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

Retinitis pigmentosa-associated cystoid macular oedema: pathogenesis and avenues of intervention

Hereditary retinal diseases are now the leading cause of blindness certification in the working age population (age 16-64 years) in England and Wales, of which retinitis pigmentosa (RP) is the most common disorder. RP may be complicated by cystoid macular oedema (CMO), causing a reduction of central vision. The underlying pathogenesis of RP-associated CMO (RP-CMO) remains uncertain, however, several mechanisms have been proposed, including: (1) breakdown of the blood-retinal barrier, (2) failure (or dysfunction) of the pumping mechanism in the retinal pigment epithelial, (3) Müller cell oedema and dysfunction, (4) antiretinal antibodies and (5) vitreous traction. There are limited data on efficacy of treatments for RP-CMO. Treatments attempted to date include oral and topical carbonic anhydrase inhibitors, oral, topical, intravitreal and periocular steroids, topical non-steroidal anti-inflammatory medications, photocoagulation, vitrectomy with internal limiting membrane peel, oral lutein and intravitreal antivascular endothelial growth factor injections. This review summarises the evidence supporting these treatment modalities. Successful management of RP-CMO should aim to improve both quality and quantity of vision in the short term and may also slow central vision loss over time

Water on hexagonal boron nitride from diffusion Monte Carlo

Despite a recent flurry of experimental and simulation studies, an accurate estimate of the interaction strength of water molecules with hexagonal boron nitride is lacking. Here we report quantum Monte Carlo results for the adsorption of a water monomer on a periodic hexagonal boron nitride sheet, which yield a water monomer interaction energy of -84 +/- 5 meV. We use the results to evaluate the performance of several widely used density functional theory (DFT) exchange correlation functionals, and find that they all deviate substantially. Differences in interaction energies between different adsorption sites are however better reproduced by DFT

Term admissions to neonatal units in England: a role for transitional care? A retrospective cohort study

Objective To identify the primary reasons for term admissions to neonatal units in England, to determine risk factors for admissions for jaundice and to estimate the proportion who can be cared for in a transitional setting without separation of mother and baby. Design Retrospective observational study using neonatal unit admission data from the National Neonatal Research Database and data of live births in England from the Office for National Statistics. Setting All 163 neonatal units in England 2011–2013. Participants 133 691 term babies born ≥37 weeks gestational age and admitted to neonatal units in England. Primary and secondary outcomes Primary reasons for admission, term babies admitted for the primary reason of jaundice, patient characteristics, postnatal age at admission, total length of stay, phototherapy, intravenous fluids, exchange transfusion and kernicterus. Results Respiratory disease was the most common reason for admission overall, although jaundice was the most common reason for admission from home (22% home vs 5% hospital). Risk factors for admission for jaundice include male, born at 37 weeks gestation, Asian ethnicity and multiple birth. The majority of babies received only a brief period of phototherapy, and only a third received intravenous fluids, suggesting that some may be appropriately managed without separation of mother and baby. Admission from home was significantly later (3.9 days) compared with those admitted from elsewhere in the hospital (1.7 days) (p<0.001). Conclusion Around two-thirds of term admissions for jaundice may be appropriately managed in a transitional care setting, avoiding separation of mother and baby. Babies with risk factors may benefit from a community midwife postnatal visit around the third day of life to enable early referral if necessary. We recommend further work at the national level to examine provision and barriers to transitional care, referral pathways between primary and secondary care, and community postnatal care

Who Receives Unemployment Insurance?

This paper uses Unemployment Insurance (UI) administrative data combined with Current Population Survey data in 2003 to examine socioeconomic patterns in UI receipt for new job losers. We find that key socioeconomic groups – women, nonwhites, youth, and workers with no high school diploma – were much less likely than average to start collecting UI benefits once they lost their jobs. These differences are partly attributable to differences in part-time employment and unionization; workers in groups with low part-time employment and high unionization rates had higher than average UI receipt rates. We also find that certain groups of job losers – women, youth, workers with no college education, and blue collar workers – collected much lower benefits once they entered the program. These differences are mainly attributed to variation in benefit entitlements and other factors. Our findings enhance our understanding of the effectiveness of the UI program to serve the diverse population of new job losers in the modern US economy

Statistical and neural classifiers in estimating rain rate from weather radar measurements

Weather radars are used to measure the electromagnetic radiation backscattered by cloud raindrops. Clouds that backscatter more electromagnetic radiation consist of larger droplets of rain and therefore they produce more rain. The idea is to estimate rain rate by using weather radar as an alternative to rain-gauges measuring rainfall on the ground. In an experiment during two days in June and August 1997 over the Italian-Swiss Alps, data from weather radar and surrounding rain-gauges were collected at the same time. The statistical KNN and the neural SOM classifiers were implemented for the classification task using the radar data as input and the rain-gauge measurements as output. The proposed system managed to identify matching pattern waveforms and the rainfall rate on the ground was estimated based on the radar reflectivities with a satisfactory error rate, outperforming the traditional <i>Z</i>/<i>R</i> relationship. It is anticipated that more data, representing a variety of possible meteorological conditions, will lead to improved results. The results in this work show that an estimation of rain rate based on weather radar measurements treated with statistical and neural classifiers is possible

Exploring water adsorption on isoelectronically doped graphene using alchemical derivatives

The design and production of novel 2-dimensional materials has seen great progress in the last decade, prompting further exploration of the chemistry of such materials. Doping and hydrogenating graphene is an experimentally realised method of changing its surface chemistry, but there is still a great deal to be understood on how doping impacts on the adsorption of molecules. Developing this understanding is key to unlocking the potential applications of these materials. High throughput screening methods can provide particularly effective ways to explore vast chemical compositions of materials. Here, alchemical derivatives are used as a method to screen the dissociative adsorption energy of water molecules on various BN doped topologies of hydrogenated graphene. The predictions from alchemical derivatives are assessed by comparison to density functional theory. This screening method is found to predict dissociative adsorption energies that span a range of more than 2 eV, with a mean absolute error $<0.1$ eV. In addition, we show that the quality of such predictions can be readily assessed by examination of the Kohn-Sham highest occupied molecular orbital in the initial states. In this way, the root mean square error in the dissociative adsorption energies of water is reduced by almost an order of magnitude (down to $\sim0.02$ eV) after filtering out poor predictions. The findings point the way towards a reliable use of first order alchemical derivatives for efficient screening procedures

Association of geopotential height patterns with heavy rainfall events in Cyprus

Dynamically induced rainfall is strongly connected with synoptic atmospheric circulation patterns at the upper levels. This study investigates the relationship between days of high precipitation volume events in the eastern Mediterranean and the associated geopotential height patterns at 500 hPa. To reduce the number of different patterns and to simplify the statistical processing, the input days were classified into clusters of synoptic cases having similar characteristics, by utilizing Kohonen Self Organizing Maps (SOM) architecture. Using this architecture, synoptic patterns were grouped into 9, 18, 27 and 36 clusters which were subsequently used in the analysis. The classification performance was tested by applying the method to extreme rainfall events in the eastern Mediterranean. The relationship of the synoptic upper air patterns (500 hPa height) and surface features (heavy rainfall events) was established, while the 36 member classification proved to be the most efficient