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1.	Prusti, T., et al. (author) The Gaia mission 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595 Journal article (peer-reviewed)abstract Gaia is a cornerstone mission in the science programme of the European Space Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page.
2.	Brown, A. G. A., et al. (author) Gaia Data Release 1 Summary of the astrometric, photometric, and survey properties 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595 Journal article (peer-reviewed)abstract Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues - a realisation of the Tycho-Gaia Astrometric Solution (TGAS) - and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of similar to 3000 Cepheid and RR Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr(-1) for the proper motions. A systematic component of similar to 0.3 mas should be added to the parallax uncertainties. For the subset of similar to 94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr(-1). For the secondary astrometric data set, the typical uncertainty of the positions is similar to 10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to similar to 0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data.
3.	Clementini, G., et al. (author) Testing parallaxes with local Cepheids and RR Lyrae stars 2017 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 605 Journal article (peer-reviewed)abstract Context. Parallaxes for 331 classical Cepheids, 31 Type II Cepheids, and 364 RR Lyrae stars in common between Gaia and the HIPPARCOS and Tycho-2 catalogues are published in Gaia Data Release 1 (DR1) as part of the Tycho-Gaia Astrometric Solution (TGAS). Aims. In order to test these first parallax measurements of the primary standard candles of the cosmological distance ladder, which involve astrometry collected by Gaia during the initial 14 months of science operation, we compared them with literature estimates and derived new period-luminosity (PL), period-Wesenheit (PW) relations for classical and Type II Cepheids and infrared PL, PL-metallicity (PLZ), and optical luminosity-metallicity (MV-[Fe/H]) relations for the RR Lyrae stars, with zero points based on TGAS.Methods. Classical Cepheids were carefully selected in order to discard known or suspected binary systems. The final sample comprises 102 fundamental mode pulsators with periods ranging from 1.68 to 51.66 days (of which 33 with sigma(omega)/omega < 0 : 5). The Type II Cepheids include a total of 26 W Virginis and BL Herculis stars spanning the period range from 1.16 to 30.00 days (of which only 7 with sigma(omega)/omega 0 : 5). The RR Lyrae stars include 200 sources with pulsation period ranging from 0.27 to 0.80 days (of which 112 with sigma(omega)/omega < 0 : 5). The new relations were computed using multi- band (V; I; J; K-s) photometry and spectroscopic metal abundances available in the literature, and by applying three alternative approaches: (i) linear least-squares fitting of the absolute magnitudes inferred from direct transformation of the TGAS parallaxes; (ii) adopting astrometry-based luminosities; and (iii) using a Bayesian fitting approach. The last two methods work in parallax space where parallaxes are used directly, thus maintaining symmetrical errors and allowing negative parallaxes to be used. The TGAS-based PL; PW; PLZ, and MV [Fe/H] relations are discussed by comparing the distance to the Large Magellanic Cloud provided by different types of pulsating stars and alternative fitting methods.Results. Good agreement is found from direct comparison of the parallaxes of RR Lyrae stars for which both TGAS and HST measurements are available. Similarly, very good agreement is found between the TGAS values and the parallaxes inferred from the absolute magnitudes of Cepheids and RR Lyrae stars analysed with the Baade-Wesselink method. TGAS values also compare favourably with the parallaxes inferred by theoretical model fitting of the multi-band light curves for two of the three classical Cepheids and one RR Lyrae star, which were analysed with this technique in our samples. The K-band PL relations show the significant improvement of the TGAS parallaxes for Cepheids and RR Lyrae stars with respect to the HIPPARCOS measurements. This is particularly true for the RR Lyrae stars for which improvement in quality and statistics is impressive.Conclusions. TGAS parallaxes bring a significant added value to the previous HIPPARCOS estimates. The relations presented in this paper represent the first Gaia-calibrated relations and form a work-in-progress milestone report in the wait for Gaia-only parallaxes of which a first solution will become available with Gaia Data Release 2 (DR2) in 2018.
4.	van Leeuwen, F., et al. (author) Gaia Data Release 1 : Open cluster astrometry: Performance, limitations, and future prospects 2017 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 601 Journal article (peer-reviewed)abstract Context. The first Gaia Data Release contains the Tycho-Gaia Astrometric Solution (TGAS). This is a subset of about 2 million stars for which, besides the position and photometry, the proper motion and parallax are calculated using Hipparcos and Tycho-2 positions in 1991.25 as prior information. Aims. We investigate the scientific potential and limitations of the TGAS component by means of the astrometric data for open clusters. Methods. Mean cluster parallax and proper motion values are derived taking into account the error correlations within the astrometric solutions for individual stars, an estimate of the internal velocity dispersion in the cluster, and, where relevant, the effects of the depth of the cluster along the line of sight. Internal consistency of the TGAS data is assessed. Results. Values given for standard uncertainties are still inaccurate and may lead to unrealistic unit-weight standard deviations of least squares solutions for cluster parameters. Reconstructed mean cluster parallax and proper motion values are generally in very good agreement with earlier Hipparcos-based determination, although the Gaia mean parallax for the Pleiades is a significant exception. We have no current explanation for that discrepancy. Most clusters are observed to extend to nearly 15 pc from the cluster centre, and it will be up to future Gaia releases to establish whether those potential cluster-member stars are still dynamically bound to the clusters. Conclusions. The Gaia DR1 provides the means to examine open clusters far beyond their more easily visible cores, and can provide membership assessments based on proper motions and parallaxes. A combined HR diagram shows the same features as observed before using the Hipparcos data, with clearly increased luminosities for older A and F dwarfs.
5.	Brown, A. G. A., et al. (author) Gaia Data Release 2 Summary of the contents and survey properties 2018 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 616 Journal article (peer-reviewed)abstract Context. We present the second Gaia data release, Gaia DR2, consisting of astrometry, photometry, radial velocities, and information on astrophysical parameters and variability, for sources brighter than magnitude 21. In addition epoch astrometry and photometry are provided for a modest sample of minor planets in the solar system. Aims. A summary of the contents of Gaia DR2 is presented, accompanied by a discussion on the differences with respect to Gaia DR1 and an overview of the main limitations which are still present in the survey. Recommendations are made on the responsible use of Gaia DR2 results. Methods. The raw data collected with the Gaia instruments during the first 22 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into this second data release, which represents a major advance with respect to Gaia DR1 in terms of completeness, performance, and richness of the data products. Results. Gaia DR2 contains celestial positions and the apparent brightness in G for approximately 1.7 billion sources. For 1.3 billion of those sources, parallaxes and proper motions are in addition available. The sample of sources for which variability information is provided is expanded to 0 : 5 million stars. This data release contains four new elements: broad-band colour information in the form of the apparent brightness in the G(BP) (330-680 nm) and G(RP) (630-1050 nm) bands is available for 1.4 billion sources; median radial velocities for some 7 million sources are presented; for between 77 and 161 million sources estimates are provided of the stellar effective temperature, extinction, reddening, and radius and luminosity; and for a pre-selected list of 14 000 minor planets in the solar system epoch astrometry and photometry are presented. Finally, Gaia DR2 also represents a new materialisation of the celestial reference frame in the optical, the Gaia-CRF2, which is the first optical reference frame based solely on extragalactic sources. There are notable changes in the photometric system and the catalogue source list with respect to Gaia DR1, and we stress the need to consider the two data releases as independent. Conclusions. Gaia DR2 represents a major achievement for the Gaia mission, delivering on the long standing promise to provide parallaxes and proper motions for over 1 billion stars, and representing a first step in the availability of complementary radial velocity and source astrophysical information for a sample of stars in the Gaia survey which covers a very substantial fraction of the volume of our galaxy.
6.	Spoto, F., et al. (author) Gaia Data Release 2 : Observations of solar system objects 2018 In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 616 Journal article (peer-reviewed)abstract Context: The Gaia spacecraft of the European Space Agency (ESA) has been securing observations of solar system objects (SSOs) since the beginning of its operations. Data Release 2 (DR2) contains the observations of a selected sample of 14,099 SSOs. These asteroids have been already identified and have been numbered by the Minor Planet Center repository. Positions are provided for each Gaia observation at CCD level. As additional information, complementary to astrometry, the apparent brightness of SSOs in the unfiltered G band is also provided for selected observations.Aims: We explain the processing of SSO data, and describe the criteria we used to select the sample published in Gaia DR2. We then explore the data set to assess its quality.Methods: To exploit the main data product for the solar system in Gaia DR2, which is the epoch astrometry of asteroids, it is necessary to take into account the unusual properties of the uncertainty, as the position information is nearly one-dimensional. When this aspect is handled appropriately, an orbit fit can be obtained with post-fit residuals that are overall consistent with the a-priori error model that was used to define individual values of the astrometric uncertainty. The role of both random and systematic errors is described. The distribution of residuals allowed us to identify possible contaminants in the data set (such as stars). Photometry in the G band was compared to computed values from reference asteroid shapes and to the flux registered at the corresponding epochs by the red and blue photometers (RP and BP).Results: The overall astrometric performance is close to the expectations, with an optimal range of brightness G similar to 12 - 17. In this range, the typical transit-level accuracy is well below 1 mas. For fainter asteroids, the growing photon noise deteriorates the performance. Asteroids brighter than G similar to 12 are affected by a lower performance of the processing of their signals. The dramatic improvement brought by Gaia DR2 astrometry of SSOs is demonstrated by comparisons to the archive data and by preliminary tests on the detection of subtle non-gravitational effects.
7.	Babusiaux, C., et al. (author) Observational Hertzsprung-Russell diagrams 2018 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 616 Journal article (peer-reviewed)abstract Context. Gaia Data Release 2 provides high-precision astrometry and three-band photometry for about 1.3 billion sources over the full sky. The precision, accuracy, and homogeneity of both astrometry and photometry are unprecedented. Aims. We highlight the power of the Gaia DR2 in studying many fine structures of the Hertzsprung-Russell diagram (HRD). Gaia allows us to present many different HRDs, depending in particular on stellar population selections. We do not aim here for completeness in terms of types of stars or stellar evolutionary aspects. Instead, we have chosen several illustrative examples. Methods. We describe some of the selections that can be made in Gaia DR2 to highlight the main structures of the Gaia HRDs. We select both field and cluster (open and globular) stars, compare the observations with previous classifications and with stellar evolutionary tracks, and we present variations of the Gaia HRD with age, metallicity, and kinematics. Late stages of stellar evolution such as hot subdwarfs, post-AGB stars, planetary nebulae, and white dwarfs are also analysed, as well as low-mass brown dwarf objects. Results. The Gaia HRDs are unprecedented in both precision and coverage of the various Milky Way stellar populations and stellar evolutionary phases. Many fine structures of the HRDs are presented. The clear split of the white dwarf sequence into hydrogen and helium white dwarfs is presented for the first time in an HRD. The relation between kinematics and the HRD is nicely illustrated. Two different populations in a classical kinematic selection of the halo are unambiguously identified in the HRD. Membership and mean parameters for a selected list of open clusters are provided. They allow drawing very detailed cluster sequences, highlighting fine structures, and providing extremely precise empirical isochrones that will lead to more insight in stellar physics. Conclusions. Gaia DR2 demonstrates the potential of combining precise astrometry and photometry for large samples for studies in stellar evolution and stellar population and opens an entire new area for HRD-based studies.
8.	Katz, D., et al. (author) Gaia Data Release 2 Mapping the Milky Way disc kinematics 2018 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 616 Journal article (peer-reviewed)abstract Context. The second Gaia data release (Gaia DR2) contains high-precision positions, parallaxes, and proper motions for 1.3 billion sources as well as line-of-sight velocities for 7.2 million stars brighter than G(RVS) = 12 mag. Both samples provide a full sky coverage. Aims. To illustrate the potential of Gaia DR2, we provide a first look at the kinematics of the Milky Way disc, within a radius of several kiloparsecs around the Sun. Methods. We benefit for the first time from a sample of 6.4 million F-G-K stars with full 6D phase-space coordinates, precise parallaxes (sigma((omega) over bar)/(omega) over bar <= 20%), and precise Galactic cylindrical velocities (median uncertainties of 0.9-1.4 km s(-1) and 20% of the stars with uncertainties smaller than 1 km s(-1) on all three components). From this sample, we extracted a sub-sample of 3.2 million giant stars to map the velocity field of the Galactic disc from similar to 5 kpc to similar to 13 kpc from the Galactic centre and up to 2 kpc above and below the plane. We also study the distribution of 0.3 million solar neighbourhood stars (r < 200 pc), with median velocity uncertainties of 0.4 km s(-1), in velocity space and use the full sample to examine how the over-densities evolve in more distant regions. Results. Gaia DR2 allows us to draw 3D maps of the Galactocentric median velocities and velocity dispersions with unprecedented accuracy, precision, and spatial resolution. The maps show the complexity and richness of the velocity field of the galactic disc. We observe streaming motions in all the components of the velocities as well as patterns in the velocity dispersions. For example, we confirm the previously reported negative and positive galactocentric radial velocity gradients in the inner and outer disc, respectively. Here, we see them as part of a non-axisymmetric kinematic oscillation, and we map its azimuthal and vertical behaviour. We also witness a new global arrangement of stars in the velocity plane of the solar neighbourhood and in distant regions in which stars are organised in thin substructures with the shape of circular arches that are oriented approximately along the horizontal direction in the U - V plane. Moreover, in distant regions, we see variations in the velocity substructures more clearly than ever before, in particular, variations in the velocity of the Hercules stream. Conclusions. Gaia DR2 provides the largest existing full 6D phase-space coordinates catalogue. It also vastly increases the number of available distances and transverse velocities with respect to Gaia DR1. Gaia DR2 offers a great wealth of information on the Milky Way and reveals clear non-axisymmetric kinematic signatures within the Galactic disc, for instance. It is now up to the astronomical community to explore its full potential.
9.	Mignard, F., et al. (author) Gaia Data Release 2 The celestial reference frame (Gaia-CRF2) 2018 In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 616 Journal article (peer-reviewed)abstract Context: The second release of Gaia data (Gaia DR2) contains the astrometric parameters for more than half a million quasars. This set defines a kinematically non-rotating reference frame in the optical domain. A subset of these quasars have accurate VLBI positions that allow the axes of the reference frame to be aligned with the International Celestial Reference System (ICRF) radio frame.Aims: We describe the astrometric and photometric properties of the quasars that were selected to represent the celestial reference frame of Gaia DR2 (Gaia-CRF2), and to compare the optical and radio positions for sources with accurate VLBI positions.Methods: Descriptive statistics are used to characterise the overall properties of the quasar sample. Residual rotation and orientation errors and large-scale systematics are quantified by means of expansions in vector spherical harmonics. Positional differences are calculated relative to a prototype version of the forthcoming ICRF3.Results: Gaia-CRF2 consists of the positions of a sample of 556 869 sources in Gaia DR2, obtained from a positional cross-match with the ICRF3-prototype and AllWISE AGN catalogues. The sample constitutes a clean, dense, and homogeneous set of extragalactic point sources in the magnitude range G similar or equal to 16 to 21 mag with accurately known optical positions. The median positional uncertainty is 0.12 mas for G < 18 mag and 0.5 mas at G = 20 mag. Large-scale systematics are estimated to be in the range 20 to 30 mu as. The accuracy claims are supported by the parallaxes and proper motions of the quasars in Gaia DR2. The optical positions for a subset of 2820 sources in common with the ICRF3-prototype show very good overall agreement with the radio positions, but several tens of sources have significantly discrepant positions.Conclusions: Based on less than 40% of the data expected from the nominal Gaia mission, Gaia-CRF2 is the first realisation of a non-rotating global optical reference frame that meets the ICRS prescriptions, meaning that it is built only on extragalactic sources. Its accuracy matches the current radio frame of the ICRF, but the density of sources in all parts of the sky is much higher, except along the Galactic equator.
10.	Helmi, A., et al. (author) Gaia Data Release 2 Kinematics of globular clusters and dwarf galaxies around the Milky Way 2018 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 616:A12 Journal article (peer-reviewed)abstract Aims The goal of this paper is to demonstrate the outstanding quality of the second data release of the Gaia mission and its power for constraining many different aspects of the dynamics of the satellites of the Milky Way. We focus here on determining the proper motions of 75 Galactic globular clusters, nine dwarf spheroidal galaxies, one ultra-faint system, and the Large and Small Magellanic Clouds.Methods Using data extracted from the Gaia archive, we derived the proper motions and parallaxes for these systems, as well as their uncertainties. We demonstrate that the errors, statistical and systematic, are relatively well understood. We integrated the orbits of these objects in three different Galactic potentials, and characterised their properties. We present the derived proper motions, space velocities, and characteristic orbital parameters in various tables to facilitate their use by the astronomical community.Results Our limited and straightforward analyses have allowed us for example to (i) determine absolute and very precise proper motions for globular clusters; (ii) detect clear rotation signatures in the proper motions of at least five globular clusters; (iii) show that the satellites of the Milky Way are all on high-inclination orbits, but that they do not share a single plane of motion; (i v) derive a lower limit for the mass of the Milky Way of 9.1(-2.6)(+6.2) x 10(11) M-circle dot based on the assumption that the Leo I dwarf spheroidal is bound; (v) derive a rotation curve for the Large Magellanic Cloud based solely on proper motions that is competitive with line-of-sight velocity curves, now using many orders of magnitude more sources; and (v i) unveil the dynamical effect of the bar on the motions of stars in the Large Magellanic Cloud.Conclusions All these results highlight the incredible power of the Gaia astrometric mission, and in particular of its second data release.
11.	Babusiaux, C., et al. (author) Observational Hertzsprung-Russell diagrams 2018 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 16:A10 Journal article (peer-reviewed)
12.	Kotfis, K, et al. (author) A worldwide perspective of sepsis epidemiology and survival according to age: Observational data from the ICON audit 2019 In: Journal of critical care. - : Elsevier BV. - 1557-8615 .- 0883-9441. ; 51, s. 122-132 Journal article (peer-reviewed)
13.	Guillevin, L, et al. (author) Functional impairment of systemic scleroderma patients with digital ulcerations: results from the DUO Registry 2013 In: CLINICAL AND EXPERIMENTAL RHEUMATOLOGY. - 0392-856X. ; 31:2, s. S71-S80 Journal article (other academic/artistic)
14.	Abe, O, et al. (author) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials 2005 In: Lancet (London, England). - 1474-547X. ; 366:9503, s. 2087-2106 Journal article (peer-reviewed)
15.	Alberro, JA, et al. (author) Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials 2018 In: The Lancet. Oncology. - 1474-5488. ; 19:1, s. 27-39 Journal article (peer-reviewed)
16.	de Jong, R. S., et al. (author) 4MOST : Project overview and information for the First Call for Proposals 2019 In: The Messenger. - : European Southern Observatory. - 0722-6691. ; 175, s. 3-11 Journal article (other academic/artistic)abstract We introduce the 4-metre Multi-Object Spectroscopic Telescope (4MOST), a new high-multiplex, wide-field spectroscopic survey facility under development for the four-metre-class Visible and Infrared Survey Telescope for Astronomy (VISTA) at Paranal. Its key specifications are: a large field of view (FoV) of 4.2 square degrees and a high multiplex capability, with 1624 fibres feeding two low-resolution spectrographs (R = λ/Δλ ~ 6500), and 812 fibres transferring light to the high-resolution spectrograph (R ~ 20 000). After a description of the instrument and its expected performance, a short overview is given of its operational scheme and planned 4MOST Consortium science; these aspects are covered in more detail in other articles in this edition of The Messenger. Finally, the processes, schedules, and policies concerning the selection of ESO Community Surveys are presented, commencing with a singular opportunity to submit Letters of Intent for Public Surveys during the first five years of 4MOST operations.
17.	Abe, O, et al. (author) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials 2005 In: Lancet (London, England). - : Elsevier BV. - 1474-547X. ; 365:9472, s. 1687-1717 Journal article (peer-reviewed)
18.	Abe, O, et al. (author) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials 2005 In: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717 Journal article (peer-reviewed)abstract Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
19.	Gilmore, G., et al. (author) The Gaia-ESO Public Spectroscopic Survey : Motivation, implementation, GIRAFFE data processing, analysis, and final data products star 2022 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 666 Journal article (peer-reviewed)abstract Context. The Gaia-ESO Public Spectroscopic Survey is an ambitious project designed to obtain astrophysical parameters and elemental abundances for 100 000 stars, including large representative samples of the stellar populations in the Galaxy, and a well-defined sample of 60 (plus 20 archive) open clusters. We provide internally consistent results calibrated on benchmark stars and star clusters, extending across a very wide range of abundances and ages. This provides a legacy data set of intrinsic value, and equally a large wide-ranging dataset that is of value for the homogenisation of other and future stellar surveys and Gaia's astrophysical parameters. Aims. This article provides an overview of the survey methodology, the scientific aims, and the implementation, including a description of the data processing for the GIRAFFE spectra. A companion paper introduces the survey results. Methods. Gaia-ESO aspires to quantify both random and systematic contributions to measurement uncertainties. Thus, all available spectroscopic analysis techniques are utilised, each spectrum being analysed by up to several different analysis pipelines, with considerable effort being made to homogenise and calibrate the resulting parameters. We describe here the sequence of activities up to delivery of processed data products to the ESO Science Archive Facility for open use. Results. The Gaia-ESO Survey obtained 202 000 spectra of 115 000 stars using 340 allocated VLT nights between December 2011 and January 2018 from GIRAFFE and UVES. Conclusions. The full consistently reduced final data set of spectra was released through the ESO Science Archive Facility in late 2020, with the full astrophysical parameters sets following in 2022. A companion article reviews the survey implementation, scientific highlights, the open cluster survey, and data products.
20.	Randich, S., et al. (author) The Gaia-ESO Public Spectroscopic Survey : Implementation, data products, open cluster survey, science, and legacy 2022 In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 666 Journal article (peer-reviewed)abstract Context. In the last 15 years different ground-based spectroscopic surveys have been started (and completed) with the general aim of delivering stellar parameters and elemental abundances for large samples of Galactic stars, complementing Gaia astrometry. Among those surveys, the Gaia-ESO Public Spectroscopic Survey, the only one performed on a 8m class telescope, was designed to target 100 000 stars using FLAMES on the ESO VLT (both Giraffe and UVES spectrographs), covering all the Milky Way populations, with a special focus on open star clusters. Aims. This article provides an overview of the survey implementation (observations, data quality, analysis and its success, data products, and releases), of the open cluster survey, of the science results and potential, and of the survey legacy. A companion article reviews the overall survey motivation, strategy, Giraffe pipeline data reduction, organisation, and workflow. Methods. We made use of the information recorded and archived in the observing blocks; during the observing runs; in a number of relevant documents; in the spectra and master catalogue of spectra; in the parameters delivered by the analysis nodes and the working groups; in the final catalogue; and in the science papers. Based on these sources, we critically analyse and discuss the output and products of the Survey, including science highlights. We also determined the average metallicities of the open clusters observed as science targets and of a sample of clusters whose spectra were retrieved from the ESO archive. Results. The Gaia-ESO Survey has determined homogeneous good-quality radial velocities and stellar parameters for a large fraction of its more than 110 000 unique target stars. Elemental abundances were derived for up to 31 elements for targets observed with UVES. Lithium abundances are delivered for about 1/3 of the sample. The analysis and homogenisation strategies have proven to be successful; several science topics have been addressed by the Gaia-ESO consortium and the community, with many highlight results achieved. Conclusions. The final catalogue will be released through the ESO archive in the first half of 2022, including the complete set of advanced data products. In addition to these results, the Gaia-ESO Survey will leave a very important legacy, for several aspects and for many years to come.
21.	Klionsky, Daniel J., et al. (author) Guidelines for the use and interpretation of assays for monitoring autophagy 2012 In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544 Research review (peer-reviewed)abstract In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
22.	Sobanski, V, et al. (author) Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis 2019 In: Arthritis & rheumatology (Hoboken, N.J.). - : Wiley. - 2326-5205 .- 2326-5191. ; 71:9, s. 1553-1570 Journal article (peer-reviewed)
23.	Smiljanic, R., et al. (author) The Gaia-ESO Survey: The analysis of high-resolution UVES spectra of FGK-type stars 2014 In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 570 Journal article (peer-reviewed)abstract Context. The ongoing Gaia-ESO Public Spectroscopic Survey is using FLAMES at the VLT to obtain high-quality medium-resolution Giraffe spectra for about 10(5) stars and high-resolution UVES spectra for about 5000 stars. With UVES, the Survey has already observed 1447 FGK-type stars. Aims. These UVES spectra are analyzed in parallel by several state-of-the-art methodologies. Our aim is to present how these analyses were implemented, to discuss their results, and to describe how a final recommended parameter scale is defined. We also discuss the precision (method-to-method dispersion) and accuracy (biases with respect to the reference values) of the final parameters. These results are part of the Gaia-ESO second internal release and will be part of its first public release of advanced data products. Methods. The final parameter scale is tied to the scale defined by the Gaia benchmark stars, a set of stars with fundamental atmospheric parameters. In addition, a set of open and globular clusters is used to evaluate the physical soundness of the results. Each of the implemented methodologies is judged against the benchmark stars to define weights in three different regions of the parameter space. The final recommended results are the weighted medians of those from the individual methods. Results. The recommended results successfully reproduce the atmospheric parameters of the benchmark stars and the expected T-eff-log g relation of the calibrating clusters. Atmospheric parameters and abundances have been determined for 1301 FGK-type stars observed with UVES. The median of the method-to-method dispersion of the atmospheric parameters is 55K for T-eff, 0.13dex for log g and 0.07 dex for [Fe/H]. Systematic biases are estimated to be between 50-100 K for T-eff, 0.10-0.25 dex for log g and 0.05-0.10 dex for [Fe/H]. Abundances for 24 elements were derived: C, N, O, Na, Mg, Al, Si, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Mo, Ba, Nd, and Eu. The typical method-to-method dispersion of the abundances varies between 0.10 and 0.20 dex. Conclusions. The Gaia-ESO sample of high-resolution spectra of FGK-type stars will be among the largest of its kind analyzed in a homogeneous way. The extensive list of elemental abundances derived in these stars will enable significant advances in the areas of stellar evolution and Milky Way formation and evolution.
24.	Casey, A. R., et al. (author) The Gaia-ESO Survey : Revisiting the Li-rich giant problem 2016 In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 461:3, s. 3336-3352 Journal article (peer-reviewed)abstract The discovery of lithium-rich giants contradicts expectations from canonical stellar evolution. Here we report on the serendipitous discovery of 20 Li-rich giants observed during the Gaia-ESO Survey, which includes the first nine Li-rich giant stars known towards the CoRoT fields. Most of our Li-rich giants have near-solar metallicities and stellar parameters consistent with being before the luminosity bump. This is difficult to reconcile with deep mixing models proposed to explain lithium enrichment, because these models can only operate at later evolutionary stages: at or past the luminosity bump. In an effort to shed light on the Li-rich phenomenon, we highlight recent evidence of the tidal destruction of close-in hot Jupiters at the sub-giant phase.We note that when coupled with models of planet accretion, the observed destruction of hot Jupiters actually predicts the existence of Li-rich giant stars, and suggests that Li-rich stars should be found early on the giant branch and occur more frequently with increasing metallicity. A comprehensive review of all known Li-rich giant stars reveals that this scenario is consistent with the data. However, more evolved or metal-poor stars are less likely to host close-in giant planets, implying that their Li-rich origin requires an alternative explanation, likely related to mixing scenarios rather than external phenomena.
25.	Pancino, E., et al. (author) The Gaia-ESO Survey : Calibration strategy 2017 In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 598 Journal article (peer-reviewed)abstract The Gaia-ESO survey (GES) is now in its fifth and last year of observations and has produced tens of thousands of high-quality spectra of stars in all Milky Way components. This paper presents the strategy behind the selection of astrophysical calibration targets, ensuring that all GES results on radial velocities, atmospheric parameters, and chemical abundance ratios will be both internally consistent and easily comparable with other literature results, especially from other large spectroscopic surveys and from Gaia. The calibration of GES is particularly delicate because of (i) the large space of parameters covered by its targets, ranging from dwarfs to giants, from O to M stars; these targets have a large wide of metallicities and also include fast rotators, emission line objects, and stars affected by veiling; (ii) the variety of observing setups, with different wavelength ranges and resolution; and (iii) the choice of analyzing the data with many different state-of-the-art methods, each stronger in a different region of the parameter space, which ensures a better understanding of systematic uncertainties. An overview of the GES calibration and homogenization strategy is also given, along with some examples of the usage and results of calibrators in GES iDR4, which is the fourth internal GES data release and will form the basis of the next GES public data release. The agreement between GES iDR4 recommended values and reference values for the calibrating objects are very satisfactory. The average off sets and spreads are generally compatible with the GES measurement errors, which in iDR4 data already meet the requirements set by the main GES scientific goals.
26.	Chiappini, C., et al. (author) 4MOST Consortium Survey 3: Milky Way Disc and Bulge Low-Resolution Survey (4MIDABLE-LR) 2019 In: The Messenger. - 0722-6691. ; 175, s. 30-34 Journal article (other academic/artistic)
27.	Zouganelis, I., et al. (author) The Solar Orbiter Science Activity Plan : Translating solar and heliospheric physics questions into action 2020 In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 642 Journal article (peer-reviewed)abstract Solar Orbiter is the first space mission observing the solar plasma both in situ and remotely, from a close distance, in and out of the ecliptic. The ultimate goal is to understand how the Sun produces and controls the heliosphere, filling the Solar System and driving the planetary environments. With six remote-sensing and four in-situ instrument suites, the coordination and planning of the operations are essential to address the following four top-level science questions: (1) What drives the solar wind and where does the coronal magnetic field originate?; (2) How do solar transients drive heliospheric variability?; (3) How do solar eruptions produce energetic particle radiation that fills the heliosphere?; (4) How does the solar dynamo work and drive connections between the Sun and the heliosphere? Maximising the mission's science return requires considering the characteristics of each orbit, including the relative position of the spacecraft to Earth (affecting downlink rates), trajectory events (such as gravitational assist manoeuvres), and the phase of the solar activity cycle. Furthermore, since each orbit's science telemetry will be downloaded over the course of the following orbit, science operations must be planned at mission level, rather than at the level of individual orbits. It is important to explore the way in which those science questions are translated into an actual plan of observations that fits into the mission, thus ensuring that no opportunities are missed. First, the overarching goals are broken down into specific, answerable questions along with the required observations and the so-called Science Activity Plan (SAP) is developed to achieve this. The SAP groups objectives that require similar observations into Solar Orbiter Observing Plans, resulting in a strategic, top-level view of the optimal opportunities for science observations during the mission lifetime. This allows for all four mission goals to be addressed. In this paper, we introduce Solar Orbiter's SAP through a series of examples and the strategy being followed.
28.	Barnes, DR, et al. (author) Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores 2022 In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 114:1, s. 109-122 Journal article (peer-reviewed)abstract BackgroundRecent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.Methods483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)–negative (PRSER-), or ER-positive (PRSER+) breast cancer risk.ResultsPRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.ConclusionsPopulation-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.
29.	Becker, M, et al. (author) Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: a European Scleroderma Trials and Research (EUSTAR) analysis 2019 In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:9, s. 1242-1248 Journal article (peer-reviewed)abstract Mortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database.MethodsInclusion criteria were diagnosis of diffuse SSc and follow-up over 12±3 months. Disease worsening/organ progression was fulfilled if any of the following events occurred: new renal crisis; decrease of lung or heart function; new echocardiography-suspected pulmonary hypertension or death. In total, 42 clinical parameters were chosen as predictors for the analysis by using (1) imputation of missing data on the basis of multivariate imputation and (2) least absolute shrinkage and selection operator regression.ResultsOf 1451 patients meeting the inclusion criteria, 706 had complete data on outcome parameters and were included in the analysis. Of the 42 outcome predictors, eight remained in the final regression model. There was substantial evidence for a strong association between disease progression and age, active digital ulcer (DU), lung fibrosis, muscle weakness and elevated C-reactive protein (CRP) level. Active DU, CRP elevation, lung fibrosis and muscle weakness were also associated with a significantly shorter time to disease progression. A bootstrap validation step with 10 000 repetitions successfully validated the model.ConclusionsThe use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trials.
30.	Chen, A. W., et al. (author) Calibration of AGILE-GRID with in-flight data and Monte Carlo simulations 2013 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 558, s. A37- Journal article (peer-reviewed)abstract Context. AGILE is a γ-ray astrophysics mission which has been in orbit since 23 April 2007 and continues to operate reliably. The γ-ray detector, AGILE-GRID, has observed Galactic and extragalactic sources, many of which were collected in the first AGILE Catalog. Aims. We present the calibration of the AGILE-GRID using in-flight data and Monte Carlo simulations, producing instrument response functions (IRFs) for the effective area (A eff), energy dispersion probability (EDP), and point spread function (PSF), each as a function of incident direction in instrument coordinates and energy. Methods. We performed Monte Carlo simulations at different γ-ray energies and incident angles, including background rejection filters and Kalman filter-based γ-ray reconstruction. Long integrations of in-flight observations of the Vela, Crab and Geminga sources in broad and narrow energy bands were used to validate and improve the accuracy of the instrument response functions. Results. The weighted average PSFs as a function of spectra correspond well to the data for all sources and energy bands. Conclusions. Changes in the interpolation of the PSF from Monte Carlo data and in the procedure for construction of the energy-weighted effective areas have improved the correspondence between predicted and observed fluxes and spectra of celestial calibration sources, reducing false positives and obviating the need for post-hoc energy-dependent scaling factors. The new IRFs have been publicly available from the AGILE Science Data Center since November 25, 2011, while the changes in the analysis software will be distributed in an upcoming release.
31.	Guiglion, G., et al. (author) The RAdial Velocity Experiment (RAVE) : Parameterisation of RAVE spectra based on convolutional neural networks 2020 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 644 Journal article (peer-reviewed)abstract Context Data-driven methods play an increasingly important role in the field of astrophysics In the context of large spectroscopic surveys of stars, data-driven methods are key in deducing physical parameters for millions of spectra in a short time. Convolutional neural networks (CNNs) enable us to connect observables (e.g. spectra, stellar magnitudes) to physical properties (atmospheric parameters, chemical abundances, or labels in general). Aims. We test whether it is possible to transfer the labels derived from a high-resolution stellar survey to intermediate-resolution spectra of another survey by using a CNN. Methods. We trained a CNN, adopting stellar atmospheric parameters and chemical abundances from APOGEE DR16 (resolution Ra22 500) data as training set labels. As input, we used parts of the intermediate-resolution RAVE DR6 spectra (R ∼ 7500) overlapping with the APOGEE DR16 data as well as broad-band ALLWISE and 2MASS photometry, together with Gaia DR2 photometry and parallaxes. Results. We derived precise atmospheric parameters Teff, log(g), and [M/H], along with the chemical abundances of [Fe/H], [α/M], [Mg/Fe], [Si/Fe], [Al/Fe], and [Ni/Fe] for 420 165 RAVE spectra. The precision typically amounts to 60 K in Teff, 0.06 in log(g) and 0.02-0.04 dex for individual chemical abundances. Incorporating photometry and astrometry as additional constraints substantially improves the results in terms of the accuracy and precision of the derived labels, as long as we operate in those parts of the parameter space that are well-covered by the training sample. Scientific validation confirms the robustness of the CNN results. We provide a catalogue of CNN-Trained atmospheric parameters and abundances along with their uncertainties for 420 165 stars in the RAVE survey. Conclusions. CNN-based methods provide a powerful way to combine spectroscopic, photometric, and astrometric data without the need to apply any priors in the form of stellar evolutionary models. The developed procedure can extend the scientific output of RAVE spectra beyond DR6 to ongoing and planned surveys such as Gaia RVS, 4MOST, and WEAVE. We call on the community to place a particular collective emphasis and on efforts to create unbiased training samples for such future spectroscopic surveys.
32.	Luyssaert, S., et al. (author) CO2 balance of boreal, temperate, and tropical forests derived from a global database 2007 In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 13:12, s. 2509-2537 Research review (peer-reviewed)abstract Terrestrial ecosystems sequester 2.1 Pg of atmospheric carbon annually. A large amount of the terrestrial sink is realized by forests. However, considerable uncertainties remain regarding the fate of this carbon over both short and long timescales. Relevant data to address these uncertainties are being collected at many sites around the world, but syntheses of these data are still sparse. To facilitate future synthesis activities, we have assembled a comprehensive global database for forest ecosystems, which includes carbon budget variables (fluxes and stocks), ecosystem traits (e.g. leaf area index, age), as well as ancillary site information such as management regime, climate, and soil characteristics. This publicly available database can be used to quantify global, regional or biome-specific carbon budgets; to re-examine established relationships; to test emerging hypotheses about ecosystem functioning [e.g. a constant net ecosystem production (NEP) to gross primary production (GPP) ratio]; and as benchmarks for model evaluations. In this paper, we present the first analysis of this database. We discuss the climatic influences on GPP, net primary production (NPP) and NEP and present the CO2 balances for boreal, temperate, and tropical forest biomes based on micrometeorological, ecophysiological, and biometric flux and inventory estimates. Globally, GPP of forests benefited from higher temperatures and precipitation whereas NPP saturated above either a threshold of 1500 mm precipitation or a mean annual temperature of 10 degrees C. The global pattern in NEP was insensitive to climate and is hypothesized to be mainly determined by nonclimatic conditions such as successional stage, management, site history, and site disturbance. In all biomes, closing the CO2 balance required the introduction of substantial biome-specific closure terms. Nonclosure was taken as an indication that respiratory processes, advection, and non-CO2 carbon fluxes are not presently being adequately accounted for.
33.	Valentini, M, et al. (author) RAVE stars in K2 : I. Improving RAVE red giants spectroscopy using asteroseismology from K2 Campaign 1 2017 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 600 Journal article (peer-reviewed)abstract We present a set of 87 RAVE stars with detected solar like oscillations, observed during Campaign 1 of the K2 mission (RAVE K2-C1 sample). This data set provides a useful benchmark for testing the gravities provided in RAVE data release 4 (DR4), and is key for the calibration of the RAVE data release 5 (DR5). The RAVE survey collected medium-resolution spectra (R = 7500) centred in the Ca II triplet(8600 Å) wavelength interval, which although being very useful for determining radial velocity and metallicity, even at low S/N, is known be affected by a log (g)-Teff degeneracy. This degeneracy is the cause of the large spread in the RAVE DR4 gravities for giants. The understanding of the trends and offsets that affects RAVE atmospheric parameters, and in particular log (g), is a crucial step in obtaining not only improved abundance measurements, but also improved distances and ages. In the present work, we use two different pipelines, GAUFRE and Sp-Ace, to determine atmospheric parameters and abundances by fixing log (g) to the seismic one. Our strategy ensures highly consistent values among all stellar parameters, leading to more accurate chemical abundances. A comparison of the chemical abundances obtained here with and without the use of seismic log (g) information has shown that an underestimated (overestimated) gravity leads to an underestimated (overestimated) elemental abundance (e.g. [Mg/H] is underestimated by ∼0.25 dex when the gravity is underestimated by 0.5 dex). We then perform a comparison between the seismic gravities and the spectroscopic gravities presented in the RAVE DR4 catalogue, extracting a calibration for log (g) of RAVE giants in the colour interval 0.50 < (J-KS) < 0.85. Finally, we show a comparison of the distances, temperatures, extinctions (and ages) derived here for our RAVE K2-C1 sample with those derived in RAVE DR4 and DR5. DR5 performs better than DR4 thanks to the seismic calibration, although discrepancies can still be important for objects for which the difference between DR4/DR5 and seismic gravities differ by more than ∼0.5 dex. The method illustrated in this work will be used for analysing RAVE targets present in the other K2 campaigns, in the framework of Galactic Archaeology investigations.
34.	Luyssaert, S, et al. (author) Global patterns in forest CO2-balance – An analysis based on a new global database 2007 In: Global Change Biology. - 1354-1013. ; 13, s. 1-29 Journal article (peer-reviewed)
35.	Marcelli, L., et al. (author) Integration, qualification, and launch of the Mini-EUSO telescope on board the ISS 2023 In: Rendiconti Lincei SCIENZE FISICHE E NATURALI. - : Springer Nature. - 2037-4631 .- 1720-0776. ; 34:1, s. 23-35 Journal article (peer-reviewed)abstract Mini-EUSO is a high-sensitivity imaging telescope that observes the Earth from the ISS in the near ultraviolet band (290÷ 430 nm), through the nadir-facing, UV-transparent window in the Russian Zvezda module. The instrument, launched in 2019, has a field of view of 44∘, a spatial resolution on the Earth’s surface of 6.3 km and a temporal sampling rate of 2.5 microseconds. Thanks to its triggering and on-board processing, the telescope is capable of detecting UV emissions of cosmic, atmospheric, and terrestrial origin on different time scales, from a few microseconds up to tens of milliseconds. The optics is composed of two Fresnel lenses focusing light onto an array of 36 Hamamatsu Multi-Anode PhotoMultiplier Tubes, for a total of 2304 pixels. The telescope also contains two cameras in the near-infrared and visible, an 8-by-8 array of Silicon-PhotoMultipliers and a series of UV sensors to manage night-day transitions. The scientific objectives range from the observation of atmospheric phenomena [lightning, Transient Luminous Events (TLEs), ELVES], the study of meteoroids, the search of interstellar meteoroids and strange quark matter, mapping of the Earth’s nocturnal emissions in the ultraviolet range, and the search of cosmic rays with energy above 1021 eV. The instrument has been integrated and qualified in 2019, with the final tests in Baikonur prior to its launch. Operations involve periodic installation in the Zvezda module of the station with observations during the crew night time, with periodic downlink of data samples, with the full data being sent to the ground via pouches containing the data disks. Mission planning involves the selection of the optimal orbits to maximize the scientific return of the instrument. In this work, we will describe the various phases of construction, testing, and qualification prior to the launch and the in-flight operations of the instrument on board the ISS.
36.	Miglio, A., et al. (author) PLATO as it is : A legacy mission for Galactic archaeology 2017 In: Astronomical Notes - Astronomische Nachrichten. - : WILEY-V C H VERLAG GMBH. - 0004-6337 .- 1521-3994. ; 338:6, s. 644-661 Journal article (peer-reviewed)abstract Deciphering the assembly history of the Milky Way is a formidable task, which becomes possible only if one can produce high-resolution chrono-chemo-kinematical maps of the Galaxy. Data from large-scale astrometric and spectroscopic surveys will soon provide us with a well-defined view of the current chemo-kinematical structure of the Milky Way, but it will only enable a blurred view on the temporal sequence that led to the present-day Galaxy. As demonstrated by the (ongoing) exploitation of data from the pioneering photometric missions CoRoT, Kepler, and K2, asteroseismology provides the way forward: solar-like oscillating giants are excellent evolutionary clocks thanks to the availability of seismic constraints on their mass and to the tight age-initial mass relation they adhere to. In this paper we identify five key outstanding questions relating to the formation and evolution of the Milky Way that will need precise and accurate ages for large samples of stars to be addressed, and we identify the requirements in terms of number of targets and the precision on the stellar properties that are needed to tackle such questions. By quantifying the asteroseismic yields expected from PLATO for red giant stars, we demonstrate that these requirements are within the capabilities of the current instrument design, provided that observations are sufficiently long to identify the evolutionary state and allow robust and precise determination of acoustic-mode frequencies. This will allow us to harvest data of sufficient quality to reach a 10% precision in age. This is a fundamental prerequisite to then reach the more ambitious goal of a similar level of accuracy, which will be possible only if we have at hand a careful appraisal of systematic uncertainties on age deriving from our limited understanding of stellar physics, a goal that conveniently falls within the main aims of PLATO's core science. We therefore strongly endorse PLATO's current design and proposed observational strategy, and conclude that PLATO, as it is, will be a legacy mission for Galactic archaeology.
37.	Nepal, S., et al. (author) The Gaia-ESO Survey : Preparing the ground for 4MOST and WEAVE galactic surveys: Chemical evolution of lithium with machine learning 2023 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 671 Journal article (peer-reviewed)abstract Context. With its origin coming from several sources (Big Bang, stars, cosmic rays) and given its strong depletion during its stellar lifetime, the lithium element is of great interest as its chemical evolution in the Milky Way is not well understood at present. To help constrain stellar and galactic chemical evolution models, numerous and precise lithium abundances are necessary for a large range of evolutionary stages, metallicities, and Galactic volume. Aims. In the age of stellar parametrization on industrial scales, spectroscopic surveys such as APOGEE, GALAH, RAVE, and LAMOST have used data-driven methods to rapidly and precisely infer stellar labels (atmospheric parameters and abundances). To prepare the ground for future spectroscopic surveys such as 4MOST and WEAVE, we aim to apply machine learning techniques to lithium measurements and analyses. Methods. We trained a convolution neural network (CNN), coupling Gaia-ESO Survey iDR6 stellar labels (Teff, log(g), [Fe/H], and A(Li)) and GIRAFFE HR15N spectra, to infer the atmospheric parameters and lithium abundances for 40 000 stars. The CNN architecture and accompanying notebooks are available online via GitHub. Results. We show that the CNN properly learns the physics of the stellar labels, from relevant spectral features through a broad range of evolutionary stages and stellar parameters. The lithium feature at 6707.8 A is successfully singled out by our CNN, among the thousands of lines in the GIRAFFE HR15N setup. Rare objects such as lithium-rich giants are found in our sample. This level of performance is achieved thanks to a meticulously built, high-quality, and homogeneous training sample. Conclusions. The CNN approach is very well adapted for the next generations of spectroscopic surveys aimed at studying (among other elements) lithium, such as the 4MIDABLE-LR/HR (4MOST Milky Way disk and bulge low-And high-resolution) surveys. In this context, the caveats of machine-learning applications should be appropriately investigated, along with the realistic label uncertainties and upper limits for abundances.
38.	Spiro, S., et al. (author) Low luminosity Type II supernovae - II. Pointing towards moderate mass precursors 2014 In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 439:3, s. 2873-2892 Journal article (peer-reviewed)abstract We present new data for five underluminous Type II-plateau supernovae (SNe IIP), namely SN 1999gn, SN 2002gd, SN 2003Z, SN 2004eg and SN 2006ov. This new sample of low-luminosity SNe IIP (LL SNe IIP) is analysed together with similar objects studied in the past. All of them show a flat light-curve plateau lasting about 100 d, an underluminous late-time exponential tail, intrinsic colours that are unusually red, and spectra showing prominent and narrow P Cygni lines. A velocity of the ejected material below 10(3) km s(-1) is inferred from measurements at the end of the plateau. The Ni-56 masses ejected in the explosion are very small (< 10(-2) M-circle dot). We investigate the correlations among Ni-56 mass, expansion velocity of the ejecta and absolute magnitude in the middle of the plateau, confirming the main findings of Hamuy, according to which events showing brighter plateau and larger expansion velocities are expected to produce more Ni-56. We propose that these faint objects represent the LL tail of a continuous distribution in parameters space of SNe IIP. The physical properties of the progenitors at the explosion are estimated through the hydrodynamical modelling of the observables for two representative events of this class, namely SN 2005cs and SN 2008in. We find that the majority of LL SNe IIP, and quite possibly all, originate in the core collapse of intermediate-mass stars, in the mass range 10-15 M-circle dot.
39.	Cederholm, Tommy, et al. (author) ESPEN guidelines on definitions and terminology of clinical nutrition 2017 In: Clinical Nutrition. - 0261-5614 .- 1532-1983. ; 36:1, s. 49-64 Journal article (peer-reviewed)abstract BackgroundA lack of agreement on definitions and terminology used for nutrition-related concepts and procedures limits the development of clinical nutrition practice and research.ObjectiveThis initiative aimed to reach a consensus for terminology for core nutritional concepts and procedures.MethodsThe European Society of Clinical Nutrition and Metabolism (ESPEN) appointed a consensus group of clinical scientists to perform a modified Delphi process that encompassed e-mail communication, face-to-face meetings, in-group ballots and an electronic ESPEN membership Delphi round.ResultsFive key areas related to clinical nutrition were identified: concepts; procedures; organisation; delivery; and products. One core concept of clinical nutrition is malnutrition/undernutrition, which includes disease-related malnutrition (DRM) with (eq. cachexia) and without inflammation, and malnutrition/undernutrition without disease, e.g. hunger-related malnutrition. Over-nutrition (overweight and obesity) is another core concept. Sarcopenia and frailty were agreed to be separate conditions often associated with malnutrition. Examples of nutritional procedures identified include screening for subjects at nutritional risk followed by a complete nutritional assessment. Hospital and care facility catering are the basic organizational forms for providing nutrition. Oral nutritional supplementation is the preferred way of nutrition therapy but if inadequate then other forms of medical nutrition therapy, i.e. enteral tube feeding and parenteral (intravenous) nutrition, becomes the major way of nutrient delivery.ConclusionAn agreement of basic nutritional terminology to be used in clinical practice, research, and the ESPEN guideline developments has been established. This terminology consensus may help to support future global consensus efforts and updates of classification systems such as the International Classification of Disease (ICD). The continuous growth of knowledge in all areas addressed in this statement will provide the foundation for future revisions.
40.	Smiljanic, R., et al. (author) The Gaia-ESO Survey : properties of newly discovered Li-rich giants 2018 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 617 Journal article (peer-reviewed)abstract Aims. We report 20 new lithium-rich giants discovered within the Gaia-ESO Survey, including the first Li-rich giant with an evolutionary stage confirmed by CoRoT (Convection, Rotation and planetary Transits) data. We present a detailed overview of the properties of these 20 stars. Methods. Atmospheric parameters and abundances were derived in model atmosphere analyses using medium-resolution GIRAFFE or high-resolution UVES (Ultraviolet and Visual Echelle Spectrograph) spectra. These results are part of the fifth internal data release of the Gaia-ESO Survey. The Li abundances were corrected for non-local thermodynamical equilibrium effects. Other stellar properties were investigated for additional peculiarities (the core of strong lines for signs of magnetic activity, infrared magnitudes, rotational velocities, chemical abundances, and Galactic velocities). We used Gaia DR2 parallaxes to estimate distances and luminosities. Results. The giants have A(Li) > 2.2 dex. The majority of them (14 of 20 stars) are in the CoRoT fields. Four giants are located in the field of three open clusters, but are not members. Two giants were observed in fields towards the Galactic bulge, but likely lie in the inner disc. One of the bulge field giants is super Li-rich with A(Li) = 4.0 dex. Conclusions. We identified one giant with infrared excess at 22 mu m. Two other giants, with large v sin i, might be Li-rich because of planet engulfment. Another giant is found to be barium enhanced and thus could have accreted material from a former asymptotic giant branch companion. Otherwise, in addition to the Li enrichment, the evolutionary stages are the only other connection between these new Li-rich giants. The CoRoT data confirm that one Li-rich giant is at the core-He burning stage. The other giants are concentrated in close proximity to the red giant branch luminosity bump, the core-He burning stages, or the early-asymptotic giant branch. This is very clear from the Gaia-based luminosities of the Li-rich giants. This is also seen when the CoRoT Li-rich giants are compared to a larger sample of 2252 giants observed in the CoRoT fields by the Gaia-ESO Survey, which are distributed throughout the red giant branch in the T-eff-log g diagram. These observations show that the evolutionary stage is a major factor for the Li enrichment in giants. Other processes, such as planet accretion, contribute at a smaller scale.
41.	Guiglion, G., et al. (author) Beyond Gaia DR3 : Tracing the [α/M] - [M/H] bimodality from the inner to the outer Milky Way disc with Gaia-RVS and convolutional neural networks 2024 In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 682 Journal article (peer-reviewed)abstract Context. In June 2022, Gaia DR3 provided the astronomy community with about one million spectra from the Radial Velocity Spectrometer (RVS) covering the CaII triplet region. In the next Gaia data releases, we anticipate the number of RVS spectra to successively increase from several 10 million spectra to eventually more than 200 million spectra. Thus, stellar spectra are projected to be produced on an ‘industrial scale’, with numbers well above those for current and anticipated ground-based surveys. However, one-third of the published spectra have 15 ≤ S /N ≤ 25 per pixel such that they pose problems for classical spectral analysis pipelines, and therefore, alternative ways to tap into these large datasets need to be devised.Aims. We aim to leverage the versatility and capabilities of machine learning techniques for supercharged stellar parametrisation by combining Gaia-RVS spectra with the full set of Gaia products and high-resolution, high-quality ground-based spectroscopic reference datasets.Methods. We developed a hybrid convolutional neural network (CNN) that combines the Gaia DR3 RVS spectra, photometry (G, G_BP, G_RP), parallaxes, and XP coefficients to derive atmospheric parameters (Teff, log(g) as well as overall [M/H]) and chemical abundances ([Fe/H] and [α/M]). We trained the CNN with a high-quality training sample based on APOGEE DR17 labels.Results. With this CNN, we derived homogeneous atmospheric parameters and abundances for 886 080 RVS stars that show remarkable precision and accuracy compared to external datasets (such as GALAH and asteroseismology). The CNN is robust against noise in the RVS data, and we derive very precise labels down to S/N =15. We managed to characterise the [α/M] - [M/H] bimodality from the inner regions to the outer parts of the Milky Way, which has never been done using RVS spectra or similar datasets.Conclusions. This work is the first to combine machine learning with such diverse datasets and paves the way for large-scale machine learning analysis of Gaia-RVS spectra from future data releases. Large, high-quality datasets can be optimally combined thanks to the CNN, thereby realising the full power of spectroscopy, astrometry, and photometry.
42.	Janier, M, et al. (author) Author Correction: EMPReSS: standardized phenotype screens for functional annotation of the mouse genome 2022 In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:3, s. 358-360 Journal article (other academic/artistic)
43.	Kehoe, Laura, et al. (author) Make EU trade with Brazil sustainable 2019 In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341- Journal article (other academic/artistic)
44.	Mansoor, Rashid, et al. (author) Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data 2022 In: BMC Medicine. - : Springer Nature. - 1741-7015. ; 20:1 Journal article (peer-reviewed)abstract BackgroundPlasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia.MethodsIndividual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7.ResultsA total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39-3.05], p < 0.001).ConclusionsIn patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery.
45.	Meehan, TF, et al. (author) INFRAFRONTIER--providing mutant mouse resources as research tools for the international scientific community 2015 In: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 43:D1Database issue, s. D1171-D1175 Journal article (peer-reviewed)
46.	Parsons, Sam, et al. (author) A community-sourced glossary of open scholarship terms 2022 In: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 6:3, s. 312-318 Journal article (peer-reviewed)
47.	Veronese, N., et al. (author) Inverse relationship between body mass index and mortality in older nursing home residents : a meta-analysis of 19,538 elderly subjects 2015 In: Obesity Reviews. - : Wiley. - 1467-7881 .- 1467-789X. ; 16:11, s. 1001-1015 Research review (peer-reviewed)abstract Body mass index (BMI) and mortality in old adults from the general population have been related in a U-shaped or J-shaped curve. However, limited information is available for elderly nursing home populations, particularly about specific cause of death. A systematic PubMed/EMBASE/CINAHL/SCOPUS search until 31 May 2014 without language restrictions was conducted. As no published study reported mortality in standard BMI groups (<18.5, 18.5-24.9, 25-29.9, 30kg/m(2)), the most adjusted hazard ratios (HRs) according to a pre-defined list of covariates were obtained from authors and pooled by random-effect model across each BMI category. Out of 342 hits, 20 studies including 19,538 older nursing home residents with 5,223 deaths during a median of 2 years of follow-up were meta-analysed. Compared with normal weight, all-cause mortality HRs were 1.41 (95% CI=1.26-1.58) for underweight, 0.85 (95% CI=0.73-0.99) for overweight and 0.74 (95% CI=0.57-0.96) for obesity. Underweight was a risk factor for higher mortality caused by infections (HR=1.65 [95% CI=1.13-2.40]). RR results corroborated primary HR results, with additionally lower infection-related mortality in overweight and obese than in normal-weight individuals. Like in the general population, underweight is a risk factor for mortality in old nursing home residents. However, uniquely, not only overweight but also obesity is protective, which has relevant nutritional goal implications in this population/setting.
48.	Abdulla, S, et al. (author) Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data 2015 In: BMC medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 13, s. 212- Journal article (peer-reviewed)
49.	af Klinteberg, C, et al. (author) Diode Laser-Mediated ALA-PDT Guided by Laser-Induced Fluorescence Imaging 2002 Reports (other academic/artistic)
50.	Aquilante, Francesco, et al. (author) Molcas 8 : New capabilities for multiconfigurational quantum chemical calculations across the periodic table 2016 In: Journal of Computational Chemistry. - : Wiley. - 0192-8651 .- 1096-987X. ; 37:5, s. 506-541 Journal article (peer-reviewed)abstract In this report, we summarize and describe the recent unique updates and additions to the Molcas quantum chemistry program suite as contained in release version 8. These updates include natural and spin orbitals for studies of magnetic properties, local and linear scaling methods for the Douglas-Kroll-Hess transformation, the generalized active space concept in MCSCF methods, a combination of multiconfigurational wave functions with density functional theory in the MC-PDFT method, additional methods for computation of magnetic properties, methods for diabatization, analytical gradients of state average complete active space SCF in association with density fitting, methods for constrained fragment optimization, large-scale parallel multireference configuration interaction including analytic gradients via the interface to the Columbus package, and approximations of the CASPT2 method to be used for computations of large systems. In addition, the report includes the description of a computational machinery for nonlinear optical spectroscopy through an interface to the QM/MM package Cobramm. Further, a module to run molecular dynamics simulations is added, two surface hopping algorithms are included to enable nonadiabatic calculations, and the DQ method for diabatization is added. Finally, we report on the subject of improvements with respects to alternative file options and parallelization.

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