| 1. |
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| 2. |
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| 3. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
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| 5. |
- Namkoong, H, et al.
(författare)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 6. |
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| 7. |
- Wang, QBS, et al.
(författare)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Tidskriftsartikel (refereegranskat)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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| 8. |
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| 9. |
- Aharonian, Felix, et al.
(författare)
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Atmospheric gas dynamics in the Perseus cluster observed with Hitomi
- 2018
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Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
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Tidskriftsartikel (refereegranskat)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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| 10. |
- Aharonian, Felix, et al.
(författare)
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Atomic data and spectral modeling constraints from high-resolution X-ray observations of the Perseus cluster with Hitomi
- 2018
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Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
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Tidskriftsartikel (refereegranskat)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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| 11. |
- Aharonian, Felix, et al.
(författare)
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Detection of polarized gamma-ray emission from the Crab nebula with the Hitomi Soft Gamma-ray Detector
- 2018
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Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:6
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Tidskriftsartikel (refereegranskat)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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| 12. |
- Aharonian, Felix, et al.
(författare)
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Glimpse of the highly obscured HMXB IGR J16318-4848 with Hitomi
- 2018
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Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
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Tidskriftsartikel (refereegranskat)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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| 13. |
- Aharonian, Felix, et al.
(författare)
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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
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Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
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Tidskriftsartikel (refereegranskat)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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| 14. |
- Aharonian, Felix, et al.
(författare)
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Hitomi observations of the LMC SNR N 132 D : Highly redshifted X-ray emission from iron ejecta
- 2018
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Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
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Tidskriftsartikel (refereegranskat)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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| 15. |
- Aharonian, Felix, et al.
(författare)
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Hitomi X-ray observation of the pulsar wind nebula G21.5-0.9
- 2018
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Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:3
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Tidskriftsartikel (refereegranskat)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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| 16. |
- Aharonian, Felix, et al.
(författare)
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Hitomi X-ray studies of giant radio pulses from the Crab pulsar
- 2018
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Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
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Tidskriftsartikel (refereegranskat)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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| 17. |
- Aharonian, Felix, et al.
(författare)
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Measurements of resonant scattering in the Perseus Cluster core with Hitomi SXS
- 2018
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Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
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Tidskriftsartikel (refereegranskat)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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| 18. |
- Aharonian, Felix, et al.
(författare)
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Search for thermal X-ray features from the Crab nebula with the Hitomi soft X-ray spectrometer
- 2018
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Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
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Tidskriftsartikel (refereegranskat)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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| 19. |
- Aharonian, Felix, et al.
(författare)
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Solar abundance ratios of the iron-peak elements in the Perseus cluster
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 551:7681, s. 478-
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Tidskriftsartikel (refereegranskat)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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| 20. |
- Aharonian, Felix, et al.
(författare)
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Temperature structure in the Perseus cluster core observed with Hitomi
- 2018
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Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
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Tidskriftsartikel (refereegranskat)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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| 21. |
- Matsubara, K., et al.
(författare)
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No Interstitial Telomeres on Autosomes but Remarkable Amplification of Telomeric Repeats on the W Sex Chromosome in the Sand Lizard (Lacerta agilis)
- 2015
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Ingår i: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 106:6, s. 753-757
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Tidskriftsartikel (refereegranskat)abstract
- Telomeres are repeat ( TTAGGG) (n) sequences that form terminal ends of chromosomes and have several functions, such as protecting the coding DNA from erosion at mitosis. Due to chromosomal rearrangements through evolutionary history ( e.g., inversions and fusions), telomeric sequences are also found between the centromere and the terminal ends ( i.e., at interstitial telomeric sites, ITSs). ITS telomere sequences have been implicated in heritable disease caused by genomic instability of ITS polymorphic variants, both with respect to copy number and sequence. In the sand lizard ( Lacerta agilis), we have shown that telomere length is predictive of lifetime fitness in females but not males. To assess whether this sex specific fitness effect could be traced to ITSs differences, we mapped ( TTAGGG) n sequences using fluorescence in situ hybridization in fibroblast cells cultured from 4 specimens of known sex. No ITSs could be found on autosomes in either sex. However, females have heterogametic sex chromosomes in sand lizards ( ZW, 2n = 38) and the female W chromosome showed degeneration and remarkable ( TTAGGG) n amplification, which was absent in the Z chromosomes. This work warrants further research on sex chromosome content, in particular of the degenerate W chromosome, and links to female fitness in sand lizards.
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| 22. |
- Srikulnath, K., et al.
(författare)
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Identification of the linkage group of the Z sex chromosomes of the sand lizard (Lacerta agilis, Lacertidae) and elucidation of karyotype evolution in lacertid lizards
- 2014
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Ingår i: Chromosoma. - : Springer Science and Business Media LLC. - 0009-5915 .- 1432-0886. ; 123:6, s. 563-575
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Tidskriftsartikel (refereegranskat)abstract
- The sand lizard (Lacerta agilis, Lacertidae) has a chromosome number of 2n = 38, with 17 pairs of acrocentric chromosomes, one pair of microchromosomes, a large acrocentric Z chromosome, and a micro-W chromosome. To investigate the process of karyotype evolution in L. agilis, we performed chromosome banding and fluorescent in situ hybridization for gene mapping and constructed a cytogenetic map with 86 functional genes. Chromosome banding revealed that the Z chromosome is the fifth largest chromosome. The cytogenetic map revealed homology of the L. agilis Z chromosome with chicken chromosomes 6 and 9. Comparison of the L. agilis cytogenetic map with those of four Toxicofera species with many microchromosomes (Elaphe quadrivirgata, Varanus salvator macromaculatus, Leiolepis reevesii rubritaeniata, and Anolis carolinensis) showed highly conserved linkage homology of L. agilis chromosomes (LAG) 1, 2, 3, 4, 5(Z), 7, 8, 9, and 10 with macrochromosomes and/or macrochromosome segments of the four Toxicofera species. Most of the genes located on the microchromosomes of Toxicofera were localized to LAG6, small acrocentric chromosomes (LAG11-18), and a microchromosome (LAG19) in L. agilis. These results suggest that the L. agilis karyotype resulted from frequent fusions of microchromosomes, which occurred in the ancestral karyotype of Toxicofera and led to the disappearance of microchromosomes and the appearance of many small macrochromosomes.
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| 23. |
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| 24. |
- Blennow, Jörgen, 1966, et al.
(författare)
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Sequential Comparative Study of Dielectric Response and Analyses of Oil and Paper from a Power Transformer Undergoing Repair
- 2005
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Ingår i: In Proc. 14th International Symposium on High Voltage Engineering.
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Konferensbidrag (refereegranskat)abstract
- Methods, based on characterisation of dielectric response, for assessing moisture content in pressboard and paper are gaining ground. However, there is a need for calibrating obtained results with results from other techniques. This communication presents results from a study of a 50/10 kV - 40 MVA power transformer, which was sent to a workshop for repair, thus allowing for collecting samples of the solid insulation. Dielectric spectroscopy measurements in frequency domain were conducted at several occasions before and after the repair. Moisture estimation based on dielectric response measurements as well as on titration of oil samples yielded similar results to those obtained by direct titration of paper samples, as long as appropriate temperature values were used in all the analyses mentioned. The temperature value during measurements should be used for the analysis of the dielectric response, while in-service temperature of oil should be used for the evaluation based on Karl Fisher titration.
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| 25. |
- Byungura, Jean Claude, 1979-, et al.
(författare)
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Online learning for continuous professional development of healthcare workers : an exploratory study on perceptions of healthcare managers in Rwanda
- 2022
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Ingår i: BMC Medical Education. - London : BioMed Central (BMC). - 1472-6920. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Due to outbreaks of new diseases, development of new treatment regimens and requirement of evidence-based practice, health professionals continuously need to acquire updated knowledge and skills. This type of learning is known as continuous professional development (CPD). The scarcity of skilled health care professionals in developing countries further increases the need of CPD. Traditionally, face-to-face approach has been preferred as the best mode of CPD. Currently, health professionals have started using online learning for continued professional growth in different parts of the world. Consequently, research studies from different settings are needed to investigate the significance of online learning for CPD. Therefore, the aim of this study was to investigate the importance and challenges attributed to online learning by the managers of health facilities in Rwanda. Moreover, the study aimed to identify the status of infrastructures that could support online CPD, and assess the perceived enhancement and barriers for implementing online CPD. Methods: The study used a convergence mixed-method design to explore quantitative and qualitative data from 42 health care managers. A descriptive analysis was conducted on quantitative data while qualitative data were thematically analyzed to inform the study findings. Results: It was revealed that 90.5% of managers, who participated in this study, consider positively the use of online learning for CPD. All managers acknowledged that online learning could improve the knowledge and practice skills of health care professionals. Nevertheless, 52.4% of health institutions who participated in this study currently do not use online for CPD. Participants demonstrated challenges such as the lack of access to digital devices, poor or lack of internet access, poor online learning design, low digital skills of healthcare professionals, lack of time dedicated to online learning, and heavy workload of staff. Conclusion: These findings indicate then that the managers of health institutions value the importance of online learning for CPD of health professionals. However, online learning should be designed to fit for the purpose and with a high consideration on needs and preferences of healthcare professionals and thereby improve information communication technology infrastructure that support online learning for CPD. Traditional in-person CPD courses are still recommended in health institutions with shortage in resources and technology. Also, the barriers of online CPD delivery such as low internet connectivity and lack of access to digital devices by healthcare professionals need to be co-creatively addressed through the pyramidal structure of the Rwandan health system. © 2022, The Author(s).
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| 26. |
- D'Andrea, David, et al.
(författare)
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Association of patients' sex with treatment outcomes after intravesical bacillus Calmette-Guerin immunotherapy for T1G3/HG bladder cancer
- 2021
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Ingår i: World journal of urology. - : Springer Nature. - 0724-4983 .- 1433-8726. ; 39:9, s. 3337-3344
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the association of patients' sex with recurrence and disease progression in patients treated with intravesical bacillus Calmette-Guerin (BCG) for T1G3/HG urinary bladder cancer (UBC).Materials and methods: We analyzed the data of 2635 patients treated with adjuvant intravesical BCG for T1 UBC between 1984 and 2019. We accounted for missing data using multiple imputations and adjusted for covariate imbalance between males and females using inverse probability weighting (IPW). Crude and IPW-adjusted Cox regression analyses were used to estimate the hazard ratios (HR) with their 95% confidence intervals (CI) for the association of patients' sex with HG-recurrence and disease progression.Results: A total of 2170 (82%) males and 465 (18%) females were available for analysis. Overall, 1090 (50%) males and 244 (52%) females experienced recurrence, and 391 (18%) males and 104 (22%) females experienced disease progression. On IPW-adjusted Cox regression analyses, female sex was associated with disease progression (HR 1.25, 95%CI 1.01-1.56, p = 0.04) but not with recurrence (HR 1.06, 95%CI 0.92-1.22, p = 0.41). A total of 1056 patients were treated with adequate BCG. In these patients, on IPW-adjusted Cox regression analyses, patients' sex was not associated with recurrence (HR 0.99, 95%CI 0.80-1.24, p = 0.96), HG-recurrence (HR 1.00, 95%CI 0.78-1.29, p = 0.99) or disease progression (HR 1.12, 95%CI 0.78-1.60, p = 0.55).Conclusion: Our analysis generates the hypothesis of a differential response to BCG between males and females if not adequately treated. Further studies should focus on sex-based differences in innate and adaptive immune system and their association with BCG response.
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| 27. |
- Dyrskjøt, Lars, et al.
(författare)
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Gene expression signatures predict outcome in non-muscle-invasive bladder carcinoma : a multicenter validation study
- 2007
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:12, s. 3545-3551
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Clinically useful molecular markers predicting the clinical course of patients diagnosed with non–muscle-invasive bladder cancer are needed to improve treatment outcome. Here, we validated four previously reported gene expression signatures for molecular diagnosis of disease stage and carcinoma in situ (CIS) and for predicting disease recurrence and progression. Experimental Design: We analyzed tumors from 404 patients diagnosed with bladder cancer in hospitals in Denmark, Sweden, England, Spain, and France using custom microarrays. Molecular classifications were compared with pathologic diagnosis and clinical outcome. Results: Classification of disease stage using a 52-gene classifier was found to be highly significantly correlated with pathologic stage (P < 0.001). Furthermore, the classifier added information regarding disease progression of Ta or T1 tumors (P < 0.001). The molecular 88-gene progression classifier was highly significantly correlated with progression-free survival (P < 0.001) and cancer-specific survival (P = 0.001). Multivariate Cox regression analysis showed the progression classifier to be an independently significant variable associated with disease progression after adjustment for age, sex, stage, grade, and treatment (hazard ratio, 2.3; P = 0.007). The diagnosis of CIS using a 68-gene classifier showed a highly significant correlation with histopathologic CIS diagnosis (odds ratio, 5.8; P < 0.001) in multivariate logistic regression analysis. Conclusion: This multicenter validation study confirms in an independent series the clinical utility of molecular classifiers to predict the outcome of patients initially diagnosed with non–muscle-invasive bladder cancer. This information may be useful to better guide patient treatment.
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| 28. |
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| 29. |
- Gontero, Paolo, et al.
(författare)
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Prognostic Factors and Risk Groups in T1G3 Non-Muscle-invasive Bladder Cancer Patients Initially Treated with Bacillus Calmette-Guerin : Results of a Retrospective Multicenter Study of 2451 Patients
- 2015
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 67:1, s. 74-82
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Tidskriftsartikel (refereegranskat)abstract
- Background: The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. Objective: To assess prognostic factors in patients who received bacillus Calmette Guerin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. Design, setting, and participants: Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. Outcome measurements and statistical analysis: Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). Results and limitations: With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age >= 70 yr, size >= 3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients >= 70 yr with tumor size >= 3 cm and 13% otherwise. Conclusions: T1G3 patients >= 70 yr with tumors >= 3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. Patient summary: Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guerin, there is a subgroup of T1G3 patients with age >= 70 yr, tumor size >= 3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.
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| 30. |
- Gontero, Paolo, et al.
(författare)
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The impact of re-transurethral resection on clinical outcomes in a large multicentre cohort of patients with T1 high-grade/Grade 3 bladder cancer treated with bacille Calmette-Guérin
- 2016
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Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 118:1, s. 44-52
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To determine if a re-transurethral resection (TUR), in the presence or absence of muscle at the first TUR in patients with T1-high grade (HG)/Grade 3 (G3) bladder cancer, makes a difference in recurrence, progression, cancer specific (CSS) and overall survival (OS).PATIENTS AND METHODS: In a large retrospective multicentre cohort of 2451 patients with T1-HG/G3 initially treated with bacille Calmette-Guérin, 935 (38%) had a re-TUR. According to the presence or absence of muscle in the specimen of the primary TUR, patients were divided in four groups: group 1 (no muscle, no re-TUR), group 2 (no muscle, re-TUR), group 3 (muscle, no re-TUR) and group 4 (muscle, re-TUR). Clinical outcomes were compared across the four groups.RESULTS: Re-TUR had a positive impact on recurrence, progression, CSS and OS only if muscle was not present in the primary TUR specimen. Adjusting for the most important prognostic factors, re-TUR in the absence of muscle had a borderline significant effect on time to recurrence [hazard ratio (HR) 0.67, P = 0.08], progression (HR 0.46, P = 0.06), CSS (HR 0.31, P = 0.07) and OS (HR 0.48, P = 0.05). Re-TUR in the presence of muscle in the primary TUR specimen did not improve the outcome for any of the endpoints.CONCLUSIONS: Our retrospective analysis suggests that re-TUR may not be necessary in patients with T1-HG/G3, if muscle is present in the specimen of the primary TUR.
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| 31. |
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| 32. |
- Letocha, H, et al.
(författare)
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Positron emission tomography with L-methyl-11C-methionine in the monitoring of therapy response in muscle-invasive transitional cell carcinoma of the urinary bladder
- 1994
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Ingår i: British Journal of Urology. - 0007-1331 .- 1365-2176. ; 74:6, s. 767-774
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate whether positron emission tomography (PET) with L-methyl-11C-methionine as a tracer could be used for diagnostic purposes and for evaluation of therapy in patients with varying stages of urinary bladder cancer treated with chemotherapy. PATIENTS AND METHODS: PET was employed in 44 separate examinations involving 29 patients (24 men and five women with a median age of 68 years [mean 66, range 47-78]) with localized or metastatic transitional cell carcinoma of the urinary bladder. In four patients PET examinations were performed prior to the commencement of chemotherapy, and after one course and after three courses. RESULTS: The diagnostic accuracy of PET was poor. The technique did not monitor the therapeutic effect of neoadjuvant chemotherapy, producing results that correlated with therapy outcome. PET identified those patients who responded less successfully to therapy. CONCLUSION: PET with L-methyl-11C-methionine demonstrates alterations in tumour metabolism long before visible changes appear on computed tomography or magnetic resonance imaging. Further work is required to develop more specific tracers.
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| 33. |
- Nyiringango, Gerard, et al.
(författare)
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Acceptance of virtual patients as a continuous professional development approach among practicing nurses in primary health care settings in a low-income country : a quasi-experimental posttest setup design
- 2024
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Ingår i: BMC Nursing. - London : BioMed Central (BMC). - 1472-6955. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Virtual patients are an educational technological approach used in healthcare education. Its distinctive features have rendered virtual patient technology appealing for the training of medical and healthcare students, particularly in the enhancement of clinical reasoning. Virtual patients are less often applied for continuous professional development for practicing healthcare providers, and there is a scarcity of studies exploring this possibility. This study aimed to assess the acceptability of nurses for using virtual patients as a continuous professional development approach. Method: The study used a quasi-experimental posttest setup design. The study was conducted in ten primary healthcare settings in Rwanda. Among 76 nurses who consented to participate in the study, 56 completed the intervention and responded to the study questionnaire. Following a one-week program of continuous professional development on four non-communicable diseases, the study used a self-administered questionnaire based on the Technology Acceptance Model 3 to collect data. Descriptive analysis served as the primary method for analyzing participants’ responses. The study also used a correlation test to assess the relationship of variables. Results: Across all items in the questionnaire, the median response tended towards either agree or strongly agree, with only a minority number of participants expressing strong disagreement, disagreement, or neutrality. The results indicated a significant positive correlation between perceived usefulness and behavior intention (p < 0.001). Conclusion: The findings indicate an acceptability and behavioral intention of adopting virtual patients as an alternative continuous professional development approach among nurses working at health centers in Rwanda or other locations with similar contexts. © The Author(s) 2024.
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| 34. |
- Nyiringango, Gerard, 1979-, et al.
(författare)
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Enhancing clinical reasoning for management of non-communicable diseases : virtual patient cases as a learning strategy for nurses in primary healthcare centers: a pre-post study design
- 2024
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Ingår i: BMC Medical Education. - 1472-6920. ; 24
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Tidskriftsartikel (refereegranskat)abstract
- Background In Rwanda, nurses manage all primary care at health centres, and therefore are their clinical reasoning skills important. In this study, a web-based software that allows the creation of virtual patient cases (VP cases) has been used for studying the possibility of using VP cases for the continuous professional development of nurses in primary health care in Rwanda. Previous studies in pre-service education have linked VP cases with the enhancement of clinical reasoning, a critical competence for nurses. This study investigated the feasibility of continuous professional development through VP cases to further train in-service nurses in clinical reasoning.Method The study used a pre-post test design. Initially, seventy-six participants completed a questionnaire as part of the pre-test phase, subsequently invited to engage with all four VP cases, and finally responded to the post-test questionnaire evaluating clinical reasoning skills. Fifty-six participants successfully completed the entire study process and were considered in the analysis. The primary outcomes of this study were evaluated using a paired t-test for the statistical analysis.Results The results show that the mean score of clinical reasoning increased significantly from the pre-test to the post-test for all four illness areas (p < 0.001). The study findings showed no statistically significant difference in participants’ scores based on demographic factors, including whether they worked in urban or rural areas. Conclusion and recommendation Utilizing VP cases appears to significantly enhance the continuous professional development of nurses, fostering a deliberate learning process that enables them to reflect on how they manage cases and, in turn, refine their clinical reasoning skills. This study strongly recommends incorporating VP cases in the continuous professional development of nurses at the primary health level (health centers). This is especially pertinent in a context where nurses are required to perform diagnostic processes similar to those employed by physicians.
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| 35. |
- Palou, J., et al.
(författare)
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Recurrence, progression and cancer-specific mortality according to stage at re-TUR in T1G3 bladder cancer patients treated with BCG : not as bad as previously thought
- 2018
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Ingår i: World journal of urology. - : SPRINGER. - 0724-4983 .- 1433-8726. ; 36:10, s. 1621-1627
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis to adequately stage and treat the patient. Persistent disease after TUR is not uncommon and is why re-TUR is recommended in T1G3 patients. When there is T1 tumor in the re-TUR specimen, very high risks of progression (82%) have been reported. We analyze the risks of recurrence, progression to muscle-invasive disease and cancer-specific mortality (CSM) according to tumor stage at re-TUR in T1G3 patients treated with BCG.Methods: In our retrospective cohort of 2451 T1G3 patients, 934 patients (38.1%) underwent re-TUR. 667 patients had residual disease (71.4%): Ta in 378 (40.5%), T1 in 289 (30.9%) patients. Times to recurrence, progression and CSM in the three groups were estimated using cumulative incidence functions and compared using the Cox regression model.Results:During a median follow-up of 5.2years, 512 patients recurred. The recurrence rate was significantly higher in patients with a T1 at re-TUR (P<0.001). Progression rates differed according to the pathology at re-TUR, 25.3% in T1, 14.6% in Ta and 14.2% in case of no residual tumor (P<0.001). Similar trends were seen in both patients with and without muscle in the original TUR specimen.Conclusions: Patients with T1G3 tumors and no residual disease or Ta at re-TUR have better recurrence, progression and CSM rates than previously reported, with a CSM rate of 13.1 and a 25.3% progression rate in re-TUR T1 disease.
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| 36. |
- Rockström, Johan, et al.
(författare)
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A safe operating space for humanity
- 2009
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7263, s. 472-475
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Tidskriftsartikel (refereegranskat)
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| 37. |
- Rockström, Johan, et al.
(författare)
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Planetary Boundaries : Exploring the Safe Operating Space for Humanity
- 2009
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Ingår i: Ecology and Society. - 1708-3087. ; 14:2, s. 32-
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Tidskriftsartikel (refereegranskat)abstract
- Anthropogenic pressures on the Earth System have reached a scale where abrupt global environmental change can no longer be excluded. We propose a new approach to global sustainability in which we define planetary boundaries within which we expect that humanity can operate safely. Transgressing one or more planetary boundaries may be deleterious or even catastrophic due to the risk of crossing thresholds that will trigger non-linear, abrupt environmental change within continental- to planetary-scale systems. We have identified nine planetary boundaries and, drawing upon current scientific understanding, we propose quantifications for seven of them. These seven are climate change (CO2 concentration in the atmosphere <350 ppm and/or a maximum change of +1 W m(-2) in radiative forcing); ocean acidification (mean surface seawater saturation state with respect to aragonite >= 80% of pre-industrial levels); stratospheric ozone (<5% reduction in O-3 concentration from pre-industrial level of 290 Dobson Units); biogeochemical nitrogen (N) cycle (limit industrial and agricultural fixation of N-2 to 35 Tg N yr(-1)) and phosphorus (P) cycle (annual P inflow to oceans not to exceed 10 times the natural background weathering of P); global freshwater use (<4000 km(3) yr(-1) of consumptive use of runoff resources); land system change (<15% of the ice-free land surface under cropland); and the rate at which biological diversity is lost (annual rate of <10 extinctions per million species). The two additional planetary boundaries for which we have not yet been able to determine a boundary level are chemical pollution and atmospheric aerosol loading. We estimate that humanity has already transgressed three planetary boundaries: for climate change, rate of biodiversity loss, and changes to the global nitrogen cycle. Planetary boundaries are interdependent, because transgressing one may both shift the position of other boundaries or cause them to be transgressed. The social impacts of transgressing boundaries will be a function of the social-ecological resilience of the affected societies. Our proposed boundaries are rough, first estimates only, surrounded by large uncertainties and knowledge gaps. Filling these gaps will require major advancements in Earth System and resilience science. The proposed concept of "planetary boundaries" lays the groundwork for shifting our approach to governance and management, away from the essentially sectoral analyses of limits to growth aimed at minimizing negative externalities, toward the estimation of the safe space for human development. Planetary boundaries define, as it were, the boundaries of the "planetary playing field" for humanity if we want to be sure of avoiding major human-induced environmental change on a global scale.
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| 38. |
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| 39. |
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