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51.	Martin, N. F., et al. (author) A stellar stream remnant of a globular cluster below the metallicity floor 2022 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 601:7891, s. 45-48 Journal article (peer-reviewed)abstract Stellar ejecta gradually enrich the gas out of which subsequent stars form, making the least chemically enriched stellar systems direct fossils of structures formed in the early Universe1. Although a few hundred stars with metal content below 1,000th of the solar iron content are known in the Galaxy2–4, none of them inhabit globular clusters, some of the oldest known stellar structures. These show metal content of at least approximately 0.2% of the solar metallicity ([Fe / H] ≳ − 2.7). This metallicity floor appears universal5,6, and it has been proposed that protogalaxies that merged into the galaxies we observe today were simply not massive enough to form clusters that survived to the present day7. Here we report observations of a stellar stream, C-19, whose metallicity is less than 0.05% of the solar metallicity ([Fe/H]=−3.38±0.06(statistical)±0.20(systematic)). The low metallicity dispersion and the chemical abundances of the C-19 stars show that this stream is the tidal remnant of the most metal-poor globular cluster ever discovered, and is significantly below the purported metallicity floor: clusters with significantly lower metallicities than observed today existed in the past and contributed their stars to the Milky Way halo.
52.	Mohammed Taha, Hiba, et al. (author) The NORMAN Suspect List Exchange (NORMAN-SLE) : facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry 2022 In: Environmental Sciences Europe. - : Springer. - 2190-4707 .- 2190-4715. ; 34:1 Journal article (peer-reviewed)abstract Background: The NORMAN Association (https://www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for “suspect screening” lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide.Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https://zenodo.org/communities/norman-sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA’s CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101).Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the “one substance, one assessment” approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-network.com/nds/SLE/).
53.	Schijven, Dick, et al. (author) Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium 2023 In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:14 Journal article (peer-reviewed)abstract Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
54.	Akiyama, Kazunori, et al. (author) First Sagittarius A * Event Horizon Telescope Results. I. The Shadow of the Supermassive Black Hole in the Center of the Milky Way 2022 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2 Journal article (peer-reviewed)abstract We present the first Event Horizon Telescope (EHT) observations of Sagittarius A* (Sgr A), the Galactic center source associated with a supermassive black hole. These observations were conducted in 2017 using a global interferometric array of eight telescopes operating at a wavelength of λ = 1.3 mm. The EHT data resolve a compact emission region with intrahour variability. A variety of imaging and modeling analyses all support an image that is dominated by a bright, thick ring with a diameter of 51.8 ± 2.3 μas (68% credible interval). The ring has modest azimuthal brightness asymmetry and a comparatively dim interior. Using a large suite of numerical simulations, we demonstrate that the EHT images of Sgr A are consistent with the expected appearance of a Kerr black hole with mass ∼4 × 106 M☉, which is inferred to exist at this location based on previous infrared observations of individual stellar orbits, as well as maser proper-motion studies. Our model comparisons disfavor scenarios where the black hole is viewed at high inclination (i > 50°), as well as nonspinning black holes and those with retrograde accretion disks. Our results provide direct evidence for the presence of a supermassive black hole at the center of the Milky Way, and for the first time we connect the predictions from dynamical measurements of stellar orbits on scales of 103-105 gravitational radii to event-horizon-scale images and variability. Furthermore, a comparison with the EHT results for the supermassive black hole M87* shows consistency with the predictions of general relativity spanning over three orders of magnitude in central mass.
55.	Akiyama, Kazunori, et al. (author) First Sagittarius A* Event Horizon Telescope Results. III. Imaging of the Galactic Center Supermassive Black Hole 2022 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2 Journal article (peer-reviewed)abstract We present the first event-horizon-scale images and spatiotemporal analysis of Sgr A* taken with the Event Horizon Telescope in 2017 April at a wavelength of 1.3 mm. Imaging of Sgr A* has been conducted through surveys over a wide range of imaging assumptions using the classical CLEAN algorithm, regularized maximum likelihood methods, and a Bayesian posterior sampling method. Different prescriptions have been used to account for scattering effects by the interstellar medium toward the Galactic center. Mitigation of the rapid intraday variability that characterizes Sgr A* has been carried out through the addition of a "variability noise budget" in the observed visibilities, facilitating the reconstruction of static full-track images. Our static reconstructions of Sgr A* can be clustered into four representative morphologies that correspond to ring images with three different azimuthal brightness distributions and a small cluster that contains diverse nonring morphologies. Based on our extensive analysis of the effects of sparse (u, v)-coverage, source variability, and interstellar scattering, as well as studies of simulated visibility data, we conclude that the Event Horizon Telescope Sgr A* data show compelling evidence for an image that is dominated by a bright ring of emission with a ring diameter of similar to 50 mu as, consistent with the expected "shadow" of a 4 x 10(6) M (circle dot) black hole in the Galactic center located at a distance of 8 kpc.
56.	Akiyama, Kazunori, et al. (author) First Sagittarius A* Event Horizon Telescope Results. IV. Variability, Morphology, and Black Hole Mass 2022 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2 Journal article (peer-reviewed)abstract In this paper we quantify the temporal variability and image morphology of the horizon-scale emission from Sgr A, as observed by the EHT in 2017 April at a wavelength of 1.3 mm. We find that the Sgr A data exhibit variability that exceeds what can be explained by the uncertainties in the data or by the effects of interstellar scattering. The magnitude of this variability can be a substantial fraction of the correlated flux density, reaching similar to 100% on some baselines. Through an exploration of simple geometric source models, we demonstrate that ring-like morphologies provide better fits to the Sgr A* data than do other morphologies with comparable complexity. We develop two strategies for fitting static geometric ring models to the time-variable Sgr A* data; one strategy fits models to short segments of data over which the source is static and averages these independent fits, while the other fits models to the full data set using a parametric model for the structural variability power spectrum around the average source structure. Both geometric modeling and image-domain feature extraction techniques determine the ring diameter to be 51.8 +/- 2.3 mu as (68% credible intervals), with the ring thickness constrained to have an FWHM between similar to 30% and 50% of the ring diameter. To bring the diameter measurements to a common physical scale, we calibrate them using synthetic data generated from GRMHD simulations. This calibration constrains the angular size of the gravitational radius to be 4.8(-0.7)(+1.4) mu as, which we combine with an independent distance measurement from maser parallaxes to determine the mass of Sgr A* to be 4.0(-0.6)(+1.1) x 10(6) M-circle dot.
57.	Akiyama, Kazunori, et al. (author) First Sagittarius A* Event Horizon Telescope Results. V. Testing Astrophysical Models of the Galactic Center Black Hole 2022 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2 Journal article (peer-reviewed)abstract In this paper we provide a first physical interpretation for the Event Horizon Telescope's (EHT) 2017 observations of Sgr A*. Our main approach is to compare resolved EHT data at 230 GHz and unresolved non-EHT observations from radio to X-ray wavelengths to predictions from a library of models based on time-dependent general relativistic magnetohydrodynamics simulations, including aligned, tilted, and stellar-wind-fed simulations; radiative transfer is performed assuming both thermal and nonthermal electron distribution functions. We test the models against 11 constraints drawn from EHT 230 GHz data and observations at 86 GHz, 2.2 mu m, and in the X-ray. All models fail at least one constraint. Light-curve variability provides a particularly severe constraint, failing nearly all strongly magnetized (magnetically arrested disk (MAD)) models and a large fraction of weakly magnetized models. A number of models fail only the variability constraints. We identify a promising cluster of these models, which are MAD and have inclination i <= 30 degrees. They have accretion rate (5.2-9.5) x 10(-9) M (circle dot) yr(-1), bolometric luminosity (6.8-9.2) x 10(35) erg s(-1), and outflow power (1.3-4.8) x 10(38) erg s(-1). We also find that all models with i >= 70 degrees fail at least two constraints, as do all models with equal ion and electron temperature; exploratory, nonthermal model sets tend to have higher 2.2 mu m flux density; and the population of cold electrons is limited by X-ray constraints due to the risk of bremsstrahlung overproduction. Finally, we discuss physical and numerical limitations of the models, highlighting the possible importance of kinetic effects and duration of the simulations.
58.	Akiyama, Kazunori, et al. (author) First Sagittarius A* Event Horizon Telescope Results. VI. Testing the Black Hole Metric 2022 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2 Journal article (peer-reviewed)abstract Astrophysical black holes are expected to be described by the Kerr metric. This is the only stationary, vacuum, axisymmetric metric, without electromagnetic charge, that satisfies Einstein's equations and does not have pathologies outside of the event horizon. We present new constraints on potential deviations from the Kerr prediction based on 2017 EHT observations of Sagittarius A* (Sgr A). We calibrate the relationship between the geometrically defined black hole shadow and the observed size of the ring-like images using a library that includes both Kerr and non-Kerr simulations. We use the exquisite prior constraints on the mass-to-distance ratio for Sgr A to show that the observed image size is within similar to 10% of the Kerr predictions. We use these bounds to constrain metrics that are parametrically different from Kerr, as well as the charges of several known spacetimes. To consider alternatives to the presence of an event horizon, we explore the possibility that Sgr A* is a compact object with a surface that either absorbs and thermally reemits incident radiation or partially reflects it. Using the observed image size and the broadband spectrum of Sgr A*, we conclude that a thermal surface can be ruled out and a fully reflective one is unlikely. We compare our results to the broader landscape of gravitational tests. Together with the bounds found for stellar-mass black holes and the M87 black hole, our observations provide further support that the external spacetimes of all black holes are described by the Kerr metric, independent of their mass.
59.	Broderick, Avery E., et al. (author) Characterizing and Mitigating Intraday Variability: Reconstructing Source Structure in Accreting Black Holes with mm-VLBI 2022 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2 Journal article (peer-reviewed)abstract The extraordinary physical resolution afforded by the Event Horizon Telescope has opened a window onto the astrophysical phenomena unfolding on horizon scales in two known black holes, M87* and Sgr A. However, with this leap in resolution has come a new set of practical complications. Sgr A exhibits intraday variability that violates the assumptions underlying Earth aperture synthesis, limiting traditional image reconstruction methods to short timescales and data sets with very sparse (u, v) coverage. We present a new set of tools to detect and mitigate this variability. We develop a data-driven, model-agnostic procedure to detect and characterize the spatial structure of intraday variability. This method is calibrated against a large set of mock data sets, producing an empirical estimator of the spatial power spectrum of the brightness fluctuations. We present a novel Bayesian noise modeling algorithm that simultaneously reconstructs an average image and statistical measure of the fluctuations about it using a parameterized form for the excess variance in the complex visibilities not otherwise explained by the statistical errors. These methods are validated using a variety of simulated data, including general relativistic magnetohydrodynamic simulations appropriate for Sgr A* and M87. We find that the reconstructed source structure and variability are robust to changes in the underlying image model. We apply these methods to the 2017 EHT observations of M87, finding evidence for variability across the EHT observing campaign. The variability mitigation strategies presented are widely applicable to very long baseline interferometry observations of variable sources generally, for which they provide a data-informed averaging procedure and natural characterization of inter-epoch image consistency.
60.	Chen, J, et al. (author) Long-Term Exposure to Fine Particle Elemental Components and Natural and Cause-Specific Mortality-a Pooled Analysis of Eight European Cohorts within the ELAPSE Project 2021 In: Environmental health perspectives. - 1552-9924. ; 129:4, s. 47009- Journal article (peer-reviewed)
61.	Crowley, JJ, et al. (author) Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study protocol 2023 In: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. - 1552-485X. ; 195:4, s. e32962- Journal article (peer-reviewed)
62.	Goddi, Ciriaco, et al. (author) Polarimetric Properties of Event Horizon Telescope Targets from ALMA 2021 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 910:1 Journal article (peer-reviewed)abstract We present the results from a full polarization study carried out with the Atacama Large Millimeter/submillimeter Array (ALMA) during the first Very Long Baseline Interferometry (VLBI) campaign, which was conducted in 2017 April in the lambda 3 mm and lambda 1.3 mm bands, in concert with the Global mm-VLBI Array (GMVA) and the Event Horizon Telescope (EHT), respectively. We determine the polarization and Faraday properties of all VLBI targets, including Sgr A, M87, and a dozen radio-loud active galactic nuclei (AGNs), in the two bands at several epochs in a time window of 10 days. We detect high linear polarization fractions (2%-15%) and large rotation measures (RM > 10(3.3)-10(5.5) rad m(-2)), confirming the trends of previous AGN studies at millimeter wavelengths. We find that blazars are more strongly polarized than other AGNs in the sample, while exhibiting (on average) order-of-magnitude lower RM values, consistent with the AGN viewing angle unification scheme. For Sgr A we report a mean RM of (-4.2 0.3) x 10(5) rad m(-2) at 1.3 mm, consistent with measurements over the past decade and, for the first time, an RM of (-2.1 0.1) x 10(5) rad m(-2) at 3 mm, suggesting that about half of the Faraday rotation at 1.3 mm may occur between the 3 mm photosphere and the 1.3 mm source. We also report the first unambiguous measurement of RM toward the M87 nucleus at millimeter wavelengths, which undergoes significant changes in magnitude and sign reversals on a one year timescale, spanning the range from -1.2 to 0.3 x 10(5) rad m(-2) at 3 mm and -4.1 to 1.5 x 10(5) rad m(-2) at 1.3 mm. Given this time variability, we argue that, unlike the case of Sgr A*, the RM in M87 does not provide an accurate estimate of the mass accretion rate onto the black hole. We put forward a two-component model, comprised of a variable compact region and a static extended region, that can simultaneously explain the polarimetric properties observed by both the EHT (on horizon scales) and ALMA (which observes the combined emission from both components). These measurements provide critical constraints for the calibration, analysis, and interpretation of simultaneously obtained VLBI data with the EHT and GMVA.
63.	Gurvits, L. I., et al. (author) The science case and challenges of spaceborne sub-millimeter interferometry: the study case of TeraHertz Exploration and Zooming-in for Astrophysics (THEZA) 2021 In: Proceedings of the International Astronautical Congress, IAC. - 0074-1795. ; A7 Conference paper (peer-reviewed)abstract Ultra-high angular resolution in astronomy has always been an important vehicle for making fundamental discoveries. Recent results in direct imaging of the vicinity of the super-massive black hole in the nucleus of the radio galaxy M87 by the millimeter VLBI system Event Horizon Telescope (EHT) and various pioneering results of the Space VLBI mission RadioAstron provided new momentum in high angular resolution astrophysics. In both mentioned cases, the angular resolution reached the values of about 10−20 microrcseconds (0.05−0.1 nanoradian). Angular resolution is proportional to the observing wavelength and inversely proportional to the interferometer baseline length. In the case of Earth-based EHT, the highest angular resolution was achieved by combining the shortest possible wavelength of 1.3 mm with the longest possible baselines, comparable to the Earth’s diameter. For RadioAstron, operational wavelengths were in the range from 92 cm down to 1.3 cm, but the baselines were as long as ∼350,000 km. However, these two highlights of radio astronomy, EHT and RadioAstron do not”saturate” the interest to further increase in angular resolution. Quite opposite: the science case for further increase in angular resolution of astrophysical studies becomes even stronger. A natural and, in fact, the only possible way of moving forward is to enhance mm/sub-mm VLBI by extending baselines to extraterrestrial dimensions, i.e. creating a mm/sub-mm Space VLBI system. The inevitable move toward space-borne mm/sub-mm VLBI is a subject of several concept studies. In this presentation we will focus on one of them called TeraHertz Exploration and Zooming-in for Astrophysics (THEZA), prepared in response to the ESA’s call for its next major science program Voyage 2050 (Gurvits et al. 2021). The THEZA rationale is focused at the physics of spacetime in the vicinity of super-massive black holes as the leading science drive. However, it will also open up a sizable new range of hitherto unreachable parameters of observational radio astrophysics and create a multi-disciplinary scientific facility and offer a high degree of synergy with prospective “single dish” space-borne sub-mm astronomy (e.g., Wiedner et al. 2021) and infrared interferometry (e.g., Linz et al. 2021). As an amalgam of several major trends of modern observational astrophysics, THEZA aims at facilitating a breakthrough in high-resolution high image quality astronomical studies.
64.	Hochhaus, A., et al. (author) European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia 2020 In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 34:4, s. 966-984 Research review (peer-reviewed)abstract The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available first-line). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR.
65.	Janssen, O., et al. (author) Real-world evidence in Alzheimer's disease: The ROADMAP Data Cube 2020 In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:3, s. 461-471 Journal article (peer-reviewed)abstract Introduction: The ROADMAP project aimed to provide an integrated overview of European real-world data on Alzheimer's disease (AD) across the disease spectrum. Methods: Metadata were identified from data sources in catalogs of European AD projects. Priority outcomes for different stakeholders were identified through systematic literature review, patient and public consultations, and stakeholder surveys. Results: Information about 66 data sources and 13 outcome domains were integrated into a Data Cube. Gap analysis identified cognitive ability, functional ability/independence, behavioral/neuropsychiatric symptoms, treatment, comorbidities, and mortality as the outcomes collected most. Data were most lacking in caregiver-related outcomes. In general, electronic health records covered a broader, less detailed data spectrum than research cohorts. Discussion: This integrated real-world AD data overview provides an intuitive visual model that facilitates initial assessment and identification of gaps in relevant outcomes data to inform future prospective data collection and matching of data sources and outcomes against research protocols.
66.	Jorstad, S.G., et al. (author) The Event Horizon Telescope Image of the Quasar NRAO 530 2023 In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 943:2 Journal article (peer-reviewed)abstract We report on the observations of the quasar NRAO 530 with the Event Horizon Telescope (EHT) on 2017 April 5-7, when NRAO 530 was used as a calibrator for the EHT observations of Sagittarius A*. At z = 0.902, this is the most distant object imaged by the EHT so far. We reconstruct the first images of the source at 230 GHz, at an unprecedented angular resolution of similar to 20 mu as, both in total intensity and in linear polarization (LP). We do not detect source variability, allowing us to represent the whole data set with static images. The images reveal a bright feature located on the southern end of the jet, which we associate with the core. The feature is linearly polarized, with a fractional polarization of similar to 5%-8%, and it has a substructure consisting of two components. Their observed brightness temperature suggests that the energy density of the jet is dominated by the magnetic field. The jet extends over 60 mu as along a position angle similar to -28 degrees. It includes two features with orthogonal directions of polarization (electric vector position angle), parallel and perpendicular to the jet axis, consistent with a helical structure of the magnetic field in the jet. The outermost feature has a particularly high degree of LP, suggestive of a nearly uniform magnetic field. Future EHT observations will probe the variability of the jet structure on microarcsecond scales, while simultaneous multiwavelength monitoring will provide insight into the high-energy emission origin.
67.	Narayan, Ramesh, et al. (author) The Polarized Image of a Synchrotron-emitting Ring of Gas Orbiting a Black Hole 2021 In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 912:1 Journal article (peer-reviewed)abstract Synchrotron radiation from hot gas near a black hole results in a polarized image. The image polarization is determined by effects including the orientation of the magnetic field in the emitting region, relativistic motion of the gas, strong gravitational lensing by the black hole, and parallel transport in the curved spacetime. We explore these effects using a simple model of an axisymmetric, equatorial accretion disk around a Schwarzschild black hole. By using an approximate expression for the null geodesics derived by Beloborodov and conservation of the Walker-Penrose constant, we provide analytic estimates for the image polarization. We test this model using currently favored general relativistic magnetohydrodynamic simulations of M87, using ring parameters given by the simulations. For a subset of these with modest Faraday effects, we show that the ring model broadly reproduces the polarimetric image morphology. Our model also predicts the polarization evolution for compact flaring regions, such as those observed from Sgr A with GRAVITY. With suitably chosen parameters, our simple model can reproduce the EVPA pattern and relative polarized intensity in Event Horizon Telescope images of M87*. Under the physically motivated assumption that the magnetic field trails the fluid velocity, this comparison is consistent with the clockwise rotation inferred from total intensity images.
68.	Solanes, A, et al. (author) Combining MRI and clinical data to detect high relapse risk after the first episode of psychosis 2022 In: Schizophrenia (Heidelberg, Germany). - : Springer Science and Business Media LLC. - 2754-6993. ; 8:1, s. 100- Journal article (peer-reviewed)abstract Detecting patients at high relapse risk after the first episode of psychosis (HRR-FEP) could help the clinician adjust the preventive treatment. To develop a tool to detect patients at HRR using their baseline clinical and structural MRI, we followed 227 patients with FEP for 18–24 months and applied MRIPredict. We previously optimized the MRI-based machine-learning parameters (combining unmodulated and modulated gray and white matter and using voxel-based ensemble) in two independent datasets. Patients estimated to be at HRR-FEP showed a substantially increased risk of relapse (hazard ratio = 4.58, P < 0.05). Accuracy was poorer when we only used clinical or MRI data. We thus show the potential of combining clinical and MRI data to detect which individuals are more likely to relapse, who may benefit from increased frequency of visits, and which are unlikely, who may be currently receiving unnecessary prophylactic treatments. We also provide an updated version of the MRIPredict software.
69.	Torne, Pablo, et al. (author) A Search for Pulsars around Sgr A* in the First Event Horizon Telescope Data Set 2023 In: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 959:1 Journal article (peer-reviewed)abstract In 2017 the Event Horizon Telescope (EHT) observed the supermassive black hole at the center of the Milky Way, Sagittarius A* (Sgr A), at a frequency of 228.1 GHz (lambda = 1.3 mm). The fundamental physics tests that even a single pulsar orbiting Sgr A would enable motivate searching for pulsars in EHT data sets. The high observing frequency means that pulsars-which typically exhibit steep emission spectra-are expected to be very faint. However, it also negates pulse scattering, an effect that could hinder pulsar detections in the Galactic center. Additionally, magnetars or a secondary inverse Compton emission could be stronger at millimeter wavelengths than at lower frequencies. We present a search for pulsars close to Sgr A* using the data from the three most sensitive stations in the EHT 2017 campaign: the Atacama Large Millimeter/submillimeter Array, the Large Millimeter Telescope, and the IRAM 30 m Telescope. We apply three detection methods based on Fourier-domain analysis, the fast folding algorithm, and single-pulse searches targeting both pulsars and burst-like transient emission. We use the simultaneity of the observations to confirm potential candidates. No new pulsars or significant bursts were found. Being the first pulsar search ever carried out at such high radio frequencies, we detail our analysis methods and give a detailed estimation of the sensitivity of the search. We conclude that the EHT 2017 observations are only sensitive to a small fraction (less than or similar to 2.2%) of the pulsars that may exist close to Sgr A*, motivating further searches for fainter pulsars in the region.
70.	van Roessel, S, et al. (author) Evaluation of Adjuvant Chemotherapy in Patients With Resected Pancreatic Cancer After Neoadjuvant FOLFIRINOX Treatment 2020 In: JAMA ONCOLOGY. - : American Medical Association (AMA). - 2374-2437. ; 6:11, s. 1733-1740 Journal article (other academic/artistic)
71.	Wielgus, Maciek, et al. (author) Millimeter Light Curves of Sagittarius A* Observed during the 2017 Event Horizon Telescope Campaign 2022 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2 Journal article (peer-reviewed)abstract The Event Horizon Telescope (EHT) observed the compact radio source, Sagittarius A* (Sgr A), in the Galactic Center on 2017 April 5-11 in the 1.3 mm wavelength band. At the same time, interferometric array data from the Atacama Large Millimeter/submillimeter Array and the Submillimeter Array were collected, providing Sgr A light curves simultaneous with the EHT observations. These data sets, complementing the EHT very long baseline interferometry, are characterized by a cadence and signal-to-noise ratio previously unattainable for Sgr A* at millimeter wavelengths, and they allow for the investigation of source variability on timescales as short as a minute. While most of the light curves correspond to a low variability state of Sgr A, the April 11 observations follow an X-ray flare and exhibit strongly enhanced variability. All of the light curves are consistent with a red-noise process, with a power spectral density (PSD) slope measured to be between -2 and -3 on timescales between 1 minute and several hours. Our results indicate a steepening of the PSD slope for timescales shorter than 0.3 hr. The spectral energy distribution is flat at 220 GHz, and there are no time lags between the 213 and 229 GHz frequency bands, suggesting low optical depth for the event horizon scale source. We characterize Sgr A's variability, highlighting the different behavior observed just after the X-ray flare, and use Gaussian process modeling to extract a decorrelation timescale and a PSD slope. We also investigate the systematic calibration uncertainties by analyzing data from independent data reduction pipelines.
72.	Akiyama, Kazunori, et al. (author) First M87 Event Horizon Telescope Results. VII. Polarization of the Ring 2021 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 910:1 Journal article (peer-reviewed)abstract In 2017 April, the Event Horizon Telescope (EHT) observed the near-horizon region around the supermassive black hole at the core of the M87 galaxy. These 1.3 mm wavelength observations revealed a compact asymmetric ring-like source morphology. This structure originates from synchrotron emission produced by relativistic plasma located in the immediate vicinity of the black hole. Here we present the corresponding linear-polarimetric EHT images of the center of M87. We find that only a part of the ring is significantly polarized. The resolved fractional linear polarization has a maximum located in the southwest part of the ring, where it rises to the level of similar to 15%. The polarization position angles are arranged in a nearly azimuthal pattern. We perform quantitative measurements of relevant polarimetric properties of the compact emission and find evidence for the temporal evolution of the polarized source structure over one week of EHT observations. The details of the polarimetric data reduction and calibration methodology are provided. We carry out the data analysis using multiple independent imaging and modeling techniques, each of which is validated against a suite of synthetic data sets. The gross polarimetric structure and its apparent evolution with time are insensitive to the method used to reconstruct the image. These polarimetric images carry information about the structure of the magnetic fields responsible for the synchrotron emission. Their physical interpretation is discussed in an accompanying publication.
73.	Akiyama, Kazunori, et al. (author) First M87 Event Horizon Telescope Results. VIII. Magnetic Field Structure near The Event Horizon 2021 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 910:1 Journal article (peer-reviewed)abstract Event Horizon Telescope (EHT) observations at 230 GHz have now imaged polarized emission around the supermassive black hole in M87 on event-horizon scales. This polarized synchrotron radiation probes the structure of magnetic fields and the plasma properties near the black hole. Here we compare the resolved polarization structure observed by the EHT, along with simultaneous unresolved observations with the Atacama Large Millimeter/submillimeter Array, to expectations from theoretical models. The low fractional linear polarization in the resolved image suggests that the polarization is scrambled on scales smaller than the EHT beam, which we attribute to Faraday rotation internal to the emission region. We estimate the average density n(e) similar to 10(4-7) cm(-3), magnetic field strength B similar to 1-30 G, and electron temperature T-e similar to (1-12) x 10(10) K of the radiating plasma in a simple one-zone emission model. We show that the net azimuthal linear polarization pattern may result from organized, poloidal magnetic fields in the emission region. In a quantitative comparison with a large library of simulated polarimetric images from general relativistic magnetohydrodynamic (GRMHD) simulations, we identify a subset of physical models that can explain critical features of the polarimetric EHT observations while producing a relativistic jet of sufficient power. The consistent GRMHD models are all of magnetically arrested accretion disks, where near-horizon magnetic fields are dynamically important. We use the models to infer a mass accretion rate onto the black hole in M87 of (3-20) x 10(-4) M yr(-1).
74.	Arentsen, A., et al. (author) The Pristine Inner Galaxy Survey (PIGS) I : tracing the kinematics of metal-poor stars in the Galactic bulge 2020 In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966 .- 1745-3925 .- 1745-3933. ; 491:1, s. L11-L16 Journal article (peer-reviewed)abstract Our Galaxy is known to contain a central boxy/peanut-shaped bulge, yet the importance of a classical, pressure-supported component within the central part of the Milky Way is still being debated. It should be most visible at low metallicity, a regime that has not yet been studied in detail. Using metallicity-sensitive narrow-band photometry, the Pristine Inner Galaxy Survey (PIGS) has collected a large sample of metal-poor ([Fe/H] < -1.0) stars in the inner Galaxy to address this open question. We use PIGS to trace the metal-poor inner Galaxy kinematics as function of metallicity for the first time. We find that the rotational signal decreases with decreasing [Fe/H], until it becomes negligible for the most metal-poor stars. Additionally, the velocity dispersion increases with decreasing metallicity for -3.0 < [Fe/II] < -0.5, with a gradient of -44 +/- 41un s(-1)dex(-1). These observations may signal a transition between Galactic components of different metallicities and kinematics, a different mapping on to the boxy/peanut-shaped bulge for former disc stars of different metallicities and/or the secular dynamical and gravitational influence of the bar on the pressure-supported component. Our results provide strong constraints on models that attempt to explain the properties of the inner Galaxy.
75.	de Vries, Claire E. E., et al. (author) Outcomes of the first global multidisciplinary consensus meeting including persons living with obesity to standardize patient-reported outcome measurement in obesity treatment research 2022 In: Obesity Reviews. - : John Wiley & Sons. - 1467-7881 .- 1467-789X. ; 23:8 Journal article (peer-reviewed)abstract Quality of life is a key outcome that is not rigorously measured in obesity treatment research due to the lack of standardization of patient-reported outcomes (PROs) and PRO measures (PROMs). The S.Q.O.T. initiative was founded to Standardize Quality of life measurement in Obesity Treatment. A first face-to-face, international, multidisciplinary consensus meeting was conducted to identify the key PROs and preferred PROMs for obesity treatment research. It comprised of 35 people living with obesity (PLWO) and healthcare providers (HCPs). Formal presentations, nominal group techniques, and modified Delphi exercises were used to develop consensus-based recommendations. The following eight PROs were considered important: self-esteem, physical health/functioning, mental/psychological health, social health, eating, stigma, body image, and excess skin. Self-esteem was considered the most important PRO, particularly for PLWO, while physical health was perceived to be the most important among HCPs. For each PRO, one or more PROMs were selected, except for stigma. This consensus meeting was a first step toward standardizing PROs (what to measure) and PROMs (how to measure) in obesity treatment research. It provides an overview of the key PROs and a first selection of the PROMs that can be used to evaluate these PROs.
76.	Everaert, G., et al. (author) Risks of floating microplastic in the global ocean 2020 In: Environmental Pollution. - : Elsevier BV. - 0269-7491. ; 267 Journal article (peer-reviewed)abstract Despite the ubiquitous and persistent presence of microplastic (MP) in marine ecosystems, knowledge of its potential harmful ecological effects is low. In this work, we assessed the risk of floating MP (1 μm–5 mm) to marine ecosystems by comparing ambient concentrations in the global ocean with available ecotoxicity data. The integration of twenty-three species-specific effect threshold concentration data in a species sensitivity distribution yielded a median unacceptable level of 1.21 ∗ 105 MP m−³ (95% CI: 7.99 ∗ 103–1.49 ∗ 106 MP m−³). We found that in 2010 for 0.17% of the surface layer (0–5 m) of the global ocean a threatening risk would occur. By 2050 and 2100, this fraction increases to 0.52% and 1.62%, respectively, according to the worst-case predicted future plastic discharge into the ocean. Our results reveal a spatial and multidecadal variability of MP-related risk at the global ocean surface. For example, we have identified the Mediterranean Sea and the Yellow Sea as hotspots of marine microplastic risks already now and even more pronounced in future decades. © 2020 The Author(s)
77.	Farah, Joseph, et al. (author) Selective Dynamical Imaging of Interferometric Data 2022 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2 Journal article (peer-reviewed)abstract Recent developments in very long baseline interferometry (VLBI) have made it possible for the Event Horizon Telescope (EHT) to resolve the innermost accretion flows of the largest supermassive black holes on the sky. The sparse nature of the EHT's (u, v)-coverage presents a challenge when attempting to resolve highly time-variable sources. We demonstrate that the changing (u, v)-coverage of the EHT can contain regions of time over the course of a single observation that facilitate dynamical imaging. These optimal time regions typically have projected baseline distributions that are approximately angularly isotropic and radially homogeneous. We derive a metric of coverage quality based on baseline isotropy and density that is capable of ranking array configurations by their ability to produce accurate dynamical reconstructions. We compare this metric to existing metrics in the literature and investigate their utility by performing dynamical reconstructions on synthetic data from simulated EHT observations of sources with simple orbital variability. We then use these results to make recommendations for imaging the 2017 EHT Sgr A* data set.
78.	Galosi, Serena, et al. (author) De novo DHDDS variants cause a neurodevelopmental and neurodegenerative disorder with myoclonus 2022 In: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 145:1, s. 208-223 Journal article (peer-reviewed)abstract Subcellular membrane systems are highly enriched in dolichol, whose role in organelle homeostasis and endosomal-lysosomal pathway remains largely unclear besides being involved in protein glycosylation. DHDDS encodes for the catalytic subunit (DHDDS) of the enzyme cis-prenyltransferase (cis-PTase), involved in dolichol biosynthesis and dolichol-dependent protein glycosylation in the endoplasmic reticulum. An autosomal recessive form of retinitis pigmentosa (retinitis pigmentosa 59) has been associated with a recurrent DHDDS variant. Moreover, two recurring de novo substitutions were detected in a few cases presenting with neurodevelopmental disorder, epilepsy, and movement disorder. We evaluated a large cohort of patients (n=25) with de novo pathogenic variants in DHDDS and provided the first systematic description of the clinical features and long-term outcome of this new neurodevelopmental and neurodegenerative disorder. The functional impact of the identified variants was explored by yeast complementation system and enzymatic assay. Patients presented during infancy or childhood with a variable association of neurodevelopmental disorder, generalized epilepsy, action myoclonus/cortical tremor, and ataxia. Later in the disease course they experienced a slow neurological decline with the emergence of hyperkinetic and/or hypokinetic movement disorder, cognitive deterioration, and psychiatric disturbances. Storage of lipidic material and altered lysosomes were detected in myelinated fibers and fibroblasts, suggesting a dysfunction of the lysosomal enzymatic scavenger machinery. Serum glycoprotein hypoglycosylation was not detected and, in contrast to retinitis pigmentosa and other congenital disorders of glycosylation involving dolichol metabolism, the urinary dolichol D18/D19 ratio was normal. Mapping the disease-causing variants into the protein structure revealed that most of them clustered around the active site of the DHDDS subunit. Functional studies using yeast complementation assay and in vitro activity measurements confirmed that these changes affected the catalytic activity of the cis-PTase and showed growth defect in yeast complementation system as compared with the wild-type enzyme and retinitis pigmentosa-associated protein. In conclusion, we characterized a distinctive neurodegenerative disorder due to de novo DHDDS variants, which clinically belongs to the spectrum of genetic progressive encephalopathies with myoclonus. Clinical and biochemical data from this cohort depicted a condition at the intersection of congenital disorders of glycosylation and inherited storage diseases with several features akin to of progressive myoclonus epilepsy such as neuronal ceroid lipofuscinosis and other lysosomal disorders.
79.	Hernández-Durán, S., et al. (author) European women in neurosurgery: I – A chronology of trailblazers 2021 In: Journal of Clinical Neuroscience. - : Elsevier BV. - 0967-5868. ; 86, s. 316-323 Journal article (peer-reviewed)abstract Neurosurgery as a distinct speciality has been around for 100 years. Some of the earliest women neurosurgeons were European, emerging from the 1920′s onwards. Here we detail the rise of women in neurosurgery across Europe with a decade by decade account of big events and firsts across the continent. The emerging themes are seen in stories of pioneers with enormous resilience, camaraderie, trailblazing and triumphing in a system with great obstacles and challenges. Our journey through this chronology brings us to the modern day, where most European countries have or have had a woman neurosurgeon and the future for women in neurosurgery in the continent is very bright. © 2021
80.	Issaoun, Sara, et al. (author) Resolving the Inner Parsec of the Blazar J1924-2914 with the Event Horizon Telescope 2022 In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 934:2 Journal article (peer-reviewed)abstract The blazar J1924-2914 is a primary Event Horizon Telescope (EHT) calibrator for the Galactic center's black hole Sagittarius A*. Here we present the first total and linearly polarized intensity images of this source obtained with the unprecedented 20 mu as resolution of the EHT. J1924-2914 is a very compact flat-spectrum radio source with strong optical variability and polarization. In April 2017 the source was observed quasi-simultaneously with the EHT (April 5-11), the Global Millimeter VLBI Array (April 3), and the Very Long Baseline Array (April 28), giving a novel view of the source at four observing frequencies, 230, 86, 8.7, and 2.3 GHz. These observations probe jet properties from the subparsec to 100 pc scales. We combine the multifrequency images of J1924-2914 to study the source morphology. We find that the jet exhibits a characteristic bending, with a gradual clockwise rotation of the jet projected position angle of about 90 degrees between 2.3 and 230 GHz. Linearly polarized intensity images of J1924-2914 with the extremely fine resolution of the EHT provide evidence for ordered toroidal magnetic fields in the blazar compact core.
81.	Murphy, M., et al. (author) European women in neurosurgery: II – Historical characters and living legends 2021 In: Journal of Clinical Neuroscience. - : Elsevier BV. - 0967-5868. ; 86, s. 324-331 Journal article (peer-reviewed)abstract A collaborative global working group of women neurosurgeons in multiple countries at different stages of their neurosurgical careers undertook the task of researching the history of European women in neurosurgery. While doing so, we happened upon many remarkable female neurosurgeons who overcame great adversity, made tremendous contributions to society and institutional neurosurgery, and displayed numerous talents beyond the operating room. In the first part of this paper, we recounted a chronology of female neurosurgeons in Europe, highlighting the most remarkable achievements of women in every decade, from the 1920’s to 2020. In this paper, we honor fascinating women in European neurosurgery, both historical characters and living legends. These women have overcome great adversity and have also excelled in a huge variety of pursuits. While some were themselves refugees, we also have uncovered noteworthy examples of women who immersed themselves in humanitarian missions and who tried to better the world through political action. There are stories of women beating the odds, taking on biased institutions and proving their worth, in spite of the prevailing system. Most inspirational, we have discovered through our comprehensive research on the history of women in European neurosurgery that the future is increasingly female. © 2021 Elsevier Ltd
82.	Satapathy, Kaushik, et al. (author) The Variability of the Black Hole Image in M87 at the Dynamical Timescale 2022 In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 925:1 Journal article (peer-reviewed)abstract The black hole images obtained with the Event Horizon Telescope (EHT) are expected to be variable at the dynamical timescale near their horizons. For the black hole at the center of the M87 galaxy, this timescale (5-61 days) is comparable to the 6 day extent of the 2017 EHT observations. Closure phases along baseline triangles are robust interferometric observables that are sensitive to the expected structural changes of the images but are free of station-based atmospheric and instrumental errors. We explored the day-to-day variability in closure-phase measurements on all six linearly independent nontrivial baseline triangles that can be formed from the 2017 observations. We showed that three triangles exhibit very low day-to-day variability, with a dispersion of similar to 3 degrees-5 degrees. The only triangles that exhibit substantially higher variability (similar to 90 degrees-180 degrees) are the ones with baselines that cross the visibility amplitude minima on the u-v plane, as expected from theoretical modeling. We used two sets of general relativistic magnetohydrodynamic simulations to explore the dependence of the predicted variability on various black hole and accretion-flow parameters. We found that changing the magnetic field configuration, electron temperature model, or black hole spin has a marginal effect on the model consistency with the observed level of variability. On the other hand, the most discriminating image characteristic of models is the fractional width of the bright ring of emission. Models that best reproduce the observed small level of variability are characterized by thin ring-like images with structures dominated by gravitational lensing effects and thus least affected by turbulence in the accreting plasmas.
83.	Sestito, Federico, et al. (author) The Pristine survey – X. A large population of low-metallicity stars permeates the Galactic disc 2020 In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966 .- 1745-3925 .- 1745-3933. ; 497:1, s. L7-L12 Journal article (peer-reviewed)abstract The orbits of the least chemically enriched stars open a window on the formation of our Galaxy when it was still in its infancy. The common picture is that these low-metallicity stars are distributed as an isotropic, pressure-supported component since these stars were either accreted from the early building blocks of the assembling Milky Way (MW), or were later brought by the accretion of faint dwarf galaxies. Combining the metallicities and radial velocities from the Pristine and LAMOST surveys and Gaia DR2 parallaxes and proper motions for an unprecedented large and unbiased sample of 1027 very metal poor stars at [Fe/H] ≤ −2.5 dex, we show that this picture is incomplete. We find that 31 per cent of the stars that currently reside spatially in the disc (⁠\|Z\|≤3kpc⁠) do not venture outside of the disc plane throughout their orbit. Moreover, this sample shows strong statistical evidence (at the 5.0σ level) of asymmetry in their kinematics, favouring prograde motion. The discovery of this population implies that a significant fraction of stars with iron abundances [Fe/H] ≤ −2.5 dex merged into, formed within, or formed concurrently with the MW disc and that the history of the disc was quiet enough to allow them to retain their disc-like orbital properties, challenging theoretical and cosmological models.
84.	Si, SQ, et al. (author) Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study 2024 In: Molecular psychiatry. - 1476-5578. ; 29:2, s. 496-504 Journal article (peer-reviewed)
85.	Stafoggia, M, et al. (author) Long-term exposure to low ambient air pollution concentrations and mortality among 28 million people: results from seven large European cohorts within the ELAPSE project 2022 In: The Lancet. Planetary health. - 2542-5196. ; 6:1, s. e9-e18 Journal article (peer-reviewed)
86.	Stoop, Thomas F., et al. (author) Pathological complete response in patients with resected pancreatic adenocarcinoma after preoperative chemotherapy 2024 In: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 7:6 Journal article (peer-reviewed)abstract Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking.Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy.Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months.Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection.Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively.Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89).Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.
87.	Uszko-Lencer, Nhmk, et al. (author) Clustering based on comorbidities in patients with chronic heart failure: an illustration of clinical diversity 2022 In: ESC Heart Failure. - : Wiley. - 2055-5822. ; 9:1, s. 614-626 Journal article (peer-reviewed)abstract Aims It is increasingly recognized that the presence of comorbidities substantially contributes to the disease burden in patients with heart failure (HF). Several reports have suggested that clustering of comorbidities can lead to improved characterization of the disease phenotypes, which may influence management of the individual patient. Therefore, we aimed to cluster patients with HF based on medical comorbidities and their treatment and, subsequently, compare the clinical characteristics between these clusters. Methods and results A total of 603 patients with HF entering an outpatient HF rehabilitation programme were included [median age 65 years (interquartile range 56-71), 57% ischaemic origin of cardiomyopathy, and left ventricular ejection fraction 35% (26-45)]. Exercise performance, daily life activities, disease-specific health status, coping styles, and personality traits were assessed. In addition, the presence of 12 clinically relevant comorbidities was recorded, based on targeted diagnostics combined with applicable pharmacotherapies. Self-organizing maps (SOMs; ) were used to visualize clusters, generated by using a hybrid algorithm that applies the classical hierarchical cluster method of Ward on top of the SOM topology. Five clusters were identified: (1) a least comorbidities cluster; (2) a cachectic/implosive cluster; (3) a metabolic diabetes cluster; (4) a metabolic renal cluster; and (5) a psychologic cluster. Exercise performance, daily life activities, disease-specific health status, coping styles, personality traits, and number of comorbidities were significantly different between these clusters. Conclusions Distinct combinations of comorbidities could be identified in patients with HF. Therapy may be tailored based on these clusters as next step towards precision medicine. The effect of such an approach needs to be prospectively tested.
88.	Verberkt, C. A., et al. (author) Healthcare and Societal Costs in Patients with COPD and Breathlessness after Completion of a Comprehensive Rehabilitation Program 2021 In: COPD: Journal of Chronic Obstructive Pulmonary Disease. - : Informa UK Limited. - 1541-2555 .- 1541-2563. ; 18:2, s. 170-180 Journal article (peer-reviewed)abstract Breathlessness is one of the most frequent symptoms in chronic obstructive pulmonary disease (COPD). COPD may result in disability, decreased productivity and increased healthcare costs. The presence of comorbidities increases healthcare utilization. However, the impact of breathlessness burden on healthcare utilization and daily activities is unclear. This study’s goal was to analyze the impact of breathlessness burden on healthcare and societal costs. In this observational single-center study, patients with COPD were followed-up for 24 months after completion of a comprehensive pulmonary rehabilitation program. Every three months participants completed a cost questionnaire, covering healthcare utilization and impact on daily activities. The results were compared between participants with low (modified Medical Research Council (mMRC) grade <2; LBB) and high baseline breathlessness burden (mMRC grade ≥2; HBB). Healthcare costs in year 1 were €7302 (95% confidence interval €6476–€8258) for participants with LBB and €10,738 (€9141–€12,708) for participants with HBB. In year 2, costs were €8830 (€7372-€10,562) and €14,933 (€12,041–€18,520), respectively. Main cost drivers were hospitalizations, contact with other healthcare professionals and rehabilitation. Costs outside the healthcare sector in year 1 were €682 (€520–€900) for participants with LBB and €1520 (€1210–€1947) for participants with HBB. In year 2, costs were €829 (€662–€1046) and €1457 (€1126–€1821) respectively. HBB in patients with COPD is associated with higher healthcare and societal costs, which increases over time. This study highlights the relevance of reducing costs with adequate breathlessness relief. When conventional approaches fail to improve breathlessness, a personalized holistic approach is warranted. © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
89.	Wolf, K, et al. (author) Long-term exposure to low-level ambient air pollution and incidence of stroke and coronary heart disease: a pooled analysis of six European cohorts within the ELAPSE project 2021 In: The Lancet. Planetary health. - 2542-5196. ; 5:9, s. E620-E632 Journal article (peer-reviewed)
90.	Ali, M, et al. (author) T cells targeted to TdT kill leukemic lymphoblasts while sparing normal lymphocytes 2022 In: Nature biotechnology. - : Springer Science and Business Media LLC. - 1546-1696 .- 1087-0156. ; 40:4, s. 488- Journal article (peer-reviewed)abstract Unlike chimeric antigen receptors, T-cell receptors (TCRs) can recognize intracellular targets presented on human leukocyte antigen (HLA) molecules. Here we demonstrate that T cells expressing TCRs specific for peptides from the intracellular lymphoid-specific enzyme terminal deoxynucleotidyl transferase (TdT), presented in the context of HLA-A*02:01, specifically eliminate primary acute lymphoblastic leukemia (ALL) cells of T- and B-cell origin in vitro and in three mouse models of disseminated B-ALL. By contrast, the treatment spares normal peripheral T- and B-cell repertoires and normal myeloid cells in vitro, and in vivo in humanized mice. TdT is an attractive cancer target as it is highly and homogeneously expressed in 80–94% of B- and T-ALLs, but only transiently expressed during normal lymphoid differentiation, limiting on-target toxicity of TdT-specific T cells. TCR-modified T cells targeting TdT may be a promising immunotherapy for B-ALL and T-ALL that preserves normal lymphocytes.
91.	Almora, Osbel, et al. (author) Device Performance of Emerging Photovoltaic Materials (Version 1) 2020 In: Advanced Energy Materials. - : Wiley. - 1614-6832 .- 1614-6840. ; 11:11 Journal article (peer-reviewed)abstract Emerging photovoltaics (PVs) focus on a variety of applications complementing large scale electricity generation. Organic, dye-sensitized, and some perovskite solar cells are considered in building integration, greenhouses, wearable, and indoor applications, thereby motivating research on flexible, transparent, semitransparent, and multi-junction PVs. Nevertheless, it can be very time consuming to find or develop an up-to-date overview of the state-of-the-art performance for these systems and applications. Two important resources for recording research cells efficiencies are the National Renewable Energy Laboratory chart and the efficiency tables compiled biannually by Martin Green and colleagues. Both publications provide an effective coverage over the established technologies, bridging research and industry. An alternative approach is proposed here summarizing the best reports in the diverse research subjects for emerging PVs. Best performance parameters are provided as a function of the photovoltaic bandgap energy for each technology and application, and are put into perspective using, e.g., the Shockley–Queisser limit. In all cases, the reported data correspond to published and/or properly described certified results, with enough details provided for prospective data reproduction. Additionally, the stability test energy yield is included as an analysis parameter among state-of-the-art emerging PVs.
92.	Barth, Claudia, et al. (author) In vivo white matter microstructure in adolescents with early-onset psychosis : a multi-site mega-analysis 2023 In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 28, s. 1159-1169 Journal article (peer-reviewed)abstract Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls using diffusion tensor imaging (DTI). Our sample included 321 adolescents with EOP (median age=16.6 years, interquartile range (IQR)=2.14, 46.4% females) and 265 adolescent healthy controls (median age=16.2 years, IQR=2.43, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for 25 white matter regions of interest per participant. ComBat harmonization was performed for all DTI measures to adjust for scanner differences. Multiple linear regression models were fitted to investigate case-control differences and associations with clinical variables in regional DTI measures. We found widespread lower FA in EOP compared to healthy controls, with the largest effect sizes in the superior longitudinal fasciculus (Cohen's d=0.37), posterior corona radiata (d=0.32), and superior fronto-occipital fasciculus (d=0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. Using the largest EOP DTI sample to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male individuals with early-onset schizophrenia and individuals with a shorter duration of illness.
93.	Brunekreef, B, et al. (author) Mortality and Morbidity Effects of Long-Term Exposure to Low-Level PM2.5, BC, NO2, and O3: An Analysis of European Cohorts in the ELAPSE Project 2021 In: Research report (Health Effects Institute). - 1041-5505. ; :208, s. 1-127 Journal article (peer-reviewed)
94.	Coleman, E, et al. (author) Standards of Care for the Health of Transgender and Gender Diverse People, Version 8 2022 In: International journal of transgender health. - : Informa UK Limited. - 2689-5277 .- 2689-5269. ; 23:Suppl 1, s. S1-S258 Journal article (peer-reviewed)
95.	de Boer, E, et al. (author) A MT-TL1 variant identified by whole exome sequencing in an individual with intellectual disability, epilepsy, and spastic tetraparesis 2021 In: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 29:9, s. 1359-1368 Journal article (peer-reviewed)abstract The genetic etiology of intellectual disability remains elusive in almost half of all affected individuals. Within the Solve-RD consortium, systematic re-analysis of whole exome sequencing (WES) data from unresolved cases with (syndromic) intellectual disability (n = 1,472 probands) was performed. This re-analysis included variant calling of mitochondrial DNA (mtDNA) variants, although mtDNA is not specifically targeted in WES. We identified a functionally relevant mtDNA variant in MT-TL1 (NC_012920.1:m.3291T > C; NC_012920.1:n.62T > C), at a heteroplasmy level of 22% in whole blood, in a 23-year-old male with severe intellectual disability, epilepsy, episodic headaches with emesis, spastic tetraparesis, brain abnormalities, and feeding difficulties. Targeted validation in blood and urine supported pathogenicity, with heteroplasmy levels of 23% and 58% in index, and 4% and 17% in mother, respectively. Interestingly, not all phenotypic features observed in the index have been previously linked to this MT-TL1 variant, suggesting either broadening of the m.3291T > C-associated phenotype, or presence of a co-occurring disorder. Hence, our case highlights the importance of underappreciated mtDNA variants identifiable from WES data, especially for cases with atypical mitochondrial phenotypes and their relatives in the maternal line.
96.	Durcik, Martina, et al. (author) New Dual Inhibitors of Bacterial Topoisomerases with Broad-Spectrum Antibacterial Activity and In Vivo Efficacy against Vancomycin-Intermediate Staphylococcus aureus 2023 In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 66:6, s. 3968-3994 Journal article (peer-reviewed)abstract A new series of dual low nanomolar benzothiazole inhibitors of bacterial DNA gyrase and topoisomerase IV were developed. The resulting compounds show excellent broad-spectrum antibacterial activities against Gram-positive Enterococcus faecalis, Enterococcus faecium and multidrug resistant (MDR) Staphylococcus aureus strains [best compound minimal inhibitory concentrations (MICs): range, <0.03125–0.25 μg/mL] and against the Gram-negatives Acinetobacter baumannii and Klebsiella pneumoniae (best compound MICs: range, 1–4 μg/mL). Lead compound 7a was identified with favorable solubility and plasma protein binding, good metabolic stability, selectivity for bacterial topoisomerases, and no toxicity issues. The crystal structure of 7a in complex with Pseudomonas aeruginosa GyrB24 revealed its binding mode at the ATP-binding site. Expanded profiling of 7a and 7h showed potent antibacterial activity against over 100 MDR and non-MDR strains of A. baumannii and several other Gram-positive and Gram-negative strains. Ultimately, in vivo efficacy of 7a in a mouse model of vancomycin-intermediate S. aureus thigh infection was also demonstrated.
97.	Flygt, H, et al. (author) Correction: Treatment-free remission after a second TKI discontinuation attempt in patients with Chronic Myeloid Leukemia re-treated with dasatinib - interim results from the DAstop2 trial 2024 In: Leukemia. - 1476-5551. ; 38:54, s. 925-925 Journal article (other academic/artistic)
98.	Gauld, Jethro G., et al. (author) Hotspots in the grid : Avian sensitivity and vulnerability to collision risk from energy infrastructure interactions in Europe and North Africa 2022 In: Journal of Applied Ecology. - : John Wiley & Sons. - 0021-8901 .- 1365-2664. ; 59:6, s. 1496-1512 Journal article (peer-reviewed)abstract Wind turbines and power lines can cause bird mortality due to collision or electrocution. The biodiversity impacts of energy infrastructure (EI) can be minimised through effective landscape-scale planning and mitigation. The identification of high-vulnerability areas is urgently needed to assess potential cumulative impacts of EI while supporting the transition to zero carbon energy. We collected GPS location data from 1,454 birds from 27 species susceptible to collision within Europe and North Africa and identified areas where tracked birds are most at risk of colliding with existing EI. Sensitivity to EI development was estimated for wind turbines and power lines by calculating the proportion of GPS flight locations at heights where birds were at risk of collision and accounting for species' specific susceptibility to collision. We mapped the maximum collision sensitivity value obtained across all species, in each 5 x 5 km grid cell, across Europe and North Africa. Vulnerability to collision was obtained by overlaying the sensitivity surfaces with density of wind turbines and transmission power lines. Results: Exposure to risk varied across the 27 species, with some species flying consistently at heights where they risk collision. For areas with sufficient tracking data within Europe and North Africa, 13.6% of the area was classified as high sensitivity to wind turbines and 9.4% was classified as high sensitivity to transmission power lines. Sensitive areas were concentrated within important migratory corridors and along coastlines. Hotspots of vulnerability to collision with wind turbines and transmission power lines (2018 data) were scattered across the study region with highest concentrations occurring in central Europe, near the strait of Gibraltar and the Bosporus in Turkey. Synthesis and applications. We identify the areas of Europe and North Africa that are most sensitive for the specific populations of birds for which sufficient GPS tracking data at high spatial resolution were available. We also map vulnerability hotspots where mitigation at existing EI should be prioritised to reduce collision risks. As tracking data availability improves our method could be applied to more species and areas to help reduce bird-EI conflicts.
99.	Geelen, Inge G. P., et al. (author) Switching from imatinib to nilotinib plus pegylated interferon-α2b in chronic phase CML failing to achieve deep molecular response : clinical and immunological effects 2023 In: Annals of Hematology. - : Springer. - 0939-5555 .- 1432-0584. ; 102:6, s. 1395-1408 Journal article (peer-reviewed)abstract In order to improve molecular response for a discontinuation attempt in chronic myeloid leukemia (CML) patients in chronic phase, who had not achieved at least a molecular response <0.01% BCR-ABL1IS (MR4.0) after at least 2 years of imatinib therapy, we prospectively evaluated whether they could attain MR4.0 after a switch to a combination of nilotinib and 9 months of pegylated interferon-α2b (PegIFN). The primary endpoint of confirmed MR4.0 at month 12 (a BCR-ABL1IS level ≤ 0.01% both at 12 and 15 months) was reached by 44% (7/16 patients, 95% confidence interval (CI): 23- 67%) of patients, with 81% (13/16 patients, 95% CI: 57-93%) of patients achieving an unconfirmed MR4.0. The scheduled combination was completed by 56% of the patients, with premature discontinuations, mainly due to mood disturbances after the introduction of PegIFN, questioning the feasibility of the combination of nilotinib and PegIFN for this patient population and treatment goal. A comprehensive clinical substudy program was implemented to characterize the impact of the treatment changes on the immunological profile.
100.	Gurvits,, et al. (author) The science case and challenges of space-borne sub-millimeter interferometry 2022 In: Acta Astronautica. - : Elsevier BV. - 0094-5765. ; 196, s. 314-333 Journal article (peer-reviewed)abstract Ultra-high angular resolution in astronomy has always been an important vehicle for making fundamental discoveries. Recent results in direct imaging of the vicinity of the supermassive black hole in the nucleus of the radio galaxy M87 by the millimeter VLBI system Event Horizon Telescope and various pioneering results of the Space VLBI mission RadioAstron provided new momentum in high angular resolution astrophysics. In both mentioned cases, the angular resolution reached the values of about 10???20 microarcseconds (0.05???0.1 nanoradian). Further developments towards at least an order of magnitude ???sharper???values, at the level of 1 microarcsecond are dictated by the needs of advanced astrophysical studies. The paper emphasis that these higher values can only be achieved by placing millimeter and submillimeter wavelength interferometric systems in space. A concept of such the system, called Terahertz Exploration and Zooming-in for Astrophysics, has been proposed in the framework of the ESA Call for White Papers for the Voyage 2050 long term plan in 2019. In the current paper we present new science objectives for such the concept based on recent results in studies of active galactic nuclei and supermassive black holes. We also discuss several approaches for addressing technological challenges of creating a millimeter/sub-millimeter wavelength interferometric system in space. In particular, we consider a novel configuration of a space-borne millimeter/sub-millimeter antenna which might resolve several bottlenecks in creating large precise mechanical structures. The paper also presents an overview of prospective space-qualified technologies of low-noise analogue front-end instrumentation for millimeter/sub-millimeter telescopes. Data handling and processing instrumentation is another key technological component of a sub-millimeter Space VLBI system. Requirements and possible implementation options for this instrumentation are described as an extrapolation of the current state-of-the-art Earth-based VLBI data transport and processing instrumentation. The paper also briefly discusses approaches to the interferometric baseline state vector determination and synchronisation and heterodyning system. The technology-oriented sections of the paper do not aim at presenting a complete set of technological solutions for sub-millimeter (terahertz) space-borne interferometers. Rather, in combination with the original ESA Voyage 2050 White Paper, it sharpens the case for the next generation microarcsecond-level imaging instruments and provides starting points for further in-depth technology trade-off studies.

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