Equine Rabies

Rabies in the horse can be obscured by atypical clinical signs. One such case is discussed which resulted in exposure to four people. The clinical signs of equine rabies are reviewed, and a differential diagnosis is discussed. The policy of including rabies in your differential when a CNS problem is observed is again emphasized

Entropy and Barrier-Hopping Determine Conformational Viscoelasticity in Single Biomolecules

Biological macromolecules have complex and non-trivial energy landscapes, endowing them a unique conformational adaptability and diversity in function. Hence, understanding the processes of elasticity and dissipation at the nanoscale is important to molecular biology and also emerging fields such as nanotechnology. Here we analyse single molecule fluctuations in an atomic force microscope (AFM) experiment using a generic model of biopolymer viscoelasticity that importantly includes sources of local `internal' conformational dissipation. Comparing two biopolymers, dextran and cellulose, polysaccharides with and without the well-known `chair-to-boat' transition, reveals a signature of this simple conformational change as minima in both the elasticity and internal friction around a characteristic force. A calculation of two-state populations dynamics offers a simple explanation in terms of an elasticity driven by the entropy, and friction by barrier-controlled hopping, of populations on a landscape. The microscopic model, allows quantitative mapping of features of the energy landscape, revealing unexpectedly slow dynamics, suggestive of an underlying roughness to the free energy.Comment: 25 pages, 7 figures, naturemag.bst, modified nature.cls (naturemodified.cls

How proteins' negative cooperativity emerges from entropic optimisation of versatile collective fluctuations

The fact that allostery, a nonlocal signaling between distant binding sites, can arise mainly from the entropy balance of collective thermal modes, without conformational changes, is by now well known. However, the propensity to generate negative cooperativity is still unclear. Starting from an elastic-network picture of small protein complexes, in which effector binding is modeled by locally altering interaction strengths in lieu of adding a node-spring pair, we elucidate mechanisms particularly for such negative cooperativity. The approach via a few coupled harmonic oscillators with internal elastic strengths allows us to trace individual eigenmodes, their frequencies, and their statistical weights through successive bindings. We find that the alteration of the oscillators' couplings is paramount to covering both signs of allostery. Binding-modified couplings create a rich set of eigenmodes individually for each binding state, modes inaccessible to an ensemble of noninteracting units. The associated shifts of collective-mode frequencies, nonuniform with respect to modes and binding states, result in an enhanced optimizability, reflected by a subtle phase map of allosteric behaviors

Color-coordinate system from a 13th-century account of rainbows.

We present a new analysis of Robert Grosseteste’s account of color in his treatise De iride (On the Rainbow), dating from the early 13th century. The work explores color within the 3D framework set out in Grosseteste’s De colore [see J. Opt. Soc. Am. A 29, A346 (2012)], but now links the axes of variation to observable properties of rainbows. We combine a modern understanding of the physics of rainbows and of human color perception to resolve the linguistic ambiguities of the medieval text and to interpret Grosseteste’s key terms

Shear flow effects on phase separation of entangled polymer blends

We introduce an entanglement model mixing rule for stress relaxation in a polymer blend to a modified Cahn-Hilliard equation of motion for concentration fluctuations in the presence of shear flow. Such an approach predicts both shear-induced mixing and demixing, depending on the relative relaxation times and plateau moduli of the two components

Challenges of a simplified opt-out consent process in a neonatal randomised controlled trial: a qualitative study of parents’ and health professionals’ views and experiences

Background: More effective recruitment strategies like alternative approaches to consent are needed to facilitate adequately powered trials. WithHolding Enteral feeds Around Transfusion (WHEAT) was a multicentre, randomised, pilot trial that compared withholding and continuing feeds around transfusion. The primary clinical outcome was necrotising enterocolitis (NEC). The trial used simplified opt-out consent with concise parent information and no consent form. Objective: To explore the views and experiences of parents and health professionals on the acceptability and feasibility of opt-out consent in randomised comparative effectiveness trials. Methods: A qualitative, descriptive interview-based study nested within a randomised trial. Semi-structured interview transcripts were analysed using inductive thematic analysis. Setting: Eleven neonatal units in England. Participants: Eleven parents and ten health professionals with experience of simplified consent. Results: Five themes emerged: ‘Opt-out consent operationalised as verbal opt-in consent’, ‘Opt-out consent normalises participation while preserving parental choice’, ‘Opt-out consent as an ongoing process of informed choice’, ‘Consent without a consent form’ and ‘Choosing to opt out of a comparative effectiveness trial’, with two subthemes: ‘Wanting “normal care”’ and ‘A belief that feeding is better’. Conclusions: Introducing a novel form of consent proved challenging in practice. The principle of simplified, opt-out approach to consent was generally considered feasible and acceptable by health professionals for a neonatal comparative effectiveness trial. The priority for parents was having the right to decide about trial participation, and they did not see opt-out consent as undermining this. Describing a study as ‘opt-out’ can help to normalise participation and emphasise that parents can withdraw consent