Meningiomas occurring during long-term survival after treatment for childhood cancer

Childhood cancer is rare but improvements in treatment over the past five decades have resulted in a cohort of more than 30,000 long-term survivors of childhood cancer in the UK with more added annually. These long-term survivors are at risk of late effects of cancer treatment which replace original tumour recurrence as the leading cause of premature death. Second neoplasms are a particular risk and in the central nervous system meningiomas occur increasingly with increased radiation dose to central nervous system tissue and length of time after exposure, resulting in a 500-fold increase above that expected in the normal population by 40 years of follow up. This multidisciplinary author group and others met to discuss the issue. Our pooled information, and consensus that screening should only follow symptoms, was published online by the Royal College of Radiologists in 2013. We outline here the current knowledge and management of these neoplasms secondary to childhood cancer treatment

‘Better off, as judged by themselves’:A reply to Cass Sunstein

This paper is a reply to Sunstein’s comment on my paper ‘Do people really want to be nudged towards healthy lifestyles?’ The central claim of that paper was that, in their book Nudge, Thaler and Sunstein switch between two different interpretations of the ‘better off, as judged by themselves’ criterion, and that consistent use of one or other interpretation would have blunted the persuasive power of the book. In this reply, I defend that claim against Sunstein’s counter-arguments

A dynamically extending exclusion process

An extension of the totally asymmetric exclusion process, which incorporates a dynamically extending lattice is explored. Although originally inspired as a model for filamentous fungal growth, here the dynamically extending exclusion process (DEEP) is studied in its own right, as a nontrivial addition to the class of nonequilibrium exclusion process models. Here we discuss various mean-field approximation schemes and elucidate the steady state behaviour of the model and its associated phase diagram. Of particular note is that the dynamics of the extending lattice leads to a new region in the phase diagram in which a shock discontinuity in the density travels forward with a velocity that is lower than the velocity of the tip of the lattice. Thus in this region the shock recedes from both boundaries.Comment: 20 pages, 12 figure

Networking Effects on Cooperation in Evolutionary Snowdrift Game

The effects of networking on the extent of cooperation emerging in a competitive setting are studied. The evolutionary snowdrift game, which represents a realistic alternative to the well-known Prisoner's Dilemma, is studied in the Watts-Strogatz network that spans the regular, small-world, and random networks through random re-wiring. Over a wide range of payoffs, a re-wired network is found to suppress cooperation when compared with a well-mixed or fully connected system. Two extinction payoffs, that characterize the emergence of a homogeneous steady state, are identified. It is found that, unlike in the Prisoner's Dilemma, the standard deviation of the degree distribution is the dominant network property that governs the extinction payoffs.Comment: Changed conten

Emergence of the Shackleton Range from beneath the Antarctic Ice Sheet due to glacial erosion

This paper explores the long-term evolution of a subglacial fjord landscape in the Shackleton Range, Antarctica. We propose that prolonged ice-sheet erosion across a passive continental margin caused troughs to deepen and lower the surrounding ice-sheet surface, leaving adjacent mountains exposed. Geomorphological evidence suggests a change in the direction of regional ice flow accompanied emergence. Simple calculations suggest that isostatic compensation caused by the deepening of bounding ice-stream troughs lowered the ice-sheet surface relative to the mountains by ~800m. Use of multiple cosmogenic isotopes on bedrock and erratics (26Al, 10Be, 21Ne) provides evidence that overriding of the massif and the deepening of the adjacent troughs occurred earlier than the Quaternary. Perhaps this occurred in the mid-Miocene, as elsewhere in East Antarctica in the McMurdo Dry Valleys and the Lambert basin. The implication is that glacial erosion instigates feedback that can change ice-sheet thickness, extent, and direction of flow. Indeed, as the subglacial troughs evolve over millions of years, they increase topographic relief; and this changes the dynamics of the ice sheet. © 2013 Elsevier B.V

Memory-Based Snowdrift Game on Networks

We present a memory-based snowdrift game (MBSG) taking place on networks. We found that, when a lattice is taken to be the underlying structure, the transition of spatial patterns at some critical values of the payoff parameter is observable for both 4 and 8-neighbor lattices. The transition points as well as the styles of spatial patterns can be explained by local stability analysis. In sharp contrast to previously reported results, cooperation is promoted by the spatial structure in the MBSG. Interestingly, we found that the frequency of cooperation of the MBSG on a scale-free network peaks at a specific value of the payoff parameter. This phenomenon indicates that properly encouraging selfish behaviors can optimally enhance the cooperation. The memory effects of individuals are discussed in detail and some non-monotonous phenomena are observed on both lattices and scale-free networks. Our work may shed some new light on the study of evolutionary games over networks.Comment: 6 pages, 6 figures, to be published in Phys. Rev.

The cardiomyocyte "redox rheostat": Redox signalling via the AMPK-mTOR axis and regulation of gene and protein expression balancing survival and death.

Reactive oxygen species (ROS) play a key role in development of heart failure but, at a cellular level, their effects range from cytoprotection to induction of cell death. Understanding how this is regulated is crucial to develop novel strategies to ameliorate only the detrimental effects. Here, we revisited the fundamental hypothesis that the level of ROS per se is a key factor in the cellular response by applying different concentrations of H2O2 to cardiomyocytes. High concentrations rapidly reduced intracellular ATP and inhibited protein synthesis. This was associated with activation of AMPK which phosphorylated and inhibited Raptor, a crucial component of mTOR complex-1 that regulates protein synthesis. Inhibition of protein synthesis by high concentrations of H2O2 prevents synthesis of immediate early gene products required for downstream gene expression, and such mRNAs (many encoding proteins required to deal with oxidant stress) were only induced by lower concentrations. Lower concentrations of H2O2 promoted mTOR phosphorylation, associated with differential recruitment of some mRNAs to the polysomes for translation. Some of the upregulated genes induced by low H2O2 levels are cytoprotective. We identified p21Cip1/WAF1 as one such protein, and preventing its upregulation enhanced the rate of cardiomyocyte apoptosis. The data support the concept of a "redox rheostat" in which different degrees of ROS influence cell energetics and intracellular signalling pathways to regulate mRNA and protein expression. This sliding scale determines cell fate, modulating survival vs death