1. |
- Schael, S, et al.
(author)
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Precision electroweak measurements on the Z resonance
- 2006
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In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Research review (peer-reviewed)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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2. |
- Schael, S., et al.
(author)
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Electroweak measurements in electron positron collisions at W-boson-pair energies at LEP
- 2013
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In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 532:4, s. 119-244
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Research review (peer-reviewed)abstract
- Electroweak measurements performed with data taken at the electron positron collider LEP at CERN from 1995 to 2000 are reported. The combined data set considered in this report corresponds to a total luminosity of about 3 fb(-1) collected by the four LEP experiments ALEPH, DELPHI, 13 and OPAL, at centre-of-mass energies ranging from 130 GeV to 209 GeV. Combining the published results of the four LEP experiments, the measurements include total and differential cross-sections in photon-pair, fermion-pair and four-fermion production, the latter resulting from both double-resonant WW and ZZ production as well as singly resonant production. Total and differential cross-sections are measured precisely, providing a stringent test of the Standard Model at centre-of-mass energies never explored before in electron positron collisions. Final-state interaction effects in four-fermion production, such as those arising from colour reconnection and Bose Einstein correlations between the two W decay systems arising in WW production, are searched for and upper limits on the strength of possible effects are obtained. The data are used to determine fundamental properties of the W boson and the electroweak theory. Among others, the mass and width of the W boson, m(w) and Gamma(w), the branching fraction of W decays to hadrons, B(W -> had), and the trilinear gauge-boson self-couplings g(1)(Z), K-gamma and lambda(gamma), are determined to be: m(w) = 80.376 +/- 0.033 GeV Gamma(w) = 2.195 +/- 0.083 GeV B(W -> had) = 67.41 +/- 0.27% g(1)(Z) = 0.984(-0.020)(+0.018) K-gamma - 0.982 +/- 0.042 lambda(gamma) = 0.022 +/- 0.019. (C) 2013 Elsevier B.V. All rights reserved.
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3. |
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4. |
- Hudson, Lawrence N, et al.
(author)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Journal article (peer-reviewed)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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5. |
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6. |
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7. |
- Sartelli, Massimo, et al.
(author)
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Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
- 2023
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In: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
-
Research review (peer-reviewed)abstract
- Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
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8. |
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9. |
- Schweinsberg, Martin, et al.
(author)
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Same data, different conclusions : Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis
- 2021
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In: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 165, s. 228-249
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Journal article (peer-reviewed)abstract
- In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists' gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for orga-nizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed.
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10. |
- Osinski, V., et al.
(author)
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In vivo liposomal delivery of PPAR alpha/gamma dual agonist tesaglitazar in a model of obesity enriches macrophage targeting and limits liver and kidney drug effects
- 2020
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In: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 10:2, s. 585-601
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Journal article (peer-reviewed)abstract
- Macrophages are important regulators of obesity-associated inflammation and PPAR alpha and -gamma agonism in macrophages has anti-inflammatory effects. In this study, we tested the efficacy with which liposomal delivery could target the PPAR alpha/gamma dual agonist tesaglitazar to macrophages while reducing drug action in common sites of drug toxicity: the liver and kidney, and whether tesaglitazar had anti-inflammatory effects in an in vivo model of obesity-associated dysmetabolism. Methods: Male leptin-deficient (ob/ob) mice were administered tesaglitazar or vehicle for one week in a standard oral formulation or encapsulated in liposomes. Following the end of treatment, circulating metabolic parameters were measured and pro-inflammatory adipose tissue macrophage populations were quantified by flow cytometry. Cellular uptake of liposomes in tissues was assessed using immunofluorescence and a broad panel of cell subset markers by flow cytometry. Finally, PPAR alpha/gamma gene target expression levels in the liver, kidney, and sorted macrophages were quantified to determine levels of drug targeting to and drug action in these tissues and cells. Results: Administration of a standard oral formulation of tesaglitazar effectively treated symptoms of obesity-associated dysmetabolism and reduced the number of pro-inflammatory adipose tissue macrophages. Macrophages are the major cell type that took up liposomes with many other immune and stromal cell types taking up liposomes to a lesser extent. Liposome delivery of tesaglitazar did not have effects on inflammatory macrophages nor did it improve metabolic parameters to the extent of a standard oral formulation. Liposomal delivery did, however, attenuate effects on liver weight and liver and kidney expression of PPAR alpha and -gamma gene targets compared to oral delivery. Conclusions: These findings reveal for the first time that tesaglitazar has anti-inflammatory effects on adipose tissue macrophage populations in vivo. These data also suggest that while nanoparticle delivery reduced off-target effects, yet the lack of tesaglitazar actions in non-targeted cells such (as hepatocytes and adipocytes) and the uptake of drug-loaded liposomes in many other cell types, albeit to a lesser extent, may have impacted overall therapeutic efficacy. This fulsome analysis of cellular uptake of tesaglitazar-loaded liposomes provides important lessons for future studies of liposome drug delivery.
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11. |
- Aharonian, Felix, et al.
(author)
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Atmospheric gas dynamics in the Perseus cluster observed with Hitomi
- 2018
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In: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
-
Journal article (peer-reviewed)abstract
- Extending the earlier measurements reported in Hitomi collaboration (2016, Nature, 535, 117), we examine the atmospheric gas motions within the central 100 kpc of the Perseus cluster using observations obtained with the Hitomi satellite. After correcting for the point spread function of the telescope and using optically thin emission lines, we find that the line-of-sight velocity dispersion of the hot gas is remarkably low and mostly uniform. The velocity dispersion reaches a maxima of approximately 200 km s(-1) toward the central active galactic nucleus (AGN) and toward the AGN inflated northwestern ghost bubble. Elsewhere within the observed region, the velocity dispersion appears constant around 100 km s(-1). We also detect a velocity gradient with a 100 km s(-1) amplitude across the cluster core, consistent with large-scale sloshing of the core gas. If the observed gas motions are isotropic, the kinetic pressure support is less than 10% of the thermal pressure support in the cluster core. The well-resolved, optically thin emission lines have Gaussian shapes, indicating that the turbulent driving scale is likely below 100 kpc, which is consistent with the size of the AGN jet inflated bubbles. We also report the first measurement of the ion temperature in the intracluster medium, which we find to be consistent with the electron temperature. In addition, we present a new measurement of the redshift of the brightest cluster galaxy NGC 1275.
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12. |
- Aharonian, Felix, et al.
(author)
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Atomic data and spectral modeling constraints from high-resolution X-ray observations of the Perseus cluster with Hitomi
- 2018
-
In: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
-
Journal article (peer-reviewed)abstract
- The Hitomi Soft X-ray Spectrometer spectrum of the Perseus cluster, with similar to 5 eV resolution in the 2-9 keV band, offers an unprecedented benchmark of the atomic modeling and database for hot collisional plasmas. It reveals both successes and challenges of the current atomic data and models. The latest versions of AtomDB/APEC (3.0.8), SPEX (3.03.00), and CHIANTI (8.0) all provide reasonable fits to the broad-band spectrum, and are in close agreement on best-fit temperature, emission measure, and abundances of a few elements such as Ni. For the Fe abundance, the APEC and SPEX measurements differ by 16%, which is 17 times higher than the statistical uncertainty. This is mostly attributed to the differences in adopted collisional excitation and dielectronic recombination rates of the strongest emission lines. We further investigate and compare the sensitivity of the derived physical parameters to the astrophysical source modeling and instrumental effects. The Hitomi results show that accurate atomic data and models are as important as the astrophysical modeling and instrumental calibration aspects. Substantial updates of atomic databases and targeted laboratory measurements are needed to get the current data and models ready for the data from the next Hitomi-level mission.
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13. |
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14. |
- Aharonian, Felix, et al.
(author)
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Detection of polarized gamma-ray emission from the Crab nebula with the Hitomi Soft Gamma-ray Detector
- 2018
-
In: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:6
-
Journal article (peer-reviewed)abstract
- We present the results from the Hitomi Soft Gamma-ray Detector (SGD) observation of the Crab nebula. The main part of SGD is a Compton camera, which in addition to being a spectrometer, is capable of measuring polarization of gamma-ray photons. The Crab nebula is one of the brightest X-ray / gamma-ray sources on the sky, and, the only source from which polarized X-ray photons have been detected. SGD observed the Crab nebula during the initial test observation phase of Hitomi. We performed the data analysis of the SGD observation, the SGD background estimation and the SGD Monte Carlo simulations, and, successfully detected polarized gamma-ray emission from the Crab nebula with only about 5 ks exposure time. The obtained polarization fraction of the phase-integrated Crab emission (sum of pulsar and nebula emissions) is (22.1% +/- 10.6%), and, the polarization angle is 110.degrees 7 + 13.degrees 2 /-13.degrees 0 in the energy range of 60-160 keV (The errors correspond to the 1 sigma deviation). The confidence level of the polarization detection was 99.3%. The polarization angle measured by SGD is about one sigma deviation with the projected spin axis of the pulsar, 124.degrees 0 +/- 0.degrees 1.
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15. |
- Aharonian, Felix, et al.
(author)
-
Glimpse of the highly obscured HMXB IGR J16318-4848 with Hitomi
- 2018
-
In: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
-
Journal article (peer-reviewed)abstract
- We report on a Hitomi observation of IGR J16318-4848, a high-mass X-ray binary system with an extremely strong absorption of N-H similar to 10(24) cm(-2). Previous X-ray studies revealed that its spectrum is dominated by strong fluorescence lines of Fe as well as continuum emission lines. For physical and geometrical insight into the nature of the reprocessing material, we utilized the high spectroscopic resolving power of the X-ray microcalorimeter (the soft X-ray spectrometer: SXS) and the wide-band sensitivity by the soft and hard X-ray imagers (SXI and HXI) aboard Hitomi. Even though the photon counts are limited due to unintended off-axis pointing, the SXS spectrum resolves Fe K alpha(1) and K alpha(2) lines and puts strong constraints on the line centroid and line width. The line width corresponds to a velocity of 160(-70)(+300) km s(-1). This represents the most accurate, and smallest, width measurement of this line made so far from the any X-ray binary, much less than the Doppler broadening and Doppler shift expected from speeds that are characteristic of similar systems. Combined with the K-shell edge energy measured by the SXI and HXI spectra, the ionization state of Fe is estimated to be in the range of Fe I-IV. Considering the estimated ionization parameter and the distance between the X-ray source and the absorber, the density and thickness of the materials are estimated. The extraordinarily strong absorption and the absence of a Compton shoulder component have been confirmed. These characteristics suggest reprocessing materials that are distributed in a narrow solid angle or scattering, primarily by warm free electrons or neutral hydrogen. This measurement was achieved using the SXS detection of 19 photons. It provides strong motivation for follow-up observations of this and other X-ray binaries using the X-ray Astrophysics Recovery Mission and other comparable future instruments.
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16. |
- Aharonian, Felix, et al.
(author)
-
Hitomi observation of radio galaxy NGC 1275 : The first X-ray microcalorimeter spectroscopy of Fe-K alpha line emission from an active galactic nucleus
- 2018
-
In: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
-
Journal article (peer-reviewed)abstract
- The origin of the narrow Fe-K alpha fluorescence line at 6.4 keV from active galactic nuclei has long been under debate; some of the possible sites are the outer accretion disk, the broad line region, a molecular torus, or interstellar/intracluster media. In 2016 February-March, we performed the first X-ray microcalorimeter spectroscopy with the Soft X-ray Spectrometer (SXS) on board the Hitomi satellite of the Fanaroff-Riley type I radio galaxy NGC 1275 at the center of the Perseus cluster of galaxies. With the high-energy resolution of similar to 5 eV at 6 keV achieved by Hitomi/SXS, we detected the Fe-K alpha line with similar to 5.4 sigma significance. The velocity width is constrained to be 500-1600 km s(-1) (FWHM for Gaussian models) at 90% confidence. The SXS also constrains the continuum level from the NGC 1275 nucleus up to similar to 20 keV, giving an equivalent width of similar to 20 eV for the 6.4 keV line. Because the velocity width is narrower than that of the broad H alpha line of similar to 2750 km s(-1), we can exclude a large contribution to the line flux from the accretion disk and the broad line region. Furthermore, we performed pixel map analyses on the Hitomi/SXS data and image analyses on the Chandra archival data, and revealed that the Fe-K alpha line comes from a region within similar to 1.6 kpc of the NGC 1275 core, where an active galactic nucleus emission dominates, rather than that from intracluster media. Therefore, we suggest that the source of the Fe-K alpha line from NGC 1275 is likely a low-covering-fraction molecular torus or a rotating molecular disk which probably extends from a parsec to hundreds of parsecs scale in the active galactic nucleus system.
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17. |
- Aharonian, Felix, et al.
(author)
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Hitomi observations of the LMC SNR N 132 D : Highly redshifted X-ray emission from iron ejecta
- 2018
-
In: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
-
Journal article (peer-reviewed)abstract
- We present Hitomi observations of N 132 D, a young, X-ray bright, O-rich core-collapse supernova remnant in the Large Magellanic Cloud (LMC). Despite a very short observation of only 3.7 ks, the Soft X-ray Spectrometer (SXS) easily detects the line complexes of highly ionized S K and Fe K with 16-17 counts in each. The Fe feature is measured for the first time at high spectral resolution. Based on the plausible assumption that the Fe K emission is dominated by He-like ions, we find that the material responsible for this Fe emission is highly redshifted at similar to 800 km s(-1) compared to the local LMC interstellar medium (ISM), with a 90% credible interval of 50-1500 km s(-1) if a weakly informative prior is placed on possible line broadening. This indicates (1) that the Fe emission arises from the supernova ejecta, and (2) that these ejecta are highly asymmetric, since no blueshifted component is found. The S K velocity is consistent with the local LMC ISM, and is likely from swept-up ISM material. These results are consistent with spatial mapping that shows the He-like Fe concentrated in the interior of the remnant and the S tracing the outer shell. The results also show that even with a very small number of counts, direct velocity measurements from Doppler-shifted lines detected in extended objects like supernova remnants are now possible. Thanks to the very low SXS background of similar to 1 event per spectral resolution element per 100 ks, such results are obtainable during short pointed or slew observations with similar instruments. This highlights the power of high-spectral-resolution imaging observations, and demonstrates the new window that has been opened with Hitomi and will be greatly widened with future missions such as the X-ray Astronomy Recovery Mission (XARM) and Athena.
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18. |
- Aharonian, Felix, et al.
(author)
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Hitomi X-ray observation of the pulsar wind nebula G21.5-0.9
- 2018
-
In: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:3
-
Journal article (peer-reviewed)abstract
- We present results from the Hitomi X-ray observation of a young composite-type supernova remnant (SNR) G21.5-0.9, whose emission is dominated by the pulsar wind nebula (PWN) contribution. The X-ray spectra in the 0.8-80 keV range obtained with the Soft X-ray Spectrometer (SXS), Soft X-ray Imager, and Hard X-ray Imager (HXI) show a significant break in the continuum as previously found with the NuSTAR observation. After taking into account all known emissions from the SNR other than the PWN itself, we find that the Hitomi spectra can be fitted with a broken power law with photon indices of Gamma(1) = 1.74 +/- 0.02 and Gamma(2) = 2.14 +/- 0.01 below and above the break at 7.1 +/- 0.3 keV, which is significantly lower than the NuSTAR result (similar to 9.0 keV). The spectral break cannot be reproduced by time-dependent particle injection one-zone spectral energy distribution models, which strongly indicates that a more complex emission model is needed, as suggested by recent theoretical models. We also search for narrow emission or absorption lines with the SXS, and perform a timing analysis of PSR J1833-1034 with the HXI and the Soft Gamma-ray Detector. No significant pulsation is found from the pulsar. However, unexpectedly, narrow absorption line features are detected in the SXS data at 4.2345 keV and 9.296 keV with a significance of 3.65 sigma. While the origin of these features is not understood, their mere detection opens up a new field of research and was only possible with the high resolution, sensitivity, and ability to measure extended sources provided by an X-ray microcalorimeter.
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19. |
- Aharonian, Felix, et al.
(author)
-
Hitomi X-ray studies of giant radio pulses from the Crab pulsar
- 2018
-
In: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
-
Journal article (peer-reviewed)abstract
- To search for giant X-ray pulses correlated with the giant radio pulses (GRPs) from the Crab pulsar, we performed a simultaneous observation of the Crab pulsar with the X-ray satellite Hitomi in the 2-300 keV band and the Kashima NICT radio telescope in the 1.4-1.7 GHz band with a net exposure of about 2 ks on 2016 March 25, just before the loss of the Hitomi mission. The timing performance of the Hitomi instruments was confirmed to meet the timing requirement and about 1000 and 100 GRPs were simultaneously observed at the main pulse and inter-pulse phases, respectively, and we found no apparent correlation between the giant radio pulses and the X-ray emission in either the main pulse or inter-pulse phase. All variations are within the 2 sigma fluctuations of the X-ray fluxes at the pulse peaks, and the 3 sigma upper limits of variations of main pulse or inter-pulse GRPs are 22% or 80% of the peak flux in a 0.20 phase width, respectively, in the 2-300 keV band. The values for main pulse or inter-pulse GRPs become 25% or 110%, respectively, when the phase width is restricted to the 0.03 phase. Among the upper limits from the Hitomi satellite, those in the 4.5-10 keV and 70-300 keV bands are obtained for the first time, and those in other bands are consistent with previous reports. Numerically, the upper limits of the main pulse and inter-pulse GRPs in the 0.20 phase width are about (2.4 and 9.3) x 10(-11) erg cm(-2), respectively. No significant variability in pulse profiles implies that the GRPs originated from a local place within the magneto-sphere. Although the number of photon-emitting particles should temporarily increase to account for the brightening of the radio emission, the results do not statistically rule out variations correlated with the GRPs, because the possible X-ray enhancement may appear due to a > 0.02% brightening of the pulse-peak flux under such conditions.
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20. |
- Aharonian, Felix, et al.
(author)
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Measurements of resonant scattering in the Perseus Cluster core with Hitomi SXS
- 2018
-
In: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
-
Journal article (peer-reviewed)abstract
- Thanks to its high spectral resolution (similar to 5 eV at 6 keV), the Soft X-ray Spectrometer (SXS) on board Hitomi enables us to measure the detailed structure of spatially resolved emission lines from highly ionized ions in galaxy clusters for the first time. In this series of papers, using the SXS we have measured the velocities of gas motions, metallicities and the multi-temperature structure of the gas in the core of the Perseus Cluster. Here, we show that when inferring physical properties from line emissivities in systems like Perseus, the resonant scattering effect should be taken into account. In the Hitomi waveband, resonant scattering mostly affects the Fe XXV He alpha line (w)-the strongest line in the spectrum. The flux measured by Hitomi in this line is suppressed by a factor of similar to 1.3 in the inner similar to 30 kpc, compared to predictions for an optically thin plasma; the suppression decreases with the distance from the center. The w line also appears slightly broader than other lines from the same ion. The observed distortions of the w line flux, shape, and distance dependence are all consistent with the expected effect of the resonant scattering in the Perseus core. By measuring the ratio of fluxes in optically thick (w) and thin (Fe XXV forbidden, He beta, Ly alpha) lines, and comparing these ratios with predictions from Monte Carlo radiative transfer simulations, the velocities of gas motions have been obtained. The results are consistent with the direct measurements of gas velocities from line broadening described elsewhere in this series, although the systematic and statistical uncertainties remain significant. Further improvements in the predictions of line emissivities in plasma models, and deeper observations with future X-ray missions offering similar or better capabilities to the Hitomi SXS, will enable resonant scattering measurements to provide powerful constraints on the amplitude and anisotropy of cluster gas motions.
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21. |
- Aharonian, Felix, et al.
(author)
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Search for thermal X-ray features from the Crab nebula with the Hitomi soft X-ray spectrometer
- 2018
-
In: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
-
Journal article (peer-reviewed)abstract
- The Crab nebula originated from a core-collapse supernova (SN) explosion observed in 1054 AD. When viewed as a supernova remnant (SNR), it has an anomalously low observed ejecta mass and kinetic energy for an Fe-core-collapse SN. Intensive searches have been made for a massive shell that solves this discrepancy, but none has been detected. An alternative idea is that SN 1054 is an electron-capture (EC) explosion with a lower explosion energy by an order of magnitude than Fe-core-collapse SNe. X-ray imaging searches were performed for the plasma emission from the shell in the Crab outskirts to set a stringent upper limit on the X-ray emitting mass. However, the extreme brightness of the source hampers access to its vicinity. We thus employed spectroscopic technique using the X-ray micro-calorimeter on board the Hitomi satellite. By exploiting its superb energy resolution, we set an upper limit for emission or absorption features from as yet undetected thermal plasma in the 2-12 keV range. We also re-evaluated the existing Chandra and XMM-Newton data. By assembling these results, a new upper limit was obtained for the X-ray plasma mass of less than or similar to 1 M-circle dot for a wide range of assumed shell radius, size, and plasma temperature values both in and out of collisional equilibrium. To compare with the observation, we further performed hydrodynamic simulations of the Crab SNR for two SN models (Fe-core versus EC) under two SN environments (uniform interstellar medium versus progenitor wind). We found that the observed mass limit can be compatible with both SN models if the SN environment has a low density of less than or similar to 0.03 cm(-3) (Fe core) or less than or similar to 0.1 cm(-3) (EC) for the uniform density, or a progenitor wind density somewhat less than that provided by amass loss rate of 10(-5) M-circle dot yr(-1) at 20 km s(-1) for the wind environment.
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22. |
- Aharonian, Felix, et al.
(author)
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Solar abundance ratios of the iron-peak elements in the Perseus cluster
- 2017
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 551:7681, s. 478-
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Journal article (peer-reviewed)abstract
- The metal abundance of the hot plasma that permeates galaxy clusters represents the accumulation of heavy elements produced by billions of supernovae(1). Therefore, X-ray spectroscopy of the intracluster medium provides an opportunity to investigate the nature of supernova explosions integrated over cosmic time. In particular, the abundance of the iron-peak elements (chromium, manganese, iron and nickel) is key to understanding how the progenitors of typical type Ia supernovae evolve and explode(2-6). Recent X-ray studies of the intracluster medium found that the abundance ratios of these elements differ substantially from those seen in the Sun(7-11), suggesting differences between the nature of type Ia supernovae in the clusters and in the Milky Way. However, because the K-shell transition lines of chromium and manganese are weak and those of iron and nickel are very close in photon energy, highresolution spectroscopy is required for an accurate determination of the abundances of these elements. Here we report observations of the Perseus cluster, with statistically significant detections of the resonance emission from chromium, manganese and nickel. Our measurements, combined with the latest atomic models, reveal that these elements have near-solar abundance ratios with respect to iron, in contrast to previous claims. Comparison between our results and modern nucleosynthesis calculations(12-14) disfavours the hypothesis that type Ia supernova progenitors are exclusively white dwarfs with masses well below the Chandrasekhar limit (about 1.4 times the mass of the Sun). The observed abundance pattern of the iron-peak elements can be explained by taking into account a combination of near-and sub-Chandrasekhar-mass type Ia supernova systems, adding to the mounting evidence that both progenitor types make a substantial contribution to cosmic chemical enrichment(5,15,16).
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23. |
- Aharonian, Felix, et al.
(author)
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Temperature structure in the Perseus cluster core observed with Hitomi
- 2018
-
In: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
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Journal article (peer-reviewed)abstract
- The present paper explains the temperature structure of X-ray emitting plasma in the core of the Perseus cluster based on 1.8-20.0 keV data obtained with the Soft X-ray Spectrometer (SXS) on board the Hitomi Observatory. A series of four observations was carried out, with a total effective exposure time of 338 ks that covered a central region of similar to 7' in diameter. SXS was operated with an energy resolution of similar to 5 eV (full width at half maximum) at 5.9 keV. Not only fine structures of K-shell lines in He-like ions, but also transitions from higher principal quantum numbers were clearly resolved from Si through Fe. That enabled us to perform temperature diagnostics using the line ratios of Si, S, Ar, Ca, and Fe, and to provide the first direct measurement of the excitation temperature and ionization temperature in the Perseus cluster. The observed spectrum is roughly reproduced by a single-temperature thermal plasma model in collisional ionization equilibrium, but detailed line-ratio diagnostics reveal slight deviations from this approximation. In particular, the data exhibit an apparent trend of increasing ionization temperature with the atomic mass, as well as small differences between the ionization and excitation temperatures for Fe, the only element for which both temperatures could be measured. The best-fit two-temperature models suggest a combination of 3 and 5 keV gas, which is consistent with the idea that the observed small deviations from a single-temperature approximation are due to the effects of projecting the known radial temperature gradient in the cluster core along the line of sight. A comparison with the Chandra/ACIS and the XMM-Newton/RGS results, on the other hand, suggests that additional lower-temperature components are present in the intracluster medium (ICM), but not detectable with Hitomi/SXS giving its 1.8-20 keV energy band.
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24. |
- Bauknight, D. K., et al.
(author)
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Importance of thorough tissue and cellular level characterization of targeted drugs in the evaluation of pharmacodynamic effects
- 2019
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:11
-
Journal article (peer-reviewed)abstract
- Targeted nanoparticle delivery is a promising strategy for increasing efficacy and limiting side effects of therapeutics. When designing a targeted liposomal formulation, the in vivo biodistribution of the particles must be characterized to determine the value of the targeting approach. Peroxisome proliferator-activated receptor (PPAR) agonists effectively treat metabolic syndrome by decreasing dyslipidemia and insulin resistance but side effects have limited their use, making them a class of compounds that could benefit from targeted liposomal delivery. The adipose targeting sequence peptide (ATS) could fit this role, as it has been shown to bind to adipose tissue endothelium and induce weight loss when delivered conjugated to a pro-apoptotic peptide. To date, however, a full assessment of ATS in vivo biodistribution has not been reported, leaving important unanswered questions regarding the exact mechanisms whereby ATS targeting enhances therapeutic efficacy. We designed this study to evaluate the biodistribution of ATS-conjugated liposomes loaded with the PPARα/γ dual agonist tesaglitazar in leptin-deficient ob/ob mice. The ATS-liposome biodistribution in adipose tissue and other organs was examined at the cellular and tissue level using microscopy, flow cytometry, and fluorescent molecular tomography. Changes in metabolic parameters and gene expression were measured by target and off-target tissue responses to the treatment. Unexpectedly, ATS targeting did not increase liposomal uptake in adipose relative to other tissues, but did increase uptake in the kidneys. Targeting also did not significantly alter metabolic parameters. Analysis of the liposome cellular distribution in the stromal vascular fraction with flow cytometry revealed high uptake by multiple cell types. Our findings highlight the need for thorough study of in vivo biodistribution when evaluating a targeted therapy. © 2019 Bauknight et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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25. |
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26. |
- Leenhardt, R., et al.
(author)
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A guide for assessing the clinical relevance of findings in small bowel capsule endoscopy : analysis of 8064 answers of international experts to an illustrated script questionnaire
- 2021
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In: Clinics and Research in Hepatology and Gastroenterology. - : Elsevier BV. - 2210-7401. ; 45:6
-
Journal article (peer-reviewed)abstract
- Background and aim: Although recommended, the P-score used for assessing the pertinence / relevance of findings seen in small bowel (SB) capsule endoscopy (CE) is based on a low level of knowledge. The aim of this study was to evaluate the clinical relevance of the most frequent SBCE findings through an illustrated script questionnaire. Materials and Methods: Sixteen types of SBCE findings were illustrated four times each in three different settings (occult and overt obscure gastrointestinal bleeding and suspected Crohn's disease), and with a variable number (n = 1/n = 2–5/n ≥ 6), thus providing a questionnaire with 192 scenarios and 576 illustrated questions. Fifteen international experts were asked to rate the finding's relevance for each question as very unlikely (−2) / unlikely (−1) / doubtful (0) / likely (+1) / very likely (+2). The median score (≤−0.75, between -0.75 and 0.75, or ≥0.75) obtained for each scenario determined a low (P0), intermediate (P1) or high (P2) relevance, respectively. Results: 8064 answers were analyzed. Participation and completion rates were 93% and 100%, respectively. In overt or occult OGIB, resultant P2 findings were 'typical angiectasia', 'deep ulceration', 'stenosis', and'blood', whatever their numbers, and 'superficial ulcerations' when multiple. While in suspected CD, consensus P2 lesions were 'deep ulceration' and 'stenosis' whatever their numbers, and 'aphthoid erosions' and 'superficial ulcerations' when multiple. Conclusion: This study establishes a guide for the evaluation of relevance of SBCE findings. It represents a step forward for SB-CE interpretation and is intended to be used as a tool for teaching and academic research.
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27. |
- dos Remedios, C. G., et al.
(author)
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The Sydney Heart Bank : improving translational research while eliminating or reducing the use of animal models of human heart disease
- 2017
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In: Biophysical Reviews. - : Springer Nature. - 1867-2450 .- 1867-2469. ; 9:4, s. 431-441
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Journal article (peer-reviewed)abstract
- The Sydney Heart Bank (SHB) is one of the largest human heart tissue banks in existence. Its mission is to provide high-quality human heart tissue for research into the molecular basis of human heart failure by working collaboratively with experts in this field. We argue that, by comparing tissues from failing human hearts with age-matched non-failing healthy donor hearts, the results will be more relevant than research using animal models, particularly if their physiology is very different from humans. Tissue from heart surgery must generally be used soon after collection or it significantly deteriorates. Freezing is an option but it raises concerns that freezing causes substantial damage at the cellular and molecular level. The SHB contains failing samples from heart transplant patients and others who provided informed consent for the use of their tissue for research. All samples are cryopreserved in liquid nitrogen within 40 min of their removal from the patient, and in less than 5–10 min in the case of coronary arteries and left ventricle samples. To date, the SHB has collected tissue from about 450 failing hearts (>15,000 samples) from patients with a wide range of etiologies as well as increasing numbers of cardiomyectomy samples from patients with hypertrophic cardiomyopathy. The Bank also has hearts from over 120 healthy organ donors whose hearts, for a variety of reasons (mainly tissue-type incompatibility with waiting heart transplant recipients), could not be used for transplantation. Donor hearts were collected by the St Vincent’s Hospital Heart and Lung transplantation team from local hospitals or within a 4-h jet flight from Sydney. They were flushed with chilled cardioplegic solution and transported to Sydney where they were quickly cryopreserved in small samples. Failing and/or donor samples have been used by more than 60 research teams around the world, and have resulted in more than 100 research papers. The tissues most commonly requested are from donor left ventricles, but right ventricles, atria, interventricular system, and coronary arteries vessels have also been reported. All tissues are stored for long-term use in liquid N or vapor (170–180 °C), and are shipped under nitrogen vapor to avoid degradation of sensitive molecules such as RNAs and giant proteins. We present evidence that the availability of these human heart samples has contributed to a reduction in the use of animal models of human heart failure.
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28. |
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29. |
- Stephens, P. A., et al.
(author)
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The scaling of diving time budgets: Insights from an optimality approach
- 2008
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In: American Naturalist. - : University of Chicago Press. - 0003-0147 .- 1537-5323. ; 171:3, s. 305-314
-
Journal article (peer-reviewed)abstract
- Simple scaling arguments suggest that, among air-breathing divers, dive duration should scale approximately with mass to the one-third power. Recent phylogenetic analyses appear to confirm this. The same analyses showed that duration of time spent at the surface between dives has scaling very similar to that of dive duration, with the result that the ratio of dive duration to surface pause duration is approximately mass invariant. This finding runs counter to other arguments found in the diving literature that suggest that surface pause duration should scale more positively with mass, leading to a negative scaling of the dive-pause ratio. We use a published model of optimal time allocation in the dive cycle to show that optimal decisions can predict approximate mass invariance in the dive-pause ratio, especially if metabolism scales approximately with mass to the two-thirds power (as indicated by some recent analyses) and oxygen uptake is assumed to have evolved to supply the body tissues at the required rate. However, emergent scaling rules are sensitive to input parameters, especially to the relationship between the scaling of metabolism and oxygen uptake rate at the surface. Our results illustrate the utility of an optimality approach for developing predictions and identifying key areas for empirical research on the allometry of diving behavior.
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30. |
- Adeloye, Davies, et al.
(author)
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Research priorities to address the global burden of chronic obstructive pulmonary disease (COPD) in the next decade
- 2021
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In: Journal of Global Health. - : International Global Health Society. - 2047-2986 .- 2047-2978. ; 11, s. 15003-15003
-
Journal article (peer-reviewed)abstract
- Background: The global prevalence of chronic obstructive pulmonary disease (COPD) has increased markedly in recent decades. Given the scarcity of resources available to address global health challenges and respiratory medicine being relatively under-invested in, it is important to define research priorities for COPD globally. In this paper, we aim to identify a ranked set of COPD research priorities that need to be addressed in the next 10 years to substantially reduce the global impact of COPD. Methods: We adapted the Child Health and Nutrition Research Initiative (CHNRI) methodology to identify global COPD research priorities. Results: 62 experts contributed 230 research ideas, which were scored by 34 researchers according to six pre-defined criteria: answerability, effectiveness, feasibility, deliverability, burden reduction, and equity. The top-ranked research priority was the need for new effective strategies to support smoking cessation. Of the top 20 overall research priorities, six were focused on feasible and cost-effective pulmonary rehabilitation delivery and access, particularly in primary/community care and low-resource settings. Three of the top 10 overall priorities called for research on improved screening and accurate diagnostic methods for COPD in low-resource primary care settings. Further ideas that drew support involved a better understanding of risk factors for COPD, development of effective training programmes for health workers and physicians in low resource settings, and evaluation of novel interventions to encourage physical activity. Conclusions: The experts agreed that the most pressing feasible research questions to address in the next decade for COPD reduction were on prevention, diagnosis and rehabilitation of COPD, especially in low resource settings. The largest gains should be expected in low- and middle-income countries (LMIC) settings, as the large majority of COPD deaths occur in those settings. Research priorities identified by this systematic international process should inform and motivate policymakers, funders, and researchers to support and conduct research to reduce the global burden of COPD.
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36. |
- Kroon, Tobias, et al.
(author)
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PPARγ and PPARα synergize to induce robust browning of white fat in vivo
- 2020
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In: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 36
-
Journal article (peer-reviewed)abstract
- Objective: Peroxisome proliferator-activated receptors (PPARs) are key transcription factors that regulate adipose development and function, and the conversion of white into brown-like adipocytes. Here we investigated whether PPARα and PPARγ activation synergize to induce the browning of white fat. Methods: A selection of PPAR activators was tested for their ability to induce the browning of both mouse and human white adipocytes in vitro, and in vivo in lean and obese mice. Results: All dual PPARα/γ activators tested robustly increased uncoupling protein 1 (Ucp1) expression in both mouse and human adipocytes in vitro, with tesaglitazar leading to the largest Ucp1 induction. Importantly, dual PPARα/γ activator tesaglitazar strongly induced browning of white fat in vivo in both lean and obese male mice at thermoneutrality, greatly exceeding the increase in Ucp1 observed with the selective PPARγ activator rosiglitazone. While selective PPARγ activation was sufficient for the conversion of white into brown-like adipocytes in vitro, dual PPARα/γ activation was superior to selective PPARγ activation at inducing white fat browning in vivo. Mechanistically, the superiority of dual PPARα/γ activators is mediated at least in part via a PPARα-driven increase in fibroblast growth factor 21 (FGF21). Combined treatment with rosiglitazone and FGF21 resulted in a synergistic increase in Ucp1 mRNA levels both in vitro and in vivo. Tesaglitazar-induced browning was associated with increased energy expenditure, enhanced insulin sensitivity, reduced liver steatosis, and an overall improved metabolic profile compared to rosiglitazone and vehicle control groups. Conclusions: PPARγ and PPARα synergize to induce robust browning of white fat in vivo, via PPARγ activation in adipose, and PPARα-mediated increase in FGF21. © 2020 The Authors
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37. |
- Leenhardt, R., et al.
(author)
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Key research questions for implementation of artificial intelligence in capsule endoscopy
- 2022
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In: Therapeutic Advances in Gastroenterology. - : SAGE Publications. - 1756-283X .- 1756-2848. ; 15
-
Journal article (peer-reviewed)abstract
- Background: Artificial intelligence (AI) is rapidly infiltrating multiple areas in medicine, with gastrointestinal endoscopy paving the way in both research and clinical applications. Multiple challenges associated with the incorporation of AI in endoscopy are being addressed in recent consensus documents. Objectives: In the current paper, we aimed to map future challenges and areas of research for the incorporation of AI in capsule endoscopy (CE) practice. Design: Modified three-round Delphi consensus online survey. Methods: The study design was based on a modified three-round Delphi consensus online survey distributed to a group of CE and AI experts. Round one aimed to map out key research statements and challenges for the implementation of AI in CE. All queries addressing the same questions were merged into a single issue. The second round aimed to rank all generated questions during round one and to identify the top-ranked statements with the highest total score. Finally, the third round aimed to redistribute and rescore the top-ranked statements. Results: Twenty-one (16 gastroenterologists and 5 data scientists) experts participated in the survey. In the first round, 48 statements divided into seven themes were generated. After scoring all statements and rescoring the top 12, the question of AI use for identification and grading of small bowel pathologies was scored the highest (mean score 9.15), correlation of AI and human expert reading-second (9.05), and real-life feasibility-third (9.0). Conclusion: In summary, our current study points out a roadmap for future challenges and research areas on our way to fully incorporating AI in CE reading.
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38. |
- Levy, P, et al.
(author)
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Application of Neonatologist Performed Echocardiography in the Assessment and Management of Neonatal Heart Failure unrelated to Congenital Heart Disease
- 2018
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In: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 84:1Suppl 1, s. 78-88
-
Journal article (peer-reviewed)abstract
- Neonatal heart failure (HF) is a progressive disease caused by cardiovascular and non-cardiovascular abnormalities. The most common cause of neonatal HF is structural congenital heart disease, while neonatal cardiomyopathy represents the most common cause of HF in infants with a structurally normal heart. Neonatal cardiomyopathy is a group of diseases manifesting with various morphological and functional phenotypes that affect the heart muscle and alter cardiac performance at, or soon after birth. The clinical presentation of neonates with cardiomyopathy is varied, as are the possible causes of the condition and the severity of disease presentation. Echocardiography is the selected method of choice for diagnostic evaluation, follow-up and analysis of treatment results for cardiomyopathies in neonates. Advances in neonatal echocardiography now permit a more comprehensive assessment of cardiac performance that could not be previously achieved with conventional imaging. In this review, we discuss the current and emerging echocardiographic techniques that aid in the correct diagnostic and pathophysiological assessment of some of the most common etiologies of HF that occur in neonates with a structurally normal heart and acquired cardiomyopathy and we provide recommendations for using these techniques to optimize the management of neonate with HF.
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39. |
- Mangan, A. M., et al.
(author)
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Effect of Macronutrient Type and Gastrointestinal Release Site on PYY Response in Normal Healthy Subjects
- 2019
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In: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 104:9, s. 3661-3669
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Journal article (peer-reviewed)abstract
- Background and Aims: Enteroendocrine L cells release satiety inducing hormones in response to stimulation by luminal macronutrients. We sought to profile the differential effect of macronutrient type and site of release on circulating concentrations of the L cell-derived enteroendocrine hormone peptide tyrosine tyrosine (amino acids 1 to 36) (PYY). Materials and Methods: Eight healthy volunteers were recruited to a randomized, double-blinded, six-way crossover study. At each visit, the participants consumed a 500-kcal drink containing carbohydrate, protein, or fat in either gastric or small intestinal release formulations. Plasma PYY concentrations and hunger ratings were assessed for 3 hours after consumption of the test drink. The food intake was recorded thereafter at an ad libitum lunch. Results: Microcapsular formulations targeting the distal small intestinal delivery of fat, but not carbohydrate or protein, markedly enhance PYY release relative to macronutrient delivery in gastric release formulations. Food intake at an ad libitum meal was lowest after consumption of the formulation releasing fat at the distal small intestine. Conclusion: Targeting of fat to the distal small intestine in delayed release microcapsules enhanced PYY release and was associated with reductions in food intake.
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40. |
- McNamara, R. L., et al.
(author)
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International comparisons of the management of patients with non-ST segment elevation acute myocardial infarction in the United Kingdom, Sweden, and the United States: The MINAP/NICOR, SWEDEHEART/RIKS-HIA, and ACTION Registry-GWTG/NCDR registries
- 2014
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 175:2, s. 240-247
-
Journal article (peer-reviewed)abstract
- Objectives: To compare management of patients with acute non-ST segment elevation myocardial infarction (NSTEMI) in three developed countries with national ongoing registries. Background: Results from clinical trials suggest significant variation in care across the world. However, international comparisons in "real world" registries are limited. Methods: We compared the use of in-hospital procedures and discharge medications for patients admitted with NSTEMI from 2007 to 2010 using the unselective MINAP/NICOR [England and Wales (UK); n = 137,009], the unselective SWEDEHEART/RIKS-HIA (Sweden; n = 45,069), and the selective ACTION Registry-GWTG/NCDR [United States (US); n = 147,438] clinical registries. Results: Patients enrolled among the three registries were generally similar except those in the US who were younger but had higher rates of smoking, diabetes, hypertension, prior heart failure, and prior MI than in Sweden or in UK. Angiography and percutaneous coronary intervention (PCI) were performed more often in the US (76% and 44%) and Sweden (65% and 42%) relative to the UK (32% and 22%). Discharge betablockers were also prescribed more often in the US (89%) and Sweden (89%) than in the UK (76%). In contrast, discharge statins, angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB), and dual antiplatelet agents (among those not receiving PCI) were higher in the UK (92%, 79%, and 71%) than in the US (85%, 65%, 41%) and Sweden (81%, 69%, and 49%). Conclusions: The care for patients with NSTEMI differed substantially among the three countries. These differences in care among countries provide an opportunity for future comparative effectiveness research as well as identify opportunities for global quality improvement. (C) 2014 The Authors. Published by Elsevier Ireland Ltd.
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42. |
- Pinese, Mark, et al.
(author)
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The Medical Genome Reference Bank contains whole genome and phenotype data of 2570 healthy elderly
- 2020
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
-
Journal article (peer-reviewed)abstract
- Population health research is increasingly focused on the genetic determinants of healthy ageing, but there is no public resource of whole genome sequences and phenotype data from healthy elderly individuals. Here we describe the first release of the Medical Genome Reference Bank (MGRB), comprising whole genome sequence and phenotype of 2570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. We analyse the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes. MGRB individuals have fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK Biobank cohorts, consistent with risk depletion. Age-related somatic changes are correlated with grip strength in men, suggesting blood-derived whole genomes may also provide a biologic measure of age-related functional deterioration. The MGRB provides a broadly applicable reference cohort for clinical genetics and genomic association studies, and for understanding the genetics of healthy ageing. Healthspan and healthy aging are areas of research with potential socioeconomic impact. Here, the authors present the Medical Genome Reference Bank (MGRB) which consist of over 4,000 individuals aged 70 years and older without a history of the major age-related diseases and report on results from whole-genome sequencing and association analyses.
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49. |
- McNamara, John M., et al.
(author)
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Environmental variability can select for optimism or pessimism
- 2011
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In: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 14:1, s. 58-62
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Journal article (peer-reviewed)abstract
- We propose operational definitions of reproductive optimism and pessimism; optimism involves behaving in a way that gives too much weight (in terms of producing surviving offspring) to positive events, pessimism gives too much weight to negative events. Natural selection maximizes the long-term growth of a lineage rather than short-term measures such as numbers of offspring. Consequently, optimism or pessimism can be favoured by natural selection, even though such biases appear irrational from a short-term perspective. We investigate the evolution of optimism in a metapopulation. The circumstances of a patch change over time, independently of other patches. With sufficient dispersal between patches, stochasticity affects members of a lineage largely independently and optimism is favoured. With little dispersal, the temporal fluctuations of a patch affect many members similarly; pessimism is then favoured. Our results establish that the spatial and temporal structure of the environment is crucial in determining the direction of evolved biases. © 2010 Blackwell Publishing Ltd/CNRS.
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50. |
- Zetterberg, Per, et al.
(author)
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Performance of multiple-receive multiple-transmit beamforming in WLAN-type systems under power or EIRP constraints with delayed channel estimates
- 2002
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In: IEEE 55TH VEHICULAR TECHNOLOGY CONFERENCE, VTC SPRING 2002, VOLS 1-4, PROCEEDINGS. - 0780374843 ; , s. 1906-1910
-
Conference paper (peer-reviewed)abstract
- Downlink beamforming in a WLAN-type system employing access points and mobiles equipped with multiple antennas and associated receivers and transmitters are considered. The beamforming aims at maximizing the performance under constraints on transmit power or equivalent isotropic radiated power (EIRP). Solutions for the two constraints are derived and investigated using simulated and measured channels. Our simulation and experimental results shows that performance gains of 8-10dB when using four directional transmitter antennas and two receive antennas (as compared with a base-line one-transmit two-receive), are possible under both constraints. For simulated channels, a delay between channel estimation and use of the same channel of up to 10% of the (inverse of the) Doppler frequency only degrades performance some tenths of a dB. In our measurements, very small degradations are seen with delays of up to 130ms. The measurements were made under relatively stationary conditions with only occasionally moving people Two different strategies for updating the beamforming vectors: sounding and ping-pong, are also considered in the paper.
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