Bottom-up control of sardine and anchovy population cycles in the canary current: insights from an end-to-end model simulation

Sardine and anchovy can exhibit dramatic decadal-scale shifts in abundance in response to climate variability. Sharpe declines of these populations entail particularly serious commercial and ecological consequences in eastern boundary current ecosystems, where they sustain major world fisheries and provide the forage for a broad variety of predators. Understanding the mechanisms and environmental forcing that drive the observed fish variability remains a challenging problem. The modelling study presented here provides an approach that bridges a comprehensive database with an end-to-end modelling framework enabling the investigation of the sources of variability of sardine and anchovy in the Canary Current System. Different biological traits and behaviour prescribed for sardine and anchovy gave rise to different distribution and displacements of the populations, but to a rather synchronous variability in terms of abundance and biomass, in qualitative agreement with historical landing records. Analysis of years with anomalously high increase and decline of the adult population points to food availability (instead of temperature or other environmental drivers) as the main environmental factor determining recruitment for both sardine (via spawning and survival of feeding age-0 individuals) and anchovy (via survival of feeding age-0). Consistent with this, the two species thrive under enhanced upwelling-favourable winds, but only up to some threshold of the wind velocity beyond which larval drift mortality exceeds the positive effect of the extra food supply. Based on the analysis of the simulation, we found that anchovy larvae are particularly vulnerable to enhanced wind-driven advection, and as such do better with more moderate upwelling than sardines.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Multifamily Determination of Phytohormones and Acidic Herbicides in Fruits and Vegetables by Liquid Chromatography–Tandem Mass Spectrometry under Accredited Conditions

A 7-min multifamily residue method for the simultaneous quantification and confirmation of 8 phytohormones and 27 acidic herbicides in fruit and vegetables using ultra high-performance liquid chromatography (UHPLC) coupled to tandem mass spectrometry (MS/MS) was developed, validated according to SANTE 12682/2019, and accredited according to UNE-EN-ISO/IEC 17025:2017. Due to the special characteristics of these kinds of compounds, a previous step of alkaline hydrolysis was carried out for breaking conjugates that were potentially formed due to the interactions of the analytes with other components present in the matrix. Sample treatment was based on QuEChERS extraction and optimum detection conditions were individually optimized for each analyte. Cucumber (for high water content commodities) and orange (for high acid and high water content samples) were selected as representative matrices. Matrix-matched calibration was used, and all the validation criteria established in the SANTE guidelines were satisfied. Uncertainty estimation for each target compound was included in the validation process. The proposed method was applied to the analysis of more than 450 samples of cucumber, orange, tomato, watermelon, and zucchini during one year. Several compounds, such as 2,4-dichlorophenoxyacetic acid (2,4-D), 4-(3-indolyl)butyric acid (IBA), dichlorprop (2,4-DP), 2-methyl-4-chlorophenoxy acetic acid (MCPA), and triclopyr were found, but always at concentrations lower than the maximum residue level (MRL) regulated by the EU

Efficacy, Safety and Cost-Effectiveness of Methotrexate, Adalimumab or Their Combination in Non-infectious Non-anterior Uveitis: A Protocol for a Multicentre, Randomised, Parallel Three Arms, Active-Controlled, Phase III Open Label With Blinded Outcome Assessment Study

[Abstract] Introduction: Non-infectious uveitis include a heterogeneous group of sight-threatening and incapacitating conditions. Their correct management sometimes requires the use of immunosuppressive drugs (ISDs), prescribed in monotherapy or in combination. Several observational studies showed that the use of ISDs in combination could be more effective than and as safe as their use in monotherapy. However, a direct comparison between these two treatment strategies has not been carried out yet. Methods and analysis: The Combination THerapy with mEthotrexate and adalImumAb for uveitis (CoTHEIA) study is a phase III, multicentre, prospective, randomised, single-blinded with masked outcome assessment, parallel three arms with 1:1:1 allocation, active-controlled, superiority study design, comparing the efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis. We aim to recruit 192 subjects. The duration of the treatment and follow-up will last up to 52 weeks, plus 70 days follow-up with no treatment. The complete and maintained resolution of the ocular inflammation will be assessed by masked evaluators (primary outcome). In addition to other secondary measurements of efficacy (quality of life, visual acuity and costs) and safety, we will identify subjects’ subgroups with different treatment responses by developing prediction models based on machine learning techniques using genetic and proteomic biomarkers. Ethics and dissemination: The protocol, annexes and informed consent forms were approved by the Reference Clinical Research Ethic Committee at the Hospital Clínico San Carlos (Madrid, Spain) and the Spanish Agency for Medicines and Health Products. We will elaborate a dissemination plan including production of materials adapted to several formats to communicate the clinical trial progress and findings to a broad group of stakeholders. The promoter will be the only access to the participant-level data, although it can be shared within the legal situation. Trial registration number: 2020-000130-18; NCT04798755.This work was supported by the Instituto de Salud Carlos III, grant number [ICI19/00020]. Sponsor: Fundación para la Investigacion Biomédica del Hospital Clínico San Carlos. Executive Committee: Administrative and executive arm of the clinical trial, providing overall oversight for the study and making decisions on day-to-day operational issues (Study Coordinator (Luis Rodriguez-Rodriguez), a representative from the Spanish Clinical Trial Network (Amanda López Picado), and 5 Site Directors (these seats will be rotatory, with changes every 6 months months)); Data Coordinating and Analysis Committee: Supervising data collection,management and quality control, designing the statistical analysis plan, performing unmasked data analysis and preparing interim and final reports for the Data Security Monitoring Board and the Executy Committee (Study Coordinator (Luis Rodriguez-Rodriguez), a representative from the Spanish Clinical Trial Network (Amanda López Picado) and Ester Carreño); Biobank and Biomarker Identification Committee (Maintaining an up-to-date manual of operations for blood extraction, processing and storage, and monitoring procedures adherence, supervising biological sample collection, sample shipment coordination, coordinating the phamacogenetic and proteomic analysis (Study Coordinator (Luis Rodriguez-Rodriguez), a representative from the Instituto de Salud Carlos III Biobank Platform (Elena Molino), a representative the Instituto de Investigación Biomédica de A Coruña, a representative from, the Data Coordinating and Analysis Committee); Data Security Monitoring Committee (PierGiogio Neri, Andrew Dick, Loreto Carmona

BIM and mTOR expression levels predict outcome to erlotinib in EGFR-mutant non-small-cell lung cancer

Altres ajuts: Fellowship Award of the International Association for the Study of Lung Cancer i grant of the Italian Association for Cancer Research (AIRC My First AIRC Grant n° 14282).Abstract.BIM is a proapoptotic protein that initiates apoptosis triggered by EGFR tyrosine kinase inhibitors (TKI). mTOR negatively regulates apoptosis and may influence response to EGFR TKI. We examined mRNA expression of BIM and MTOR in 57 patients with EGFR-mutant NSCLC from the EURTAC trial. Risk of mortality and disease progression was lower in patients with high BIM compared with low/intermediate BIM mRNA levels. Analysis of MTOR further divided patients with high BIM expression into two groups, with those having both high BIM and MTOR experiencing shorter overall and progression-free survival to erlotinib. Validation of our results was performed in an independent cohort of 19 patients with EGFR-mutant NSCLC treated with EGFR TKIs. In EGFR-mutant lung adenocarcinoma cell lines with high BIM expression, concomitant high mTOR expression increased IC50 of gefitinib for cell proliferation. We next sought to analyse the signalling pattern in cell lines with strong activation of mTOR and its substrate P-S6. We showed that mTOR and phosphodiesterase 4D (PDE4D) strongly correlate in resistant EGFR-mutant cancer cell lines. These data suggest that the combination of EGFR TKI with mTOR or PDE4 inhibitors could be adequate therapy for EGFR-mutant NSCLC patients with high pretreatment levels of BIM and mTOR

Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing : results of the RING observational trial.

Abstract Several platforms for noninvasive EGFR testing are currently used in the clinical setting with sensitivities ranging from 30% to 100%. Prospective studies evaluating agreement and sources for discordant results remain lacking. Herein, seven methodologies including two next-generation sequencing (NGS)-based methods, three high-sensitivity PCR-based platforms, and two FDA-approved methods were compared using 72 plasma samples, from EGFR-mutant non-small-cell lung cancer (NSCLC) patients progressing on a first-line tyrosine kinase inhibitor (TKI). NGS platforms as well as high-sensitivity PCR-based methodologies showed excellent agreement for EGFR-sensitizing mutations (K = 0.80-0.89) and substantial agreement for T790M testing (K = 0.77 and 0.68, respectively). Mutant allele frequencies (MAFs) obtained by different quantitative methods showed an excellent reproducibility (intraclass correlation coefficients 0.86-0.98). Among other technical factors, discordant calls mostly occurred at mutant allele frequencies (MAFs) ≤ 0.5%. Agreement significantly improved when discarding samples with MAF ≤ 0.5%. EGFR mutations were detected at significantly lower MAFs in patients with brain metastases, suggesting that these patients risk for a false-positive result. Our results support the use of liquid biopsies for noninvasive EGFR testing and highlight the need to systematically report MAFs. Keywords: NGS; circulating free DNA; epidermal growth factor receptor; non-small-cell lung cancer; osimertinib; tyrosine kinase inhibitor

Charged-particle multiplicities in pp interactions at root s=900 GeV measured with the ATLAS detector at the LHC

22 páginas, 4 figuras, 1 tabla.-- et al.(ATLAS Collaboration).-- arXiv:1003.3124v2The first measurements from proton-proton collisions recorded with the ATLAS detector at the LHC are presented. Data were collected in December 2009 using a minimum-bias trigger during collisions at a centre-of-mass energy of 900 GeV. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity. and the relationship between mean transverse momentum and charged-particle multiplicity are measured for events with at least one charged particle in the kinematic range vertical bar eta vertical bar 500 MeV. The measurements are compared to Monte Carlo models of proton-proton collisions and to results from other experiments at the same centre-of-mass energy. The charged-particle multiplicity per event and unit of pseudorapidity eta = 0 is measured to be 1.333 +/- 0.003(stat.) +/- 0.040(syst.), which is 5-15% higher than the Monte Carlo models predict.We are greatly indebted to all CERN’s departments and to the LHC project for their immense efforts not only in building the LHC, but also for their direct contributions to the construction and installation of the ATLAS detector and its infrastructure. All our congratulations go to the LHC operation team for the superb performance during this initial data-taking period. We acknowledge equally warmly all our technical colleagues in the collaborating Institutions without whom the ATLAS detector could not have been built. Furthermore we are grateful to all the funding agencies which supported generously the construction and the commissioning of the ATLAS detector and also provided the computing infrastructure. The ATLAS detector design and construction has taken about fifteen years, and our thoughts are with all our colleagues who sadly could not see its final realisation. We acknowledge the support of ANPCyT, Argentina; Yerevan Physics Institute, Armenia; ARC and DEST, Australia; Bundesministerium für Wissenschaft und Forschung, Austria; National Academy of Sciences of Azerbaijan; State Committee on Science & Technologies of the Republic of Belarus; CNPq and FINEP, Brazil; NSERC, NRC, and CFI, Canada; CERN; CONICYT, Chile; NSFC, China; COLCIENCIAS, Colombia; Ministry of Education, Youth and Sports of the Czech Republic, Ministry of Industry and Trade of the Czech Republic, and Committee for Collaboration of the Czech Republic with CERN; Danish Natural Science Research Council and the Lundbeck Foundation; European Commission, through the ARTEMIS Research Training Network; IN2P3-CNRS and Dapnia-CEA, France; Georgian Academy of Sciences; BMBF, HGF, DFG and MPG, Germany; Ministry of Education and Religion, through the EPEAEK program PYTHAGORAS II and GSRT, Greece; ISF, MINERVA, GIF, DIP, and Benoziyo Center, Israel; INFN, Italy; MEXT, Japan; CNRST, Morocco; FOM and NWO, Netherlands; The Research Council of Norway; Ministry of Science and Higher Education, Poland; GRICES and FCT, Portugal; Ministry of Education and Research, Romania; Ministry of Education and Science of the Russian Federation and State Atomic Energy Corporation “Rosatom”; JINR; Ministry of Science, Serbia; Department of International Science and Technology Cooperation, Ministry of Education of the Slovak Republic; Slovenian Research Agency, Ministry of Higher Education, Science and Technology, Slovenia; Ministerio de Educación y Ciencia, Spain; The Swedish Research Council, The Knut and Alice Wallenberg Foundation, Sweden; State Secretariat for Education and Science, Swiss National Science Foundation, and Cantons of Bern and Geneva, Switzerland; National Science Council, Taiwan; TAEK, Turkey; The Science and Technology Facilities Council and The Leverhulme Trust, United Kingdom; DOE and NSF, United States of America.Peer reviewe

Investigación Educativa en las Ciencias Sociales

El libro se organiza en cinco grandes secciones, cada una con diferentes capítulos: La primera de ellas, rescata dos temas vinculados con aspectos teórico metodológicos de la Investigación Educativa; La segunda sección recoge algunos planteamientos del nivel básico; en tanto que la tercera, concentra dos capítulos de investigación en el nivel superior; la cuarta parte recupera y muestra dos aportes de nivel posgrado y, finalmente, se cierra con una quinta sección donde se concentran, distintos capítulos, de tópicos diversos

Towards a dynamic checklist of lichen-forming, lichenicolous and allied fungi of Ecuador – using the <i>Consortium of Lichen Herbaria</i> to manage fungal biodiversity in a megadiverse country

peer reviewedA checklist of Lichen-forming, Lichenicolous and Allied Fungi of Ecuador is presented with a total of 2599 species, of which 39 are reported for the first time from the country. The names of three species, Hypotrachyna montufariensis, H. subpartita and Sticta hypoglabra, previously not validly published, are validated. Pertusaria oahuensis, originally introduced by Magnusson as ‘ad interim’, is validated as Lepra oahuensis. The form Leucodermia leucomelos f. albociliata is validated. Two new combinations, Fissurina tectigera and F. timida, are made, and Physcia mobergii is introduced as a replacement name for the illegitimate P. lobulata Moberg non (Flörke) Arnold. In an initial step, the checklist was compiled by reviewing literature records of Ecuadorian lichen biota spanning from the late 19th century to the present day. Subsequently, records were added based on vouchers from 56 collections participating in the Consortium of Lichen Herbaria, a Symbiota-based biodiversity platform with particular focus on, but not exclusive to, North and South America. Symbiota provides sophisticated tools to manage biodiversity data, such as occurrence records, a taxonomic thesaurus, and checklists. The thesaurus keeps track of frequently changing names, distinguishing taxa currently accepted from ones considered synonyms. The software also provides tools to create and manage checklists, with an emphasis on selecting vouchers based on occurrence records that can be verified for identification accuracy. Advantages and limitations of creating checklists in Symbiota versus traditional ways of compiling these lists are discussed. Traditional checklists are well suited to document current knowledge as a ‘snapshot in time’. They are important baselines, frequently used by ecologists and conservation scientists as an established naming convention for citing species reported from a country. Compiling these lists, however, requires an immense effort, only to inadequately address the dynamic nature of scientific discovery. Traditional checklists are thus quickly out of date, particularly in groups with rapidly changing taxonomy, such as lichenized fungi. Especially in megadiverse countries, where new species and new occurrences continue to be discovered, traditional checklists are not easily updated; these lists necessarily fall short of efficiently managing immense data sets, and they rely primarily on secondary evidence (i.e. literature records rather than specimens). Ideally, best practices make use of dynamic database platforms such as Symbiota to assess occurrence records based both on literature citations and voucher specimens. Using modern data management tools comes with a learning curve. Systems like Symbiota are not necessarily intuitive and their functionality can still be improved, especially when handling literature records. However, online biodiversity data platforms have much potential in more efficiently managing and assessing large biodiversity data sets, particularly when investigating the lichen biota of megadiverse countries such as Ecuador

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.info:eu-repo/semantics/publishedVersio