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

Superlattice barrier varactors

SBV (Single Barrier Varactor) diodes have been proposed as alternatives to Schottky barrier diodes for harmonic multiplier applications. However, these show a higher current than expected. The excess current is due to X valley transport in the barrier. We present experimental results showing that the use of a superlattice barrier and doping spikes in the GaAs depletion regions on either side of the barrier can reduce the excess current and improve the control of the capacitance vs. voltage characteristic. The experimental results consist of data taken from two types of device structures. The first test structure was used to study the performance of AlAs/GaAs superlattice barriers. The wafer was fabricated into 90 micron diameter mesa diodes and the resulting current vs. voltage characteristics were measured. A 10 period superlattice structure with a total thickness of approximately 400 A worked well as an electron barrier. The structure had a current density of about one A/sq cm at one volt at room temperature. The capacitance variation of these structures was small because of the design of the GaAs cladding layers. The second test structure was used to study cladding layer designs. These wafers were InGaAs and InAlAs layers lattice matched to an InP substrate. The layers have n(+) doping spikes near the barrier to increase the zero bias capacitance and control the shape of the capacitance vs. voltage characteristic. These structures have a capacitance ratio of 5:1 and an abrupt change from maximum to minimum capacitance. The measurements were made at 80 K. Based on the information obtained from these two structures, we have designed a structure that combines the low current density barrier with the improved cladding layers. The capacitance and current-voltage characteristics from this structure are presented

Eccentric black hole-neutron star mergers: effects of black hole spin and equation of state

There is a high level of interest in black hole-neutron star binaries, not only because their mergers may be detected by gravitational wave observatories in the coming years, but also because of the possibility that they could explain a class of short duration gamma-ray bursts. We study black hole-neutron star mergers that occur with high eccentricity as may arise from dynamical capture in dense stellar regions such as nuclear or globular clusters. We perform general relativistic simulations of binaries with a range of impact parameters, three different initial black hole spins (zero, aligned and anti-aligned with the orbital angular momentum), and neutron stars with three different equations of state. We find a rich diversity across these parameters in the resulting gravitational wave signals and matter dynamics, which should also be reflected in the consequent electromagnetic emission. Before tidal disruption, the gravitational wave emission is significantly larger than perturbative predictions suggest for periapsis distances close to effective innermost stable separations, exhibiting features reflecting the zoom-whirl dynamics of the orbit there. Guided by the simulations, we develop a simple model for the change in orbital parameters of the binary during close encounters. Depending upon the initial parameters of the system, we find that mass transfer during non-merging close encounters can range from essentially zero to a sizable fraction of the initial neutron star mass. The same holds for the amount of material outside the black hole post-merger, and in some cases roughly half of this material is estimated to be unbound. We also see that non-merging close encounters generically excite large oscillations in the neutron star that are qualitatively consistent with f-modes.Comment: 19 pages, 13 figures, revised according to referee comment

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

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

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

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

RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma.

Activating mutations in KRAS occur in 32% of lung adenocarcinomas (LUAD). Despite leading to aggressive disease and resistance to therapy in preclinical studies, the KRAS mutation does not predict patient outcome or response to treatment, presumably due to additional events modulating RAS pathways. To obtain a broader measure of RAS pathway activation, we developed RAS84, a transcriptional signature optimised to capture RAS oncogenic activity in LUAD. We report evidence of RAS pathway oncogenic activation in 84% of LUAD, including 65% KRAS wild-type tumours, falling into four groups characterised by coincident alteration of STK11/LKB1, TP53 or CDKN2A, suggesting that the classifications developed when considering only KRAS mutant tumours have significance in a broader cohort of patients. Critically, high RAS activity patient groups show adverse clinical outcome and reduced response to chemotherapy. Patient stratification using oncogenic RAS transcriptional activity instead of genetic alterations could ultimately assist in clinical decision-making

EMP control and characterisation on high-power laser systems

Giant electromagnetic pulses (EMP) generated during the interaction of high-power lasers with solid targets can seriously degrade electrical mea- surements and equipment. EMP emission is caused by the acceleration of hot electrons in- side the target, which produce radiation across a wide band from DC to terahertz frequencies. Improved understanding and control of EMP is vital as we enter a new era of high repetition rate, high intensity lasers (e.g. ELI, the Extreme Light Infrastructure). We present recent data from the VULCAN laser facility that demonstrates how EMP can be readily and effectively reduced. Characterisation of the EMP was achieved using B-dot and D-dot probes that took measurements for a range of different target and laser parame- ters. We demonstrate that target stalk geometry, material composition and foil surface area can all play a significant role in the reduction of EMP. A combination of electromagnetic wave and 3D particle-in-cell simulations are used to inform our conclusions about the effects of stalk geometry on EMP, providing an opportunity for comparison with existing charge separation models