Dating fault-generated pseudotachylytes: comparison of Ar-40/Ar-39 stepwise-heating, laser ablation and Rb-Sr microsampling analyses

Three different geochronological techniques (stepwise-heating, laser-ablation 40Ar/39Ar, Rb-Sr microsampling) have been evaluated for dating fault-generated pseudotachylytes sampled along the Periadriatic Fault System (PAF) of the Alps. Because pseudotachylytes are whole-rock systems composed of melt, clast and alteration phases, chemical control from both Ar isotopes (Cl/K, Ca/K ratios) and EMPA analyses is crucial for their discrimination. When applied to stepwise-heating 40Ar/39Ar analyses, this approach yields accurate melt-related ages, even for complex age spectra. The spatial resolution of laser-ablation 40Ar/39Ar analyses is capable of contrasting melt, clast and alteration phases in situ, provided the clasts are not too fine grained, the latter of which results in integrated "mixed" ages without geological information. Elevated Cl/K and Ca/K ratios were found to be an invaluable indicator for the presence of clast admixture or inherited 40Ar. Due to incomplete isotopic resetting during frictional melting, Rb-Sr microsampling dating did not furnish geologically meaningful ages. On the basis of isotopic disequilibria among pseudotachylyte matrix phases, and independent Rb-Sr microsampling dating of cogenetic (ultra) mylonites, the concordant 40Ar/39Ar pseudotachylyte ages are interpreted as formation ages. The investigated pseudotachylytes altogether reveal a Cretaceous to Miocene history for the entire PAF, consistent with independent geological evidence. Individual faults, however, consistently reveal narrower intervals of enhanced activity lasting a few million years. Electronic supplementary material to this paper can be obtained by using the Springer LINK server at http://dx.doi.org/ 10.1007/s00410-002-0381-6

Combination of Ipilimumab and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma

PurposeAdoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) for metastatic melanoma can be highly effective, but attrition due to progression before TIL administration (32% in prior institutional experience) remains a limitation. We hypothesized that combining ACT with cytotoxic T lymphocyte-associated antigen 4 blockade would decrease attrition and allow more patients to receive TIL.Experimental designThirteen patients with metastatic melanoma were enrolled. Patients received four doses of ipilimumab (3 mg/kg) beginning 2 weeks prior to tumor resection for TIL generation, then 1 week after resection, and 2 and 5 weeks after preconditioning chemotherapy and TIL infusion followed by interleukin-2. The primary endpoint was safety and feasibility. Secondary endpoints included of clinical response at 12 weeks and at 1 year after TIL transfer, progression free survival (PFS), and overall survival (OS).ResultsAll patients received at least two doses of ipilimumab, and 12 of the 13 (92%) received TIL. A median of 6.5 × 1010 (2.3 × 1010 to 1.0 × 1011) TIL were infused. At 12 weeks following infusion, there were five patients who experienced objective response (38.5%), four of whom continued in objective response at 1 year and one of which became a complete response at 52 months. Median progression-free survival was 7.3 months (95% CI 6.1–29.9 months). Grade ≥ 3 immune-related adverse events included hypothyroidism (3), hepatitis (2), uveitis (1), and colitis (1).ConclusionIpilimumab plus ACT for metastatic melanoma is feasible, well tolerated, and associated with a low rate of attrition due to progression during cell expansion. This combination approach serves as a model for future efforts to improve the efficacy of ACT