatment sessions plus exercise therapy and cryotherapy. Outcome measures: A visual analogue scale (VAS), the Constant-Murley Scale (CMS) and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire were administered pre-treatment (baseline), post-treatment and 1 month post-treatment. Results: At baseline, there were no differences between the groups. Post-treatment, VAS score improved by -1.2 points and CMS score improved by 8.9 points in the ultrasound group compared with the iontophoresis group [95% confidence interval (CI) -0.2 to -2.2 and 95% CI 17.0 to 0.7, respectively]. CMS score improved by 7.1 points in the phonophoresis group compared with the iontophoresis group (95% CI 14.8 to -0.7). At 1 month post-treatment, no significant differences were detected between the groups. VAS, CMS and DASH scores of all groups improved post-treatment and at 1 month post-treatment. Conclusion: Ultrasound, iontophoresis with dexketoprofen and phonophoresis with dexketoprofen can improve pain, shoulder function, and physical functioning and symptoms in the upper limb in patients with SIS without a complete

Hodgkin lymphoma (HL) is an uncommon B cell lymphoid malignancy representing approximately 10–15 % of all lymphomas. HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte-predominant HL. An accurate assessment of the stage of disease and prognostic factors that identify patients at low or high risk for recurrence are used to optimize therapy. Patients with early stage disease are treated with combined modality strategies using abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. Brentuximab vedotin should be considered for patients who fail HDCT with ASCT.

Follicular non-Hodgkin’s lymphoma (FL) is a nodal B lymphoid malignancy that originates from the germinal center of a lymph node. FL is the second most frequent lymphoma subtype. The course of the disease is usually characterised by a typically indolent clinical course, with a median survival rate of 8–10 years, although most patients relapse after treatment. Diagnosis should always be based on a surgical specimen like an excisional node lymph biopsy. The first-line treatment of FL will depend of extension disease, tumour burden, patient symptoms, performance status and also patient decision. The addition of rituximab to conventional chemotherapy has improved ORR, PFS and OS. As first line in patients that need treatment, a combination of chemotherapy with rituximab induction followed by 2 years of rituximab maintenance is the best option. High-dose chemotherapy with autologous stem-cell transplantation in first line has not shown improvement and is not recommended as first-line therapy. Before any treatment decision in relapsed patients, a repeat biopsy is mandatory to rule out a transformation into large cell aggressive lymphoma. Standard treatment is controversial, depends on the efficacy of prior treatment, duration of the time-to-relapse, patient’s age and histological findings at relapse.