New and emerging technologies for the treatment of inherited retinal diseases: a horizon scanning review.

The horizon scanning review aimed to identify new and emerging technologies in development that have the potential to slow or stop disease progression and/or reverse sight loss in people with inherited retinal diseases (IRDs). Potential treatments were identified using recognized horizon scanning methods. These included a combination of online searches using predetermined search terms, suggestions from clinical experts and patient and carer focus groups, and contact with commercial developers. Twenty-nine relevant technologies were identified. These included 9 gene therapeutic approaches, 10 medical devices, 5 pharmacological agents, and 5 regenerative and cell therapies. A further 11 technologies were identified in very early phases of development (typically phase I or pre-clinical) and were included in the final report to give a complete picture of developments 'on the horizon'. Clinical experts and patient and carer focus groups provided helpful information and insights, such as the availability of specialised services for patients, the potential impacts of individual technologies on people with IRDs and their families, and helped to identify additional relevant technologies. This engagement ensured that important areas of innovation were not missed. Most of the health technologies identified are still at an early stage of development and it is difficult to estimate when treatments might be available. Further, well designed trials that generate data on efficacy, applicability, acceptability, and costs of the technologies, as well as the long-term impacts for various conditions are required before these can be considered for adoption into routine clinical practice

Benchmarking the performance of Density Functional Theory and Point Charge Force Fields in their Description of sI Methane Hydrate against Diffusion Monte Carlo

High quality reference data from diffusion Monte Carlo calculations are presented for bulk sI methane hydrate, a complex crystal exhibiting both hydrogen-bond and dispersion dominated interactions. The performance of some commonly used exchange-correlation functionals and all-atom point charge force fields is evaluated. Our results show that none of the exchange-correlation functionals tested are sufficient to describe both the energetics and the structure of methane hydrate accurately, whilst the point charge force fields perform badly in their description of the cohesive energy but fair well for the dissociation energetics. By comparing to ice Ih, we show that a good prediction of the volume and cohesive energies for the hydrate relies primarily on an accurate description of the hydrogen bonded water framework, but that to correctly predict stability of the hydrate with respect to dissociation to ice Ih and methane gas, accuracy in the water-methane interaction is also required. Our results highlight the difficulty that density functional theory faces in describing both the hydrogen bonded water framework and the dispersion bound methane.Comment: 8 pages, 4 figures, 1 table. Minor typos corrected and clarification added in Method

Communication: Truncated non-bonded potentials can yield unphysical behavior in molecular dynamics simulations of interfaces

Non-bonded potentials are included in most force fields and therefore widely used in classical molecular dynamics simulations of materials and interfacial phenomena. It is commonplace to truncate these potentials for computational efficiency based on the assumption that errors are negligible for reasonable cutoffs or compensated for by adjusting other interaction parameters. Arising from a metadynamics study of the wetting transition of water on a solid substrate, we find that the influence of the cutoff is unexpectedly strong and can change the character of the wetting transition from continuous to first order by creating artificial metastable wetting states. Common cutoff corrections such as the use of a force switching function, a shifted potential, or a shifted force do not avoid this. Such a qualitative difference urges caution and suggests that using truncated non-bonded potentials can induce unphysical behavior that cannot be fully accounted for by adjusting other interaction parameters

Understanding the role of ions and water molecules in the NaCl dissolution process

The dissolution of NaCl in water is one of the most common everyday processes, yet it remains poorly understood at the molecular level. Here we report the results of an extensive density functional theory study in which the initial stages of NaCl dissolution have been examined at low water coverages. Our specific approach is to study how the energetic cost of moving an ion or a pair of ions to a less coordinated site at the surface of various NaCl crystals varies with the number of water molecules adsorbed on the surface. This "microsolvation" approach allows us to study the dependence of the defect energies on the number of water molecules in the cluster and thus to establish when and where dissolution becomes favorable. Moreover, this approach allows us to understand the roles of the individual ions and water molecules in the dissolution process. Consistent with previous work we identify a clear preference for dissolution of Cl ions over Na ions. However, the detailed information obtained here leads to the conclusion that the process is governed by the higher affinity of the water molecules to Na ions than to Cl ions. The Cl ions are released first as this exposes more Na ions at the surface creating favorable adsorption sites for water. We discuss how this mechanism is likely to be effective for other alkali halides

Semantic annotation in ubiquitous healthcare skills-based learning environments

This paper describes initial work on developing a semantic annotation system for the augmentation of skills-based learning for Healthcare. Scenario driven skills-based learning takes place in an augmented hospital ward simulation involving a patient simulator known as SimMan. The semantic annotation software enables real-time annotations of these simulations for debriefing of the students, student self study and better analysis of the learning approaches of mentors. A description of the developed system is provided with initial findings and future directions for the work.<br/

Ordering of small particles in one-dimensional coherent structures by time-periodic flows

Small particles transported by a fluid medium do not necessarily have to follow the flow. We show that for a wide class of time-periodic incompressible flows inertial particles have a tendency to spontaneously align in one-dimensional dynamic coherent structures. This effect may take place for particles so small that often they would be expected to behave as passive tracers and be used in PIV measurement technique. We link the particle tendency to form one-dimensional structures to the nonlinear phenomenon of phase locking. We propose that this general mechanism is, in particular, responsible for the enigmatic formation of the `particle accumulation structures' discovered experimentally in thermocapillary flows more than a decade ago and unexplained until now

Tuning dissociation using isoelectronically doped graphene and hexagonal boron nitride: water and other small molecules

Novel uses for 2-dimensional materials like graphene and hexagonal boron nitride (h-BN) are being frequently discovered especially for membrane and catalysis applications. Still however, a great deal remains to be understood about the interaction of environmentally and industrially elevant molecules such as water with these materials. Taking inspiration from advances in hybridising graphene and h-BN, we explore using density functional theory, the dissociation of water, hydrogen, methane, and methanol on graphene, h-BN, and their isoelectronic doped counterparts: BN doped graphene and C doped h-BN. We find that doped surfaces are considerably more reactive than their pristine counterparts and by comparing the reactivity of several small molecules we develop a general framework for dissociative adsorption. From this a particularly attractive consequence of isoelectronic doping emerges: substrates can be doped to enhance their reactivity specifically towards either polar or non-polar adsorbates. As such, these substrates are potentially viable candidates for selective catalysts and membranes, with the implication that a range of tuneable materials can be designed

Compound-specific amino acid ¹⁵N stable isotope probing of nitrogen assimilation by the soil microbial biomass using gas chromatography/combustion/isotope ratio mass spectrometry

RATIONALE: Organic nitrogen (N) greatly exceeds inorganic N in soils, but the complexity and heterogeneity of this important soil N pool make investigations into the fate of N‐containing additions and soil organic N cycling challenging. This paper details a novel approach to investigate the fate of applied N in soils, generating quantitative measures of microbial assimilation and of newly synthesized soil protein. METHODS: Laboratory incubation experiments applying (15)N‐ammonium, (15)N‐nitrate and (15)N‐glutamate were carried out and the high sensitivity and selectivity of gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) exploited for compound‐specific (15)N stable isotope probing ((15)N‐SIP) of extracted incubation soil amino acids (AAs; as N‐acetyl, O‐isopropyl derivatives). We then describe the interpretation of these data to obtain a measure of the assimilation of the applied (15)N‐labelled substrate by the soil microbial biomass and an estimate of newly synthesised soil protein. RESULTS: The cycling of agriculturally relevant N additions is undetectable via bulk soil N content and δ (15)N values and AA concentrations. The assimilation pathways of the three substrates were revealed via patterns in AA δ (15)N values with time, reflecting known biosynthetic pathways (e.g. ammonium uptake occurs first via glutamate) and these data were used to expose differences in the rates and fluxes of the applied N substrates into the soil protein pool (glutamate > ammonium > nitrate). CONCLUSIONS: Our compound‐specific (15)N‐SIP approach using GC/C/IRMS offers a number of insights, inaccessible via existing techniques, into the fate of applied (15)N in soils and is potentially widely applicable to the study of N cycling in any soil, or indeed, in any complex ecosystem. © 2016 The Authors. Rapid Communications in Mass Spectrometry Published by John Wiley & Sons Ltd

Shared visiting in Equator city

In this paper we describe an infrastructure and prototype system for sharing of visiting experiences across multiple media. The prototype supports synchronous co-visiting by physical and digital visitors, with digital access via either the World Wide Web or 3-dimensional graphics