How much of the variation in the mutation rate along the human genome can be explained?

It has been claimed recently that it may be possible to predict the rate of de novo mutation of each site in the human genome with a high degree of accuracy [Michaelson et al. (2012), Cell 151: 143121442]. We show that this claim is unwarranted. By considering the correlation between the rate of de novo mutation and the predictions from the model of Michaelson et al., we show there could be substantial unexplained variance in the mutation rate. We investigate whether the model of Michaelson et al. captures variation at the single nucleotide level that is not due to simple context. We show that the model captures a substantial fraction of this variation at CpG dinucleotides but fails to explain much of the variation at non-CpG sites

What can a participatory approach to evaluation contribute to the field of integrated care?

© 2017 BMJ Publishing Group. All rights reserved. Better integration of care within the health sector and between health and social care is seen in many countries as an essential way of addressing the enduring problems of dwindling resources, changing demographics and unacceptable variation in quality of care. Current research evidence about the effectiveness of integration efforts supports neither the enthusiasm of those promoting and designing integrated care programmes nor the growing efforts of practitioners attempting to integrate care on the ground. In this paper we present a methodological approach, based on the principles of participatory research, that attempts to address this challenge. Participatory approaches are characterised by a desire to use social science methods to solve practical problems and a commitment on the part of researchers to substantive and sustained collaboration with relevant stakeholders. We describe how we applied an emerging practical model of participatory research, the researcher-in-residence model, to evaluate a large-scale integrated care programme in the UK. We propose that the approach added value to the programme in a number of ways: by engaging stakeholders in using established evidence and with the benefits of rigorously evaluating their work, by providing insights for local stakeholders that they were either not familiar with or had not fully considered in relation to the development and implementation of the programme and by challenging established mindsets and norms. While there is still much to learn about the benefits and challenges of applying participatory approaches in the health sector, we demonstrate how using such approaches have the potential to help practitioners integrate care more effectively in their daily practice and help progress the academic study of integrated care

Work relations for a system governed by Tsallis statistics

We derive analogues of the Jarzynski equality and Crooks relation to characterise the nonequilibrium work associated with changes in the spring constant of an overdamped oscillator in a quadratically varying spatial temperature profile. The stationary state of such an oscillator is described by Tsallis statistics, and the work relations for certain processes may be expressed in terms of q-exponentials. We suggest that these identities might be a feature of nonequilibrium processes in circumstances where Tsallis distributions are found

Controlling the accuracy of unconditionally stable algorithms in Cahn-Hilliard Equation

Given an unconditionally stable algorithm for solving the Cahn-Hilliard equation, we present a general calculation for an analytic time step \d \tau in terms of an algorithmic time step \dt. By studying the accumulative multi-step error in Fourier space and controlling the error with arbitrary accuracy, we determine an improved driving scheme \dt=At^{2/3} and confirm the numerical results observed in a previous study \cite{Cheng1}.Comment: 4 pages, late

Evidence of widespread degradation of gene control regions in hominid genomes

Although sequences containing regulatory elements located close to protein-coding genes are often only weakly conserved during evolution, comparisons of rodent genomes have implied that these sequences are subject to some selective constraints. Evolutionary conservation is particularly apparent upstream of coding sequences and in first introns, regions that are enriched for regulatory elements. By comparing the human and chimpanzee genomes, we show here that there is almost no evidence for conservation in these regions in hominids. Furthermore, we show that gene expression is diverging more rapidly in hominids than in murids per unit of neutral sequence divergence. By combining data on polymorphism levels in human noncoding DNA and the corresponding human¿chimpanzee divergence, we show that the proportion of adaptive substitutions in these regions in hominids is very low. It therefore seems likely that the lack of conservation and increased rate of gene expression divergence are caused by a reduction in the effectiveness of natural selection against deleterious mutations because of the low effective population sizes of hominids. This has resulted in the accumulation of a large number of deleterious mutations in sequences containing gene control elements and hence a widespread degradation of the genome during the evolution of humans and chimpanzees

Towards a new European Global Security Strategy: challenges and Opportunities

This report briefly examines the interplay between the European security strategic vision and capabilities, its institutional architecture and policy implementation practices, with a particular focus on the EU consular affairs, EU democracy promotion and EU engagement in frozen conflicts under the Neighbourhood Policy (Appendices 1-3). This report contends that in order for the EU to develop an effective and sustainable global security strategy, it first, has to reconcile the vision of its strategic priorities within its inter- and intra-institutional settings. Second, a serious effort is required to develop an integrated view on European security, which does not only focus on the internal dimensions of the EU Security strategy (capabilities), but also equally draws on its external aspects - a genuinely inclusive approach that would blur internal and external dimensions of security. For this to succeed a deeper understanding of a partnership-building process (especially of strategic partnership) is needed. Finally, while legitimation of the new security vision is essential within the EU, a greater emphasis should be placed on its external environment, which must not only include a cross-cutting approach to multiple policy instruments as suggested by the EEAs, but more essentially, their connection with the interests and needs of third parties. Case-studies in appendices elaborate further on some specific aspects of the EU security within the eastern neighbourhood context

Review of Andréas Stauder, Linguistic Dating of Middle Egyptian Literary Texts

Revie