Revitalizing public spaces: experiences form three renewed neighbourhoods

Ponència presentada a: Session 8: Post-ocupación / Post-occupancy: buildings and citie

Switching from natalizumab to fingolimod: an observational study

Background – Multiple sclerosis patients who discontinue using natalizumab are at risk of a rebound in disease activity. However, the optimal alternative therapy is not currently known. Aims of the study – We report on clinical and MRI data and patient safety in a group of relapsing–remitting multiple sclerosis patients who tested seropositive for the JC virus and who have switched from natalizumab to fingolimod because of concerns regarding PML risks. Methods – The test for JC virus antibodies was performed in 18 relapsing–remitting multiple sclerosis patients who were being treated with natalizumab for more than 1 year. Eight seropositive patients switched to fingolimod while the seronegative patients continued with natalizumab. Results – After switching to fingolimod, five of eight patients (63%) experienced clinical relapses, and MRI activity was detected in six of eight patients (75%). Neither clinical relapses nor MRI activity was observed in the patients who continued with natalizumab. No serious adverse effects were detected. Conclusions – Natalizumab is an effective treatment for relapsing–remitting multiple sclerosis, but its discontinuation continues to be a complex problem. All of the therapies tried thus far, including fingolimod, have been unable to control the reactivation of the disease. Further studies addressing alternative therapies after natalizumab discontinuation are necessary

SMOS soil moisture product validation in croplands

A validation campaign has been carried out to evaluate the Level 2 Soil Moisture (SM) product (version 5.51) given by the European Space Agency (ESA) Soil Moisture and Ocean Salinity (SMOS) satellite in the Pampean Region of Argentina. The study region was selected because it is a plain, avoiding topography problems, with an SMOS nominal land use class (low vegetation crops, 1-2m height). Transects of ground SM measurements were collected at 5-cm and 6-cm depth using Delta-T ThetaProbe ML2x and Stevens Hydra Probe II SM sensors, respectively. The volumetric measurements were calibrated using gravimetric and bulk density data collected at the same time as the SM sensor measurements. The SM transects covered ISEA-grid SMOS nodes over four extensive agricultural areas with prevalence of soy crops (site 1: -32.982N, -62.505E; site 2: -32.510N, -62.788E; site 3: -32.024N, -63.692E; and site 4: -37.315N, -58.868E, WGS84). The validation sites were selected taking as reference the locations of permanent SM stations property of the Argentinean Comisión Nacional de Actividades Espaciales (CONAE, National Commission of Space Activities), Instituto Nacional de Tecnología Agropecuaria (INTA, National Institute of Farming Technology) and Instituto de Hidrología de Llanuras (IHLLA, Plain Hydrology Institute). Therefore, additionally to validate the SMOS SM product with the ground data collected during the experimental campaign, the measurements are useful to evaluate the station SM data reliability at the SMOS spatial resolution with the aim of using station data series as reference to test different versions of the SMOS SM product. Previously to the campaign, SMOS SM data variability, ESA Globcover land use classification, soil edaphic properties, water bodies and topography were analyzed around the station locations to select the best sites and the experimental methodology. Temperature vegetation dryness index (TVDI) temporal and spatial variability was also studied at the sites. Additionally, transects of land surface temperature were carried out with Cimel Electronique CE312 6-band radiometers concurrently with thermal-infrared (TIR) satellite overpasses. In previous works, we studied the dependence of land surface emissivities on SM. The analysis of concurrent TIR and SM data make possible to evaluate the utility of the SMOS SM product to improve land surface emissivities and temperature determinations from satellite, giving an added value to the research

Health-related quality of life in well-differentiated metastatic gastroenteropancreatic neuroendocrine tumors

Spanish Neuroendocrine Tumor Group (GETNE)© 2015, Springer Science+Business Media New York. Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms capable of producing hormones. The development of new treatments has improved progression-free survival, albeit with increased toxicity. Health-related quality of life (HRQoL) has become an important endpoint in clinical research to evaluate patients’ well-being in such a contradictory scenario. In this review, we examine key reported outcomes across clinical studies exploring HRQoL in patients with GEP-NETs. We have conducted a review of the literature using PubMed, The Cochrane Library, EMBASE, and Google Scholar. Selection criteria for articles were (1) publication in English between 1995 and 2014, (2) patients with GEP-NET, and (3) analysis of HRQoL, including mental health and psychological symptoms. Forty-nine studies met the inclusion criteria (31 clinical trials, 14 observational studies, and 4 developments of NET-specific HRQoL instruments). The scope and nature of the literature was diverse with 27 instruments used to measure aspects of HRQoL. EORTC QLQ-C30 was the most frequently used, in 38 of the 49 studies. Standardized measures revealed that in spite of generally good HRQoL, GEP-NET patients have specific psychological and physical complaints. The clinical benefit of somatostatin analogs and sunitinib has been clearly supported by HRQoL assessment. Improvement in HRQoL scores or symptom relief over time was also reported in 14 trials of peptide receptor radionuclide therapy, however the absence of randomized studies obviate definitive conclusions. We have also identified several unanswered questions that should be addressed in further research concerning chemotherapy, everolimus, surgery, local ablative therapies, and chemoembolization. Future research should incorporate GEP-NET-specific HRQoL instruments into phase III trials. This review may help both clinicians and researchers to select the most appropriate tools to assess changes in HRQoL in this population.This project was funded in part by a restricted educational grant from Novartis Spain and by support from the Spanish Neuroendocrine Tumor Group (GETNE).Peer Reviewe

Is trivial the antiferromagnetic RP(2) model in four dimensions?

We study the antiferromagnetic RP(2) model in four dimensions. We find a second order transition with two order parameters, one ferromagnetic and the other antiferromagnetic. The antiferromagnetic sector has mean-field critical exponents and a renormalized coupling which goes to zero in the continuum limit. The exponents of the ferromagnetic channel are not the mean-field ones, but the difference can be interpreted as logarithmic corrections. We perform a detailed analysis of these corrections and conclude the triviality of the continuum limit of this model.Comment: 21 pages, 5 figures, LaTeX2

Monte Carlo flattening filter design to high energy intraoperative electron beam homogenization

[EN] Intraoperative radiotherapy using mobile linear accelerators is used for a wide variety of malignancies. However, when large fields are used in combination with high energies, a deterioration of the flatness dose profile is measured with respect to smaller fields and lower energies. Indeed, for the LIAC HWL of Sordina, this deterioration is observed for the 12 MeV beam combined with 10 cm (or larger) diameter applicator. Aimed to solve this problem, a flattening filter has been designed and validated evaluating the feasibility of its usage at the upper part of the applicator. The design of the filter was based on Monte Carlo simulations because of its accuracy in modeling components of clinical devices, among other purposes. The LIAC 10 cm diameter applicator was modeled and simulated independently by two different research groups using two different MC codes, reproducing the heterogeneity of the 12 MeV energy beam. Then, an iterative process of filter design was carried out. Finally, the MC designed conical filter with the optimal size and height to obtain the desired flattened beam was built in-house using a 3D printer. During the experimental validation of the applicator-filter, percentage depth dose, beam profiles, absolute and peripheral dose measurements were performed to demonstrate the effectiveness of the filter addition in the applicator. These measurements conclude that the beam has been flattened, from 5.9% with the standard configuration to 1.6% for the configuration with the filter, without significant increase of the peripheral dose. Consequently, the new filter-applicator LIAC configuration can be used also in a conventional surgery room. A reduction of 16% of the output dose and a reduction of 1.1 mm in the D50 of the percentage depth dose was measured with respect to the original configuration. This work is a proof-of-concept that demonstrates that it is possible to add a filter able to flatten the beam delivered by the Sordina LIAC HWL. Future studies will focus on more refined technical solutions fully compatible with the integrity of the applicator, including its sterilization, to be safely introduced in the clinical practice.The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Giuseppe Felici reports a relationship with S.I.T. Sordina IORT Technologies S.p.A. that includes: employment. We thank the professionals and facilities at the 3D printing and metrology department in the Mechanics Unit at IFIC. JV thanks I. Diaz for measuring the PLA density. We thank S.I.T. SORDINA IORT Tech-nologies SpA for providing the applicator used for testing the filter during the measurements. JV, FB, and JP would like to acknowledge the Spanish "Ministerio de Ciencia e Innovacion" (MCIN) grant PID2021-125096NB-I00 funded by MCIN/AEI/10.13039 and the "Generalitat Valenciana" (GVA) grant PROMETEO/2021/064.Oliver-Gil, S.; Vijande, J.; Tejedor-Aguilar, N.; Miró Herrero, R.; Rovira-Escutia, JJ.; Ballester, F.; Juste-Vidal, B.... (2023). Monte Carlo flattening filter design to high energy intraoperative electron beam homogenization. Radiation Physics and Chemistry. 212. https://doi.org/10.1016/j.radphyschem.2023.11110221

The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis

Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P = 1.34×10<sup>−8</sup>, OR = 1.22, CI 95% = 1.14–1.30; rs2004640: P = 4.60×10<sup>−7</sup>, OR = 0.84, CI 95% = 0.78–0.90; rs10488631: P = 7.53×10<sup>−20</sup>, OR = 1.63, CI 95% = 1.47–1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P = 9.04×10<sup>−22</sup>, OR = 1.75, CI 95% = 1.56–1.97) better explained the observed association (likelihood P-value = 1.48×10<sup>−4</sup>), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific

A comprehensive database for integrated analysis of omics data in autoimmune diseases

This work is partially funded by FEDER/Junta de Andalucia-Consejeria de Economia y Conocimiento (Grant CV20-36723), Consejeria de Salud (Grant PI-0173-2017) and by EU/EFPIA Innovative Medicines Initiative Joint Undertaking PRECISESADS (115565). JMM is partially funded by Ministerio de Economia, Industria y Competitividad. None of the funding bodies played any role in the design of the study and collection, analysis, and interpretation of data nor in writing the manuscript.Background: Autoimmune diseases are heterogeneous pathologies with difficult diagnosis and few therapeutic options. In the last decade, several omics studies have provided significant insights into the molecular mechanisms of these diseases. Nevertheless, data from different cohorts and pathologies are stored independently in public repositories and a unified resource is imperative to assist researchers in this field. Results: Here, we present Autoimmune Diseases Explorer (https:// adex. genyo. es), a database that integrates 82 curated transcriptomics and methylation studies covering 5609 samples for some of the most common autoimmune diseases. The database provides, in an easy-to-use environment, advanced data analysis and statistical methods for exploring omics datasets, including meta-analysis, differential expression or pathway analysis. Conclusions: This is the first omics database focused on autoimmune diseases. This resource incorporates homogeneously processed data to facilitate integrative analyses among studies.FEDER/Junta de Andalucia-Consejeria de Economia y Conocimiento CV20-36723Consejeria de Salud PI-0173-2017EU/EFPIA Innovative Medicines Initiative Joint Undertaking PRECISESADS 115565Ministerio de Economia, Industria y Competitivida

Sea surface emissivity observations at L-band: first results of the Wind and Salinity Experiment WISE 2000

Sea surface salinity can be measured by passive microwave remote sensing at L-band. In May 1999, the European Space Agency (ESA) selected the Soil Moisture and Ocean Salinity (SMOS) Earth Explorer Opportunity Mission to provide global coverage of soil moisture and ocean salinity. To determine the effect of wind on the sea surface emissivity, ESA sponsored the Wind and Salinity Experiment (WISE 2000). This paper describes the field campaign, the measurements acquired with emphasis in the radiometric measurements at L-band, their comparison with numerical models, and the implications for the remote sensing of sea salinity.Peer ReviewedPostprint (published version