Monitoring observations of SMC X-1's excursions (MOOSE)-II: A new excursion accompanies spin-up acceleration

SMC X-1 is a high-mass X-ray binary showing superorbital modulation with an unstable period. Previous monitoring shows three excursion events in 1996--1998, 2005--2007, and 2014--2016. The superorbital period drifts from >60 days to <40 days and then evolves back during an excursion. Here we report a new excursion event of SMC X-1 in 2020--2021, indicating that the superorbital modulation has an unpredictable, chaotic nature. We trace the spin-period evolution and find that the spin-up rate accelerated one year before the onset of this new excursion, which suggests a possible inside-out process connecting the spin-up acceleration and the superorbital excursion. This results in a deviation of the spin period residual, similar to the behaviour of the first excursion in 1996--1998. In further analysis of the pulse profile evolution, we find that the pulsed fraction shows a long-term evolution and may be connected to the superorbital excursion. These discoveries deepen the mystery of SMC X-1 because they cannot be solely interpreted by the warped disc model. Upcoming pointed observations and theoretical studies may improve our understanding of the detailed accretion mechanisms taking place.Comment: 7 pages, 3 figures, Accepted for publication in MNRA

The Milky Way Bulge extra-tidal star survey: BH 261 (AL 3)

The Milky Way Bulge extra-tidal star survey (MWBest) is a spectroscopic survey with the goal of identifying stripped globular cluster stars from inner Galaxy clusters. In this way, an indication of the fraction of metal-poor bulge stars that originated from globular clusters can be determined. We observed and analyzed stars in and around BH 261, an understudied globular cluster in the bulge. From seven giants within the tidal radius of the cluster, we measured an average heliocentric radial velocity of = -61 +- 2.6 km/s with a radial velocity dispersion of \sigma = 6.1 +- 1.9 km/s. The large velocity dispersion may have arisen from tidal heating in the cluster's orbit about the Galactic center, or because BH 261 has a high dynamical mass as well as a high mass-to-light ratio. From spectra of five giants, we measure an average metallicity of = -1.1 +- 0.2 dex. We also spectroscopically confirm an RR Lyrae star in BH 261, which yields a distance to the cluster of 7.1 +- 0.4~kpc. Stars with 3D velocities and metallicities consistent with BH 261 reaching to ~0.5 degrees from the cluster are identified. A handful of these stars are also consistent with the spatial distribution of that potential debris from models focussing on the most recent disruption of the cluster.Comment: accepted for publication in The Astronomical Journa

Extragalactic Star Cluster Science with the Nancy Grace Roman Space Telescope's High Latitude Wide Area Survey and the Vera C. Rubin Observatory

The Nancy Grace Roman Telescope's High Latitude Wide Area Survey will have a number of synergies with the Vera Rubin Observatory's Legacy Survey of Space and Time (LSST), particularly for extragalactic star clusters. Understanding the nature of star clusters and star cluster systems are key topics in many areas of astronomy, chief among them stellar evolution, high energy astrophysics, galaxy assembly/dark matter, the extragalactic distance scale, and cosmology. One of the challenges will be disentangling the age/metallicity degeneracy because young ($\sim$Myr) metal-rich clusters have similar SEDs to old ($\sim$Gyr) metal-poor clusters. Rubin will provide homogeneous, $ugrizy$ photometric coverage, and measurements in the red Roman filters will help break the age-metallicity and age-extinction degeneracies, providing the first globular cluster samples that cover wide areas while essentially free of contamination from Milky Way stars. Roman's excellent spatial resolution will also allow measurements of cluster sizes. We advocate for observations of a large sample of galaxies with a range of properties and morphologies in the Rubin/LSST footprint matching the depth of the LSST Wide-Fast-Deep field $i$ band limit (26.3 mag), and recommend adding the F213 filter to the survey.Comment: white paper submitted for Roman CCS inpu

Assessing the reach, effectiveness, adoption, implementation, and maintenance of the ProACTIVE SCI physical activity counseling intervention among physiotherapists and SCI peer coaches during the transition from rehabilitation to community

IntroductionPhysical Activity (PA) levels for individuals with spinal cord injury (SCI) peak during rehabilitation and sharply decline post-discharge. The ProACTIVE SCI intervention has previously demonstrated very large-sized effects on PA; however, it has not been adapted for use at this critically understudied timepoint. The objective is to evaluate the reach, effectiveness, adoption, implementation, and maintenance of the ProACTIVE SCI intervention delivered by physiotherapists and SCI peer coaches during the transition from rehabilitation to community.MethodsA single-group, within-subjects, repeated measures design was employed. The implementation intervention consisted of PA counseling training, champion support, prompts and cues, and follow-up training/community of practice sessions. Physiotherapists conducted counseling sessions in hospital, then referred patients to SCI peer coaches to continue counseling for 1-year post-discharge in the community. The RE-AIM Framework was used to guide intervention evaluation.ResultsReach: 82.3% of patients at the rehabilitation hospital were reached by the intervention. Effectiveness: Interventionists (physiotherapists and SCI peer coaches) perceived that PA counseling was beneficial for patients. Adoption: 100% of eligible interventionists attended at least one training session. Implementation: Interventionists demonstrated high fidelity to the intervention. Intervention strategy highlights included a feasible physiotherapist to SCI peer coach referral process, flexibility in timepoint for intervening, and time efficiency. Maintenance: Ongoing training, PA counseling tracking forms, and the ability to refer to SCI peer coaches at discharge are core components needed to sustain this intervention.DiscussionThe ProACTIVE SCI intervention was successfully adapted for use by physiotherapists and SCI peer coaches during the transition from rehabilitation to community. Findings are important for informing intervention sustainability and scale-up

From Concept to Clinical Product: A Brief History of the Novel Shigella Invaplex Vaccine&rsquo;s Refinement and Evolution

The Shigella invasin complex or Invaplex vaccine is a unique subunit approach to generate a protective immune response. Invaplex is a large, macromolecular complex consisting of the major Shigella antigens: lipopolysaccharide (LPS) and the invasion plasmid antigen (Ipa) proteins B and C. Over the past several decades, the vaccine has progressed from initial observations through pre-clinical studies to cGMP manufacture and clinical evaluations. The Invaplex product maintains unique biological properties associated with the invasiveness of virulent shigellae and also presents both serotype-specific epitopes, as well as highly conserved invasin protein epitopes, to the immunized host. The vaccine product has evolved from a native product isolated from wild-type shigellae (native Invaplex) to a more defined vaccine produced from purified LPS and recombinant IpaB and IpaC (artificial Invaplex). Each successive &ldquo;generation&rdquo; of the vaccine is derived from earlier versions, resulting in improved immunogenicity, homogeneity and effectiveness. The current vaccine, detoxified artificial Invaplex (InvaplexAR-Detox), was developed for parenteral administration by incorporating LPS with under-acylated lipid A. InvaplexAR-Detox has demonstrated an excellent safety and immunogenicity profile in initial clinical studies and is advancing toward evaluations in the target populations of children and travelers to endemic countries

From Concept to Clinical Product: A Brief History of the Novel <i>Shigella</i> Invaplex Vaccine’s Refinement and Evolution

The Shigella invasin complex or Invaplex vaccine is a unique subunit approach to generate a protective immune response. Invaplex is a large, macromolecular complex consisting of the major Shigella antigens: lipopolysaccharide (LPS) and the invasion plasmid antigen (Ipa) proteins B and C. Over the past several decades, the vaccine has progressed from initial observations through pre-clinical studies to cGMP manufacture and clinical evaluations. The Invaplex product maintains unique biological properties associated with the invasiveness of virulent shigellae and also presents both serotype-specific epitopes, as well as highly conserved invasin protein epitopes, to the immunized host. The vaccine product has evolved from a native product isolated from wild-type shigellae (native Invaplex) to a more defined vaccine produced from purified LPS and recombinant IpaB and IpaC (artificial Invaplex). Each successive “generation” of the vaccine is derived from earlier versions, resulting in improved immunogenicity, homogeneity and effectiveness. The current vaccine, detoxified artificial Invaplex (InvaplexAR-Detox), was developed for parenteral administration by incorporating LPS with under-acylated lipid A. InvaplexAR-Detox has demonstrated an excellent safety and immunogenicity profile in initial clinical studies and is advancing toward evaluations in the target populations of children and travelers to endemic countries

Long-term properties of accretion discs in X-ray binaries – III. A search for spin–superorbital correlation in SMC X-1

International audienceDue to long-term X-ray monitoring, a number of interacting binaries are now known to show X-ray periodicities on time-scales of tens to hundreds of binary orbits. In some systems, precession of a warped accretion disc is the leading model to explain the superorbital modulation. The High-Mass X-ray Binary SMC X-1 showed two excursions in superorbital period (from ∼60 d to ∼45 d) during the 1996–2011 interval, suggesting that some characteristic of the accretion disc is varying on a time-scale of years. Because its behaviour as an X-ray pulsar has also been intensively monitored, SMC X-1 offers the rare chance to track changes in both the accretion disc and pulsar behaviours over the same interval. We have used archival X-ray observations of SMC X-1 to investigate whether the evolution of its superorbital variation and pulse period are correlated. We use the 16-year data set afforded by the RXTE All-Sky Monitor to trace the behaviour of the warped accretion disc in this system, and use published pulse-period histories to trace the behaviour of the pulsar. While we cannot claim a strong detection of correlation, the first superorbital period excursion near MJD 50 800 does coincide with structure in SMC X-1’s pulse-period history. Our preferred interpretation is that the superorbital period excursion coincides with a change in the long-term spin-up rate of the SMC X-1 pulsar. In this scenario, the pulsar and the accretion disc are both responding to a change in the accretion flow, which the disc itself may regulate

Assembly, Biochemical Characterization, Immunogenicity, Adjuvanticity, and Efficacy of Shigella Artificial Invaplex

ABSTRACT The native Invaplex (InvaplexNAT) vaccine and adjuvant is an ion exchange-purified product derived from the water extract of virulent Shigella species. The key component of InvaplexNAT is a high-molecular-mass complex (HMMC) consisting of the Shigella lipopolysaccharide (LPS) and the invasin proteins IpaB and IpaC. To improve product purity and immunogenicity, artificial Invaplex (InvaplexAR) was developed using recombinant IpaB and IpaC proteins and purified Shigella LPS to assemble an HMMC consisting of all three components. Characterization of InvaplexAR by various methods demonstrated similar characteristics as the previously reported HMMC in InvaplexNAT. The well-defined InvaplexAR vaccine consistently contained greater quantities of IpaB, IpaC, and LPS than InvaplexNAT. InvaplexAR and InvaplexNAT immunogenicities were compared in mouse and guinea pig dose escalation studies. In both models, immunization induced antibody responses specific for InvaplexNAT and LPS while InvaplexAR induced markedly higher anti-IpaB and -IpaC serum IgG and IgA endpoint titers. In the murine model, homologous protection was achieved with 10-fold less InvaplexAR than InvaplexNAT and mice receiving InvaplexAR lost significantly less weight than mice receiving the same amount of InvaplexNAT. Moreover, mice immunized with InvaplexAR were protected from challenge with both homologous and heterologous Shigella serotypes. Guinea pigs receiving approximately 5-fold less InvaplexAR compared to cohorts immunized with InvaplexNAT were protected from ocular challenge. Furthermore, adjuvanticity previously attributed to InvaplexNAT was retained with InvaplexAR. The second-generation Shigella Invaplex vaccine, InvaplexAR, offers significant advantages over InvaplexNAT in reproducibility, flexible yet defined composition, immunogenicity, and protective efficacy. IMPORTANCE Shigella species are bacteria that cause severe diarrheal disease worldwide, primarily in young children. Treatment of shigellosis includes oral fluids and antibiotics, but the high burden of disease, increasing prevalence of antibiotic resistance, and long-term health consequences clearly warrant the development of an effective vaccine. One Shigella vaccine under development is termed the invasin complex or Invaplex and is designed to drive an immune response to specific antigens of the bacteria in an effort to protect an individual from infection. The work presented here describes the production and evaluation of a new generation of Invaplex. The improved vaccine stimulates the production of antibodies in immunized mice and guinea pigs and protects these animals from Shigella infection. The next step in the product’s development will be to test the safety and immune response induced in humans immunized with Invaplex

Ubiquitous Flame-Retardant Toxicants Impair Spermatogenesis in a Human Stem Cell Model

Summary: Sperm counts have rapidly declined in Western males over the past four decades. This rapid decline remains largely unexplained, but exposure to environmental toxicants provides one potential explanation for this decline. Flame retardants are highly prevalent and persistent in the environment, but many have not been assessed for their effects on human spermatogenesis. Using a human stem cell-based model of spermatogenesis, we evaluated two major flame retardants, hexabromocyclododecane (HBCDD) and tetrabromobisphenol A (TBBPA), under acute conditions simulating occupational-level exposures. Here we show that HBCDD and TBBPA are human male reproductive toxicants in vitro. Although these toxicants do not specifically affect the survival of haploid spermatids, they affect spermatogonia and primary spermatocytes through mitochondrial membrane potential perturbation and reactive oxygen species generation, ultimately causing apoptosis. Taken together, these results show that HBCDD and TBBPA affect human spermatogenesis in vitro and potentially implicate this highly prevalent class of toxicants in the decline of Western males' sperm counts. : Flame Retardant; Toxicology; Male Reproductive Endocrinology; Stem Cells Research Subject Areas: Flame Retardant, Toxicology, Male Reproductive Endocrinology, Stem Cells Researc