The Cone Dysfunction Syndromes

The cone dysfunction syndromes are a heterogeneous group of inherited, predominantly stationary retinal disorders characterised by reduced central vision, and varying degrees of colour vision abnormalities, nystagmus and photophobia. This review details the following conditions: complete and incomplete achromatopsia, blue-cone monochromatism, oligocone trichromacy, bradyopsia, and Bornholm eye disease. We describe the clinical, psychophysical, electrophysiological and imaging findings that are characteristic to each condition, in order to aid their accurate diagnosis, as well as highlight some classically held notions about these diseases that have come to be challenged over recent years. The latest data regarding the genetic aetiology and pathological changes observed in the cone dysfunction syndromes are discussed, and, where relevant, translational avenues of research, including completed and anticipated interventional clinical trials, for some of the diseases described herein will be presented. Finally, we briefly review the current management of these disorders

Workplace design

Purpose: Although both the job and its broader context are likely to drive motivation, little is known about the specific workplace characteristics that are important for motivation. We present the Workplace Characteristics Model, which describes the workplace characteristics that can foster motivation, and the corresponding multilevel Workplace Design Questionnaire. Design/methodology/approach: The model is configured as nine workplace attributes describing climate for motivation at two levels, psychological and organizational. The multilevel multi-time questionnaire was validated with data from 4287 individuals and 212 workplaces and integrated regulation as the criterion outcome. Findings: Multilevel factor analysis and regression indicated good internal reliability, construct validity, and stability over time, and excellent concurrent and predictive validity of the questionnaire. Research/Practical implications: The model could help to optimize job and workplace design by contextualizing motivation. The questionnaire offers advancement over single-level climate measures as it is validated simultaneously at two levels. Further research should focus on overcoming the low response rate typical for online surveys, on need fulfillment as the mediating variable, and on the joint influence of job and workplace characteristics on organizational behavior. Originality/value: This work responds to calls to incorporate context in research into organizational behavior and job design. An understanding of the workplace is a first step in this direction. The questionnaire is the first to be validated at multiple levels of analysis. Ultimately, workplace design could support job design and the development of inherently motivating workplaces

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

Quantum effects in the diffusion of hydrogen on Ru(0001)

An understanding of hydrogen diffusion on metal surfaces is important, not just for its role in heterogeneous catalysis and hydrogen fuel cell technology, but also because it provides model systems where tunneling can be studied under well-defined conditions. Here we report helium spin-echo measurements of the atomic-scale motion of hydrogen on the Ru(0001) surface between 75 and 250 K. Quantum effects are evident at temperatures as high as 200 K, while below 120 K we observe a tunneling-dominated temperature independent jump rate of 1.9$\times$10$^9$ s$^{-1}$, many orders of magnitude faster than previously seen. Quantum transition state theory calculations based on ab initio path-integral simulations reproduce the temperature dependence of the rate at higher temperatures and predict a crossover to tunneling-dominated diffusion at low temperatures, although the tunneling rate is under-estimated, highlighting the need for future experimental and theoretical studies of hydrogen diffusion on well-defined surfaces.Comment: 15 pages, 3 figure

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

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

OCT angiography in the management of choroidal neovascular membrane secondary to Sorsby fundus dystrophy

We describe the management of a woman aged 52 years with molecularly confirmed Sorsby fundus dystrophy, who presented with acute visual deterioration in her right eye. Fundus examination identified a right macular lesion suggestive of a choroidal neovascular membrane (CNVM). Optical coherence tomography angiography (OCTA) confirmed the presence of a CNVM. She was treated with 2 monthly intravitreal injections of bevacizumab, associated with OCTA evidence of regression of the CNVM and improvement in her visual acuity. OCTA is a novel, non-invasive method of imaging the retinal vasculature. Images are acquired rapidly, with no associated side effects, offering advantages over the current gold standard technique-fundus fluorescein angiography

Molecular simulations of heterogeneous ice nucleation. I. Controlling ice nucleation through surface hydrophilicity

Ice formation is one of the most common and important processes on earth and almost always occurs at the surface of a material. A basic understanding of how the physicochemical properties of a material's surface affect its ability to form ice has remained elusive. Here, we use molecular dynamics simulations to directly probe heterogeneous ice nucleation at a hexagonal surface of a nanoparticle of varying hydrophilicity. Surprisingly, we find that structurally identical surfaces can both inhibit and promote ice formation and analogous to a chemical catalyst, it is found that an optimal interaction between the surface and the water exists for promoting ice nucleation. We use our microscopic understanding of the mechanism to design a modified surface in silico with enhanced ice nucleating ability.Comment: 5 pages; 3 figures; Title changed from previous version on arXi

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/

Stargardt disease: clinical features, molecular genetics, animal models and therapeutic options

Stargardt disease (STGD1; MIM 248200) is the most prevalent inherited macular dystrophy and is associated with disease-causing sequence variants in the gene ABCA4 Significant advances have been made over the last 10 years in our understanding of both the clinical and molecular features of STGD1, and also the underlying pathophysiology, which has culminated in ongoing and planned human clinical trials of novel therapies. The aims of this review are to describe the detailed phenotypic and genotypic characteristics of the disease, conventional and novel imaging findings, current knowledge of animal models and pathogenesis, and the multiple avenues of intervention being explored