KEYNOTE-716: Phase III study of adjuvant pembrolizumab versus placebo in resected high-risk stage II melanoma.

Patients with high-risk stage II melanoma are at significant risk for recurrence after surgical resection. Adjuvant treatment options to lower the risk for distant metastases are limited. Although adjuvant IFN-α2b is associated with improved relapse-free survival in patients with high-risk melanoma, toxicity and limited overall survival benefits limit its use. Adjuvant treatment with the PD-1 inhibitor pembrolizumab significantly improved recurrence-free survival, compared with placebo, in patients with resected stage III melanoma in the Phase III KEYNOTE-054 trial; efficacy in patients with stage II disease has not been established. This article describes the design and rationale of KEYNOTE-716 (NCT03553836), a two-part, randomized, placebo-controlled, multicenter Phase III study of adjuvant pembrolizumab in patients with surgically resected high-risk stage II melanoma. Clinical trial registry & ID: ClinicalTrials.gov, NCT0355383

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

Estimation of cooling rates during close-coupled gas atomization using secondary dendrite arm spacing measurement

Al-4 wt pct Cu alloy has been gas atomized using a commercial close-coupled gas-atomization system. The resulting metal powders have been sieved into six size fractions, and the SDAS has been determined using electron microscopy. Cooling rates for the powders have been estimated using a range of published conversion factors for Al-Cu alloy, with reasonable agreement being found between sources. We find that cooling rates are very low relative to those often quoted for gas-atomized powders, of the order of 10 K s for sub-38 μm powders. We believe that a number of numerical studies of gas atomization have overestimated the cooling rate during solidification, probably as a consequence of overestimating the differential velocity between the gas and the particles. From the cooling rates measured in the current study, we estimate that such velocities are unlikely to exceed 20 m s

Interaction of similarly charged surfaces mediated by nanoparticles

We study the interaction between two like charged surfaces embedded in a solution of oppositely charged multivalent rod-like counterions. The counterions consist of two rigidly bonded point charges, each of valency Z. The strength of the electrostatic coupling increases with increasing surface charge density or valency of the charges. The system is analyzed by employing a self-consistent field theory, which treats the short and long range interactions of the counterions within different approximations. We find that in the weak coupling limit, the interactions are only repulsive. In the intermediate coupling regime, the multivalent rod-like counterions can mediate attractive interactions between the surfaces. For sufficiently long rods, bridging contributes to the attractive interaction. In the strong coupling limit, the charge correlations can contribute to the attractive interactions at short separations between the charged surfaces. Two minima can then appear in the force curve between surfaces