2,298 research outputs found
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
RAS signalling through PI3-Kinase controls cell migration via modulation of Reelin expression.
RAS signalling through phosphoinositide 3-kinase (PI3-Kinase) has been shown to have an essential role in tumour initiation and maintenance. RAS also regulates cell motility and tumour invasiveness, but the role of direct RAS binding to PI3-Kinase in this remains uncertain. Here, we provide evidence that disruption of RAS interaction with PI3-Kinase p110α decreases cell motility and prevents activation of Rac GTPase. Analysis of gene expression in cells lacking RAS interaction with p110α reveals increased levels of the extracellular matrix glycoprotein Reelin and activation of its downstream pathway resulting in upregulation of E-cadherin expression. Induction of the Reelin/E-cadherin axis is also observed in Kras mutant lung tumours that are regressing due to blockade of RAS interaction with PI3-Kinase. Furthermore, loss of Reelin correlates with decreased survival of lung and breast cancer patients. Reelin thus plays a role in restraining RAS and PI3-kinase promotion of cell motility and potentially tumour metastasis
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
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
Ranks of ideals in inverse semigroups of difunctional binary relations
The set Dn of all difunctional relations on an n element set is an inverse semigroup under a variation of the usual composition operation. We solve an open problem of Kudryavtseva and Maltcev (Publ Math Debrecen 78(2):253–282, 2011), which asks: What is the rank (smallest size of a generating set) of Dn? Specifically, we show that the rank of Dn is B(n)+n, where B(n) is the nth Bell number. We also give the rank of an arbitrary ideal of Dn. Although Dn bears many similarities with families such as the full transformation semigroups and symmetric inverse semigroups (all contain the symmetric group and have a chain of J-classes), we note that the fast growth of rank(Dn) as a function of n is a property not shared with these other families
The Investigation of Space Charge Dominated Beams in a Synchrotron
This research was sponsored by the National Science Foundation Grant NSF PHY-931478
Development, implementation and evaluation of a clinical research engagement and leadership capacity building program in a large Australian health care service
BACKGROUND: Health professionals need to be integrated more effectively in clinical research to ensure that research addresses clinical needs and provides practical solutions at the coal face of care. In light of limited evidence on how best to achieve this, evaluation of strategies to introduce, adapt and sustain evidence-based practices across different populations and settings is required. This project aims to address this gap through the co-design, development, implementation, evaluation, refinement and ultimately scale-up of a clinical research engagement and leadership capacity building program in a clinical setting with little to no co-ordinated approach to clinical research engagement and education. METHODS/DESIGN: The protocol is based on principles of research capacity building and on a six-step framework, which have previously led to successful implementation and long-term sustainability. A mixed methods study design will be used. Methods will include: (1) a review of the literature about strategies that engage health professionals in research through capacity building and/or education in research methods; (2) a review of existing local research education and support elements; (3) a needs assessment in the local clinical setting, including an online cross-sectional survey and semi-structured interviews; (4) co-design and development of an educational and support program; (5) implementation of the program in the clinical environment; and (6) pre- and post-implementation evaluation and ultimately program scale-up. The evaluation focuses on research activity and knowledge, attitudes and preferences about clinical research, evidence-based practice and leadership and post implementation, about their satisfaction with the program. The investigators will evaluate the feasibility and effect of the program according to capacity building measures and will revise where appropriate prior to scale-up. DISCUSSION: It is anticipated that this clinical research engagement and leadership capacity building program will enable and enhance clinically relevant research to be led and conducted by health professionals in the health setting. This approach will also encourage identification of areas of clinical uncertainty and need that can be addressed through clinical research within the health setting
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
-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 Commissioners Report to Edward Kent, Esq. Governor of the State of Maine 1838
https://digitalmaine.com/northeast_boundary_dispute/1003/thumbnail.jp
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