A phase 1 study of mTORC1/2 inhibitor BI 860585 as a single agent or with exemestane or paclitaxel in patients with advanced solid tumors

This phase 1 trial (NCT01938846) determined the maximum tolerated dose (MTD) of the mTOR serine/threonine kinase inhibitor, BI 860585, as monotherapy and with exemestane or paclitaxel in patients with advanced solid tumors. This 3+3 dose-escalation study assessed BI 860585 monotherapy (5–300 mg/day; Arm A), BI 860585 (40–220 mg/day; Arm B) with 25 mg/day exemestane, and BI 860585 (80–220 mg/day; Arm C) with 60–80 mg/m2 /week paclitaxel, in 28-day cycles. Primary endpoints were the number of patients with dose-limiting toxicities (DLTs) in cycle 1 and the MTD. Forty-one, 25, and 24 patients were treated (Arms A, B, and C). DLTs were observed in four (rash (n = 2), elevated alanine aminotransferase/aspartate aminotransferase, diarrhea), four (rash (n = 3), stomatitis, and increased gamma-glutamyl transferase), and two (diarrhea, increased blood creatine phosphokinase) patients in cycle 1. The BI 860585 MTD was 220 mg/day (Arm A) and 160 mg/day (Arms B and C). Nine patients achieved an objective response (Arm B: Four partial responses (PRs); Arm C: Four PRs; one complete response). The disease control rate was 20%, 28%, and 58% (Arms A, B, and C). The most frequent treatment-related adverse events (AEs) were hyperglycemia (54%) and diarrhea (39%) (Arm A); diarrhea (40%) and stomatitis (40%) (Arm B); fatigue (58%) and diarrhea (58%) (Arm C). The MTD was determined in all arms. Antitumor activity was observed with BI 860585 monotherapy and in combination with exemestane or paclitaxel

Ichnological evidence for meiofaunal bilaterians from the terminal Ediacaran and earliest Cambrian of Brazil

The evolutionary events during the Ediacaran–Cambrian transition (~541 Myr ago) are unparalleled in Earth history. The fossil record suggests that most extant animal phyla appeared in a geologically brief interval, with the oldest unequivocal bilaterian body fossils found in the Early Cambrian. Molecular clocks and biomarkers provide independent estimates for the timing of animal origins, and both suggest a cryptic Neoproterozoic history for Metazoa that extends considerably beyond the Cambrian fossil record. We report an assemblage of ichnofossils from Ediacaran–Cambrian siltstones in Brazil, alongside U–Pb radioisotopic dates that constrain the age of the oldest specimens to 555–542 Myr. X-ray microtomography reveals three-dimensionally preserved traces ranging from 50 to 600 μm in diameter, indicative of small-bodied, meiofaunal tracemakers. Burrow morphologies suggest they were created by a nematoid-like organism that used undulating locomotion to move through the sediment. This assemblage demonstrates animal–sediment interactions in the latest Ediacaran period, and provides the oldest known fossil evidence for meiofaunal bilaterians. Our discovery highlights meiofaunal ichnofossils as a hitherto unexplored window for tracking animal evolution in deep time, and reveals that both meiofaunal and macrofaunal bilaterians began to explore infaunal niches during the late Ediacaran

Ichnological evidence for meiofaunal bilaterians from the terminal Ediacaran and earliest Cambrian of Brazil

The evolutionary events during the Ediacaran–Cambrian transition (~541 Myr ago) are unparalleled in Earth history. The fossil record suggests that most extant animal phyla appeared in a geologically brief interval, with the oldest unequivocal bilaterian body fossils found in the Early Cambrian. Molecular clocks and biomarkers provide independent estimates for the timing of animal origins, and both suggest a cryptic Neoproterozoic history for Metazoa that extends considerably beyond the Cambrian fossil record. We report an assemblage of ichnofossils from Ediacaran–Cambrian siltstones in Brazil, alongside U–Pb radioisotopic dates that constrain the age of the oldest specimens to 555–542 Myr. X-ray microtomography reveals three-dimensionally preserved traces ranging from 50 to 600 μm in diameter, indicative of small-bodied, meiofaunal tracemakers. Burrow morphologies suggest they were created by a nematoid-like organism that used undulating locomotion to move through the sediment. This assemblage demonstrates animal–sediment interactions in the latest Ediacaran period, and provides the oldest known fossil evidence for meiofaunal bilaterians. Our discovery highlights meiofaunal ichnofossils as a hitherto unexplored window for tracking animal evolution in deep time, and reveals that both meiofaunal and macrofaunal bilaterians began to explore infaunal niches during the late Ediacaran

Skin, paper, tiles: a cross-cultural history of Kadiwéu art

This article focuses on the global traffic in images relating to Kadiwéu culture in South America, analyzing the extent to which they are entangled in the group’s continuing sense of presence. It begins with Kadiwéu designs as they appeared in the sketchbook of the artist-explorer Guido Boggiani in the late nineteenth century. It then explores the mapping of Kadiwéu territory and the practices and protocols informing a politics of land rights, cultural property and economic survival, looking in particular at the commissioning of Kadiwéu designs for a housing estate and an associated exhibition in Berlin early in the twentieth-first century. By developing a cross-cultural history of Kadiwéu art that considers the transnational networks across different times and spaces, including the case of a transcultural history of copyright, the article seeks to contribute to the ongoing re-thinking of the colonial archive and its afterlife

Arqueologia e história indígena no Pantanal

O artigo apresenta uma síntese dos dados arqueológicos sobre o Pantanal e o seu entorno, principalmente em Mato Grosso e Mato Grosso do Sul. Elaborado com base na noção de arqueologia como história indígena de longa duração, o artigo considera as trajetórias de estabelecimento e consolidação territorial da ocupação indígena regional, os processos de formação da configuração etnográfica encontrada pelos europeus e os impactos do colonialismo. O principal objetivo consiste em mostrar que a diversidade cultural característica do cenário etnográfico pantaneiro está associada à dinâmica histórica e cultural da ocupação indígena desde períodos anteriores à chegada dos conquistadores e colonizadores de origem europeia.The article presents an overview of the archaeological data on the Pantanal and its surrounding areas, mainly in Mato Grosso and Mato Grosso do Sul. Prepared based on the notion of archeology as long term indigenous history, the article considers the trajectories of territorial establishment and consolidation of the regional indigenous occupation, the formation processes of ethnographic setting found by Europeans and the impact of colonialism. The main objective is to show that cultural diversity characteristic of the Pantanal ethnographic scenario is associated with historical and cultural dynamics of indigenous occupation from periods prior to the arrival of the conquistadors and settlers of European origin