Athletes' Perspectives of the Classification System in Para Alpine Skiing for Those With Visual Impairment.

This study explored the classification experiences and views of Para Alpine skiers with visual impairment. Data from 11  interviews were analyzed using reflexive thematic analysis to generate three themes: Suitability-The skiers questioned the suitability of the visual measurements, testing environment, and the information they received regarding classification; Exclusivity-Skiers felt certain aspects of the system remain exclusive due to the restrictions of sport classes and lack of the athlete voice; and (Dis)trust-Skiers felt distrust in those implementing the system and in other athletes due to intentional misrepresentation. Speculation surrounding this resulted in the skiers' feeling doubt in their own classification. While there is not a "one size fits all" approach to classification, understanding skiers' experiences can be a vital first step and will help to guide future research into the evolution of this sport's classification.

Hydration in Deep Eutectic Solvents Induces Non-monotonic Changes in the Conformation and Stability of Proteins.

The preservation of labile biomolecules presents a major challenge in chemistry, and deep eutectic solvents (DESs) have emerged as suitable environments for this purpose. However, how the hydration of DESs impacts the behavior of proteins is often neglected. Here, we demonstrate that the amino acid environment and secondary structure of two proteins (bovine serum albumin and lysozyme) and an antibody (immunoglobulin G) in 1:2 choline chloride:glycerol and 1:2 choline chloride:urea follow a re-entrant behavior with solvent hydration. A dome-shaped transition is observed with a folded or partially folded structure at very low (<10 wt % H2O) and high (>40 wt % H2O) DES hydration, while protein unfolding increases between those regimes. Hydration also affects protein conformation and stability, as demonstrated for bovine serum albumin in hydrated 1:2 choline chloride:glycerol. In the neat DES, bovine serum albumin remains partially folded and unexpectedly undergoes unfolding and oligomerization at low water content. At intermediate hydration, the protein begins to refold and gradually retrieves the native monomer-dimer equilibrium. However, ca. 36 wt % H2O is required to recover the native folding fully. The half-denaturation temperature of the protein increases with decreasing hydration, but even the dilute DESs significantly enhance the thermal stability of bovine serum albumin. Also, protein unfolding can be reversed by rehydrating the sample to the high hydration regime, also recovering protein function. This correlation provides a new perspective to understanding protein behavior in hydrated DESs, where quantifying the DES hydration becomes imperative to identifying the folding and stability of proteins.

Long-Range Electrostatic Colloidal Interactions and Specific Ion Effects in Deep Eutectic Solvents.

While the traditional consensus dictates that high ion concentrations lead to negligible long-range electrostatic interactions, we demonstrate that electrostatic correlations prevail in deep eutectic solvents where intrinsic ion concentrations often surpass 2.5 M. Here we present an investigation of intermicellar interactions in 1:2 choline chloride:glycerol and 1:2 choline bromide:glycerol using small-angle neutron scattering. Our results show that long-range electrostatic repulsions between charged colloidal particles occur in these solvents. Interestingly, micelle morphology and electrostatic interactions are modulated by specific counterion condensation at the micelle interface despite the exceedingly high concentration of the native halide from the solvent. This modulation follows the trends described by the Hofmeister series for specific ion effects. The results are rationalized in terms of predominant ion-ion correlations, which explain the reduction in the effective ionic strength of the continuum and the observed specific ion effects.

Bayesian determination of the effect of a deep eutectic solvent on the structure of lipid monolayers.

In this work, we present the first example of the self-assembly of phospholipid monolayers at the interface between air and an ionic solvent. Deep eutectic solvents are a novel class of environmentally friendly, non-aqueous, room temperature liquids with tunable properties, that have wide-ranging potential applications and are capable of promoting the self-assembly of surfactant molecules. We use a chemically-consistent Bayesian modelling of X-ray and neutron reflectometry measurements to show that these monolayers broadly behave as they do on water. This method allows for the monolayer structure to be determined, alongside the molecular volumes of the individual monolayer components, without the need for water-specific constraints to be introduced. Furthermore, using this method we are able to better understand the correlations present between parameters in the analytical model. This example of a non-aqueous phospholipid monolayer has important implications for the potential uses of these solvents and for our understanding of how biomolecules behave in the absence of water.

Surfactant-Solvent Interaction Effects on the Micellization of Cationic Surfactants in a Carboxylic Acid-Based Deep Eutectic Solvent.

Deep eutectic solvents have been demonstrated to support amphiphile self-assembly, providing potential alternatives as structure-directing agents in the synthesis of nanostructures, and drug delivery. Here we have expanded on this recent research to investigate the self-assembly of alkyltrimethylammonium bromide surfactants in choline chloride:malonic acid deep eutectic solvent and mixtures of the solvent with water. Surface tension and small-angle neutron scattering were used to determine the behavior of the amphiphiles. Surfactants were found to remain active in the solvent, and surface tension measurements revealed changes in the behavior of the surfactants with different levels of hydration. Small-angle neutron scattering shows that in this solvent the micelle shape depends on the surfactant chain length, varying from globular micelles (aspect ratio ∼2) for short chain surfactants to elongated micelles (aspect ratio ∼14) for long chain surfactants even at low surfactant concentration. We suggest that the formation of elongated micelles can be explained through the interaction of the solvent with the surfactant headgroup, since ion-ion interactions between surfactant headgroups and solvent may modify the morphology of the micelles. The presence of water in the deep eutectic solvents promotes an increase in the charge density at the micelle interface and therefore the formation of less elongated, globular micelles.

Micellization of alkyltrimethylammonium bromide surfactants in choline chloride:glycerol deep eutectic solvent.

Deep eutectic solvents have shown the ability to promote the self-assembly of surfactants in solution. However, some differences have been found compared with self-assembly in pure water and other polar organic solvents. The behaviour of alkyltrimethylammonium bromides in choline chloride:glycerol deep eutectic solvent has been studied by means of surface tension, X-ray and neutron reflectivity and small-angle neutron scattering. The surfactants were found to remain surface active and showed comparable critical micelle concentrations to the same surfactants in water. Our scattering studies demonstrate that these surfactants form globular micelles with ellipsoidal shape in solution. The size, shape and aggregation number of the aggregates were found to vary with the chain length of the surfactant. Specific solvent-headgroup interactions were not found in this system, unlike those we have previously postulated for anionic surfactants in choline chloride deep eutectic solvents.

Unusual excess free energies of mixing in mixtures of partially fluorinated and hydrocarbon surfactants at the air-water interface: correlation with the structure of the layer.

The air-water interface of three mixtures of partially fluorinated surfactants and hydrocarbon surfactants, C4F9C11H22N(CH3)3Br (fC4hC11TAB) with hexadecyltrimethylammonium bromide (C16TAB), (CF3)2C3F6C10H20N(CH3)3Br (fC5hC10TAB) with C16TAB, and C8F17C6H12N(CH3)3Br (fC8hC6TAB) with C18TAB, have been investigated using surface tension (ST) and neutron reflection (NR). Using the composition of the layer determined by NR, the pseudophase separation model was used to fit the variation of concentration for a specific ST to a free energy of mixing, G(E), that included adjustable quadratic, cubic and quartic terms. In all three cases, G(E) was found to be highly unsymmetrical, being approximately ideal at low surface fractions of hydrocarbon surfactant and repulsive at high fractions with a maximum value of 0.2-0.3RT. The corresponding structure of the layer was also determined by NR and showed that the initial ideal behavior of G(E) probably results from a balance of a gain in energy from a reduced immersion of the fluorocarbon chain, brought about by screening of the fluorocarbon from water by the hydrocarbon surfactant, and a loss from increased fluorocarbon-hydrocarbon repulsion. At higher concentration, there is no space in the layer for further screening and the fluorocarbon-hydrocarbon repulsion leads to the expected positive G(E). The calculated G(E) also indicated that there should be phase separation of the two components in the interface over a bulk composition range of about 60-95% hydrocarbon surfactant. However, experiment indicates no phase separation. It is suggested that there are a number of possible additional negative contributions to G(E) close to a phase transition, which are not possible for a true bulk phase separation, and which prevent surface phase separation unless it is strongly favored.

Cephalic arch stenosis: angioplasty to preserve a brachiocephalic fistula or new brachiobasilic fistula? A cost-effectiveness study.

BACKGROUND: Our aim was to evaluate the cost-effectiveness of repeat angioplasty versus new brachiobasilic fistula (BBF) in patients with symptomatic cephalic arch stenosis (CAS). METHODS: Patients presenting with symptomatic CAS (n = 22) underwent angioplasty. They were compared to patients undergoing BBF creation (n = 51). Primary outcomes were functional primary arteriovenous fistulae patency at 3, 6 and 12 months. Data were collected on number of interventions, alternative accesses and hospital days for access-related complications. Quality of life was assessed using Kidney Disease Quality of Life-36 scores. Decision tree, Monte Carlo simulation and sensitivity analysis permitted cost-utility analysis. Healthcare costs were derived from Department of Health figures and are presented as cost (£)/patient/year, cost/access preserved and cost/quality of life-adjusted year (QALY) for each of the treatment strategies. RESULTS: Functional primary patency rates at 3, 6, 12 months were 87.5%, 81% and 43% for repeated angioplasty and 78%, 63% and 41% for BBF. The angioplasty cohort required 1.64 ± 0.23 angioplasties/patient and 0.64 ± 0.34 lines/patient. BBF required 0.36 ± 0.12 angioplasties/patient and 1.2 ± 0.2 lines/patient. Patients in the BBF cohort spent an additional 0.9 days/year in hospital due to access-related complications. Mean cost/patient/year in the angioplasty group was £5247.72/patient/year versus £3807.55/patient/year in the BBF cohort. Mean cost per access saved was £11,544.98 (angioplasty) versus £4979.10 (BBF). Average cost per QALY was £13,809.79 (angioplasty) versus £10,878.72 per QALY (BBF). CONCLUSIONS: CAS poses a difficult management problem with poor outcomes from conventional angioplasty. Optimal management will depend on patient factors, local outcomes and expertise, but consideration should be given to creation of a new BBF as a cost-effective means to manage this difficult problem.

Pharmacotherapy to improve outcomes in vascular access surgery: a review of current treatment strategies.

BACKGROUND: Renal failure is a major cause of morbidity in western Europe, with rising prevalence. Vascular access complications are the leading cause of morbidity among patients on haemodialysis. Considering the health care burden of vascular access failure, there is limited research dedicated to the topic. METHODS: Randomised control trials of medications aimed at improving vascular access patency were identified using a medline search between January 1950 and January 2011. RESULTS: Thirteen randomised trials were identified, investigating antiplatelets, anticoagulants and fish oil in preserving vascular access patency. Outcomes are presented and reviewed in conjunction with the underlying pathophysiological mechanisms of failure of vascular access. DISCUSSION: Vascular access failure is a complex process. Most clinical trials so far have involved medications primarily aimed at preventing thrombosis. Other contributing pathways such as neointimal hyperplasia have not been investigated clinically. Improved outcomes may be seen by linking future therapies to these pathways.

Structural changes in block copolymer micelles induced by cosolvent mixtures.

We investigated the influence of tetrahydrofuran (THF) addition on the structure of poly(1,2-butadiene-b-ethylene oxide) [PB-PEO] micelles in aqueous solution. Our studies showed that while the micelles remained starlike, the micelle core-corona interfacial tension and micelle size decreased upon THF addition. The detailed effects of the reduction in interfacial tension were probed using contrast variations in small angle neutron scattering (SANS) experiments. At low THF contents (high interfacial tensions), the SANS data were fit to a micelle form factor that incorporated a radial density distribution of corona chains to account for the starlike micelle profile. However, at higher THF contents (low interfacial tensions), the presence of free chains in solution affected the scattering at high q and required the implementation of a linear combination of micelle and Gaussian coil form factors. These SANS data fits indicated that the reduction in interfacial tension led to broadening of the core-corona interface, which increased the PB chain solvent accessibility at intermediate THF solvent fractions. We also noted that the micelle cores swelled with increasing THF addition, suggesting that previous assumptions of the micelle core solvent content in cosolvent mixtures may not be accurate. Control over the size, corona thickness, and extent of solvent accessible PB in these micelles can be a powerful tool in the development of targeting delivery vehicles.

Complex by design: Hydrotrope-induced micellar growth in deep eutectic solvents.

HYPOTHESIS: The self-assembly of ionic surfactants in deep eutectic solvents has recently been demonstrated, opening up new possibilities in terms of the development of formulated products and templating of nanostructured materials. As it occurs in an aqueous environment, the solvophobic effect drives the formation of micelles in these solvents and specific-ion interactions alter the resulting structures. We hypothesized that the presence of hydrotropic salts would greatly affect the micellar structure in deep eutectic solvents, ultimately leading to the formation of worm-like aggregates. EXPERIMENTS: A systematic investigation performed on hydrotrope-surfactant assemblies in neat and hydrated 1:2 choline chloride:glycerol is presented. The effect of choline salicylate on the micellization of hexadecyltrimethylammonium chloride at different hydrotrope-to-surfactant ratios was probed by contrast variation small-angle neutron scattering. FINDINGS: Here the first investigation on salt-induced micellar growth in deep eutectic solvents is presented. The microscopic characterization of the system shows that the micelle-hydrotrope interaction in pure and hydrated deep eutectic solvents results in a significant increase in micelle elongation. The condensation of the hydrotrope on the micelle, which alters the effective monomer packing, leads to the formation of worm-like micelles with tunable morphology and flexibility. The results presented here present new possibilities in terms of self-assembly and co-assembly in neoteric solvents, where micelle morphology can be controlled through surfactant-salt interactions.

Pharmacotherapy to improve outcomes in infrainguinal bypass graft surgery: a review of current treatment strategies.

A total of 12,000 infrainguinal bypass grafts are performed annually in the United Kingdom, with outcomes suboptimal: 20% of above-knee vein grafts require intervention by 3 years. Transatlantic Inter-Society Consensus (TASC) guidelines exist on pharmacological management of peripheral vascular disease patients, however, little is recommended regarding optimum pharmacological management following revascularization to improve graft patency. The current recommendation is that all patients are on an antiplatelet agent following bypass grafting, the only intervention with significant evidence supporting use. This article will review pharmacological strategies aimed at improving the survival of infrainguinal vein grafts and the current evidence base for their use.

NUrF-Optimization of in situ UV-vis and fluorescence and autonomous characterization techniques with small-angle neutron scattering instrumentation.

We have designed, built, and validated a (quasi)-simultaneous measurement platform called NUrF, which consists of neutron small-angle scattering, UV-visible, fluorescence, and densitometry techniques. In this contribution, we illustrate the concept and benefits of the NUrF setup combined with high-performance liquid chromatography pumps to automate the preparation and measurement of a mixture series of Brij35 nonionic surfactants with perfluorononanoic acid in the presence of a reporter fluorophore (pyrene).

Wavelength frame multiplication for reflectometry at long-pulse neutron sources.

The European Spallation Source (ESS), which is under construction in Lund (Sweden), will be the next leading neutron facility with an unprecedented brilliance and novel long-pulse time structure. A long-pulse source not only provides a high time-average flux but also opens the possibility to tune the resolution by using pulse shaping choppers. Thus, an instrument can readily be operated in either a high flux or a high resolution mode. Several of the shorter instruments at the ESS will employ Wavelength Frame Multiplication (WFM) in order to enable a sufficient resolution while offering a continuous and broad wavelength range. A test beamline was operated until the end of 2019 at the research reactor in Berlin to test components and methods, including WFM, in order to prepare the new facility for the operation of neutron instruments and successful first science. We herein demonstrate the implementation of WFM for reflectometry. By selecting a short pulse mode under the same geometrical configuration, we compare and discuss the results for two reference samples. The reported experiments not only serve to prove the reliability of the WFM approach but also, for the first time, demonstrate the full instrument control, data acquisition and data reduction chain that will be implemented at the ESS.

Effect of a simulated tactical occupation task on physiological strain index, stress and inflammation.

Background. This study aimed to evaluate the physiological strain index (PSI) along with specific immune system markers in response to a simulated firefighting occupation workload. Methods. Ten healthy male adults completed a 6-min simulated fire stair climb (SFSC) at 60 steps/min. The protocol consisted of four conditions, some including wearing a 34.04-kg vest to simulate personal protective equipment (PPE) and/or inclusion of a color-word interference test (CWIT) as a distracting mechanism. The PSI was evaluated by continuously monitoring the heart rate and core temperature. Salivary cortisol (CORT) was measured at baseline, mid SFSC and post SFSC. C-reactive protein (CRP) was evaluated at baseline and 1 h post SFSC. Results. Repeated-measures analysis of variance showed a significantly different PSI across conditions (p = 0.001). A significantly elevated PSI was exhibited during all 6 min of SFSC for both PPE and PPE + CWIT conditions. Neither CORT (p = 0.116) nor CRP (p = 0.700) was significantly different across conditions or from baseline. Conclusion. These findings suggest that firefighters are potentially at a substantial degree of physiological stress from exercise and the weight of gear alone. Further work should be conducted to further evaluate the usefulness of the PSI as a means to monitor firefighters during fire suppression.

Spontaneous recanalization of a middle cerebral artery occlusion with subsequent carotid endarterectomy.

We report the case of a 55-year-old man who presented with a left hemisphere stroke. The initial computed tomography scan demonstrated a cerebral infarct in association with a left middle cerebral artery occlusion. Carotid duplex ultrasound imaging revealed a surgical grade stenosis of the proximal left internal carotid artery; however, in view of the uncertain benefits of internal carotid endarterectomy in the face of ipsilateral middle cerebral artery occlusion, surgery was deferred. Subsequent surveillance by transcranial Doppler imaging and repeat computed tomography demonstrated spontaneous recanalization. The patient proceeded to carotid endarterectomy with no complications.

Ultra-small-angle neutron scattering: a tool to study packing of relatively monodisperse polymer spheres and their binary mixtures.

We measured ultra-small-angle neutron scattering (USANS) from polymethylmethacrylate spheres tamped down in air. Two slightly polydisperse pure sphere sizes (1.5 and 7.5 microm diameters) and five mixtures of these were used. All were loose packed (packing fractions of 0.3-0.6) with nongravitational forces (e.g., friction) important, preventing close packing. The USANS data are rich in information on powder packing. A modified Percus-Yevick fluid model was used to parametrize the data-adequately but not well. The modifications required the introduction of small voids, less than the sphere size, and a parameter reflecting substantial deviation from the Percus-Yevick prediction of the sphere-sphere correlation function. The mixed samples fitted less well, and two further modifying factors were necessary. These were local inhomogeneities, where the concentration of same-size spheres, both large and small, deviated from the mean packing, and a factor accounting for the presence within these "clusters" of self-avoidance of the large spheres (that is, large spheres coated with more small spheres than Percus-Yevick would predict). The overall deviations from the hard-sphere Percus-Yevick model that we find here suggest that fluid models of loose packed powders are unlikely to be successful but lay the ground work for future theoretical and computational works.

Soybean oleosomes studied by small angle neutron scattering (SANS).

HYPOTHESIS: Oleosomes are stabilized by a complex outer phospholipid-protein-layer. To improve understanding of its structure and stabilization mechanism, this shell has to be studied in extracellular native conditions. This should be possible by SANS using contrast variation. Oleosomes are expected to be highly temperature stable, with molecular changes occurring first in the protein shell. Direct measurements of changes in the shell structure are also important for processing methods, e.g. encapsulation. EXPERIMENTS: Extracted soybean oleosomes were studied directly and after encapsulation with pectin by SANS using contrast variation. In order to determine structure and size, a shell model of oleosomes was developed. The method was tested against a simple phospholipid-stabilized emulsion. The oleosomes' temperature stability was investigated by performing SANS at elevated temperatures. FINDINGS: Size (Rg = 1380 Å) and shell thickness of native and encapsulated oleosomes have been determined. This is the first report measuring the shell thickness of oleosomes directly. For native oleosomes, a shell of 9 nm thickness surrounds the oil core, corresponding to a layer of phospholipids and proteins. Up to 90 °C, no structural change was observed, confirming the oleosomes' high temperature stability. Successful coavervation of oleosomes was shown by an increase in shell thickness of 10 nm after electrostatic deposition of pectin.

Resilience of Malic Acid Natural Deep Eutectic Solvent Nanostructure to Solidification and Hydration.

Little is presently known about the unique nanostructure of deep eutectic solvents (DES). The order of the liquid-solid phase transition is contended and whether DES-water mixtures are merely aqueous solutions, or have properties dominated by the eutectic pair, is unclear. Here, we unambiguously show the structure of choline chloride-malic acid (malicine) as a liquid, and also in solid and hydrated forms, using neutron total scattering on D/H isotope-substituted samples, and quasi-elastic neutron scattering (QENS). Data were refined using empirical potential structure refinement. We show evidence for a stoichiometric complex ion cluster in the disordered liquid, with strong choline-chloride bonding and a hydrogen bond donor (HBD) contribution. The 1:1 eutectic stoichiometry makes these ionic domains more well-defined, with less HBD clustering than seen previously for reline. There is minimal structural difference for the solidified material, demonstrating that this DES solidification is a glass transition rather than a first order phase change. QENS data support this by showing a gradual change in solvent dynamics rather than a step change. The DES structure is mostly retained upon hydration, with water acting both as a secondary smaller HBD at closer range to choline than malic acid, and forming transient wormlike aggregates. This new understanding of DES structure will aid understanding of the properties of these novel green solvents on the molecular length scale in chemical processes, as well as giving an insight into the apparent role of natural DESs in plant physiology.