PURPOSE BRCA1 or BRCA2 ( BRCA) alterations are common in men with metastatic castration-resistant prostate cancer (mCRPC) and may confer sensitivity to poly(ADP-ribose) polymerase inhibitors. We present results from patients with mCRPC associated with a BRCA alteration treated with rucaparib 600 mg twice daily in the phase II TRITON2 study. METHODS We enrolled patients who progressed after one to two lines of next-generation androgen receptor–directed therapy and one taxane-based chemotherapy for mCRPC. Efficacy and safety populations included patients with a deleterious BRCA alteration who received ≥ 1 dose of rucaparib. Key efficacy end points were objective response rate (ORR; per RECIST/Prostate Cancer Clinical Trials Working Group 3 in patients with measurable disease as assessed by blinded, independent radiology review and by investigators) and locally assessed prostate-specific antigen (PSA) response (≥ 50% decrease from baseline) rate. RESULTS Efficacy and safety populations included 115 patients with a BRCA alteration with or without measurable disease. Confirmed ORRs per independent radiology review and investigator assessment were 43.5% (95% CI, 31.0% to 56.7%; 27 of 62 patients) and 50.8% (95% CI, 38.1% to 63.4%; 33 of 65 patients), respectively. The confirmed PSA response rate was 54.8% (95% CI, 45.2% to 64.1%; 63 of 115 patients). ORRs were similar for patients with a germline or somatic BRCA alteration and for patients with a BRCA1 or BRCA2 alteration, while a higher PSA response rate was observed in patients with a BRCA2 alteration. The most frequent grade ≥ 3 treatment-emergent adverse event was anemia (25.2%; 29 of 115 patients). CONCLUSION Rucaparib has antitumor activity in patients with mCRPC and a deleterious BRCA alteration, but with a manageable safety profile consistent with that reported in other solid tumor types.

Association for Cancer Research. D. Campbell has nothing to disclose. A. Patnaik has served in a consulting or advisory role for Exelixis, Janssen, and Jounce Therapeutics; has received honoraria from Clovis Oncology, Merck, Prime Inc, and Roche; and has received research funding from Clovis Oncology, Bristol-Myers Squibb, and GlaxoSmithKline. J. Shapiro has served in a consulting or advisory role for Amgen, Astellas, Ipsen, Merck, and Roche and received financial support for travel from Amgen and Merck. B. Sautois has served a consulting or advisory role for Clovis Oncology, Astellas, Janssen, and Sanofi and received financial support for travel and/or accommodation from Janssen. N.J. Vogelzang has served in a consulting or advisory role for Clovis Oncology,

Abstract. The subfamily Ambleminae is the most diverse subfamily of fresh-water mussels (order Unionoida), a globally diverse and ecologically prominent group of bivalves. About 250 amblemine species occur in North America; however, this diversity is highly imperiled, with the majority of species at risk. Assessing and protecting this diversity has been hampered by the uncertain systematics of this group. This study sought to provide an improved phylogenetic framework for the Ambleminae. Currently, 37 North American genera are recognized in Ambleminae. Previous phylogenetic studies of amblemines highlighted the need for more extensive sampling due to the uncertainties arising from polyphyly of many currently recognized taxa. The present study incorporated all amblemine genera occurring in North America north of the Rio Grande, with multiple species of most genera, including the type species for all but seven genera. A total of 192 new DNA sequences were obtained for three mitochondrial gene regions: COI, 16S, and ND1. In combination with published data, this produced a data matrix incorporating 357 gene sequences for 143 operational taxonomic units, representing 107 currently recognized species. Inclusion of published data provides additional taxa and a summary of present molecular evidence on amblemine phylogeny, if at the cost of increasing the amount of missing data. Parsimony and Bayesian analyses suggest that most amblemine genera, as currently defined, are polyphyletic. At higher taxonomic levels, the tribes Quadrulini, Lampsilini, and Pleurobemini were supported; the extent of Amblemini and the relationships of some genera previously assigned to that tribe remain unclear. The eastern North American amblemines appear monophyletic. Gonidea and some Eurasian taxa place as probable sister taxa for the eastern North American Ambleminae. The results also highlight problematic taxa of particular interest for further work.

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We address the question of the late Cenozoic geomorphological evolution of the central Chile Andes (33°–35°S), using uplift markers, river incision, previous and new ages of volcanic bodies, and new fission track ages. The uplift markers consist of relicts of high elevated peneplains that evidence >2 km of regional surface uplift lasting ∼2 Ma with variable amount along an E‐W transect. The eastern Coastal Cordillera was uplifted 1.5–2.1 km at 33–34°S and <1 km at 35°S, the western Principal Cordillera was uplifted ∼2 km, and the central eastern Principal Cordillera was uplifted >2.5 at 33°45′S and ∼1.5 km at 34°30′S. Erosional response to uplift was characterized by the retreat of a sharp knickpoint with celerities between 10 and 40 mm a−1. Extrapolation using a stream power law shows that uplift began shortly before 4 Ma or at 10.5–4.6 Ma (7.6 Ma central age) depending on the morphostructural units involved. The first alternative implies simultaneous uplift of the continental margin. The second model (the most reliable one) implies that the uplift affected together the eastern Coastal Cordillera and the Principal Cordillera, while the rest of the western fore arc subsided. This regional uplift can be mostly balanced by crustal thickening resulting from coeval shortening related to the out‐of‐sequence thrusting event in the Principal Cordillera and the uplift of the Frontal Cordillera. Simultaneously, emplacement of the southern edge of the flat slab subduction zone might have partially contributed to this uplift event.

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Leaders of nonprofit organizations face a particular bind inT HERE IS AN UNDENIABLE commonsense appeal of paying attention not just to what organizations do but to what they achieve that is of value. As a result, outcomes assessment is now being seen as a key element in a variety of reform initiatives with contrasting purposes. These purposes include strengthening