Bleeding and thrombotic risk in pregnant women with Fontan physiology

Background/objectives Pregnancy may potentiate the inherent hypercoagulability of the Fontan circulation, thereby amplifying adverse events. This study sought to evaluate thrombosis and bleeding risk in pregnant women with a Fontan.  Methods We performed a retrospective observational cohort study across 13 international centres and recorded data on thrombotic and bleeding events, antithrombotic therapies and pre-pregnancy thrombotic risk factors.  Results We analysed 84 women with Fontan physiology undergoing 108 pregnancies, average gestation 33 +/- 5 weeks. The most common antithrombotic therapy in pregnancy was aspirin (ASA, 47 pregnancies (43.5%)). Heparin (unfractionated (UFH) or low molecular weight (LMWH)) was prescribed in 32 pregnancies (30%) and vitamin K antagonist (VKA) in 10 pregnancies (9%). Three pregnancies were complicated by thrombotic events (2.8%). Thirty-eight pregnancies (35%) were complicated by bleeding, of which 5 (13%) were severe. Most bleeds were obstetric, occurring antepartum (45%) and postpartum (42%). The use of therapeutic heparin (OR 15.6, 95% CI 1.88 to 129, p=0.006), VKA (OR 11.7, 95% CI 1.06 to 130, p=0.032) or any combination of anticoagulation medication (OR 13.0, 95% CI 1.13 to 150, p=0.032) were significantly associated with bleeding events, while ASA (OR 5.41, 95% CI 0.73 to 40.4, p=0.067) and prophylactic heparin were not (OR 4.68, 95% CI 0.488 to 44.9, p=0.096). Conclusions Current antithrombotic strategies appear effective at attenuating thrombotic risk in pregnant women with a Fontan. However, this comes with high (>30%) bleeding risk, of which 13% are life threatening. Achieving haemostatic balance is challenging in pregnant women with a Fontan, necessitating individualised risk-adjusted counselling and therapeutic approaches that are monitored during the course of pregnancy

X-ray polarimetry reveals the magnetic field topology on sub-parsec scales in Tycho's supernova remnant

Supernova remnants are commonly considered to produce most of the Galactic cosmic rays via diffusive shock acceleration. However, many questions about the physical conditions at shock fronts, such as the magnetic-field morphology close to the particle acceleration sites, remain open. Here we report the detection of a localized polarization signal from some synchrotron X-ray emitting regions of Tycho's supernova remnant made by the Imaging X-ray Polarimetry Explorer. The derived polarization degree of the X-ray synchrotron emission is 9+/-2% averaged over the whole remnant, and 12+/-2% at the rim, higher than the 7-8% polarization value observed in the radio band. In the west region the polarization degree is 23+/-4%. The X-ray polarization degree in Tycho is higher than for Cassiopeia A, suggesting a more ordered magnetic-field or a larger maximum turbulence scale. The measured tangential polarization direction corresponds to a radial magnetic field, and is consistent with that observed in the radio band. These results are compatible with the expectation of turbulence produced by an anisotropic cascade of a radial magnetic-field near the shock, where we derive a magnetic-field amplification factor of 3.4+/-0.3. The fact that this value is significantly smaller than those expected from acceleration models is indicative of highly anisotropic magnetic-field turbulence, or that the emitting electrons either favor regions of lower turbulence, or accumulate close to where the magnetic-field orientation is preferentially radially oriented due to hydrodynamical instabilities.Comment: 31 pages, 7 figures, 3 tables. Accepted for publication in ApJ. Revised versio

Observations of 4U 1626-67 with the Imaging X-ray Polarimetry Explorer

We present measurements of the polarization of X-rays in the 2-8 keV band from the pulsar in the ultracompact low mass X-ray binary 4U1626-67 using data from the Imaging X-ray Polarimetry Explorer (IXPE). The 7.66 s pulsations were clearly detected throughout the IXPE observations as well as in the NICER soft X-ray observations, which we use as the basis for our timing analysis and to constrain the spectral shape over 0.4-10 keV energy band. Chandra HETGS high-resolution X-ray spectra were also obtained near the times of the IXPE observations for firm spectral modeling. We find an upper limit on the pulse-averaged linear polarization of <4% (at 95% confidence). Similarly, there was no significant detection of polarized flux in pulse phase intervals when subdividing the bandpass by energy. However, spectropolarimetric modeling over the full bandpass in pulse phase intervals provide a marginal detection of polarization of the power-law spectral component at the 4.8 +/- 2.3% level (90% confidence). We discuss the implications concerning the accretion geometry onto the pulsar, favoring two-component models of the pulsed emission.Comment: 19 pages, 7 figures, 7 tables; accepted for publication in the Astrophysical Journa

The Inflammatory Kinase MAP4K4 Promotes Reactivation of Kaposi's Sarcoma Herpesvirus and Enhances the Invasiveness of Infected Endothelial Cells

Kaposi's sarcoma (KS) is a mesenchymal tumour, which is caused by Kaposi's sarcoma herpesvirus (KSHV) and develops under inflammatory conditions. KSHV-infected endothelial spindle cells, the neoplastic cells in KS, show increased invasiveness, attributed to the elevated expression of metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). The majority of these spindle cells harbour latent KSHV genomes, while a minority undergoes lytic reactivation with subsequent production of new virions and viral or cellular chemo- and cytokines, which may promote tumour invasion and dissemination. In order to better understand KSHV pathogenesis, we investigated cellular mechanisms underlying the lytic reactivation of KSHV. Using a combination of small molecule library screening and siRNA silencing we found a STE20 kinase family member, MAP4K4, to be involved in KSHV reactivation from latency and to contribute to the invasive phenotype of KSHV-infected endothelial cells by regulating COX-2, MMP-7, and MMP-13 expression. This kinase is also highly expressed in KS spindle cells in vivo. These findings suggest that MAP4K4, a known mediator of inflammation, is involved in KS aetiology by regulating KSHV lytic reactivation, expression of MMPs and COX-2, and, thereby modulating invasiveness of KSHV-infected endothelial cells. © 2013 Haas et al

Magnetic structures and turbulence in SN 1006 revealed with imaging X-ray polarimetry

Young supernova remnants (SNRs) strongly modify surrounding magnetic fields, which in turn play an essential role in accelerating cosmic rays (CRs). X-ray polarization measurements probe magnetic field morphology and turbulence at the immediate acceleration site. We report the X-ray polarization distribution in the northeastern shell of SN1006 from a 1 Ms observation with the Imaging X-ray Polarimetry Explorer (IXPE). We found an average polarization degree of $22.4\pm 3.5\%$ and an average polarization angle of $-45.4\pm 4.5^\circ$ (measured on the plane of the sky from north to east). The X-ray polarization angle distribution reveals that the magnetic fields immediately behind the shock in the northeastern shell of SN 1006 are nearly parallel to the shock normal or radially distributed, similar to that in the radio observations, and consistent with the quasi-parallel CR acceleration scenario. The X-ray emission is marginally more polarized than that in the radio band. The X-ray polarization degree of SN 1006 is much larger than that in Cas A and Tycho, together with the relatively tenuous and smooth ambient medium of the remnant, favoring that CR-induced instabilities set the turbulence in SN 1006 and CR acceleration is environment-dependent.Comment: 15 pages, 4 Figures, 2 Tables; accepted for publication in The Astrophysical Journa

X-ray pulsar GRO J1008−-57 as an orthogonal rotator

X-ray polarimetry is a unique way to probe geometrical configuration of highly-magnetized accreting neutron stars (X-ray pulsars). GRO J1008$-$57 is the first transient X-ray pulsar observed at two different flux levels by the Imaging X-ray Polarimetry Explorer (IXPE) during its outburst in November 2022. The polarization properties were found to be independent of the source luminosity, with the polarization degree varying between non-detection to about 15% over the pulse phase. Fitting the phase-resolved spectro-polarimetric data with the rotating vector model allowed us to estimate the pulsar inclination (130 deg, which is in good agreement with the orbital inclination), the position angle (75 deg) of the pulsar spin axis, and the magnetic obliquity (74 deg). This makes GRO J1008$-$57 the first confidently identified X-ray pulsar as a nearly orthogonal rotator. The results are discussed in the context of the neutron star atmosphere models and theories of pulsars' axis alignment.Comment: 11 pages, 7 figures, submitted to A&A. arXiv admin note: text overlap with arXiv:2209.0244

X-ray Polarization of the Eastern Lobe of SS 433

How astrophysical systems translate the kinetic energy of bulk motion into the acceleration of particles to very high energies is a pressing question. SS 433 is a microquasar that emits TeV gamma-rays indicating the presence of high-energy particles. A region of hard X-ray emission in the eastern lobe of SS 433 was recently identified as an acceleration site. We observed this region with the Imaging X-ray Polarimetry Explorer and measured a polarization degree in the range 38% to 77%. The high polarization degree indicates the magnetic field has a well ordered component if the X-rays are due to synchrotron emission. The polarization angle is in the range -12 to +10 degrees (east of north) which indicates that the magnetic field is parallel to the jet. Magnetic fields parallel to the bulk flow have also been found in supernova remnants and the jets of powerful radio galaxies. This may be caused by interaction of the flow with the ambient medium.Comment: 8 pages, accepted in the Astrophysical Journal Letter

X-ray polarimetry of the accreting pulsar GX 301-2

The phase- and energy-resolved polarization measurements of accreting X-ray pulsars (XRPs) allow us to test different theoretical models of their emission, as well as to provide an avenue to determine the emission region geometry. We present the results of the observations of the XRP GX 301-2 performed with the Imaging X-ray Polarimetry Explorer (IXPE). GX 301-2 is a persistent XRP with one of the longest known spin periods of ~680 s. A massive hyper-giant companion star Wray 977 supplies mass to the neutron star via powerful stellar winds. We do not detect significant polarization in the phase-averaged data using spectro-polarimetric analysis, with the upper limit on the polarization degree (PD) of 2.3% (99% confidence level). Using the phase-resolved spectro-polarimetric analysis we get a significant detection of polarization (above 99% c.l.) in two out of nine phase bins and marginal detection in three bins, with a PD ranging between ~3% and ~10%, and a polarization angle varying in a very wide range from ~0 deg to ~160 deg. Using the rotating vector model we obtain constraints on the pulsar geometry using both phase-binned and unbinned analysis getting excellent agreement. Finally, we discuss possible reasons for a low observed polarization in GX 301-2.Comment: 10 pages, 10 figures, submitted to A&

IXPE Observations of the Quintessential Wind-accreting X-Ray Pulsar Vela X-1

The radiation from accreting X-ray pulsars was expected to be highly polarized, with some estimates for the polarization degree of up to 80%. However, phase-resolved and energy-resolved polarimetry of X-ray pulsars is required in order to test different models and to shed light on the emission processes and the geometry of the emission region. Here we present the first results of the observations of the accreting X-ray pulsar Vela X-1 performed with the Imaging X-ray Polarimetry Explorer. Vela X-1 is considered to be the archetypal example of a wind-accreting, high-mass X-ray binary system, consisting of a highly magnetized neutron star accreting matter from its supergiant stellar companion. The spectropolarimetric analysis of the phase-averaged data for Vela X-1 reveals a polarization degree (PD) of 2.3% ± 0.4% at the polarization angle (PA) of −47.°3 ± 5.°4. A low PD is consistent with the results obtained for other X-ray pulsars and is likely related to the inverse temperature structure of the neutron star atmosphere. The energy-resolved analysis shows the PD above 5 keV reaching 6%–10% and a ∼90° difference in the PA compared to the data in the 2–3 keV range. The phase-resolved spectropolarimetric analysis finds a PD in the range 0%–9% with the PA varying between −80° and 40°

A polarimetrically oriented X-ray stare at the accreting pulsar EXO 2030+375

Accreting X-ray pulsars (XRPs) are presumably ideal targets for polarization measurements, as their high magnetic field strength is expected to polarize the emission up to a polarization degree of ~80%. However, such expectations are being challenged by recent observations of XRPs with the Imaging X-ray Polarimeter Explorer (IXPE). Here we report on the results of yet another XRP, EXO 2030+375, observed with IXPE and contemporarily monitored with Insight-HXMT and SRG/ART-XC. In line with recent results obtained with IXPE for similar sources, analysis of the EXO 2030+375 data returns a low polarization degree of 0%-3% in the phase-averaged study and variation in the range 2%-7% in the phase-resolved study. Using the rotating vector model we constrain the geometry of the system and obtain a value for the magnetic obliquity of ~$60^{\circ}$. Considering also the estimated pulsar inclination of ~$130^{\circ}$, this indicates that the magnetic axis swings close to the observer line of sight. Our joint polarimetric, spectral and timing analysis hint to a complex accreting geometry where magnetic multipoles with asymmetric topology and gravitational light bending significantly affect the observed source behavior.Comment: A&A accepted. Proofs versio