Patients with treated indolent lymphomas immunized with BNT162b2 have reduced anti-spike neutralizing IgG to SARS-CoV-2 variants, but preserved antigen-specific T cell responses

Patients with indolent lymphoma undertaking recurrent or continuous B cell suppression are at risk of severe COVID-19. Patients and healthy controls (HC; N = 13) received two doses of BNT162b2: follicular lymphoma (FL; N = 35) who were treatment naïve (TN; N = 11) or received immunochemotherapy (ICT; N = 23) and Waldenström's macroglobulinemia (WM; N = 37) including TN (N = 9), ICT (N = 14), or treated with Bruton's tyrosine kinase inhibitors (BTKi; N = 12). Anti-spike immunoglobulin G (IgG) was determined by a high-sensitivity flow-cytometric assay, in addition to live-virus neutralization. Antigen-specific T cells were identified by coexpression of CD69/CD137 and CD25/CD134 on T cells. A subgroup (N = 29) were assessed for third mRNA vaccine response, including omicron neutralization. One month after second BNT162b2, median anti-spike IgG mean fluorescence intensity (MFI) in FL ICT patients (9977) was 25-fold lower than TN (245 898) and HC (228 255, p =.0002 for both). Anti-spike IgG correlated with lymphocyte count (r =.63; p =.002), and time from treatment (r =.56; p =.007), on univariate analysis, but only with lymphocyte count on multivariate analysis (p =.03). In the WM cohort, median anti-spike IgG MFI in BTKi patients (39 039) was reduced compared to TN (220 645, p =.0008) and HC (p <.0001). Anti-spike IgG correlated with neutralization of the delta variant (r =.62, p <.0001). Median neutralization titer for WM BTKi (0) was lower than HC (40, p <.0001) for early-clade and delta. All cohorts had functional T cell responses. Median anti-spike IgG decreased 4-fold from second to third dose (p =.004). Only 5 of 29 poor initial responders assessed after third vaccination demonstrated seroconversion and improvement in neutralization activity, including to the omicron variant

Surviving rather than thriving: Understanding the experiences of women coaches using a theory of gendered social well-being

In shifting our gaze to the sociological impact of being in the minority, the purpose of this study was to substantiate a model of gendered social well-being to appraise women coaches’ circumstances, experiences and challenges as embedded within the social structures and relations of their profession. This is drawn on indepth interviews with a sample of head women coaches within the UK. The findings demonstrate that personal lives, relationships, social and family commitments were sidelined by many of the participants in order to meet the expectations of being a (woman) coach. We locate these experiences in the organisational practices of high performance sport which hinder women coaches from having meaningful control over their lives. The complexities of identity are also revealed through the interplay of gender with (dis)ability, age and whiteness as evidence of hegemonic femininity within the coaching profession. Consequently, for many women, coaching is experienced as a ‘developmental dead-end’

First X-ray polarization measurement confirms the low black-hole spin in LMC X-3

X-ray polarization is a powerful tool to investigate the geometry of accreting material around black holes, allowing independent measurements of the black hole spin and orientation of the innermost parts of the accretion disk. We perform the X-ray spectro-polarimetric analysis of an X-ray binary system in the Large Magellanic Cloud, LMC X-3, that hosts a stellar-mass black hole, known to be persistently accreting since its discovery. We report the first detection of the X-ray polarization in LMC X-3 with the Imaging X-ray Polarimetry Explorer, and find the average polarization degree of 3.2% +- 0.6% and a constant polarization angle -42 deg +- 6 deg over the 2-8 keV range. Using accompanying spectroscopic observations by NICER, NuSTAR, and the Neil Gehrels Swift observatories, we confirm previous measurements of the black hole spin via the X-ray continuum method, a ~ 0.2. From polarization analysis only, we found consistent results with low black-hole spin, with an upper limit of a < 0.7 at a 90% confidence level. A slight increase of the polarization degree with energy, similar to other black-hole X-ray binaries in the soft state, is suggested from the data but with a low statistical significance.Comment: 14 pages, 8 figures, submitted to Ap

Endogenous Retinoic Acid Activity in Principal Cells and Intercalated Cells of Mouse Collecting Duct System

Background: Retinoic acid is the bioactive derivative of vitamin A, which plays an indispensible role in kidney development by activating retinoic acid receptors. Although the location, concentration and roles of endogenous retinoic acid in postnatal kidneys are poorly defined, there is accumulating evidence linking post-natal vitamin A deficiency to impaired renal concentrating and acidifying capacity associated with increased susceptibility to urolithiasis, renal inflammation and scarring. The aim of this study is to examine the presence and the detailed localization of endogenous retinoic acid activity in neonatal, young and adult mouse kidneys, to establish a fundamental ground for further research into potential target genes, as well as physiological and pathophysiological roles of endogenous retinoic acid in the post-natal kidneys.Methodology/Principal Findings: RARE-hsp68-lacZ transgenic mice were employed as a reporter for endogenous retinoic acid activity that was determined by X-gal assay and immunostaining of the reporter gene product, beta-galactosidase. Double immunostaining was performed for beta-galactosidase and markers of kidney tubules to localize retinoic acid activity. Distinct pattern of retinoic acid activity was observed in kidneys, which is higher in neonatal and 1- to 3-week-old mice than that in 5- and 8-week-old mice. The activity was present specifically in the principal cells and the intercalated cells of the collecting duct system in all age groups, but was absent from the glomeruli, proximal tubules, thin limbs of Henle's loop and distal tubules.Conclusions/Significance: Endogenous retinoic acid activity exists in principal cells and intercalated cells of the mouse collecting duct system after birth and persists into adulthood. This observation provides novel insights into potential roles for endogenous retinoic acid beyond nephrogenesis and warrants further studies to investigate target genes and functions of endogenous retinoic acid in the kidney after birth, particularly in the collecting duct system

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 Dipping Accreting Neutron Star 4U 1624-49

We present the first X-ray polarimetric study of the dipping accreting neutron star 4U 1624$-$49 with the Imaging X-ray Polarimetry Explorer (IXPE). We report a detection of polarization in the non-dip time intervals with a confidence level of 99.99%. We find an average polarization degree (PD) of $3.1\pm0.7$% and a polarization angle of $81\pm6$ degrees east of north in the 2-8 keV band. We report an upper limit on the PD of 22% during the X-ray dips with 95% confidence. The PD increases with energy, reaching from $3.0\pm0.9$% in the 4-6 keV band to $6\pm2$% in the 6-8 keV band. This indicates the polarization likely arises from Comptonization. The high PD observed is unlikely to be produced by Comptonization in the boundary layer or spreading layer alone. It can be produced by the addition of an extended geometrically thin slab corona covering part of the accretion disk, as assumed in previous models of dippers, and/or a reflection component from the accretion disk

The first X-ray polarimetric observation of the black hole binary LMC X-1

We report on an X-ray polarimetric observation of the high-mass X-ray binary LMC X-1 in the high/soft state, obtained by the Imaging X-ray Polarimetry Explorer (IXPE) in October 2022. The measured polarization is below the minimum detectable polarization of 1.1 per cent (at the 99 per cent confidence level). Simultaneously, the source was observed with the NICER, NuSTAR and SRG/ART-XC instruments, which enabled spectral decomposition into a dominant thermal component and a Comptonized one. The low 2-8 keV polarization of the source did not allow for strong constraints on the black-hole spin and inclination of the accretion disc. However, if the orbital inclination of about 36 degrees is assumed, then the upper limit is consistent with predictions for pure thermal emission from geometrically thin and optically thick discs. Assuming the polarization degree of the Comptonization component to be 0, 4, or 10 per cent, and oriented perpendicular to the polarization of the disc emission (in turn assumed to be perpendicular to the large scale ionization cone orientation detected in the optical band), an upper limit to the polarization of the disc emission of 1.0, 0.9 or 0.9 per cent, respectively, is found (at the 99 per cent confidence level).Comment: 12 pages, 9 figures, 4 tables. Accepted for publication in MNRA

Tracking the X-ray Polarization of the Black Hole Transient Swift J1727.8-1613 during a State Transition

We report on a campaign on the bright black hole X-ray binary Swift J1727.8$-$1613 centered around five observations by the Imaging X-ray Polarimetry Explorer (IXPE). This is the first time it has been possible to trace the evolution of the X-ray polarization of a black hole X-ray binary across a hard to soft state transition. The 2--8 keV polarization degree slowly decreased from $\sim$4\% to $\sim$3\% across the five observations, but remained in the North-South direction throughout. Using the Australia Telescope Compact Array (ATCA), we measure the intrinsic 7.25 GHz radio polarization to align in the same direction. Assuming the radio polarization aligns with the jet direction (which can be tested in the future with resolved jet images), this implies that the X-ray corona is extended in the disk plane, rather than along the jet axis, for the entire hard intermediate state. This in turn implies that the long ($\gtrsim$10 ms) soft lags that we measure with the Neutron star Interior Composition ExploreR (NICER) are dominated by processes other than pure light-crossing delays. Moreover, we find that the evolution of the soft lag amplitude with spectral state differs from the common trend seen for other sources, implying that Swift J1727.8$-$1613 is a member of a hitherto under-sampled sub-population.Comment: Submitted to ApJ. 20 pages, 8 figure

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes