Table of Contents and Prologue

Editorial board, Table of contents, and Prologue, an introduction to volume

Major surgery induces acute changes in measured DNA methylation associated with immune response pathways

Surgery is an invasive procedure evoking acute inflammatory and immune responses that can influence risk for postoperative complications including cognitive dysfunction and delirium. Although the specific mechanisms driving these responses have not been well-characterized, they are hypothesized to involve the epigenetic regulation of gene expression. We quantified genome-wide levels of DNA methylation in peripheral blood mononuclear cells (PBMCs) longitudinally collected from a cohort of elderly patients undergoing major surgery, comparing samples collected at baseline to those collected immediately post-operatively and at discharge from hospital. We identified acute changes in measured DNA methylation at sites annotated to immune system genes, paralleling changes in serum-levels of markers including C-reactive protein (CRP) and Interleukin 6 (IL-6) measured in the same individuals. Many of the observed changes in measured DNA methylation were consistent across different types of major surgery, although there was notable heterogeneity between surgery types at certain loci. The acute changes in measured DNA methylation induced by surgery are relatively stable in the post-operative period, generally persisting until discharge from hospital. Our results highlight the dramatic alterations in gene regulation induced by invasive surgery, primarily reflecting upregulation of the immune system in response to trauma, wound healing and anaesthesia.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This work was supported by the Medical Research Council (Grant MR/M008924/1), the Sasakawa Foundation (Butterfield Awards B108) and the UK National Institute for Health Research (NIHR) Exeter Clinical Research Facility (Exeter CRF).Published version, Accepted version, Submitted versio

Tailoring the nonlinear response of hollow-core photonic bandgap fibres

International audienceWe have fabricated 7-cell and 3-cell core hollow-core photonic bandgap fibres with core sizes ranging from 16.7 mu m to 6.5 mu m. A numerical study of the nonlinear coefficient of fibres with different core sizes is carried out. We show that the nonlinearity is more effectively increased by a 3-cell core design than by reducing the size of a seven-cell core

Directed vaccination against pneumococcal disease

Immunization strategies against commensal bacterial pathogens have long focused on eradicating asymptomatic carriage as well as disease, resulting in changes in the colonizing microflora with unknown future consequences. Additionally, current vaccines are not easily adaptable to sequence diversity and immune evasion. Here, we present a "smart" vaccine that leverages our current understanding of disease transition from bacterial carriage to infection with the pneumococcus serving as a model organism. Using conserved surface proteins highly expressed during virulent transition, the vaccine mounts an immune response specifically against disease-causing bacterial populations without affecting carriage. Aided by a delivery technology capable of multivalent surface display, which can be adapted easily to a changing clinical picture, results include complete protection against the development of pneumonia and sepsis during animal challenge experiments with multiple, highly variable, and clinically relevant pneumococcal isolates. The approach thus offers a unique and dynamic treatment option readily adaptable to other commensal pathogens

What influences recruitment to randomised controlled trials? A review of trials funded by two UK funding agencies.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: A commonly reported problem with the conduct of multicentre randomised controlled trials (RCTs) is that recruitment is often slower or more difficult than expected, with many trials failing to reach their planned sample size within the timescale and funding originally envisaged. The aim of this study was to explore factors that may have been associated with good and poor recruitment in a cohort of multicentre trials funded by two public bodies: the UK Medical Research Council (MRC) and the Health Technology Assessment (HTA) Programme. METHODS: The cohort of trials was identified from the administrative databases held by the two funding bodies. 114 trials that recruited participants between 1994 and 2002 met the inclusion criteria. The full scientific applications and subsequent trial reports submitted by the trial teams to the funders provided the principal data sources. Associations between trial characteristics and recruitment success were tested using the Chi-squared test, or Fisher's exact test where appropriate. RESULTS: Less than a third (31%) of the trials achieved their original recruitment target and half (53%) were awarded an extension. The proportion achieving targets did not appear to improve over time. The overall start to recruitment was delayed in 47 (41%) trials and early recruitment problems were identified in 77 (63%) trials. The inter-relationship between trial features and recruitment success was complex. A variety of strategies were employed to try to increase recruitment, but their success could not be assessed. CONCLUSION: Recruitment problems are complex and challenging. Many of the trials in the cohort experienced recruitment difficulties. Trials often required extended recruitment periods (sometimes supported by additional funds). While this is of continuing concern, success in addressing the trial question may be more important than recruitment alone.Published versio

Synchronously pumped mid-IR hollow core fiber gas laser

We report a synchronously pumped 3.16 μm acetylene fiber laser based entirely on low-loss silica hollow-core fiber. Our system oscillates at 2.568 MHz repetition rate, when pumped with a modulated amplified 1.53 μm diode laser.</p

Temporal variability is a personalized feature of the human microbiome

Background: It is now apparent that the complex microbial communities found on and in the human body vary across individuals. What has largely been missing from previous studies is an understanding of how these communities vary over time within individuals. To the extent to which it has been considered, it is often assumed that temporal variability is negligible for healthy adults. Here we address this gap in understanding by profiling the forehead, gut (fecal), palm, and tongue microbial communities in 85 adults, weekly over 3 months. Results: We found that skin (forehead and palm) varied most in the number of taxa present, whereas gut and tongue communities varied more in the relative abundances of taxa. Within each body habitat, there was a wide range of temporal variability across the study population, with some individuals harboring more variable communities than others. The best predictor of these differences in variability across individuals was microbial diversity; individuals with more diverse gut or tongue communities were more stable in composition than individuals with less diverse communities. Conclusions: Longitudinal sampling of a relatively large number of individuals allowed us to observe high levels of temporal variability in both diversity and community structure in all body habitats studied. These findings suggest that temporal dynamics may need to be considered when attempting to link changes in microbiome structure to changes in health status. Furthermore, our findings show that, not only is the composition of an individual's microbiome highly personalized, but their degree of temporal variability is also a personalized feature

How European Union Membership Can Undermine the Rule of Law in Emerging Democracies

The European Union views the spread of economic prosperity and rule of law to countries emerging from dictatorship as among its primary goals when considering countries as candidates for membership. Existing literature often suggests that EU membership confers significant benefits on the accession countries, and these countries are willing to undergo costly and difficult reforms to reap these benefits. Through strict membership conditions, member states force accession countries to commit to democracy. Drawing on theoretical work in the fields of law, politics, and economics, this article reassesses the conventional wisdom. It argues that, under certain conditions, the reforms required of would-be members could have the perverse effect of undermining the establishment of legitimate law in transitional democracies. Using an agent-based model, the article elucidates a theory in which placing laws on the books around which no societal consensus exists can create perverse incentives for citizens and government officials and may lead to an erosion of the rule of law

Solitons in hollow core photonic crystal fiber:Engineering nonlinearity and compressing pulses

International audienc