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

Elbow

The Elbow, the part of the human body that a blind or partially sighted person takes hold of, four fingers on the inside, thumb on the outside; holding with a firm grip to assist them with navigation. It is a common guiding technique linking two people into an unfamiliar choreography. In the summer of 2015 C&C Gallery hosted an innovative residency programme, transforming the gallery space into a dynamic studio environment in order to respond to ideas surrounding the condition of blindness. During this time eight artists variously came and went, engaging with a whole repertoire of processes, from casting to laser scanning, leaving a variety of traces of their activities. Much of the work, arrived at through a collaborative approach has sought to obliquely cast a shadow across the subject, remaining open towards the process of making, and the work remains in a state of uncertainty even at the time of writing. During a workshop in the space hosted by John Dickinson-Lilley, the artists wore blind glasses and stumbled rather pathetically around the gallery and the local high street, feeling unsure, insecure and inept, grounded only by the feeling of the floor beneath ones feet and ones fingers upon a companions elbow. Within the space; chalk lines, floor to ceiling columns and laser scanning targets have created an installation for measurement, where diverse material usage- including borax, expanding foam and cat litter humorously confound expectation

Phylogenetic relationships within the speciose family Characidae (Teleostei: Ostariophysi: Characiformes) based on multilocus analysis and extensive ingroup sampling

<p>Abstract</p> <p>Background</p> <p>With nearly 1,100 species, the fish family Characidae represents more than half of the species of Characiformes, and is a key component of Neotropical freshwater ecosystems. The composition, phylogeny, and classification of Characidae is currently uncertain, despite significant efforts based on analysis of morphological and molecular data. No consensus about the monophyly of this group or its position within the order Characiformes has been reached, challenged by the fact that many key studies to date have non-overlapping taxonomic representation and focus only on subsets of this diversity.</p> <p>Results</p> <p>In the present study we propose a new definition of the family Characidae and a hypothesis of relationships for the Characiformes based on phylogenetic analysis of DNA sequences of two mitochondrial and three nuclear genes (4,680 base pairs). The sequences were obtained from 211 samples representing 166 genera distributed among all 18 recognized families in the order Characiformes, all 14 recognized subfamilies in the Characidae, plus 56 of the genera so far considered <it>incertae sedis </it>in the Characidae. The phylogeny obtained is robust, with most lineages significantly supported by posterior probabilities in Bayesian analysis, and high bootstrap values from maximum likelihood and parsimony analyses.</p> <p>Conclusion</p> <p>A monophyletic assemblage strongly supported in all our phylogenetic analysis is herein defined as the Characidae and includes the characiform species lacking a supraorbital bone and with a derived position of the emergence of the hyoid artery from the anterior ceratohyal. To recognize this and several other monophyletic groups within characiforms we propose changes in the limits of several families to facilitate future studies in the Characiformes and particularly the Characidae. This work presents a new phylogenetic framework for a speciose and morphologically diverse group of freshwater fishes of significant ecological and evolutionary importance across the Neotropics and portions of Africa.</p

Sensitivity to CT-optimal, Affective Touch Depends on Adult Attachment Style

Affective touch supports affiliative bonds and social cognition. In particular, gentle, stroking touch, which has recently been associated with the C Tactile (CT) system, is typically perceived as pleasant and prosocial. However, it remains unknown whether pre-existing models of social relating influence the perception of CT-optimal touch. In this study (N = 44 adults), we examined how individual differences in attachment styles relate to the perception of CT-optimal touch, as well as to a different modality of interoception, namely heartbeat perception. Using the gold-standard assessment of attachment (Adult Attachment Interview), we found that insecure attachment was associated with reduced pleasantness discrimination between CT-optimal vs. non-CT optimal touch. Acknowledging the different traditions in measuring attachment, we also used a well-validated self-report questionnaire that pertains to explicit representations of current close relationships. Using this measure, we found that higher scores in attachment anxiety (but not attachment avoidance) were associated with reduced pleasantness discrimination between CT-optimal vs. non-CT optimal touch. Attachment patterns (in both measures) were not related to cardiac perception accuracy. These results corroborate and extend previous literature on CT-optimal touch and its relation with affiliative bonds and social cognition. Given that attachment was not related to perceived cardiac accuracy, these findings point to the specificity of the relationship between CT-optimal touch and attachment

Risks, alternative knowledge strategies and democratic legitimacy: the conflict over co-incineration of hazardous industrial waste in Portugal.

The decision to incinerate hazardous industrial waste in cement plants (the socalled ‘co-incineration’ process) gave rise to one of the most heated environmental conflicts ever to take place in Portugal. The bitterest period was between 1997 and 2002, after the government had made a decision. Strong protests by residents, environmental organizations, opposition parties, and some members of the scientific community forced the government to backtrack and to seek scientific legitimacy for the process through scientific expertise. The experts ratified the government’s decision, stating that the risks involved were socially acceptable. The conflict persisted over a decade and ended up clearing the way for a more sustainable method over which there was broad social consensus – a multifunctional method which makes it possible to treat, recover and regenerate most wastes. Focusing the analysis on this conflict, this paper has three aims: (1) to discuss the implications of the fact that expertise was ‘confiscated’ after the government had committed itself to the decision to implement co-incineration and by way of a reaction to the atmosphere of tension and protest; (2) to analyse the uses of the notions of ‘risk’ and ‘uncertainty’ in scientific reports from both experts and counter-experts’ committees, and their different assumptions about controllability and criteria for considering certain practices to be sufficiently safe for the public; and (3) to show how the existence of different technical scientific and political attitudes (one more closely tied to government and the corporate interests of the cement plants, the other closer to the environmental values of reuse and recycling and respect for the risk perception of residents who challenged the facilities) is closely bound up with problems of democratic legitimacy. This conflict showed how adopting more sustainable and lower-risk policies implies a broader view of democratic legitimacy, one which involves both civic movements and citizens themselves

The Muon Spectrometer Barrel Level-1 Trigger of the ATLAS Experiment at LHC

The proton-proton beam crossing at the LHC accelerator at CERN will have a rate of 40 MHz at the project luminosity. The ATLAS Trigger System has been designed in three levels in order to select only interesting physics events reducing from that rate of 40 MHz to the foreseen storage rate of about 200 Hz. The First Level reduces the output rate to about 100 kHz. The ATLAS Muon Spectrometer has been designed to perform stand-alone triggering and measurement of muon transverse momentum up to 1 TeV/c with good resolution (from 3% at 10 GeV/c up to 10% at 1 TeV/c). In the Barrel region of the Muon Spectrometer the Level-1 trigger is given by means of three layers of Resistive Plate Chamber detectors (RPC): a gaseous detector working in avalanche mode composed by two plates of high-resistivity bakelite and two orthogonal planes of read-out strips. The logic of the Level-1 barrel muon trigger is based on the search of patterns of RPC hits in the three layers consistent with a high transverse momentum muon track originated from the interaction vertex. The associated trigger electronics is based on dedicated processors, the Coincidence Matrix boards, performing space coincidences and time gates and providing the RPC readout as well. A detailed simulation of the ATLAS Experiment and of both the hardware components and the logic of the Level-1 Muon Trigger in the barrel of the Muon Spectrometer has been performed. This simulation has been used not only to evaluate the performances of the system but also to define the hardware set-up such as the cabling of both the trigger detectors and the trigger electronics modules. A description of both the Level-1 Muon Trigger system in the barrel and the RPC detectors, with their cosmic rays quality tests, will be presented together with the trigger performances and rates calculations evaluated for muons over a wide range of pT and preliminary studies on the impact of accidental triggers due to low energy background particles in the experimental area