Los sistemas de pago por servicios ambientales entre la adicionalidad y la subsidiariedad: aplicación a la belleza escénica en el pantano de San Juan, Madrid, España

A payment for environmental services (PES) based on the beauty of the San Juan dam landscape is proposed containing two innovative aspect in regard to previous PES systems: the elaboration of a diagnosis oriented to obtain a shared vision of the area based in a participative process including all relevant local stakeholders, and the integration of the PES mechanism into the regional public environmental policy. The proposed system also identifies the offer and the demand of the environmental service. It shows the main problems associated to the preservation of the service and proposes management plans oriented to its conservation. Finally, the economic viability of the system is studied comparing three different scenarios according to the grade of integration of the PES model into the regional conservation public policy. This paper shows how a PES system can be used to guarantee public investments in nature conservation through a private management.Se plantea un sistema de pago por servicios ambientales (PSA) basado en la valoración de la belleza escénica en la zona del pantano de San Juan, Madrid, con dos aspectos novedosos respecto a estudios PSA previos: la elaboración de un diagnóstico basado en un proceso participativo que involucra a todos los actores sociales locales y cuyo fin es el de obtener una visión compartida sobre el área, y la integración del mecanismo PSA en la gestión pública regional de la conservación de la naturaleza. El sistema propuesto además identifica los oferentes y demandantes del servicio ambiental, muestra los principales problemas asociados a la conservación del servicio y plantea programas de gestión orientados a contribuir a su conservación. Se estudia, por último, la viabilidad económica del sistema comparando tres escenarios hipotéticos en función del grado de integración del sistema PSA en las políticas públicas de conservación de la naturaleza regionales. El trabajo muestra como un sistema PSA puede servir para garantizar las inversiones públicas en conservación a través de la gestión privada

Aspergillus fumigatus Fumagillin Contributes to Host Cell Damage

The activity of fumagillin, a mycotoxin produced by Aspergillus fumigatus, has not been studied in depth. In this study, we used a commercial fumagillin on cultures of two cell types (A549 pneumocytes and RAW 264.7 macrophages). This toxin joins its target, MetAP2 protein, inside cells and, as a result, significantly reduces the electron chain activity, the migration, and the proliferation ability on the A549 cells, or affects the viability and proliferation ability of the RAW 264.7 macrophages. However, the toxin stimulates the germination and double branch hypha production of fungal cultures, pointing out an intrinsic resistant mechanism to fumagillin of fungal strains. In this study, we also used a fumagillin non-producer A. fumigatus strain (∆fmaA) as well as its complemented strain (∆fmaA::fmaA) and we tested the fumagillin secretion of the fungal strains using an Ultra High-Performance Liquid Chromatography (UHPLC) method. Furthermore, fumagillin seems to protect the fungus against phagocytosis in vitro, and during in vivo studies using infection of immunosuppressed mice, a lower fungal burden in the lungs of mice infected with the ∆fmaA mutant was demonstrated.This research was funded by the Basque Government: grant number IT1362-19. X.G. and S.C.-S. received a Ph.D. fellowship from the Basque Government; and U.P.-C. from the University of the Basque Country

The mitochondrial negative regulator MCJ is a therapeutic target for acetaminophen-induced liver injury

Acetaminophen (APAP) is the active component of many medications used to treat pain and fever worldwide. Its overuse provokes liver injury and it is the second most common cause of liver failure. Mitochondrial dysfunction contributes to APAP-induced liver injury but the mechanism by which APAP causes hepatocyte toxicity is not completely understood. Therefore, we lack efficient therapeutic strategies to treat this pathology. Here we show that APAP interferes with the formation of mitochondrial respiratory supercomplexes via the mitochondrial negative regulator MCJ, and leads to decreased production of ATP and increased generation of ROS. In vivo treatment with an inhibitor of MCJ expression protects liver from acetaminophen-induced liver injury at a time when N-acetylcysteine, the standard therapy, has no efficacy. We also show elevated levels of MCJ in the liver of patients with acetaminophen overdose. We suggest that MCJ may represent a therapeutic target to prevent and rescue liver injury caused by acetaminophen

Prognostic factors in left-sided endocarditis: results from the andalusian multicenter cohort

<p>Abstract</p> <p>Background</p> <p>Despite medical advances, mortality in infective endocarditis (IE) is still very high. Previous studies on prognosis in IE have observed conflicting results. The aim of this study was to identify predictors of in-hospital mortality in a large multicenter cohort of left-sided IE.</p> <p>Methods</p> <p>An observational multicenter study was conducted from January 1984 to December 2006 in seven hospitals in Andalusia, Spain. Seven hundred and five left-side IE patients were included. The main outcome measure was in-hospital mortality. Several prognostic factors were analysed by univariate tests and then by multilogistic regression model.</p> <p>Results</p> <p>The overall mortality was 29.5% (25.5% from 1984 to 1995 and 31.9% from 1996 to 2006; Odds Ratio 1.25; 95% Confidence Interval: 0.97-1.60; p = 0.07). In univariate analysis, age, comorbidity, especially chronic liver disease, prosthetic valve, virulent microorganism such as <it>Staphylococcus aureus</it>, <it>Streptococcus agalactiae </it>and fungi, and complications (septic shock, severe heart failure, renal insufficiency, neurologic manifestations and perivalvular extension) were related with higher mortality. Independent factors for mortality in multivariate analysis were: Charlson comorbidity score (OR: 1.2; 95% CI: 1.1-1.3), prosthetic endocarditis (OR: 1.9; CI: 1.2-3.1), <it>Staphylococcus aureus </it>aetiology (OR: 2.1; CI: 1.3-3.5), severe heart failure (OR: 5.4; CI: 3.3-8.8), neurologic manifestations (OR: 1.9; CI: 1.2-2.9), septic shock (OR: 4.2; CI: 2.3-7.7), perivalvular extension (OR: 2.4; CI: 1.3-4.5) and acute renal failure (OR: 1.69; CI: 1.0-2.6). Conversely, <it>Streptococcus viridans </it>group etiology (OR: 0.4; CI: 0.2-0.7) and surgical treatment (OR: 0.5; CI: 0.3-0.8) were protective factors.</p> <p>Conclusions</p> <p>Several characteristics of left-sided endocarditis enable selection of a patient group at higher risk of mortality. This group may benefit from more specialised attention in referral centers and should help to identify those patients who might benefit from more aggressive diagnostic and/or therapeutic procedures.</p

Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA

The screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E−4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p < 0.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n = 67 for CML and n = 62 for B-ALL patients). A total of 162 samples (n = 86 CML and n = 76 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite BCR::ABL1 < 1%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E−4 sensitivity by NGS using DNA as starting material even in patients with low levels of disease.Tis project was funded in part by CRIS CANCER FOUNDATION

Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study

BACKGROUND: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population. METHODS: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases. FINDINGS: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism. INTERPRETATION: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term. FUNDING: None

gSeaGen: The KM3NeT GENIE-based code for neutrino telescopes

Program summary Program Title: gSeaGen CPC Library link to program files: http://dx.doi.org/10.17632/ymgxvy2br4.1 Licensing provisions: GPLv3 Programming language: C++ External routines/libraries: GENIE [1] and its external dependencies. Linkable to MUSIC [2] and PROPOSAL [3]. Nature of problem: Development of a code to generate detectable events in neutrino telescopes, using modern and maintained neutrino interaction simulation libraries which include the state-of-the-art physics models. The default application is the simulation of neutrino interactions within KM3NeT [4]. Solution method: Neutrino interactions are simulated using GENIE, a modern framework for Monte Carlo event generators. The GENIE framework, used by nearly all modern neutrino experiments, is considered as a reference code within the neutrino community. Additional comments including restrictions and unusual features: The code was tested with GENIE version 2.12.10 and it is linkable with release series 3. Presently valid up to 5 TeV. This limitation is not intrinsic to the code but due to the present GENIE valid energy range. References: [1] C. Andreopoulos at al., Nucl. Instrum. Meth. A614 (2010) 87. [2] P. Antonioli et al., Astropart. Phys. 7 (1997) 357. [3] J. H. Koehne et al., Comput. Phys. Commun. 184 (2013) 2070. [4] S. Adrián-Martínez et al., J. Phys. G: Nucl. Part. Phys. 43 (2016) 084001.The gSeaGen code is a GENIE-based application developed to efficiently generate high statistics samples of events, induced by neutrino interactions, detectable in a neutrino telescope. The gSeaGen code is able to generate events induced by all neutrino flavours, considering topological differences between tracktype and shower-like events. Neutrino interactions are simulated taking into account the density and the composition of the media surrounding the detector. The main features of gSeaGen are presented together with some examples of its application within the KM3NeT project.French National Research Agency (ANR) ANR-15-CE31-0020Centre National de la Recherche Scientifique (CNRS)European Union (EU)Institut Universitaire de France (IUF), FranceIdEx program, FranceUnivEarthS Labex program at Sorbonne Paris Cite ANR-10-LABX-0023 ANR-11-IDEX-000502Paris Ile-de-France Region, FranceShota Rustaveli National Science Foundation of Georgia (SRNSFG), Georgia FR-18-1268German Research Foundation (DFG)Greek Ministry of Development-GSRTIstituto Nazionale di Fisica Nucleare (INFN)Ministry of Education, Universities and Research (MIUR)PRIN 2017 program Italy NAT-NET 2017W4HA7SMinistry of Higher Education, Scientific Research and Professional Training, MoroccoNetherlands Organization for Scientific Research (NWO) Netherlands GovernmentNational Science Centre, Poland 2015/18/E/ST2/00758National Authority for Scientific Research (ANCS), RomaniaMinisterio de Ciencia, Innovacion, Investigacion y Universidades (MCIU): Programa Estatal de Generacion de Conocimiento, Spain (MCIU/FEDER) PGC2018-096663-B-C41 PGC2018-096663-A-C42 PGC2018-096663-BC43 PGC2018-096663-B-C44Severo Ochoa Centre of Excellence and MultiDark Consolider (MCIU), Junta de Andalucia, Spain SOMM17/6104/UGRGeneralitat Valenciana: Grisolia, Spain GRISOLIA/2018/119GenT, Spain CIDEGENT/2018/034La Caixa Foundation LCF/BQ/IN17/11620019EU: MSC program, Spain 71367

Implementation and first results of the KM3NeT real-time core-collapse supernova neutrino search

The authors acknowledge the financial support of the funding agencies: Agence Nationale de la Recherche (contract ANR-15-CE31-0020), Centre National de la Recherche Scientifique (CNRS), Commission Europeenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), LabEx UnivEarthS (ANR-10-LABX-0023 and ANR-18-IDEX-0001), Paris ile-de-France Region, France; Shota Rustaveli National Science Foundation of Georgia (SRNSFG, FR-18-1268), Georgia; Deutsche Forschungsgemeinschaft (DFG), Germany; The General Secretariat of Research and Technology (GSRT), Greece; Istituto Nazionale di Fisica Nucleare (INFN), Ministero dell'Universita e della Ricerca (MIUR), PRIN 2017 program (Grant NAT-NET 2017W4HA7S) Italy; Ministry of Higher Education Scientific Research and Professional Training, ICTP through Grant AF-13, Morocco; Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; The National Science Centre, Poland (2015/18/E/ST2/00758); National Authority for Scientific Research (ANCS), Romania; Ministerio de Ciencia, Innovacion, Investigacion y Universidades (MCIU): Programa Estatal de Generacion de Conocimiento (refs. PGC2018-096663-B-C41, -A-C42, -B-C43, -B-C44) (MCIU/FEDER), Generalitat Valenciana: Prometeo (PROMETEO/2020/019), Grisolia (ref. GRISOLIA/2018/119) and GenT (refs. CIDEGENT/2018/034, /2019/043, /2020/049) programs, Junta de Andalucia (ref. A-FQM-053-UGR18), La Caixa Foundation (ref. LCF/BQ/IN17/11620019), EU: MSC program (ref. 101025085), Spain.The KM3NeT research infrastructure is unconstruction in the Mediterranean Sea. KM3NeT will study atmospheric and astrophysical neutrinos with two multipurpose neutrino detectors, ARCA and ORCA, primarily aimed at GeV–PeV neutrinos. Thanks to the multiphotomultiplier tube design of the digital optical modules, KM3NeT is capable of detecting the neutrino burst from a Galactic or near-Galactic core-collapse supernova. This potential is already exploitable with the first detection units deployed in the sea. This paper describes the real-time implementation of the supernova neutrino search, operating on the two KM3NeT detectors since the first months of 2019. A quasi-online astronomy analysis is introduced to study the time profile of the detected neutrinos for especially significant events. Themechanism of generation and distribution of alerts, aswell as the integration into theSNEWSandSNEWS 2.0 global alert systems, are described. The approach for the follow-up of external alerts with a search for a neutrino excess in the archival data is defined. Finally, an overviewof the current detector capabilities and a report after the first two years of operation are given.French National Research Agency (ANR)European Commission ANR-15-CE31-0020Centre National de la Recherche Scientifique (CNRS)Commission EuropeenneInstitut Universitaire de France (IUF)LabEx UnivEarthS ANR-10-LABX-0023 ANR-18-IDEX-0001Shota Rustaveli National Science Foundation of Georgia (SRNSFG), Georgia FR-18-1268German Research Foundation (DFG)Greek Ministry of Development-GSRTIstituto Nazionale di Fisica Nucleare (INFN)Ministry of Education, Universities and Research (MIUR)PRIN 2017 program, Italy NAT-NET 2017W4HA7SMinistry of Higher Education Scientific Research and Professional Training, ICTP, Morocco AF-13Netherlands Organization for Scientific Research (NWO) Netherlands GovernmentNational Science Centre, Poland 2015/18/E/ST2/00758National Authority for Scientific Research (ANCS), RomaniaMinisterio de Ciencia, Innovacion, Investigacion y Universidades (MCIU): Programa Estatal de Generacion de Conocimiento PGC2018-096663-B-C41 PGC2018-096663-A-C42 PGC2018-096663-B-C43 PGC2018-096663-B-C44Generalitat Valenciana PROMETEO/2020/019Grisolia program GRISOLIA/2018/119 CIDEGENT/2018/034Junta de Andalucia A-FQM-053-UGR18La Caixa Foundation LCF/BQ/IN17/11620019EU: MSC program 101025085Paris Ile-de-France Region, FranceGenT program CIDEGENT/2018/034 CIDEGENT/2019/043 CIDEGENT/2020/04

Deep-sea deployment of the KM3NeT neutrino telescope detection units by self-unrolling

KM3NeT is a research infrastructure being installed in the deep Mediterranean Sea. It will house a neutrino telescope comprising hundreds of networked moorings — detection units or strings — equipped with optical instrumentation to detect the Cherenkov radiation generated by charged particles from neutrino-induced collisions in its vicinity. In comparison to moorings typically used for oceanography, several key features of the KM3NeT string are different: the instrumentation is contained in transparent and thus unprotected glass spheres; two thin Dyneema® ropes are used as strength members; and a thin delicate backbone tube with fibre-optics and copper wires for data and power transmission, respectively, runs along the full length of the mooring. Also, compared to other neutrino telescopes such as ANTARES in the Mediterranean Sea and GVD in Lake Baikal, the KM3NeT strings are more slender to minimise the amount of material used for support of the optical sensors. Moreover, the rate of deploying a large number of strings in a period of a few years is unprecedented. For all these reasons, for the installation of the KM3NeT strings, a custom-made, fast deployment method was designed. Despite the length of several hundreds of metres, the slim design of the string allows it to be compacted into a small, re-usable spherical launching vehicle instead of deploying the mooring weight down from a surface vessel. After being lowered to the seafloor, the string unfurls to its full length with the buoyant launching vehicle rolling along the two ropes. The design of the vehicle, the loading with a string, and its underwater self-unrolling are detailed in this paper.French National Research Agency (ANR) ANR-15-CE31-0020Centre National de la Recherche Scientifique (CNRS)European Union (EU)Institut Universitaire de France (IUF)LabEx UnivEarthS ANR-10-LABX-0023 ANR-18-IDEX-0001Paris Ile-de-France Region, FranceShota Rustaveli National Science Foundation of Georgia (SRNSFG), Georgia FR-18-1268German Research Foundation (DFG)Greek Ministry of Development-GSRTIstituto Nazionale di Fisica Nucleare (INFN), Ministero dell'Universita e della Ricerca (MUR), PRIN Italy NAT-NET 2017W4HA7SMinistry of Higher Education, Scientific Research and Professional Training, MoroccoNetherlands Organization for Scientific Research (NWO) Netherlands GovernmentNational Science Center, Poland National Science Centre, Poland 2015/18/E/ST2/00758National Authority for Scientific Research (ANCS), RomaniaMinisterio de Ciencia, Innovación, Investigación y Universidades (MCIU): Programa Estatal de Generación de Conocimiento (MCIU/FEDER) PGC2018-096663-B-C41 PGC2018-096663-B-A-C42 PGC2018-096663-B-BC43 PGC2018-096663-B-B-C44Severo Ochoa Centre of Excellence and MultiDark Consolider (MCIU), Junta de Andalucía SOMM17/6104/UGRGeneralitat Valenciana GRISOLIA/2018/119 CIDEGENT/2018/034La Caixa Foundation LCF/BQ/IN17/11620019EU: MSC program, Spain 71367

Embedded Software of the KM3NeT Central Logic Board

The KM3NeT Collaboration is building and operating two deep sea neutrino telescopes at the bottom of the Mediterranean Sea. The telescopes consist of latices of photomultiplier tubes housed in pressure-resistant glass spheres, called digital optical modules and arranged in vertical detection units. The two main scientific goals are the determination of the neutrino mass ordering and the discovery and observation of high-energy neutrino sources in the Universe. Neutrinos are detected via the Cherenkov light, which is induced by charged particles originated in neutrino interactions. The photomultiplier tubes convert the Cherenkov light into electrical signals that are acquired and timestamped by the acquisition electronics. Each optical module houses the acquisition electronics for collecting and timestamping the photomultiplier signals with one nanosecond accuracy. Once finished, the two telescopes will have installed more than six thousand optical acquisition nodes, completing one of the more complex networks in the world in terms of operation and synchronization. The embedded software running in the acquisition nodes has been designed to provide a framework that will operate with different hardware versions and functionalities. The hardware will not be accessible once in operation, which complicates the embedded software architecture. The embedded software provides a set of tools to facilitate remote manageability of the deployed hardware, including safe reconfiguration of the firmware. This paper presents the architecture and the techniques, methods and implementation of the embedded software running in the acquisition nodes of the KM3NeT neutrino telescopes