Free electron laser generation of X-ray Poincaré beams

An optics-free method is proposed to generate x-ray radiation with spatially variant states of polarization via an afterburner extension to a free electron laser. Control of the polarization in the transverse plane is obtained through the overlap of different coherent transverse light distributions radiated from a bunched electron beam in two consecutive orthogonally polarised undulators. Different transverse profiles are obtained by emitting at a higher harmonic in one or both of the undulators. This method enables the generation of beams structured in their intensity, phase, and polarization - so-called Poincaré beams - at high powers with tunable wavelengths. Simulations are used to demonstrate the generation of two different classes of light with spatially inhomogeneous polarization - cylindrical vector beams and full Poincaré beams

Blocking two-component signalling enhances Candida albicans virulence and reveals adaptive mechanisms that counteract sustained SAPK activation

This work was funded by the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk] JQ (BB/K016393/1); AJPB (BB/K017365/1). The work was also supported by the Wellcome Trust [www.wellcome.ac.uk], JQ (086048, 097377); AJPB (097377)); LPE (097377). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Overscreening and Underscreening in Solid-Electrolyte Grain Boundary Space-Charge Layers

Polycrystalline solids can exhibit material properties that differ significantly from those of equivalent single-crystal samples, in part, because of a spontaneous redistribution of mobile point defects into so-called space-charge regions adjacent to grain boundaries. The general analytical form of these space-charge regions is known only in the dilute limit, where defect-defect correlations can be neglected. Using kinetic Monte Carlo simulations of a three-dimensional Coulomb lattice gas, we show that grain-boundary space-charge regions in non-dilute solid electrolytes exhibit overscreening -- damped oscillatory space-charge profiles -- and underscreening -- decay lengths that are longer than the corresponding Debye length and that increase with increasing defect-defect interaction strength. Overscreening and underscreening are known phenomena in concentrated liquid electrolytes, and the observation of functionally analogous behaviour in solid electrolyte space-charge regions suggests that the same underlying physics drives behaviour in both classes of systems. We therefore expect theoretical approaches developed to study non-dilute liquid electrolytes to be equally applicable to future studies of solid electrolytes

Prehension deficits in amblyopia.

PURPOSE. Visual defects associated with amblyopia have been extensively studied, but their impact on the performance of everyday visuomotor tasks is unclear. This study evaluates eye-hand coordination (prehension) skills in adult amblyopes compared with normal subjects. METHODS. Twenty amblyopes (10 strabismic, 10 nonstrabismic) with different degrees of visual acuity loss (mild, moderate, or severe) and stereodeficiency (reduced or undetectable) participated, along with 20 matched control subjects. Subjects reached, precision grasped, and lifted cylindrical household objects (two sizes, four locations) using binocular vision or just the dominant or amblyopic (nondominant) eye, while the actions of the preferred hand were recorded. Various indices of prehension planning and online control were quantified for all trials (n ϭ 48) performed under each viewing condition. RESULTS. Initial reaching behavior and grip shaping before object contact, which result from movement programming, were relatively normal in the amblyopic subjects, despite their vision losses. By contrast, they exhibited a range of deficits under both binocular and nondominant eye conditions in their final approach to the object (terminal reach) and when closing and applying a grasp. These impairments included prolonged execution times and more errors compared with control subjects, the extents of which covaried with the existing depth of amblyopia, although not with its underlying cause. CONCLUSIONS. Visuomotor adaptations in amblyopes are relatively minor and limited to aspects of movement planning. Their deficits in movement execution should benefit, however, from treatments that restore spatial acuity and binocularity to progressively normal levels and so deserve more explicit consideration when assessing therapeutic outcomes. (Invest Ophthalmol Vis Sci

Post-Depositional Movement of Methanesulphonic Acid at Law Dome, Antarctica, and the Influence of Accumulation Rate

A series of ice cores from sites with different snow-accumulation rates across Law Dome, East Antarctica, was investigated for methanesulphonic acid (MSA) movement. The precipitation at these sites (up to 35 km apart) is influenced by the same air masses, the principal difference being the accumulation rate. At the low-accumulation-rate W20k site (0.17 in ice equivalent), MSA was completely relocated from the summer to winter layer. Moderate movement was observed at the intermediate-accumulation-rate site (0.7 in ice equivalent), Dome Summit South (DSS), while there was no evidence of movement at the high-accumulation-rate DE08 site (1.4 in ice equivalent). The main DSS record of MSA covered the epoch AD 1727-2000 and was used to investigate temporal post-depositional changes. Co-deposition of MSA and sea-salt ions was observed of the surface layers, outside of the main summer MSA peak, which complicates interpretation of these peaks as evidence of movement in deeper layers. A seasonal study of the 273 year DSS record revealed MSA migration predominantly from summer into autumn (in the up-core direction), but this migration was suppressed during the Tambora (1815) and unknown (1809) volcanic eruption period, and enhanced during an epoch (1770-1800) with high summer nitrate levels. A complex interaction between the gradients in nss-sulphate, nitrate and sea salts (which are influenced by accumulation rate) is believed to control the rate and extent of movement of MSA

CD147 mediates intrahepatic leukocyte aggregation and determines the extent of liver injury

Background: Chronic inflammation is the driver of liver injury and results in progressive fibrosis and eventual cirrhosis with consequences including both liver failure and liver cancer. We have previously described increased expression of the highly multifunctional glycoprotein CD147 in liver injury. This work describes a novel role of CD147 in liver inflammation and the importance of leukocyte aggregates in determining the extent of liver injury. Methods: Non-diseased, progressive injury, and cirrhotic liver from humans and mice were examined using a mAb targeting CD147. Inflammatory cell subsets were assessed by multiparameter flow cytometry. Results: In liver injury, we observe abundant, intrahepatic leukocyte clusters defined as ≥5 adjacent CD45+ cells which we have termed “leukocyte aggregates”. We have shown that these leukocyte aggregates have a significant effect in determining the extent of liver injury. If CD147 is blocked in vivo, these leukocyte aggregates diminish in size and number, together with a marked significant reduction in liver injury including fibrosis. This is accompanied by no change in overall intrahepatic leukocyte numbers. Further, blocking of aggregation formation occurs prior to an appreciable increase in inflammatory markers or fibrosis. Additionally, there were no observed, “off-target” or unpredicted effects in targeting CD147. Conclusion: CD147 mediates leukocyte aggregation which is associated with the development of liver injury. This is not a secondary effect, but a cause of injury as aggregate formation proceeds other markers of injury. Leukocyte aggregation has been previously described in inflammation dating back over many decades. Here we demonstrate that leukocyte aggregates determine the extent of liver injury

Consolidation of weathered limestone using nanolime

Limestone sourced from Salisbury Cathedral and Bath Abbey (UK) was treated with commercially available nanolime of concentration 25 g/l. The response of the stones to the treatment was studied using a variety of analysis techniques including optical microscopy, electron microscopy, drilling resistance measurement and mercury intrusion porosimetry. Weathered and non-weathered surfaces of both types of stones were compared. All the specimens were characterised before and after the treatment to determine any changes in their properties caused by their weathering and by the treatment itself. Results show that the degradation processes of the stones strongly affect their interaction with nanolime consolidation treatments. Drilling resistance measurements of treated and untreated samples were compared. After 20 days significant increases in sub-surface drilling resistance was observed in the non-weathered Bath stone and a small increase in the weathered Bath stone after 6 months was also noted. Both weathered and non-weathered Chilmark stone showed an increase in drilling resistance after 6 months, however at 20 days this was most evident in the samples treated with nanolime in isopropanol as opposed to ethanol

Analysis of the role of 13 major fimbrial subunits in colonisation of the chicken intestines by Salmonella enterica serovar Enteritidis reveals a role for a novel locus

<p>Abstract</p> <p>Background</p> <p><it>Salmonella enterica </it>is a facultative intracellular pathogen of worldwide importance. Over 2,500 serovars exist and infections in humans and animals may produce a spectrum of symptoms from enteritis to typhoid depending on serovar- and host-specific factors. <it>S</it>. Enteritidis is the most prevalent non-typhoidal serovar isolated from humans with acute diarrhoeal illness in many countries. Human infections are frequently associated with direct or indirect contact with contaminated poultry meat or eggs owing to the ability of the organism to persist in the avian intestinal and reproductive tract. The molecular mechanisms underlying colonisation of poultry by <it>S</it>. Enteritidis are ill-defined. Targeted and genome-wide mutagenesis of <it>S</it>. Typhimurium has revealed conserved and host-specific roles for selected fimbriae in intestinal colonisation of different hosts. Here we report the first systematic analysis of each chromosomally-encoded major fimbrial subunit of <it>S</it>. Enteritidis in intestinal colonisation of chickens.</p> <p>Results</p> <p>The repertoire, organisation and sequence of the fimbrial operons within members of <it>S. enterica </it>were compared. No single fimbrial locus could be correlated with the differential virulence and host range of serovars by comparison of available genome sequences. Fimbrial operons were highly conserved among serovars in respect of gene number, order and sequence, with the exception of <it>safA</it>. Thirteen predicted major fimbrial subunit genes were separately inactivated by lambda Red recombinase-mediated linear recombination followed by P22/int transduction. The magnitude and duration of intestinal colonisation by mutant and parent strains was measured after oral inoculation of out-bred chickens. Whilst the majority of <it>S</it>. Enteritidis major fimbrial subunit genes played no significant role in colonisation of the avian intestines, mutations affecting <it>pegA </it>in two different <it>S</it>. Enteritidis strains produced statistically significant attenuation. Plasmid-mediated <it>trans</it>-complementation partially restored the colonisation phenotype.</p> <p>Conclusion</p> <p>We describe the fimbrial gene repertoire of the predominant non-typhoidal <it>S. enterica </it>serovar affecting humans and the role played by each predicted major fimbrial subunit in intestinal colonisation of the primary reservoir. Our data support a role for PegA in the colonisation of poultry by <it>S</it>. Enteritidis and aid the design of improved vaccines.</p

Developing feasible person-centred care alternatives to emergency department responses for adults with epilepsy: a discrete choice analysis mixed-methods study

Background: Calls have been made for paramedics to have some form of care pathway that they could use to safely divert adults with epilepsy away from emergency departments and instigate ambulatory care improvements. Different configurations are possible. To know which to prioritise for implementation/evaluation, there is a need to determine which are acceptable to service users and likely National Health Service-feasible. // Objective(s): (1) Identify configurations being considered, (2) understand service users’ views of them and current provision, (3) identify what sort of care service users want and (4) determine which configuration(s) is considered to achieve optimal balance in meeting users’ preference and being National Health Service-feasible. // Design: Service providers were surveyed to address objective 1. Interviews with service users addressed objective 2. Objective 3 was addressed by completing discrete choice experiments. These determined users’ care preferences for different seizure scenarios. Objective 4 was addressed by completing ‘knowledge exchange’ workshops. At these, stakeholders considered the findings on users’ stated preferences and judged different pathway configurations against Michie’s ‘acceptability, practicability, effectiveness, affordability, side-effects and equity’ feasibility criteria. // Setting: This project took place in England. The survey recruited representatives from neurology and neuroscience centres and from urgent and emergency care providers. For the interviews, recruitment occurred via third-sector support groups. Recruitment for discrete choice experiments occurred via the North West Ambulance Service NHS Trust and public advert. Workshop participants were recruited from neurology and neuroscience centres, urgent and emergency care providers, support groups and commissioning networks. // Participants: Seventy-two services completed the survey. Interviews were conducted with 25 adults with epilepsy (and 5 relatives) who had emergency service contact in the prior 12 months. Discrete choice experiments were completed by 427 adults with epilepsy (and 167 relatives) who had ambulance service contact in the prior 12 months. Workshops were completed with 27 stakeholders. // Results: The survey identified a range of pathway configurations. They differed in where they would take the patient and their potential to instigate ambulatory care improvements. Users had been rarely consulted in designing them. The discrete choice experiments found that users want a configuration of care markedly different to that offered. Across the seizure scenarios, users wanted their paramedic to have access to their medical records; for an epilepsy specialist (e.g. an epilepsy nurse, neurologist) to be available to advise; for their general practitioner to receive a report; for the incident to generate an appointment with an epilepsy specialist; for the care episode to last < 6 hours; and there was a pattern of preference to avoid conveyance to emergency departments and stay where they were. Stakeholders judged this configuration to be National Health Service-feasible within 5–10 years, with some elements being immediately deployable. // Limitations: The discrete choice experiment sample was broadly representative, but those reporting recent contact with an epilepsy specialist were over-represented. // Conclusions: Users state they want a configuration of care that is markedly different to current provision. The configuration they prefer was, with support and investment, judged to likely be National Health Service-feasible. The preferred configuration should now be developed and evaluated to determine its actual deliverability and efficacy