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The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms. Here, we provide an updated overview of the GO knowledgebase, as well as the efforts of the broad, international consortium of scientists that develops, maintains, and updates the GO knowledgebase. The GO knowledgebase consists of three components: (1) the GO—a computational knowledge structure describing the functional characteristics of genes; (2) GO annotations—evidence-supported statements asserting that a specific gene product has a particular functional characteristic; and (3) GO Causal Activity Models (GO-CAMs)—mechanistic models of molecular “pathways” (GO biological processes) created by linking multiple GO annotations using defined relations. Each of these components is continually expanded, revised, and updated in response to newly published discoveries and receives extensive QA checks, reviews, and user feedback. For each of these components, we provide a description of the current contents, recent developments to keep the knowledgebase up to date with new discoveries, and guidance on how users can best make use of the data that we provide. We conclude with future directions for the project.

Celia M Zubrinich,1,2 Robert M Puy,3 Robyn E O’Hehir,1,3 Mark Hew1,2 1Allergy, Asthma & Clinical Immunology, Alfred Health, Melbourne, Victoria, Australia; 2School of Public Health & Preventive Medicine, Monash University, Melbourne, Victoria, Australia; 3Allergy and Clinical Immunology Laboratory, Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, AustraliaCorrespondence: Celia M Zubrinich, Email c.zubrinich@alfred.org.auBackground: Different phenotypes of food allergy may exist, exhibiting distinct clinical features, and driven by different pathogenic mechanisms. We compared omega-5-gliadin (O5G) allergy to peanut allergy, focusing on clinical features, reaction rates and triggers, and quality of life (QOL).Methods: We surveyed adults with O5G allergy and peanut allergy regarding their diagnosis, co-morbidities, allergic reactions, and QOL measured by the FAQLQ-AF.Results: We received responses from 43/80 (54%) individuals with O5G allergy and 43/130 (33%) with peanut allergy. Compared to peanut allergic individuals, those with O5G allergy were older at age of onset (37.2 vs 2.5 years, p < 0.001), had fewer additional atopic conditions (0.88 vs 2.93, p < 0.001) or food allergies (0.15 vs 1.86, p < 0.001), and more frequent reactions before diagnosis (1.085 vs 0.29 per month, p < 0.05) Reaction rates improved in both groups following diagnosis. Reactions to peanut were more often triggered by accidental exposure (84% vs 26%, p < 0.001) and being away from home (65% vs 28%, p < 0.001), while reactions to O5G were more often due to deliberate ingestion (30% vs 9%, p < 0.05) or unexpected exercise (35% vs 2%, p < 0.001). Overall QOL score was similar between groups (4.2 in O5G allergy, 4.7 in peanut allergy, p = 0.12), but worse among women and those with additional food allergies.Conclusion: Phenotypic differences between O5G and peanut allergy support the development of different clinical approaches and the possibility of targeting distinct pathogenic mechanisms for prevention and treatment. Quality of life was impaired to a similar degree between groups.Keywords: omega-5-gliadin allergy, wheat allergy, peanut allergy, food allergy, anaphylaxis, wheat-dependent exercise-induced allergy, WDEIA, food-dependent exercise-induced allergy, FDEIA, quality of life, QOL, Australia

La majorité des personnes transgenres envisage de fonder une famille, mais leur fertilité peut être altérée par l’affirmation du genre. L’hormonothérapie peut affecter durablement la production de gamètes, notamment chez les femmes trans. La chirurgie de réassignation sexuelle entraîne une stérilité définitive. En France, des réseaux de professionnels de santé se sont organisés. Ils recommandent l’accès à la préservation de la fertilité dans le cadre de la transidentité. Cependant, le recueil de gamètes reste souvent difficile en raison de l’incongruence hormonale pour les femmes trans, ou du caractère invasif de la procédure pour les hommes trans. De futures études permettront de statuer sur l’utilisation des gamètes autoconservés.

This paper explores the potential of elections to change our emotions and modify the relevance that voters assign to self-interest and group-identity issues. We examine this question by analyzing the 1998–2016 period of the Catalan and Basque regional elections. The analysis exploits that Basques pushed to leave Spain in the early 2000s, and Catalans pursued independence about fifteen years later. When the separatist goal emerges, two issues gain relevance. First, there is a significant rise of identity politics, associated with the territory’s culture and language, to the detriment of other issues that traditionally explain vote choice, such as the left-right ideology, the degree of regional autonomy, or the economic discontent. Second, the territory becomes more divisive, big cities align against dominant separatist parties, and rural areas align with independentists. We conclude that material self-interests dilute and group-identity factors emerge to determine vote decisions in times of national dissolution.

Several studies have addressed the potential biorefinery, through small-scale pyrolysis, of coffee silverskin (CSS), grape pomace (GP) and olive mill waste (OMW), which are respectively the main solid residues from coffee roasting, wine making and olive oil production processes. However, increasing the scale of reactor to bring these studies to an industrial level may affect the properties, and hence applications, of the resulting products. The aim of this study is therefore to perform pilot scale experiments to compare and verify the results of analytical study (TGA) and bench scale reactor runs, in order to understand the fundamental differences and create correlations between pyrolysis runs at different scales. To this end, pyrolysis liquids and biochars from the slow pyrolysis of CSS, GP and OMW, performed using different scale auger reactors (15 kg/h and 0.3 kg/h), have been analysed (TGA, pH, density, proximate and ultimate analyses, HHV, FTIR, GCMS) and compared. The results showed no major differences in biochars when the temperature and the solid residence time were fixed. However, regarding pyrolysis liquids, compounds from the lab reactor were more degraded than pilot plant ones, due to, in this case, the vapour residence time was longer. Regarding the properties of the pyrolysis products, GP 400 °C biochars showed the best properties for combustion; CSS biochars were especially rich in nitrogen, and 400 °C GP and OMW pyrolysis liquids showed the highest number of phenolics. Hence, this study is considered a first step towards industrial scale CSS, GP and OMW pyrolysis-based biorefinery.

Cesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy located in the lower uterine segment. The current increase in the percentage of cesarean sections is accompanied by significant growth in the incidence of CSP, while advances in ultrasound diagnostic techniques have led to a greater number of CSP diagnoses. A misdiagnosed CSP, or one that is diagnosed too late, is life-threatening to the pregnant patient and predisposes her to complications such as uterine bleeding or rupture, which often require hysterectomy and thus result in the irreversible loss of fertility. We present the case of a 50-year-old woman with a history of undiagnosed CSP after multiple consultations for intermittent bleeding and hemorrhage. She was diagnosed by ultrasound and the diagnosis was confirmed by hysteroscopy. She underwent conservative medical treatment that was successful.

La presente investigación se realizó con el fin de conocer los procesos de integración de las políticas de género en la educación y de forma específica en el campo de la arquitectura. Para ello se ejecutó una revisión bibliográfica de la integración de la mujer en el campo del diseño y de la arquitectura. Posteriormente se realizó una revisión bibliográfica y en campo (encuestas y entrevistas con directores de escuelas mexicanas) sobre la importancia de la integración de políticas de género a la educación en la época actual, para posteriormente enunciar aquellos indicadores de análisis para lograr la integración. Se realiza la revisión de programas de Arquitectura para observar el funcionamiento actual y determinar estrategias que podrán aplicarse en corto plazo. Todo ello basado en la teoría de identidad de género. Con el estudio de la presencia de las mujeres en los programas educativos, en este caso en México, así como de los lineamientos relacionados, se observó un cambio generacional importante en materia de pensamiento, lo que a su vez se traduce en la sociedad. Las conclusiones versan sobre la importancia que tiene la educación en la incorporación de políticas de género enfocadas a la equidad. Este trabajo pretende dar una clara idea del rumbo que debe tomar la educación hacia la generación de mundo más equitativo.

Background: Diffusion-weighted imaging lesion reversal (DWIR) is frequently observed after mechanical thrombectomy for acute ischemic stroke, but little is known about age-related differences and impact on outcome. We aimed to compare, in patients Methods: We retrospectively analyzed data of patients treated for an anterior circulation acute ischemic stroke with large vessel occlusion in 2 French hospitals, who underwent baseline and 24-hour follow-up magnetic resonance imaging, with baseline DWI lesion volume ≥10 cc. The percentage of DWIR (DWIR%), was calculated as follows: DWIR%=(DWIR volume/baseline DWI volume)×100. Data on demographics, medical history, and baseline clinical and radiological characteristics were collected. Results: Among 433 included patients (median age, 68 years), median DWIR% after mechanical thrombectomy was 22% (6–35) in patients ≥80, and 19% (interquartile range, 10–34) in patients P =0.948). In multivariable analyses, successful recanalization after mechanical thrombectomy was associated with higher median DWIR% in both ≥80 ( P =0.004) and P =0.002) patients. In subgroup analyses performed on a minority of subjects, collateral vessels status score (n=87) and white matter hyperintensity volume (n=131) were not associated with DWIR% ( P >0.2). In multivariable analyses, DWIR% was associated with increased rates of favorable 3-month outcomes in both ≥80 ( P =0.003) and P =0.013) patients; the effect of DWIR% on outcome was not influenced by the age group ( P interaction=0.185) Conclusions: DWIR might be an important and nonage-dependent effect of arterial recanalization, as it seems to beneficially impact 3-month outcomes of both younger and older subjects treated with mechanical thrombectomy for acute ischemic stroke and large vessel occlusion.

Comprehensive set of seismic and potential field data from the whole European Variscan belt is used to interpret the structure and evolution of the European Variscides as defined by Martínez Catalán et al. (2021). The gravity data show the presence of high amplitude, short-wavelength gravity anomalies correlated with the outcrops of eclogites, ultramafic rocks and ophiolites delineating the main body of the Mid-Variscan Allochthon (MVA) and the Devonian Mid-Variscan suture (MVS). The medium amplitude and elongated long-wavelength gravity highs, aligned parallel to the Variscan structural grain, correspond to the low-grade Proterozoic rocks of the MVA and Devonian arc – back-arc system. On the other hand, the short wavelength negative gravity anomalies developed in the central part of the belt coincide with Carboniferous (330–310 Ma) per- to meta-aluminous magmatic bodies. The magnetic data show two belts correlated with Carboniferous Rhenohercynian and Devonian Mid-Variscan magmatic arc granitoids. The Rhenohercynian and Mid-Variscan subduction systems are also well-imaged by moderately dipping primary reflectors in reflection seismic lines. Younger moderately dipping reflectors in the upper-middle crust coincide with outcrops of Carboniferous detachments, limiting granite plutons and core complexes along-strike the core of the Variscan orogeny. Deep crustal reflectors are considered as an expression of lower crustal flow resulting from extensional re-equilibration of the previously thickened Variscan crust. A P-wave velocity logs synthesis shows a high-velocity cratonic crust surrounding a thin Variscan orogenic crust defined by low-velocity lower and middle crusts. The latter crustal type coincides with regional outcrops of 330–310 Ma per- to meta- aluminous granitoids and associated gravity lows along-strike the belt. All these data are used to define the primary polarity of Devonian subduction systems defining the European Variscan belt (Schulmann et al., 2022) and discuss the Carboniferous extension forming specific structure of the Variscan crust. This geodynamic evolution is integrated into a paleomagnetically constrained model of the movements of continental plates and intervening oceans (Edel et al., 2018; Martínez Catalán et al., 2021).REFERENCES:Catalan, J.R.M., Schulmann, K. and Ghienne, J.F., 2021. The Mid-Variscan Allochthon: Keys from correlation, partial retrodeformation and plate-tectonic reconstruction to unlock the geometry of a non-cylindrical belt. Earth-Science Reviews, 220, 1–65.Edel, J.B., Schulmann, K., Lexa, O. and Lardeaux, J.M., 2018. Late Palaeozoic palaeomagnetic and tectonic constraints for amalgamation of Pangea supercontinent in the European Variscan belt. Earth-science reviews, 177, 589-612.Schulmann, K., Edel, J.B., Catalán, J.R.M., Mazur, S., Guy, A., Lardeaux, J.M., Ayarza, P. and Palomeras, I., 2022. Tectonic evolution and global crustal architecture of the European Variscan belt constrained by geophysical data. Earth-Science Reviews, 234, p.104195.

The late Variscan gravitational collapse and coeval magmatism are getting the attention of the community due to their role in the generation of strategic mineral resources. In this regard, the GOLDFINGER project’s main scope is to study how the Variscan orogenic architecture controls the generation of strategic ore deposits (i.e. Sn, W, Nb, Ta, Sc, Au, Sb). With this goal, a 3D model of a gneissic dome with several mineral deposits will be constructed based on high-resolution geophysics (Seismic/Gravity/Magnetism), and regional geology. The study area encompasses the Martinamor gneiss dome which represents a Late-Variscan syn-collisional extensional system with a well-preserved architecture. This gneiss dome structure presents low topography, relatively flat structural geometry in-depth, and contrasting lithotypes regarding seismic, gravity, and magnetic properties. As part of the project, in spring 2022 the area was covered by 30 low-period seismic recorders with 2Hz sensors in a regular grid. The 35x40 km grid consisted of 60 nodes, separated by approximately 4.5 km. To achieve the final node number, the stations were deployed twice, first in a regular grid with nodes each 6 km, and then the grid was moved 3 km to the west and to the south for a second deployment. The seismic stations were continuously recording in the field for up to 40 days in each deployment. We are using a state-of-the-art technique to retrieve high-resolution seismic images of the Martinamor gneiss dome using seismic interferometry applied to seismic background noise (SBN). The preliminary results show that SBN interferometry allows us to 1) detect and track discontinuities that can be related to the structures that control the ore deposits, and 2) identify the location of deep intrusions that are inferred as sources of metallogenic fluids. In this contribution, we present the GOLDFINGER geophysical experiment and the preliminary results.Funding: grant PID2020-117332GB-C21 funded by MCIN/ AEI /10.13039/501100011033; EIT-Raw Materials project 17024 (SIT4ME: Seismic Imaging Techniques for Mineral Exploration); SA085P20 from the JCYL government, and TED2021-130440B-I00 by MCIN. IP is funded by MCIU and USal (BEAGAL18/00090).

The active Taiwan mountain belt is located in a complex geodynamic setting that involves two subduction processes. To the northeast, the Philippine Sea Plate subducts northward beneath the Eurasian Plate at the Ryukyu Trench, while in the southwestern part, the Eurasian Plate subducts eastward under the Philippine Sea Plate, where it obliquely collides with the Luzon Volcanic Arc. The Taiwan thrust-and-fold belt is created as a result of this ongoing arc-continent collision. Regardless of the predominance of compression in the overall structure of the island, several studies have also reported normal faulting. This study aims to estimate the local and regional stress field using earthquake focal mechanism data to contribute to a better understanding of crustal deformation in the complex tectonic setting of Taiwan.Manually clustered earthquake focal mechanisms are inverted to obtain an estimate of the principal stress (σ1, σ2, σ3) orientations and the stress ratio (σ1-σ2)/(σ1-σ3), from which the direction of the maximum horizontal stress (SH) is calculated. The initial data set contains 11,587 earthquake focal mechanisms compiled from several sources dating between 1990 and 2020. All deep earthquakes in the Ryukyu subduction zone were removed from the data set. The Chi-Chi 1999 and other major earthquakes and aftershocks were also removed as they may reflect a distorted stress field. After preprocessing, a database consisting of 8,510 events with focal depths between 1-144 km and magnitudes ML=0.7-5.9 was used in the inversion. Depth division was performed in a regular 7 km grid up to 28 km depth, all events deeper than 28 km being considered in the same layer.Preliminary results show that, to the southwest, the notable clockwise rotation of SH from SW-NE to a W-E direction and a change in the fault type from strike-slip to reverse to the east coincides with the interaction between the ENE-striking reactivated inherited structures of the Eurasian continental margin and the NNE-striking thrust faults of the foreland thrust-and-fold belt. To the centre-east, results show normal faulting in the upper crust, which changes to reverse faulting with depth, suggesting that there is a stress transition at approximately 14 km. Beneath that depth, there is a general state of compression. Ongoing research aims at integrating these results with those of numerical modelling and with field data in an effort to understand the locus of deformation and the occurrence of extensional tectonics in compressional settings, here and in other mountains belts worldwide.This research is part of project PGC2018-094227-B-I00 funded by the Spanish Research Agency of the Ministry of Science and Innovation of Spain. Olivia Lozano acknowledges funding from the same agency through contract PRE2019-091431. Funding from SERA European Union H2020 INFRAIA-2016-2017 Agreement, 170522 is also acknowledged.

The Iberian Massif presents a complex Late Paleozoic evolution, with intense compressional tectonics followed by gravitational collapse of the thickened crust and orocline development. In NW Iberia, extensional detachments and associated shear zones developed during high temperature-low pressure metamorphism in relation to partial melting in gneiss domes. These structures also feature a conspicuous relationship with magnetic anomalies that define a curvature, delineating the geometry of the internal part of the Central Iberian Arc. Regardless of the geometry of these anomalies and their relationship to extensional tectonics, their source probably differs from northern to central and western Iberia. While in northern Iberia extensional tectonics triggered oxidation and development of magnetite in migmatites and S-type granites, in central Iberia basic rocks associated with I-type granites seem to be the carriers of the magnetization. This study aims to describe the western branch of the Central Iberian Arc magnetic anomaly: the Porto-Viseu-Guarda Magnetic Anomaly (PVGMA) and its metallogenetic potential previously related with magnetite-type granites.Polyphase deformation within the Porto-Viseu metamorphic belt later affected by the Douro-Beira shear zone and Porto-Tomar fault presents syn-tectonic staurolite and sillimanite-bearing schists and migmatites (Mindelo Migmatite Complex), great abundance of syn and late S-type two mica-granites, and a post-orogenic porphyritic biotite I-type granite with uncommon high values of magnetic susceptibility (Lavadores granite). These rocks crop out at the northwestern tip of the PVGMA and are thought to be related to it. We sampled migmatites, calc-silicate resisters embedded on them and Lavadores granite for its mineralogical and magnetic characterization.Anisotropy of the magnetic susceptibility sometimes show stable N-S to N90°E, 0°-20° E to NE plunge magnetic lineations and a WNW-ESE magnetic foliation subparallel to the shearing in the area. In migmatites, thin sections feature the expected high temperature metamorphism manifested by sillimanite and ptygmatic folding. Here, rock magnetism studies show Curie temperatures (Tc) around 300°C and low coercivities indicative of titanomagnetite or some sort of multidomain pyrrhotite. Low to moderate magnetic susceptibilities contrast with very high magnetic remanences leading to Königsberger ratios (Qn) of up to 22 in resisters and 10 in the migmatites. Contrarily, the Lavadores granite has high magnetic susceptibilities and moderate Qn (0.1-2). These rocks feature higher Tc=550° and low coercivities indicative of magnetite. Paleomagnetic results show heterogenous directions for both lithologies implying complicated thermal evolutions and possibly late tilting. Despite their proximity, no relationship seems to exist between the Lavadores granite and the Mindelo Migmatite complex protolith. Contrarily to what it is found in northern Iberia, no relationship has been found between extensional features and magnetic mineralization, so if these rocks are the source of the PVGMA, it is most probably related to the characteristics of the protoliths.Despite the PVGMA lies on top of the Sn belt across Portugal, geochemical results do not support Lavadores as a potential Sn metallogenetic granite, further indicating the lack of relationship between the formation of magnetite and that of Sn mineralizations.Acknowledgements: Project SA084P20 (regional CYL government); Grants PID2020-117332GB-C21 funded by MCIN/AEI/10.13039/501100011033 and TED2021-130440B-I00; Projects UIDB/04683/2020 and UIDP/04683/2020 (Portugal).

Arcuate trace of large structures characterizes many mountain chains. The Variscan Belt is not an exception, and depicts one of the tightest oroclines in the world, the Ibero-Armorican Arc. In addition, the belt features a few more open arcs in the Eastern Moroccan Meseta, Central Iberia, the French Massif Central and the Bohemian Massif. All Variscan arcs are considered oroclines or secondary oroclines according to definitions by Weil and Sussman (2004) and Johnston et al. (2013) respectively. They are also essentially late orogenic features, but their timing and deformation mechanisms differ. Models explaining their origin have been proposed for some individual arcs, and are generally controversial.This contribution aims at interpreting the ensemble of Variscan arcs paying attention to their age relative to previous orogenic features as well as to those associated with arc development. Such features include first order structures, metamorphism and plutonism, as well as magnetic and gravimetric anomalies. Development of the arcs is viewed as somehow related with late Variscan dextral transpression provoked by the relative displacement of Laurussia to the East relatively to Gondwana during the Pennsylvanian and early Permian (325-290 Ma; Arthaud and Matte, 1977; Shelley and Bossière, 2000; Martínez Catalán et al., 2021). But several mechanisms operated to form the arcs, the most important of them being ductile transcurrent shearing, indentation and shortening perpendicular and parallel to the orogenic trend. These mechanisms acted at different time intervals and their participation or relative importance varies for each arc, as well as their involvement in the development of the structural, metamorphic and igneous features and in the geophysical characteristics.REFERENCES:Arthaud, F. and Matte, P. 1977. Late Paleozoic strike-slip faulting in southern Europe and northern Africa: result of a right-lateral shear zone between the Appalachians and the Urals. Geological Society of America Bulletin, 88, 1305-1320.Johnston, S.T., Weil, A.B. and Gutiérrez-Alonso, G. 2013. Oroclines: Thick and thin. Geological Society of America Bulletin, 125 (5-6), 643-663.Martínez Catalán, J.R., Schulmann, K. and Ghienne, J.F. 2021. The Mid-Variscan Allochthon: Keys from correlation, partial retrodeformation and plate-tectonic reconstruction to unlock the geometry of a non-cylindrical belt. Earth-Science Reviews, 220, 103700, 1-65.Shelley, D. and Bossière, G. 2000. A new model for the Hercynian Orogen of Gondwanan France and Iberia. Journal of Structural Geology, 22 (6), 757-776.Acknowledgement: Spanish Ministry of Science and Innovation, project PID2020-117332GB-C21.

The Iberian Massif presents a geometry characterized by two oroclines: the conspicuous and tight Ibero-armorican arc to the north and the older and less pronounced Central Iberian Arc (CIA) to the south. The latter is clearly depicted by low amplitude, short wavelength magnetic anomalies in its external part and long wavelength, higher amplitude magnetic anomalies in its internal part. The origin of these is under study as they seem to be indicators of the deep evolution of this orogen in the Iberian Peninsula.Three magnetic anomalies stand out in the internal part of the CIA. To the north, the Eastern Galicia Magnetic Anomaly overlaps the Lugo Gneiss Dome, a structure delineated by extensional detachments. Here, the exhumation at high temperatures during late Variscan gravitational collapse triggered the formation of magnetite in metasediments, migmatites and S-type syn-orogenic granites, thus stablishing a clear relationship between tectonics and magnetization. To the west, the Porto-Viseu-Guarda Magnetic Anomaly has still an unclear origin, but it also overlaps an area characterized by extensional tectonics, gneiss domes development and granite intrusion. However, the most magnetic outcropping rocks are late Variscan I-type granites (Lavadores granite) and the Mindelo Migmatitic Complex. None of them shows a relationship between magnetization and extension. Contrarily, magnetic minerals seem to be related to the composition of the resisters in migmatites and to the formation of the Lavadores granite itself. Finally, the Spanish Central System Magnetic Anomaly, at the core of the CIA, also overlaps the exhumed products of late Variscan extension (granites and migmatites). The magnetic anomaly associated to this part of the arc has been studied in the Castellanos Antiform, a discrete extensional dome located in its northern part, where the interaction between high degree metasediments, extension, and migmatization can be revised. New high resolution magnetic and gravity data indicate that the magnetic anomaly coincides with a high Bouguer gravity anomaly, and overlaps an outcrop of granitoids with tonalitic xenoliths and gabbros. The relationship between gravity and magnetic anomalies, together with the lack of outcropping magnetic granitoids and/or migmatites in the Central System, and the high amount of heterogeneous xenoliths, including basic rocks, suggest that in central Iberia, late Variscan extension might have involved deeper levels of the crust and maybe the mantle. Considering the location of this area, in the core of the CIA, and the simultaneity between late Variscan extension and the CIA formation, we suggest that the development of the latter might have played an important role in the supply of mantle material.Funding: grant PID2020-117332GB-C21 and projects SA084P20, MCIN/AEI/10.13039/501100011033 and TED2021-130440B-I

As a result of the collision of Gondwana, peri-Gondwanan terranes, and Laurussia in the Upper Devonian to early Permian, various Paleozoic oceans are thought to have closed, leading to the formation of the Variscan belt. The belt experienced oroclinal bending in the latter phases of the orogeny, a process that became significant in the Iberian Massif, the westernmost part of the European Variscan belt. There, the belt acquired an S-shaped attitude defined by the Central Iberian Arc (CIA) to the south and the Ibero-Armorican Arc (IAA) to the north. The early Variscan structures, the magnetic anomalies, and the tectonostratigraphic zonation of the Iberian Massif are all bent by both arcs.The IAA is extensively studied, but the tectonic evolution of the CIA is not well resolved because a large part of it is covered by sediments of the Paleogene Duero basin. Paleomagnetism is a very useful tool used to identify possible vertical axis rotations. Therefore, we carefully searched for outcrops that may record paleomagnetic directions that could shed some light on the development of the CIA.Weakly metamorphic Cambrian limestones from the southern limb of the CIA were subjected to magnetic and paleomagnetic investigations. 32 sites in 5 outcropping structures in the Urda-Los Navalucillos Formation of Montes de Toledo (Central Iberian Zone, Spain), close to the CIA hinge zone, yielded more than 270 cores. These outcrops were affected by two regional-scale Variscan folding phases, namely C1 and C3, which developed interference patterns. A characteristic paleomagnetic component was found at 19 sites in 4 of the structures. This component reveals different temporal correlations with C3 folds, from syn-folding to certainly post-folding. The resulting mean directions of the magnetic vector, in geographic coordinates, consistently display northward to north-western declinations and negative, low inclinations, indicating that they have been acquired before the geomagnetic reverse polarity Kiaman superchron when Iberia was in the southern hemisphere. Although the inclination of the paleomagnetic mean directions is consistent amongst structures, the declination varies from N to NW, suggesting a vertical axis rotation synkinematic to C3 folding previous to 318 Ma. These directions indicate that the early evolution of the southern limb of the CIA was differentially recorded by the paleomagnetic directions of the different structures and underwent a 42º clockwise rotation during the late Carboniferous. The later development of the IAA was associated with a significant counterclockwise rotation that affected the entire paleomagnetic record. (Research support: SA084P20, PID2020-117332GB-C21, PID2019-108753GB-C21, AEI/10.13039/501100011033, FPU16/00980, PTA2017-14779-I and FJC2019-041058-I)

Hemorrhage remains a major complication of anticoagulants, with bleeding leading to serious and even life-threatening outcomes in rare settings. Currently available anticoagulants target either multiple coagulation factors or specifically coagulation factor (F) Xa or thrombin; however, inhibiting these pathways universally impairs hemostasis. Bleeding complications are especially salient in the medically complex population who benefit from medical devices. Extracorporeal devices—such as extracorporeal membrane oxygenation, hemodialysis, and cardiac bypass—require anticoagulation for optimal use. Nonetheless, bleeding complications are common, and with certain devices, highly morbid. Likewise, pharmacologic prophylaxis to prevent thrombosis is not commonly used with many medical devices like central venous catheters due to high rates of bleeding. The contact pathway members FXI, FXII, and prekallikrein serve as a nexus, connecting biomaterial surface-mediated thrombin generation and inflammation, and may represent safe, druggable targets to improve medical device hemocompatibility and thrombogenicity. Recent in vivo and clinical data suggest that selectively targeting the contact pathway of coagulation through the inhibition of FXI and FXII can reduce the incidence of medical device-associated thrombotic events, and potentially systemic inflammation, without impairing hemostasis. In the following review, we will outline the current in vivo and clinical data encompassing the mechanism of action of drugs targeting the contact pathway. This new class of inhibitors has the potential to herald a new era of effective and low-risk anticoagulation for the management of patients requiring the use of medical devices.

Legend for Supplemental Figure 1.

Schematic representation of the IL-17A and REG3β signaling pathway and PDAC development.

PDF file, 57K, Primers used for real time qRT-PCR.

Coagulation factor XI (FXI) has increasingly been shown to play an integral role in several physiologic and pathological processes. FXI is among several zymogens within the blood coagulation cascade that are activated by proteolytic cleavage, with FXI converting to the active serine protease form (FXIa). The evolutionary origins of FXI trace back to duplication of the gene that transcribes plasma prekallikrein, a key factor in the plasma kallikrein–kinin system, before further genetic divergence led to FXI playing a unique role in blood coagulation. While FXIa is canonically known for activating the intrinsic pathway of coagulation by catalyzing the conversion of FIX into FIXa, it is promiscuous in nature and has been shown to contribute to thrombin generation independent of FIX. In addition to its role in the intrinsic pathway of coagulation, FXI also interacts with platelets, endothelial cells, and mediates the inflammatory response through activation of FXII and cleavage of high-molecular-weight kininogen to generate bradykinin. In this manuscript, we critically review the current body of knowledge surrounding how FXI navigates the interplay of hemostasis, inflammatory processes, and the immune response and highlight future avenues for research. As FXI continues to be clinically explored as a druggable therapeutic target, understanding how this coagulation factor fits into physiological and disease mechanisms becomes increasingly important.

Background: To further our understanding of the pathophysiology of spontaneous intracerebral hemorrhage (ICH) and related injury, we provided a postmortem neuropathological examination of acute microvascular lesions (microbleeds and microinfarcts) within the perihematomal area. Methods: We included all consecutive cases (2005–2019) from the Lille University Hospital brain bank of ICH patients who died within the first month. Paraffin-embedded tissue sections from the perihematomal area were processed for several stainings and immunolabelings to investigate the presence of acute microbleeds and microinfarcts in the perihematomal area and to characterize surrounding neuronal and systemic inflammatory reaction (macrophages and neutrophils). Results: We included 14 ICH cases (median age, 78 years; 10 females). Acute microbleeds were observed in the perihematomal area in 12/14 patients (86%, ranging from 1 through >10) and microinfarcts in 5/14 (36%, ranging from 1 through 4). Microbleeds were observed whatever the delay from ICH onset to death was, while most cases with acute microinfarcts were observed between day 3 and day 7 (n=3/5). Both lesions were characterized by an abundant accumulation of systemic inflammatory cells and necrotic areas. Conclusions: Acute microbleeds and microinfarcts might contribute to the propagation of secondary brain tissue damages after ICH. Our examinations also question the potential role of massive systemic inflammatory cells recruitment in the genesis of these microvascular injuries.

Point of injection scatter (SPI) confounds breast cancer sentinel lymph node detection. Round flat lead shields (FLSs) incompletely reduce SPI, requiring repositioning. We designed lead shields that reduce SPI and acquisition time. Two concave lead shields, a semioval lead shield (OLS) and a semispherical lead alloy shield (SLS), were created with a SICNOVA JCR 1000 3D printer to cover the point of injection (patent no. ES1219895U). Twenty breast cancer patients had anterior and anterior oblique imaging, 5 minutes and 2 hours after a single 111 MBq nanocolloid in 0.2 mL intratumoral or periareolar injection. Each acquisition was 2 minutes. Absolute and normalized background corrected scatter counts (CSCs) and scatter reduction percentage (%SR) related to the FLS were calculated. Repositionings were recorded. Differences between means of %SR (t test) and between means of CSC (analysis of variance) with Holm multiple comparison tests were determined. Mean %SR was 91.8% with OLS and 92% using SLS in early images (P = 0.91) and 87.2%SR in OLS and 88.5% in late images (P = 0.66). There were significant differences between CSC using FLS and OLS (P We designed 2 concave lead shields that significantly reduce the SPI and repositioning with sentinel lymph node lymphoscintigraphy.

Guy Rohrbaugh and Allan Hazlett have provided two arguments against the thesis that musical works are types. In short, they assume that, according to our modal talk and intuitions, musical works are modally flexible entities; since types are modally inflexible entities, musical works are not types. I argue that Rohrbaugh’s and Hazlett’s arguments fail and that the type/token theorist can preserve the truth of our modal claims and intuitions even if types are modally inflexible entities. First, I consider two alternatives for the type/token theorist proposed in recent literature about the topic: the created types’ solution and the created abstract objects’ solution. I argue that none of them is attractive for the type/token theorist because they do not preserve the theoretical advantages of type/token theories to explain musical works’ repeatable nature. Then, I focus on the arguments’ common premise that musical works are modally flexible entities. A deeper analysis of musical practice will show that this premise is not true: our modal claims do not imply that musical works could have had different intrinsic but, instead, extrinsic properties. Finally, I show how the nested types theory may offer a satisfactory explanation of this fact and how it captures the truth of our modal talk about musical works.

International audience; Iron deficiency is frequent in patients with chronic inflammatory conditions (e.g., chronic heart failure, chronic kidney disease, cancers, and bowel inflammatory diseases). Indeed, high concentrations of inflammatory cytokines increase hepcidin concentrations that lead to the sequestration of iron in cells of the reticuloendothelial system (functional iron deficiency). Iron parameters are often assessed only in the context of anemia, but iron deficiency, even without anemia, is present in about half of patients with inflammatory conditions. Iron deficiency worsens underlying chronic diseases and is an independent factor of morbidity and mortality. In daily practice, the most effective biomarkers of iron status are serum ferritin, which reflects iron storage, and transferrin saturation, which reflects the transport of iron. Serum ferritin is increased in an inflammatory context, and there is still no consensus on the threshold to be used in chronic inflammatory conditions. Nevertheless, recent recommendations of international guidelines agreed to define iron deficiency by serum ferritin

International audience; The functioning of the heart muscle is particularly sensitive to iron deficiency, the easily curable comorbidity most frequently associated with heart failure. Iron-deficient heart failure patients are more often rehospitalized and have reduced survival. Heart muscle function is particularly susceptible to martial deficiency. Recent randomized studies have shown that exogenous iron intake is accompanied by improved functional capacity (walking test), quality of life, and re-hospitalization rate in these patients. The symptoms of iron deficiency are not very specific and often confused with those of heart failure or other comorbidities, which explains why management is often too late. Anemia is only a late consequence of this iron deficiency. Due to the inflammatory state associated with chronic heart failure, only the parenteral route can bypass the macrophage tissue sequestration of iron and inhibit its intestinal absorption. Recent European guidelines recommend screening for iron deficiency (serum ferritin and transferrin saturation coefficient) in all patients with suspected heart failure, routine iron parameters assessment in all patients with heart failure, and intravenous iron supplementation in case of deficiency in symptomatic patients. Given the pejorative nature of iron deficiency on disease progression, the frequency and financial impact of hospitalizations linked to episodes of decompensation, as well as the effectiveness of simple supplementation, screening for this comorbidity, screening for this frequent comorbidity should now be part of routine testing in all heart failure patients.

In patients with acute intermittent porphyria (AIP), induction of delta aminolevulinic acid synthase 1 (ALAS1) leads to haem precursor accumulation that may cause recurring acute attacks. In a recent phase III trial, givosiran significantly reduced the attack rate in severe AIP patients. Frequent adverse events were injection-site reaction, fatigue, nausea, chronic kidney disease and increased alanine aminotransferase.To describe the efficacy and safety of givosiran based on a personalized medical approach.We conducted a retrospective patient file study in 25 severe AIP patients treated with givosiran in France. We collected data on clinical and biochemical efficacy along with reports of adverse events.Givosiran drastically reduced the attack rate in our cohort, as 96% were attack-free at the time of the study. The sustained efficacy of givosiran in most patients allowed us to personalize dosing frequency. In 42%, givosiran was only given when haem precursor levels were increasing. Our data suggest that givosiran is most effective when given early in the disease course. We confirmed a high prevalence of adverse events. One patient discontinued treatment due to acute pancreatitis. All patients had hyperhomocysteinemia, and all patients with initial homocysteine levels available showed an increase under treatment. In this context, one patient was diagnosed with pulmonary embolism.The sustained effect of givosiran allowed a decrease in dosing frequency without compromising treatment efficacy. The high prevalence of adverse events emphasizes the importance of restricting the treatment to severe AIP and administering the minimum effective dose for each patient.

[Background and Aims] The observed positive diversity effect on ecosystem functioning has rarely been assessed in terms of intraspecific trait variability within populations. Intraspecific phenotypic variability could stem both from underlying genetic diversity and from plasticity in response to environmental cues. The latter might derive from modifications to a plant’s epigenome and potentially last multiple generations in response to previous environmental conditions. We experimentally disentangled the role of genetic diversity and diversity of parental environments on population productivity, resistance against environmental fluctuations and intraspecific phenotypic variation. [Methods} A glasshouse experiment was conducted in which different types of Arabidopsis thaliana populations were established: one population type with differing levels of genetic diversity and another type, genetically identical, but with varying diversity levels of the parental environments (parents grown in the same or different environments). The latter population type was further combined, or not, with experimental demethylation to reduce the potential epigenetic diversity produced by the diversity of parental environments. Furthermore, all populations were each grown under different environmental conditions (control, fertilization and waterlogging). Mortality, productivity and trait variability were measured in each population. [Key Results] Parental environments triggered phenotypic modifications in the offspring, which translated into more functionally diverse populations when offspring from parents grown under different conditions were brought together in mixtures. In general, neither the increase in genetic diversity nor the increase in diversity of parental environments had a remarkable effect on productivity or resistance to environmental fluctuations. However, when the epigenetic variation was reduced via demethylation, mixtures were less productive than monocultures (i.e. negative net diversity effect), caused by the reduction of phenotypic differences between different parental origins. [Conclusions] A diversity of environmental parental origins within a population could ameliorate the negative effect of competition between coexisting individuals by increasing intraspecific phenotypic variation. A diversity of parental environments could thus have comparable effects to genetic diversity. Disentangling the effect of genetic diversity and that of parental environments appears to be an important step in understanding the effect of intraspecific trait variability on coexistence and ecosystem functioning., This work was supported by the Czech Science Foundation (GACR 20-00871S) and the Estonian Research Council (project PSG293 to C.P.C.) and the European Union through the European Regional Development Fund (Centre of Excellence EcolChange to C.P.C.).

International audience; Aim: To compare methods of quantifying serum hepcidin (based on MS and ELISA) and their ability to diagnose true iron deficiency anemia in critically ill patients. Materials & methods: Serum hepcidin was measured in 119 critically ill patients included in the HEPCIDANE clinical trial, using either an ultra-sensitive ELISA kit (from DRG) or two different MS methods. Results: The results show a good correlation between the different methods studied. The Bland–Altman analysis and the Kappa test for clinical groups show a good or very good agreement between the different tests. Conclusion: ELISA or MS show a satisfactory commutability to quantify serum hepcidin. This is of great importance for the determination of therapeutic strategies in iron deficiency.

Context Subclinical thyroid dysfunction and anemia are common disorders, and both have increasing prevalence with advancing age. Objective The aim of this study was to assess whether levothyroxine treatment leads to a rise in hemoglobin levels in older persons with subclinical hypothyroidism. Methods This preplanned combined analysis of 2 randomized controlled trials included community-dwelling persons aged 65 years and older with subclinical hypothyroidism who were randomly assigned to levothyroxine or placebo treatment. The levothyroxine dose was periodically titrated aiming at thyroid stimulating hormone (TSH) level within the reference range, with mock titrations in the placebo group. The main outcome measure was the change in hemoglobin level after 12 months. Results Analyses included 669 participants (placebo n = 337, levothyroxine n = 332) with a median age of 75 years (range, 65-97) and mean baseline hemoglobin of 13.8 ± 1.3 g/dL. Although levothyroxine treatment resulted in a reduction in TSH from baseline after 12 months of follow-up compared with placebo, the change in hemoglobin level was not different between the levothyroxine and the placebo groups (−0.03 g/dL [95% CI, −0.16 to 0.11]). Similar results were found in stratified analyses including sex, age, or TSH levels. No difference in change of hemoglobin levels after 12 months was identified in 69 participants with anemia at baseline (−0.33 g/dL [95% CI, −0.87 to 0.21]). Conclusion In persons aged 65 years and older with subclinical hypothyroidism, treatment with levothyroxine does not lead to a rise in hemoglobin levels, regardless of the presence of anemia.

The Mendelian inheritance pattern of acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria is autosomal dominant, but the clinical phenotype is heterogeneous. Within the general population, penetrance is low, but among first-degree relatives of a symptomatic proband, penetrance is higher. These observations suggest that genetic factors, in addition to mutation of the specific enzyme of the biosynthetic pathway of heme, contribute to the clinical phenotype. Recent studies by others suggested that the genotype of the transporter protein ABCB6 contribute to the porphyria phenotype. Identifying the molecule(s) that are transported by ABCB6 has been problematic and has led to uncertainty with respect to how or if variants/mutants contribute to phenotypic heterogeneity. Knockout mouse models of Abcb6 have not provided a direction for investigation as homozygous knockout animals do not have a discrete phenotype. To address the proposed link between ABC6 genotype and porphyria phenotype, a large cohort of patients with acute hepatic porphyria and erythropoietic protoporphyria was analyzed. Our studies showed that ABCB6 genotype did not correlate with disease severity. Therefore, genotyping of ABCB6 in patients with acute hepatic porphyria and erythropoietic protoporphyria is not warranted.

Premise of research. Root traits of annual plants are known to vary across environmentally manipulated conditions in controlled settings. Roots absorb nutrients and water, essential for individual ...

Animals moving together in groups are believed to interact among each other with effective social forces, such as attraction, repulsion and alignment. Such forces can be inferred using 'force maps', i.e. by analysing the dependency of the acceleration of a focal individual on relevant variables. Here we introduce a force map technique for alignment depending on relative velocities between an individual and its neighbours. After the force map approach is validated with an agent-based model, we apply it to experimental data of schooling fish, where we observe signatures of an effective alignment force with faster neighbours, and an unexpected anti-alignment with slower neighbours. Instead of an explicit anti-alignment behaviour, we suggest that the observed pattern is a result of a selective attention mechanism, where fish pay less attention to slower neighbours. We present support for this hypothesis both from agent-based modeling, as well as from exploring leader-follower relationships between faster and slower neighbouring fish in the experimental data., Comment: Main paper (12 pages) + Supplementary Information (14 pages)

The maintenance of hemostasis to ensure vascular integrity is dependent upon the rapid conversion of zymogen species of the coagulation cascade to their enzymatically active forms. This process culminates in the generation of the serine protease thrombin and polymerization of fibrin to prevent vascular leak at sites of endothelial cell injury or loss of cellular junctions. Thrombin generation can be initiated by the extrinsic pathway of coagulation through exposure of blood to tissue factor at sites of vascular damage, or alternatively by the coagulation factor (F) XII activated by foreign surfaces with negative charges, such as glass, through the contact activation pathway. Here, we used transient particle tracking microrheology to investigate the mechanical properties of fibrin in response to thrombin generation downstream of both coagulation pathways. We found that the structural heterogeneity of fibrin formation was dependent on the reaction kinetics of thrombin generation. Pharmacological inhibition of FXII activity prolonged the time to form fibrin and increased the degree of heterogeneity of fibrin, resulting in fibrin clots with reduced mechanical properties. Taken together, this study demonstrates a dependency of the physical biology of fibrin formation on activation of the contact pathway of coagulation.

Casting semantic segmentation of outdoor LiDAR point clouds as a 2D problem, e.g., via range projection, is an effective and popular approach. These projection-based methods usually benefit from fast computations and, when combined with techniques which use other point cloud representations, achieve state-of-the-art results. Today, projection-based methods leverage 2D CNNs but recent advances in computer vision show that vision transformers (ViTs) have achieved state-of-the-art results in many image-based benchmarks. In this work, we question if projection-based methods for 3D semantic segmentation can benefit from these latest improvements on ViTs. We answer positively but only after combining them with three key ingredients: (a) ViTs are notoriously hard to train and require a lot of training data to learn powerful representations. By preserving the same backbone architecture as for RGB images, we can exploit the knowledge from long training on large image collections that are much cheaper to acquire and annotate than point clouds. We reach our best results with pre-trained ViTs on large image datasets. (b) We compensate ViTs' lack of inductive bias by substituting a tailored convolutional stem for the classical linear embedding layer. (c) We refine pixel-wise predictions with a convolutional decoder and a skip connection from the convolutional stem to combine low-level but fine-grained features of the the convolutional stem with the high-level but coarse predictions of the ViT encoder. With these ingredients, we show that our method, called RangeViT, outperforms existing projection-based methods on nuScenes and SemanticKITTI. The code is available at https://github.com/valeoai/rangevit., Comment: CVPR 2023. Code at https://github.com/valeoai/rangevit

Learning models on one labeled dataset that generalize well on another domain is a difficult task, as several shifts might happen between the data domains. This is notably the case for lidar data, for which models can exhibit large performance discrepancies due for instance to different lidar patterns or changes in acquisition conditions. This paper addresses the corresponding Unsupervised Domain Adaptation (UDA) task for semantic segmentation. To mitigate this problem, we introduce an unsupervised auxiliary task of learning an implicit underlying surface representation simultaneously on source and target data. As both domains share the same latent representation, the model is forced to accommodate discrepancies between the two sources of data. This novel strategy differs from classical minimization of statistical divergences or lidar-specific state-of-the-art domain adaptation techniques. Our experiments demonstrate that our method achieves a better performance than the current state of the art in synthetic-to-real and real-to-real scenarios., Comment: Project repository: github.com/valeoai/SALUDA

The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms. Here, we provide an updated overview of the GO knowledgebase, as well as the efforts of the broad, international consortium of scientists that develops, maintains, and updates the GO knowledgebase. The GO knowledgebase consists of three components: (1) the GO-a computational knowledge structure describing the functional characteristics of genes; (2) GO annotations-evidence-supported statements asserting that a specific gene product has a particular functional characteristic; and (3) GO Causal Activity Models (GO-CAMs)-mechanistic models of molecular "pathways" (GO biological processes) created by linking multiple GO annotations using defined relations. Each of these components is continually expanded, revised, and updated in response to newly published discoveries and receives extensive QA checks, reviews, and user feedback. For each of these components, we provide a description of the current contents, recent developments to keep the knowledgebase up to date with new discoveries, and guidance on how users can best make use of the data that we provide. We conclude with future directions for the project.

Semantic segmentation of point clouds in autonomous driving datasets requires techniques that can process large numbers of points over large field of views. Today, most deep networks designed for this task exploit 3D sparse convolutions to reduce memory and computational loads. The best methods then further exploit specificities of rotating lidar sampling patterns to further improve the performance, e.g., cylindrical voxels, or range images (for feature fusion from multiple point cloud representations). In contrast, we show that one can build a well-performing point-based backbone free of these specialized tools. This backbone, WaffleIron, relies heavily on generic MLPs and dense 2D convolutions, making it easy to implement, and contains just a few parameters easy to tune. Despite its simplicity, our experiments on SemanticKITTI and nuScenes show that WaffleIron competes with the best methods designed specifically for these autonomous driving datasets. Hence, WaffleIron is a strong, easy-to-implement, baseline for semantic segmentation of sparse outdoor point clouds.

The diversity of diatoms in the hot springs of the Comanjilla geothermal zone in northern Guanajuato, Mexico was studied. Hot springs are extreme ecosystems that, despite having high temperatures, constitute an environment for many thermophilic microorganisms (bacteria, cyanobacteria, and diatoms). The thermal water studied is classified as hyperthermal water (45°C to 100°C), of deep origin, and with low mineralization, are of type sulfuric sodium chloride, since the dissolved content of hydrogen sulfide (H2S) is found in concentrations higher than 1mg/L, and its smell is similar to the one of rotten eggs, presents a pH of 7.6 to 9.1 that represents neutrophilic to alkaliphilic environments, with a variable electrical conductivity (EC) (658-698 µs / cm) and total dissolved solids (TDS) (314-24 ppm). In the same way, these hot springs present microbial mats that consist of several stratified layers of green and orange color of 100 cm2, each one, which are dominated by specific types of microorganisms such as bacteria, cyanobacteria, but mainly diatoms, the latter were studied applying the scanning electron microscope and the optical microscope. The morphological characteristics observed in the optical microscope and in the scanning electron microscopy indicate the presence of diatoms of the Bacillariophyceae class, represented by Sellaphora disjuncta (55%), Achnanthes brevipes var. intermedia (45%). This diatom present in thermophilic microbial mats in the sulphurous geothermal zone of Comanjilla represents: a) the first report of said microorganisms in the study area and Mexico; b) an ecosystem of great interest from the biotechnological and industrial point of view; c) an important taxon in terms of diversity and technology; d) an applications in biofuels, environmental monitoring, wastewater treatment, manufacture of fertilizers, production of secondary metabolites, medical compounds, energy sources and food industry and within nanotechnology. It is important to mention that the physical and chemical characteristics of thermal water such as temperature, pH, dissolved solids, electrical conductivity, hardness, alkalinity and silica concentrations, were the major environmental factors influencing the distribution of diatoms in sulphurous hot springs.

This paper aims to shed light on the question of whether musical appropriation is ethically unobjectionable. James Young (2021) has recently advanced a position on this topic, according to which, whereas the appropriation of a whole work is uncontroversially non-permissible, the appropriation of parts of a work is usually permissible. He grounds this view in ontological matters and in a criterion of fair use in terms of economic harm to the source work’s composer. I argue that, pace Young, we cannot make general ethical claims about musical appropriation because their truth is sensitive to the musical genres that the involved works belong to. First, I clarify the scope of musical appropriation by means of considerations on musical practices and ontology. This will reveal that versions and covers are not genuine cases of musical appropriation. In a second step, I consider a specific kind of musical appropriation: using the first measures of a source work as the first measures of a secondary work. I show that, even if we assume Young’s ontological framework and his criterion on fair use, the instances of this kind of musical appropriation count as fair or unfair depending on the musical genres of the involved works due to their normative implications for the composition and appreciation of those works.

Resumen Introduccion Nuestro objetivo ha sido informar de los resultados oncologicos de pacientes con ERET y antecedentes de neoplasias urologicas que fueron sometidos posteriormente a un trasplante renal (TR). Material y metodo Estudio retrospectivo llevado a cabo en el registro de la Fundacion Puigvert (Barcelona) con 1.200 TR realizados entre 1988 y 2018. Se identificaron 85 neoplasias urologicas que recibieron tratamiento previo al TR en 81 pacientes: 15 (18%) canceres de prostata, 49 (58%) carcinoma de celulas renales (CCR), 19 (22%) carcinomas uroteliales y 2 (2%) canceres de testiculo. Se registraron datos de las caracteristicas basales, la estadificacion del cancer, el tratamiento y el seguimiento, y sobre la cronologia del inicio de dialisis, la inscripcion en la lista de espera y el TR. Los criterios de valoracion fueron la recidiva del cancer, la progresion metastasica, la muerte especifica por cancer y la supervivencia global. Resultados En una mediana de seguimiento de 13,1 anos (2,2-32), se registraron 16/85 (19%) recidivas del cancer, con 3 (4%) progresiones a metastasis y muerte por cancer. La mediana de supervivencia global tras el tratamiento del cancer fue de 25,3 anos y la supervivencia por cancer especifica fue del 95% a los 25 anos. La mediana de tiempo desde el tratamiento del cancer hasta el trasplante de rinon fue de 4,8 anos: 3,7 anos en el cancer de prostata, 3,9 anos en el CCR y 8,8 anos en el cancer vesical. La mediana de tiempo desde el inicio de dialisis hasta el TR fue de 1,8 anos en los pacientes con antecedentes de neoplasia urologica, frente a 0,5 anos en la cohorte total de 1.200 trasplantes renales durante el mismo periodo. Conclusiones Los pacientes con antecedentes de neoplasias urologicas bien seleccionados se pueden beneficiar enormemente del trasplante de rinon con una recidiva del cancer tardia y poco frecuente. Para el cancer de prostata de bajo riesgo y el CCR, podria optimizarse el tiempo de espera, pero se necesitan datos mas solidos en este contexto.