La gestación por sustitución en el punto de mira de la bioética

Surrogate gestation is gestation agreed by means of a contract, with or without a price, in which a woman renounces the maternal filiation of the future child (the legal bond that unites mother and unborn child), in favour of the contracting party or a third party. Although this practice is null and void in Spain by Law 14/2006, of 26 May, on Assisted Human Reproduction Techniques, there are different international legislations that allow it in other countries. For this reason, it is important to carry out a bioethical analysis of the facts and values underlying this practice, such as commercialisation, mother-fetus bonds, the best interests of minors, as well as a global perspective with a gender and planetary perspective. This analysis will allow us to provide arguments from a bioethical point of view against a practice that undermines women's rights, harms the best interests of children and increases inequality on a planetary levelLa gestación por sustitución es la gestación convenida mediante un contrato, con o sin precio, en el que una mujer renuncia a la filiación materna del futuro hijo/a (vínculo jurídico que une a madre y nasciturus), a favor del contratante o de un tercero. A pesar de que esta práctica es nula de pleno derecho en España por la Ley 14/2006, de 26 de mayo, sobre Técnicas de Reproducción Humana Asistida, existen distintas legislaciones internacionales que la permiten en otros países. Por este motivo, es importante realizar un análisis con mirada bioética a los hechos y valores que subyacen bajo esta práctica, como la comercialización, los vínculos madre-feto, el interés superior de los/las menores así como una mirada global con perspectiva de género y planetaria. Este análisis nos va a permitir aportar argumentos desde el punto de vista bioético contra una práctica que entraña un menoscabo de los derechos de la mujer, un daño a los intereses superiores de los/las menores y un aumento de la desigualdad a nivel planetario

A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis

We report a medium‐throughput drug‐screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood–brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastasis, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug‐screening and unbiased omic approaches that is compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere

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

Combined fit to the spectrum and composition data measured by the Pierre Auger Observatory including magnetic horizon effects

The measurements by the Pierre Auger Observatory of the energy spectrum and mass composition of cosmic rays can be interpreted assuming the presence of two extragalactic source populations, one dominating the flux at energies above a few EeV and the other below. To fit the data ignoring magnetic field effects, the high-energy population needs to accelerate a mixture of nuclei with very hard spectra, at odds with the approximate E$^{-2}$ shape expected from diffusive shock acceleration. The presence of turbulent extragalactic magnetic fields in the region between the closest sources and the Earth can significantly modify the observed CR spectrum with respect to that emitted by the sources, reducing the flux of low-rigidity particles that reach the Earth. We here take into account this magnetic horizon effect in the combined fit of the spectrum and shower depth distributions, exploring the possibility that a spectrum for the high-energy population sources with a shape closer to E$^{-2}$ be able to explain the observations

Studies of the mass composition of cosmic rays and proton-proton interaction cross-sections at ultra-high energies with the Pierre Auger Observatory

In this work, we present an estimate of the cosmic-ray mass composition from the distributions of the depth of the shower maximum (Xmax) measured by the fluorescence detector of the Pierre Auger Observatory. We discuss the sensitivity of the mass composition measurements to the uncertainties in the properties of the hadronic interactions, particularly in the predictions of the particle interaction cross-sections. For this purpose, we adjust the fractions of cosmic-ray mass groups to fit the data with Xmax distributions from air shower simulations. We modify the proton-proton cross-sections at ultra-high energies, and the corresponding air shower simulations with rescaled nucleus-air cross-sections are obtained via Glauber theory. We compare the energy-dependent composition of ultra-high-energy cosmic rays obtained for the different extrapolations of the proton-proton cross-sections from low-energy accelerator data

Study of downward Terrestrial Gamma-ray Flashes with the surface detector of the Pierre Auger Observatory

The surface detector (SD) of the Pierre Auger Observatory, consisting of 1660 water-Cherenkov detectors (WCDs), covers 3000 km2 in the Argentinian pampa. Thanks to the high efficiency of WCDs in detecting gamma rays, it represents a unique instrument for studying downward Terrestrial Gamma-ray Flashes (TGFs) over a large area. Peculiar events, likely related to downward TGFs, were detected at the Auger Observatory. Their experimental signature and time evolution are very different from those of a shower produced by an ultrahigh-energy cosmic ray. They happen in coincidence with low thunderclouds and lightning, and their large deposited energy at the ground is compatible with that of a standard downward TGF with the source a few kilometers above the ground. A new trigger algorithm to increase the TGF-like event statistics was installed in the whole array. The study of the performance of the new trigger system during the lightning season is ongoing and will provide a handle to develop improved algorithms to implement in the Auger upgraded electronic boards. The available data sample, even if small, can give important clues about the TGF production models, in particular, the shape of WCD signals. Moreover, the SD allows us to observe more than one point in the TGF beam, providing information on the emission angle

The dynamic range of the upgraded surface-detector stations of AugerPrime

The detection of ultra-high-energy cosmic rays by means of giant detector arrays is often limited by the saturation of the recorded signals near the impact point of the shower core at the ground, where the particle density dramatically increases. The saturation affects in particular the highest energy events, worsening the systematic uncertainties in the reconstruction of the shower characteristics. The upgrade of the Pierre Auger Observatory, called AugerPrime, includes the installation of an 1-inch Small PhotoMultiplier Tube (SPMT) inside each water-Cherenkov station (WCD) of the surface detector array. The SPMT allows an unambiguous measurement of signals down to about 250m from the shower core, thus reducing the number of events featuring a saturated station to a negligible level. In addition, a 3.8m2 plastic scintillator (Scintillator Surface Detector, SSD) is installed on top of each WCD. The SSD is designed to match the WCD (with SPMT) dynamic range, providing a complementary measurement of the shower components up to the highest energies. In this work, the design and performances of the upgraded AugerPrime surface-detector stations in the extended dynamic range are described, highlighting the accuracy of the measurements. A first analysis employing the unsaturated signals in the event reconstruction is also presented

Investigating multiple elves and halos above strong lightning with the fluorescence detectors of the Pierre Auger Observatory

ELVES are being studied since 2013 with the twenty-four FD Telescopes of the Pierre Auger Observatory, in the province of Mendoza (Argentina), the world’s largest facility for the study of ultra-high energy cosmic rays. This study exploits a dedicated trigger and extended readout. Since December 2020, this trigger has been extended to the three High levation Auger Telescopes (HEAT), which observe the night sky at elevation angles between 30 and 60 degrees, allowing a study of ELVES from closer lightning. The high time resolution of the Auger telescopes allows us to upgrade reconstruction algorithms and to do detailed studies on multiple ELVES. The origin of multiple elves can be studied by analyzing the time difference and the amplitude ratio between flashes and comparing them with the properties of radio signals detected by the ENTLN lightning network since 2018. A fraction of multi-ELVES can also be interpreted as halos following ELVES. Halos are disc-shaped light transients emitted at 70-80 km altitudes, appearing at the center of the ELVES rings, due to the rearrangement of electric charges at the base of the ionosphere after a strong lightning event