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A pediatric dosage form for crizotinib (Xalkori) was commercialized using quality-by-design principles in a material-sparing fashion. The dosage form consists of spherical multiparticulates (microspheres or pellets) that are coated and encapsulated in capsules for opening. The crizotinib (Xalkori)-coated pellet product is approved in the US for pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) and unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive. The product is also approved in the US for adult patients with non-small cell lung cancer (NSCLC) who are unable to swallow intact capsules. The lipid multiparticulate is composed of a lipid matrix, a dissolution enhancer, and an active pharmaceutical ingredient (API). The API, which remains crystalline, is embedded within the microsphere at a 60% drug loading in the uncoated lipid multiparticulate to enable dose flexibility. The melt spray congealing technique using a rotary atomizer is used to manufacture the lipid multiparticulate. Following melt spray congealing, a barrier coating is applied via fluid bed coating. Due to their particle size and content uniformity, this dosage form provides the dosing flexibility and swallowability needed for the pediatric population. The required pediatric dose is achieved by opening the capsules and combining doses of different encapsulated dose strengths, followed by administration of the multiparticulates directly to the mouth. The encapsulation process was optimized through equipment modifications and by using a design of experiments approach to understand the operating space. A limited number of development batches produced using commercial-scale equipment were leveraged to design, understand, and verify the manufacturing process space. The quality by design and material-sparing approach taken to design the melt spray congeal and encapsulation manufacturing processes resulted in a pediatric product with exceptional content uniformity (a 95% confidence and 99% probability of passing USP content uniformity testing for future batches).

Hot Jupiters were many of the first exoplanets discovered in the 1990s, but in the decades since their discovery the mysteries surrounding their origins have remained. Here we present nine new hot Jupiters (TOI-1855 b, TOI-2107 b, TOI-2368 b, TOI-3321 b, TOI-3894 b, TOI-3919 b, TOI-4153 b, TOI-5232 b, and TOI-5301 b) discovered by NASA’s TESS mission and confirmed using ground-based imaging and spectroscopy. These discoveries are the first in a series of papers named the Migration and Evolution of giant ExoPlanets survey and are part of an ongoing effort to build a complete sample of hot Jupiters orbiting FGK stars, with a limiting Gaia G -band magnitude of 12.5. This effort aims to use homogeneous detection and analysis techniques to generate a set of precisely measured stellar and planetary properties that is ripe for statistical analysis. The nine planets presented in this work occupy a range of masses (0.55 M _J < M _P < 3.88 M _J ) and sizes (0.967 R _J < R _P < 1.438 R _J ) and orbit stars that have an effective temperature in the range of 5360 K < T _eff < 6860 K with Gaia G -band magnitudes ranging from 11.1 to 12.7. Two of the planets in our sample have detectable orbital eccentricity: TOI-3919 b ( $e={0.259}_{-0.036}^{+0.033}$ ) and TOI-5301 b ( $e={0.33}_{-0.10}^{+0.11}$ ). These eccentric planets join a growing sample of eccentric hot Jupiters that are consistent with high-eccentricity tidal migration, one of the three most prominent theories explaining hot Jupiter formation and evolution.

The impact of the Double Asteroid Redirection Test spacecraft into Dimorphos, moon of the asteroid Didymos, changed Dimorphos’s orbit substantially, largely from the ejection of material. We present results from 12 Earth-based facilities involved in a world-wide campaign to monitor the brightness and morphology of the ejecta in the first 35 days after impact. After an initial brightening of ∼1.4 mag, we find consistent dimming rates of 0.11–0.12 mag day ^−1 in the first week, and 0.08–0.09 mag day ^−1 over the entire study period. The system returned to its pre-impact brightness 24.3–25.3 days after impact though the primary ejecta tail remained. The dimming paused briefly eight days after impact, near in time to the appearance of the second tail. This was likely due to a secondary release of material after re-impact of a boulder released in the initial impact, though movement of the primary ejecta through the aperture likely played a role.

Introduction. Urogenital and vascular anomalies, including a left duplex kidney and a left aberrant renal artery that gave rise to the left ovarian artery, were observed in a 77-year-old female cadaver during a routine dissection. Description. A left aberrant renal artery, which gave rise to the left ovarian artery, was observed originating from the aorta 4 cm below the left renal artery. Two independent contributions to a bifid ureter were found originating from the hilum of the left kidney. These two contributions descended 12.4 cm and 10.6 cm, respectively, posterior to the left aberrant renal artery and lateral to the left ovarian artery before uniting anterior to the psoas major muscle to descend 12.7 cm to the bladder. Significance. While the duplex kidney is a relatively common congenital anomaly that can be asymptomatic, it can also potentially be associated with compression of renal vasculature or the ureter. Ureteral compression can then result in several pathologies including reflux, urinary tract infection (UTI), ureteropelvic junction obstruction, or hydronephrosis. Compression of renal and ovarian vasculature can result in altered blood flow to the kidney and ovary, potentially causing fibrosis, atrophy, or organ failure. Current imaging techniques alone are insufficient for correct diagnostics of such complications, and they must be supplemented with a thorough understanding of the respective anatomical variations.