Generalized Arago-Fresnel laws: The EME-flow-line description

We study experimentally and theoretically the influence of light polarization on the interference patterns behind a diffracting grating. Different states of polarization and configurations are been considered. The experiments are analyzed in terms of electromagnetic energy (EME) flow lines, which can be eventually identified with the paths followed by photons. This gives rise to a novel trajectory interpretation of the Arago-Fresnel laws for polarized light, which we compare with interpretations based on the concept of "which-way" (or "which-slit") information.Comment: 14 pages, 6 figure

Direct Formation of Supermassive Black Holes via Multi-Scale Gas Inflows in Galaxy Mergers

Observations of distant bright quasars suggest that billion solar mass supermassive black holes (SMBHs) were already in place less than a billion years after the Big Bang. Models in which light black hole seeds form by the collapse of primordial metal-free stars cannot explain their rapid appearance due to inefficient gas accretion. Alternatively, these black holes may form by direct collapse of gas at the center of protogalaxies. However, this requires metal-free gas that does not cool efficiently and thus is not turned into stars, in contrast with the rapid metal enrichment of protogalaxies. Here we use a numerical simulation to show that mergers between massive protogalaxies naturally produce the required central gas accumulation with no need to suppress star formation. Merger-driven gas inflows produce an unstable, massive nuclear gas disk. Within the disk a second gas inflow accumulates more than 100 million solar masses of gas in a sub-parsec scale cloud in one hundred thousand years. The cloud undergoes gravitational collapse, which eventually leads to the formation of a massive black hole. The black hole can grow to a billion solar masses in less than a billion years by accreting gas from the surrounding disk.Comment: 26 pages, 4 Figures, submitted to Nature (includes Supplementary Information

Broken symmetry and the variation of critical properties in the phase behaviour of supramolecular rhombus tilings

The degree of randomness, or partial order, present in two-dimensional supramolecular arrays of isophthalate tetracarboxylic acids is shown to vary due to subtle chemical changes such as the choice of solvent or small differences in molecular dimensions. This variation may be quantified using an order parameter and reveals a novel phase behaviour including random tiling with varying critical properties as well as ordered phases dominated by either parallel or non-parallel alignment of neighbouring molecules, consistent with long-standing theoretical studies. The balance between order and randomness is driven by small differences in the intermolecular interaction energies, which we show, using numerical simulations, can be related to the measured order parameter. Significant variations occur even when the energy difference is much less than the thermal energy highlighting the delicate balance between entropic and energetic effects in complex self-assembly processes

Red blood cell distribution width: Genetic evidence for aging pathways in 116,666 volunteers

This is the final version of the article. Available from Public Library of Science via the DOI in this record.INTRODUCTION: Variability in red blood cell volumes (distribution width, RDW) increases with age and is strongly predictive of mortality, incident coronary heart disease and cancer. We investigated inherited genetic variation associated with RDW in 116,666 UK Biobank human volunteers. RESULTS: A large proportion RDW is explained by genetic variants (29%), especially in the older group (60+ year olds, 33.8%, <50 year olds, 28.4%). RDW was associated with 194 independent genetic signals; 71 are known for conditions including autoimmune disease, certain cancers, BMI, Alzheimer's disease, longevity, age at menopause, bone density, myositis, Parkinson's disease, and age-related macular degeneration. Exclusion of anemic participants did not affect the overall findings. Pathways analysis showed enrichment for telomere maintenance, ribosomal RNA, and apoptosis. The majority of RDW-associated signals were intronic (119 of 194), including SNP rs6602909 located in an intron of oncogene GAS6, an eQTL in whole blood. CONCLUSIONS: Although increased RDW is predictive of cardiovascular outcomes, this was not explained by known CVD or related lipid genetic risks, and a RDW genetic score was not predictive of incident disease. The predictive value of RDW for a range of negative health outcomes may in part be due to variants influencing fundamental pathways of aging.This work was supported by an award to DM, TF, AM and LH by the UK Medical Research Council (grant number MR/M023095/1). SEJ is funded by the Medical Research Council (grant: MR/M005070/1). JT is funded by a Diabetes Research and Wellness Foundation Fellowship. RB is funded by the Wellcome Trust and Royal Society grant: 104150/Z/14/Z. MAT, MNW and AM are supported by the Wellcome Trust Institutional Strategic Support Award (WT097835MF). ARW, HY, and TF are supported by the European Research Council grant: 323195:GLUCOSEGENES-FP7-IDEAS-ERC. LF is supported by the Intramural Research Program of the National Institute on Aging, U.S. National Institutes of Health. Input from MD, CLK and GK was supported by the University of Connecticut Health Center. This research has been conducted using the UK Biobank Resource under Application Number 14631. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The Debrisoft ® monofilament debridement pad for use in acute or chronic wounds: A NICE medical technology guidance

As part of its Medical Technology Evaluation Programme, the National Institute for Health and Care Excellence (NICE) invited a manufacturer to provide clinical and economic evidence for the evaluation of the Debrisoft ® monofilament debridement pad for use in acute or chronic wounds. The University of Birmingham and Brunel University, acting as a consortium, was commissioned to act as an External Assessment Centre (EAC) for NICE, independently appraising the submission. This article is an overview of the original evidence submitted, the EAC’s findings and the final NICE guidance issued. The sponsor submitted a simple cost analysis to estimate the costs of using Debrisoft® to debride wounds compared with saline and gauze, hydrogel and larvae. Separate analyses were conducted for applications in home and applications in a clinic setting. The analysis took an UK National Health Service (NHS) perspective. It incorporated the costs of the technologies and supplementary technologies (such as dressings) and the costs of their application by a district nurse. The sponsor concluded that Debrisoft® was cost saving relative to the comparators. The EAC made amendments to the sponsor analysis to correct for errors and to reflect alternative assumptions. Debrisoft® remained cost saving in most analyses and savings ranged from £77 to £222 per patient compared with hydrogel, from £97 to £347 compared with saline and gauze, and from £180 to £484 compared with larvae depending on the assumptions included in the analysis and whether debridement took place in a home or clinic setting. All analyses were severely limited by the available data on effectiveness, in particular a lack of comparative studies and that the effectiveness data for the comparators came from studies reporting different clinical endpoints compared with Debrisoft®. The Medical Technologies Advisory Committee made a positive recommendation for adoption of Debrisoft® and this has been published as a NICE medical technology guidance (MTG17).The Birmingham and Brunel Consortium is funded by NICE to act as an External Assessment Centre for the Medical Technologies Evaluation Programme

Salt-inducible kinases (SIKs) regulate TGFβ-mediated transcriptional and apoptotic responses

The signalling pathways initiated by members of the transforming growth factor-β (TGFβ) family of cytokines control many metazoan cellular processes, including proliferation and differentiation, epithelial-mesenchymal transition (EMT) and apoptosis. TGFβ signalling is therefore strictly regulated to ensure appropriate context-dependent physiological responses. In an attempt to identify novel regulatory components of the TGFβ signalling pathway, we performed a pharmacological screen by using a cell line engineered to report the endogenous transcription of the TGFβ-responsive target gene PAI-1. The screen revealed that small molecule inhibitors of salt-inducible kinases (SIKs) attenuate TGFβ-mediated transcription of PAI-1 without affecting receptor-mediated SMAD phosphorylation, SMAD complex formation or nuclear translocation. We provide evidence that genetic inactivation of SIK isoforms also attenuates TGFβ-dependent transcriptional responses. Pharmacological inhibition of SIKs by using multiple small-molecule inhibitors potentiated apoptotic cell death induced by TGFβ stimulation. Our data therefore provide evidence for a novel function of SIKs in modulating TGFβ-mediated transcriptional and cellular responses.</p

To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

Catastrophizing mediates the relationship between the personal belief in a just world and pain outcomes among chronic pain support group attendees

Health-related research suggests the belief in a just world can act as a personal resource that protects against the adverse effects of pain and illness. However, currently, little is known about how this belief, particularly in relation to one’s own life, might influence pain. Consistent with the suggestions of previous research, the present study undertook a secondary data analysis to investigate pain catastrophizing as a mediator of the relationship between the personal just world belief and chronic pain outcomes in a sample of chronic pain support group attendees. Partially supporting the hypotheses, catastrophizing was negatively correlated with the personal just world belief and mediated the relationship between this belief and pain and disability, but not distress. Suggestions for future research and intervention development are made

Emergent complex neural dynamics

A large repertoire of spatiotemporal activity patterns in the brain is the basis for adaptive behaviour. Understanding the mechanism by which the brain's hundred billion neurons and hundred trillion synapses manage to produce such a range of cortical configurations in a flexible manner remains a fundamental problem in neuroscience. One plausible solution is the involvement of universal mechanisms of emergent complex phenomena evident in dynamical systems poised near a critical point of a second-order phase transition. We review recent theoretical and empirical results supporting the notion that the brain is naturally poised near criticality, as well as its implications for better understanding of the brain