Prospective study on nanoparticle albumin-bound paclitaxel in advanced breast cancer. Clinical results and biological observations in taxane-pretreated patients

Background: There is a deep need to improve the care of metastatic breast cancer (MBC) patients, since even today it remains an incurable disease. Taxanes are considered the most effective cytotoxic drugs for the treatment of MBC, both in monotherapy and in combined schedules, but the need for synthetic solvents contributes to the severe toxicities and may have a negative impact on the efficacy. Nanoparticle albumin-bound paclitaxel (Nab-paclitaxel) is a colloidal suspension of paclitaxel and human serum albumin initially developed to avoid the toxicities associated with conventional taxanes. Patients and methods: The aim of this prospective, single-center open-label, noncomparative study was to evaluate the efficacy and safety of nab-paclitaxel in MBC patients pretreated with taxanes. The patients were treated with nab-paclitaxel as a single agent, 260 mg/m2 on day 1 of each 3-week cycle or 125 mg/m2 weekly. The primary endpoint was the overall response rate (ORR). Secondary objectives were duration of response, clinical benefit rate, progression-free survival (PFS), overall survival, and safety. Results: A total of 42 patients (median age 48 years, median Eastern Cooperative Oncology Group performance status 0, triple-negative MBC 19%, all pretreated with a taxane-based therapy, mainly in advanced disease) were enrolled in the study. The ORR was 23.8%, including one complete response (2.4%) and nine partial responses (21.4%); the disease control rate was 50%. The median duration of response was 7.2 months. After a median follow-up of 9 months, the median PFS was 4.6 months. ORR and PFS were similar irrespective of the previous chemotherapy lines, metastatic sites, and biomolecular expression. Nab-paclitaxel was well tolerated, and the most frequent treatment-related toxicities were mild to moderate (grades 1–2). Conclusion: This real-life study shows that nab-paclitaxel has a significant antitumor activity and a manageable safety profile in patients pretreated with taxanes and experiencing a treatment failure after at least one line of chemotherapy

Herbivory promotes dental disparification and macroevolutionary dynamics in grunters (teleostei: Terapontidae), a freshwater adaptive radiation

Trophic shifts into new adaptive zones have played major (although often conflicting) roles in reshaping the evolutionary trajectories of many lineages. We analyze data on diet, tooth, and oral morphology and relate these traits to phenotypic disparification and lineage diversification rates across the ecologically diverse Terapontidae, a family of Australasian fishes. In contrast to carnivores and most omnivores, which have retained relatively simple, ancestral caniniform tooth shapes, herbivorous terapontids appear to have evolved a variety of novel tooth shapes at significantly faster rates to meet the demands of plant-based diets. The evolution of herbivory prompted major disparification, significantly expanding the terapontid adaptive phenotypic continuum into an entirely novel functional morphospace. There was minimal support for our hypothesis of faster overall rates of integrated tooth shape, spacing, and jaw biomechanical evolution in herbivorous terapontids in their entirety, compared with other trophic strategies. There was, however, considerable support for accelerated disparification within a diverse freshwater clade containing a range of specialized freshwater herbivores. While the evolutionary transition to herbivorous diets has played a central role in terapontid phenotypic diversification by pushing herbivores toward novel fitness peaks, there was little support for herbivory driving significantly higher lineage diversification compared with background rates across the family

Ageing test of the ATLAS RPCs at X5-GIF

An ageing test of three ATLAS production RPC stations is in course at X5-GIF, the CERN irradiation facility. The chamber efficiencies are monitored using cosmic rays triggered by a scintillator hodoscope. Higher statistics measurements are made when the X5 muon beam is available. We report here the measurements of the efficiency versus operating voltage at different source intensities, up to a maximum counting rate of about 700Hz/cm^2. We describe the performance of the chambers during the test up to an overall ageing of 4 ATLAS equivalent years corresponding to an integrated charge of 0.12C/cm^2, including a safety factor of 5.Comment: 4 pages. Presented at the VII Workshop on Resistive Plate Chambers and Related Detectors; Clermont-Ferrand October 20th-22nd, 200

System Test of the ATLAS Muon Spectrometer in the H8 Beam at the CERN SPS

An extensive system test of the ATLAS muon spectrometer has been performed in the H8 beam line at the CERN SPS during the last four years. This spectrometer will use pressurized Monitored Drift Tube (MDT) chambers and Cathode Strip Chambers (CSC) for precision tracking, Resistive Plate Chambers (RPCs) for triggering in the barrel and Thin Gap Chambers (TGCs) for triggering in the end-cap region. The test set-up emulates one projective tower of the barrel (six MDT chambers and six RPCs) and one end-cap octant (six MDT chambers, A CSC and three TGCs). The barrel and end-cap stands have also been equipped with optical alignment systems, aiming at a relative positioning of the precision chambers in each tower to 30-40 micrometers. In addition to the performance of the detectors and the alignment scheme, many other systems aspects of the ATLAS muon spectrometer have been tested and validated with this setup, such as the mechanical detector integration and installation, the detector control system, the data acquisition, high level trigger software and off-line event reconstruction. Measurements with muon energies ranging from 20 to 300 GeV have allowed measuring the trigger and tracking performance of this set-up, in a configuration very similar to the final spectrometer. A special bunched muon beam with 25 ns bunch spacing, emulating the LHC bunch structure, has been used to study the timing resolution and bunch identification performance of the trigger chambers. The ATLAS first-level trigger chain has been operated with muon trigger signals for the first time

The first molecular phylogeny of Chilodontidae (Teleostei: Ostariophysi: Characiformes) reveals cryptic biodiversity and taxonomic uncertainty

Chilodontidae is a small family of eight described characiform species popularly known as headstanders. These small to moderately sized fishes are well known to aquarists, who prize their striking spotted pigmentation and unusual behaviors, and to systematists, who have revised both chilodontid genera in recent memory and studied their phylogenetic relationships using a comprehensive morphological dataset. However, no molecular phylogeny for the family has ever been proposed. Here, we reconstruct phylogenetic relationships for all eight known chilodontid species using three mitochondrial and two nuclear loci. Results largely agree with the previous morphological hypothesis, and confirm the monophyly of the family as well as its included genera, Caenotropus and Chilodus. The molecular topology differs slightly from the morphological hypothesis by placing Caenotropus maculosus rather than C. mestomorgmatos as the sister to the remaining three congeners, and by reconstructing the Curimatidae as the closest outgroup family, rather than the Anostomidae. However, the topologies supported by the morphological data were only slightly less likely and could not be rejected via Shimodaira-Hasegawa tests. Within Chilodus, two described species with distinctive pigmentation (C. fritillus and C. zunevei) appear embedded within the broad distributed C. punctatus clade, suggesting the presence of cryptic taxa with polymorphic pigmentation within the present concept of C. punctatus. Future work should combine morphological and molecular data to revisit the taxonomy and systematics of Chilodus and determine species limits within the C. punctatus-group sensu lato.Keywords: Freshwater fishes, Headstanders, Multilocus analysis, AmazonKeywords: Freshwater fishes, Headstanders, Multilocus analysis, Amazo

Ecological Factors and Diversification among Neotropical Characiforms

Morphological and DNA sequence data has been used to propose hypotheses of relationships within the Characiformes with minimal comparative discussion of causes underpinning the major intraordinal diversification patterns. We explore potential primary morphological factors controlling the early diversification process in some Neotropical characiforms as the first step to identifying factors contributing to the pronounced intraordinal morphological and species diversity. A phylogenetic reconstruction based on 16S rDNA (mitochondrial) and 18S rDNA (nuclear) genes provided the framework for the identification of the main morphological differences among the Acestrorhynchidae, Anostomidae, Characidae, Ctenoluciidae, Curimatidae, Cynodontidae, Gasteropelecidae, Prochilodontidae and Serrasalmidae. Results indicate an initial split into two major groupings: (i) species with long dorsal-fin bases relative to the size of other fins (Curimatidae, Prochilodontidae, Anostomidae, Serrasalmidae) which primarily inhabit lakes, swamps, and rivers (lineage I); and (ii) species with short dorsal-fin bases (Acestrorhynchidae, Gasteropelecidae, Characidae) which primarily inhabit creeks and streams (lineage II). The second diversification stage in lineage I involved substantial morphological diversification associated with trophic niche differences among the monophyletic families which range from detritivores to large item predators. Nonmonophyly of the Characidae complicated within lineage II analyzes but yielded groupings based on differences in pectoral and anal fin sizes correlated with life style differencesThis study was supported by the AMAPEZ project (CGL2006-02155 BOS) of the MEC (Ministry of Education and Science) under FEDER funds from the XUNTA de Galicia and by contributions from the Universidad de Vigo, the Universidad de Antioquia, and the Universidad Nacional de Colombia. A. Manjarrés-Hernández gratefully acknowledges a grant from COLCIENCIASS