Monitoring of mitochondrial oxygenation during perioperative blood loss

One of the challenges in the management of acute blood loss is to differentiate whether blood transfusion is required or not. The sole use of haemoglobin values might lead to unnecessary transfusion in individual cases. The suggestion is that mitochondrial oxygen tension can be used as an additional monitoring technique to determine when blood transfusion is required. In this case report, we report mitochondrial oxygen measurements in a patient with perioperative blood loss requiring blood transfusion

A drug repurposing screen for whipworms informed by comparative genomics.

Hundreds of millions of people worldwide are infected with the whipworm Trichuris trichiura. Novel treatments are urgently needed as current drugs, such as albendazole, have relatively low efficacy. We have investigated whether drugs approved for other human diseases could be repurposed as novel anti-whipworm drugs. In a previous comparative genomics analysis, we identified 409 drugs approved for human use that we predicted to target parasitic worm proteins. Here we tested these ex vivo by assessing motility of adult worms of Trichuris muris, the murine whipworm, an established model for human whipworm research. We identified 14 compounds with EC50 values of ≤50 μM against T. muris ex vivo, and selected nine for testing in vivo. However, the best worm burden reduction seen in mice was just 19%. The high number of ex vivo hits against T. muris shows that we were successful at predicting parasite proteins that could be targeted by approved drugs. In contrast, the low efficacy of these compounds in mice suggest challenges due to their chemical properties (e.g. lipophilicity, polarity, molecular weight) and pharmacokinetics (e.g. absorption, distribution, metabolism, and excretion) that may (i) promote absorption by the host gastrointestinal tract, thereby reducing availability to the worms embedded in the large intestine, and/or (ii) restrict drug uptake by the worms. This indicates that identifying structural analogues that have reduced absorption by the host, and increased uptake by worms, may be necessary for successful drug development against whipworms

Quantisation of Monopoles with Non-abelian Magnetic Charge

Magnetic monopoles in Yang-Mills-Higgs theory with a non-abelian unbroken gauge group are classified by holomorphic charges in addition to the topological charges familiar from the abelian case. As a result the moduli spaces of monopoles of given topological charge are stratified according to the holomorphic charges. Here the physical consequences of the stratification are explored in the case where the gauge group SU(3) is broken to U(2). The description due to A. Dancer of the moduli space of charge two monopoles is reviewed and interpreted physically in terms of non-abelian magnetic dipole moments. Semi-classical quantisation leads to dyonic states which are labelled by a magnetic charge and a representation of the subgroup of U(2) which leaves the magnetic charge invariant (centraliser subgroup). A key result of this paper is that these states fall into representations of the semi-direct product U(2) \semidir R^4. The combination rules (Clebsch-Gordan coefficients) of dyonic states can thus be deduced. Electric-magnetic duality properties of the theory are discussed in the light of our results, and supersymmetric dyonic BPS states which fill the SL(2,Z)-orbit of the basic massive W-bosons are found.Comment: 57 pages, harvmac, amssym, two eps figures, minor mistakes and typos corrected, references added; to appear in Nucl. Phys.

Relativistic Hydrodynamic Evolutions with Black Hole Excision

We present a numerical code designed to study astrophysical phenomena involving dynamical spacetimes containing black holes in the presence of relativistic hydrodynamic matter. We present evolutions of the collapse of a fluid star from the onset of collapse to the settling of the resulting black hole to a final stationary state. In order to evolve stably after the black hole forms, we excise a region inside the hole before a singularity is encountered. This excision region is introduced after the appearance of an apparent horizon, but while a significant amount of matter remains outside the hole. We test our code by evolving accurately a vacuum Schwarzschild black hole, a relativistic Bondi accretion flow onto a black hole, Oppenheimer-Snyder dust collapse, and the collapse of nonrotating and rotating stars. These systems are tracked reliably for hundreds of M following excision, where M is the mass of the black hole. We perform these tests both in axisymmetry and in full 3+1 dimensions. We then apply our code to study the effect of the stellar spin parameter J/M^2 on the final outcome of gravitational collapse of rapidly rotating n = 1 polytropes. We find that a black hole forms only if J/M^2<1, in agreement with previous simulations. When J/M^2>1, the collapsing star forms a torus which fragments into nonaxisymmetric clumps, capable of generating appreciable ``splash'' gravitational radiation.Comment: 17 pages, 14 figures, submitted to PR

A NuSTAR Survey of Nearby Ultraluminous Infrared Galaxies

We present a Nuclear Spectroscopic Telescope Array (NuSTAR), Chandra, and XMM-Newton survey of nine of the nearest ultraluminous infrared galaxies (ULIRGs). The unprecedented sensitivity of NuSTAR at energies above 10 keV enables spectral modeling with far better precision than was previously possible. Six of the nine sources observed were detected sufficiently well by NuSTAR to model in detail their broadband X-ray spectra, and recover the levels of obscuration and intrinsic X-ray luminosities. Only one source (IRAS 13120–5453) has a spectrum consistent with a Compton-thick active galactic nucleus (AGN), but we cannot rule out that a second source (Arp 220) harbors an extremely highly obscured AGN as well. Variability in column density (reduction by a factor of a few compared to older observations) is seen in IRAS 05189–2524 and Mrk 273, altering the classification of these borderline sources from Compton-thick to Compton-thin. The ULIRGs in our sample have surprisingly low observed fluxes in high-energy (>10 keV) X-rays, especially compared to their bolometric luminosities. They have lower ratios of unabsorbed 2–10 keV to bolometric luminosity, and unabsorbed 2–10 keV to mid-IR [O iv] line luminosity than do Seyfert 1 galaxies. We identify IRAS 08572+3915 as another candidate intrinsically X-ray weak source, similar to Mrk 231. We speculate that the X-ray weakness of IRAS 08572+3915 is related to its powerful outflow observed at other wavelengths

NuSTAR unveils a Compton-thick type 2 quasar in MrK 34

We present Nuclear Spectroscopic Telescope Array (NuSTAR) 3-40 keV observations of the optically selected Type 2 quasar (QSO2) SDSS J1034+6001 or Mrk 34. The high-quality hard X-ray spectrum and archival XMM-Newton data can be fitted self-consistently with a reflection-dominated continuum and a strong Fe K? fluorescence line with equivalent width &gt;1 keV. Prior X-ray spectral fitting below 10 keV showed the source to be consistent with being obscured by Compton-thin column densities of gas along the line of sight, despite evidence for much higher columns from multiwavelength data. NuSTAR now enables a direct measurement of this column and shows that N H lies in the Compton-thick (CT) regime. The new data also show a high intrinsic 2-10 keV luminosity of L 2-10 ~ 1044 erg s–1, in contrast to previous low-energy X-ray measurements where L 2-10 lesssim 1043 erg s–1 (i.e., X-ray selection below 10 keV does not pick up this source as an intrinsically luminous obscured quasar). Both the obscuring column and the intrinsic power are about an order of magnitude (or more) larger than inferred from pre-NuSTAR X-ray spectral fitting. Mrk 34 is thus a "gold standard" CT QSO2 and is the nearest non-merging system in this class, in contrast to the other local CT quasar NGC 6240, which is currently undergoing a major merger coupled with strong star formation. For typical X-ray bolometric correction factors, the accretion luminosity of Mrk 34 is high enough to potentially power the total infrared luminosity. X-ray spectral fitting also shows that thermal emission related to star formation is unlikely to drive the observed bright soft component below ~3 keV, favoring photoionization instead

NuSTAR J033202-2746.8: Direct Constraints on the Compton Reflection in a Heavily Obscured Quasar at z ≈ 2

We report Nuclear Spectroscopic Telescope Array (NuSTAR) observations of NuSTAR J033202-2746.8, a heavily obscured, radio-loud quasar detected in the Extended Chandra Deep Field-South, the deepest layer of the NuSTAR extragalactic survey (~400 ks, at its deepest). NuSTAR J033202-2746.8 is reliably detected by NuSTAR only at E > 8 keV and has a very flat spectral slope in the NuSTAR energy band ($\Gamma =0.55^{+0.62}_{-0.64}$; 3-30 keV). Combining the NuSTAR data with extremely deep observations by Chandra and XMM-Newton (4 Ms and 3 Ms, respectively), we constrain the broad-band X-ray spectrum of NuSTAR J033202-2746.8, indicating that this source is a heavily obscured quasar ($N_{\rm H}=5.6^{+0.9}_{-0.8}\times 10^{23}$ cm–2) with luminosity L 10-40 keV ≈ 6.4 × 1044 erg s–1. Although existing optical and near-infrared (near-IR) data, as well as follow-up spectroscopy with the Keck and VLT telescopes, failed to provide a secure redshift identification for NuSTAR J033202-2746.8, we reliably constrain the redshift z = 2.00 ± 0.04 from the X-ray spectral features (primarily from the iron K edge). The NuSTAR spectrum shows a significant reflection component ($R=0.55^{+0.44}_{-0.37}$), which was not constrained by previous analyses of Chandra and XMM-Newton data alone. The measured reflection fraction is higher than the R ~ 0 typically observed in bright radio-loud quasars such as NuSTAR J033202-2746.8, which has L 1.4 GHz ≈ 1027 W Hz–1. Constraining the spectral shape of active galactic nuclei (AGNs), including bright quasars, is very important for understanding the AGN population, and can have a strong impact on the modeling of the X-ray background. Our results show the importance of NuSTAR in investigating the broad-band spectral properties of quasars out to high redshift

The NuSTAR Serendipitous Survey: Hunting for the Most Extreme Obscured AGN at >10 keV

We identify sources with extremely hard X-ray spectra (i.e., with photon indices of ${\rm{\Gamma }}\lesssim 0.6$) in the 13 deg2 NuSTAR serendipitous survey, to search for the most highly obscured active galactic nuclei (AGNs) detected at $\gt 10\,\mathrm{keV}$. Eight extreme NuSTAR sources are identified, and we use the NuSTAR data in combination with lower-energy X-ray observations (from Chandra, Swift XRT, and XMM-Newton) to characterize the broadband (0.5–24 keV) X-ray spectra. We find that all of the extreme sources are highly obscured AGNs, including three robust Compton-thick (CT; ${N}_{{\rm{H}}}\gt 1.5\times {10}^{24}$ cm−2) AGNs at low redshift ($z\lt 0.1$) and a likely CT AGN at higher redshift (z = 0.16). Most of the extreme sources would not have been identified as highly obscured based on the low-energy ($\lt 10$ keV) X-ray coverage alone. The multiwavelength properties (e.g., optical spectra and X-ray–mid-IR luminosity ratios) provide further support for the eight sources being significantly obscured. Correcting for absorption, the intrinsic rest-frame 10–40 keV luminosities of the extreme sources cover a broad range, from $\approx 5\times {10}^{42}$ to 1045 erg s−1. The estimated number counts of CT AGNs in the NuSTAR serendipitous survey are in broad agreement with model expectations based on previous X-ray surveys, except for the lowest redshifts ($z\lt 0.07$), where we measure a high CT fraction of ${f}_{\mathrm{CT}}^{\mathrm{obs}}={30}_{-12}^{+16} \%$. For the small sample of CT AGNs, we find a high fraction of galaxy major mergers (50% ± 33%) compared to control samples of "normal" AGNs

The NuSTAR Extragalactic Survey: A First Sensitive Look at the High-energy Cosmic X-Ray Background Population

We report on the first 10 identifications of sources serendipitously detected by the Nuclear Spectroscopic Telescope Array (NuSTAR) to provide the first sensitive census of the cosmic X-ray background source population at gsim 10 keV. We find that these NuSTAR-detected sources are ≈100 times fainter than those previously detected at gsim 10 keV and have a broad range in redshift and luminosity (z = 0.020-2.923 and L 10-40 keV ≈ 4 × 1041-5 × 1045 erg s–1); the median redshift and luminosity are z ≈ 0.7 and L 10-40 keV ≈ 3 × 1044 erg s–1, respectively. We characterize these sources on the basis of broad-band ≈0.5-32 keV spectroscopy, optical spectroscopy, and broad-band ultraviolet-to-mid-infrared spectral energy distribution analyses. We find that the dominant source population is quasars with L 10-40 keV > 1044 erg s–1, of which ≈50% are obscured with N H gsim 1022 cm–2. However, none of the 10 NuSTAR sources are Compton thick (N H gsim 1024 cm–2) and we place a 90% confidence upper limit on the fraction of Compton-thick quasars (L 10-40 keV > 1044 erg s–1) selected at gsim 10 keV of lsim 33% over the redshift range z = 0.5-1.1. We jointly fitted the rest-frame ≈10-40 keV data for all of the non-beamed sources with L 10-40 keV > 1043 erg s–1 to constrain the average strength of reflection; we find R < 1.4 for Γ = 1.8, broadly consistent with that found for local active galactic nuclei (AGNs) observed at gsim 10 keV. We also constrain the host-galaxy masses and find a median stellar mass of ≈1011 M ☉, a factor ≈5 times higher than the median stellar mass of nearby high-energy selected AGNs, which may be at least partially driven by the order of magnitude higher X-ray luminosities of the NuSTAR sources. Within the low source-statistic limitations of our study, our results suggest that the overall properties of the NuSTAR sources are broadly similar to those of nearby high-energy selected AGNs but scaled up in luminosity and mass

Improved W boson mass measurement with the D0 detector

We have measured the W boson mass using the D0 detector and a data sample of 82 pb^-1 from the Tevatron collider. This measurement used W -> e nu decays, where the electron is close to a boundary of a central electromagnetic calorimeter module. Such 'edge' electrons have not been used in any previous D0 analysis, and represent a 14% increase in the W boson sample size. For these electrons, new response and resolution parameters are determined, and revised backgrounds and underlying event energy flow measurements are made. When the current measurement is combined with previous D0 W boson mass measurements, we obtain M_W = 80.483 +/- 0.084 GeV. The 8% improvement from the previous D0 measurement is primarily due to the improved determination of the response parameters for non-edge electrons using the sample of Z bosons with non-edge and edge electrons.Comment: submitted to Phys. Rev. D; 20 pages, 18 figures, 9 table