Timing Analysis of the 2022 Outburst of the Accreting Millisecond X-Ray Pulsar SAX J1808.4-3658: Hints of an Orbital Shrinking

We present a pulse timing analysis of NICER observations of the accreting millisecond X-ray pulsar SAX J1808.4-3658 during the outburst that started on 2022 August 19. Similar to previous outbursts, after decaying from a peak luminosity of ≃1 × 1036 erg s-1 in about a week, the pulsar entered a ~1 month long reflaring stage. Comparison of the average pulsar spin frequency during the outburst with those previously measured confirmed the long-term spin derivative of ν˙SD=−(1.15±0.06)×10−15 Hz s-1, compatible with the spin-down torque of a ≈1026 G cm3 rotating magnetic dipole. For the first time in the last twenty years, the orbital phase evolution shows evidence for a decrease of the orbital period. The long-term behavior of the orbit is dominated by an ~11 s modulation of the orbital phase epoch consistent with a ~21 yr period. We discuss the observed evolution in terms of a coupling between the orbit and variations in the mass quadrupole of the companion star

Evidence of intra-binary shock emission from the redback pulsar PSR J1048+2339

We present simultaneous multiwavelength observations of the 4.66 ms redback pulsar PSR J1048+2339. We performed phase-resolved spectroscopy with the Very Large Telescope (VLT) searching for signatures of a residual accretion disk or intra-binary shock emission, constraining the companion radial velocity semi-amplitude ($K_2$), and estimating the neutron star mass ($M_{\rm NS}$). Using the FORS2-VLT intermediate-resolution spectra, we measured a companion velocity of $291 < K_2 < 348$ km s$^{-1}$ and a binary mass ratio of $0.209 < q < 0.250$. Combining our results for $K_2$ and $q$, we constrained the mass of the neutron star and the companion to $(1.0 < M_{\rm NS} < 1.6){\rm sin}^{-3}i\,M_{\odot}$ and $(0.24 < M_2 < 0.33){\rm sin}^{-3}i\,M_{\odot}$, respectively, where $i$ is the system inclination. The Doppler map of the H$\alpha$ emission line exhibits a spot feature at the expected position of the companion star and an extended bright spot close to the inner Lagrangian point. We interpret this extended emission as the effect of an intra-binary shock originating from the interaction between the pulsar relativistic wind and the matter leaving the companion star. The mass loss from the secondary star could be either due to Roche-lobe overflow or to the ablation of its outer layer by the energetic pulsar wind. Contrastingly, we find no evidence for an accretion disk. We report on the results of the SRT and the LOFAR simultaneous radio observations at three different frequencies (150 MHz, 336 MHz, and 1400 MHz). No pulsed radio signal is found in our search. This is probably due to both scintillation and the presence of material expelled from the system which can cause the absorption of the radio signal at low frequencies. Finally, we report on an attempt to search for optical pulsations using IFI+Iqueye mounted at the 1.2 m Galileo telescope at the Asiago Observatory.Comment: 12 pages, 10 figures, accepted for publication in A&

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Optical and ultraviolet pulsed emission from an accreting millisecond pulsar

Millisecond spinning, low-magnetic-field neutron stars are believed to attain their fast rotation in a 0.1–1-Gyr-long phase during which they accrete matter endowed with angular momentum from a low-mass companion star1. Despite extensive searches, coherent periodicities originating from accreting neutron star magnetospheres have been detected only at X-ray energies2 and in ~10% of the currently known systems3. Here we report the detection of optical and ultraviolet coherent pulsations at the X-ray period of the transient low-mass X-ray binary system SAX J1808.4−3658, during an accretion outburst that occurred in August 20194. At the time of the observations, the pulsar was surrounded by an accretion disk, displayed X-ray pulsations and its luminosity was consistent with magnetically funnelled accretion onto the neutron star. Current accretion models fail to account for the luminosity of both optical and ultraviolet pulsations; these are instead more likely to be driven by synchro-curvature radiation5,6 in the pulsar magnetosphere or just outside of it. This interpretation would imply that particle acceleration can take place even when mass accretion is going on, and opens up new perspectives in the study of coherent optical/ultraviolet pulsations from fast-spinning accreting neutron stars in low-mass X-ray binary systems

Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis: analysis by the Pharmachild Safety Adjudication Committee

Background To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC). Methods The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI. Results A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI. Conclusions We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies

Subcutaneous abatacept in patients with polyarticular-course juvenile idiopathic arthritis : results from a phase III open-label study

OBJECTIVE : To investigate the pharmacokinetics, effectiveness, and safety of subcutaneous (SC) abatacept treatment over 24 months in patients with polyarticular‐course juvenile idiopathic arthritis (JIA). METHODS: In this phase III, open‐label, international, multicenter, single‐arm study, patients with polyarticular JIA (cohort 1, ages 6–17 years and cohort 2, ages 2–5 years) in whom treatment with ≥1 disease‐modifying antirheumatic drug was unsuccessful received weight‐tiered SC abatacept weekly: 10 to <25 kg (50 mg), 25 to <50 kg (87.5 mg), ≥50 kg (125 mg). Patients who had met the JIA–American College of Rheumatology 30% improvement criteria (achieved a JIA‐ACR 30 response) at month 4 were given the option to continue SC abatacept to month 24. The primary end point was the abatacept steady‐state serum trough concentration (Cminss) in cohort 1 at month 4. Other outcome measures included JIA‐ACR 30, 50, 70, 90, 100, and inactive disease status, the median Juvenile Arthritis Disease Activity Score in 71 joints using the C‐reactive protein level (JADAS‐71–CRP) over time, safety, and immunogenicity. RESULTS : The median abatacept Cminss at month 4 (primary end point) and at month 24 was above the target therapeutic exposure (10 μg/ml) in both cohorts. The percentage of patients who had achieved JIA‐ACR 30, 50, 70, 90, or 100 responses or had inactive disease responses at month 4 (intent‐to‐treat population) was 83.2%, 72.8%, 52.6%, 28.3%, 14.5%, and 30.1%, respectively, in cohort 1 (n = 173) and 89.1%, 84.8%, 73.9%, 58.7%, 41.3%, and 50.0%, respectively, in cohort 2 (n = 46); the responses were maintained to month 24. The median (interquartile range) JADAS‐71–CRP improved from baseline to month 4: cohort 1, from 21.0 (13.5, 30.3) to 4.6 (2.1, 9.4); cohort 2, from 18.1 (14.0, 23.1) to 2.1 (0.3, 4.4). Improvements were sustained to month 24, at which time 27 of 173 patients (cohort 1) and 11 of 22 patients (cohort 2) had achieved JADAS‐71–CRP remission. No unexpected adverse events were reported; 4 of 172 patients (2.3%) in cohort 1 and 4 of 46 (8.7%) in cohort 2 developed anti‐abatacept antibodies, with no clinical effects. CONCLUSION : Weight‐stratified SC abatacept yielded target therapeutic exposures across age and weight groups, was well tolerated, and improved polyarticular JIA symptoms over 24 months.Results From a Phase III Open‐Label StudyWriting assistance was funded by Bristol‐Myers Squibb.https://onlinelibrary.wiley.com/journal/23265205am2018Internal Medicin

Probing Jet Launching in Neutron Star X-Ray Binaries: The Variable and Polarized Jet of SAX J1808.4–3658

International audienceWe report on an optical photometric and polarimetric campaign on the accreting millisecond X-ray pulsar (AMXP) SAX J1808.4–3658 during its 2019 outburst. The emergence of a low-frequency excess in the spectral energy distribution in the form of a red excess above the disk spectrum (seen most prominently in the z, i, and R bands) is observed as the outburst evolves. This is indicative of optically thin synchrotron emission due to a jet, as seen previously in this source and in other AMXPs during outburst. At the end of the outburst decay, the source enters a reflaring state. The low-frequency excess is still observed during the reflares. Our optical (BVRI) polarimetric campaign shows variable linear polarization (LP) throughout the outburst. We show that this is intrinsic to the source, with low-level but significant detections (0.2%–2%) in all bands. The LP spectrum is red during both the main outburst and the reflaring state, favoring a jet origin for this variable polarization over other interpretations, such as Thomson scattering with free electrons from the disk or the propelled matter. During the reflaring state, a few episodes with stronger LP levels (1%–2%) are observed. The low-level, variable LP is suggestive of strongly tangled magnetic fields near the base of the jet. These results clearly demonstrate how polarimetry is a powerful tool for probing the magnetic field structure in X-ray binary jets, as for active galactic nuclei jets

Evidence of intra-binary shock emission from the redback pulsar PSR J1048+2339

We present simultaneous multiwavelength observations of the 4.66 ms redback pulsar PSR J1048+2339. We performed phase-resolved spectroscopy with the Very Large Telescope (VLT) searching for signatures of a residual accretion disk or intra-binary shock emission, constraining the companion radial velocity semi-amplitude (K2), and estimating the neutron star mass (MNS). Using the FORS2-VLT intermediate-resolution spectra, we measured a companion velocity of 291 < K2 < 348 km s−1 and a binary mass ratio of 0.209 < q < 0.250. Combining our results for K2 and q, we constrained the mass of the neutron star and the companion to (1.0 < MNS < 1.6) sin−3 i M⊙ and (0.24 < M2 < 0.33) sin−3i M⊙, respectively, where i is the system inclination. The Doppler map of the Hα emission line exhibits a spot feature at the expected position of the companion star and an extended bright spot close to the inner Lagrangian point. We interpret this extended emission as the effect of an intra-binary shock originating from the interaction between the pulsar relativistic wind and the matter leaving the companion star. The mass loss from the secondary star could be either due to Roche-lobe overflow or to the ablation of its outer layer by the energetic pulsar wind. Contrastingly, we find no evidence for an accretion disk. We report on the results of the Sardinia Radio Telescope (SRT) and the Low-Frequency Array (LOFAR) telescope simultaneous radio observations at three different frequencies (150 MHz, 336 MHz, and 1400 MHz). No pulsed radio signal is found in our search. This is probably due to both scintillation and the presence of material expelled from the system which can cause the absorption of the radio signal at low frequencies. The confirmation of this hypothesis is given by another SRT observation (L-band) taken in 2019, in which a pulsed signal is detected. Finally, we report on an attempt to search for optical pulsations using IFI+Iqueye mounted at the 1.2 m Galileo telescope at the Asiago Observatory

Subcutaneous Abatacept in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis: Results From a Phase III Open-Label Study

none59Objective: To investigate the pharmacokinetics, effectiveness, and safety of subcutaneous (SC) abatacept treatment over 24 months in patients with polyarticular-course juvenile idiopathic arthritis (JIA). Methods: In this phase III, open-label, international, multicenter, single-arm study, patients with polyarticular JIA (cohort 1, ages 6–17 years and cohort 2, ages 2–5 years) in whom treatment with ≥1 disease-modifying antirheumatic drug was unsuccessful received weight-tiered SC abatacept weekly: 10 to &lt;25 kg (50 mg), 25 to &lt;50 kg (87.5 mg), ≥50 kg (125 mg). Patients who had met the JIA–American College of Rheumatology 30% improvement criteria (achieved a JIA-ACR 30 response) at month 4 were given the option to continue SC abatacept to month 24. The primary end point was the abatacept steady-state serum trough concentration (Cminss) in cohort 1 at month 4. Other outcome measures included JIA-ACR 30, 50, 70, 90, 100, and inactive disease status, the median Juvenile Arthritis Disease Activity Score in 71 joints using the C-reactive protein level (JADAS-71–CRP) over time, safety, and immunogenicity. Results: The median abatacept Cminss at month 4 (primary end point) and at month 24 was above the target therapeutic exposure (10 μg/ml) in both cohorts. The percentage of patients who had achieved JIA-ACR 30, 50, 70, 90, or 100 responses or had inactive disease responses at month 4 (intent-to-treat population) was 83.2%, 72.8%, 52.6%, 28.3%, 14.5%, and 30.1%, respectively, in cohort 1 (n&nbsp;=&nbsp;173) and 89.1%, 84.8%, 73.9%, 58.7%, 41.3%, and 50.0%, respectively, in cohort 2 (n&nbsp;= 46); the responses were maintained to month 24. The median (interquartile range) JADAS-71–CRP improved from baseline to month 4: cohort 1, from 21.0 (13.5, 30.3) to 4.6 (2.1, 9.4); cohort 2, from 18.1 (14.0, 23.1) to 2.1 (0.3, 4.4). Improvements were sustained to month 24, at which time 27 of 173 patients (cohort 1) and 11 of 22 patients (cohort 2) had achieved JADAS-71–CRP remission. No unexpected adverse events were reported; 4 of 172 patients (2.3%) in cohort 1 and 4 of 46 (8.7%) in cohort 2 developed anti-abatacept antibodies, with no clinical effects. Conclusion: Weight-stratified SC abatacept yielded target therapeutic exposures across age and weight groups, was well tolerated, and improved polyarticular JIA symptoms over 24 months.noneBrunner H.I.; Tzaribachev N.; Vega-Cornejo G.; Louw I.; Berman A.; Calvo Penades I.; Anton J.; Avila-Zapata F.; Cuttica R.; Horneff G.; Foeldvari I.; Keltsev V.; Kingsbury D.J.; Viola D.O.; Joos R.; Lauwerys B.; Paz Gastanaga M.E.; Rama M.E.; Wouters C.; Bohnsack J.; Breedt J.; Fischbach M.; Lutz T.; Minden K.; Miraval T.; Ally M.M.T.M.; Rubio-Perez N.; Solau Gervais E.; van Zyl R.; Li X.; Nys M.; Wong R.; Banerjee S.; Lovell D.J.; Martini A.; Ruperto N.; Becker M.L.; Ilowite N.T.; Dare J.A.; Morris P.K.; Beukelman T.G.; Wagner-Weiner L.; Zemel L.; Quartier P.; Kone-Paut I.; Belot A.; Gerloni V.; Ferrandiz M.; Van Rensburg D.J.; Scheibel I.M.; Goldstein-Schainberg C.; Silva C.; Terreri M.T.S.E.L.A.; Gamir M.; Burgos Vargas R.; Faugier Fuentes E.; Cimaz R.; Alessio M.; Espada G.Brunner, H. I.; Tzaribachev, N.; Vega-Cornejo, G.; Louw, I.; Berman, A.; Calvo Penades, I.; Anton, J.; Avila-Zapata, F.; Cuttica, R.; Horneff, G.; Foeldvari, I.; Keltsev, V.; Kingsbury, D. J.; Viola, D. O.; Joos, R.; Lauwerys, B.; Paz Gastanaga, M. E.; Rama, M. E.; Wouters, C.; Bohnsack, J.; Breedt, J.; Fischbach, M.; Lutz, T.; Minden, K.; Miraval, T.; Ally, M. M. T. M.; Rubio-Perez, N.; Solau Gervais, E.; van Zyl, R.; Li, X.; Nys, M.; Wong, R.; Banerjee, S.; Lovell, D. J.; Martini, A.; Ruperto, N.; Becker, M. L.; Ilowite, N. T.; Dare, J. A.; Morris, P. K.; Beukelman, T. G.; Wagner-Weiner, L.; Zemel, L.; Quartier, P.; Kone-Paut, I.; Belot, A.; Gerloni, V.; Ferrandiz, M.; Van Rensburg, D. J.; Scheibel, I. M.; Goldstein-Schainberg, C.; Silva, C.; Terreri, M. T. S. E. L. A.; Gamir, M.; Burgos Vargas, R.; Faugier Fuentes, E.; Cimaz, R.; Alessio, M.; Espada, G