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1.
  • Mishra, A, et al. (author)
  • Diminishing benefits of urban living for children and adolescents' growth and development
  • 2023
  • In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
  • Journal article (peer-reviewed)abstract
    • Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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6.
  • Bousquet, J, et al. (author)
  • Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
  • 2020
  • In: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
  • Journal article (peer-reviewed)abstract
    • There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
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  • de Rojas, I., et al. (author)
  • Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
  • 2021
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Journal article (peer-reviewed)abstract
    • Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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8.
  • Bouyoucef, S E, et al. (author)
  • Poster Session 2 : Monday 4 May 2015, 08
  • 2015
  • In: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
  • Journal article (peer-reviewed)
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9.
  • Morales, J. C., et al. (author)
  • A giant exoplanet orbiting a very-low-mass star challenges planet formation models
  • 2019
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 365:6460, s. 1441-1445
  • Journal article (peer-reviewed)abstract
    • Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.46 Jupiter masses, very high for such a small host star, and an eccentric 204-day orbit. Dynamical models show that the high eccentricity is most likely due to planet-planet interactions. We use simulations to demonstrate that the GJ 3512 planetary system challenges generally accepted formation theories, and that it puts constraints on the planet accretion and migration rates. Disk instabilities may be more efficient in forming planets than previously thought.
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10.
  • Bluhm, P., et al. (author)
  • Precise mass and radius of a transiting super-Earth planet orbiting the M dwarf TOI-1235: a planet in the radius gap?
  • 2020
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 639
  • Journal article (peer-reviewed)abstract
    • We report the confirmation of a transiting planet around the bright weakly active M0.5 V star TOI-1235 (TYC 4384-1735-1, V ≈ 11.5 mag), whose transit signal was detected in the photometric time series of sectors 14, 20, and 21 of the TESS space mission. We confirm the planetary nature of the transit signal, which has a period of 3.44 d, by using precise RV measurements with the CARMENES, HARPS-N, and iSHELL spectrographs, supplemented by high-resolution imaging and ground-based photometry. A comparison of the properties derived for TOI-1235 b with theoretical models reveals that the planet has a rocky composition, with a bulk density slightly higher than that of Earth. In particular, we measure a mass of Mp = 5.9 ± 0.6 M⊕ and a radius of Rp = 1.69 ± 0.08 R⊕, which together result in a density of ρp = 6.7- 1.1+ 1.3 g cm-3. When compared with other well-characterized exoplanetary systems, the particular combination of planetary radius and mass places our discovery in the radius gap, which is a transition region between rocky planets and planets with significant atmospheric envelopes. A few examples of planets occupying the radius gap are known to date. While the exact location of the radius gap for M dwarfs is still a matter of debate, our results constrain it to be located at around 1.7 R⊕ or larger at the insolation levels received by TOI-1235 b (~60 S⊕). This makes it an extremely interesting object for further studies of planet formation and atmospheric evolution.
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13.
  • Abgrall, N., et al. (author)
  • The large enriched germanium experiment for neutrinoless double beta decay (LEGEND)
  • 2017
  • In: AIP Conference Proceedings. - : Author(s). - 1551-7616 .- 0094-243X. ; 1894
  • Conference paper (peer-reviewed)abstract
    • The observation of neutrinoless double-beta decay (0νββ) would show that lepton number is violated, reveal that neu-trinos are Majorana particles, and provide information on neutrino mass. A discovery-capable experiment covering the inverted ordering region, with effective Majorana neutrino masses of 15 - 50 meV, will require a tonne-scale experiment with excellent energy resolution and extremely low backgrounds, at the level of ∼0.1 count /(FWHM·t·yr) in the region of the signal. The current generation 76Ge experiments GERDA and the Majorana Demonstrator, utilizing high purity Germanium detectors with an intrinsic energy resolution of 0.12%, have achieved the lowest backgrounds by over an order of magnitude in the 0νββ signal region of all 0νββ experiments. Building on this success, the LEGEND collaboration has been formed to pursue a tonne-scale 76Ge experiment. The collaboration aims to develop a phased 0νββ experimental program with discovery potential at a half-life approaching or at 1028 years, using existing resources as appropriate to expedite physics results.
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  • Fridlund, Malcolm, 1952, et al. (author)
  • The TOI-763 system: Sub-Neptunes orbiting a Sun-like star
  • 2020
  • In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 498:3, s. 4503-4517
  • Journal article (peer-reviewed)abstract
    • We report the discovery of a planetary system orbiting TOI-763(aka CD-39 7945), a V = 10.2, high proper motion G-type dwarf star that was photometrically monitored by the TESS space mission in Sector 10. We obtain and model the stellar spectrum and find an object slightly smaller than the Sun, and somewhat older, but with a similar metallicity. Two planet candidates were found in the light curve to be transiting the star. Combining TESS transit photometry with HARPS high-precision radial velocity (RV) follow-up measurements confirm the planetary nature of these transit signals. We determine masses, radii, and bulk densities of these two planets. A third planet candidate was discovered serendipitously in the RV data. The inner transiting planet, TOI-763 b, has an orbital period of Pb = 5.6 d, a mass of Mb = 9.8 ± 0.8 M⊕, and a radius of Rb = 2.37 ± 0.10 R⊕. The second transiting planet, TOI-763 c, has an orbital period of Pc = 12.3 d, a mass of Mc = 9.3 ± 1.0 M⊕, and a radius of Rc = 2.87 ± 0.11 R⊕. We find the outermost planet candidate to orbit the star with a period of ∼48 d. If confirmed as a planet, it would have a minimum mass of Md = 9.5 ± 1.6 M⊕. We investigated the TESS light curve in order to search for a mono transit by planet d without success. We discuss the importance and implications of this planetary system in terms of the geometrical arrangements of planets orbiting G-type stars.
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  • Nielsen, L. D., et al. (author)
  • Mass determinations of the three mini-Neptunes transiting TOI-125
  • 2020
  • In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 492:4, s. 5399-5412
  • Journal article (peer-reviewed)abstract
    • The Transiting Exoplanet Survey Satellite, TESS, is currently carrying out an all-sky search for small planets transiting bright stars. In the first year of the TESS survey, a steady progress was made in achieving the mission's primary science goal of establishing bulk densities for 50 planets smaller than Neptune. During that year, the TESS's observations were focused on the southern ecliptic hemisphere, resulting in the discovery of three mini-Neptunes orbiting the star T01-125, a V = 11,0 KO dwarf. We present intensive HARPS radial velocity observations, yielding precise mass measurements for TO1-125b, TOI-125c, and TOI-125d. TOI-125b has an orbital period of 4,65 d, a radius of 2,726 + 0,075 RE, a mass of 9,50 0,88 ME, and is near the 2:1 mean motion resonance with TOI-125c at 9.15 d. TOI-125c has a similar radius of 2,759 0.10 RE and a mass of 6,63 + 0,99 ME, being the puffiest of the three planets. T01-125d has an orbital period of 19,98 d and a radius of 2.93 + 0,17 RE and mass 13,6 1,2 ME, For T01-125b and d, we find unusual high eccentricities of 0.19 0.04 and 0.17+(c):(!,(, respectively. Our analysis also provides upper mass limits for the two low-SNR planet candidates in the system; for T01-125.04 (Rp = 1.36 RE, P = 0.53 d), we find a 2a upper mass limit of 1.6 ME, whereas T01-125.05 (RP = 4.2-'2E44 RE, P = 13.28 d) is unlikely a viable planet candidate with an upper mass limit of 2.7 ME. We discuss the internal structure of the three confirmed planets, as well as dynamical stability and system architecture for this intriguing exoplanet system.
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  • Buunen, M, et al. (author)
  • COLOR II. A randomized clinical trial comparing laparoscopic and open surgery for rectal cancer.
  • 2009
  • In: Danish medical bulletin. - 1603-9629 .- 0907-8916. ; 56:2, s. 89-91
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: Laparoscopic resection of rectal cancer has been proven efficacious but morbidity and oncological outcome need to be investigated in a randomized clinical trial. Trial design: Non-inferiority randomized clinical trial. METHODS: The COLOR II trial is an ongoing international randomized clinical trial. Currently 27 hospitals from Europe, South Korea and Canada are including patients. The primary endpoint is loco-regional recurrence rate three years post-operatively. Secondary endpoints cover quality of life, overall and disease free survival, post-operative morbidity and health economy analysis. RESULTS: By July 2008, 27 hospitals from the Netherlands, Belgium, Germany, Sweden, Spain, Denmark, South Korea and Canada had included 739 patients. The intra-operative conversion rate in the laparoscopic group was 17%. Distribution of age, location of the tumor and radiotherapy were equal in both treatment groups. Most tumors are located in the mid-rectum (41%). CONCLUSION: Laparoscopic surgery in the treatment of rectal cancer is feasible. The results and safety of laparoscopic surgery in the treatment of rectal cancer remain unknown, but are subject of interim analysis within the COLOR II trial. Completion of inclusion is expected by the end of 2009. Trial registration: Clinicaltrials.gov, identifier: NCT00297791 (www.clinicaltrials.gov).
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  • Nijs, Jo, et al. (author)
  • Towards precision pain medicine for pain after cancer: the Cancer Pain Phenotyping Network multidisciplinary international guidelines for pain phenotyping using nociplastic pain criteria
  • 2023
  • In: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912. ; 130:5, s. 611-621
  • Journal article (peer-reviewed)abstract
    • Pain after cancer remains underestimated and undertreated. Precision medicine is a recent concept that refers to the ability to classify patients into subgroups that differ in their susceptibility to, biology, or prognosis of a particular disease, or in their response to a specific treatment, and thus to tailor treatment to the individual patient characteristics. Applying this to pain after cancer, the ability to classify post-cancer pain into the three major pain phenotypes (i.e. nociceptive, neuropathic, and nociplastic pain) and tailor pain treatment accordingly, is an emerging issue. This is especially relevant because available evidence suggests that nociplastic pain is present in an important subgroup of those patients experiencing post-cancer pain. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system for nociplastic pain account for the need to identify and correctly classify patients according to the pain phenotype early in their treatment. These criteria are an important step towards precision pain medicine with great potential for the field of clinical oncology. Within this framework, the Cancer Pain Phenotyping (CANPPHE) Network, an international and interdisciplinary group of oncology clinicians and researchers from seven countries, applied the 2021 IASP clinical criteria for nociplastic pain to the growing population of those experiencing post-cancer pain. A manual is provided to allow clinicians to differentiate between predominant nociceptive, neuropathic, or nociplastic pain after cancer. A seven-step diagnostic approach is presented and illustrated using cases to enhance understanding and encourage effective implementation of this approach in clinical practice.
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  • Gandolfi, D., et al. (author)
  • The Transiting Multi-planet System HD15337: Two Nearly Equal-mass Planets Straddling the Radius Gap
  • 2019
  • In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 876:2
  • Journal article (peer-reviewed)abstract
    • We report the discovery of a super-Earth and a sub-Neptune transiting the star HD 15337 (TOI-402, TIC 120896927), a bright (V = 9) K1 dwarf observed by the Transiting Exoplanet Survey Satellite (TESS) in Sectors 3 and 4. We combine the TESS photometry with archival High Accuracy Radial velocity Planet Searcher spectra to confirm the planetary nature of the transit signals and derive the masses of the two transiting planets. With an orbital period of 4.8 days, a mass of {7.51}-1.01+1.09 {M}\oplus and a radius of 1.64 ± 0.06 R ⊕, HD 15337 b joins the growing group of short-period super-Earths known to have a rocky terrestrial composition. The sub-Neptune HD 15337 c has an orbital period of 17.2 days, a mass of {8.11}-1.69+1.82 {{{M}}}\oplus , and a radius of 2.39 ± 0.12 R ⊕, suggesting that the planet might be surrounded by a thick atmospheric envelope. The two planets have similar masses and lie on opposite sides of the radius gap, and are thus an excellent testbed for planet formation and evolution theories. Assuming that HD 15337 c hosts a hydrogen-dominated envelope, we employ a recently developed planet atmospheric evolution algorithm in a Bayesian framework to estimate the history of the high-energy (extreme ultraviolet and X-ray) emission of the host star. We find that at an age of 150 Myr, the star possessed on average between 3.7 and 127 times the high-energy luminosity of the current Sun.
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  • Nijs, Jo, et al. (author)
  • Central sensitisation in chronic pain conditions: latest discoveries and their potential for precision medicine
  • 2021
  • In: Lancet Rheumatology. - : Elsevier BV. - 2665-9913. ; 3:5
  • Journal article (peer-reviewed)abstract
    • Chronic pain is a leading cause of disability globally and associated with enormous health-care costs. The discrepancy between the extent of tissue damage and the magnitude of pain, disability, and associated symptoms represents a diagnostic challenge for rheumatology specialists. Central sensitisation, defined as an amplification of neural signalling within the CNS that elicits pain hypersensitivity, has been investigated as a reason for this discrepancy. Features of central sensitisation have been documented in various pain conditions common in rheumatology practice, including fibromyalgia, osteoarthritis, rheumatoid arthritis, Ehlers-Danlos syndrome, upper extremity tendinopathies, headache, and spinal pain. Within individual pain conditions, there is substantial variation among patients in terms of presence and magnitude of central sensitisation, stressing the importance of individual assessment. Central sensitisation predicts poor treatment outcomes in multiple patient populations. The available evidence supports various pharmacological and non-pharmacological strategies to reduce central sensitisation and to improve patient outcomes in several conditions commonly seen in rheumatology practice. These data open up new treatment perspectives, with the possibility for precision pain medicine treatment according to pain phenotyping as a logical next step. With this view, studies suggest the possibility of matching non-pharmacological approaches, or medications, or both to the central sensitisation pain
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  • Siegel, R., et al. (author)
  • Laparoscopic extraperitoneal rectal cancer surgery : the clinical practice guidelines of the European Association for Endoscopic Surgery (EAES)
  • 2011
  • In: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 0930-2794 .- 1432-2218. ; 25:8, s. 2423-2440
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The laparoscopic approach is increasingly applied in colorectal surgery. Although laparoscopic surgery in colon cancer has been proved to be safe and feasible with equivalent long-term oncological outcome compared to open surgery, safety and long-term oncological outcome of laparoscopic surgery for rectal cancer remain controversial. Laparoscopic rectal cancer surgery might be efficacious, but indications and limitations are not clearly defined. Therefore, the European Association for Endoscopic Surgery (EAES) has developed this clinical practice guideline. METHODS: An international expert panel was invited to appraise the current literature and to develop evidence-based recommendations. The expert panel constituted for a consensus development conference in May 2010. Thereafter, the recommendations were presented at the annual congress of the EAES in Geneva in June 2010 in a plenary session. A second consensus process (Delphi process) of the recommendations with the explanatory text was necessary due to the changes after the consensus conference. RESULTS: Laparoscopic surgery for extraperitoneal (mid- and low-) rectal cancer is feasible and widely accepted. The laparoscopic approach must offer the same quality of surgical specimen as in open surgery. Short-term outcomes such as bowel function, surgical-site infections, pain and hospital stay are slightly improved with the laparoscopic approach. Laparoscopic resection of rectal cancer is not inferior to the open in terms of disease-free survival, overall survival or local recurrence. Laparoscopic pelvic dissection may impair genitourinary and sexual function after rectal resection, like in open surgery. CONCLUSIONS: Laparoscopic surgery for mid- and low-rectal cancer can be recommended under optimal conditions. Still, most level 1 evidence is for colon cancer surgery rather than rectal cancer. Upcoming results from large randomised trials are awaited to strengthen the evidence for improved short-term results and equal long-term results in comparison with the open approach.
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  • Carleo, Ilaria, et al. (author)
  • The Multiplanet System TOI-421*
  • 2020
  • In: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 160:3
  • Journal article (peer-reviewed)abstract
    • We report the discovery of a warm Neptune and a hot sub-Neptune transiting TOI-421 (BD-14 1137, TIC 94986319), a bright (V = 9.9) G9 dwarf star in a visual binary system observed by the Transiting Exoplanet Survey Satellite (TESS) space mission in Sectors 5 and 6. We performed ground-based follow-up observations-comprised of Las Cumbres Observatory Global Telescope transit photometry, NIRC2 adaptive optics imaging, and FIbre-fed Echelle Spectrograph, CORALIE, High Accuracy Radial velocity Planet Searcher, High Resolution echelle Spectrometer, and Planet Finder Spectrograph high-precision Doppler measurements-and confirmed the planetary nature of the 16 day transiting candidate announced by the TESS team. We discovered an additional radial velocity signal with a period of five days induced by the presence of a second planet in the system, which we also found to transit its host star. We found that the inner mini-Neptune, TOI-421 b, has an orbital period of P-b = 5.19672 +/- 0.00049 days, a mass of M-b = 7.17 +/- 0.66 M-circle plus, and a radius of R-b = R-circle plus, whereas the outer warm Neptune, TOI-421 c, has a period of P-c = 16.06819 +/- 0.00035 days, a mass of M-c = 16.42(-1.04)(+1.06)M(circle plus), a radius of R-c = 5.09(-0.15)(+0.16)R(circle plus), and a density of rho(c) = 0.685(-0.072)(+0.080) cm(-3). With its characteristics, the outer planet (rho(c) = 0.685(-0.0072)(+0.080) cm(-3)) is placed in the intriguing class of the super-puffy mini-Neptunes. TOI-421 b and TOI-421 c are found to be well-suited for atmospheric characterization. Our atmospheric simulations predict significant Ly alpha transit absorption, due to strong hydrogen escape in both planets, as well as the presence of detectable CH4 in the atmosphere of TOI-421 c if equilibrium chemistry is assumed.
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  • Hatzes, A., et al. (author)
  • A Radial Velocity Study of the Planetary System of π Mensae: Improved Planet Parameters for pi Mensae c and a Third Planet on a 125 Day Orbit
  • 2022
  • In: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 163:5
  • Journal article (peer-reviewed)abstract
    • π Men hosts a transiting planet detected by the Transiting Exoplanet Survey Satellite space mission and an outer planet in a 5.7 yr orbit discovered by radial velocity (RV) surveys. We studied this system using new RV measurements taken with the HARPS spectrograph on ESO's 3.6 m telescope, as well as archival data. We constrain the stellar RV semiamplitude due to the transiting planet, π Men c, as K c = 1.21 ± 0.12 m s-1, resulting in a planet mass of M c = 3.63 ± 0.38 M. A planet radius of R c = 2.145 ± 0.015 R yields a bulk density of ρ c = 2.03 ± 0.22 g cm-3. The precisely determined density of this planet and the brightness of the host star make π Men c an excellent laboratory for internal structure and atmospheric characterization studies. Our HARPS RV measurements also reveal compelling evidence for a third body, π Men d, with a minimum mass M d sin i d = 13.38 ± 1.35 M orbiting with a period of P orb,d = 125 days on an eccentric orbit (e d = 0.22). A simple dynamical analysis indicates that the orbit of π Men d is stable on timescales of at least 20 Myr. Given the mutual inclination between the outer gaseous giant and the inner rocky planet and the presence of a third body at 125 days, π Men is an important planetary system for dynamical and formation studies.
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  • Martens, Marvin, et al. (author)
  • ELIXIR and Toxicology : a community in development
  • 2021
  • In: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 10, s. 1129-1129
  • Journal article (peer-reviewed)abstract
    • Toxicology has been an active research field for many decades, with academic, industrial and government involvement. Modern omics and computational approaches are changing the field, from merely disease-specific observational models into target-specific predictive models. Traditionally, toxicology has strong links with other fields such as biology, chemistry, pharmacology and medicine. With the rise of synthetic and new engineered materials, alongside ongoing prioritisation needs in chemical risk assessment for existing chemicals, early predictive evaluations are becoming of utmost importance to both scientific and regulatory purposes. ELIXIR is an intergovernmental organisation that brings together life science resources from across Europe. To coordinate the linkage of various life science efforts around modern predictive toxicology, the establishment of a new ELIXIR Community is seen as instrumental. In the past few years, joint efforts, building on incidental overlap, have been piloted in the context of ELIXIR. For example, the EU-ToxRisk, diXa, HeCaToS, transQST, and the nanotoxicology community have worked with the ELIXIR TeSS, Bioschemas, and Compute Platforms and activities. In 2018, a core group of interested parties wrote a proposal, outlining a sketch of what this new ELIXIR Toxicology Community would look like. A recent workshop (held September 30th to October 1st, 2020) extended this into an ELIXIR Toxicology roadmap and a shortlist of limited investment-high gain collaborations to give body to this new community. This Whitepaper outlines the results of these efforts and defines our vision of the ELIXIR Toxicology Community and how it complements other ELIXIR activities.  
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  • Veldkamp, R., et al. (author)
  • Laparoscopic resection of colon Cancer: consensus of the European Association of Endoscopic Surgery (EAES)
  • 2004
  • In: Surgical endoscopy. - : Springer Science and Business Media LLC. - 1432-2218 .- 0930-2794. ; 18:8, s. 1163-85
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The European Association of Endoscopic Surgery (EAES) initiated a consensus development conference on the laparoscopic resection of colon cancer during the annual congress in Lisbon, Portugal, in June 2002. METHODS: A systematic review of the current literature was combined with the opinions, of experts in the field of colon cancer surgery to formulate evidence-based statements and recommendations on the laparoscopic resection of colon cancer. RESULTS: Advanced age, obesity, and previous abdominal operations are not considered absolute contraindications for laparoscopic colon cancer surgery. The most common cause for conversion is the presence of bulky or invasive tumors. Laparoscopic operation takes longer to perform than the open counterpart, but the outcome is similar in terms of specimen size and pathological examination. Immediate postoperative morbidity and mortality are comparable for laparoscopic and open colonic cancer surgery. The laparoscopically operated patients had less postoperative pain, better-preserved pulmonary function, earlier restoration of gastrointestinal function, and an earlier discharge from the hospital. The postoperative stress response is lower after laparoscopic colectomy. The incidence of port site metastases is <1%. Survival after laparoscopic resection of colon cancer appears to be at least equal to survival after open resection. The costs of laparoscopic surgery for colon cancer are higher than those for open surgery. CONCLUSION: Laparoscopic resection of colon cancer is a safe and feasible procedure that improves short-term outcome. Results regarding the long-term survival of patients enrolled in large multicenter trials will determine its role in general surgery.
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  • Borroto-Escuela, DO, et al. (author)
  • The oxytocin receptor represents a key hub in the GPCR heteroreceptor network: potential relevance for brain and behavior
  • 2022
  • In: Frontiers in molecular neuroscience. - : Frontiers Media SA. - 1662-5099. ; 15, s. 1055344-
  • Journal article (peer-reviewed)abstract
    • In the last 10 years, it has become increasingly clear that large numbers of axon collaterals extend from the oxytocin (OXT) hypothalamic axons, especially the parvocellular components, to other brain regions. Consequently, the OXT signaling system forms, like other monoamine axons, a rich functional network across several brain regions. In this manuscript, we review the recently indicated higher order G-protein coupled heteroreceptor complexes of the oxytocin receptor (OXTR), and how these, via allosteric receptor-receptor interactions modulate the recognition, signaling, and trafficking of the participating receptor protomers and their potential impact for brain and behavior. The major focus will be on complexes of the OXTR protomer with the dopamine D2 receptor (D2R) protomer and the serotonin 2A (5-HT2AR) and 2C (5-HT2CR) receptor protomers. Specifically, the existence of D2R-OXTR heterocomplexes in the nucleus accumbens and the caudate putamen of rats has led to a postulated function for this heteromer in social behavior. Next, a physical interaction between OXTRs and the growth hormone secretagogue or ghrelin receptor (GHS-R1a) was demonstrated, which consequently was able to attenuate OXTR-mediated Gαq signaling. This highlights the potential of ghrelin-targeted therapies to modulate oxytocinergic signaling with relevance for appetite regulation, anxiety, depression, and schizophrenia. Similarly, evidence for 5-HT2AR-OXTR heteromerization in the pyramidal cell layer of CA2 and CA3 in the dorsal hippocampus and in the nucleus accumbens shell was demonstrated. This complex may offer new strategies for the treatment of both mental disease and social behavior. Finally, the 5-HT2CR-OXTR heterocomplexes were demonstrated in the CA1, CA2, and CA3 regions of the dorsal hippocampus. Future work should be done to investigate the precise functional consequence of region-specific OXTR heteromerization in the brain, as well across the periphery, and whether the integration of neuronal signals in the brain may also involve higher order OXTR-GHS-R1a heteroreceptor complexes including the dopamine (DA), noradrenaline (NA) or serotonin (5-HT) receptor protomers or other types of G-protein coupled receptors (GPCRs).
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31.
  • Castro-González, A., et al. (author)
  • The K2-OjOS Project*New and revisited planets and candidates in K2 campaigns 5, 16, & 18
  • 2022
  • In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 509:1, s. 1075-1095
  • Journal article (peer-reviewed)abstract
    • We present the first results of K2-OjOS, a collaborative project between professional and amateur astronomers primarily aimed to detect, characterize, and validate new extrasolar planets. For this work, 10 amateur astronomers looked for planetary signals by visually inspecting the 20 427 light curves of K2 campaign 18 (C18). They found 42 planet candidates, of which 18 are new detections and 24 had been detected in the overlapping C5 by previous works. We used archival photometric and spectroscopic observations, as well as new high-spatial resolution images in order to carry out a complete analysis of the candidates found, including a homogeneous characterization of the host stars, transit modelling, search for transit timing variations and statistical validation. As a result, we report four new planets (K2-355 b, K2-356 b, K2-357 b, and K2-358 b) and 14 planet candidates. Besides, we refine the transit ephemeris of the previously published planets and candidates by modelling C5, C16 (when available) and C18 photometric data jointly, largely improving the period and mid-transit time precision. Regarding individual systems, we highlight the new planet K2-356 b and candidate EPIC 211537087.02 being near a 2:1 period commensurability, the detection of significant TTVs in the bright star K2-184 (V = 10.35), the location of K2-103 b inside the habitable zone according to optimistic models, the detection of a new single transit in the known system K2-274, and the disposition reassignment of K2-120 b, which we consider as a planet candidate as the origin of the signal cannot be ascertained.
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32.
  • Deijen, Charlotte L., et al. (author)
  • Ten-year outcomes of a randomised trial of laparoscopic versus open surgery for colon cancer
  • 2017
  • In: Surgical Endoscopy. - : SPRINGER. - 0930-2794 .- 1432-2218. ; 31:6, s. 2607-2615
  • Journal article (peer-reviewed)abstract
    • Laparoscopic surgery for colon cancer is associated with improved recovery and similar cancer outcomes at 3 and 5 years in comparison with open surgery. However, long-term survival rates have rarely been reported. Here, we present survival and recurrence rates of the Dutch patients included in the COlon cancer Laparoscopic or Open Resection (COLOR) trial at 10-year follow-up. Between March 1997 and March 2003, patients with non-metastatic colon cancer were recruited by 29 hospitals in eight countries and randomised to either laparoscopic or open surgery. Main inclusion criterion for the COLOR trial was solitary adenocarcinoma of the left or right colon. The primary outcome was disease-free survival at 3 years, and secondary outcomes included overall survival and recurrence. The 10-year follow-up data of all Dutch patients were collected. Analysis was by intention-to-treat. The trial was registered at ClinicalTrials.gov (NCT00387842). In total, 1248 patients were randomised, of which 329 were Dutch. Fifty-eight Dutch patients were excluded and 15 were lost to follow-up, leaving 256 patients for 10-year analysis. Median follow-up was 112 months. Disease-free survival rates were 45.2 % in the laparoscopic group and 43.2 % in the open group (difference 2.0 %; 95 % confidence interval (CI) -10.3 to 14.3; p = 0.96). Overall survival rates were 48.4 and 46.7 %, respectively (difference 1.7 %; 95 % CI -10.6 to 14.0; p = 0.83). Stage-specific analysis revealed similar survival rates for both groups. Sixty-two patients were diagnosed with recurrent disease, accounting for 29.4 % in the laparoscopic group and 28.2 % in the open group (difference 1.2 %; 95 % CI -11.1 to 13.5; p = 0.73). Seven patients had port- or wound-site recurrences (laparoscopic n = 3 vs. open n = 4). Laparoscopic surgery for non-metastatic colon cancer is associated with similar rates of disease-free survival, overall survival and recurrences as open surgery at 10-year follow-up.
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33.
  • Diaz, Matias R., et al. (author)
  • TOI-132 b: A short-period planet in the Neptune desert transiting a V=11.3 G-type star
  • 2020
  • In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 493:1, s. 973-985
  • Journal article (peer-reviewed)abstract
    • The Neptune desert is a feature seen in the radius-period plane, whereby a notable dearth of short period, Neptune-like planets is found. Here, we report the Transiting Exoplanet Survey Satellite (TESS) discovery of a new short-period planet in the Neptune desert, orbiting the G-type dwarf TYC 8003-1117-1 (TOI-132). TESS photometry shows transit-like dips at the level of similar to 1400 ppm occurring every similar to 2.11 d. High-precision radial velocity follow-up with High Accuracy Radial Velocity Planet Searcher confirmed the planetary nature of the transit signal and provided a semi-amplitude radial velocity variation of 11.38(-0.85)(+0.84) m s(-1), which, when combined with the stellar mass of 0.97 +/- 0.06 M-circle dot, provides a planetary mass of 22.40(-1.92)(+1.90) M-circle plus. Modelling the TESS light curve returns a planet radius of 3.42(-0.14)(+0.13) R-circle plus , and therefore the planet bulk density is found to be 3.08(-0.46)(+0.44) g cm(-3). Planet structure models suggest that the bulk of the planet mass is in the form of a rocky core, with an atmospheric mass fraction of 4.3(-2.3)(+1.2) percent. TOI-132 b is a TESS Level 1 Science Requirement candidate, and therefore priority follow-up will allow the search for additional planets in the system, whilst helping to constrain low-mass planet formation and evolution models, particularly valuable for better understanding of the Neptune desert.
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34.
  • Dreijer, J., et al. (author)
  • Telefonica - Potential victim of american espionage
  • 2012
  • In: 11th European Conference on Information Warfare and Security 2012, ECIW 2012. - 9781622765379 ; , s. 104-112
  • Conference paper (peer-reviewed)abstract
    • During the year of 2010, a set of reports were released that contained important information regarding European multinationals and local governments. These reports were published by Wikileaks and were described as 'cables'. These cables were sent from American embassies to the United States' government. Suspicions were raised that the United States might have been spying on European countries, companies and their respective partners. One of the companies being mentioned in the cable files is Telefonica. Telefonica is a major Spanish telecom, television and Internet service provider operating in Europe and Latin America. The United States could have political and/or economic reasons to spy the Southern American continent. The main question during our research is to find out what reasons the United States might have to spy on Latin American countries and if the rumors were true that they have indeed spied upon Telefonica. And if these rumors are true, what profits there to be found within the cables and other relevant sources? During our research, we found relevant data containing possible evidence related to American espionage. The data found within the cables contain information about America's interest in Telefonica and the pressure being put on their investments in Latin America. The cables contain quotes referring to America's interest in Venezuela and Cuba. The cables contain messages being sent to an American official, stating that the United States should be aware of Telefonicas vast growing market share and influences in Southern American countries. Other relevant cables contain quotes referring to 'informed sources'. Who are these sources and how did they obtain relevant information about Telefonicas expenses? Most of the other relevant cables refer to other investments being done in Latin America, especially in Brazil and Mexico. The United States have good knowledge about the investments being done in Latin America by Telefonica. Unfortunately, none of these cables contained actual proof that the US had directly spied on Telefonica. The cables only contain relevant information regarding America's interest in Telefonica. Even though these cables contain shady and maybe suspicious quotes; this cannot be identified as evidence regarding possible espionage.
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35.
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36.
  • Kabath, Petr, et al. (author)
  • TOI-2046b, TOI-1181b, and TOI-1516b, three new hot Jupiters from TESS: planets orbiting a young star, a subgiant, and a normal star
  • 2022
  • In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 513:4, s. 5955-5972
  • Journal article (peer-reviewed)abstract
    • We present the confirmation and characterization of three hot Jupiters, TOI-118 lb, TOI-1516b, and TOI-2046b, discovered by the "NESS space mission. The reported hot Jupiters have orbital periods between 1.4 and 2.05 d. The masses of the three planets are 1.18 +/- 0.14 Mj, 3.16 +/- 0.12 Mj, and 2.30 +/- 0.28 Mj, for TOI-1181b, TOI-1516b, and TOI-2046b, respectively. The stellar host of TOI-1181b is a F9IV star, whereas TOI-1516b and TOI-2046b orbit F main sequence host stars. The ages of the first two systems are in the range of 2-5 Gyrs. However, TOI-2046 is among the few youngest known planetary systems hosting a hot Jupiter, with an age estimate of 100-400 Myrs. The main instruments used for the radial velocity follow-up of these three planets are located at OndIejov, Tautenburg, and McDonald Observatory, and all three are mounted on 2-3 m aperture telescopes, demonstrating that mid-aperture telescope networks can play a substantial role in the follow-up of gas giants discovered by TESS and in the future by PLATO.
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37.
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38.
  • Kuhry, E., et al. (author)
  • Impact of hospital case volume on short-term outcome after laparoscopic operation for colonic cancer
  • 2005
  • In: Surgical endoscopy. - 1432-2218. ; 19:5, s. 687-92
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: High hospital case volume has been associated with improved outcome after open operation for colorectal malignancies. METHODS: To assess the impact of hospital case volume on short-term outcome after laparoscopic operation for colon cancer, we conducted an analysis of patients who underwent laparoscopic colon resection within the COlon Cancer Laparoscopic or Open Resection (COLOR) trial. RESULTS: A total of 536 patients with adenocarcinoma of the colon were included in the analysis. Median operating time was 240, 210 and 188 min in centers with low, medium, and high case volumes, respectively (p < 0.001). A significant difference in conversion rate was observed among low, medium, and high case volume hospitals (24% vs 24% vs 9%; p < 0.001). A higher number of lymph nodes were harvested at high case volume hospitals (p < 0.001). After operation, fewer complications (p = 0.006) and a shorter hospital stay (p < 0.001) were observed in patients treated at hospitals with high caseloads. CONCLUSIONS: Laparoscopic operation for colon cancer at hospitals with high caseloads appears to be associated with improved short-term results.
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39.
  • Linnell, Stephanie F., et al. (author)
  • Enhanced oxygen redox reversibility and capacity retention of titanium-substituted Na-4/7[1/7Ti1/7Mn5/7]O-2 in sodium-ion batteries
  • 2022
  • In: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488 .- 2050-7496. ; 10:18, s. 9941-9953
  • Journal article (peer-reviewed)abstract
    • Anion redox reactions offer a means of enhancing the capacity of layered sodium transition metal oxide positive electrode materials. However, oxygen redox reactions typically show limited reversibility and irreversible structural changes upon cycling, resulting in rapid capacity loss. Here, the Ti-substituted Na-4/7[1/7Ti1/7Mn5/7]O-2 (where represents a transition metal vacancy) is presented as a positive electrode material for sodium-ion batteries. Na-4/7[1/7Ti1/7Mn5/7]O-2 delivers a reversible capacity of 167 mA h g(-1) after 25 cycles at 10 mA g(-1) within the voltage range of 1.6-4.4 V and presents enhanced stability compared with Na-4/7[Mn-1/7(6/7)]O-2 over the voltage range 3.0-4.4 V. The structural and electronic structural changes of this Ti4+ substituted phase are investigated by powder X-ray diffraction, X-ray absorption spectroscopy, electron paramagnetic resonance and Raman spectroscopy, supported by density functional theory calculations. These results show that the Na-4/7[Mn-1/7(6/7)]O-2 structure is maintained between 3.0 and 4.4 V, and the presence of TiO6 octahedra in Na-4/7[1/7Ti1/7Mn5/7]O-2 relieves structural distortions from Jahn-Teller distorted Mn3+O6 between 1.6 and 4.4 V. Furthermore, Ti4+ substitution stabilises the adjacent O 2p orbitals and raises the ionicity of the Mn-O bonds, increasing the operating potential of Na-4/7[1/7Ti1/7Mn5/7]O-2. Thereby providing evidence that the improved electrochemical performance of Na-4/7[1/7Ti1/7Mn5/7]O-2 can be attributed to Ti4+ substitution. This work provides insight and strategies for improving the structural stability and electrochemical performance of sodium layered oxides.
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40.
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41.
  • Mauritsen, Thorsten, et al. (author)
  • Developments in the MPI-M Earth System Model version 1.2 (MPI-ESM1.2) and Its Response to Increasing CO2
  • 2019
  • In: Journal of Advances in Modeling Earth Systems. - 1942-2466. ; 11:4, s. 998-1038
  • Journal article (peer-reviewed)abstract
    • A new release of the Max Planck Institute for Meteorology Earth System Model version 1.2 (MPI-ESM1.2) is presented. The development focused on correcting errors in and improving the physical processes representation, as well as improving the computational performance, versatility, and overall user friendliness. In addition to new radiation and aerosol parameterizations of the atmosphere, several relatively large, but partly compensating, coding errors in the model's cloud, convection, and turbulence parameterizations were corrected. The representation of land processes was refined by introducing a multilayer soil hydrology scheme, extending the land biogeochemistry to include the nitrogen cycle, replacing the soil and litter decomposition model and improving the representation of wildfires. The ocean biogeochemistry now represents cyanobacteria prognostically in order to capture the response of nitrogen fixation to changing climate conditions and further includes improved detritus settling and numerous other refinements. As something new, in addition to limiting drift and minimizing certain biases, the instrumental record warming was explicitly taken into account during the tuning process. To this end, a very high climate sensitivity of around 7 K caused by low-level clouds in the tropics as found in an intermediate model version was addressed, as it was not deemed possible to match observed warming otherwise. As a result, the model has a climate sensitivity to a doubling of CO2 over preindustrial conditions of 2.77 K, maintaining the previously identified highly nonlinear global mean response to increasing CO2 forcing, which nonetheless can be represented by a simple two-layer model. 
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42.
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43.
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44.
  • Minikel, EV, et al. (author)
  • Quantifying prion disease penetrance using large population control cohorts
  • 2016
  • In: Science translational medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 8:322, s. 322ra9-
  • Journal article (peer-reviewed)abstract
    • Large genomic reference data sets reveal a spectrum of pathogenicity in the prion protein gene and provide genetic validation for a therapeutic strategy in prion disease.
  •  
45.
  • Oppewal, A, et al. (author)
  • Correlates of Sedentary Behaviour in Adults with Intellectual Disabilities-A Systematic Review
  • 2018
  • In: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 15:10
  • Journal article (peer-reviewed)abstract
    • Individuals with intellectual disabilities (ID) are at high risk for high levels of sedentary behaviour. To inform the development of programmes to reduce sedentary behaviour, insight into the correlates is needed. Therefore, the aim of this study is to review the evidence on correlates of sedentary behaviour in adults with ID. We performed a systematic literature search in Ovid Medline, Ovid Embase, Web of Science and Google Scholar up to 19 January 2018, resulting in nine included studies that were published from 2011 to 2018. Correlates were categorized according to the ecological model. Studies predominantly focused on individual level correlates. Of those correlates studied in more than one study, having epilepsy was associated with less sedentary behaviour and inconsistent results were found for sex, genetic syndromes, weight status, physical health, mobility, level of ID, and mental health. Of the few interpersonal and environmental factors studied, only living arrangements were studied in more than one study, with inconsistent results. To date, we have limited and inconclusive evidence about correlates of sedentary behaviour in adults with ID. Only when future studies unravel correlates and determinants, across all domains of the ecological model, will the potential opportunities to improve health by reducing sedentary behaviour come within reach.
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46.
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47.
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48.
  • Subjak, Jan, et al. (author)
  • TOI-503: The First Known Brown-dwarf Am-star Binary from the TESS Mission
  • 2020
  • In: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 159:4
  • Journal article (peer-reviewed)abstract
    • We report the discovery of an intermediate-mass transiting brown dwarf (BD), TOI-503b, from the TESS mission. TOI-503b is the first BD discovered by TESS, and it has circular orbit around a metallic-line A-type star with a period of P.=.3.6772.+/-.0.0001 days. The light curve from TESS indicates that TOI-503b transits its host star in a grazing manner, which limits the precision with which we measure the BD's radius ( = R 1.34+ R b 0.150.26 J). We obtained highresolution spectroscopic observations with the FIES, Ondr.ejov, PARAS, Tautenburg, and TRES spectrographs, and measured the mass of TOI-503b to be Mb.=.53.7.+/-.1.2 MJ. The host star has a mass of Ma.=.1.80.+/-.0.06Me, a radius of Ra.=.1.70.+/-.0.05Re, an effective temperature of Teff.=.7650.+/-.160 K, and a relatively high metallicity of 0.61.+/-.0.07 dex. We used stellar isochrones to derive the age of the system to be 180 Myr, which places its age between that of RIK 72b (a 10 Myr old BD in the Upper Scorpius stellar association) and AD 3116b (a 600 Myr old BD in the Praesepe cluster). Given the difficulty in measuring the tidal interactions between BDs and their host stars, we cannot precisely say whether this BD formed in situ or has had its orbit circularized by its host star over the relatively short age of the system. Instead, we offer an examination of plausible values for the tidal quality factor for the star and BD. TOI-503b joins a growing number of known short-period, intermediate-mass BDs orbiting mainsequence stars, and is the second such BD known to transit an A star, after HATS-70b. With the growth in the population in this regime, the driest region in the BD desert (35-55MJ sin i) is reforesting.
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