A new role of the Rac-GAP β2-chimaerin in cell adhesion reveals opposite functions in breast cancer initiation and tumor progression

β2-chimaerin is a Rac1-specific negative regulator and a candidate tumor suppressor in breast cancer but its precise function in mammary tumorigenesis in vivo is unknown. Here, we study for the first time the role of β2-chimaerin in breast cancer using a mouse model and describe an unforeseen role for this protein in epithelial cell-cell adhesion. We demonstrate that expression of β2-chimaerin in breast cancer epithelial cells reduces E-cadherin protein levels, thus loosening cell-cell contacts. In vivo, genetic ablation of β2-chimaerin in the MMTV-Neu/ErbB2 mice accelerates tumor onset, but delays tumor progression. Finally, analysis of clinical databases revealed an inverse correlation between β2-chimaerin and E-cadherin gene expressions in Her2+ breast tumors. Furthermore, breast cancer patients with low β2-chimaerin expression have reduced relapse free survival but develop metastasis at similar times. Overall, our data redefine the role of β2-chimaerin as tumor suppressor and provide the first in vivo evidence of a dual function in breast cancer, suppressing tumor initiation but favoring tumor progression

Characterization of plasmid-mediated beta-lactamases in fecal colonizing patients in the hospital and community setting in Spain

Aim: Active surveillance of plasmid-mediated ß-lactamase-producing Enterobacteriaceae (PMBL-E) in fecal carriers in the hospital and in the community setting in a non-outbreak period of time. Methods: Patients were screened for carriage of Enterobacteriaceae resistant to expanded-spectrum cephalosporins and PMBL-E were characterized (extended-spectrum-ß-lactamase [ESBL], plasmid-mediated AmpC ß-lactamase [pAmpC], and carbapenemases) by PCR and sequencing. Results: The prevalence of ESBL and pAmpC carriers was 5.06% and 0.59%, respectively. Overall, CTX-M-like enzymes were the ESBL dominate enzymes (96.15%). The group CTX-M-9 was the most prevalent (81, 54%) [CTX-M-14 (74, 91.35%), CTX-M-9 (5, 6.17%), CTX-M-24 (1, 1.23%), and CTX-M-27 (1, 1.23%)] followed by the group CTX-M-1 (64, 42.67%) [CTX-M-15 (42, 65.63%), CTX-M-1 (13, 20.31%), CTX-M-32 (8, 12.5%), and CTX-M-3 (1, 1.56%)]. One CTX-M-10, one CTX-M-59, and three CTX-M-8 were also found. A very small representation of SHV or TEM ESBL enzymes was found (3.2% and 0.64%, respectively). pAmpC characterization revealed a predominance of CMY-2 (81.25%), followed by DHA-1 (18.75%). We did not detect the presence of carbapenemase producers. Conclusions: The prevalence of ESBL-producers from fecal carriers is stable in our area, but colonization by pAmpC producers has emerged recently as we have confirmed. Periodic active surveillance is useful to identify these human reservoirs and control the evolution of PMBL carriage in a community over time

COST 733 - WG4: Applications of weather type classification

The main objective of the COST Action 733 is to achieve a general numerical method for assessing, comparing and classifying typical weather situations in the European regions. To accomplish this goal, different workgroups are established, each with their specific aims: WG1: Existing methods and applications (finished); WG2: Implementation and development of weather types classification methods; WG3: Comparison of selected weather types classifications; WG4: Testing methods for various applications. The main task of Workgroup 4 (WG4) in COST 733 implies the testing of the selected weather type methods for various classifications. In more detail, WG4 focuses on the following topics:• Selection of dedicated applications (using results from WG1), • Performance of the selected applications using available weather types provided by WG2, • Intercomparison of the application results as a results of different methods • Final assessment of the results and uncertainties, • Presentation and release of results to the other WGs and external interested • Recommend specifications for a new (common) method WG2 Introduction In order to address these specific aims, various applications are selected and WG4 is divided in subgroups accordingly: 1.Air quality 2. Hydrology (& Climatological mapping) 3. Forest fires 4. Climate change and variability 5. Risks and hazards Simultaneously, the special attention is paid to the several wide topics concerning some other COST Actions such as: phenology (COST725), biometeorology (COST730), agriculture (COST 734) and mesoscale modelling and air pollution (COST728). Sub-groups are established to find advantages and disadvantages of different classification methods for different applications. Focus is given to data requirements, spatial and temporal scale, domain area, specifi

Benzotrithiophenes vs. Benzo/Naptha-dithiophenes: The Effect of Star-Shaped versus Linear Conjugation on Their Electronic Structures

Star-shaped complexes of π-conjugated chromophores are currently of great interest for use in optoelectronic devices.1 Recently, different planar central cores involving three thiophene rings fused to a benzenic ring (BTTs) have been described. In these systems, the coplanarity and extended π-conjugation of the BTT skeleton should promote intermolecular π-stacking, which would induce strong aggregation and enhanced packing in the solid state of BTT-containing molecules. We propose here the study of a BTT conjugated system with DPPT fragments, in which three DPP2T units are linked to a central rigid trithienobenzene core. Comparison with homologous linear systems, based on the benzodithiophene (BDT) unit and the naphtodithiophene (NDT) unit,2 will be carried out in order to elucidate the effect of star-shaped configuration versus linear conformation on the optical and electrical properties.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Progress in Detection and Projection of Climate Change in Spain since the 2010 CLIVAR-Spain regional climate change assessment report

The Iberian Peninsula region offers a challenging benchmark for climate variability studies for several reasons. It exhibits a wide variety of climatic regimes, ranging from wet Atlantic climates with annual precipitation around 2000 mm, to extensive semiarid regions with severe hydrological stress, to even cold alpine environments in some isolated areas

Analisis de las respuestas moleculares profundas alcanzadas por las multiples secuencias de tratamientos con ITKS en LMC. Estudio de largo seguimiento del registro español de LMC

Poster [PC-231] Introducción: Cinco inhibidores de tirosina cinasa (ITKs) están disponibles para el tratamiento de pacientes con leucemia mieloide crónica en fase crónica (LMC-FC). Analizamos las diferentes secuencias de ITKs utilizadas como terapia para la LMC-FC en un análisis a largo plazo en vida real. Métodos: En un análisis retrospectivo de cohortes, se incluyeron pacientes con LMC-FC tratados en la práctica clínica con diferentes ITKs en el Registro Español de LMC (RELMC) (17 hospitales de todo el país) entre 2000 y 2014. El objetivo principal del estudio fue describir la secuencia del tratamiento con ITKs en la práctica de la vida real y la última respuesta molecular profunda (DMR) (MR4, MR4.5 o transcrito indetectable) para cada esquema. Resultados: Nuestro análisis incluyó 862 pacientes con LMC en 1º FC tratados con ITKs en 1ª línea o después de interferón alfa. Datos demográficos demográficos: 517 H, 345 M, mediana de edad: 52 años (14-94a). Distribución del Índice Sokal (bajo 49% Inter 38% Alto 13%), Índice EURO (bajo 50% Inter 45% Alto 5%), Índice EUTOS (bajo 93% Alto 7%), Índice LT-EUTOS (bajo 68 % Inter 25% Alto 7%). Esquemas de tratamiento: la Tabla 1 resume todos los esquemas utilizados y la última respuesta molecular. Los pacientes se dividieron en 4 grupos según el tratamiento con ITKs. Grupo 1: solo tratados con Imatinib 394 p (45, 7%) Grupo 2: Imatinib y luego 2ºGITKs debido a intolerancia o fallo 170 p (19, 7%) (12 esquemas de tratamiento secuenciales diferentes con ITKs) Grupo 3: 2ºGITKs en 1ª línea 91 p (13 esquemas secuenciales) (10, 5%) Grupo 4: Interferón alfa y luego ITKs 207 p (24%) (9 esquemas secuenciales). La Figura 1 resume la evolución de diferentes tratamientos alrededor de los 14 años. Última respuesta molecular profunda: con una mediana de seguimiento de 82 meses (1-351 m) desde el diagnóstico, 77 m (1-311 m) desde el primer tratamiento y 70 m (1-191 m) desde el primer tratamiento con ITK. Las tasas de respuesta molecular profunda para cada grupo fueron (G1: DMR 65% MMR 13% No MMR 15%, G2: DMR 46% MMR 24% No MMR 17%, G3: DMR 62% MMR 13% No MMR 12%, G4: DMR 53% MMR 17% No MMR 18%). Supervivencia a largo plazo (SLP o SG): no se encontraron diferencias estadísticas entre los grupos de tratamiento, ya sea desde el diagnóstico, el primer tratamiento o el primer ITK. Alcanzar una respuesta profunda garantiza mejores resultados. Variables predictivas de respuesta: los índices SOKAL, EUTOS, EURO y LT-EUTOS continúan siendo útiles para predecir el resultado a largo plazo. Conclusiones: En el contexto de un registro multicéntrico basado en hospitales, el tratamiento con ITKs es muy variable, con un gran número de secuencias diferentes de ITKs. Con una mediana de seguimiento de 7 años la tasa de respuesta molecular profunda es aproximadamente del 60% en pacientes tratados con imatinib y que no necesitan cambio de ITKs, y en aquellos tratados en 1º línea con 2ºGITKs(a pesar de su corto seguimiento), pero parece menor en pacientes tratados con imatinib que necesitan cambiar a 2ºGITKs. Los resultados de supervivencia fueron similares para todos los grupos

Results of an early access treatment protocol of daratumumab monotherapy in spanish patients with relapsed or refractory multiple myeloma

Daratumumab is a human CD38-targeted monoclonal antibody approved as monotherapy for heavily pretreated relapsed and refractory multiple myeloma. We report findings for the Spanish cohort of an open-label treatment protocol that provided early access to daratumumab monotherapy and collected safety and patient-reported outcomes data for patients with relapsed or refractory multiple myeloma. At 15 centers across Spain, intravenous daratumumab (16mg/kg) was administered to 73 patients who had ≥3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, or who were double refractory to both. The median duration of daratumumab treatment was 3.3 (range: 0.03–13.17) months, with a median number of 12 (range: 1–25) infusions. Grade 3/4 treatment-emergent adverse events were reported in 74% of patients and included lymphopenia (28.8%), thrombocytopenia (27.4%), neutropenia (21.9%), leukopenia (19.2%), and anemia (15.1%). Common (>5%) serious treatmentemergent adverse events included respiratory tract infection (9.6%), general physical health deterioration (6.8%), and back pain (5.5%). Infusion-related reactions occurred in 45% of patients. The median change from baseline in all domains of the EQ-5D-5L and EORTC QLQ-C30 was mostly 0. A total of 18 (24.7%) patients achieved a partial response or better, with 10 (13.7%) patients achieving a very good partial response or better. Median progression-free survival was 3.98 months. The results of this early access treatment protocol are consistent with previously reported trials of daratumumab monotherapy and confirm its safety and antitumoral efficacy in Spanish patients with heavily treated relapsed or refractory multiple myeloma

Multiple myeloma and SARS-CoV-2 infection : clinical characteristics and prognostic factors of inpatient mortality

There is limited information on the characteristics, prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with COVID-19. This retrospective case series investigated 167 patients reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in March and April, 2020. Outcomes were compared with 167 randomly selected, contemporary, age-/sex-matched noncancer patients with COVID-19 admitted at six participating hospitals. Among MM and noncancer patients, median age was 71 years, and 57% of patients were male; 75 and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity was moderate-severe in 77 and 89% of patients and critical in 8 and 4%, respectively. Supplemental oxygen was required by 47 and 55% of MM and noncancer patients, respectively, and 21%/9% vs 8%/6% required noninvasive/invasive ventilation. Inpatient mortality was 34 and 23% in MM and noncancer patients, respectively. Among MM patients, inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM at hospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independent prognostic factors on adjusted multivariate analysis. This case series demonstrates the increased risk and identifies predictors of inpatient mortality among MM patients hospitalized with COVID-19

Hadron Energy Reconstruction for the ATLAS Calorimetry in the Framework of the Non-parametrical Method

This paper discusses hadron energy reconstruction for the ATLAS barrel prototype combined calorimeter (consisting of a lead-liquid argon electromagnetic part and an iron-scintillator hadronic part) in the framework of the non-parametrical method. The non-parametrical method utilizes only the known $e/h$ ratios and the electron calibration constants and does not require the determination of any parameters by a minimization technique. Thus, this technique lends itself to an easy use in a first level trigger. The reconstructed mean values of the hadron energies are within $\pm 1$ of the true values and the fractional energy resolution is $[(58\pm3)/\sqrt{E}+(2.5\pm0.3)$. The value of the $e/h$ ratio obtained for the electromagnetic compartment of the combined calorimeter is $1.74\pm0.04$ and agrees with the prediction that $e/h > 1.7$ for this electromagnetic calorimeter. Results of a study of the longitudinal hadronic shower development are also presented. The data have been taken in the H8 beam line of the CERN SPS using pions of energies from 10 to 300 GeV.Comment: 33 pages, 13 figures, Will be published in NIM