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Fishery Discards are one of the most important topics in fisheries management. Nowadays, there is a social agreement that perceives discards as very negative and that solutions have to be implemented in order to avoid the purposeless waste of these valuable biomass. It is a fact that any fishing operation has an unavoidable percentage of discards, from long-liners (2-10%) to trawlers (up to 90%). Sustainability is therefore a basic premise for the economic and social future of European fisheries and the key objective of the reform of the Common Fisheries Policy. With the entry into force of the new measures of the CFP, and in the case of successfully implementation of LIFE iSEAS, it is foreseeable that the quantity of biomass previously referred as discards available in land will be lower. Therefore, a balance/complement of this raw material supplied to developed in-land facilities with other products available in-land would be required. In this framework, the main objective of LIFE iSEAS is to demonstrate that a sustainable scenario (in terms of biological and socioeconomic indicators) of the European Fisheries is possible through the enhancement of the real application on the fishing sector of existent knowledge and innovative solutions on discards reduction and management. According to this objective, the aims of this project are: 1. To test the implementation and performance of the iObserver on board oceanographic vessels. 2. To optimize the fishing activity through the definition of a reliable tool based on mathematical models that analyze the spatio-temporal conditions of considered fishing areas. This tool will help: 2a) to take real time decisions over fishing activity, defining more appropriate areas/periods/species in terms of lower discard levels, and to develop effective short-time policies over marine resources/fishing areas that guarantee the stocks populations while maximizing the yield of the fishing activity. 2b) to perform more selective fishing, saving fuel and on-board caught processing times. 3. To define a real fully operative in-land demonstration facility for discards valorization processes and trade named iDPV (Integral Discards Processing and Valorization Point). 4. To demonstrate the environmental and socio-economic impacts/benefits that the implementation of proposed innovative solutions and the new management model will have in the fishing sector.

Background: The RegistEM is a non-interventional cohort study enrolling 1,867 patients (pts) (males or females) with advanced breast cancer diagnosed from January 2016 to December 2019, either after recurrence or as first diagnosis, in 38 Spanish sites. Triple negative BC (TNBC) is clinically defined based on lack of expression of both estrogen and progesterone receptors, and HER2 overexpression, and constitutes approximately 16% of BC cases. It is a particularly proliferative and aggressive BC subtype characterized by higher rates of relapse, greater metastatic potential, and shorter overall survival compared with other BC subtypes. Recent studies have shown hormone receptor status can change from the primary (P) to the recurrence tumor (M) in a proportion of cases, inducing a switch to TNBC in the recurrence, while other remains TNBC both in the P and M setting. This feature might impact survival and treatment options. Methods: We selected TNBC pts from the RegistEM study with ctDNA plasma samples available from the relapse. TNBC pts were classified into 2 groups according to clinical subtype (CS): 1) CS-converted (CS-C), with a discordant phenotype (TN subtype in M but not in P); and 2) CS-non-converted (CS-NC), with TN phenotype in P and M. To compare the mutation profiles of the 2 groups, next-generation sequencing (NGS) was performed using the AVENIO Expanded ctDNA Analysis Kit (Roche Sequencing Solutions, Inc; 77 genes; SNPs, indels, fusions and CNVs). Genomics alterations at individual level and grouped by pathway were explored for pathogenic and probably pathogenics variants. Genomics findings were correlated with clinicopathological data and outcomes, in terms of progression-free survival (PFS) and response to first line chemotherapy treatment. Kaplan-Meier estimator and Cox regression model were used to analyze PFS, and Fisher’s test to analyze contingency tables. Bonferroni correction was used for multiple testing. Results: NGS data was available from 32 (17%) TNBC pts; 22 (69%) pts CS-NC and 10 (31%) CS-C. The time from diagnosis to relapse was 29.2 months (m) for CS-NC and 60.2m for CS-C (HR=4.81, 95% confidence interval (CI) (1.59-14.59), p=0.0055; adjusted for confounders: menopausal status, grade, stage). In the metastatic setting, CS-NC had similar PFS than CS-C (8.3m CS-C vs 5.3m CS-NC; HR=1.63, 95% CI (0.71-3.72), p=0.2442). A median of 3 genomic alterations were found, similar in both groups. The most frequent somatic alterations were TP53 (50%), MAP2K1 (25%) and APC (25%). CS-C were enriched for MAP2K1 (60% vs. 9% in CS-NC; p=0.0243). No single genomic alteration was associated with outcome. Forty-percent of tumors harbored at least 1 mutation in PI3K-AKT-mTOR pathway (PIK3CA, PIK3R1, AKT1, AKT2, PTEN or MTOR genes), with similar incidence between CS-NC and CS-C. Pts with an altered PI3K-AKT-mTOR pathway had poor PFS (3.9m mutant vs 6.7m wild-type (WT); HR=3.02, 95% CI (1.4-6.56), p=0.0033) and a trend to worse response (complete or parcial response and stable disease: 23% mutant vs 77% WT, p=0.1581). CS-C tumors presented an altered MAPK-ERK pathway (mutations in KRAS, NRAS, BRAF, MAP2K1 or RAF1 genes) more frequently in comparison to CS-NC (60% vs 23%, p=0.0557), with no differences in response or PFS. Finally tumors with a high mutation allele frequency (≥mean) showed poor PFS (HR=3.64, 95% CI (1.52-8.75), p=0.0038). Conclusion: Analysis of ctDNA reveals diverse mutational spectrum in metastatic TNBC, suggesting that the presence of PI3K-AKT-mTOR pathway alterations associates with worse outcome and poor response to standard therapies. The clinical subtype conversions from luminal primary tumor are enriched in MAPK-ERK pathway alterations. Citation Format: Angel Guerrero-Zotano, Carlos Jara, Sara López-Tarruella, César A Rodríguez, Encarna Adrover, Catalina Falo, Purificación Martínez, Silvia Antolín, Mireia Margeli, Josefina Cruz, Alvaro Rodríguez-Lescure, Vega Iranzo, César Gómez-Raposo, Jose Juan Illarramendi, Diego Malón, Jose Luis Alonso, Antonio Antón, Raquel Andrés, Jesús Herranz, Susana Bezares, Rosalía Caballero, Isabel Álvarez, Federico Rojo. Mutational profile from circulating tumor DNA in triple negative breast cancer: Results from the prospective registry of unresectable locally advanced or metastatic breast cancer GEICAM/2014-03 (RegistEM) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-22.

Background: CDK 4/6 inhibitors (CDK 4/6i) with endocrine therapy (ET) combination therapy have improved outcomes in patients (pts) with hormonal receptor positive (HR+)/human epidermal growth factor receptor negative (HER2-) advanced breast cancer (ABC). However, most pts eventually develop resistance to these drugs, and one third never respond. Aside from HR positivity, predictive markers of clinical benefit from CDK 4/6i remains elusive. We aimed to identify biomarkers of response to palbociclib (PAL) and analyze potential therapeutic targets to reverse resistance. Methods: PEARL trial is a multicenter phase 3 study that assigned 601 postmenopausal HR+/HER2- ABC pts, whose disease progressed on aromatase inhibitors (AIs), to receive PAL + ET vs capecitabine (CAPE). We performed a differential gene expression analysis in pre-treatment tumors in extreme responders to PAL using the HTG EdgeSeq Oncology Biomarker Panel (HTG Molecular Diagnostics, Inc.), containing 2534 cancer related genes. Samples were subset in 2 categories: refractory (progressive disease as best response) vs sensitive (progression-free survival (PFS) within the upper quartile). Cox regression and Significance Analysis of Microarrays (SAM) analysis adjusting for multiple comparisons were performed. Results: We analyzed 455 (75.7%) pts with pre-treatment tumors available [from them, PAL + ET arm: 229 (50.3%) pts; CAPE arm: 226 (49.7%) pts]. Fifty genes (false discovery rate (FDR) median) of PLK1 (PLK1-high) treated with PAL, had a worse PFS in a multivariate model (5.7 months (m) vs 9.3 m of median PFS in PLK1-High vs -Low; HR=1.64, 95% CI (1.25-2.34), p=0.0008; adjusted model for confounders: age, site of disease, sites of metastasis, prior chemotherapy and Ki67). There were no differences in population treated with CAPE (9.9 m vs 9.4 m, PLK1-High vs -Low; HR=0.82, 95% CI (0.56-1.21), p=0.3189). In the METABRIC cohort, PLK1-High was associated with worse overall survival in HR+/HER2- BC but not in triple negative nor in HER2+ tumors. Among HR+/HER2- tumors, PLK1 expression was higher in luminal B and HER2-enriched intrinsic subtypes. We interrogated DepMap database and found that in BC cells lines there was an inverse correlation between PLK1 expression and effect on cell viability of CDK4 CRISPR knock-out (Pearson correlation r:0.54, p=0.009), but not of CDK6 knock-out. Also, HR+/HER2-/High Ki67 BC cell lines (HCC1428, EFM19 and MCF7) showed resistance to PAL on cell proliferation assays but sensitivity to the PLK1 inhibitor BI-2536. Conclusion: High expression of PLK1 is associated with intrinsic resistance to PAL and ET, this might be overcome with PLK1 inhibition. Table 1PATIENT CHARACTERISTICSCluster 1Cluster 2ALLn=57n=47n=104RespondersSensitive42 (73.68%)14 (29.79%)56 (53.85%)Refractory15 (26.32%)33 (70.21%)48 (46.15%)ESR1Mutated9 (15.79%)13 (27.66%)22 (21.15%)Wild type45 (78.95%)34 (72.34%)79 (75.96%)Unknown3 (5.26%)0 (0%)3 (2.88%)PriorQTN42 (73.68%)31 (65.96%)73 (70.19%)Y15 (26.32%)16 (34.04%)31 (29.81%)SubtypeLumA43 (75.44%)10 (21.28%)53 (50.96%)LumB14 (24.56%)28 (59.57%)42 (40.38%)Non Luminal0 (0%)9 (19.15%)9 (8.65%)MetastasisOne21 (36.84%)15 (31.91%)36 (34.62%)Multiple36 (63.16%)32 (68.09%)68 (65.38%)KI67 20%KI67 Citation Format: Angel Guerrero- Zotano, Christoph Zielinski, Miguel Gil-Gil, Manuel Ruiz-Borrego, Eva M. Ciruelos, Montserrat Munoz, Begoña Bermejo, Mireia Margeli, Antonio Antón, Tibor Csöszi, Andrés García-Palomo, Ana Santaballa, Jose Luis Alonso, Antonio Fernández, Massimo Corsaro, Jesús Herranz, Paula López, Rosalia Caballero, Christiane Thallinger, Miguel Martin. Plk1 expression & efficacy of palbociclib in advanced hormonal receptor-positive breast cancer patients from PEARL study (GEICAM 2012-03) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-01.

Responding to the pressures of current theoretical trends toward models of cultural globalization, the essays collected here bring a historical focus to literary studies. They suggest that only by exploring the particularities of regional historical cultures can the multiple meanings of American identities be understood. Representing a broad range of contemporary criticism, this volume features many short essays by the most well-known and respected Latin Americanists, each devoting attention to specific matters of history. The topics range from Incan architecture to Chicano and Nuyorican habitats; from turn of the century Argentine criminology to Caribbean homophobia; from the rhetorics of independence and dictatorship to Mexican ambivalence about opera and Brazil’s move beyond monarchy; and from the precarious survival of Spanish language in Latin America to its paradoxical legacy of enlightenment in the Philippines. Originally published as a special issue of Modern Language Quarterly (June 1996), this expanded edition includes a new introduction by Doris Sommer and a new essay by Vincente Rafael. Viewed together, these essays reveal a cultural richness that is sure to interest literary scholars and Latin Americanists alike. Contributors. Carlos J. Alonso, Antonio Benitez-Rojo, John Beverley, Debra A. Castillo, Arcadio Diaz-Quinones, Juan Flores, Mary M. Gaylord, Jose Limon, Josefina Ludmer, Francine Masiello, Antonio Mazzotti, Walter D. Mignolo, Sylvia Molloy, Mary Louise Pratt, Vincente Rafael, Julio Ramos, Susana Rotker, Roberto Schwarz, Diana Taylor, Nancy Vogeley