| 1. |
- Abdalla, H., et al.
(author)
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Gamma-ray blazar spectra with HESS II mono analysis : The case of PKS2155-304 and PG1553+113
- 2017
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 600
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Journal article (peer-reviewed)abstract
- Context. The addition of a 28 m Cherenkov telescope (CT5) to the H.E.S.S. array extended the experiment's sensitivity to lower energies. The lowest energy threshold is obtained using monoscopic analysis of data taken with CT5, providing access to gamma-ray energies below 100 GeV for small zenith angle observations. Such an extension of the instrument's energy range is particularly beneficial for studies of active galactic nuclei with soft spectra, as expected for those at a redshift >= 0.5. The high-frequency peaked BL Lac objects PKS 2155-304 (z = 0.116) and PG 1553 + 113 (0.43 < z < 0.58) are among the brightest objects in the gamma-ray sky, both showing clear signatures of gamma-ray absorption at E > 100 GeV interpreted as being due to interactions with the extragalactic background light (EBL). Aims. The aims of this work are twofold: to demonstrate the monoscopic analysis of CT5 data with a low energy threshold, and to obtain accurate measurements of the spectral energy distributions (SED) of PKS 2155-304 and PG 1553 + 113 near their SED peaks at energies approximate to 100 GeV. Methods. Multiple observational campaigns of PKS 2155 304 and PG 1553 + 113 were conducted during 2013 and 2014 using the full H.E.S.S. II instrument (CT1-5). A monoscopic analysis of the data taken with the new CT5 telescope was developed along with an investigation into the systematic uncertainties on the spectral parameters which are derived from this analysis. Results. Using the data from CT5, the energy spectra of PKS 2155 304 and PG 1553 + 113 were reconstructed down to conservative threshold energies of 80 GeV for PKS 2155 304, which transits near zenith, and 110 GeV for the more northern PG 1553 + 113. The measured spectra, well fitted in both cases by a log-parabola spectral model ( with a 5.0 similar to statistical preference for non-zero curvature for PKS 2155 304 and 4.5 sigma for PG 1553+113), were found consistent with spectra derived from contemporaneous Fermi-LAT data, indicating a sharp break in the observed spectra of both sources at E approximate to 100 GeV. When corrected for EBL absorption, the intrinsic H.E.S.S. II mono and Fermi-LAT spectrum of PKS 2155 304 was found to show significant curvature. For PG 1553+113, however, no significant detection of curvature in the intrinsic spectrum could be found within statistical and systematic uncertainties.
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| 2. |
- Kinyoki, DK, et al.
(author)
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Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
- 2020
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In: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 26:5, s. 750-759
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Journal article (peer-reviewed)abstract
- A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic.
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| 3. |
- Cossarizza, A., et al.
(author)
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Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
- 2019
-
In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
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Journal article (peer-reviewed)abstract
- These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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| 4. |
- Petroff, E., et al.
(author)
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A polarized fast radio burst at low Galactic latitude
- 2017
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In: Monthly notices of the Royal Astronomical Society. - : Oxford Academic. - 0035-8711 .- 1365-2966. ; 469:4, s. 4465-4482
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Journal article (peer-reviewed)abstract
- We report on the discovery of a new fast radio burst (FRB), FRB 150215, with the Parkes radio telescope on 2015 February 15. The burst was detected in real time with a dispersion measure (DM) of 1105.6 +/- 0.8 pc cm(-3), a pulse duration of 2.8(-0.5)(+1.2) ms, and a measured peak flux density assuming that the burst was at beam centre of 0.7(-0.1)(+0.2) Jy. The FRB originated at a Galactic longitude and latitude of 24.66 degrees, 5.28 degrees and 25 degrees away from the Galactic Center. The burst was found to be 43 +/- 5 per cent linearly polarized with a rotation measure (RM) in the range -9 < RM < 12 rad m(-2) (95 per cent confidence level), consistent with zero. The burst was followed up with 11 telescopes to search for radio, optical, X-ray, gamma-ray and neutrino emission. Neither transient nor variable emission was found to be associated with the burst and no repeat pulses have been observed in 17.25 h of observing. The sightline to the burst is close to the Galactic plane and the observed physical properties of FRB 150215 demonstrate the existence of sight lines of anomalously low RM for a given electron column density. The Galactic RM foreground may approach a null value due to magnetic field reversals along the line of sight, a decreased total electron column density from the Milky Way, or some combination of these effects. A lower Galactic DM contribution might explain why this burst was detectable whereas previous searches at low latitude have had lower detection rates than those out of the plane.
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| 5. |
- Abdalla, H., et al.
(author)
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HESS discovery of very high energy gamma-ray emission from PKS 0625-354
- 2018
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 476:3, s. 4187-4198
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Journal article (peer-reviewed)abstract
- PKS 0625-354 (z = 0.055) was observed with the four High Energy Stereoscopic System (H.E.S.S.) telescopes in 2012 during 5.5 h. The source was detected above an energy threshold of 200 GeV at a significance level of 6.1 sigma. No significant variability is found in these observations. The source is well described with a power-law spectrum with photon index Gamma = 2.84 +/- 0.50(stat) +/- 0.10(syst) and normalization (at E-0 = 1.0 TeV) N-0(E-0)=(0.58 +/- 0.22(stat) +/- 0.12(syst)) x 10(-12) TeV-1 cm(-2) s(-1). Multiwavelength data collected with Fermi-LAT, Swift-XRT, Swift-UVOT, ATOM and WISE are also analysed. Significant variability is observed only in the Fermi-LAT gamma-ray and Swift-XRT X-ray energy bands. Having a good multiwavelength coverage from radio to very high energy, we performed a broad-band modelling from two types of emission scenarios. The results from a one zone lepto-hadronic and a multizone leptonic models are compared and discussed. On the grounds of energetics, our analysis favours a leptonic multizone model. Models associated to the X-ray variability constraint support previous results, suggesting a BL Lac nature of PKS 0625-354 with, however, a large-scale jet structure typical of a radio galaxy.
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| 6. |
- Acero, F., et al.
(author)
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Prospects for Cherenkov Telescope Array Observations of the Young Supernova Remnant RX J1713.7-3946
- 2017
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In: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 840:2
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Journal article (peer-reviewed)abstract
- We perform simulations for future Cherenkov Telescope Array (CTA) observations of RX J1713.7-3946, a young supernova remnant (SNR) and one of the brightest sources ever discovered in very high energy (VHE) gamma rays. Special attention is paid to exploring possible spatial (anti) correlations of gamma rays with emission at other wavelengths, in particular X-rays and CO/H I emission. We present a series of simulated images of RX J1713.7-3946 for CTA based on a set of observationally motivated models for the gamma-ray emission. In these models, VHE gamma rays produced by high-energy electrons are assumed to trace the nonthermal X-ray emission observed by XMM-Newton, whereas those originating from relativistic protons delineate the local gas distributions. The local atomic and molecular gas distributions are deduced by the NANTEN team from CO and H I observations. Our primary goal is to show how one can distinguish the emission mechanism(s) of the gamma rays (i.e., hadronic versus leptonic, or a mixture of the two) through information provided by their spatial distribution, spectra, and time variation. This work is the first attempt to quantitatively evaluate the capabilities of CTA to achieve various proposed scientific goals by observing this important cosmic particle accelerator.
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| 7. |
- Abramowski, A., et al.
(author)
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Long-term monitoring of PKS2155-304 with ATOM and HESS:investigation of optical/gamma-ray correlations in different spectral states
- 2014
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 571
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Journal article (peer-reviewed)abstract
- In this paper we report on the analysis of all the available optical and very high-energy gamma-ray (> 200 GeV) data for the BL Lac object PKS 2155-304, collected simultaneously with the ATOM and H.E.S.S. telescopes from 2007 until 2009. This study also includes X-ray (RXTE, Swift) and high-energy gamma-ray (Fermi-LAT) data. During the period analysed, the source was transitioning from its flaring to quiescent optical states, and was characterized by only moderate flux changes at different wavelengths on the timescales of days and months. A flattening of the optical continuum with an increasing optical flux can be noted in the collected dataset, but only occasionally and only at higher flux levels. We did not find any universal relation between the very high-energy gamma-ray and optical flux changes on the timescales from days and weeks up to several years. On the other hand, we noted that at higher flux levels the source can follow two distinct tracks in the optical flux-colour diagrams, which seem to be related to distinct gamma-ray states of the blazar. The obtained results therefore indicate a complex scaling between the optical and gamma-ray emission of PKS 2155 304, with different correlation patterns holding at different epochs, and a gamma-ray flux depending on the combination of an optical flux and colour rather than a flux alone.
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| 8. |
- Abdo, A. A., et al.
(author)
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Gamma-ray emission concurrent with the nova in the symbiotic binary V407 cygni
- 2010
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 329:5993, s. 817-821
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Journal article (peer-reviewed)abstract
- Novae are thermonuclear explosions on a white dwarf surface fueled by mass accreted from a companion star. Current physical models posit that shocked expanding gas from the nova shell can produce x-ray emission, but emission at higher energies has not been widely expected. Here, we report the Fermi Large Area Telescope detection of variable γ-ray emission (0.1 to 10 billion electron volts) from the recently detected optical nova of the symbiotic star V407 Cygni. We propose that the material of the nova shell interacts with the dense ambient medium of the red giant primary and that particles can be accelerated effectively to produce π0 decay γ-rays from proton-proton interactions. Emission involving inverse Compton scattering of the red giant radiation is also considered and is not ruled out.
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| 9. |
- Mayer, Manuel, et al.
(author)
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Constraints on particle acceleration in SS433/W50 from MAGIC and HESS observations
- 2018
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
-
Journal article (peer-reviewed)abstract
- Context. The large jet kinetic power and non-thermal processes occurring in the microquasar SS 433 make this source a good candidate for a very high-energy (VHE) gamma-ray emitter. Gamma-ray fluxes above the sensitivity limits of current Cherenkov telescopes have been predicted for both the central X-ray binary system and the interaction regions of SS 433 jets with the surrounding W50 nebula. Non-thermal emission at lower energies has been previously reported, indicating that efficient particle acceleration is taking place in the system. Aims. We explore the capability of SS 433 to emit VHE gamma rays during periods in which the expected flux attenuation due to periodic eclipses (P-orb similar to 13.1 days) and precession of the circumstellar disk (P-pre similar to 162 days) periodically covering the central binary system is expected to be at its minimum. The eastern and western SS 433/W50 interaction regions are also examined using the whole data set available. We aim to constrain some theoretical models previously developed for this system with our observations. Methods. We made use of dedicated observations from the Major Atmospheric Gamma Imaging Cherenkov telescopes (MAGIC) and High Energy Spectroscopic System (H.E.S.S.) of SS 433 taken from 2006 to 2011. These observation were combined for the first time and accounted for a total effective observation time of 16.5 h, which were scheduled considering the expected phases of minimum absorption of the putative VHE emission. Gamma-ray attenuation does not affect the jet/medium interaction regions. In this case, the analysis of a larger data set amounting to similar to 40-80 h, depending on the region, was employed. Results. No evidence of VHE gamma-ray emission either from the central binary system or from the eastern/western interaction regions was found. Upper limits were computed for the combined data set. Differential fluxes from the central system are found to be less than or similar to 10(-12)-10(-13) TeV-1 cm(-2) s(-1) in an energy interval ranging from similar to few x 100 GeV to similar to few TeV. Integral flux limits down to similar to 10(-12)-10(-13) ph cm(-2) s(-1) and similar to 10(-13)-10(-14) ph cm(-2) s(-1) are obtained at 300 and 800 GeV, respectively. Our results are used to place constraints on the particle acceleration fraction at the inner jet regions and on the physics of the jet/medium interactions. Conclusions. Our findings suggest that the fraction of the jet kinetic power that is transferred to relativistic protons must be relatively small in SS 433, q(p) <= 2.5 x 10(-5), to explain the lack of TeV and neutrino emission from the central system. At the SS 433/W50 interface, the presence of magnetic fields greater than or similar to 10 mu G is derived assuming a synchrotron origin for the observed X-ray emission. This also implies the presence of high-energy electrons with E-e up to 50 TeV, preventing an efficient production of gamma-ray fluxes in these interaction regions.
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| 10. |
- Abdalla, H., et al.
(author)
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Simultaneous observations of the blazar PKS 2155-304 from ultra-violet to TeV energies
- 2020
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 639, s. 1-13
-
Journal article (peer-reviewed)abstract
- Here we report the results of the first ever contemporaneous multi-wavelength observation campaign on the BL Lac object PKS 2155-304 involving Swift, NuSTAR, Fermi-LAT, and H.E.S.S. The use of these instruments allows us to cover a broad energy range, which is important for disentangling the different radiative mechanisms. The source, observed from June 2013 to October 2013, was found in a low flux state with respect to previous observations but exhibited highly significant flux variability in the X-rays. The high-energy end of the synchrotron spectrum can be traced up to 40 keV without significant contamination by high-energy emission. A one-zone synchrotron self-Compton model was used to reproduce the broadband flux of the source for all the observations presented here but failed for previous observations made in April 2013. A lepto-hadronic solution was then explored to explain these earlier observational results.
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| 11. |
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| 12. |
- Akiyama, Kazunori, et al.
(author)
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First Sagittarius A* Event Horizon Telescope Results. II. EHT and Multiwavelength Observations, Data Processing, and Calibration
- 2022
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In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
-
Journal article (peer-reviewed)abstract
- We present Event Horizon Telescope (EHT) 1.3 mm measurements of the radio source located at the position of the supermassive black hole Sagittarius A* (Sgr A*), collected during the 2017 April 5-11 campaign. The observations were carried out with eight facilities at six locations across the globe. Novel calibration methods are employed to account for Sgr A*'s flux variability. The majority of the 1.3 mm emission arises from horizon scales, where intrinsic structural source variability is detected on timescales of minutes to hours. The effects of interstellar scattering on the image and its variability are found to be subdominant to intrinsic source structure. The calibrated visibility amplitudes, particularly the locations of the visibility minima, are broadly consistent with a blurred ring with a diameter of similar to 50 mu as, as determined in later works in this series. Contemporaneous multiwavelength monitoring of Sgr A* was performed at 22, 43, and 86 GHz and at near-infrared and X-ray wavelengths. Several X-ray flares from Sgr A* are detected by Chandra, one at low significance jointly with Swift on 2017 April 7 and the other at higher significance jointly with NuSTAR on 2017 April 11. The brighter April 11 flare is not observed simultaneously by the EHT but is followed by a significant increase in millimeter flux variability immediately after the X-ray outburst, indicating a likely connection in the emission physics near the event horizon. We compare Sgr A*'s broadband flux during the EHT campaign to its historical spectral energy distribution and find that both the quiescent emission and flare emission are consistent with its long-term behavior.
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| 13. |
- Zheng, TH, et al.
(author)
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Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease
- 2021
-
In: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 70:8, s. 1538-1549
-
Journal article (peer-reviewed)abstract
- Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date.DesignWe conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry.ResultsWe demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix.ConclusionHEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Pessi, T., et al.
(author)
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A characterization of ASAS-SN core-collapse supernova environments with VLT+MUSE I. Sample selection, analysis of local environments, and correlations with light curve properties
- 2023
-
In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 677
-
Journal article (peer-reviewed)abstract
- Context. The analysis of core-collapse supernova (CCSN) environments can provide important information on the life cycle of massive stars and constrain the progenitor properties of these powerful explosions. The MUSE instrument at the Very Large Telescope (VLT) enables detailed local environment constraints of the progenitors of large samples of CCSNe. Using a homogeneous SN sample from the All-Sky Automated Survey for Supernovae (ASAS-SN) survey, an untargeted and spectroscopically complete transient survey, has enabled us to perform a minimally biased statistical analysis of CCSN environments.Aims. We analyze 111 galaxies observed by MUSE that hosted 112 CCSNe – 78 II, nine IIn, seven IIb, four Ic, seven Ib, three Ibn, two Ic-BL, one ambiguous Ibc, and one superluminous SN – detected or discovered by the ASAS-SN survey between 2014 and 2018. The majority of the galaxies were observed by the All-weather MUse Supernova Integral field Nearby Galaxies (AMUSING) survey. Here we analyze the immediate environment around the SN locations and compare the properties between the different CCSN types and their light curves.Methods. We used stellar population synthesis and spectral fitting techniques to derive physical parameters for all H II regions detected within each galaxy, including the star formation rate (SFR), Hα equivalent width (EW), oxygen abundance, and extinction.Results. We found that stripped-envelope supernovae (SESNe) occur in environments with a higher median SFR, Hα EW, and oxygen abundances than SNe II and SNe IIn/Ibn. Most of the distributions have no statistically significant differences, except between oxygen abundance distributions of SESNe and SNe II, and between Hα EW distributions of SESNe and SNe II. The distributions of SNe II and IIn are very similar, indicating that these events explode in similar environments. For the SESNe, SNe Ic have higher median SFRs, Hα EWs, and oxygen abundances than SNe Ib. SNe IIb have environments with similar SFRs and Hα EWs to SNe Ib, and similar oxygen abundances to SNe Ic. We also show that the postmaximum decline rate, s, of SNe II correlates with the Hα EW, and that the luminosity and the Δm15 parameter of SESNe correlate with the oxygen abundance, Hα EW, and SFR at their environments. This suggests a connection between the explosion mechanisms of these events to their environment properties.
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| 18. |
- Ramonet, M., et al.
(author)
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The fingerprint of the summer 2018 drought in Europe on ground-based atmospheric CO 2 measurements : Atmospheric CO 2 anomaly
- 2020
-
In: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 375:1810
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Journal article (peer-reviewed)abstract
- During the summer of 2018, a widespread drought developed over Northern and Central Europe. The increase in temperature and the reduction of soil moisture have influenced carbon dioxide (CO 2) exchange between the atmosphere and terrestrial ecosystems in various ways, such as a reduction of photosynthesis, changes in ecosystem respiration, or allowing more frequent fires. In this study, we characterize the resulting perturbation of the atmospheric CO 2 seasonal cycles. 2018 has a good coverage of European regions affected by drought, allowing the investigation of how ecosystem flux anomalies impacted spatial CO 2 gradients between stations. This density of stations is unprecedented compared to previous drought events in 2003 and 2015, particularly thanks to the deployment of the Integrated Carbon Observation System (ICOS) network of atmospheric greenhouse gas monitoring stations in recent years. Seasonal CO 2 cycles from 48 European stations were available for 2017 and 2018. Earlier data were retrieved for comparison from international databases or national networks. Here, we show that the usual summer minimum in CO 2 due to the surface carbon uptake was reduced by 1.4 ppm in 2018 for the 10 stations located in the area most affected by the temperature anomaly, mostly in Northern Europe. Notwithstanding, the CO 2 transition phases before and after July were slower in 2018 compared to 2017, suggesting an extension of the growing season, with either continued CO 2 uptake by photosynthesis and/or a reduction in respiration driven by the depletion of substrate for respiration inherited from the previous months due to the drought. For stations with sufficiently long time series, the CO 2 anomaly observed in 2018 was compared to previous European droughts in 2003 and 2015. Considering the areas most affected by the temperature anomalies, we found a higher CO 2 anomaly in 2003 (+3 ppm averaged over 4 sites), and a smaller anomaly in 2015 (+1 ppm averaged over 11 sites) compared to 2018. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.
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| 19. |
- Angelbratt, Jon, 1981, et al.
(author)
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A new method to detect long term trends of methane (CH4) and nitrous oxide (N2O) total columns measured within the NDACC ground-based high resolution solar FTIR network
- 2011
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In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:13, s. 6167-6183
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Journal article (peer-reviewed)abstract
- Total columns measured with the ground-based solar FTIR technique are highly variable in time due to atmospheric chemistry and dynamics in the atmosphere above the measurement station. In this paper, a multiple regression model with anomalies of air pressure, total columns of hydrogen fluoride (HF) and carbon monoxide (CO) and tropopause height are used to reduce the variability in the methane (CH(4)) and nitrous oxide (N(2)O) total columns to estimate reliable linear trends with as small uncertainties as possible. The method is developed at the Harestua station (60 degrees N, 11 degrees E, 600 ma.s.l.) and used on three other European FTIR stations, i.e. Jungfraujoch (47 degrees N, 8 degrees E, 3600 ma.s.l.), Zugspitze (47 degrees N, 11 degrees E, 3000 ma.s.l.), and Kiruna (68 degrees N, 20 degrees E, 400 ma.s.l.). Linear CH(4) trends between 0.13 +/- 0.01-0.25 +/- 0.02% yr(-1) were estimated for all stations in the 1996-2009 period. A piecewise model with three separate linear trends, connected at change points, was used to estimate the short term fluctuations in the CH(4) total columns. This model shows a growth in 1996-1999 followed by a period of steady state until 2007. From 2007 until 2009 the atmospheric CH(4) amount increases between 0.57 +/- 0.22-1.15 +/- 0.17% yr(-1). Linear N(2)O trends between 0.19 +/- 0.01-0.40 +/- 0.02% yr(-1) were estimated for all stations in the 1996-2007 period, here with the strongest trend at Harestua and Kiruna and the lowest at the Alp stations. From the N(2)O total columns crude tropospheric and stratospheric partial columns were derived, indicating that the observed difference in the N(2)O trends between the FTIR sites is of stratospheric origin. This agrees well with the N(2)O measurements by the SMR instrument onboard the Odin satellite showing the highest trends at Harestua, 0.98 +/- 0.28% yr(-1), and considerably smaller trends at lower latitudes, 0.27 +/- 0.25% yr(-1). The multiple regression model was compared with two other trend methods, the ordinary linear regression and a Bootstrap algorithm. The multiple regression model estimated CH(4) and N(2)O trends that differed up to 31% compared to the other two methods and had uncertainties that were up to 300% lower. Since the multiple regression method were carefully validated this stresses the importance to account for variability in the total columns when estimating trend from solar FTIR data.
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| 20. |
- Angelbratt, Jon, 1981, et al.
(author)
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Carbon monoxide (CO) and ethane (C2H6) trends from ground-based solar FTIR measurements at six European stations, comparison and sensitivity analysis with the EMEP model
- 2011
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In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:17, s. 9253-9269
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Journal article (peer-reviewed)abstract
- Trends in the CO and C(2)H(6) partial columns (similar to 0-15 km) have been estimated from four European ground-based solar FTIR (Fourier Transform InfraRed) stations for the 1996-2006 time period. The CO trends from the four stations Jungfraujoch, Zugspitze, Harestua and Kiruna have been estimated to -0.45 +/- 0.16%yr(-1), -1.00 +/- 0.24%yr(-1), -0.62 +/- 0.19%yr(-1) and -0.61 +/- 0.16%yr(-1), respectively. The corresponding trends for C(2)H(6) are -1.51 +/- 0.23%yr(-1), -2.11 +/- 0.30%yr(-1), -1.09 +/- 0.25%yr(-1) and -1.14 +/- 0.18%yr(-1). All trends are presented with their 2-sigma confidence intervals. To find possible reasons for the CO trends, the global-scale EMEP MSC-W chemical transport model has been used in a series of sensitivity scenarios. It is shown that the trends are consistent with the combination of a 20% decrease in the anthropogenic CO emissions seen in Europe and North America during the 1996-2006 period and a 20% increase in the anthropogenic CO emissions in East Asia, during the same time period. The possible impacts of CH(4) and biogenic volatile organic compounds (BVOCs) are also considered. The European and global-scale EMEP models have been evaluated against the measured CO and C(2)H(6) partial columns from Jungfraujoch, Zugspitze, Bremen, Harestua, Kiruna and Ny-Alesund. The European model reproduces, on average the measurements at the different sites fairly well and within 10-22% deviation for CO and 14-31% deviation for C(2)H(6). Their seasonal amplitude is captured within 6-35% and 9-124% for CO and C(2)H(6), respectively. However, 61-98% of the CO and C(2)H(6) partial columns in the European model are shown to arise from the boundary conditions, making the global-scale model a more suitable alternative when modeling these two species. In the evaluation of the global model the average partial columns for 2006 are shown to be within 1-9% and 37-50% of the measurements for CO and C(2)H(6), respectively. The global model sensitivity for assumptions made in this paper is also analyzed.
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| 21. |
- Botticella, M. T., et al.
(author)
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Supernova 2009kf : An Ultraviolet Bright Type IIP Supernova Discovered with Pan-STARRS 1 and GALEX
- 2010
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 717, s. L52-L56
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Journal article (peer-reviewed)abstract
- We present photometric and spectroscopic observations of a luminous Type IIP Supernova (SN) 2009kf discovered by the Pan-STARRS 1 (PS1) survey and also detected by the Galaxy Evolution Explorer. The SN shows a plateau in its optical and bolometric light curves, lasting approximately 70 days in the rest frame, with an absolute magnitude of M V = -18.4 mag. The P-Cygni profiles of hydrogen indicate expansion velocities of 9000 km s-1 at 61 days after discovery which is extremely high for a Type IIP SN. SN 2009kf is also remarkably bright in the near-ultraviolet (NUV) and shows a slow evolution 10-20 days after optical discovery. The NUV and optical luminosity at these epochs can be modeled with a blackbody with a hot effective temperature (T ~ 16,000 K) and a large radius (R ~ 1 × 1015 cm). The bright bolometric and NUV luminosity, the light curve peak and plateau duration, the high velocities, and temperatures suggest that 2009kf is a Type IIP SN powered by a larger than normal explosion energy. Recently discovered high-z SNe (0.7 < z < 2.3) have been assumed to be IIn SNe, with the bright UV luminosities due to the interaction of SN ejecta with a dense circumstellar medium. UV-bright SNe similar to SN 2009kf could also account for these high-z events, and its absolute magnitude M NUV = -21.5 ± 0.5 mag suggests such SNe could be discovered out to z ~ 2.5 in the PS1 survey.
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| 22. |
- Cederroth, CR, et al.
(author)
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Medicine in the Fourth Dimension
- 2019
-
In: Cell metabolism. - : Elsevier BV. - 1932-7420 .- 1550-4131. ; 30:2, s. 238-250
-
Journal article (peer-reviewed)
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| 23. |
- Evans, P. A., et al.
(author)
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Swift and NuSTAR observations of GW170817 : Detection of a blue kilonova
- 2017
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 358:6370, s. 1565-1569
-
Journal article (peer-reviewed)abstract
- With the first direct detection of merging black holes in 2015, the era of gravitational wave (GW) astrophysics began. A complete picture of compact object mergers, however, requires the detection of an electromagnetic (EM) counterpart. We report ultraviolet (UV) and x-ray observations by Swift and the Nuclear Spectroscopic Telescope Array of the EM counter part of the binary neutron star merger GW170817. The bright, rapidly fading UV emission indicates a high mass (approximate to 0.03 solar masses) wind-driven outflow with moderate electron fraction (Y-e approximate to 0.27). Combined with the x-ray limits, we favor an observer viewing angle of approximate to 30 degrees away from the orbital rotation axis, which avoids both obscuration from the heaviest elements in the orbital plane and a direct view of any ultrarelativistic, highly collimated ejecta (a gamma-ray burst afterglow).
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| 24. |
- Norin, U., et al.
(author)
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Endophilin A2 deficiency protects rodents from autoimmune arthritis by modulating T cell activation
- 2021
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Journal article (peer-reviewed)abstract
- The introduction of the CTLA-4 recombinant fusion protein has demonstrated therapeutic effects by selectively modulating T-cell activation in rheumatoid arthritis. Here we show, using a forward genetic approach, that a mutation in the SH3gl1 gene encoding the endocytic protein Endophilin A2 is associated with the development of arthritis in rodents. Defective expression of SH3gl1 affects T cell effector functions and alters the activation threshold of autoreactive T cells, thereby leading to complete protection from chronic autoimmune inflammatory disease in both mice and rats. We further show that SH3GL1 regulates human T cell signaling and T cell receptor internalization, and its expression is upregulated in rheumatoid arthritis patients. Collectively our data identify SH3GL1 as a key regulator of T cell activation, and as a potential target for treatment of autoimmune diseases. The autoimmune disorder, rheumatoid arthritis (RA), has been associated with multiple pathophysiological factors. Here the authors show that deficiency in endophilin A2 in rodents protects them from experimental arthritis by altering T cell activation threshold and effector functions, thereby hinting a potential target for RA therapy.
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| 25. |
- Ridker, P. M., et al.
(author)
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Antiinflammatory therapy with canakinumab for atherosclerotic disease
- 2017
-
In: New England Journal of Medicine. - 0028-4793. ; 377:12, s. 1119-1131
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. Copyright © 2017 Massachusetts Medical Society.
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| 26. |
- Sutton, LA, et al.
(author)
-
Comparative analysis of targeted next-generation sequencing panels for the detection of gene mutations in chronic lymphocytic leukemia: an ERIC multi-center study
- 2021
-
In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 106:3, s. 682-691
-
Journal article (peer-reviewed)abstract
- Next-generation sequencing (NGS) has transitioned from research to clinical routine, yet the comparability of different technologies for mutation profiling remains an open question. We performed a European multicenter (n=6) evaluation of three amplicon-based NGS assays targeting 11 genes recurrently mutated in chronic lymphocytic leukemia. Each assay was assessed by two centers using 48 pre-characterized chronic lymphocytic leukemia samples; libraries were sequenced on the Illumina MiSeq instrument and bioinformatics analyses were centralized. Across all centers the median percentage of target reads ≥100x ranged from 94.2-99.8%. To rule out assay-specific technical variability, we first assessed variant calling at the individual assay level i.e. pairwise analysis of variants detected amongst partner centers. After filtering for variants present in the paired normal sample and removal of PCR/sequencing artefacts, the panels achieved 96.2% (Multiplicom), 97.7% (TruSeq) and 90% (HaloPlex) concordance at a VAF >0.5%. Reproducibility was assessed by looking at the inter-laboratory variation in detecting mutations and 107/115 (93% concordance) of mutations were detected by all 6 centers, while the remaining 8/115 (7%) variants were undetected by a single center and 6/8 of these variants concerned minor subclonal mutations (VAF <5%). We sought to investigate low-frequency mutations further by using a high-sensitivity assay containing unique molecular identifiers, which confirmed the presence of several minor subclonal mutations. Thus, while amplicon-based approaches can be adopted for somatic mutation detection with VAFs >5%, after rigorous validation, the use of unique molecular identifiers may be necessary to reach a higher sensitivity and ensure consistent and accurate detection of low-frequency variants.
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| 27. |
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| 28. |
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| 29. |
- Baijens, Laura W J, et al.
(author)
-
European society for swallowing disorders - European union geriatric medicine society white paper : Oropharyngeal dysphagia as a geriatric syndrome
- 2016
-
In: Clinical Interventions in Aging. - 1176-9092. ; 11, s. 1403-1428
-
Research review (peer-reviewed)abstract
- This position document has been developed by the Dysphagia Working Group, a committee of members from the European Society for Swallowing Disorders and the European Union Geriatric Medicine Society, and invited experts. It consists of 12 sections that cover all aspects of clinical management of oropharyngeal dysphagia (OD) related to geriatric medicine and discusses prevalence, quality of life, and legal and ethical issues, as well as health economics and social burden. OD constitutes impaired or uncomfortable transit of food or liquids from the oral cavity to the esophagus, and it is included in the World Health Organization’s classification of diseases. It can cause severe complications such as malnutrition, dehydration, respiratory infections, aspiration pneumonia, and increased readmissions, institutionalization, and morbimortality. OD is a prevalent and serious problem among all phenotypes of older patients as oropharyngeal swallow response is impaired in older people and can cause aspiration. Despite its prevalence and severity, OD is still underdiagnosed and untreated in many medical centers. There are several validated clinical and instrumental methods (videofluoroscopy and fiberoptic endoscopic evaluation of swallowing) to diagnose OD, and treatment is mainly based on compensatory measures, although new treatments to stimulate the oropharyngeal swallow response are under research. OD matches the definition of a geriatric syndrome as it is highly prevalent among older people, is caused by multiple factors, is associated with several comorbidities and poor prognosis, and needs a multidimensional approach to be treated. OD should be given more importance and attention and thus be included in all standard screening protocols, treated, and regularly monitored to prevent its main complications. More research is needed to develop and standardize new treatments and management protocols for older patients with OD, which is a challenging mission for our societies.
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| 30. |
- Bellouin, N., et al.
(author)
-
Bounding Global Aerosol Radiative Forcing of Climate Change
- 2020
-
In: Reviews of geophysics. - 8755-1209 .- 1944-9208. ; 58:1
-
Research review (peer-reviewed)abstract
- Aerosols interact with radiation and clouds. Substantial progress made over the past 40 years in observing, understanding, and modeling these processes helped quantify the imbalance in the Earth's radiation budget caused by anthropogenic aerosols, called aerosol radiative forcing, but uncertainties remain large. This review provides a new range of aerosol radiative forcing over the industrial era based on multiple, traceable, and arguable lines of evidence, including modeling approaches, theoretical considerations, and observations. Improved understanding of aerosol absorption and the causes of trends in surface radiative fluxes constrain the forcing from aerosol-radiation interactions. A robust theoretical foundation and convincing evidence constrain the forcing caused by aerosol-driven increases in liquid cloud droplet number concentration. However, the influence of anthropogenic aerosols on cloud liquid water content and cloud fraction is less clear, and the influence on mixed-phase and ice clouds remains poorly constrained. Observed changes in surface temperature and radiative fluxes provide additional constraints. These multiple lines of evidence lead to a 68% confidence interval for the total aerosol effective radiative forcing of -1.6 to -0.6Wm(-2), or -2.0 to -0.4Wm(-2) with a 90% likelihood. Those intervals are of similar width to the last Intergovernmental Panel on Climate Change assessment but shifted toward more negative values. The uncertainty will narrow in the future by continuing to critically combine multiple lines of evidence, especially those addressing industrial-era changes in aerosol sources and aerosol effects on liquid cloud amount and on ice clouds. Plain Language Summary Human activities emit into the atmosphere small liquid and solid particles called aerosols. Those aerosols change the energy budget of the Earth and trigger climate changes, by scattering and absorbing solar and terrestrial radiation and playing important roles in the formation of cloud droplets and ice crystals. But because aerosols are much more varied in their chemical composition and much more heterogeneous in their spatial and temporal distributions than greenhouse gases, their perturbation to the energy budget, called radiative forcing, is much more uncertain. This review uses traceable and arguable lines of evidence, supported by aerosol studies published over the past 40 years, to quantify that uncertainty. It finds that there are two chances out of three that aerosols from human activities have increased scattering and absorption of solar radiation by 14% to 29% and cloud droplet number concentration by 5 to 17% in the period 2005-2015 compared to the year 1850. Those increases exert a radiative forcing that offsets between a fifth and a half of the radiative forcing by greenhouse gases. The degree to which human activities affect natural aerosol levels, and the response of clouds, and especially ice clouds, to aerosol perturbations remain particularly uncertain.
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| 31. |
- Beyer, K., et al.
(author)
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Association and linkage of atopic dermatitis with chromosome 13q12-14 and 5q31-33 markers
- 2000
-
In: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 115:5, s. 906-908
-
Journal article (peer-reviewed)abstract
- Atopic dermatitis is a chronic inflammatory skin disease that affects 10-20% of the population. Linkage of atopy, asthma, allergic rhinitis, and total serum IgE levels to several different chromosomal regions have been described extensively, but little is known about the genetic control of atopic dermatitis. We tested for the association and linkage between atopic dermatitis and five chromosomal regions: 5q31-33, 6p21.3, 12q15-24.1, 13q12-31, and 14q11.2/14q32.1-32.3. Marker analysis was performed in two Caucasian populations: (i) 192 unrelated German children with atopic dermatitis and 59 non-atopic children from a German birth cohort study (MAS '90), parental DNA was tested in 77 of 192 children with atopic dermatitis, (ii) 40 Swedish families with at least one family member with atopic dermatitis selected from the International Study of Asthma and Allergy in Children. Evidence for linkage and allelic association for atopic dermatitis was observed for markers on chromosome 13q12-14 and 5q31-33.
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| 32. |
- Borgatti, Antonella, et al.
(author)
-
Safe and Effective Sarcoma Therapy through Bispecific Targeting of EGFR and uPAR.
- 2017
-
In: Molecular Cancer Therapeutics. - 1535-7163 .- 1538-8514. ; 16:5, s. 956-965
-
Journal article (peer-reviewed)abstract
- Sarcomas differ from carcinomas in their mesenchymal origin. Therapeutic advancements have come slowly so alternative drugs and models are urgently needed. These studies report a new drug for sarcomas that simultaneously targets both tumor and tumor neovasculature. eBAT is a bispecific angiotoxin consisting of truncated, deimmunized Pseudomonas exotoxin fused to epidermal growth factor (EGF) and the amino terminal fragment (ATF) of urokinase. Here, we study the drug in an in vivo "ontarget" companion dog trial since eBAT effectively kills canine hemangiosarcoma (HSA) and human sarcoma cells in vitro. We reasoned the model has value due to the common occurrence of spontaneous sarcomas in dogs and a limited lifespan allowing for rapid accrual and data collection. Splenectomized dogs with minimal residual disease were given one cycle of eBAT followed by adjuvant doxorubicin in an adaptive dose-finding, phase I-II study of 23 dogs with spontaneous, stage I-II, splenic HSA. eBAT improved 6-month survival from <40% in a comparison population to ~70% in dogs treated at a biologically active dose (50 µg/kg). Six dogs were long-term survivors, living >450 days. eBAT abated expected toxicity associated with EGFR-targeting, a finding supported by mouse studies. Urokinase plasminogen activator receptor (uPAR) and EGFR are targets for human sarcomas, so thorough evaluation is crucial for validation of the dog model. Thus, we validated these markers for human sarcoma targeting in the study of 212 human and 97 canine sarcoma samples. Our results support further translation of eBAT for human patients with sarcomas and perhaps other EGFR-expressing malignancies.
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| 33. |
- Borodina, I., et al.
(author)
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Establishing a synthetic pathway for high-level production of 3-hydroxypropionic acid in Saccharomyces cerevisiae via beta-alanine
- 2015
-
In: Metabolic Engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 27, s. 57-64
-
Journal article (peer-reviewed)abstract
- Microbial fermentation of renewable feedstocks into plastic monomers can decrease our fossil dependence and reduce global CO2 emissions. 3-Hydroxypropionic acid (3HP) is a potential chemical building block for sustainable production of superabsorbent polymers and acrylic plastics. With the objective of developing Saccharolnyces cerevisiae as an efficient cell factory for high-level production of 3HP, we identified the beta-alanine biosynthetic route as the most economically attractive according to the metabolic modeling. We engineered and optimized a synthetic pathway for de novo biosynthesis of beta-alanine and its subsequent conversion into 3HP using a novel beta-alanine-pyruvate aminotransferase discovered in Bacillus cereus. The final strain produced 3HP at a titer of 13.7 +/- 0.3 g L-1 with a 0.14 +/- 0.0 C-mol C-mol(-1) yield on glucose in 80 h in controlled fed-batch fermentation in mineral medium at pH 5, and this work therefore lays the basis for developing a process for biological 3HP production.
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| 34. |
- Chiodin, G, et al.
(author)
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High surface IgM levels associate with shorter response to ibrutinib and BTK bypass in patients with CLL
- 2022
-
In: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 6:18, s. 5494-5504
-
Journal article (peer-reviewed)abstract
- Chronic lymphocytic leukemia (CLL) cells have variably low surface IgM (sIgM) levels/signaling capacity, influenced by chronic antigen engagement at tissue sites. Within these low levels, CLL with relatively high sIgM (CLLhigh) progresses more rapidly than CLL with low sIgM (CLLlow). During ibrutinib therapy, surviving CLL cells redistribute into the peripheral blood and can recover sIgM expression. Return of CLL cells to tissue may eventually recur, where cells with high sIgM could promote tumor growth. We analyzed time to new treatment (TTNT) following ibrutinib in 70 patients with CLL (median follow-up of 66 months) and correlated it with pretreatment sIgM levels and signaling characteristics. Pretreatment sIgM levels correlated with signaling capacity, as measured by intracellular Ca2+ mobilization (iCa2+), in vitro (r = 0.70; P < .0001). High sIgM levels/signaling strongly correlated with short TTNT (P < .05), and 36% of patients with CLLhigh vs 8% of patients with CLLlow progressed to require a new treatment. In vitro, capacity of ibrutinib to inhibit sIgM-mediated signaling inversely correlated with pretherapy sIgM levels (r = −0.68; P = .01) or iCa2+ (r = −0.71; P = .009). In patients, sIgM-mediated iCa2+ and ERK phosphorylation levels were reduced by ibrutinib therapy but not abolished. The residual signaling capacity downstream of BTK was associated with high expression of sIgM, whereas it was minimal when sIgM expression was low (P < .05). These results suggested that high sIgM levels facilitated CLL cell resistance to ibrutinib in patients. The CLL cells, surviving in the periphery with high sIgM expression, include a dangerous fraction that is able to migrate to tissue and receive proliferative stimuli, which may require targeting by combined approaches.
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| 35. |
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| 36. |
- Forster, T, et al.
(author)
-
Cetuximab in Pancreatic Cancer Therapy: A Systematic Review and Meta-Analysis
- 2020
-
In: Oncology. - : S. Karger AG. - 1423-0232 .- 0030-2414. ; 98:1, s. 53-60
-
Journal article (peer-reviewed)abstract
- <b><i>Introduction:</i></b> The present study evaluated the potential benefit of adding cetuximab to neoadjuvant, adjuvant, or palliative standard therapy for pancreatic cancer. <b><i>Methods:</i></b> A systematic literature search was performed in MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL). Only randomised controlled trials (RCTs) investigating the effect of adding cetuximab to standard chemotherapy in pancreatic cancer were included. Evaluated outcomes were overall survival, progression-free survival, objective response, and toxicity. For overall survival and progression-free survival, hazard ratios (HR) with 95% confidence intervals (CI) were chosen as effect measure. For objective response, odds ratios (OR) with 95% CI were used. Analysis was based on a random effects model. <b><i>Results:</i></b> After screening 568 publications, a total of 4 RCTs with 924 patients were included. In all trials, patients were adequately randomised with balanced intervention and control groups. There was no significant difference in overall survival (HR 1.04; 95% CI: 0.90–1.19; <i>p</i> = 0.60), progression-free survival (HR 1.06; 95% CI: 0.93–1.22; <i>p</i> = 0.36), or objective response (OR 0.99; 95% CI: 0.66 –1.49; <i>p</i> = 0.96) when adding cetuximab to a standard therapy. Toxicity was the same or higher in each of the included trials. According to GRADE, the certainty of the evidence is high. Therefore, adding cetuximab to pancreatic cancer therapy has no clinically relevant benefit. <b><i>Conclusion:</i></b> In the presence of no survival benefit, increased toxicity, and higher costs, a decreased cost-benefit ratio compared to the standard care must be suggested. Conducting further RCTs in unselected pancreatic cancer populations is unlikely to change this conclusion.
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| 37. |
- Freyschlag, Christian F, et al.
(author)
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Imaging practice in low-grade gliomas among European specialized centers and proposal for a minimum core of imaging.
- 2018
-
In: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 139:3, s. 699-711
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers.METHODS: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery.RESULTS: A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI.CONCLUSION: A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of ≤ 3 mm. No common standard could be obtained regarding advanced MRI protocols and PET.IMPORTANCE OF THE STUDY: We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed "minimal core of imaging" in clinical routine will facilitate future cooperative studies.
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| 38. |
- Gezari, S., et al.
(author)
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GALEX and Pan-STARRS1 Discovery of SN IIP 2010aq : The First Few Days After Shock Breakout in a Red Supergiant Star
- 2010
-
In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 720, s. L77-L81
-
Journal article (peer-reviewed)abstract
- We present the early UV and optical light curve of Type IIP supernova (SN) 2010aq at z = 0.0862, and compare it to analytical models for thermal emission following SN shock breakout in a red supergiant star. SN 2010aq was discovered in joint monitoring between the Galaxy Evolution Explorer (GALEX) Time Domain Survey (TDS) in the NUV and the Pan-STARRS1 Medium Deep Survey (PS1 MDS) in the g, r, i, and z bands. The GALEX and Pan-STARRS1 observations detect the SN less than 1 day after the shock breakout, measure a diluted blackbody temperature of 31, 000 ± 6000 K 1 day later, and follow the rise in the UV/optical light curve over the next 2 days caused by the expansion and cooling of the SN ejecta. The high signal-to-noise ratio of the simultaneous UV and optical photometry allows us to fit for a progenitor star radius of 700 ± 200R sun, the size of a red supergiant star. An excess in UV emission two weeks after shock breakout compared with SNe well fitted by model atmosphere-code synthetic spectra with solar metallicity is best explained by suppressed line blanketing due to a lower metallicity progenitor star in SN 2010aq. Continued monitoring of PS1 MDS fields by the GALEX TDS will increase the sample of early UV detections of Type II SNe by an order of magnitude and probe the diversity of SN progenitor star properties.
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| 39. |
- Gilbert, F., et al.
(author)
-
Sediment reworking by the burrowing polychaete Hediste diversicolor modulated by environmental and biological factors across the temperate North Atlantic. A tribute to Gaston Desrosiers
- 2021
-
In: Journal of Experimental Marine Biology and Ecology. - : Elsevier BV. - 0022-0981. ; 541
-
Journal article (peer-reviewed)abstract
- Particle mixing and irrigation of the seabed by benthic fauna (bioturbation) have major impacts on ecosystem functions such as remineralization of organic matter and sediment-water exchange. As a tribute to Prof. Gaston Desrosiers by the Nereis Park association, eighteen laboratories carried out a collaborative experiment to acquire a global snapshot of particle reworking by the polychaete Hediste diversicolor at 16 sites surrounding the Northern Atlantic. Organisms and soft sediments were collected during May - July at different geographical locations and, using a common laboratory protocol, particulate fluorescent tracers (`luminophores') were used to quantify particle transport over a 10-day period. Particle mixing was quantified using the maximum penetration depth of tracers (MPD), particle diffusive coefficients (D-b), and non-local transport coefficients (r). Non-local coefficients (reflecting centimeter scale transport steps) ranged from 0.4 to 15 yr(-1), and were not correlated across sites with any measured biological (biomass, biovolume) or environmental parameters (temperature, grain size, organic matter). Maximum penetration depths (MPD) averaged similar to 10.7 cm (6.5-14.5 cm), and were similar to the global average bioturbation depth inferred from short-lived radiochemical tracers. MPD was also not correlated with measures of size (individual biomass), but increased with grain size and decreased with temperature. Bio-diffusion (D-b) correlated inversely with individual biomass (size) and directly with temperature over the environmental range (Q(10) similar to 1.7; 5-21 degrees C). The transport data were comparable in magnitude to rates reported for localized H. diversicolor populations of similar size, and confirmed some but not all correlations between sediment reworking and biological and environmental variables found in previous studies. The results imply that measures of particle reworking activities of a species from a single location can be generally extrapolated to different populations at similar conditions.
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| 40. |
- Hsiao, E. Y., et al.
(author)
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Carnegie Supernova Project-II : The Near-infrared Spectroscopy Program
- 2019
-
In: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:995
-
Journal article (peer-reviewed)abstract
- Shifting the focus of Type Ia supernova (SN Ia) cosmology to the near infrared (NIR) is a promising way to significantly reduce the systematic errors, as the strategy minimizes our reliance on the empirical width-luminosity relation and uncertain dust laws. Observations in the NIR are also crucial for our understanding of the origins and evolution of these events, further improving their cosmological utility. Any future experiments in the rest-frame NIR will require knowledge of the SN Ia NIR spectroscopic diversity, which is currently based on a small sample of observed spectra. Along with the accompanying paper, Phillips et al., we introduce the Carnegie Supernova Project-II (CSP-II), to follow-up nearby SNe Ia in both the optical and the NIR. In particular, this paper focuses on the CSP-II NIR spectroscopy program, describing the survey strategy, instrumental setups, data reduction, sample characteristics, and future analyses on the data set. In collaboration with the Harvard-Smithsonian Center for Astrophysics (CfA) Supernova Group, we obtained 661 NIR spectra of 157 SNe Ia. Within this sample, 451 NIR spectra of 90 SNe Ia have corresponding CSP-II follow-up light curves. Such a sample will allow detailed studies of the NIR spectroscopic properties of SNe Ia, providing a different perspective on the properties of the unburned material; the radioactive and stable nickel produced; progenitor magnetic fields; and searches for possible signatures of companion stars.
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| 41. |
- Huerta, E. A., et al.
(author)
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Enabling real-time multi-messenger astrophysics discoveries with deep learning
- 2019
-
In: Nature reviews physics. - : Springer Science and Business Media LLC. - 2522-5820. ; 1:10, s. 600-608
-
Research review (peer-reviewed)abstract
- Multi-messenger astrophysics is a fast-growing, interdisciplinary field that combines data, which vary in volume and speed of data processing, from many different instruments that probe the Universe using different cosmic messengers: electromagnetic waves, cosmic rays, gravitational waves and neutrinos. In this Expert Recommendation, we review the key challenges of real-time observations of gravitational wave sources and their electromagnetic and astroparticle counterparts, and make a number of recommendations to maximize their potential for scientific discovery. These recommendations refer to the design of scalable and computationally efficient machine learning algorithms; the cyber-infrastructure to numerically simulate astrophysical sources, and to process and interpret multi-messenger astrophysics data; the management of gravitational wave detections to trigger real-time alerts for electromagnetic and astroparticle follow-ups; a vision to harness future developments of machine learning and cyber-infrastructure resources to cope with the big-data requirements; and the need to build a community of experts to realize the goals of multi-messenger astrophysics. A group of experts suggests ways in which deep learning can be used to enhance the potential for discovery in multi-messenger astrophysics.
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| 42. |
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| 43. |
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| 44. |
- Kim, Jong Hyuk, et al.
(author)
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Genomically Complex Human Angiosarcoma and Canine Hemangiosarcoma Establish Convergent Angiogenic Transcriptional Programs Driven by Novel Gene Fusions
- 2021
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In: Molecular Cancer Research. - : American Association For Cancer Research (AACR). - 1541-7786 .- 1557-3125. ; 19:5, s. 847-861
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Journal article (peer-reviewed)abstract
- Sporadic angiosarcomas are aggressive vascular sarcomas whose rarity and genomic complexity present significant obstacles in deciphering the pathogenic significance of individual genetic alterations. Numerous fusion genes have been identified across multiple types of cancers, but their existence and significance remain unclear in sporadic angiosarcomas. In this study, we leveraged RNA-sequencing data from 13 human angiosarcomas and 76 spontaneous canine hemangiosarcomas to identify fusion genes associated with spontaneous vascular malignancies. Ten novel protein-coding fusion genes, including TEX2-PECAM1 and ATP8A2-FLT1, were identified in seven of the 13 human tumors, with two tumors showing mutations of TP53. HRAS and NRAS mutations were found in angiosarcomas without fusions or TP53 mutations. We found 15 novel protein-coding fusion genes including MYO16-PTK2, GABRA3-FLT1, and AKT3-XPNPEP1 in 11 of the 76 canine hemangiosarcomas; these fusion genes were seen exclusively in tumors of the angiogenic molecular subtype that contained recurrent mutations in TP53, PIK3CA, PIK3R1, and NRAS. In particular, fusion genes and mutations of TP53 cooccurred in tumors with higher frequency than expected by random chance, and they enriched gene signatures predicting activation of angiogenic pathways. Comparative transcriptomic analysis of human angiosarcomas and canine hemangiosarcomas identified shared molecular signatures associated with activation of PI3K/AKT/mTOR pathways. Our data suggest that genome instability induced by TP53 mutations might create a predisposition for fusion events that may contribute to tumor progression by promoting selection and/or enhancing fitness through activation of convergent angiogenic pathways in this vascular malignancy. Implications: This study shows that, while drive events of malignant vasoformative tumors of humans and dogs include diverse mutations and stochastic rearrangements that create novel fusion genes, convergent transcriptional programs govern the highly conserved morphologic organization and biological behavior of these tumors in both species.
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| 45. |
- Loeb, Norman G., et al.
(author)
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New Generation of Climate Models Track Recent Unprecedented Changes in Earth's Radiation Budget Observed by CERES
- 2020
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In: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 47:5
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Journal article (peer-reviewed)abstract
- We compare top-of-atmosphere (TOA) radiative fluxes observed by the Clouds and the Earth's Radiant Energy System (CERES) and simulated by seven general circulation models forced with observed sea-surface temperature (SST) and sea-ice boundary conditions. In response to increased SSTs along the equator and over the eastern Pacific (EP) following the so-called global warming hiatus of the early 21st century, simulated TOA flux changes are remarkably similar to CERES. Both show outgoing shortwave and longwave TOA flux changes that largely cancel over the west and central tropical Pacific, and large reductions in shortwave flux for EP low-cloud regions. A model's ability to represent changes in the relationship between global mean net TOA flux and surface temperature depends upon how well it represents shortwave flux changes in low-cloud regions, with most showing too little sensitivity to EP SST changes, suggesting a pattern effect that may be too weak compared to observations.
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| 46. |
- Mandonnet, Emmanuel, et al.
(author)
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Survey on current practice within the European Low-Grade Glioma Network : where do we stand and what is the next step?
- 2017
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In: Neuro-Oncology Practice. - : OXFORD UNIV PRESS. - 2054-2577 .- 2054-2585. ; 4:4, s. 241-247
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Journal article (peer-reviewed)abstract
- Diffuse low-grade glioma form a rare entity affecting young people. Despite advances in surgery, chemotherapy, and radiation therapy, diffuse low-grade glioma are still incurable. According to current guidelines, maximum safe resection, when feasible, is the first line of treatment. Apart from surgery, all other treatment modalities (temozolomide, procarbazine-CCNU-vincristine regimen, and radiation therapy) are handled very differently among different teams, and this in spite of recent results of several phase 3 studies. Based on a European survey, this paper aimed to get a picture of this heterogeneity in diffuse low-grade glioma management, to identify clinically relevant questions raised by this heterogeneity of practice, and to propose new methodological frameworks to address these questions.
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| 47. |
- McGinn, Steven, et al.
(author)
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New Technologies for DNA analysis-A review of the READNA Project.
- 2016
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In: New Biotechnology. - : Elsevier BV. - 1876-4347 .- 1871-6784.
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Research review (peer-reviewed)abstract
- The REvolutionary Approaches and Devices for Nucleic Acid analysis (READNA) project received funding from the European Commission for 4 1/2 years. The objectives of the project revolved around technological developments in nucleic acid analysis. The project partners have discovered, created and developed a huge body of insights into nucleic acid analysis, ranging from improvements and implementation of current technologies to the most promising sequencing technologies that constitute a 3(rd) and 4(th) generation of sequencing methods with nanopores and in situ sequencing, respectively.
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| 48. |
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| 49. |
- Quax, Tessa E. F., et al.
(author)
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Differential Translation Tunes Uneven Production of Operon-Encoded Proteins
- 2013
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 4:5, s. 938-944
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Journal article (peer-reviewed)abstract
- Clustering of functionally related genes in operons allows for coregulated gene expression in prokaryotes. This is advantageous when equal amounts of gene products are required. Production of protein complexes with an uneven stoichiometry, however, requires tuning mechanisms to generate subunits in appropriate relative quantities. Using comparative genomic analysis, we show that differential translation is a key determinant of modulated expression of genes clustered in operons and that codon bias generally is the best in silico indicator of unequal protein production. Variable ribosome density profiles of polycistronic transcripts correlate strongly with differential translation patterns. In addition, we provide experimental evidence that de novo initiation of translation can occur at intercistronic sites, allowing for differential translation of any gene irrespective of its position on a polycistronic messenger. Thus, modulation of translation efficiency appears to be a universal mode of control in bacteria and archaea that allows for differential production of operon-encoded proteins.
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| 50. |
- Sediva, A, et al.
(author)
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Europe Immunoglobulin Map
- 2014
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In: JOURNAL OF CLINICAL IMMUNOLOGY. - : Oxford University Press (OUP). - 0271-9142. ; 178178 Suppl 1, s. 141-143
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Conference paper (other academic/artistic)
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