Endovascular Treatment for Pseudoaneurysms after Surgical Correction of Aortic Coarctation

Late complications after surgical repair of aortic coarctation are not uncommon. Among these complications pseudoaneurysms are the most frequent complications, occurring between 3 and 38%. Reoperation in these patients is associated with high morbidity and mortality. In the last decade, endovascular techniques emerged as an alternative to conventional surgery with excellent results. We report the case of two patients who presented with pseudoaneurysms after surgical correction for aortic coarctation, which were treated by endovascular means

Somatostatin subtype-2 receptor-targeted metal-based anticancer complexes

Conjugates of a dicarba analogue of octreotide, a potent somatostatin agonist whose receptors are overexpressed on tumor cells, with [PtCl 2(dap)] (dap = 1-(carboxylic acid)-1,2-diaminoethane) (3), [(η 6-bip)Os(4-CO 2-pico)Cl] (bip = biphenyl, pico = picolinate) (4), [(η 6-p-cym)RuCl(dap)] + (p-cym = p-cymene) (5), and [(η 6-p-cym)RuCl(imidazole-CO 2H)(PPh 3)] + (6), were synthesized by using a solid-phase approach. Conjugates 3-5 readily underwent hydrolysis and DNA binding, whereas conjugate 6 was inert to ligand substitution. NMR spectroscopy and molecular dynamics calculations showed that conjugate formation does not perturb the overall peptide structure. Only 6 exhibited antiproliferative activity in human tumor cells (IC 50 = 63 ± 2 μ in MCF-7 cells and IC 50 = 26 ± 3 μ in DU-145 cells) with active participation of somatostatin receptors in cellular uptake. Similar cytotoxic activity was found in a normal cell line (IC 50 = 45 ± 2.6 μ in CHO cells), which can be attributed to a similar level of expression of somatostatin subtype-2 receptor. These studies provide new insights into the effect of receptor-binding peptide conjugation on the activity of metal-based anticancer drugs, and demonstrate the potential of such hybrid compounds to target tumor cells specifically. © 2012 American Chemical Society

Mapa de series, geoseries y geopermaseries de vegetación de España (Memoria del mapa de vegetación potencial de España). Parte II

Peer Reviewe

Recovery of critical and other raw materials from mining waste and landfills

The transition to a more circular economy is essential to develop a sustainable, low carbon, resource efficient, and competitive economy in the EU. In this context Critical Raw Materials (CRM) are defined as those which are of particularly great importance to the EU economy and at the same time there is a high risk of supply disruptions. First and foremost, improving the circular use of CRM is a key strategy in improving the security of supply and not surprisingly is an objective of various policy documents. This report delivers on action #39 of the Circular Economy Action Plan: "Sharing of best practice for the recovery of critical raw materials from mining waste and landfills". It builds on discussions held during two 2018 workshops and gathers together six examples of existing practices for the recovery of critical, precious, and other materials from extractive waste and landfills, highlighting technological innovation and contributions that have been made to a more comprehensive knowledge-base on raw materials. The report also provides various estimates of potential recovery of certain materials compared to their current demand. Lessons learnt from the practices include awareness that it is very unlikely that recovery processes can target one or just a few specific materials of great interest and disregard other elements or bulk matrixes. Especially in case of very low concentrations, most of the mineral resources and other bulk materials in which they are embedded must be valorised in order to increase economic viability and minimise waste disposal. As recovery processes can be very energy intensive, environmental and land use related aspects are also particularly relevant even though environmental gains may also occur and, moreover, land space can be liberated and reused for new purposes and services. Finally, availability of data and information on secondary materials as well as a harmonized legislative framework within the EU appear to be crucial for the large-scale deployment of recovery practices.JRC.D.3-Land Resource

The Rise and Fall of "Respectable" Spanish Liberalism, 1808-1923: An Explanatory Framework

The article focuses on the reasons behind both the consolidation of what I have termed “respectable” liberalism between the 1830s and the 1840s and its subsequent decline and fall between 1900 and 1923. In understanding both processes I study the links established between “respectable” liberals and propertied elites, the monarchy, and the Church. In the first phase these links served to consolidate the liberal polity. However, they also meant that many tenets of liberal ideology were compromised. Free elections were undermined by the operation of caciquismo, monarchs established a powerful position, and despite the Church hierarchy working with liberalism, the doctrine espoused by much of the Church was still shaped by the Counter-Reformation. Hence, “respectable” liberalism failed to achieve a popular social base. And the liberal order was increasingly denigrated as part of the corrupt “oligarchy” that ruled Spain. Worse still, between 1916 and 1923 the Church, monarch, and the propertied elite increasingly abandoned the liberal Monarchist Restoration. Hence when General Primo de Rivera launched his coup the rug was pulled from under the liberals’ feet and there was no one to cushion the fall

Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure

A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) a-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions

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

GWTC-3: Compact Binary Coalescences Observed by LIGO and Virgo During the Second Part of the Third Observing Run

The third Gravitational-wave Transient Catalog (GWTC-3) describes signals detected with Advanced LIGO and Advanced Virgo up to the end of their third observing run. Updating the previous GWTC-2.1, we present candidate gravitational waves from compact binary coalescences during the second half of the third observing run (O3b) between 1 November 2019, 15:00 UTC and 27 March 2020, 17:00 UTC. There are 35 compact binary coalescence candidates identified by at least one of our search algorithms with a probability of astrophysical origin $p_\mathrm{astro} > 0.5$. Of these, 18 were previously reported as low-latency public alerts, and 17 are reported here for the first time. Based upon estimates for the component masses, our O3b candidates with $p_\mathrm{astro} > 0.5$ are consistent with gravitational-wave signals from binary black holes or neutron star-black hole binaries, and we identify none from binary neutron stars. However, from the gravitational-wave data alone, we are not able to measure matter effects that distinguish whether the binary components are neutron stars or black holes. The range of inferred component masses is similar to that found with previous catalogs, but the O3b candidates include the first confident observations of neutron star-black hole binaries. Including the 35 candidates from O3b in addition to those from GWTC-2.1, GWTC-3 contains 90 candidates found by our analysis with $p_\mathrm{astro} > 0.5$ across the first three observing runs. These observations of compact binary coalescences present an unprecedented view of the properties of black holes and neutron stars