A genome-wide association study provides evidence for association of chromosome 8p23 (MYP10) and 10q21.1 (MYP15) with high myopia in the French population.

PURPOSE. Myopia is a complex trait affected by both genetic and environmental factors. High myopia is associated with increased risk of sight-threatening eye disorders such as retinal detachment. The purpose of this genome-wide association study was to identify susceptibility genes contributing to high myopia in the French population. METHODS. High myopic cases were genotyped using Affymetrix SNP 6.0 chips and population controls were selected from the GABRIEL French dataset in which samples were genotyped by Illumina Human610 quad array. The association study was conducted using 152,234 single nucleotide polymorphisms that were present on both manufacturers' chips in 192 high myopic cases and 1064 controls to identify associated regions. Imputation was performed on peak regions. RESULTS. Associations were found at known myopia locus MYP10 on chromosome 8p23 and MYP15 on chromosome 10q21.1. Rs189798 (8p23) and rs10825992 (10q21.1) showed the strongest associations in these regions (P=6.32x10-7 and P=2.17x10-5, respectively). The imputed results at 8p23 showed 2 peaks of interest. The first spanned 30kb including rs189798 between MIR4660 and PPP1R3B with the most significant association at rs17155227 (P=1.07x10-10). The second novel peak was 4kb in length, encompassing MIR124-1 and the MSRA gene, with the strongest association at rs55864141 (P=1.30x10-7). The peak of imputed data at 10q21.1 was 70kb in length between ZWINT and MIR3924, with rs3107503 having the lowest P value (P=1.54x10-7). CONCLUSION. We provide evidence for the association of MYP10 at 8p23 and MYP15 at 10p21.1 with high myopia in the French population and refine these regions of association.

Multidimensional modelling of X-ray spectra for AGN accretion disc outflows

We use a multidimensional Monte Carlo code to compute X-ray spectra for a variety of active galactic nucleus (AGN) disc-wind outflow geometries. We focus on the formation of blueshifted absorption features in the Fe K band and show that line features similar to those which have been reported in observations are often produced for lines of sight through disc-wind geometries. We also discuss the formation of other spectral features in highly ionized outflows. In particular, we show that, for sufficiently high wind densities, moderately strong Fe K emission lines can form and that electron scattering in the flow may cause these lines to develop extended red wings. We illustrate the potential relevance of such models to the interpretation of real X-ray data by comparison with observations of a well-known AGN, Mrk 766. Journal compilation © 2008 RAS.

Synthetic X-ray spectra for simulations of the dynamics of an accretion flow irradiated by a quasar

Ultraviolet and X-ray observations show evidence of outflowing gas around many active galactic nuclei. It has been proposed that some of these outflows are driven off gas infalling towards the central supermassive black hole. We perform radiative transfer calculations to compute the gas ionization state and the emergent X-ray spectra for both two- and three-dimensional (3D) hydrodynamical simulations of this outflow-from-inflow scenario. By comparison with observations, our results can be used to test the theoretical models and guide future numerical simulations. We predict both absorption and emission features, most of which are formed in a polar funnel of relatively dense (10 -10 g cm ) outflowing gas. This outflow causes strong absorption for observer orientation angles of ?35°. Particularly in 3D, the strength of this absorption varies significantly for different lines of sight owing to the fragmentary structure of the gas flow. Although infalling material occupies a large fraction of the simulation volume, we do not find that it imprints strong absorption features in the X-ray spectra since the ionization state is predicted to be very high. Thus, an absence of observed inflow absorption features does not exclude the models. The main spectroscopic consequence of the infalling gas is a Compton-scattered continuum component that partially re-fills the absorption features caused by the outflowing polar funnel. Fluorescence and scattering in the outflow are predicted to give rise to several emission features including a multicomponent Fe Ka emission complex for all observer orientations. For the hydrodynamical simulations considered, we predict both ionization states and column densities for the outflowing gas that are too high to be quantitatively consistent with well-observed X-ray absorption systems. Nevertheless, our results are qualitatively encouraging and further exploration of the model parameter space is warranted. Higher resolution hydrodynamic simulations are needed to determine whether the outflows fragment on scales unresolved in our current study, which may yield the denser lower ionization material that could reconcile the models and the observations. © 2012 The Authors Monthly Notices of the Royal Astronomical Society © 2012 RAS.

Punctate inner choroidopathy

Punctate inner choroidopathy (PIC) is a relatively uncommon inflammatory multifocal chorioretinopathy that affects predominantly young myopic women. It is characterized by the presence of multiple, small, well-defined, yellow-white fundus lesions frequently limited to the posterior pole in the absence of flare and inflammatory cells in the anterior chamber or vitreous cavity. Most patients with PIC do not require treatment, as the disease does not often threaten vision; however, when subfoveal choroidal neovascular membrane (CNV) ensues, patients usually lose sight rapidly, requiring immediate care. Treatment modalities that have been used to manage patients with PIC and subfoveal CNV include systemic and local steroids, other immunosuppressant agents, laser photocoagulation, photodynamic therapy, submacular surgery and, most recently, anti-vascular endothelial growth factor therapy. To date, however, there is no clear consensus on the effective therapy. Further research into this area, as well as on the cause and possible predisposing factors for PIC, is warranted. © 2011 Elsevier Inc.

The clinical effectiveness and cost-effectiveness of screening for open angle glaucoma:A systematic review and economic evaluation

Objectives: To assess whether open angle glaucoma (OAG) screening meets the UK National Screening Committee criteria, to compare screening strategies with case finding, to estimate test parameters, to model estimates of cost and cost-effectiveness, and to identify areas for future research. Data sources: Major electronic databases were searched up to December 2005. Review methods: Screening strategies were developed by wide consultation. Markov submodels were developed to represent screening strategies. Parameter estimates were determined by systematic reviews of epidemiology, economic evaluations of screening, and effectiveness (test accuracy, screening and treatment). Tailored highly sensitive electronic searches were undertaken. Results: Most potential screening tests reviewed had an estimated specificity of 85% or higher. No test was clearly most accurate, with only a few, heterogeneous studies for each test. No randomised controlled trials (RCTs) of screening were identified. Based on two treatment RCTs, early treatment reduces the risk of progression. Extrapolating from this, and assuming accelerated progression with advancing disease severity, without treatment the mean time to blindness in at least one eye was approximately 23 years, compared to 35 years with treatment. Prevalence would have to be about 3-4% in 40 year olds with a screening interval of 10 years to approach cost-effectiveness. It is predicted that screening might be cost-effective in a 50-year-old cohort at a prevalence of 4% with a 10-year screening interval. General population screening at any age, thus, appears not to be cost-effective. Selective screening of groups with higher prevalence (family history, black ethnicity) might be worthwhile, although this would only cover 6% of the population. Extension to include other at-risk cohorts (e.g. myopia and diabetes) would include 37% of the general population, but the prevalence is then too low for screening to be considered cost-effective. Screening using a test with initial automated classification followed by assessment by a specialised optometrist, for test positives, was more cost-effective than initial specialised optometric assessment. The cost-effectiveness of the screening programme was highly sensitive to the perspective on costs (NHS or societal). In the base-case model, the NHS costs of visual impairment were estimated as £669. If annual societal costs were £8800, then screening might be considered cost-effective for a 40-year-old cohort with 1% OAG prevalence assuming a willingness to pay of £30,000 per quality-adjusted life-year. Of lesser importance were changes to estimates of attendance for sight tests, incidence of OAG, rate of progression and utility values for each stage of OAG severity. Cost-effectiveness was not particularly sensitive to the accuracy of screening tests within the ranges observed. However, a highly specific test is required to reduce large numbers of false-positive referrals. The findings that population screening is unlikely to be cost-effective are based on an economic model whose parameter estimates have considerable uncertainty, in particular, if rate of progression and/or costs of visual impairment are higher than estimated then screening could be cost-effective. Conclusions: While population screening is not cost-effective, the targeted screening of high-risk groups may be. Procedures for identifying those at risk, for quality assuring the programme, as well as adequate service provision for those screened positive would all be needed. Glaucoma detection can be improved by increasing attendance for eye examination, and improving the performance of current testing by either refining practice or adding in a technology-based first assessment, the latter being the more cost-effective option. This has implications for any future organisational changes in community eye-care services. Further research should aim to develop and provide quality data to populate the economic model, by conducting a feasibility study of interventions to improve detection, by obtaining further data on costs of blindness, risk of progression and health outcomes, and by conducting an RCT of interventions to improve the uptake of glaucoma testing. © Queen's Printer and Controller of HMSO 2007. All rights reserved.

Lifetime visual prognosis of patients with glaucoma

BACKGROUND: To investigate the visual outcome of glaucoma patients.

DESIGN: This is a retrospective study of case notes of patients who died while under follow up in a glaucoma clinic of a University Hospital in Scotland between 2006 and 2009.

PARTICIPANTS: Seventy-seven patients were identified.

METHODS: Data collected included type of glaucoma, coexisting pathology and best-corrected visual acuity in Snellen (converted to decimal values) for the first and final clinic visit. The final visual status was evaluated based on the best-corrected visual acuity of the better seeing eye at the last glaucoma clinic visit. Patients who had best-corrected visual acuity of less than Snellen decimal 0.5 were considered not to meet the standards for driving.

MAIN OUTCOME MEASURES: Snellen decimal best-corrected visual acuity, fulfilment of driving standards, and eligibility for partial sight and blind registration at the last clinic visit.

RESULTS: The mean ages at presentation and death were 71.8 ± 10.3 years and 82.2 ± 8.7 years respectively. The mean Snellen decimal best-corrected visual acuity of the better eye at presentation was 0.78, and at the final clinic visit was 0.61. At the final clinic visit, no patients were partial sight registrable, four (5.2%) were blind registrable, and 27 (35.1%) did not fulfil UK driving criteria. Glaucoma patients with other ocular pathologies were more likely to fail UK driving criteria at presentation (P = 0.02) and at last clinic visit (P = 0.03).

CONCLUSION: The majority of glaucoma patients maintained good visual function at the end of their lifetime.

Just what is narrative urgency?

This article takes as its main point of departure a body of empirical research on reading and text processing, and makes particular reference to the type of experiments conducted in Egidi and Gerrig (2006) and Rapp and Gerrig (2006). Broadly put, these experiments (i) explore the psychology of readers’ preferences for narrative outcomes, (ii) examine the way readers react to characters’ goals and actions, and (iii) investigate how readers tend to identify with characters’ goals the more ‘urgently’ those goals are narrated. The present article signals how stylistics can productively enrich such experimental work. Stylistics, it is argued, is well equipped to deal with subtle and nuanced variations in textual patterns without losing sight of the broader cognitive and discoursal positioning of readers in relation to these patterns. Making particular reference to what might constitute narrative ‘urgency’, the article develops a model which amalgamates different strands of contemporary research in narrative stylistics. This model advances and elaborates three key components: a Stylistic Profile, a Burlesque Block and a Kuleshov Monitor. Developing analyses of, and informal informant tests on, examples of both fiction and film, the article calls for a more rounded and sophisticated understanding of style in empirical research on subjects’ responses to patterns in narrative.

Co-operating retrodirective system

Practical demonstration of the operational advantages gained through the use of a co-operating retrodirective array (RDA) basestation and Van Atta node arrangements is discussed. The system exploits a number of inherent RDA features to provide analogue real time multifunctional operation at low physical complexity. An active dual-conversion four element RDA is used as the power distribution source (basestation) while simultaneously achieving a receive sensitivity level of ??109 dBm and 3 dB automatic beam steering angle of ??45??. When mobile units are each equipped with a semi-passive four element Van Atta array, it is shown mobile device orientation issues are mitigated and optimal energy transfer can occur because of automatic beam formation resulting from retrodirective self-pointing action. We show that operation in multipath rich environments with or without line of sight acts to reduce average power density limits in the operating volume with high energy density occurring at mobile nodes sites only. The system described can be used as a full duplex ASK communications link, or, as a means for remote node charging by wireless means, thereby enhancing deployment opportunities between unstabilised moving platforms.

Body-centric ultra-wideband multi-channel characterisation and spatial diversity in the indoor environment

This study presents the findings of an empirical channel characterisation for an ultra-wideband off-body optic fibre-fed multiple-antenna array within an office and corridor environment. The results show that for received power experiments, the office and corridor were best modelled by lognormal and Rician distributions, respectively [for both line of sight (LOS) and non-LOS (NLOS) scenarios]. In the office, LOS measurements for t and tRMS were both described by the Normal distribution for all channels, whereas NLOS measurements for t and t were Nakagami and Weibull distributed, respectively. For the corridor measurements, LOS for t and t were either Nakagami or normally distributed for all channels, with NLOS measurements for t and t being Nakagami and normally distributed, respectively. This work also shows that achievable diversity gain was influenced by both mutual coupling and cross-correlation co-efficients. Although the best diversity gains were 1.8 dB for three-channel selective diversity combining, the authors present recommendations for improving these results. © The Institution of Engineering and Technology 2013.

Super-luminous Type Ic Supernovae: Catching a Magnetar by the Tail

We report extensive observational data for five of the lowest redshift Super-Luminous Type Ic Supernovae (SL-SNe Ic) discovered to date, namely, PTF10hgi, SN2011ke, PTF11rks, SN2011kf, and SN2012il. Photometric imaging of the transients at +50 to +230 days after peak combined with host galaxy subtraction reveals a luminous tail phase for four of these SL-SNe. A high-resolution, optical, and near-infrared spectrum from xshooter provides detection of a broad He I ?10830 emission line in the spectrum (+50 days) of SN2012il, revealing that at least some SL-SNe Ic are not completely helium-free. At first sight, the tail luminosity decline rates that we measure are consistent with the radioactive decay of 56Co, and would require 1-4 M ? of 56Ni to produce the luminosity. These 56Ni masses cannot be made consistent with the short diffusion times at peak, and indeed are insufficient to power the peak luminosity. We instead favor energy deposition by newborn magnetars as the power source for these objects. A semi-analytical diffusion model with energy input from the spin-down of a magnetar reproduces the extensive light curve data well. The model predictions of ejecta velocities and temperatures which are required are in reasonable agreement with those determined from our observations. We derive magnetar energies of 0.4 <~ E(1051 erg) lsim 6.9 and ejecta masses of 2.3 <~ M ej(M ?) lsim 8.6. The sample of five SL-SNe Ic presented here, combined with SN 2010gx—the best sampled SL-SNe Ic so far—points toward an explosion driven by a magnetar as a viable explanation for all SL-SNe Ic.

Body shadowing mitigation using differentiated LOS/NLOS channel models for RSSI-based Monte Carlo personnel localization

Research into localization has produced a wealth of algorithms and techniques to estimate the location of wireless network nodes, however the majority of these schemes do not explicitly account for non-line of sight conditions. Disregarding this common situation reduces their accuracy and their potential for exploitation in real world applications. This is a particular problem for personnel tracking where the user's body itself will inherently cause time-varying blocking according to their movements. Using empirical data, this paper demonstrates that, by accounting for non-line of sight conditions and using received signal strength based Monte Carlo localization, meter scale accuracy can be achieved for a wrist-worn personnel tracking tag in a 120 m indoor office environment. © 2012 IEEE.

Received signal characteristics of outdoor body-to-body communications channels at 2.45 GHz

In this paper we conduct a number of experiments to assess the impact of typical human body movements on the signal characteristics of outdoor body-to-body communications channels using flexible patch antennas. A modified log-distance path loss model which accounts for body shadowing and signal fading due to small movements is used to model the measured data. For line of sight channels, in which both ends of the body-to-body link are stationary, the path loss exponent is close to that for free space, although the received signal is noticeably affected by involuntary or physiological-related movements of both persons. When one person moves to obstruct the direct signal path between nodes, attenuation by the person's body can be as great as 40 dB, with even greater variation observed due to fading. The effects of movements such as rotation, tilt, walking in line of sight and non-line of sight on body-to-body communications channels are also investigated in this study. © 2011 IEEE.

Treatments for macular oedema following central retinal vein occlusion: systematic review

Objectives: To review systematically the randomised controlled trial (RCT) evidence for treatment of macular oedema due to central retinal vein occlusion (CRVO).

Data sources: MEDLINE, EMBASE, CDSR, DARE, HTA, NHSEED, CENTRAL and meeting abstracts (January 2005 to March 2013).

Study eligibility criteria, participants and interventions: RCTs with at least 12 months of follow-up assessing pharmacological treatments for CRVO were included with no language restrictions.

Study appraisal and synthesis methods: 2 authors screened titles and abstracts and conducted data extracted and Cochrane risk of bias assessment. Meta-analysis was not possible due to lack of comparable studies.

Results: 8 studies (35 articles, 1714 eyes) were included, assessing aflibercept (n=2), triamcinolone (n=2), bevacizumab (n=1), pegaptanib (n=1), dexamethasone (n=1) and ranibizumab (n=1). In general, bevacizumab, ranibizumab, aflibercept and triamcinolone resulted in clinically significant increases in the proportion of participants with an improvement in visual acuity of ≥15 letters, with 40–60% gaining ≥15 letters on active drugs, compared to 12–28% with sham. Results for pegaptanib and dexamethasone were mixed. Steroids were associated with cataract formation and increased intraocular pressure. No overall increase in adverse events was found with bevacizumab, ranibizumab, aflibercept or pegaptanib compared with control. Quality of life was poorly reported. All studies had a low or unclear risk of bias.

Limitations: All studies evaluated a relatively short primary follow-up (1 year or less). Most had an unmasked extension phase. There was no head-to-head evidence. The majority of participants included had non-ischaemic CRVO.

Conclusions and implications of key findings: Bevacizumab, ranibizumab, aflibercept and triamcinolone appear to be effective in treating macular oedema secondary to CRVO. Long-term data on effectiveness and safety are needed. Head-to-head trials and research to identify ‘responders’ is needed to help clinicians make the right choices for their patients. Research aimed to improve sight in people with ischaemic CRVO is required.

Will VEGF Trap-Eye reduce the treatment burden in neovascular age-related macular degeneration?

Evaluation of: Brown DM, Heier JS, Ciulla T et al. Primary end point results of a Phase II study of vascular endothelial growth factor trap-eye in wet age-related macular degeneration. Ophthalmology 118(6), 1089-1097 (2011); Heier JS, Boyer D, Nguyen QD et al. The 1-year results of CLEAR-IT 2, a Phase 2 study of vascular endothelial growth factor trap-eye dosed as-needed after 12-week fixed dosing. Ophthalmology 118(6), 1098-1106 (2011). Age-related macular degeneration is the most common cause of blindness in older adults in western countries, and is likely to become the largest cause of irreversible sight loss in the developing world. Treatments such as ranibizumab and bevacizumab that inhibit VEGF have improved visual outcomes markedly. Controlled trials and clinical experience have shown that the best outcomes are achieved when monthly treatment has been administered over 2 years. This poses a significant burden on health providers and patients. A novel inhibitor of VEGF, VEGF Trap-Eye, which allows less frequent dosing without loss of efficacy, has emerged as a potential treatment. CLEAR-IT 2 was a prospective randomized Phase II trial designed to assess the safety, tolerability and the anatomic and visual effects of repeated treatments with a range of doses of VEGF Trap-Eye. Impressive anatomic and visual improvements were noted with no safety concerns. © 2011 Expert Reviews Ltd.

Endothelial progenitor cells in diabetic retinopathy

Diabetic retinopathy (DR) is a leading cause of visual impairment worldwide. Patients with DR may irreversibly lose sight as a result of the development of diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR); retinal blood vessel dysfunction and degeneration plays an essential role in their pathogenesis. Although new treatments have been recently introduced for DME, including intravitreal vascular endothelial growth factor inhibitors (anti-VEGFs) and steroids, a high proportion of patients (~40-50%) do not respond to these therapies. Furthermore, for people with PDR, laser photocoagulation remains a mainstay therapy despite this being an inherently destructive procedure. Endothelial progenitor cells (EPCs) are a low-frequency population of circulating cells known to be recruited to sites of vessel damage and tissue ischemia where they promote vascular healing and re-perfusion. A growing body of evidence suggests that the number and function of EPCs are altered in patients with varying degrees of diabetes duration, metabolic control, and in the presence or absence of DR. Although there are no clear-cut outcomes from these clinical studies, there is mounting evidence that some EPC sub-types may be involved in the pathogenesis of DR and may also serve as biomarkers for disease progression and stratification. Moreover, some EPC sub-types have considerable potential as therapeutic modalities for DME and PDR in the context of cell therapy. This study presents basic clinical concepts of DR and combines this with a general insight on EPCs and their relation to future directions in understanding and treating this important diabetic complication.