The Epidemiology of Stargardt Disease in the United Kingdom

The authors thank the British Ophthalmological Surveillance Unit (BOSU) for the support received, as well as Mr Barnaby Foot, research coordinator for BOSU, for his help and advice on this project. The authors thank the following ophthalmologists who assisted with data collection for this study: N. Acharya, S. Anwar, V. Bansal, P.N. Bishop, D. Byles, J.S. Chawla, A. Churchill, M. Clarke, B. Dhillon, M. Ekstein, S. George, J. Gillian, J.T. Gillow, D. Gilmour, R. Gray, P.T.S. Gregory, R. Gupta, S.P. Kelly, I.C. Lloyd, A. Lotery, M. McKibbin, R. MacLaren, G. Menon, A.T. Moore, A. Mulvihill, Y. Osoba, R. Pilling, H. Porooshani, A. Raghu Ram, T. Rimmer, I. Russell-Eggitt, M. Sarhan, R. Savides, S. Shafquat, A. Smith, A. Tekriwal, P. Tesha, P. Watts.Peer reviewedPublisher PD

Digital control networks for virtual creatures

Robot control systems evolved with genetic algorithms traditionally take the form of floating-point neural network models. This thesis proposes that digital control systems, such as quantised neural networks and logical networks, may also be used for the task of robot control. The inspiration for this is the observation that the dynamics of discrete networks may contain cyclic attractors which generate rhythmic behaviour, and that rhythmic behaviour underlies the central pattern generators which drive lowlevel motor activity in the biological world. To investigate this a series of experiments were carried out in a simulated physically realistic 3D world. The performance of evolved controllers was evaluated on two well known control tasks—pole balancing, and locomotion of evolved morphologies. The performance of evolved digital controllers was compared to evolved floating-point neural networks. The results show that the digital implementations are competitive with floating-point designs on both of the benchmark problems. In addition, the first reported evolution from scratch of a biped walker is presented, demonstrating that when all parameters are left open to evolutionary optimisation complex behaviour can result from simple components

PIMS (Positioning In Macular hole Surgery) trial – a multicentre interventional comparative randomised controlled clinical trial comparing face-down positioning, with an inactive face-forward position on the outcome of surgery for large macular holes: study protocol for a randomised controlled trial

BACKGROUND: Idiopathic macular holes are an important cause of blindness. They have an annual incidence of 8 per 100,000 individuals, and prevalence of 0.2 to 3.3 per 1000 individuals with visual impairment. The condition occurs more frequently in adults aged 75 years or older. Macular holes can be repaired by surgery in which the causative tractional forces in the eye are released and a temporary bubble of gas is injected. To promote successful hole closure individuals may be advised to maintain a face-down position for up to 10 days following surgery. The aim of this study is to determine whether advice to position face-down improves the surgical success rate of closure of large (>400 μm) macular holes, and thereby reduces the need for further surgery. METHODS/DESIGN: This will be a multicentre interventional, comparative randomised controlled clinical trial comparing face-down positioning with face-forward positioning. At the conclusion of standardised surgery across all sites, participants still eligible for inclusion will be allocated randomly 1:1 to 1 of the 2 treatment arms stratified by site, using random permuted blocks of size 4 or 6 in equal proportions. We will recruit 192 participants having surgery for large macular holes (>400 μm); 96 in each of the 2 arms of the study. The primary objective is to determine the impact of face-down positioning on the likelihood of closure of large (≥400 μm) full-thickness macular holes following surgery. DISCUSSION: This will be the first multicentre randomised control trial to investigate the value of face-down positioning following macular hole standardised surgery. TRIAL REGISTRATION: UK CRN: 17966 (date of registration 26 November 2014)

The Role of Neuroglobin in Retinal Hemodynamics and Metabolism: A Real-Time Study

Purpose: In this study, we used broadband near-infrared spectroscopy, a non-invasive optical technique, to investigate in real time the possible role of neuroglobin in retinal hemodynamics and metabolism. / Methods: Retinae of 12 C57 mice (seven young and five old) and seven young neuroglobin knockouts (Ngb-KOs) were exposed to light from a low-power halogen source, and the back-reflected light was used to calculate changes in the concentration of oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (HHb), and oxidized cytochrome c oxidase (oxCCO). / Results: The degree of change in the near-infrared spectroscopy signals associated with HHb, HbO2, and oxCCO was significantly greater in young C57 mice compared to the old C57 mice (P < 0.05) and the Ngb-KO model (P < 0.005). / Conclusions: Our results reveal a possible role of Ngb in regulating retinal function, as its absence in the retinae of a knockout mouse model led to suppressed signals that are associated with hemodynamics and oxidative metabolism. / Translational Relevance: Near-infrared spectroscopy enabled the non-invasive detection of characteristic signals that differentiate between the retina of a neuroglobin knockout mouse model and that of a wild-type model. Further work is needed to evaluate the source of the signal differences and how these differences relate to the presence or absence of neuroglobin in the ganglion, bipolar, or amacrine cells of the retina

Evaluating research impact: The development of a research for impact tool

© 2016 Tsey, Lawson, Kinchin, Bainbridge, McCalman, Watkin, Cadet-James and Rossetto. Introduction: This paper examines the process of developing a Research for Impact Tool in the contexts of general fiscal constraint, increased competition for funding, perennial concerns about the over-researching of Aboriginal and Torres Strait Islander issues without demonstrable benefits as well as conceptual and methodological difficulties of evaluating research impact. The aim is to highlight the challenges and opportunities involved in evaluating research impact to serve as resource for potential users of the research for impact tool and others interested in assessing the impact of research. Materials and methods: A combination of literature reviews, workshops with researchers, and reflections by project team members and partners using participatory snowball techniques. Results: Assessing research impact is perceived to be difficult, akin to the so-called "wicked problem," but not impossible. Heuristic and collaborative approach to research that takes the expectations of research users, research participants and the funders of research offers a pragmatic solution to evaluating research impact. The logic of the proposed Research for Impact Tool is based on the understanding that the value of research is to create evidence and/or products to support smarter decisions so as to improve the human condition. Research is, therefore, of limited value unless the evidence created is used to make smarter decisions for the betterment of society. A practical way of approaching research impact is, therefore, to start with the decisions confronting decision makers whether they are government policymakers, industry, professional practitioners, or households and the extent to which the research supports them to make smarter policy and practice decisions and the knock-on consequences of doing so. Embedded at each step in the impact planning and tracking process is the need for appropriate mix of expertise, capacity enhancement, and collaborative participatory learning-by-doing approaches. Discussion: The tool was developed in the context of Aboriginal and Torres Strait Islander research but the basic idea that the way to assess research impact is to start upfront with the information needs of decisions makers is equally applicable to research in other settings, both applied (horizontal) and basic (vertical) research. The tool will be further tested and evaluated with researchers over the next 2 years (2016/17). The decision by the Australian Government to include 'industry engagement' and 'impact' as additions to the Excellence in Research for Australia (ERA) quality measures from 2018 makes the Research for Impact Tool a timely development. The wider challenge is to engage with major Australian research funding agencies to ensure consistent alignment and approaches across research users, communities, and funders in evaluating impact

Association of metabolic syndrome and change in Unified Parkinson\u27s Disease Rating Scale scores.

OBJECTIVE: To explore the association between metabolic syndrome and the Unified Parkinson\u27s Disease Rating Scale (UPDRS) scores and, secondarily, the Symbol Digit Modalities Test (SDMT). METHODS: This is a secondary analysis of data from 1,022 of 1,741 participants of the National Institute of Neurological Disorders and Stroke Exploratory Clinical Trials in Parkinson Disease Long-Term Study 1, a randomized, placebo-controlled trial of creatine. Participants were categorized as having or not having metabolic syndrome on the basis of modified criteria from the National Cholesterol Education Program Adult Treatment Panel III. Those who had the same metabolic syndrome status at consecutive annual visits were included. The change in UPDRS and SDMT scores from randomization to 3 years was compared in participants with and without metabolic syndrome. RESULTS: Participants with metabolic syndrome (n = 396) compared to those without (n = 626) were older (mean [SD] 63.9 [8.1] vs 59.9 [9.4] years; p \u3c 0.0001), were more likely to be male (75.3% vs 57.0%; p \u3c 0.0001), and had a higher mean uric acid level (men 5.7 [1.3] vs 5.3 [1.1] mg/dL, women 4.9 [1.3] vs 3.9 [0.9] mg/dL, p \u3c 0.0001). Participants with metabolic syndrome experienced an additional 0.6- (0.2) unit annual increase in total UPDRS (p = 0.02) and 0.5- (0.2) unit increase in motor UPDRS (p = 0.01) scores compared with participants without metabolic syndrome. There was no difference in the change in SDMT scores. CONCLUSIONS: Persons with Parkinson disease meeting modified criteria for metabolic syndrome experienced a greater increase in total UPDRS scores over time, mainly as a result of increases in motor scores, compared to those who did not. Further studies are needed to confirm this finding. CLINICALTRIALSGOV IDENTIFIER: NCT00449865

Dimethylarginine dimethylaminohydrolase-2 deficiency promotes vascular regeneration and attenuates pathological angiogenesis

AbstractIschemia-induced angiogenesis is critical for tissue repair, but aberrant neovascularization in the retina causes severe sight impairment. Nitric oxide (NO) has been implicated in neovascular eye disease because of its pro-angiogenic properties in the retina. Nitric oxide production is inhibited endogenously by asymmetric dimethylarginines (ADMA and L-NMMA) which are metabolized by dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2. The aim of this study was to determine the roles of DDAH1, DDAH2, ADMA and L-NMMA in retinal ischemia-induced angiogenesis. First, DDAH1, DDAH2, ADMA and L-NMMA levels were determined in adult C57BL/6J mice. The results obtained revealed that DDAH1 was twofold increased in the retina compared to the brain and the choroid. DDAH2 expression was approximately 150 fold greater in retinal and 70 fold greater in choroidal tissue compared to brain tissue suggesting an important tissue-specific role for DDAH2 in the retina and choroid. ADMA and L-NMMA levels were similar in the retina and choroid under physiological conditions. Next, characterization of DDAH1+/− and DDAH2−/− deficient mice by in vivo fluorescein angiography, immunohistochemistry and electroretinography revealed normal neurovascular function compared with wildtype control mice. Finally, DDAH1+/− and DDAH2−/− deficient mice were studied in the oxygen-induced retinopathy (OIR) model, a model used to emulate retinal ischemia and neovascularization, and VEGF and ADMA levels were quantified by ELISA and liquid chromatography tandem mass spectrometry. In the OIR model, DDAH1+/− exhibited a similar phenotype compared to wildtype controls. DDAH2 deficiency, in contrast, resulted in elevated retinal ADMA which was associated with attenuated aberrant angiogenesis and improved vascular regeneration in a VEGF independent manner. Taken together this study suggests, that in retinal ischemia, DDAH2 deficiency elevates ADMA, promotes vascular regeneration and protects against aberrant angiogenesis. Therapeutic inhibition of DDAH2 may therefore offer a potential therapeutic strategy to protect sight by promoting retinal vascular regeneration and preventing pathological angiogenesis

No one's discussing the elephant in the room: Contemplating questions of research impact and benefit in Aboriginal and Torres Strait Islander Australian health research

© 2015 Bainbridge et al. Background: There remains a concern that Indigenous Australians have been over-researched without corresponding improvements in their health; this trend is applicable to most Indigenous populations globally. This debate article has a dual purpose: 1) to open a frank conversation about the value of research to Indigenous Australian populations; and 2) to stimulate ways of thinking about potential resolutions to the lack of progress made in the Indigenous research benefit debate. Discussion: Capturing the meaning of research benefit takes the form of ethical value-oriented methodological considerations in the decision-making processes of Indigenous research endeavours. Because research practices come from Western knowledge bases, attaining such positions in research means reconciling both Indigenous and Western knowledge systems to produce new methodologies that guide planning, evaluating and monitoring of research practices as necessary. Increasingly, more sophisticated performance measures have been implemented to ensure academic impact and benefits are captured. Assessing societal and other non-academic impacts and benefits however, has not been accorded corresponding attention. Research reform has only focussed on research translation in more recent years. The research impact debate must take account of the various standards of accountability (to whom), impact priorities (for whom), positive and negative impacts, and biases that operate in describing impact and measuring benefit. Summary: A perennial question in Indigenous research discourse is whether the abundance of research conducted; purportedly to improve health, is justified and benefits Indigenous people in ways that are meaningful and valued by them. Different research stakeholders have different conceptions of the value and nature of research, its conduct, what it should achieve and the kinds of benefits expected. We need to work collaboratively and listen more closely to the voice of Indigenous Australians to better understand, demonstrate and measure health research benefits. The authors conclude that as an imperative, a systematic benefit assessment strategy that includes identification of research priorities and planning, monitoring and evaluation components needs to be developed and implemented across research projects. In Indigenous health research, this will often mean adopting a benefit-led approach by changing the way research is done and preferencing alternative research methodologies. As a point of departure to improving impact and reaching mutually beneficial outcomes for researchers and partners in Indigenous health research, we need to routinise the assessment of benefit from outset of research as one of the standards toward which we work

Land use change in the river basins of the Great Barrier Reef, 1860 to 2019: a foundation for understanding environmental history across the catchment to reef continuum

Land use in the catchments draining to the Great Barrier Reef lagoon has changed considerably since the introduction of livestock grazing, various crops, mining and urban development. Together these changes have resulted in increased pollutant loads and impaired coastal water quality. This study compiled records to produce annual time-series since 1860 of human population, livestock numbers and agricultural areas at the scale of surface drainage river basins, natural resource management regions and the whole Great Barrier Reef catchment area. Cattle and several crops have experienced progressive expansion interspersed by declines associated with droughts and diseases. Land uses which have experienced all time maxima since the year 2000 include cattle numbers and the areas of sugar cane, bananas and cotton. A Burdekin Basin case study shows that sediment loads initially increased with the introduction of livestock and mining, remained elevated with agricultural development, and declined slightly with the Burdekin Falls Dam construction