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Protonic Ceramic Cells (PCCs) are a promising alternative to oxygen-ion conducting solid oxide cells (SOCs), offering benefits for hydrogen separation, electrolysis and fuel cell applications. The current development stage is focusing on the scale-up of the technology to cross the gap between single cells and stacks. The design of single repeating units (SRU) is the intermediate stage of the development. This work developed a numerical model for the 3D steady-state simulations of an SRU geometry designed for a circular, anode-supported PCC. The model has been applied to the simulation of fuel cell operation and has been calibrated using experimental data from the literature. The model is able to accurately reproduce experimental results obtained at 600 °C. The simulation platform developed can be also adapted to the simulation of electrolysis operation and can be applied to the optimization of the SRU geometry.

Biological specimens and environmental data collected by observers monitoring Japanese squid driftnet fishing operations during the summers of 1990 and 1991 in the central North Pacific (37°N-46°N, and 170°E-150°W) were used to explore habitat use patterns among three small cetacean species common to that area: the Dall’s porpoise (Phocoenoides dalli), Pacific white-sided dolphin (Lagenorhynchus obliquidens) and northern right whale dolphin (Lissodelphis borealis). Sex and maturity status were determined for 805 northern right whale dolphins, 421 Pacific white-sided dolphins and 206 Dall’s porpoises incidentally taken in 800 observed gillnet sets, allowing sub-taxon comparisons of habitat use patterns. Habitat variables were based on observer records of sea surface temperature (SST), wind velocity and direction, and swell height. Current velocity and direction and SST gradients were also derived. Canonical Correspondence Analysis (CCA) was used to relate the species categories to the habitat conditions recorded for the gillnet operations in which entanglements occurred. The samples collected from the southern, middle and northern latitudes within the overall study area were examined separately to account for northward movement of the fishing fleets across the summer months. SST was the most dominant and consistent feature; northern right whale dolphins occupied the warmest waters, Dall’s porpoises the coldest; Pacific white-sided dolphins were found in-between, but more similar to the latter. Wind velocity and swell height also reflected potentially important habitat features. Young-of-the-year northern right whale dolphin showed a preference for the warmest waters observed in the middle latitude band, coincident with that species summer calving mode.

BACKGROUND The benefit of an anterior mitral line (AML) in pa-tients with persistent atrial fibrillation (AF) and anterior atrial scar undergoing ablation has never been investigated. OBJECTIVE The purpose of this study was to evaluate the outcomes of AML in addition to standard treatment compared to standard treatment alone (no AML) in this subset of patients.METHODS Patients with persistent AF and anterior low-voltage zone (LVZ) treated with AML in 3 centers were retrospectively enrolled. The patients were matched in 1:1 fashion with patients having persistent AF and anterior LVZ who underwent conventional ablation in the same centers. Matching parameters were age, LVZ burden, and repeated ablation. Primary endpoint was AF/atrial tachycardia (AT) recurrence.RESULTS One hundred eight-six patients (age 66 +/- 9 years; 34% women) were selected and divided into 2 matched groups. Bidirec-tional conduction block was achieved in 95% of AML. After median follow-up of 2 years, AF/AT recurrence occurred in 29% of the patients in the AML group vs 48% in the no AML group (log-rank P = .024). On Cox regression multivariate analysis, left atrial vol-ume (hazard ratio [HR] 1.03; P = .006) and AML (HR 0.46; P = .003) were significantly associated with the primary endpoint. On univariate logistic regression, lower body mass index, older age, extensive anterior LVZ, and position of the left atrial activation breakthrough away from the AML were associated with first-pass AML block. CONCLUSION In this retrospective matched analysis of patients with persistent AF and anterior scar, AML in addition to standard treatment was associated with improved AF/AT-free survival compared to standard treatment alone.

Central giant cell granulomas (CGCG) are rare intraosseous osteolytic lesions of uncertain aetiology. Despite the benign nature of this neoplasia, the lesions can rapidly grow and become large, painful, invasive, and destructive. The identification of molecular drivers could help in the selection of targeted therapies for specific cases. TRPV4, KRAS and FGFR1 mutations have been associated with these lesions but no correlation between the mutations and patient features was observed so far. In this study, we analysed 17 CGCG cases of an Italian cohort and identified an interesting and significant (p=0.0021) correlation between FGFR1 mutations and age. In detail, FGFR1 mutations were observed frequently and exclusively in CGCG from young (18 years old) patients (4/5 lesions, 80%). Furthermore, the combination between ours and previously published data confirmed a significant difference in the frequency of FGFR1 mutations in CGCG from patients younger than 18 years at the time of diagnosis (9/23 lesions, 39%) when compared to older patients (1/31 lesions, 0.03%; p=0.0011), thus corroborating our observation in a cohort of 54 patients. FGFR1 variants in young CGCG patients could favour fast lesion growth, implying that they seek medical attention earlier. Our observation might help prioritise candidates for FGFR1 testing, thus opening treatment options with FGFR inhibitors.

Left bundle branch block (LBBB)-induced cardiomyopathy occurs in patients with long-standing LBBB. These patients characteristically exhibit hyperresponsiveness to cardiac resynchronization therapies (CRT). However, there is scarce information on their response to medical treatment. The aim of this study was to assess the change in left ventricular ejection fraction (LVEF) after a 3-month period following titration of guideline-directed medical therapy for heart failure.This retrospective analysis included all patients assessed in the heart failure unit of a Spanish University Hospital between 2020 and 2021, who presented with de novo ventricular dysfunction (LVEF40%) and had a history of long-standing LBBB with no other possible causes of cardiomyopathy.A total of 1497 patients were analyzed, of which 21 were finally eligible. Mean time from first diagnosis of LBBB to first consultation was 4.05± 4.1 years. Mean LVEF from first consultation to end of titration improved from 29.5±5.7% to 32.7±8.6% (P = .172), but none had recovered ventricular function at the end of follow-up. New York Heart Association functional class improved from 1.91±0.46 to 1.81±0.53 (P=.542). After CRT device implantation in 8 patients, LVEF improved by 14.5±3.5% (P=.003).Guideline-directed medical therapy seems to be ineffective in improving LVEF and functional class in patients with de novo heart failure and LBBB-induced cardiomyopathy. Based on a positive response to CRT on LVEF improvement, early CRT implantation could be a reasonable strategy for these patients.

En el marco de las acreditaciones de carreras de psicología en Argentina, y considerando entre otras cosas la diferencia de los tiempos reales de graduación contra los tiempos postulados en los planes de estudio, se decidió indagar sobre aspectos como la carga de lectura exigida al estudiantado y la cantidad de horas de cursada destinadas para cada curso. Para recopilar información al respecto, se administró una encuesta a estudiantes y docentes desde la Comisión de Carrera de la Facultad de Psicología y se realizaron estudios bibliométricos. El presente estudio es resultado de esa investigación.

We use the small scales of the Dark Energy Survey (DES) Year-3 cosmic shear measurements, which are excluded from the DES Year-3 cosmological analysis, to constrain the baryonic feedback. To model the baryonic feedback, we adopt a baryonic correction model and use the numerical package \texttt{Baccoemu} to accelerate the evaluation of the baryonic nonlinear matter power spectrum. We design our analysis pipeline to focus on the constraints of the baryonic suppression effects, utilizing the implication given by a principal component analysis on the Fisher forecasts. Our constraint on the baryonic effects can then be used to better model and ameliorate the effects of baryons in producing cosmological constraints from the next generation large-scale structure surveys. We detect the baryonic suppression on the cosmic shear measurements with a $\sim 2 \sigma$ significance. The characteristic halo mass for which half of the gas is ejected by baryonic feedback is constrained to be $M_c > 10^{13.2} h^{-1} M_{\odot}$ (95\% C.L.). The best-fit baryonic suppression is $\sim 5\%$ at $k=1.0 {\rm Mpc}\ h^{-1}$ and $\sim 15\%$ at $k=5.0 {\rm Mpc} \ h^{-1}$. Our findings are robust with respect to the assumptions about the cosmological parameters, specifics of the baryonic model, and intrinsic alignments., Comment: 20 pages, 10 figures. DES Collaboration, Year-3 analysis

M. Dixon et al., We use stacked spectra of the host galaxies of photometrically identified Type Ia supernovae (SNe Ia) from the Dark Energy Survey (DES) to search for correlations between Hubble diagram residuals and the spectral properties of the host galaxies. Utilizing full spectrum fitting techniques on stacked spectra binned by Hubble residual, we find no evidence for trends between Hubble residuals and properties of the host galaxies that rely on spectral absorption features (, MD would like to acknowledge support through an Australian Government Research Training Program Scholarship. This research was supported by the Australian Research Council The Centre of Excellence for Dark Matter Particle Physics (CDM; project number CE200100008) and the Australian Research Council Centre of Excellence for Gravitational Wave Discovery (OzGrav; project number CE170100004). This project/publication was made possible through the support of a grant from the John Templeton Foundation. The authors gratefully acknowledge this grant ID 61807, Two Standard Models Meet. The opinions expressed in this publication are those of the author(s) and do not necessarily reflect the views of the John Templeton Foundation. Funding for the DES Projects has been provided by the U.S. Department of Energy, the U.S. National Science Foundation, the Ministry of Science and Education of Spain, the Science and Technology Facilities Council of the United Kingdom, the Higher Education Funding Council for England, the National Center for Supercomputing Applications at the University of Illinois at Urbana-Champaign, the Kavli Institute of Cosmological Physics at the University of Chicago, the Center for Cosmology and Astro-Particle Physics at the Ohio State University, the Mitchell Institute for Fundamental Physics and Astronomy at Texas A&M University, Financiadora de Estudos e Projetos, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Conselho Nacional de Desenvolvimento Científico e Tecnológico and the Ministério da Ciência, Tecnologia e Inovação, the Deutsche Forschungsgemeinschaft, and the Collaborating Institutions in the Dark Energy Survey. The Collaborating Institutions are Argonne National Laboratory, the University of California at Santa Cruz, the University of Cambridge, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas-Madrid, the University of Chicago, University College London, the DES-Brazil Consortium, the University of Edinburgh, the Eidgenössische Technische Hochschule (ETH) Zürich, Fermi National Accelerator Laboratory, the University of Illinois at Urbana-Champaign, the Institut de Ciències de l’Espai (IEEC/CSIC), the Institut de Física d’Altes Energies, Lawrence Berkeley National Laboratory, the Ludwig-Maximilians Universität München and the associated Excellence Cluster Universe, the University of Michigan, NSF’s NOIRLab, the University of Nottingham, The Ohio State University, the University of Pennsylvania, the University of Portsmouth, SLAC National Accelerator Laboratory, Stanford University, the University of Sussex, Texas A&M University, and the OzDES Membership Consortium. Based in part on observations at Cerro Tololo Inter-American Observatory at NSF’s NOIRLab (NOIRLab Prop. ID 2012B-0001; PI: J. Frieman), which is managed by the Association of Universities for Research in Astronomy (AURA) under a cooperative agreement with the National Science Foundation. The DES data management system is supported by the National Science Foundation under Grant Numbers AST-1138766 and AST-1536171. The DES participants from Spanish institutions are partially supported by MICINN under grants ESP2017-89838, PGC2018-094773, PGC2018-102021, SEV-2016-0588, SEV-2016-0597, and MDM-2015-0509, some of which include ERDF funds from the European Union. IFAE is partially funded by the CERCA program of the Generalitat de Catalunya. Research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Program (FP7/2007-2013) including ERC grant agreements 240672, 291329, and 306478. We acknowledge support from the Brazilian Instituto Nacional de Ciência e Tecnologia (INCT) do e-Universo (CNPq grant 465376/2014-2). This manuscript has been authored by Fermi Research Alliance, LLC under Contract No. DE-AC02-07CH11359 with the U.S. Department of Energy, Office of Science, Office of High Energy Physics. Based on data acquired at the Anglo-Australian Telescope, under program A/2013B/012. We acknowledge the traditional custodians of the land on which the AAT stands, the Gamilaraay people, and pay our respects to elders past and present.

We evaluated the clinical and neurophysiological efficacy of rituximab (RTX) in a neurophysiologically homogeneous group of patients with monoclonal gammopathy and immunoglobulin M (IgM) anti-myelin-associated glycoprotein antibody (anti-MAG) demyelinating polyneuropathy.Twenty three anti-MAG-positive polyneuropathic patients were prospectively evaluated before and for 2 years after treatment with RTX 375 mg/msup2/sup. The Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale (INCAT-ds), modified INCAT sensory score (mISS), Medical Research Council sum score, Patients' Global Impression of Change scale were used, IgM levels were assessed and extensive electrophysiological examinations were performed before (T0) and 1 year (T1) and 2 years (T2) after RTX treatment.At T1 and T2 there was a significant reduction from T0 both in mISS and in INCAT-ds, with a p valuelt; 0.001 in the inferential Friedman's test overall analysis. Ulnar nerve Terminal Latency Index and distal motor latency significantly changed from T0 to T1 and in the overall analysis (p = 0.001 and p = 0.002), and ulnar nerve sensory nerve action potential (SNAP) amplitude was significantly increased at T2 from T1, with a p valuelt; 0.001 in the overall analysis. Analysis of the receiver-operating characteristic curves showed that a 41.8% increase in SNAP amplitude in the ulnar nerve at T2 from T0 was a fair predictor of a mISS reduction of ≥2 points (area under the curve 0.85; p = 0.005; sensitivity: 90.9%, specificity: 83.3%).This study suggests that RTX is effective in patients with clinically active demyelinating anti-MAG neuropathy over 2 years of follow-up, and that some neurophysiological variables might be useful for monitoring this efficacy.

PurposeThis study aims to empirically analyze a sound commitment and a consistent integration of sustainable development goals (SDGs) in the corporate reporting and management systems of companies that have a leading position in sustainability.Design/methodology/approachThe study applies a content analysis procedure based on a proposed analytical framework to codify the commitment and the SDG integration. In order to analyze the consistency of the integration, this study has provided a “SDG integration” score based on fuzzy inference systems methods. The companies in the sample have been identified as benchmarks in terms of sustainability in a specific region of Spain.FindingsThe findings show a lack of formality regarding the SDG commitment at the highest decision-making level and a low level of SDG integration in the reporting and management systems. These results are mainly explained because the most companies do not prioritize according to the materiality analysis and those SDGs more reported have not been deployed along targets and KPIs in a consistent way.Research limitations/implicationsThe results provide practical implications that help to overcome the limitations in terms of comparison and consistency of the SDGs-reported information. It also illustrates how the leading sustainable companies are doing the SDG reporting and suggests which elements could be improved to promote a consistent integration of the SDGs in the management systems.Originality/valueThis study provides new work lines in the promotion of an effective SDG-business reporting based on a robust management structure that allows an alignment among the SDG-business decisions based on a normative, strategic and operational approach.

Introducción: La contaminación del aire incrementaría el riesgo de infección respiratoria aguda (IRA) en pediatría. Objetivo: evaluar el impacto de la contaminación del aire en las consultas por IRA realizadas en efectores del Gobierno de la Ciudad de Buenos Aires. Método: estudio ecológico, de series temporales. Fuentes de información: Agencia de Protección Ambiental, Servicio Meteorológico Nacional e Historia de Salud Integral del Sistema de Gestión Hospitalaria. Población: Pacientes menores de 2 años que consultaron por IRA a un efector del GCBA y que residían en una comuna con monitoreo ambiental continuo, durante el 2018. Variables de predicción: Niveles diarios de CO, NO2, PM10 de las estaciones de monitoreo ambiental continuo de la Ciudad Autónoma de Buenos Aires. Variables de resultado: número de consultas totales y por IRA. Variables a controlar: efector, sexo y temperatura media. Se construyó una definición operativa para seleccionar en la base de datos a las consultas objeto de estudio. Resultados: Se registraron 80.287 consultas, 24.847 por IRA (30%). Las consultas por IRA tuvieron correlación positiva en la estación “Córdoba” con el N2O (RR: 1,13 [1,00-1,28]). El número de consultas por IRA en los meses fríos fue mayor que en los cálidos (19,9% vs 11,9%; RR:1,67 [1,61-1,72]).Conclusión: Los valores promedios de PM10 y N2O muestran correlación con el número de las consultas totales y por infección respiratoria aguda, respectivamente. Las consultas se incrementaron durante el invierno.

Antecedentes: el síndrome de trombocitopenia con aplasia de radio (TAR) es un desorden congénito con un patrón de herencia autosómico recesivo de prevalencia desconocida y que afecta a menos de 1 caso por cada 100.000 nacidos vivos sin diferencia entre sexos. Se caracteriza por ausencia de radio bilateral, presencia de pulgares y trombocitopenia. Además, puede estar asociado a diversas anomalías cráneo-faciales y en extremidades inferiores, al igual que a patologías cardiacas, urogenitales y gastrointestinales. Reporte de caso: paciente primigestante, a quien se le realiza diagnóstico in utero a la semana 19 de gestación de sospecha de síndrome TAR por hallazgos ecográficos (ausencia bilateral de radios), es referida para evaluación genética y se decide realizar cordocentesis a la semana 25 evidenciando trombocitopenia y anemia. Por alto riesgo de complicaciones fetoplacentarias se realiza manejo in-útero mediante transfusión de hemoderivados y controles prenatales estrictos. El embarazo es llevado a termino y se realiza cesárea en la semana 38 sin complicaciones durante la adaptación neonatal. Conclusiones: el síndrome TAR está asociado a un alto riesgo de mortalidad durante el periodo neonatal y el primer año de vida, por lo cual, un diagnóstico prenatal temprano es de gran importancia para permitir un tratamiento oportuno y mejorar la esperanza y la calidad de vida del recién nacido y sus padres.

The increase in the population of older adults and their more significant demand for health care in Paraguay requires a multidimensional evaluation to identify risks or deteriorating conditions. The objective of this research was to evaluate the health and nutrition status of a sample of older adults who attended the Geriatric Hospital of the Social Security for outpa-tient consultation. The research had a cross-sectional descriptive observational design, which included 108 older adults who underwent the Comprehensive Geriatric Assessment (CGA) and whose nutritional parameters were evaluated. Their average age was 71 years, with a predominance of females. According to their BMI, 64% were overweight or obese. As for the CGA, 18% presented a nutritional risk, 43% had mild dependence on activities of daily living and 12% on instrumental activities, 18% had a cognitive deficit, 6% had depression, and 30% had social risk. The population was characterized by a high prevalence of overweight and hypertension and a low frequency of risk of malnutrition. The most significant limitations were in the basic activities of daily life and social risk. Being female and being overweight were significantly associated with ba-sic functional limitations. This work was one of the first in the country on am-bulatory older adults, allowing the establishment of a baseline for areas where health is compromised or at risk of decline and the development of preventive strategies and actions to promote healthy aging.

Background: In patients with metastatic breast cancer (mBC), Circulating Tumor Cells (CTC) counts have a strong prognostic impact on progression free survival (PFS) and overall survival (OS). Changes 4 weeks after the start of a new line of therapy, inform on treatment efficacy. Despite improvements in systemic treatment, metastatic BC remains mainly uncurable with alteration of health-related quality of life (HRQOL) during the course of the disease. The aim of this work was to assess impact of clinical factors and biological factors as CTC on HRQOL. Methods: The French cohort COMET is a prospective study including first line HER2 negative patients receiving weekly paclitaxel and bevacizumab according to EMA approved combination. The aim of this cohort was to evaluate clinical, biological and radiological parameters associated with patients’ outcome (CTC, CEC, serum markers, ctDNA, pharmacogenomic polymorphisms, metabolomic parameters, visceral fat assessed by initial CTscan, serum estradiol level, and quality of life). HRQOL was assessed at baseline, at every cycle until progression and then every 3 months up to death using the EORTC QLQ-C30 questionnaire and its breast cancer specific module, the EORTC QLQ-BR23. Five dimensions of HRQOL were analyzed for the primary analyses: Global health status (GHS), physical functioning (PF), Emotional functioning (EF), fatigue (FA) and pain (PA). Time until definitive deterioration (TUDD) in HRQOL was defined as the interval between inclusion and the first decrease in HRQOL score ≥ 5 compared to baseline HRQOL score with no further improvement or in case of death. CTC counts were determined using the standard CellSearch system [Menarini Silicon Biosystems]. Results: Out of 510 patients included in COMET study, 432 patients with available HRQOL data were analyzed in this study. At baseline, patients reported a mean score for GHS of 57.6 (SD=22.7), for PF of 75.8 (23.2), for EF of 62.2 (25.8), for FA of 42.2 (29.60) and for PA of 38.1 (31.5). The Median TUDDs for the 5 targeted dimensions was 10.1 months [7.5-16.9] for GHS, 6.1 months [4.1-8.9] for PF, 21.6 [18.7-31.2] for EF, 10.8 [6.2-16.6] for FA and 13.6[10.1-22.5] months for PA. CTC counts were available in 261 patients at base line and in 229 patients after 4 weeks of treatment, before second cycle of chemotherapy. CTC high count was independent of main clinical and biological characteristics except lobular subtype. We confirmed the poor outcome of patients with high CTC count at base line and after one cycle of treatment with the threshold of > 4CTC/7.5 ml of blood. Out of the 5 dimensions of HRQOL, TUDD of EF was significantly correlated with a high CTC level at base line (p=0.0262) and even more with still an elevated count of CTC after one cycle of chemotherapy(p=0.0137). There was no association of CTC with the other dimensions of HRQOL. Conclusion: This is the first study ever reporting an analysis of QoL and CTC. We observed an association of high CTC count with one component of HRQOL scale. This suggests that CTC could be complementary to clinical factors that could influence HRQOL in HER2 negative metastatic BC treated with first line chemotherapy. Citation Format: Jean-Yves Pierga, Oumar Billa, Sandrine Dabakuyo, Jérôme Lemonnier, Frédérique Berger, Olivier Trédan, William Jacot, Anthony Gonçalves, Marc Debled, Christelle Levy, Christelle Jouannaud, Marie-Ange Mouret-Reynier, Jean-Marc Ferrero, Florence Dalenc, Fatima-Zohra Toumi, Franck Bonnetain, Francois-Clement Bidard, Shufang Renault. Circulating tumor cells enumeration and Health Related Quality of Life of patients treated with first-line chemotherapy for HER2 negative metastatic breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-24.

Background: High circulating tumor cell (CTC) count (CTChigh) is a strong adverse prognostic factor in patients with metastatic breast cancer (mBC). In the STIC CTC trial (NCT01710605), run before the introduction of CDK4/6 inhibitors for ER+/HER2- mBC, we showed that CTC count (CTC arm) was non inferior to clinician’s choice (standard arm) on progression-free survival (PFS) to guide first line treatment selection between chemotherapy (CT) and endocrine therapy (ET) (Bidard et al., JAMA Oncol 2021). Of note, patients who had treatment escalated from ET (a priori clinician choice) to CT in the CTC arm, had a significantly longer PFS. We report here overall survival (OS) results of this multicenter CTC clinical utility trial. Methods: In the CTC arm, N=377 patients had their treatment determined by baseline CTC count: CT if CTChigh (≥5 CTCs/7.5 mL, CellSearch®), ET if CTClow. In the standard arm (N=378 patients), the choice was left to the investigator: CT if clinical high risk (Clinhigh), ET if clinical low risk (Clinlow). Therefore, patients with discordant Clinlow/CTChigh or Clinhigh/CTClow profiles had their first line treatment escalated from ET (standard arm) to CT (CTC arm) or de-escalated from CT (standard arm) to ET (CTC arm), respectively. Patients with concordant Clinlow/CTClow and Clinhigh/CTChigh profiles received ET and CT in both arms, respectively. Results: Among 755 randomized patients, N=189 (25.0%) had a Clinlow/CTChigh profile, N=103 (13.6%) Clinhigh/CTClow, N=363 (48.2%) Clinlow/CTClow and N=100 (13.2%) Clinhigh/CTChigh. OS was analyzed after a median follow-up of 57 months and 382 events (50.6%). In the Clinlow/CTChigh subgroup, CT in the CTC arm led a longer OS (mOS: 51.8 months [43.3-NR]) than ET in the standard arm (35.4 months [30.4-45.4]; HR=0.53 [0.36-0.78], p=0.001). In patients Clinhigh/CTClow, no significant difference was observed whether they received CT (standard arm) or ET (CTC arm) (45.9 months [36.3-59.8] vs 49.4 months [35.4-65.4]; HR=0.88 [0.51-1.51], p=0.63). Pooling the two discordant groups (Clinlow/CTChigh or Clinhigh/CTClow), the CTC-driven strategy was superior to the clinician-driven treatment decision (HR=0.63 [0.46-0.86], p=0.02). Pooling all concordant and discordant groups together, a median OS of 45.5 (95%CI=[40.9-51.1]) and 51.3 months [46.8-55.1] was observed in the standard and CTC arms, respectively (HR=0.84 [0.69-1.03], p=0.10). Conclusions: Prognostic information brought by CTC or standard factors is discordant in 40% of patients with ER+ HER2- mBC. In case of a discordant estimate, the STIC CTC trial shows the superiority on OS of the CTC-driven treatment decision strategy. These results also suggest a possible clinical utility of CTC to adjust systemic treatment for mBC in second and later lines, after progression on CDK4/6 inhibitors. Funding:The study was funded by Institut Curie; the French National Cancer Institute (INCa), as part of the Programme de Soutien aux Techniques Innovantes Coûteuses 2011 (STIC 2011); and Menarini Silicon Biosystems (Castel Maggiore, Italy). Citation Format: Francois-Clement Bidard, Nicolas Kiavue, Catherine Alix-Panabières, Sylvain Dureau, Thomas Bachelot, Hugues Bourgeois, Anthony Gonçalves, Etienne Brain, Sylvain Ladoire, Florence Dalenc, Joseph Gligorov, Luis Teixeira, George Emile, Jean-Marc Ferrero, Delphine Loirat, Luc Cabel, Véronique Diéras, Frédérique Berger, William Jacot, Jean-Yves Pierga. GS3-09 Circulating Tumor Cells-driven choice of first line therapy for ER+ HER2- metastatic breast cancer: overall survival analysis of the randomized STIC CTC trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS3-09.

Introduction: Breast cancer (BC) during pregnancy (PrBC) is an uncommon malignancy characterized by a more aggressive clinical course compared to pregnancy-unrelated BC. Specific patterns of tumor-infiltrating lymphocytes (TILs) subpopulations have been observed in these patients, with significant prognostic roles. Previous studies demonstrated the varying histopathologic and prognostic profiles of PrBC by gestational age. However, the underlying immune landscape dynamics has never been investigated. Here, we sought to provide comprehensive insights into the association between gestational age at breast cancer diagnosis and tumor immune microenvironment (TIME) composition. Materials and Methods: A total of 110 PrBC were selected from our Institutional registry and categorized based on the trimester in which they were diagnosed. All cases were subjected to TILs profiling according to the International TILs Working Group recommendations. Immunohistochemistry for CD4, CD8, forkhead box P3 (FOXP3), and PD-L1 (clone 22C3) on a Dako Omnis platform was performed. Fisher’s and Chi-squared tests, multinomial logistic regression models, ROC curve, and survival analyses were performed. Results: The proportion of patients with high histologic grades incremented with the increase in gestational age (1st, n=24, 53%; 2nd, n=27, 69.2%; 3rd trimester, n=20, 87.0%; p=0.02). Neither breast cancer subtypes nor the hormone receptor (HR) and HER2 status changed significantly according to the pregnancy trimester. In HR+/HER2- subtype, the proportion of TILs+ tumors were higher in the early phases of pregnancy (1st, n=29, 100%; 2nd, n=17, 89.5%; 3rd trimester, n=9, 81.8%; p=0.04) imprinted by FOXP3 positivity where more FOXP3+ TILs were seen in the first months and decreased progressively (1st, n=10, 55.6%; 2nd, n=2, 11.8%; 3rd trimester, n=0, 0%; p< 0.01)). While in the triple negative breast cancer (TNBC) population, the proportion of PD-L1+ tumors (i.e. CPS>1) was significantly higher in the later stages of pregnancy (1st, n=2, 16.7%; 2nd, n=2, 18.2%; 3rd trimester, n=5, 71.4%; p=0.03). Patients who relapsed after a BC diagnosis during the 1st and 2nd trimesters lacked more frequently FOXP3+ and CD8+ cells, unlike those with no disease recurrence (n=21, 77.8% vs. n=17, 48.6%; p=0.02 and n=18, 66.7% vs. n=10, 28.6%; p< 0.01, respectively). Conclusions: TIME dynamics of PrBC are different according to the gestational age in both HR+ and TNBC PrBC. Our results suggest that immune tolerance events are likely to involve PrBC at later gestational age. Specific escape mechanisms (i.e., TILs and FOXP3 decrease in HR+ and PD-L1 expression in TNBC) might explain the aggressiveness of PrBC diagnosed during the later gestational age. Citation Format: Elham Sajjadi, Konstantinos Venetis, Mariia Ivanova, Marianna Noale, Concetta Blundo, Giovanna Scarfone, Eugenia Di Loreto, Stefano Ferrero, Stefania Maggi, Paolo Veronesi, Viviana Enrica Galimbreti, Giuseppe Viale, Fedro Alessandro A. Peccatori, Elena Guerini-Rocco, Nicola Fusco. The tumor immune microenvironment composition and prognostic value in breast cancer during pregnancy is dynamic during the gestation period [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-21-04.

Background: Advances in screening and treatment have led to increase in breast cancer (BC) survival in recent years but prognoses for metastatic BC remain poor with poorer outcomes as health-related quality of life (HRQOL). Treatment as bevacizumab and paclitaxel for metastatic BC, although that can increase time to progression of disease, often carry toxicity and is not curative but rather palliative in intent with the goal to improve or maintain HRQOL. The aim of this work was to assess impact of clinical factors such as disease progression, toxicity on HRQOL. Methods: COMET study is a multicenter prospective single-arm cohort study in France whose main objective was to identify biological factor that could predict the clinical benefit of bevacizumab-paclitaxel combination therapy as first treatment in HER2 negative metastatic BC. HRQOL was assessed at baseline, at every cycle (every for 4 weeks) until progression and then every 3 months up to death using the EORTC QLQ-C30 questionnaire and its BC specific module, the EORTC QLQ-BR23. In this ancillary study, we targeted 5 dimensions HRQOL for the primary analyses: Global health status (GHS), physical functioning (PF), Emotional functioning (EF), fatigue (FA) and pain (PA). The primary endpoint was time until definitive deterioration (TUDD) in HRQOL scales that defined as time between inclusion and the first decrease HRQOL score ≥ 5 points compared to baseline score, with no further improvement of at least 5 points. Multivariable Cox model with time dependent covariate was performed to assess clinical factors associated with TUDD for each of the 5 target dimensions HRQOL. We performed 3 models for each dimension: model 1 including all covariate with p< 0.10 in univariable; model 2 including model 1 and adjusted on cancer subtype and model 3 included model 1 stratified by cancer subtype. P value < 0.01 were considered statistically significant. Results: Out of 510 patients included in COMET study, 432 patients with available HRQOL data were analyzed in this study. Median age at inclusion was 58 years (range: 29-83), and 24.4% of patients had triple negative tumor subtype. About 79 % of cancers were invasive ductal carcinoma and 43 % patients had least 3 metastasis sites at baseline. At baseline, patients reported a mean score for GHS of 57.6 (SD=22.7), for PF of 75.8 (23.2), for EF of 62.2 (25.8), for FA of 42.2 (29.60) and for PA of 38.1 (31.5). The Median TUDDs for the 5 targeted dimensions was 10.1 months [7.5-16.9] for GHS, 6.1 months [4.1-8.9] for PF, 21.6 [18.7-31.2] for EF, 10.8 [6.2-16.6] for FA and 13.6[10.1-22.5] months for PA. In multivariable analyses, Disease Progression was associated with TUDD of GHS (HR [99%CI] =2.4 [1.2-4.9] and TUDD of PF (2.1 [1.1-3.7]). After adjusted on cancer subtype, association persisted with TUDD of GHS (p=0.009). Performance Status was associated with TUDD of PF (1.6 [1.2-2.3]), and TUDD of Pain (1.6 [1.1-2.3]). Performance Status association with TUDD of PF continued after adjustment on cancer subtype (p=0.0003). Prior endocrine therapy was associated with TUDD of pain in patients with tumor with positive hormone receptor (HR+) (2.4 [1.2-4.7]). There was no factor associated with TUDD of EF and TUDD of FA. Conclusion: Results of this study have shown that among the 5 targeted dimensions HRQOL, Physical Functioning was deteriorated in the shortest time. Disease progression, base line performance status and prior endocrine therapy for HR+ subtype, are clinical factors that could influence HRQOL in HER2 negative metastatic BC treated with first line chemotherapy. Citation Format: Oumar Billa, Sandrine Dabakuyo, Marion Chevrier, Franck Bonnetain, Isabelle Desmoulins, William Jacot, Olivier Trédan, Marc Debled, Christelle Levy, Anthony Gonçalves, Jean-Marc Ferrero, Florence Dalenc, Christelle Jouannaud, Marie-Ange Mouret-Reynier, Mireille Mousseau, Julien Grenier, Jean-Philippe Jacquin, Fatima-Zohra Toumi, Frédérique Berger, Jérôme Lemonnier, Jean-Yves Pierga. Health related quality of life of patients treated with bevacizumab and paclitaxel as first-line treatment for HER2 negative metastatic breast cancer: impact of clinical factors [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-54.

Background: Residual disease (RD) following neoadjuvant chemotherapy (NAC) in early HER2-negative breast cancer (BC) remains an unmet medical need. However, no therapies to date have tested their activity directly in chemo-resistant RD. Here, we hypothesized that combining an oncolytic virus such as T-VEC with atezolizumab may offer clinical benefit in patients (pts) with RD after standard NAC. To our knowledge, PROMETEO is the first trial that examines the activity of immunotherapy in pts with RD prior to surgery. Methods: PROMETEO (NCT03802604) is a single-arm, open-label, multicenter phase II trial. Women with triple-negative BC (TNBC) or hormone receptor-positive/HER2-negative (HR+/HER2-) BC with baseline (i.e., before NAC) ki67 ≥ 20% were eligible. RD was confirmed with a magnetic resonance imaging (MRI) showing a tumor diameter ≥ 10 mm and a core-biopsy detecting the presence of invasive cells. Before surgery, T-VEC was administered intratumorally on week 1 (106 pfu/mL), then in week 4 and every 2 weeks thereafter (108 pfu/mL) for 4 injections. Atezolizumab (840 mg) was administered intravenously every 2 weeks for 4 infusions, starting at week 4. Surgery was performed in < 3 weeks after completing the treatment. The primary objective was to evaluate the efficacy of the combination, measured by the rate of residual cancer burden (RCB) class 0/1 at surgery. Tumor samples collected at 5 timepoints (before NAC, during screening period, after first dose of T-VEC, after first dose of T-VEC and atezolizumab and at surgery) were mandatory to assess gene expression, tumor-infiltrating lymphocytes (TILs), immune cells PD-L1 IHC (SP142), tumor mutational burden (TMB) by FoundationOne and other translational endpoints. Results: Between Dec 2018 to Feb 2022, 28 pts were enrolled: 20 pts with HR+/HER2- disease and 8 pts with TNBC. Median age was 47 (range 31-71) and 71% of pts were premenopausal. At diagnosis before NAC, clinical stage II disease represented 60.7%, cN+ 60.7%, median Ki-67 was 37.5% (range 20%-95%), high TILs (≥10%) 37%, median TMB was 3 (0-19) and only 1 of 27 pts (3.7%) had a PD-L1-positive tumor. After NAC, mean tumor size by MRI was 28.3 mm (10-93). Two pts discontinued from the trial (1 withdrawal of consent and 1 COVID infection). The completion of 5 cycles of treatment was achieved by 73% of pts. The overall RCB-0/1 rate was 25% (7 of 28, 95% IC 10.7 – 44.9%), all with RCB 0 (pathologic complete response [pCR]). The pCR rate was 30% in HR+/HER2- disease and 12.5 % in TNBC. Radiological response by MRI was achieved by 3 of 28 pts (10.7%). Interestingly, none of the 7 pts with a pCR had radiological response (stable disease n=5, progressive disease [PD] n=2). Six pts (21.4%) had radiological PD and had RCB 2/3. Overall, 27 (96%) patients had at least one treatment-emergent adverse event (TEAE) of any grade. Most common grade 1 or 2 AEs were fever (11 pts, 39.3%), ALT increased (9 pts, 32.1%), AST increased (8 pts, 28.6%), arthralgia (6 pts, 21.4%) and anemia (6 pts, 21.4%). Grade 3 reversible neutropenia occurred in 1 patient. Across all pts, significant increases (p< 0.001) in TILs, immune genes and immune PDL1+ cells were observed after 1 dose of TVEC, 1 dose of the combination and at surgery. Intrinsic subtype changes at surgery occurred in 73.1% of cases, mostly (46.1%) Luminal A/B converting to Normal-like. At surgery, 19 of 26 (73.1%) of tumors were PDL1+. Conclusions: Two months of T-VEC in combination with atezolizumab induced a pCR in a subgroup of pts with chemoresistant HER2- breast cancer. This effect is probably related to the immune activation provoked by the combined treatment. Interestingly, a high discrepancy was observed between the pre-surgical radiological imaging and the actual surgical pathological report. Pre-operative window-of-opportunity trials in this context might provide important clues regarding the activity of novel treatment strategies. Citation Format: Tomás Pascual, Maria Vidal, Juan Miguel Cejalvo, Estela Vega, Esther Sanfeliu, Sergi Ganau, Ana Julve, Esther Zamora, Ignacio Miranda, Ana Delgado, Begoña Bermejo, Luis de la Cruz-Merino, Manel Juan, Patricia Galván, Xavier Gonzalez-Farré, Juan Manuel Ferrero-Cafiero, Patricia Villagrasa, Mafalda Oliveira, Aleix Prat. PD11-04 Primary results of SOLTI-1503 PROMETEO phase 2 trial of Combination of Talimogene Laherparepvec (T-VEC) with Atezolizumab in patients with residual breast cancer after standard neoadjuvant multi-agent chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD11-04.

We characterise the properties and evolution of Bright Central Galaxies (BCGs) and the surrounding intracluster light (ICL) in galaxy clusters identified in overlapping regions of the Dark Energy Survey and Atacama Cosmology Telescope Survey (DES-ACT), covering the redshift range $0.20$14.4. We also measure the stellar mass - halo mass (SMHM) relation for the BCG+ICL system and find that the slope, $\beta$, which characterises the dependence of $M_{\rm 200m,SZ}$ on the BCG+ICL stellar mass, increases with radius. The outskirts are more strongly correlated with the halo than the core, which supports that the BCG+ICL system follows a two-phase growth, where recent growth ($z, Comment: 19 pages, 12 Figures, 3 Tables. Submitted to MNRAS on 9/7/2022 -- Metadata typo corrected

En los Estudios del Discurso y la Lingüística Textual, el informe se investiga en familias de géneros distintas según el contexto de producción: por ejemplo, en la de géneros evaluativos entre pares (Bosio, 2005; Sabaj et al., 2018), géneros escolares informativos (Rose y Martin, 2012/2018) o expositivos académicos en los estudios de pregrado, con límites difusos con otros géneros (cfr. la monografía, Moris y Pérez, 2014; Sologuren, 2020). Analizamos en un corpus de 30 informes de estudiantes de pregrado (10 de estudiantes de Lenguas Aplicadas, 10 de Traducción y 10 de Biomedicina) los recursos lingüístico-discursivos usados para implicarse discursivamente (Hyland y Sancho Guinda, 2012), valorar la información presentada (Martin y White, 2005) y dialogar con la comunidad académica (Gil-Salom y Soler-Monreal, 2014). Los resultados muestran que la voz del autor se manifiesta con recursos tentativos que requieren ser auto y coevaluados por los aprendices en cada disciplina particular.

La Biblioteca Central de Ciudad Universitaria es, sin lugar a dudas, uno de los edificios más emblemáticos del conjunto urbano arquitectónico edificado, hace 70 años e inscrito en la lista de Patrimonio Mundial hace 15 años. Este inmueble, en conjunto con el mosaico de piedras naturales que recubre sus cuatro fachadas exteriores, constituye un importante ejemplo de arquitectura moderna e integración plástica en México y es una de las obras más representativas de su autor, el arquitecto, pintor y muralista Juan O’Gorman.

En este artículo se analizan los adjetivos que se utilizanen los inventarios para caracterizar a los animales preferentementepor su color, pero también por otros rasgos como el tipo de cuernos,en el caso del ganado bovino; o la edad. Todos los términos que aquíse analizan están documentados en corpus formados por relacionesde bienes materiales (testamentos, cartas de dote, repartos de herencias,etc.) procedentes del Archivo Histórico Provincial de León,pertenecientes al Partido Judicial de La Bañeza, localizado en lazona suroccidental de la provincia de León y una parte noroccidentalde la provincia de Zamora. Estos documentos están fechados enel siglo XVIII, última parte del siglo XVII y principios del siglo XIX.