Genome-wide association study for sight-threatening diabetic retinopathy reveals association with genetic variation near the GRB2 gene

AIMS/HYPOTHESIS: Diabetic retinopathy is a serious complication of diabetes mellitus and can lead to blindness. A genetic component, in addition to traditional risk factors, has been well described although strong genetic factors have not yet been identified. Here, we aimed to identify novel genetic risk factors for sight-threatening diabetic retinopathy using a genome-wide association study.

METHODS: Retinopathy was assessed in white Australians with type 2 diabetes mellitus. Genome-wide association analysis was conducted for comparison of cases of sight-threatening diabetic retinopathy (n = 336) with diabetic controls with no retinopathy (n = 508). Top ranking single nucleotide polymorphisms were typed in a type 2 diabetes replication cohort, a type 1 diabetes cohort and an Indian type 2 cohort. A mouse model of proliferative retinopathy was used to assess differential expression of the nearby candidate gene GRB2 by immunohistochemistry and quantitative western blot.

RESULTS: The top ranked variant was rs3805931 with p = 2.66 × 10(-7), but no association was found in the replication cohort. Only rs9896052 (p = 6.55 × 10(-5)) was associated with sight-threatening diabetic retinopathy in both the type 2 (p = 0.035) and the type 1 (p = 0.041) replication cohorts, as well as in the Indian cohort (p = 0.016). The study-wide meta-analysis reached genome-wide significance (p = 4.15 × 10(-8)). The GRB2 gene is located downstream of this variant and a mouse model of retinopathy showed increased GRB2 expression in the retina.

CONCLUSIONS/INTERPRETATION: Genetic variation near GRB2 on chromosome 17q25.1 is associated with sight-threatening diabetic retinopathy. Several genes in this region are promising candidates and in particular GRB2 is upregulated during retinal stress and neovascularisation.

Best Practice for Providing Social Care and Support to People Living with Concurrent Sight Loss and Dementia: Professional Perspectives

Purpose-Approximately 100,000 people in the UK aged 75 and over have concurrent dementia and sight loss, but current understanding of their experiences, needs and preferences is limited. The purpose of this paper is to report on a research project that explored the provision of social care and support for older people with both conditions. Design/methodology/approach-The project was a collaboration between the universities of York, Worcester, Bournemouth and Cambridge, supported by the Thomas Pocklington Trust and the Housing and Dementia Research Consortium. Data for this paper were drawn from focus groups held in 2013 involving 47 professionals across the dementia, sight loss and housing sectors. Findings-Thematic analysis identified five main barriers to providing high-quality, cost-effective social care and support: time constraints; financial limitations; insufficient professional knowledge; a lack of joint working; and inconsistency of services. The requirements of dementia and sight loss often conflict, which can limit the usefulness of equipment, aids and adaptations. Support and information needs to address individual needs and preferences. Research limitations/implications-Unless professionals consider dementia and sight loss together, they are unlikely to think about the impact of both conditions and the potential of their own services to provide effective support for individuals and their informal carers. Failing to consider both conditions together can also limit the availability and accessibility of social care and support services. This paper is based on input from a small sample of self-selecting professionals across three geographical regions of England. More research is needed in this area. Practical implications-There are growing numbers of people living with concurrent dementia and sight loss, many of whom wish to remain living in their own homes. There is limited awareness of the experiences and needs of this group and limited provision of appropriate services aids/adaptations. A range of measures should be implemented in order to support independence and well-being for people living with both conditions and their family carers. These include increased awareness, improved assessment, more training and greater joint working. Social implications-People living with dementia or sight loss are at high risk of social isolation, increasingly so for those with both conditions. Services that take an inclusive approach to both conditions can provide crucial opportunities for social interaction. Extra care housing has the potential to provide a supportive, community-based environment that can help residents to maintain social contact. Originality/value-This paper adds much-needed evidence to the limited existing literature, and reflects the views of diverse professionals across housing, health and social care

Readjusting our Sporting Sites/Sight: Sportification and the Theatricality of Social Life

This paper points out the potential of using sport for the analysis of society. Cultivated human movement is a specific social and cultural subsystem (involving sport, movement culture and physical culture), yet it becomes a part of wider social discourses by extending some of its characteristics into various other spheres. This process, theorised as sportification, provides as useful concept to examine the permeation of certain phenomena from the area of sport into the social reality outside of sport. In this paper, we investigate the phenomena of sportification which we parallel with visual culture and spectatorship practices in the Renaissance era. The emphasis in our investigation is on theatricality and performativity; particularly, the superficial spectator engagement with modern sport and sporting spectacles. Unlike the significance afforded to visualisation and deeper symbolic interpretation in Renaissance art, contemporary cultural shifts have changed and challenged the ways in which the active and interacting body is positioned, politicised, symbolised and ultimately understood. We suggest here that the ways in which we view sport and sporting bodies within a (post)modern context (particularly with the confounding amalgamations of signs and symbols and emphasis on hyper-realities) has invariably become detached from sports’ profound metaphysical meanings and resonance. Subsequently, by emphasising the associations between social theatrics and the sporting complex, this paper aims to remind readers of ways that sport—as a nuanced phenomenon—can be operationalised to help us to contemplate questions about nature, society, ourselves and the complex worlds in which we live.

HIDING IN PLAIN SIGHT- Sustainable Physical Activity Program Development and Evaluation for Youth with Special Needs: An Evaluative Case Study

The purpose of my research was to contribute to the improvement and sustainability of the Special Needs Activity Program, and develop program implementation strategies that had practical outcomes. I conducted an evaluative case study of S.N.A.P in order to determine what a quality adapted physical activity (APA) program is, why S.N.A.P is considered a quality APA program, and what institutional policies and practices exist to support it. Data was collected via interviews, questionnaires, and observations. Data analysis involved inductive and deductive methods, and a SWOTAR evaluation. Results indicate that quality APA programs include: ‘people’, ‘environment’, and ‘expectations’; there are benefits of experiential learning; activity stations that promote creativity are valuable; several stakeholders do not know the details about S.N.A.P but recognize its value; the institution values what S.N.A.P provides, yet, there is nothing being done to sustain it. Future research should investigate the feasibility of implementing S.N.A.P in various contexts.

Nature of crossmodal plasticity in the blind brain and interplay with sight restoration

Thèse réalisée en cotutelle avec l'Université catholique de Louvain.

The sight of silence : the conceptualisation of silence in the visual cultures of sign language communities

Deaf people are perceived by hearing people as living in a silent world. Yet, silence cannot exist without sound, so if sound is not heard, can there be silence? From a linguistic point of view silence is the absence of, or intermission in, communication. Silence can be communicative or noncommunicative. Thus, silence must exist in sign languages as well. Sign languages are based on visual perception and production through movement and sight. Silence must, therefore, be visually perceptible; and, if there is such a thing as visual silence, how does it look? The paper will analyse the topic of silence from a Deaf perspective. The main aspects to be explored are the perception and evaluation of acoustic noise and silence by Deaf people; the conceptualisation of silence in visual languages, such as sign languages; the qualities of visual silence; the meaning of silence as absence of communication (particularly between hearing and Deaf people); social rules for silence; and silencing strategies.

Cognitive influences on the affective representation of touch and the sight of touch in the human brain

We show that the affective experience of touch and the sight of touch can be modulated by cognition, and investigate in an fMRI study where top-down cognitive modulations of bottom-up somatosensory and visual processing of touch and its affective value occur in the human brain. The cognitive modulation was produced by word labels, 'Rich moisturizing cream' or 'Basic cream', while cream was being applied to the forearm, or was seen being applied to a forearm. The subjective pleasantness and richness were modulated by the word labels, as were the fMRI activations to touch in parietal cortex area 7, the insula and ventral striatum. The cognitive labels influenced the activations to the sight of touch and also the correlations with pleasantness in the pregenual cingulate/orbitofrontal cortex and ventral striatum. Further evidence of how the orbitofrontal cortex is involved in affective aspects of touch was that touch to the forearm [which has C fiber Touch (CT) afferents sensitive to light touch] compared with touch to the glabrous skin of the hand (which does not) revealed activation in the mid-orbitofrontal cortex. This is of interest as previous studies have suggested that the CT system is important in affiliative caress-like touch between individuals.

DENSITY PROFILE, VELOCITY ANISOTROPY, AND LINE-OF-SIGHT EXTERNAL CONVERGENCE OF SLACS GRAVITATIONAL LENSES

Data from 58 strong-lensing events surveyed by the Sloan Lens ACS Survey are used to estimate the projected galaxy mass inside their Einstein radii by two independent methods: stellar dynamics and strong gravitational lensing. We perform a joint analysis of these two estimates inside models with up to three degrees of freedom with respect to the lens density profile, stellar velocity anisotropy, and line-of-sight (LOS) external convergence, which incorporates the effect of the large-scale structure on strong lensing. A Bayesian analysis is employed to estimate the model parameters, evaluate their significance, and compare models. We find that the data favor Jaffe`s light profile over Hernquist`s, but that any particular choice between these two does not change the qualitative conclusions with respect to the features of the system that we investigate. The density profile is compatible with an isothermal, being sightly steeper and having an uncertainty in the logarithmic slope of the order of 5% in models that take into account a prior ignorance on anisotropy and external convergence. We identify a considerable degeneracy between the density profile slope and the anisotropy parameter, which largely increases the uncertainties in the estimates of these parameters, but we encounter no evidence in favor of an anisotropic velocity distribution on average for the whole sample. An LOS external convergence following a prior probability distribution given by cosmology has a small effect on the estimation of the lens density profile, but can increase the dispersion of its value by nearly 40%.