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1.	Abe, H., et al. (author) Gamma-ray observations of MAXI J1820+070 during the 2018 outburst 2022 In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 517:4, s. 4736-4751 Journal article (peer-reviewed)abstract MAXIJ1820+070 is a low-mass X-ray binary with a black hole (BH) as a compact object. This binary underwent an exceptionally bright X-ray outburst from 2018 March to October, showing evidence of a non-thermal particle population through its radio emission during this whole period. The combined results of 59.5 h of observations of the MAXI J1820+070 outburst with the H.E.S.S., MAGIC and VERITAS experiments at energies above 200 GeV are presented, together with Fermi-LAT data between 0.1 and 500 GeV, and multiwavelength observations from radio to X-rays. Gamma-ray emission is not detected from MAXI J1820+070, but the obtained upper limits and the multiwavelength data allow us to put meaningful constraints on the source properties under reasonable assumptions regarding the non-thermal particle population and the jet synchrotron spectrum. In particular, it is possible to show that, if a high-energy (HE) gamma-ray emitting region is present during the hard state of the source, its predicted flux should be at most a factor of 20 below the obtained Fermi-LAT upper limits, and closer to them for magnetic fields significantly below equipartition. During the state transitions, under the plausible assumption that electrons are accelerated up to similar to 500 GeV, the multiwavelength data and the gamma-ray upper limits lead consistently to the conclusion that a potential HE and very-HE gamma-ray emitting region should be located at a distance from the BH ranging between 10(11) and 10(13) cm. Similar outbursts from low-mass X-ray binaries might be detectable in the near future with upcoming instruments such as CTA.
2.	Acciari, V.A., et al. (author) Monitoring the magnetar SGR 1935+2154 with the MAGIC telescopes 2022 In: Proceedings of Science. - 1824-8039. ; 395 Conference paper (peer-reviewed)abstract The Galactic magnetar SGR 1935+2154 was associated with a bright, millisecond-timescale fast radio burst (FRB) which occured in April 2020, during a flaring episode. This was the first time an FRB was unequivocally associated with a Galactic source, and the first FRB for which the nature of the emitting source was identified. Moreover, it was the first FRB with a counterpart at another wavelength correlated in time, an atypical, hard X-ray burst, which provides clear evidence for accompanying non-thermal processes. The MAGIC Telescopes are Imaging Air Cherenkov Telescopes (IACTs) sensitive to very-high-energy (VHE, E>100 GeV) gamma rays. Located at the center of the camera lies the MAGIC Central pixel, a single fully-modified photosensor-toreadout chain to measure millisecond-duration optical signals, displaying a maximum sensitivity at a wavelength of 350 nm. This allows MAGIC to operate simultaneously both as a VHE gammaray and a fast optical telescope. The MAGIC telescopes have monitored SGR 1935+2154 in a multiwavelength campaign involving X-ray, radio and optical facilities. In this contribution, we will show the results on the search for the VHE counterpart of the first SGR-FRB source in this multiwavelength context, as well as the search for fast optical bursts with the MAGIC Central Pixel.
3.	Adams, C. B., et al. (author) Observation of the Gamma-Ray Binary HESS J0632+057 with the HESS, MAGIC, and VERITAS Telescopes 2021 In: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 923:2 Journal article (peer-reviewed)abstract The results of gamma-ray observations of the binary system HESS J0632 + 057 collected during 450 hr over 15 yr, between 2004 and 2019, are presented. Data taken with the atmospheric Cherenkov telescopes H.E.S.S., MAGIC, and VERITAS at energies above 350 GeV were used together with observations at X-ray energies obtained with Swift-XRT, Chandra, XMM-Newton, NuSTAR, and Suzaku. Some of these observations were accompanied by measurements of the H alpha emission line. A significant detection of the modulation of the very high-energy gamma-ray fluxes with a period of 316.7 +/- 4.4 days is reported, consistent with the period of 317.3 +/- 0.7 days obtained with a refined analysis of X-ray data. The analysis of data from four orbital cycles with dense observational coverage reveals short-timescale variability, with flux-decay timescales of less than 20 days at very high energies. Flux variations observed over a timescale of several years indicate orbit-to-orbit variability. The analysis confirms the previously reported correlation of X-ray and gamma-ray emission from the system at very high significance, but cannot find any correlation of optical H alpha parameters with fluxes at X-ray or gamma-ray energies in simultaneous observations. The key finding is that the emission of HESS J0632 + 057 in the X-ray and gamma-ray energy bands is highly variable on different timescales. The ratio of gamma-ray to X-ray flux shows the equality or even dominance of the gamma-ray energy range. This wealth of new data is interpreted taking into account the insufficient knowledge of the ephemeris of the system, and discussed in the context of results reported on other gamma-ray binary systems.
4.	Af Burén, S, et al. (author) A 78 Seconds Complete Brain MRI Examination in Ischemic Stroke: A Prospective Cohort Study 2022 In: Journal of magnetic resonance imaging : JMRI. - 1522-2586. Journal article (peer-reviewed)
5.	Algaba, Juan-Carlos, et al. (author) Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign 2021 In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1 Research review (peer-reviewed)abstract In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
6.	Almqvist, Hakan, et al. (author) Radiological evaluation in patients with clinical suspicion of cerebral venous sinus thrombosis presenting with nontraumatic headache-a retrospective observational study with a validation cohort 2020 In: BMC Medical Imaging. - : BMC. - 1471-2342. ; 20:1 Journal article (peer-reviewed)abstract Background Clinical suspicion of cerebral venous sinus thrombosis (CVST) is imprecise due to non-specific symptoms such as headache. The aim was to retrospectively assess the diagnostic value of nonenhanced CT (neCT) in patients with nontraumatic headache and clinically suspected CVST. Methods A retrospective consecutive series of patients referred 2013-2015 for radiology were evaluated. Eligible patients had nontraumatic headache and suspicion of CVST stated in the referral, investigated with CT venography (CTV) and nonenhanced CT (neCT). neCT scans were re-evaluated for the presence of CVST or other pathology. All CTVs were checked for the presence of CVST. The validation cohort consisted of 10 patients with nontraumatic CVT (2017-2019). Results Less than 1% (1/104) had a suspected thrombus on neCT, confirmed by subsequent CTV. The remaining 99% had a CTV excluding CVST. Eleven percent had other imaging findings explaining their symptoms. In the patient with CVST, the thrombosed dural sinus was high attenuating (maximum HU 89) leading to the suspicion of CVST confirmed by CTV. The validation cohort (n = 10) confirmed the presence of a high attenuating (HU > 65) venous structure in the presence of a confirmed thrombus in all patients presenting within 10 days (suspicion written in referral, 10%). Conclusions Despite clinical suspicion, imaging findings of CVST in nontraumatic headache are uncommon. Evaluating neCT for high attenuation in dural sinuses, followed by CTV for confirmation in selected cases seems reasonable. CVST should be recognized by all radiologists and requires a high level of awareness when reading neCT for other indications.
7.	Arboleda-Velasquez, Joseph F, et al. (author) Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report. 2019 In: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 25:11, s. 1680-1683 Journal article (peer-reviewed)abstract We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease.
8.	Bhangu, A, et al. (author) Mortality of emergency abdominal surgery in high-, middle- and low-income countries 2016 In: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 103:8, s. 971-988 Journal article (peer-reviewed)
9.	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.
10.	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.
11.	Chillon, P, et al. (author) THE BIOLOGICAL HEALTH OF ADOLESCENTS IMPROVES IN THE SCHOOL CURRICULUM 2009 In: GACETA SANITARIA. - 0213-9111. ; 23, s. 252-252 Conference paper (other academic/artistic)
12.	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.
13.	de Felipe, B, et al. (author) Prospective neonatal screening for severe T- and B-lymphocyte deficiencies in Seville 2016 In: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - : Wiley. - 1399-3038. ; 27:1, s. 70-77 Journal article (peer-reviewed)
14.	Delgado, A. F., et al. (author) Arterial Spin-Labeling in Children with Brain Tumor : A Meta-Analysis 2018 In: American Journal of Neuroradiology. - : AMER SOC NEURORADIOLOGY. - 0195-6108 .- 1936-959X. ; 39:8, s. 1536-1542 Journal article (peer-reviewed)abstract BACKGROUND:The value of arterial spin-labeling in a pediatric population has not been assessed in a meta-analysis. PURPOSE:Our aim was to assess the diagnostic accuracy of arterial spin-labeling-derived cerebral blood flow to discriminate low- and high-grade tumors. DATA SOURCES:MEDLINE, EMBASE, the Web of Science Core Collection, and the Cochrane Library were used. STUDY SELECTION:Pediatric patients with arterial spin-labeling MR imaging with verified neuropathologic diagnoses were included. DATA ANALYSIS:Relative CBF and absolute CBF and tumor grade were extracted, including sequence-specific information. Mean differences in CBF between low- and high-grade tumors were calculated. Study quality was assessed. DATA SYNTHESIS:Data were aggregated using the bivariate summary receiver operating characteristic curve model. Heterogeneity was explored with meta-regression and subgroup analyses. The study protocol was published at PROSPERO (CRD42017075055). Eight studies encompassing 286 pediatric patients were included. The mean differences in absolute CBF were 29.62 mL/min/100 g (95% CI, 10.43-48.82 mL/min/100 g), I-2 = 74, P = .002, and 1.34 mL/min/100 g (95% CI, 0.95-1.74 mL/min/100 g), P < .001, I-2 = 38 for relative CBF. Pooled sensitivity for relative CBF ranged from 0.75 to 0.90, and specificity, from 0.77 to 0.92 with an area under curve = 0.92. Meta-regression showed no moderating effect of sequence parameters TE, TR, acquisition time, or ROI method. LIMITATIONS:Included tumor types, analysis method, and original data varied among included studies. CONCLUSIONS:Arterial spin-labeling-derived CBF measures showed high diagnostic accuracy for discriminating low- and high-grade tumors in pediatric patients with brain tumors. The relative CBF showed less variation among studies than the absolute CBF.
15.	Delgado, Anna F., et al. (author) Discrimination between Glioma Grades II and III Using Dynamic Susceptibility Perfusion MRI : A Meta-Analysis 2017 In: American Journal of Neuroradiology. - 0195-6108 .- 1936-959X. ; 38:7, s. 1348-1355 Journal article (peer-reviewed)abstract BACKGROUND: DSC perfusion has been evaluated in the discrimination between low-grade and high-grade glioma but the diagnostic potential to discriminate beween glioma grades II and III remains unclear.PURPOSE: Our aim was to evaluate the diagnostic accuracy of relative maximal CBV from DSC perfusion MR imaging to discriminate glioma grades II and III.DATA SOURCES: A systematic literature search was performed in PubMed/MEDLINE, Embase, Web of Science, and ClinicalTrials.gov.STUDY SELECTION: Eligible studies reported on patients evaluated with relative maximal CBV derived from DSC with a confirmed neuropathologic diagnosis of glioma World Health Organization grades II and III. Studies reporting on mean or individual patient data were considered for inclusion.DATA ANALYSIS: Data were analyzed by using inverse variance with the random-effects model and receiver operating characteristic curves describing optimal cutoffs and areas under the curve. Bivariate diagnostic random-effects meta-analysis was used to calculate diagnostic accuracy.DATA SYNTHESIS: Twenty-eight studies evaluating 727 individuals were included in the meta-analysis. Individual data were available from 10 studies comprising 190 individuals. The mean difference of relative maximal CBV between glioma grades II and III (n = 727) was 1.76 (95% CI, 1.27-2.24; P < .001). Individual patient data (n = 190) had an area under the curve of 0.77 for discriminating glioma grades II and III at an optimal cutoff of 2.02. When we analyzed astrocytomas separately, the area under the curve increased to 0.86 but decreased to 0.61 when we analyzed oligodendrogliomas.LIMITATIONS: A substantial heterogeneity was found among included studies.CONCLUSIONS: Glioma grade III had higher relative maximal CBV compared with glioma grade II. A high diagnostic accuracy was found for all patients and astrocytomas; however, the diagnostic accuracy was substantially reduced when discriminating oligodendroglioma grades II and III.
16.	Delgado, Anna Falk, et al. (author) Discrimination between primary low-grade and high-grade glioma with 11C-methionine PET : a bivariate diagnostic test accuracy meta-analysis 2018 In: British Journal of Radiology. - : British Institute of Radiology. - 0007-1285 .- 1748-880X. ; 91:1082 Research review (peer-reviewed)abstract Objective: To perform a meta-analysis evaluating the diagnostic accuracy of 11C-methionine (MET) positron emission tomography (PET) to discriminate between primary low-grade glioma (LGG) and high-grade glioma (HGG).Methods: A systematic database search was performed by a librarian in relevant databases with the latest search on 07 November 2016. Hits were assessed for inclusion independently by two authors. Individual patient data on relative MET uptake was extracted on patients examined pre-operatively with MET PET and subsequent neuropathological diagnosis of astrocytoma or oligodendroglioma. Individual patient data were analysed for diagnostic accuracy using a bivariate diagnostic random-effects meta-analysis model with restricted maximum likelihood estimation method. Bivariate meta-regression and subgroup analyses assessed study heterogeneity and validity. This study is registered with PROSPERO, number CRD42016050747.Results: Out of 1828 hits, 13 studies comprising of 241 individuals were included in the quantitative and qualitative analysis. MET PET had an area under the bivariate summary receiver operating characteristics curve of 0.78 to discriminate between LGG and HGG and a summary sensitivity of 0.80 with 95% confidence interval (CI) (0.66–0.88) and a summary false positive rate of 0.28, 95% CI (0.19–0.38). Heterogeneity was described by; bias in patient inclusion, study quality, and ratio method. Optimal cutoff for relative MET uptake was 2.21.Conclusion: MET PET had a moderately high diagnostic accuracy for the discrimination between primary LGG and HGG.Advances in knowledge: MET PET can be used as a clinical tool for the non-invasive discrimination between LGG and HGG with a moderately high accuracy at cut-off 2.21.
17.	Delgado, Anna Falk, et al. (author) Glioma Grade Discrimination with MR Diffusion Kurtosis Imaging : A Meta-Analysis of Diagnostic Accuracy 2018 In: Radiology. - : RADIOLOGICAL SOC NORTH AMERICA. - 0033-8419 .- 1527-1315. ; 287:1, s. 119-127 Journal article (peer-reviewed)abstract Purpose: To assess the diagnostic test accuracy and sources of heterogeneity for the discriminative potential of diffusion kurtosis imaging (DKI) to differentiate low-grade glioma (LGG) (World Health Organization [WHO] grade II) from high-grade glioma (HGG) (WHO grade III or IV).Materials and Methods: The Cochrane Library, Embase, Medline, and the Web of Science Core Collection were systematically searched by two librarians. Retrieved hits were screened for inclusion and were evaluated with the revised tool for quality assessment for diagnostic accuracy studies (commonly known as QUADAS-2) by two researchers. Statistical analysis comprised a random-effects model with associated heterogeneity analysis for mean differences in mean kurtosis (MK) in patients with LGG or HGG. A bivariate restricted maximum likelihood estimation method was used to describe the summary receiver operating characteristics curve and bivariate meta-regression.Results: Ten studies involving 430 patients were included. The mean difference in MK between LGG and HGG was 0.17 (95% confidence interval [CI]: 0.11, 0.22) with a z score equal to 5.86 (P<.001). The statistical heterogeneity was explained by glioma subtype, echo time, and the proportion of recurrent glioma versus primary glioma. The pooled area under the curve was 0.94 for discrimination of HGG from LGG, with 0.85 (95% CI: 0.74, 0.92) sensitivity and 0.92 (95% CI: 0.81, 0.96) specificity. Heterogeneity was driven by neuropathologic subtype and DKI technique.Conclusion: MK shows high diagnostic accuracy in the discrimination of LGG from HGG.
18.	Delgado, Anna Falk, et al. (author) Neuroimaging lesion assessment by pseudo-subtraction of overlaid semi-transparent volumes : A technical description and feasibility series 2021 In: The Neuroradiology Journal. - : Sage Publications. - 1971-4009 .- 2385-1996. ; 34:2, s. 128-130 Journal article (peer-reviewed)abstract Assessing and reporting clinical images constitutes the mainstay of clinical neuroradiology. Continually increasing numbers of neuroradiology referrals and follow-up examinations call for reproducible, accurate, and rapid workflows. Readily available and easy to use, advanced workstation tools such as co-registration of volume series can be used to overlay volume series from two different time points as semi-transparent images, with an inverse color scale. By overlaying semi-transparent inverse color maps, stationary findings will be shaded out in grey, whereas progressing or regressing lesions will be highlighted as white or black in the resulting pseudo-subtraction map. Pseudosubtraction in longitudinal neuroradiology imaging might enhance workflow and imaging assessment.
19.	Duran-Ferrer, Marti, et al. (author) The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome 2020 In: NATURE CANCER. - : Springer Nature. - 2662-1347. ; 1:11, s. 1066-1081 Journal article (peer-reviewed)abstract We report a systematic analysis of the DNA methylation variability in 1,595 samples of normal cell subpopulations and 14 tumor subtypes spanning the entire human B-cell lineage. Differential methylation among tumor entities relates to differences in cellular origin and to de novo epigenetic alterations, which allowed us to build an accurate machine learning-based diagnostic algorithm. We identify extensive individual-specific methylation variability in silenced chromatin associated with the proliferative history of normal and neoplastic B cells. Mitotic activity generally leaves both hyper- and hypomethylation imprints, but some B-cell neoplasms preferentially gain or lose DNA methylation. We construct a DNA-methylation-based mitotic clock, called epiCMIT, whose lapse magnitude represents a strong independent prognostic variable in B-cell tumors and is associated with particular driver genetic alterations. Our findings reveal DNA methylation as a holistic tracer of B-cell tumor developmental history, with implications in differential diagnosis and the prediction of clinical outcome. Martin-Subero and colleagues analyze DNA methylation patterns in B-cell tumors and their normal cells of origin, and develop epiCMIT, a methylation-based mitotic clock with prognostic relevance.
20.	Eyer, L., et al. (author) Gaia Data Release 2 Variable stars in the colour-absolute magnitude diagram 2019 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 623 Journal article (peer-reviewed)abstract Context. The ESA Gaia mission provides a unique time-domain survey for more than 1.6 billion sources with G less than or similar to 21 mag. Aims. We showcase stellar variability in the Galactic colour-absolute magnitude diagram (CaMD). We focus on pulsating, eruptive, and cataclysmic variables, as well as on stars that exhibit variability that is due to rotation and eclipses. Methods. We describe the locations of variable star classes, variable object fractions, and typical variability amplitudes throughout the CaMD and show how variability-related changes in colour and brightness induce "motions". To do this, we use 22 months of calibrated photometric, spectro-photometric, and astrometric Gaia data of stars with a significant parallax. To ensure that a large variety of variable star classes populate the CaMD, we crossmatched Gaia sources with known variable stars. We also used the statistics and variability detection modules of the Gaia variability pipeline. Corrections for interstellar extinction are not implemented in this article. Results. Gaia enables the first investigation of Galactic variable star populations in the CaMD on a similar, if not larger, scale as was previously done in the Magellanic Clouds. Although the observed colours are not corrected for reddening, distinct regions are visible in which variable stars occur. We determine variable star fractions to within the current detection thresholds of Gaia. Finally, we report the most complete description of variability-induced motion within the CaMD to date. Conclusions. Gaia enables novel insights into variability phenomena for an unprecedented number of stars, which will benefit the understanding of stellar astrophysics. The CaMD of Galactic variable stars provides crucial information on physical origins of variability in a way that has previously only been accessible for Galactic star clusters or external galaxies. Future Gaia data releases will enable significant improvements over this preview by providing longer time series, more accurate astrometry, and additional data types (time series BP and RP spectra, RVS spectra, and radial velocities), all for much larger samples of stars.
21.	Falk Delgado, Alberto, et al. (author) Arterial spin labeling MR imaging for differentiation between high- and low-grade glioma - A meta-analysis 2018 In: Neuro-Oncology. - : Oxford University Press (OUP). - 1522-8517 .- 1523-5866. ; 20:11, s. 1450-1461 Journal article (peer-reviewed)abstract Background. Arterial spin labeling is an MR imaging technique that measures cerebral blood flow (CBF) noninvasively. The aim of the study is to assess the diagnostic performance of arterial spin labeling (ASL) MR imaging for differentiation between high-grade glioma and low-grade glioma. Methods. Cochrane Library, Embase, Medline, and Web of Science Core Collection were searched. Study selection ended November 2017. This study was prospectively registered in PROSPERO (CRD42017080885). Two authors screened all titles and abstracts for possible inclusion. Data were extracted independently by 2 authors. Bivariate random effects meta-analysis was used to describe summary receiver operating characteristics. Trial sequential analysis (TSA) was performed. Results. In total, 15 studies with 505 patients were included. The diagnostic performance of ASL CBF for glioma grading was 0.90 with summary sensitivity 0.89 (0.79-0.90) and specificity 0.80 (0.72-0.89). The diagnostic performance was similar between pulsed ASL (AUC 0.90) with a sensitivity 0.85 (0.71-0.91) and specificity 0.83 (0.69- 0.92) and pseudocontinuous ASL (AUC 0.88) with a sensitivity 0.86 (0.79-0.91) and specificity 0.80 (0.65-0.87). In astrocytomas, the diagnostic performance was 0.89 with sensitivity 0.86 (0.79 to 0.91) and specificity 0.79 (0.63 to 0.89). Sensitivity analysis confirmed the robustness of the findings. TSA revealed that the meta-analysis was adequately powered. Conclusion. Arterial spin labeling MR imaging had an excellent diagnostic accuracy for differentiation between high-grade and low-grade glioma. Given its low cost, non-invasiveness, and efficacy, ASL MR imaging should be considered for implementation in the routine workup of patients with glioma.
22.	Falk Delgado, Alberto, et al. (author) Clinical outcome after surgical clipping or endovascular coiling for cerebral aneurysms : a pragmatic meta- analysis of randomized and non- randomized trials with short- and long- term follow- up 2017 In: JOURNAL OF NEUROINTERVENTIONAL SURGERY. - : BMJ PUBLISHING GROUP. - 1759-8478 .- 1759-8486. ; 9:3, s. 264- Journal article (peer-reviewed)abstract Background Two randomized trials have evaluated clipping and coiling in patients with ruptured aneurysms. Aggregated evidence for management of ruptured and unruptured aneurysms is missing. Objective To conduct a meta- analysis evaluating clinical outcome after aneurysm treatment. Methods PubMed, Cochrane Central Register of Controlled Trials, and Clinicaltrials. gov were searched for studies evaluating aneurysm treatment. The primary outcome measure was an independent clinical outcome ( modified Rankin scale 0- 2, Glasgow Outcome Scale 4- 5, or equivalent). Secondary outcomes were poor outcome and mortality. ORs were calculated on an intention- to- treat basis with 95% Cls. Outcome heterogeneity was evaluated with Cochrane's Q test ( significance level cut- off value at < 0.10) and l(2) ( significance cut- off value > 50%) with the Mantel-Haenszel method for dichotomous outcomes. A p value < 0.05 was regarded as statistically significant. Results Searches yielded 18 802 articles. All titles were assessed, 403 abstracts were evaluated, and 183 full-text articles were read. One- hundred and fifty articles were qualitatively assessed and 85 articles were included in the meta- analysis. Patients treated with coiling ( randomized controlled trials ( RCTs)) had higher independent outcome at short- term follow- up ( OR= 0.67, 95% Cl 0.57 to 0.79). Independent outcome was favored for coiling at intermediate and long- term follow-up ( RCTs and observational studies combined-OR= 0.80, 0.68 to 0.94 and OR= 0.81, 0.71 to 0.93, respectively). Independent outcome and lower mortality was favored after coiling in unruptured aneurysms ( database registry studies) at short- term follow- up ( OR= 0.34, 0.29 to 0.41 and OR= 1.74, 1.52 to 1.98, respectively). Conclusions This meta- analysis evaluating clinical outcome after coiling or clipping for intracranial aneurysms, indicates a higher independent outcome and lower mortality after coiling.
23.	Falk Delgado, Alberto, et al. (author) Complete Lymph Node Dissection in Melanoma : A Systematic Review and Meta-Analysis 2017 In: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 37:12, s. 6825-6829 Research review (peer-reviewed)abstract Background: The aim of this meta-analysis was to estimate the survival after immediate complete lymph node dissection (CLND) compared to observation only (OO) or delayed CLND in patients with melanoma and lymph node metastasis.Materials and Methods: A systematic search was performed in: PubMed, Web of Science, Cochrane Library, CINAHL, Clinical trials and Embase. Eligible studies were randomized controlled trials (RCTs) comparing: CLND with OO, or immediate CLND with delayed CLND.Results: Four RCTs were included. There was no difference in melanoma-specific survival (MSS) (HR=0.91, 95% CI=0.77-1.08, p=0.29). In a sensitivity analysis, MSS was higher after immediate CLND compared to delayed CLND in patients with nodal metastasis (HR=0.63, 95% CI=0.35-0.74, p=0.0004) without evidence of heterogeneity.Conclusion: CLND appears to have no additional survival benefit after SNB compared to OO. However, subgroup analysis suggests a time-dependent benefit for early surgical lymph node removal compared to delayed or none.
24.	Falk Delgado, Anna, et al. (author) Diagnostic value of alternative techniques to gadolinium-based contrast agents in MR neuroimaging : a comprehensive overview 2019 In: Insights into Imaging. - : Springer Science and Business Media LLC. - 1869-4101. ; 10:1 Research review (peer-reviewed)abstract Gadolinium-based contrast agents (GBCAs) increase lesion detection and improve disease characterization for many cerebral pathologies investigated with MRI. These agents, introduced in the late 1980s, are in wide use today. However, some non-ionic linear GBCAs have been associated with the development of nephrogenic systemic fibrosis in patients with kidney failure. Gadolinium deposition has also been found in deep brain structures, although it is of unclear clinical relevance. Hence, new guidelines from the International Society for Magnetic Resonance in Medicine advocate cautious use of GBCA in clinical and research practice. Some linear GBCAs were restricted from use by the European Medicines Agency (EMA) in 2017.This review focuses on non-contrast-enhanced MRI techniques that can serve as alternatives for the use of GBCAs. Clinical studies on the diagnostic performance of non-contrast-enhanced as well as contrast-enhanced MRI methods, both well established and newly proposed, were included. Advantages and disadvantages together with the diagnostic performance of each method are detailed. Non-contrast-enhanced MRIs discussed in this review are arterial spin labeling (ASL), time of flight (TOF), phase contrast (PC), diffusion-weighted imaging (DWI), magnetic resonance spectroscopy (MRS), susceptibility weighted imaging (SWI), and amide proton transfer (APT) imaging.Ten common diseases were identified for which studies reported comparisons of non-contrast-enhanced and contrast-enhanced MRI. These specific diseases include primary brain tumors, metastases, abscess, multiple sclerosis, and vascular conditions such as aneurysm, arteriovenous malformation, arteriovenous fistula, intracranial carotid artery occlusive disease, hemorrhagic, and ischemic stroke.In general, non-contrast-enhanced techniques showed comparable diagnostic performance to contrast-enhanced MRI for specific diagnostic questions. However, some diagnoses still require contrast-enhanced imaging for a complete examination.
25.	Falk Delgado, Alberto, et al. (author) Home institution bias in the New England Journal of Medicine? : A noninferiority study on citation rates 2018 In: Scientometrics. - : SPRINGER. - 0138-9130 .- 1588-2861. ; 115:1, s. 607-611 Journal article (peer-reviewed)abstract Recently, in the four top journals of humanities, an institutional bias towards publication of authors from Harvard and Yale was shown. The New England Journal of Medicine (NEJM) is today the highest ranked general medical journal. It is unknown if there exists institutional bias favoring publication of articles originating from Harvard University, since the NEJM is produced by the Massachusetts Medical Society with close connections to the Harvard University. We examined if studies originating from the Harvard University published in the NEJM were noninferior in terms of citation rates compared to articles with an origin outside Harvard University. We evaluated original research articles published in the NEJM in 2000 up until June 2001. A two-sample noninferiority test based on the primary endpoint of citations was performed. Twenty-two studies were affiliated to the Harvard University and 280 studies were not affiliated to the Harvard University. The mean number of citations for Harvard affiliated studies was 625 (95% CI 358-952, median 354) and for non-Harvard affiliated studies 493 (95% CI 421-569, median 303). The mean difference was not statistically different between affiliations, but fulfilled the requirements for noninferiority [132 (95% CI - 138-402, P = 0.343), Delta 200]. In summary, citation rates were comparable between studies origination from the Harvard University compared to non-Harvard Institutions. Based on these results there appears to be low risk of institutional bias in the publishing process of original studies in the NEJM.
26.	Falk-Delgado, Anna, et al. (author) Improved clinical outcome 3 months after endovascular treatment, including thrombectomy, in patients with acute ischemic stroke : a meta-analysis 2016 In: Journal of neurointerventional surgery. - : BMJ. - 1759-8486 .- 1759-8478. ; 8:7 Journal article (peer-reviewed)abstract BACKGROUND AND PURPOSE: Intravenous thrombolysis with tissue plasminogen activator is standard treatment in acute stroke today. The benefit of endovascular treatment has been questioned. Recently, studies evaluating endovascular treatment and intravenous thrombolysis compared with intravenous thrombolysis alone, have reported improved outcome for the intervention group. The aim of this study was to perform a meta-analysis of randomized controlled trials comparing endovascular treatment in addition to intravenous thrombolysis with intravenous thrombolysis alone.METHODS: Databases were searched for eligible randomized controlled trials. The primary outcome was a functional neurological outcome after 90 days. A secondary outcome was severe disability and death. Data were pooled in the control and intervention groups, and OR was calculated on an intention to treat basis with 95% CIs. Outcome heterogeneity was evaluated with Cochrane's Q test (significance level cut-off value at <0.10) and I(2) (significance cut-off value >50%) with the Mantel-Haenszel method for dichotomous outcomes. A p value <0.05 was regarded as statistically significant.RESULTS: Six studies met the eligibility criteria, and data from 1569 patients were analyzed. A higher probability of a functional neurological outcome after 90 days was found for the intervention group (OR 2, 95% CI 2 to 3). There was a significantly higher probability of death and severe disability in the control group compared with the intervention group.CONCLUSIONS: Endovascular treatment in addition to intravenous thrombolysis for acute ischemic stroke leads to an improved clinical outcome after 3 months, compared with patients receiving intravenous thrombolysis alone.
27.	Falk Delgado, Anna, et al. (author) [In Process Citation]. 2015 In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 112 Journal article (peer-reviewed)abstract Systemic thrombolysis is an established treatment in acute ischemic stroke. Endovascular treatment to reperfuse occluded vessels has been in clinical practice the last decade. The role of neurointervention in acute ischemic stroke has been questioned. Within the last year, several randomized controlled trials have been published, comparing endovascular treatment and systemic thrombolysis with systemic thrombolysis alone. A meta-analysis, using data from six trials treating 1569 patients, was recently published. In this meta-analysis, patients treated with endovascular therapy in addition to IV thrombolysis had a more favourable clinical outcome compared to patients receiving IV thrombolysis alone, after 3 months. Compared to the individ-ual studies, a decreased mortality in the intervention group was shown. Assessing the safety of endovascular treatment, there was no increased risk of intracranial bleed-ing, compared to IV thrombolysis alone. This meta-analysis highlights and summar-izes the scientific evidence for endovascular treatment in acute ischemic stroke.
28.	Falk Delgado, Alberto, et al. (author) Inconsistent Reporting Between Meta-analysis Protocol and Publication – A Cross-Sectional Study 2017 In: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 37:9, s. 5101-5107 Journal article (peer-reviewed)abstract Background: Inconsistent reporting in published meta-analyses compared to registered protocol are poorly understood. The aim of the study was to assess inconsistencies between registered protocols and published reports among oncology drug meta-analyses.Materials and Methods: A cross-sectional study was performed including oncology drug meta-analyses published between January 1st and November 14th 2016 with a published protocol. Two investigators extracted data on: selection criteria, outcome(s) and statistical plan in protocol and manuscript, plus self-acknowledgement of inconsistent reporting between protocol and publication.Results: Protocol registration was present in 19% (23/119) of all oncology drug meta-analyses. In meta-analyses with protocol (n= 23), 70% (16/23) had issues with inconsistent reporting between protocol and published report concerning; inclusion criteria, comparator group, intervention, outcome (PICO) or statistical analysis. Self-acknowledgement of changes between protocol and publication was found in 50% (8/16).Conclusion: In meta-analyses with protocol, discrepancies between registered protocols and publications are frequent.
29.	Falk Delgado, Alberto, et al. (author) Melanoma Sentinel-Node Metastasis. 2017 In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 377:9, s. 891-892 Journal article (peer-reviewed)
30.	Falk Delgado, Alberto, et al. (author) Outcome switching in randomized controlled oncology trials reporting on surrogate endpoints: a cross-sectional analysis 2017 In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 9206- Journal article (peer-reviewed)abstract Inconsistent reporting of clinical trials is well-known in the literature. Despite this, factors associated with poor practice such as outcome switching in clinical trials are poorly understood. We performed a cross-sectional analysis to evaluate the prevalence of, and the factors associated with outcome switching. PubMed and Embase were searched for pharmaceutical randomized controlled trials (RCTs) in oncology reporting on a surrogate primary outcome published in 2015. Outcome switching was present in 18% (39/216). First-author male sex was significantly more likely associated with outcome switching compared to female sex with an OR of 3.05 (95% CI 1.07–8.64, p = 0.04) after multivariable adjustment. For-profit funded RCTs were less likely associated with outcome switching compared to non-profit funded research with an OR of 0.22 (95% CI 0.07–0.74, p = 0.01). First author male sex was more likely associated with outcome switching compared to female sex in drug oncology RCTs reporting on a primary surrogate endpoint. For-profit funded research was less likely associated with outcome switching compared to research funded by non-profit organizations. Furthermore, 18 percent of drug oncology trials reporting on a surrogate endpoint could have a higher risk of false positive results due to primary outcome switching.
31.	Falk Delgado, Alberto, et al. (author) Ruptured carotid-ophthalmic aneurysm treatment : a non-inferiority meta-analysis comparing endovascular coiling and surgical clipping 2017 In: British Journal of Neurosurgery. - : Informa UK Limited. - 0268-8697 .- 1360-046X. ; 31:3, s. 345-349 Journal article (peer-reviewed)abstract Introduction: Aneurysms of the carotid-ophthalmic segment are relatively rare, comprising only five percent of all intracranial aneurysms. There is no consensus regarding the optimal management for ruptured carotid-ophthalmic aneurysms, whether endovascular coiling or surgical clipping provide the most favourable patient outcome. The aim of this meta-analysis is to analyse these two treatment modalities for ruptured carotid-ophthalmic aneurysms with respect to independent clinical outcome.Methods: We performed a systematic literature search in PubMed, Cochrane Central Registry of Controlled Trials and Clinicaltrials.gov for treatment of ruptured carotid-ophthalmic aneurysms, comparing endovascular coiling and surgical clipping. Primary outcome in the study was independent clinical patient outcome at follow up (defined as Glasgow Outcome Scale four–five). Secondary outcomes were poor clinical patient outcome, mortality and total angiographic occlusion. The meta-analysis was performed using the Mantel–Haenszel method for dichotomous outcome.Results: Four studies met the inclusion criteria and were included in the meta-analysis. In total, 152 patients were included. Sixty-seven of these patients were treated with endovascular coiling and 85 patients were treated with microsurgical clipping. The proportion of patients with an independent clinical outcome after coiling and clipping was comparable, OR 1.04 (95% CI: 0.40, 2.71). The proportion of patients with an independent outcome in the endovascular group was 76% and in the surgical group 71%. Mortality between the two treatment arms was equal.Conclusion: Clinical outcome after endovascular coiling and surgical clipping for ruptured carotid-ophthalmic aneurysms was comparable between surgical clipping and endovascular coiling. There was no proven difference in clinical outcome after endovascular coiling and surgical clipping for ruptured carotid-ophthalmic aneurysms but the evidence was based on few studies of moderate to low quality and we cannot rule out the possibility of a difference in clinical outcome between the two treatment modalities.
32.	Falk Delgado, Alberto, et al. (author) Self-declared stock ownership and association with positive trial outcome in randomized controlled trials with binary outcomes published in general medical journals : a cross-sectional study 2017 In: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 18 Journal article (peer-reviewed)abstract Background: Describe the prevalence and types of conflicts of interest (COI) in published randomized controlled trials (RCTs) in general medical journals with a binary primary outcome and assess the association between conflicts of interest and favorable outcome. Methods: Parallel-group RCTs with a binary primary outcome published in three general medical journals during 2013-2015 were identified. COI type, funding source, and outcome were extracted. Binomial logistic regression model was performed to assess association between COI and funding source with outcome. Results: A total of 509 consecutive parallel-group RCTs were included in the study. COI was reported in 74% in mixed funded RCTs and in 99% in for-profit funded RCTs. Stock ownership was reported in none of the non-profit RCTs, in 7% of mixed funded RCTs, and in 50% of for-profit funded RCTs. Mixed-funded RCTs had employees from the funding company in 11% and for-profit RCTs in 76%. Multivariable logistic regression revealed that stock ownership in the funding company among any of the authors was associated with a favorable outcome (odds ratio = 3.53; 95% confidence interval = 1.59-7.86; p < 0.01). Conclusion: COI in for-profit funded RCTs is extensive, because the factors related to COI are not fully independent, a multivariable analysis should be cautiously interpreted. However, after multivariable adjustment only stock ownership from the funding company among authors is associated with a favorable outcome.
33.	Falk Delgado, Alberto, et al. (author) Sentinel Lymph Node Biopsy and Complete Lymph Node Dissection for Melanoma 2019 In: Current Oncology Reports. - : SPRINGER. - 1523-3790 .- 1534-6269. ; 21:6 Research review (peer-reviewed)abstract Purpose of Review: The main surgical treatment for invasive malignant melanoma consists of wide surgical and examination of the sentinel node and in selected cases complete lymph node dissection. The aim of this review is to present data for the optimal surgical management of patients with malignant melanoma.Recent Findings: A surgical excision margin of 1-2cm is recommended for invasive melanoma depending on the thickness of the melanoma. Sentinel node biopsy may be considered for patients with at least T1b melanomas thickness 0.8 to 1.0mm or less than 0.8mm Breslow thickness with ulceration, classified as T1b lesion, per recent AJCC guidelines. Two randomized controlled trials have been publishedDeCOG (German Dermatologic Cooperative Oncology Group Selective Lymphadenectomy) and MSLT-2 (Multicenter Selective Lymphadenectomy Trial) comparing the complete lymph node dissection (CLND) with observation after positive sentinel node biopsy. In the MSLT-2 study, the disease control rate was improved in the immediate CLND group compared with observation but there was no difference in 3-year melanoma specific survival (86%1.3% and 86%+/- 1.2%, respectively; p=0.42). Isolated limb perfusion (ILP) or isolated limb infusion (ILI) with melphalan and actinomycin D is recommended for large and multiple in-transit metastases and satellite metastases in the extremities when local excision is considered ineffective or too extensive.Summary: In light of new adjuvant treatment options and new indications for checkpoint inhibitors, and the lack of survival benefit after CLND, we can expect open surgery to decrease in melanoma disease.
34.	Falk Delgado, Alberto, et al. (author) The association of funding source on effect size in randomized controlled trials : 2013-2015-a cross-sectional survey and metaanalysis 2017 In: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 18 Journal article (peer-reviewed)abstract Background: Trials financed by for-profit organizations have been associated with favorable outcomes of new treatments, although the effect size of funding source impact on outcome is unknown. The aim of this study was to estimate the effect size for a favorable outcome in randomized controlled trials (RCTs), stratified by funding source, that have been published in general medical journals. Methods: Parallel-group RCTs published in The Lancet, New England Journal of Medicine, and JAMA between 2013 and 2015 were identified. RCTs with binary primary endpoints were included. The primary outcome was the OR of patients' having a favorable outcome in the intervention group compared with the control group. The OR of a favorable outcome in each trial was calculated by the number of positive events that occurred in the intervention and control groups. A meta-analytic technique with random effects model was used to calculate summary OR. Data were stratified by funding source as for-profit, mixed, and nonprofit. Prespecified sensitivity, subgroup, and metaregression analyses were performed. Results: Five hundred nine trials were included. The OR for a favorable outcome in for-profit-funded RCTs was 1.92 (95% CI 1.72-2.14), which was higher than mixed source-funded RCTs (OR 1.34, 95% CI 1.25-1.43) and nonprofit-funded RCTs (OR 1.32, 95% CI 1.26-1.39). The OR for a favorable outcome was higher for both clinical and surrogate endpoints in for-profit-funded trials than in RCTs with other funding sources. Excluding drug trials lowered the OR for a favorable outcome in for-profit-funded RCTs. The OR for a favorable surrogate outcome in drug trials was higher in for-profit-funded trials than in nonprofit-funded trials. Conclusions: For-profit-funded RCTs have a higher OR for a favorable outcome than nonprofit-and mixed source-funded RCTs. This difference is associated mainly with the use of surrogate endpoints in for-profit-financed drug trials.
35.	Falk Delgado, Alberto, et al. (author) The language of peer review reports on articles published in the BMJ, 2014-2017 : an observational study 2019 In: Scientometrics. - : SPRINGER. - 0138-9130 .- 1588-2861. ; 120:3, s. 1225-1235 Journal article (peer-reviewed)abstract To analyse the words and expressions used in peer reviews of manuscripts that were later published as original research in the BMJ. Secondary aims were to estimate the differences in net sentiment between peer review reports on manuscripts subject to one or more rounds of peer review and and review reports on initially rejected manuscripts that were accepted after appeal. This observational study included all peer review reports published in the BMJ from September 2014 until the end of 2017. The study analysed the frequency of specific words in peer review reports for accepted manuscripts, identifying the most commonly occurring positive and negative words and their context, as well as the most common expressions. It also quantified differences in net sentiment in peer review reports between manuscripts accepted after appeal and manuscript accepted without appeal. The dataset consisting of 1716 peer review reports contained 908,932 word tokens. Among the most frequent positive words were "well", "important", "clear", "while the negative words included "risk", "bias", and "confounding". The areas where the reviewer makes the most positive and negative comments included: "well-written paper", "well-written manuscript", "this is an important topic", "answers an important question", "high risk of bias" and "selection bias". The sentiment analysis revealed that manuscripts accepted after appeal had lower scores on review reports for joy and positive sentiment, in addition to having higher scores for negative words expressing sadness, fear, disgust and anger compared with manuscripts that were not initially rejected. Peer review comments were mainly related to methodology rather than the actual results. Peer review reports on initially rejected manuscripts were more negative and more often included expressions related to a high risk of bias.
36.	Gaia Data Release 2 : The celestial reference frame (Gaia-CRF2) 2018 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 16:A14 Journal article (peer-reviewed)
37.	Garcia-Benito, R., et al. (author) CALIFA, the Calar Alto Legacy Integral Field Area survey III. Second public data release 2015 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 576:A135 Journal article (peer-reviewed)abstract This paper describes the Second Public Data Release (DR2) of the Calar Alto Legacy Integral Field Area (CALIFA) survey. The data for 200 objects are made public, including the 100 galaxies of the First Public Data Release (DR1). Data were obtained with the integral-field spectrograph PMAS /PPak mounted on the 3.5 m telescope at the Calar Alto observatory. Two different spectral setups are available for each galaxy, (i) a low-resolution V500 setup covering the wavelength range 3745-7500 angstrom with a spectral resolution of 6.0 angstrom (FWHM); and (ii) a medium-resolution V1200 setup covering the wavelength range 3650-4840 angstrom with a spectral resolution of 2.3 angstrom (FWHM). The sample covers a redshift range between 0.005 and 0.03, with a wide range of properties in the color-magnitude diagram, stellar mass, ionization conditions, and morphological types. All the cubes in the data release were reduced with the latest pipeline, which includes improved spectrophotometric calibration, spatial registration, and spatial resolution. The spectrophotometric calibration is better than 6% and the median spatial resolution is 2 4. In total, the second data release contains over 1.5 million spectra.
38.	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.
39.	Jepsen, Kim Sune, et al. (author) ‘The Public Spectre’: A Critical Concept of Public Engagement with Technology 2017 In: Technoscience and Citizenship: Ethics and Governance in the Digital Society. - 9783319324142 ; 17, s. 17-30 Book chapter (peer-reviewed)
40.	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.
41.	Lindegren, Lennart, et al. (author) Gaia Early Data Release 3 : The Gaia Catalogue of Nearby Stars 2021 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 649 Journal article (peer-reviewed)abstract Aims. We produce a clean and well-characterised catalogue of objects within 100 pc of the Sun from the Gaia Early Data Release 3. We characterise the catalogue through comparisons to the full data release, external catalogues, and simulations. We carry out a first analysis of the science that is possible with this sample to demonstrate its potential and best practices for its use.Methods. Theselection of objects within 100 pc from the full catalogue used selected training sets, machine-learning procedures, astrometric quantities, and solution quality indicators to determine a probability that the astrometric solution is reliable. The training set construction exploited the astrometric data, quality flags, and external photometry. For all candidates we calculated distance posterior probability densities using Bayesian procedures and mock catalogues to define priors. Any object with reliable astrometry and a non-zero probability of being within 100 pc is included in the catalogue.Results. We have produced a catalogue of 331 312 objects that we estimate contains at least 92% of stars of stellar type M9 within 100 pc of the Sun. We estimate that 9% of the stars in this catalogue probably lie outside 100 pc, but when the distance probability function is used, a correct treatment of this contamination is possible. We produced luminosity functions with a high signal-to-noise ratio for the main-sequence stars, giants, and white dwarfs. We examined in detail the Hyades cluster, the white dwarf population, and wide-binary systems and produced candidate lists for all three samples. We detected local manifestations of several streams, superclusters, and halo objects, in which we identified 12 members of Gaia Enceladus. We present the first direct parallaxes of five objects in multiple systems within 10 pc of the Sun.Conclusions. We provide the community with a large, well-characterised catalogue of objects in the solar neighbourhood. This is a primary benchmark for measuring and understanding fundamental parameters and descriptive functions in astronomy.
42.	Luri, X., et al. (author) Gaia Early Data Release 3 : Structure and properties of the Magellanic Clouds 2021 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 649 Journal article (peer-reviewed)
43.	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.
44.	Mishra, A., et al. (author) Stroke genetics informs drug discovery and risk prediction across ancestries 2022 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123 Journal article (peer-reviewed)abstract Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
45.	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.
46.	Ridker, PM, et al. (author) Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients 2017 In: The New England journal of medicine. - 1533-4406 .- 0028-4793. ; 376:16, s. 1527-1539 Journal article (peer-reviewed)
47.	Sanchez, L. A., et al. (author) Production, purification and characterization of serraticin A, a novel cold-active antimicrobial produced by Serratia proteamaculans 136 2010 In: Journal of Applied Microbiology. - : Oxford University Press (OUP). - 1364-5072. ; 109:3, s. 936-945 Journal article (peer-reviewed)abstract Aim: This study focuses on the production, purification and characterization of serraticin A, a novel cold-active antimicrobial produced by Serratia proteamaculans 136. Methods and Results: A Ser. proteamaculans strain producing a novel cold-active antimicrobial was isolated from Isla de los Estados, Argentina. Antimicrobial production was optimized in a BIOFLO 101 bioreactor under batch culture mode, with temperature, pH and dissolved oxygen controlled conditions. A purification protocol was developed including activated charcoal adsorption, solid-phase C18 extraction (SPE) and semi-preparative HPLC. The molecular weight was determined by LC/QTOF/MS/MS mass analysis. Conclusions: Serratia proteamaculans 136 produces a cold-active low molecular bacteriocin-like compound named serraticin A. In this work, it has been laboratory-scale produced, purified and partially characterized. Cross-immunity test revealed that serraticin A is very different from other well-known microcins assayed, with a wide inhibitory spectrum, showing an interesting biotechnology potential to be applied as a control agent against pathogenic bacteria. Significance and Impact of the Study: The present study is the first report of a cold-active compound with antimicrobial activity from Ser. proteamaculans. The work also highlights that cold environments could be a suitable source of micro-organisms with ability to produce cold-active biomolecules of biotechnological interest.
48.	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.
49.	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.
50.	2017 swepub:Mat__t

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