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Purpose/Objective(s): Ipilimumab is an immunostimulatory anti-CTLA 4 antibody that has been shown to improve survival in patients with metastatic melanoma. Unfortunately, 10-15% of patients treated with ipilimumab develop hypophysitis, which is often treated with systemic steroids or ipilimumab cessation or dose reduction. As these treatments are not optimal for patients who may be responding to ipilimumab, we present here our initial experience treating ipilimumab-induced hypophysitis with low-dose conformal radiation therapy. Materials/Methods: This is a single institution retrospective review of metastatic melanoma patients with ipilimumab-induced hypophysitis who were treated with low-dose pituitary radiation therapy. All patients had biochemical evidence of pituitary dysfunction and MRI features of hypophysitis, including diffuse pituitary enlargement and enhancement. Radiation therapy was linear accelerator-based and consisted of three daily 150 cGy fractions delivered using 6or 15-MV photons. The PTV consisted of the pituitary gland and a 0.5-1 cm margin, which was treated via a three or five field conformal plan. A thermoplastic mask was employed for immobilization. Clinical follow-up as well as preand post-treatment MRIs were used to evaluate treatment efficacy, with pituitary volumes calculated using the volumetric formula for an ellipsoid (4/3 x p x R1 x R2 x R3). Mean preand post-radiation therapy pituitary volumes were compared using the Student’s t-test. Results: Between September 10, 2010 and February 24, 2012, seven patients (3 women, 4 men) with a median age of 65 years (range, 39-88) were treated. At a median follow-up of 31 weeks (range, 1-77), no patients experienced acute radiation therapy toxicity or developed new symptoms following treatment. Mean preand post-radiation therapy pituitary volumes were 796.7 (range, 433.1-962.5) and 380.8 (range, 266.8-569.7) mm, respectively (p Z 0.005). Radiation therapy was delivered over a median of 5 days (range, 3-5) and without interruption in any patient. All patients who presented with generalized symptoms of fatigue, anorexia, and headache reported symptomatic improvement following treatment. Every patient who presented with a hormonal deficiency had persistent endocrine dysfunction at last follow-up. Conclusion: Low-dose conformal radiation therapy results in significant clinical improvement and radiographic response in patients with ipilimumab-induced hypophysitis, although there is no amelioration of endocrine dysfunction following treatment. This treatment represents a promising therapeutic option for patients with ipilimumab-induced hypophysitis whose survival may be adversely affected by treatment with systemic steroids or interference of ipilimumab administration. Additional exploration and follow-up is necessary to determine whether early treatment initiation can reverse endocrine dysfunction. Author Disclosure: P.L. Menzel: None. A. Geng: None. C. Marquez: None. M. Scala: None. D. Minor: None. R. Abendroth: None.

The problem of crack instability is examined, with the following results 1. (a) the conventional SHA defined collapse locus is a conservative assessment of the pipe loading capability within the plastic range; 2. (b) a large safety margin exists considering actual loads, even if secondary loads are included; 3. (c) a parameter is defined which gives the rate of hinge rotation increment with respect to crack extension; 4. (d) comparisons with tearing moduli are given, showing that the crack is generally stable.

Acoustic emission (AE) detected during the undirectional plastic deformation of aluminium alloys 2024 and 2124 was studied with the aim of identifying the sources of the emission. Measurements were made during tensile deformation and compressive deformation, and for loading axes parallel and perpendicular to the rolling direction. It is concluded that the fracture of brittle inclusions in the primary source of the AE detected during the tensile testing of the alloys in the temper condition T351. When aluminium alloy 2024 is solution treated, quenched and aged for short times at room temperature, AE from slip can be detected during plastic deformation, because the slip distribution is more heterogeneous than when the alloy is in the T351 condition.

Experiments designed to determine the effect of an overload on the acoustic emission (AE) detected during subsequent fatigue crack propagation between fixed load limits in aluminium alloy 2024 in the T351 temper condition are described. AE measurements were made during cycling of the alloy between fixed load limits, during application of the overload and during subsequent cycling between the previous fixed load limits. Fractographic analysis was used in the interpretation of the AE data, together with the results of previous studies, showing that the fracture of brittle inclusions is the only source of detected emission. The post-overload AE activity is less than the pre-overload activity because application of the overload results both in a decrease in crack growth rate in the post-overload period and in material “quietening” in a large zone ahead of the crack tip.

Acoustic emission (AE) detected during fatigue crack propagation in the aluminium alloys 2024-T351 and 2124-T351 was examined with the aim of identifying the source(s) of the emission. The AE activities of the two alloys were compared for crack propagation rates from 0.1 to 5 μm per load cycle; metallographic studies were used to assist in interpreting the AE results. It is concluded that inclusion fracture is the source of the detected emission in both alloys. Variability in AE activity from cycle to cycle is attributed to variations in the size of fractured inclusions and to their non-uniform spatial arrangement.

The computer program PAULA for the 3-D non linear analysis of piping is considered with particular reference to the finite elements library (straight pipe, elbow, T-joint, transition, restraint, non-linear superelement). The particular cases of the earthquake and pipe whip analysis are briefly discussed, in the latter case some attention is given to the relative merits of 2-D and 3-D analyses.

Candidal endocarditis can develop if candidemia occurs during Swan-Ganz catheterization. Candida endocarditis may persist for many months and is fatal unless the infected valve is resected. Herein is reported the first case of rupture of a mycotic pulmonary artery aneurysm caused by chronic candidal endocarditis. The endocarditis followed Swan-Ganz catheterization and aneurysm progressed despite appropriate medical and surgical therapy.