A randomised trial evaluating Bevacizumab as adjuvant therapy following resection of AJCC stage IIB, IIC and III cutaneous melanoma : an update

At present, there are no standard therapies for the adjuvant treatment of malignant melanoma. Patients with primary tumours with a high-Breslow thickness (stages IIB and IIC) or with resected loco-regional nodal disease (stage III) are at high risk of developing metastasis and subsequent disease-related death. Given this, it is important that novel therapies are investigated in the adjuvant melanoma setting. Since angiogenesis is essential for primary tumour growth and the development of metastasis, anti-angiogenic agents are attractive potential therapeutic candidates for clinical trials in the adjuvant setting. Therefore, we initiated a phase II trial in resected high-risk cutaneous melanoma, assessing the efficacy of bevacizumab versus observation. In the interim safety data analysis, we demonstrate that bevacizumab is a safe therapy in the adjuvant melanoma setting with no apparent increase in the surgical complication rate after either primary tumour resection and/or loco-regional lymphadenectomy

Nonlinear effects in the black hole ringdown: absorption-induced mode excitation

Gravitational-wave observations of black hole ringdowns are commonly used to characterize binary merger remnants and to test general relativity. These analyses assume linear black hole perturbation theory, in particular that the ringdown can be described in terms of quasinormal modes even for times approaching the merger. Here we investigate a nonlinear effect during the ringdown, namely how a mode excited at early times can excite additional modes as it is absorbed by the black hole. This is a third-order secular effect: the change in the black-hole mass causes a shift in the mode spectrum, so that the original mode is projected onto the new ones. Using nonlinear simulations, we study the ringdown of a spherically-symmetric scalar field around an asymptotically anti-de Sitter black hole, and we find that this "absorption-induced mode excitation" (AIME) is the dominant nonlinear effect. We show that this effect takes place well within the nonadiabatic regime, so we can analytically estimate it using a sudden mass-change approximation. Adapting our estimation technique to asymptotically-flat Schwarzschild black holes, we expect AIME to play a role in the analysis and interpretation of current and future gravitational wave observations

A tri-dimensional approach for auditing brand loyalty

Over the past twenty years brand loyalty has been an important topic for both marketing practitioners and academics. While practitioners have produced proprietary brand loyalty audit models, there has been little academic research to make transparent the methodology that underpins these audits and to enable practitioners to understand, develop and conduct their own audits. In this paper, we propose a framework for a brand loyalty audit that uses a tri-dimensional approach to brand loyalty, which includes behavioural loyalty and the two components of attitudinal loyalty: emotional and cognitive loyalty. In allowing for different levels and intensity of brand loyalty, this tri-dimensional approach is important from a managerial perspective. It means that loyalty strategies that arise from a brand audit can be made more effective by targeting the market segments that demonstrate the most appropriate combination of brand loyalty components. We propose a matrix with three dimensions (emotional, cognitive and behavioural loyalty) and two levels (high and low loyalty) to facilitate a brand loyalty audit. To demonstrate this matrix, we use the example of financial services, in particular a rewards-based credit card

Coral Reef Island Initiation and Development Under Higher Than Present Sea Levels

Coral reef islands are considered to be among the most vulnerable environments to future sea-level rise. However, emerging data suggest that different island types, in contrasting locations, have formed under different conditions in relation to past sea level. Uniform assumptions about reef island futures under sea-level rise may thus be inappropriate. Using chronostratigraphic analysis from atoll rim islands (sand- and gravel-based) in the southern Maldives, we show that whilst island building initiated at different times around the atoll (~2,800 cal. yr. B.P. and ~4,200 cal. yr. B.P. at windward and leeward rim sites respectively), higher than present sea levels and associated high-energy wave events were actually critical to island initiation. Findings thus suggest that projected sea-level rise and increases in the magnitude of distal high-energy wave events could reactivate this process regime which, if there is an appropriate sediment supply, may facilitate further vertical reef island-building

Measured g factors and the tidal-wave description of transitional nuclei near A = 100

The transient-field technique has been used in both conventional kinematics and inverse kinematics to measure the g factors of the 2+ states in the stable even isotopes of Ru, Pd and Cd. The statistical precision of the g(2+) values has been significantly improved, allowing a critical comparison with the tidal-wave version of the cranking model recently proposed for transitional nuclei in this region.Comment: Accepted for publication in Physical Review C, April 201

The DLV System for Knowledge Representation and Reasoning

This paper presents the DLV system, which is widely considered the state-of-the-art implementation of disjunctive logic programming, and addresses several aspects. As for problem solving, we provide a formal definition of its kernel language, function-free disjunctive logic programs (also known as disjunctive datalog), extended by weak constraints, which are a powerful tool to express optimization problems. We then illustrate the usage of DLV as a tool for knowledge representation and reasoning, describing a new declarative programming methodology which allows one to encode complex problems (up to $\Delta^P_3$-complete problems) in a declarative fashion. On the foundational side, we provide a detailed analysis of the computational complexity of the language of DLV, and by deriving new complexity results we chart a complete picture of the complexity of this language and important fragments thereof. Furthermore, we illustrate the general architecture of the DLV system which has been influenced by these results. As for applications, we overview application front-ends which have been developed on top of DLV to solve specific knowledge representation tasks, and we briefly describe the main international projects investigating the potential of the system for industrial exploitation. Finally, we report about thorough experimentation and benchmarking, which has been carried out to assess the efficiency of the system. The experimental results confirm the solidity of DLV and highlight its potential for emerging application areas like knowledge management and information integration.Comment: 56 pages, 9 figures, 6 table

The Investigation of Space Charge Dominated Beams in a Synchrotron

This research was sponsored by the National Science Foundation Grant NSF PHY-931478

Interacting effects of temperature, habitat and phenotype on predator avoidance behaviour in <i>Diadema antillarum</i>: implications for restorative conservation

Caribbean long-spined sea urchin Diadema antillarum populations crashed following a mass mortality event in 1983-1984 with cascading effects on reef health. Population restoration efforts may be hampered by unknown effects of short- and long-term elevated sea surface temperature (SST). We investigated how a key behavioural trait, predator avoidance behaviour (PAB; percentage of long defensive spines that moved in response to shadow stimuli), was affected by elevated SST in 180 individuals from 2 contrasting Honduran reefs: Utila (flattened reef structure, dearth of predation refugia) and Banco Capiro (complex reef structure, abundant refugia). Initiation of PAB is mediated by melanin, which breaks down at elevated water temperatures; thus, as SST rises, D. antillarum may become vulnerable to predation. We compared local current SST (CSST; 29.7°C) with 2 IPCC predicted long-term climate change scenarios under laboratory conditions. PAB decreased by 13.98-15.37% at CSST +1.4°C and 31.67-42.44% at CSST +3.1°C. Trial temperatures were similar to maxima recorded in the Caribbean during the 2016 El Niño, so our results also represent likely responses to worst-case short-term acute temperature anomalies. Juveniles maintained higher PAB than adults, indicating increased reliance on anti-predation behaviours. White-spined phenotypes from Utila’s flattened reef maintained higher PAB than black-spined counterparts, likely due to increased conspicuousness to visual predators. Habitat complexity may mitigate temperature-driven losses in natural behavioural defences. D. antillarum may be resilient to near-term (D. antillarum populations must be coupled to augmented reef complexity to improve future resilience

Alveolar macrophages of GM-CSF knockout mice exhibit mixed M1 and M2 phenotypes

Background Activin A is a pleiotrophic regulatory cytokine, the ablation of which is neonatal lethal. Healthy human alveolar macrophages (AMs) constitutively express activin A, but AMs of patients with pulmonary alveolar proteinosis (PAP) are deficient in activin A. PAP is an autoimmune lung disease characterized by neutralizing autoantibodies to Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF). Activin A can be stimulated, however, by GM-CSF treatment of AMs in vitro. To further explore pulmonary activin A regulation, we examined AMs in bronchoalveolar lavage (BAL) from wild-type C57BL/6 compared to GM-CSF knockout mice which exhibit a PAP-like histopathology. Both human PAP and mouse GM-CSF knockout AMs are deficient in the transcription factor, peroxisome proliferator activated receptor gamma (PPARγ). Results In sharp contrast to human PAP, activin A mRNA was elevated in mouse GM-CSF knockout AMs, and activin A protein was increased in BAL fluid. Investigation of potential causative factors for activin A upregulation revealed intrinsic overexpression of IFNγ, a potent inducer of the M1 macrophage phenotype, in GM-CSF knockout BAL cells. IFNγ mRNA was not elevated in PAP BAL cells. In vitro studies confirmed that IFNγ stimulated activin A in wild-type AMs while antibody to IFNγ reduced activin A in GM-CSF knockout AMs. Both IFNγ and Activin A were also reduced in GM-CSF knockout mice in vivo after intratracheal instillation of lentivirus-PPARγ compared to control lentivirus vector. Examination of other M1 markers in GM-CSF knockout mice indicated intrinsic elevation of the IFNγ-regulated gene, inducible Nitrogen Oxide Synthetase (iNOS), CCL5, and interleukin (IL)-6 compared to wild-type. The M2 markers, IL-10 and CCL2 were also intrinsically elevated. Conclusions Data point to IFNγ as the primary upregulator of activin A in GM-CSF knockout mice which in addition, exhibit a unique mix of M1-M2 macrophage phenotypes