Aim To examine the cancer‐specific outcomes for patients who experience immune‐related adverse events requiring immunosuppression beyond corticosteroids. Methods We performed a retrospective case series of patients between January 1, 2009 and April 1, 2018, across three metropolitan hospitals in Adelaide, South Australia. Eligible patients were identified from pharmacy records. Patients with a solid organ malignancy had discontinued checkpoint inhibitor therapy due to toxicity, and required immunosuppression in addition to corticosteroids to treat any immune‐related adverse event. Results From 3860 patient dispensation records of immunosuppressive medications, 19 eligible patients were identified. Eight received a CTLA‐4 inhibitor, four a PD‐1 inhibitor, five combination immunotherapy, and two remained blinded. Sixteen patients had melanoma and three had non‐small cell lung cancer. Median time to treatment failure was 8.7 months, and median overall survival was 9.4 months. Of those evaluable, the objective response rate was 35%, while 53% had progressive disease. Four patients died due to complications of their irAE, while six died from progressive disease. Conclusion Patients who received immunosuppression for checkpoint inhibitor therapy toxicity had variable outcomes. This in part reflects a heterogeneous population, and the evolution of irAE management over time. Several patients continued to derive a benefit after cessation of therapy despite the use of immunosuppressive medications; conversely, four died as a direct consequence of their irAE. Physicians should promptly introduce immunosuppressive therapy in patients not responding to corticosteroids to mitigate the risk of life‐threatening adverse events, given that current evidence does not clearly demonstrate a detriment to cancer‐specific outcomes.

This paper establishes a coupled model for multi-crack rotor using Timoshenko beam element with six degrees of freedom, and derives the stiffness matrix in the equations of motion accounting for the coupling between multiple cracks (the interaction between cracks). Then the effects of crack orientation angles (the relative angle between cracks, γ) on dynamic characteristics of the coupled multi- crack rotor near 1/3 and 1/2 subcritical speeds are analysed. The coupling between cracks induces more complex nonlinear dynamic characteristics such as large magnitudes of the super-harmonic components, which can be used as the indicators of early crack and for multi-crack identification. This work has a promotive significance for the application of the model-based method in the field of multi-crack detection of actual rotors.

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In this paper, a crack parameter identification method based on the coordinate of 1x intersections and Kriging surrogate model with enhanced samples is proposed to solve the crack parameter identification problem of train axles in start-stop condition. The location of the crack is identified in the first step by the x-coordinate of the linear intersection of 1x frequency components. Then, the intersecting coordinates and rigid constraint points were used to solve response curves of equal crack depth, and numerous enhanced samples of same depth at different positions were obtained to establish a Kriging model. Finally, the crack depth was directly obtained by the Kriging model. In this paper, response curve s of equal crack depth is proposed according to the symmetry of the train structure, which greatly reduces the number of samples needed to construct the Kriging model. Numerical simulation and experimental results demonstrate the effectiveness and robustness of the proposed method.