Summary Immune checkpoint inhibitors significantly improve clinical outcomes in numerous malignancies, but high-grade immune-related adverse events can occur, particularly with combination immunotherapy. Herein, we report two melanoma patients who developed fatal myocarditis following treatment with ipilimumab and nivolumab. Both patients developed myositis with rhabdomyolysis, early progressive and refractory cardiac electrical instability, and myocarditis with robust T-cell and macrophage infiltrates. Selective clonal T-cell populations infiltrating the myocardium were identical to those present in tumor and skeletal muscle. Pharmacovigilance data revealed that myocarditis occurred in 0.27% of patients treated with ipilimumab/nivolumab, suggesting this is a rare, potentially fatal, T-cell-driven drug reaction.

We present the first calculations to follow the evolution of all stable nuclei and their radioactive progenitors in stellar models computed from the onset of central hydrogen burning through explosion as Type II supernovae. Calculations are performed for Pop I stars of 15, 19, 20, 21, and 25 M ⊙ using the most recently available experimental and theoretical nuclear data, revised opacity tables, neutrino losses, and weak interaction rates, and taking into account mass loss due to stellar winds. A novel "adaptive" reaction network is employed with a variable number of nuclei (adjusted each time step) ranging from ∼ 700 on the main sequence to 2200 during the explosion. The network includes, at any given time, all relevant isotopes from hydrogen through polonium (Z = 84). Even the limited grid of stellar masses studied suggests that overall good agreement can be achieved with the solar abundances of nuclei between 16 O and 90 Zr. Interesting discrepancies are seen in the 20 M ⊙ model and, so far, only in that model, that are a consequence of the merging of the oxygen, neon, and carbon shells about a day prior to core collapse. We find that, in some stars, most of the "p-process" nuclei can be produced in the convective oxygen burning shell moments prior to collapse; in others, they are made only in the explosion. Serious deficiencies still exist in all cases for the p-process isotopes of Ru and Mo.

We present results from the JINA REACLIB project, an ongoing effort to maintain a current and accurate library of thermonuclear reaction rates for astrophysical applications. Ongoing updates are transparently documented and version tracked, and any set of rates is publicly available and can be downloaded via a web interface at http://groups.nscl.msu.edu/jina/reaclib/db/. We discuss here our library V1.0, a snapshot of recommended rates for stable and explosive hydrogen and helium burning. We show that the updated reaction rates lead to modest but significant changes in full network, full 1D X-ray burst model calculations, compared to calculations with previously used reaction rate sets. The late time behavior of X-ray burst light curves shows significant changes, suggesting that the previously found small discrepancies between model calculations and observations may be solved with a better understanding of the nuclear input. Our X-ray burst model calculations are intended to serve as a benchmark for future model comparisons and sensitivity studies, as the complete underlying nuclear physics is fully documented and publicly available.

Multizone models of Type I X-ray bursts are presented that use an adaptive nuclear reaction network of unprecedented size, up to 1300 isotopes, for energy generation and include the most recent measurements and estimates of critical nuclear physics. Convection and radiation transport are included in calculations that carefully follow the changing composition in the accreted layer, both during the bursts themselves and in their ashes. Sequences of bursts, up to 15 in one case, are followed for two choices of accretion rate and metallicity, up to the point at which a limit cycle equilibrium is established. ForṀ ¼ 1:75 Â 10 À9 M yr À1 (andṀ ¼ 3:5 Â 10 À10 M yr À1 , for low metallicity), combined hydrogen-helium flashes occur. These bursts have light curves with slow rise times (seconds) and long tails. The rise times, shapes, and tails of these light curves are sensitive to the efficiency of nuclear burning at various waiting points along the rp-process path, and these sensitivities are explored. Each displays ''compositional inertia'' in that its properties are sensitive to the fact that accretion occurs onto the ashes of previous bursts that contain leftover hydrogen, helium, and CNO nuclei. This acts to reduce the sensitivity of burst properties to metallicity. Only the first anomalous burst in one model produces nuclei as heavy as A ¼ 100. For the present choice of nuclear physics and accretion rates, other bursts and models make chiefly nuclei with A % 64. The amount of carbon remaining after hydrogen-helium bursts is typically P1% by mass and decreases further as the ashes are periodically heated by subsequent bursts. Foṙ M ¼ 3:5 Â 10 À10 M yr À1 and solar metallicity, bursts are ignited in a hydrogen-free helium layer. At the base of this layer, up to 90% of the helium has already burned to carbon prior to the unstable ignition of the helium shell. These helium-ignited bursts have (1) briefer, brighter light curves with shorter tails, (2) very rapid rise times (<0.1 s), and (3) ashes lighter than the iron group.

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