Discovery of the elusive carbonic acid (HOCOOH) in space

After a quarter century since the detection of the last interstellar carboxylic acid, acetic acid (CH$_3$COOH), we report the discovery of a new one, the cis-trans form of carbonic acid (HOCOOH), toward the Galactic Center molecular cloud G+0.693-0.027. HOCOOH stands as the first interstellar molecule containing three oxygen atoms and also the third carboxylic acid detected so far in the interstellar medium. Albeit the limited available laboratory measurements (up to 65 GHz), we have also identified several pairs of unblended lines directly in the astronomical data (between 75-120 GHz), which allowed us to slightly improve the set of spectroscopic constants. We derive a column density for cis-trans HOCOOH of $N$ = (6.4 $\pm$ 0.4) $\times$ 10$^{12}$ cm$^{-2}$, which yields an abundance with respect to molecular H$_2$ of 4.7 $\times$ 10$^{-11}$. Meanwhile, the extremely low dipole moment (about fifteen times lower) of the lower-energy conformer, cis-cis HOCOOH, precludes its detection. We obtain an upper limit to its abundance with respect to H$_2$ of $\leq$ 1.2 $\times$10$^{-9}$, which suggests that cis-cis HOCOOH might be fairly abundant in interstellar space, although it is nearly undetectable by radio astronomical observations. We derive a cis-cis/cis-trans ratio $\leq$ 25, consistent with the smaller energy difference between both conformers compared with the relative stability of trans- and cis-formic acid (HCOOH). Finally, we compare the abundance of these acids in different astronomical environments, further suggesting a relationship between the chemical content found in the interstellar medium and the chemical composition of the minor bodies of the Solar System, which could be inherited during the star formation process.Comment: Accepted for publication in The Astrophysical Journa

First glycine isomer detected in the interstellar medium: glycolamide (NH2_2C(O)CH2_2OH)

We report the first detection in the interstellar medium of a C$_2$H$_5$O$_2$N isomer: $syn$-glycolamide (NH$_2$C(O)CH$_2$OH). The exquisite sensitivity at sub-mK levels of an ultra-deep spectral survey carried out with the Yebes 40m and IRAM 30m telescopes towards the G+0.693-0.027 molecular cloud have allowed us to unambiguously identify multiple transitions of this species. We derived a column density of (7.4 $\pm$ 0.7)$\times$10$^{12}$ cm$^{-2}$, which implies a molecular abundance with respect to H$_2$ of 5.5$\times$10$^{-11}$. The other C$_2$H$_5$O$_2$N isomers, including the higher-energy $anti$ conformer of glycolamide, and two conformers of glycine, were not detected. The upper limit derived for the abundance of glycine indicates that this amino acid is surely less abundant than its isomer glycolamide in the ISM. The abundances of the C$_2$H$_5$O$_2$N isomers cannot be explained in terms of thermodynamic equilibrium, and thus chemical kinetics need to be invoked. While the low abundance of glycine might not be surprising, based on the relative low abundances of acids in the ISM compared to other compounds (e.g. alcohols, aldehydes or amines), several chemical pathways can favour the formation of its isomer glycolamide. It can be formed through radical-radical reactions on the surface of dust grains. The abundances of these radicals can be significantly boosted in an environment affected by a strong ultraviolet field induced by cosmic rays, such as that expected in G+0.693-0.027. Therefore, as shown by several recent molecular detections towards this molecular cloud, it stands out as the best target to discover new species with carbon, oxygen and nitrogen with increasing chemical complexity.Comment: Accepted in The Astrophysical Journal Letter

Precursors of the RNA-world in space: Detection of (ZZ)-1,2-ethenediol in the interstellar medium, a key intermediate in sugar formation

We present the first detection of ($Z$)-1,2-ethenediol, (CHOH)$_2$, the enol form of glycolaldehyde, in the interstellar medium towards the G+0.693-0.027 molecular cloud located in the Galactic Center. We have derived a column density of (1.8$\pm$0.1)$\times$10$^{13}$ cm$^{-2}$, which translates into a molecular abundance with respect to molecular hydrogen of 1.3$\times$10$^{-10}$. The abundance ratio between glycolaldehyde and ($Z$)-1,2-ethenediol is $\sim$5.2. We discuss several viable formation routes through chemical reactions from precursors such as HCO, H$_2$CO, CHOH or CH$_2$CHOH. We also propose that this species might be an important precursor in the formation of glyceraldehyde (HOCH$_2$CHOHCHO) in the interstellar medium through combination with the hydroxymethylene (CHOH) radical.Comment: Accepted for publication in The Astrophysical Journal Letter

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study

Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index <= 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Mar Menor: una laguna singular y sensible. Evaluación científica de su estado.

Este libro recopila las aportaciones que equipos de investigación de la Universidad de Murcia, Universidad Politécnica de Cartagena, Instituto Geológico-Minero de España, Universidad de Alicante, el Instituto Español de Oceanografía y otros organismos hicieron en las Jornadas Científicas del Mar Menor, celebradas en diciembre de 2014.La información recogida en este libro se estructura en dos grandes bloques, uno de Biología y Ecología del Mar Menor (capítulos 1 al 8) y otro de Condiciones fisicoquímicas e impacto de actividades humanas en la laguna (capítulos 9 al 14). El primer bloque resume buena parte de los estudios ecológicos realizados en el Mar Menor, que han servido para mejorar su conocimiento y también para cambiar antiguas asunciones sobre la naturaleza y el funcionamiento de estos ecosistemas lagunares (Capítulo 1). El segundo capítulo muestra que esta laguna alberga en zonas someras de su perímetro hábitats fundamentales para mantener y conservar tanto especies migratorias como residentes, que es necesario conocer para paliar el impacto de las actividades humanas que les afectan. En este sentido la reducción de la carga de nutrientes y contaminantes orgánicos e inorgánicos que fluyen hacia el Mar Menor puede ayudar a preservar la laguna en mejores condiciones, bien sea tratando las escorrentías (plantas de tratamiento, humedales artificiales u otras técnicas) y recuperar este agua para uso agrícola o evitar su descarga en la laguna (Capítulo 3). Estas actuaciones serán clave para la conservación de especies emblemáticas como el caballito de mar (Capítulo 4) y reducir el impacto de las proliferaciones masivas de medusas que se producen en la laguna desde 1993 (Capítulo 5). En este mismo sentido los cambios acaecidos en la laguna han favorecido la incursión de invertebrados marinos alóctonos (Capítulo 6) y han afectado a la respuesta de la dinámica poblacional de las aves acuáticas a distintas escalas (Capítulo 7). Para completar este bloque se ofrece una perspectiva histórica de la importancia que ha tenido la investigación sobre acuicultura realizada en esta laguna, que ha servido de base para su gran desarrollo actual (Capítulo 8). El segundo bloque se inicia con una evaluación del origen y evolución del Mar Menor desde el punto de vista geológico, y evidencia su vulnerabilidad ante el deterioro que puede sufrir la desaparición de la barrera de cierre y/o su colmatación (Capítulo 9). En el Capítulo 10 se describe la relevancia que tiene la interacción de los acuíferos del Campo de Cartagena con la laguna, que se produce no sólo a nivel superficial sino también subterráneo. Esta interacción permite el acceso de nutrientes a la laguna, a pesar de la cierta capacidad de depuración de los humedales que le circundan, y también de metales traza por los aportes de residuos mineros (Capítulo 11). De hecho los metales traza están presentes en los sedimentos de la laguna, y su distribución se ha caracterizado en la columna sedimentaria relacionándola con la granulometría y el contenido de materia orgánica del sedimento (Capítulo 12). Posteriormente se describe la entrada de diversos contaminantes orgánicos, incluyendo pesticidas y fármacos a través de la rambla del Albujón, y su distribución estacional en agua y sedimento de la laguna (Capítulo 13). Este segundo bloque finaliza con el Capítulo 14 en el que se describe la bioacumulación de hidrocarburos aromáticos policíclicos, pesticidas y fármacos en moluscos y peces del Mar Menor, así como los efectos biológicos que la carga contaminante que accede a través de la rambla del Albujón produce en los organismos que allí habitan. El libro concluye con un breve epílogo redactado por los editores de este libro.Versión del edito

Digitization and virtual reality projects in archaeological heritage. The case of the archaeological site of Motilla del Azuer in Daimiel (Ciudad Real)

[ES] Este artículo tiene como objetivo presentar el proyecto de virtualización del yacimiento arqueológico de la Motilla del Azuer, en la localidad de Daimiel (Ciudad Real, España). En líneas generales, esta actividad está posibilitando obtener unos beneficios interesantes en torno a la investigación, documentación, interpretación y divulgación de este enclave prehistórico. La incorporación de herramientas tecnológicas en el campo del patrimonio arqueológico y cultural, como la documentación digital y la realidad virtual (RV), están constituyendo un impulso relevante para favorecer la gestión de este legado. Los avances experimentados en áreas como la digitalización 3D y la RV permiten desarrollar estas técnicas sobre una amplia tipología de bienes culturales, de diferentes características y cronologías, abriendo un considerable abanico de posibilidades. En este sentido, las valoraciones que está ofreciendo la aplicación de estos instrumentos, en virtud de los resultados alcanzados en diversos lugares, están significando una experiencia positiva para cualquier territorio; útil para aproximarse a su pasado y atractivo desde el punto de vista económico, cultural y social. Es por ello que cada vez son más las instituciones y entidades interesadas en este sector. En el caso del yacimiento arqueológico de la Motilla del Azuer, las labores de digitalización y virtualización emprendidas, junto con otras actividades de difusión, han generado productos de gran utilidad para el conocimiento y promoción de este monumento. Como se expone en las siguientes páginas, la correcta combinación de la digitalización 3D y la RV está suponiendo una dinamización de sus contenidos, un estímulo para disfrutar plenamente de la riqueza de sus vestigios y una mayor accesibilidad hacia los  mismos.Destacados:• Este artículo presenta un proyecto que está permitiendo avanzar en la interpretación y difusión del yacimiento arqueológico de la Motilla del Azuer.• Apuesta por la incorporación de las nuevas tecnologías en la gestión del patrimonio arqueológico y cultural• Desarrollo de una experiencia provechosa para favorecer la accesibilidad al patrimonio e impulsar la democratización cultural a través de su proyección.[EN] This article presents the virtualization project of the Motilla del Azuer archaeological site in Daimiel (Ciudad Real, Spain). This project is using new and unique tools for the research, documentation, interpretation and dissemination of this important prehistoric site. The incorporation of advanced technological tools in the field of archaeological and cultural heritage, such as digital documentation and virtual reality (VR), are creating new avenues for managing cultural legacies. Modern advances in 3D digitization and VR allow the application of these techniques on a wide range of cultural assets with different characteristics and chronologies, opening a broad spectrum of new possibilities in research, education, and public outreach. This is an expanding area of heritage management as it creates a positive impact on the economic, cultural and social activities of local communities and regions. Because of these positive impacts, more and more stakeholders such as institutions, administrations, and heritage organisations are taking an active interest in this sector of technological development. In the case of the Motilla del Azuer archaeological site, the digitization and virtualization work undertaken, along with other dissemination activities, have provided critical products for the presentation, interpretation, and promotion of this monument.La Motilla del Azuer is one of the most unique archaeological sites in Spain. Dating from the Bronze Age, it is a fortification with a central plan, formed by three lines of concentric walls distributed around a central tower (Fig. 2). Inside, the labyrinthine shape of the access systems is remarkable, made up of narrow corridors, stairs, ramps... This defensive enclosure allowed the protection and control of essential products for the people of the Bronze Age. Its true uniqueness is that it encloses monumental water well more than 15 m deep.La Motilla del Azuer is open to the public and receives thousands of visitors each year. But for conservation reasons, the number of people who can access the site is highly controlled. Likewise, due to its defensive nature and its age, it is a space through which it is difficult to circulate, which makes it impossible for people with reduced mobility to visit. For these and other reasons, the Daimiel City Council in collaboration with the US non-profit entity Global Digital Heritage and the Spanish company Myou Software, has developed a project to digitize the archaeological site and make it accessible through an installed VR system, located permanently in the Daimiel Museum, the interpretation centre for the site (Fig. 10). This facility is designed to be used both by people in wheelchairs or with reduced mobility, as well as all visitors to the museum, and provides a realistic virtual tour of the site. To achieve this level of realism, a detailed 3D digitization of the site using photogrammetry, laser scanning, and 3D spherical photography was undertaken, and a VR installation based on the use of an HTC Vive Pro device that has motion controllers for hands (HTC Vive controllers) and feet (HTC Vive Trackers) was developed. The primary software is called Myou Engine, an open-source 3D engine compatible with XR, developed by the Myou Software company. In order to increase the immersiveness as much as possible, the Myou Software company has also developed a control system called Natural Locomotion that works by moving the arms and legs (Fig. 11).The final result of the project has allowed the implementation of an innovative VR space that increases accessibility to the archaeological site, represents a new tourist attraction for the town, and promotes new ways of managing and enjoying archaeological heritage.Torres Mas, M.; López-Menchero Bendicho, VM.; López Tercero, J.; Torrejón Valdelomar, J.; Maschner, H. (2022). Proyectos de digitalización y realidad virtual en el patrimonio arqueológico. El caso del yacimiento de la Motilla del Azuer en Daimiel (Ciudad Real). Virtual Archaeology Review. 13(26):135-146. https://doi.org/10.4995/var.2022.15004OJS1351461326Akiduki, H., Nishiike, S.,Watanabe, H., Matsuoka, K., Kubo, T., & Takeda, N. (2003). Visual-vestibular conflict induced by virtual reality in humans. 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