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Ultra-long-acting delivery platforms for HIV pre-exposure prophylaxis (PrEP) may increase adherence and maximize public health benefit. We report on an injectable, biodegradable, and removable in-situ forming implant (ISFI) that is administered subcutaneously and can release the integrase inhibitor cabotegravir (CAB) above protective benchmarks for more than 6 months. CAB ISFIs are well-tolerated in female mice and female macaques showing no signs of toxicity or chronic inflammation. In macaques, median plasma CAB concentrations exceed established PrEP protection benchmarks within 3 weeks and confer complete protection against repeated rectal SHIV challenges. Implant removal via a small incision in 2 macaques at week 12 results in a 7- to 48-fold decrease in plasma CAB levels within 72 hours. Modeling to translate CAB ISFI dosing suggests that a 3 mL injection would exceed protective benchmarks in humans for over 5 months post administration. Our results support the clinical advancement of CAB ISFIs for ultra-long-acting PrEP in humans.

 

We report on a comprehensive analysis of simultaneous X-ray polarimetric and spectral data of the bright atoll source GX 9+9 with the Imaging X-ray Polarimetry Explorer (IXPE) and NuSTAR . The source is significantly polarized in the 4–8 keV band, with a degree of 2.2%  ±  0.5% (uncertainty at the 68% confidence level). The NuSTAR broad-band spectrum clearly shows an iron line, and is well described by a model including thermal disc emission, a Comptonized component, and reflection. From a spectro-polarimetric fit, we obtain an upper limit to the polarization degree of the disc of 4% (at the 99% confidence level), while the contribution of Comptonized and reflected radiation cannot be conclusively separated. However, the polarization is consistent with resulting from a combination of Comptonization in a boundary or spreading layer, plus reflection off the disc, which significantly contributes in any realistic scenario. 

ABSTRACT X Persei is a persistent low-luminosity X-ray pulsar of period of ≈ 835 s in a Be binary system. The field strength at the neutron star surface is not known precisely, but indirect signs indicate a magnetic field above 1013 G, which makes the object one of the most magnetized known X-ray pulsars. Here we present the results of observations X Persei performed with the Imaging X-ray Polarimetry Explorer (IXPE). The X-ray polarization signal was found to be strongly dependent on the spin phase of the pulsar. The energy-averaged polarization degree in 3–8 keV band varied from several to ∼20 per cent over the pulse with a phase dependence resembling the pulse profile. The polarization angle shows significant variation and makes two complete revolutions during the pulse period, resulting in nearly nil pulse-phase averaged polarization. Applying the rotating vector model to the IXPE data we obtain the estimates for the rotation axis inclination and its position angle on the sky, as well as for the magnetic obliquity. The derived inclination is close to the orbital inclination, reported earlier for X Persei. The polarimetric data imply a large angle between the rotation and magnetic dipole axes, which is similar to the result reported recently for the X-ray pulsar GRO J1008−57. After eliminating the effect of polarization angle rotation over the pulsar phase using the best-fitting rotating vector model, the strong dependence of the polarization degree with energy was discovered, with its value increasing from 0 at ∼2 keV to 30per cent at 8 keV. 

ABSTRACT We report spectro-polarimetric results of an observational campaign of the bright neutron star low-mass X-ray binary Cyg X-2 simultaneously observed by IXPE, NICER, and INTEGRAL. Consistently with previous results, the broad-band spectrum is characterized by a lower-energy component, attributed to the accretion disc with kTin ≈ 1 keV, plus unsaturated Comptonization in thermal plasma with temperature kTe = 3 keV and optical depth τ ≈ 4, assuming a slab geometry. We measure the polarization degree in the 2–8 keV band P = 1.8 ± 0.3 per cent and polarization angle ϕ = 140° ± 4°, consistent with the previous X-ray polarimetric measurements by OSO-8 as well as with the direction of the radio jet which was earlier observed from the source. While polarization of the disc spectral component is poorly constrained with the IXPE data, the Comptonized emission has a polarization degree P = 4.0 ± 0.7 per cent and a polarization angle aligned with the radio jet. Our results strongly favour a spreading layer at the neutron star surface as the main source of the polarization signal. However, we cannot exclude a significant contribution from reflection off the accretion disc, as indicated by the presence of the iron fluorescence line. 

Typical seismic waveform data sets comprise hundreds of thousands to millions of records. Compilation is performed by time‐consuming handpicking of phase arrival times, or signal processing algorithms such as cross‐correlation. The latter generally underperform compared to handpicking. However, differences in picking methods creates variations in models and interpretation of Earth's structure. Here, we exploit the pattern recognition capabilities of Convolutional Neural Networks (CNN). Using a large handpicked data set, we train a CNN model to identify the seismic shear phase SS. This accelerates, automates, and makes consistent data compilation, a task usually completed by visual inspection and influenced by scientists' choices. The CNN model is employed to identify precursors to SS generated by mantle discontinuities. It identifies precursors in stacked and individual seismograms, producing new measurements of the mantle transition zone with quality comparable to handpicked data. This rapid acquisition of high‐quality observations has implications for automation of future seismic tomography studies.