Clinical characteristics and natural history of rho-associated retinitis pigmentosa : a long-term follow-up study

Purpose: To investigate the natural history of RHO-associated retinitis pigmentosa (RP). Methods: A multicenter, medical chart review of 100 patients with autosomal dominant RHO-associated RP. Results: Based on visual fields, time-to-event analysis revealed median ages of 52 and 79 years to reach low vision (central visual field <20 degrees) and blindness (central visual field <10 degrees), respectively. For the best-corrected visual acuity (BCVA), the median age to reach mild impairment (20/67 <= BCVA < 20/40) was 72 years, whereas this could not be computed for lower acuities. Disease progression was significantly faster in patients with a generalized RP phenotype (n = 75; 75%) than that in patients with a sector RP phenotype (n = 25; 25%), in terms of decline rates of the BCVA (P < 0.001) and V4e retinal seeing areas (P < 0.005). The foveal thickness of the photoreceptor-retinal pigment epithelium (PR + RPE) complex correlated significantly with BCVA (Spearman's rho = 0.733; P < 0.001). Conclusion: Based on central visual fields, the optimal window of intervention for RHO-associated RP is before the 5th decade of life. Significant differences in disease progression are present between generalized and sector RP phenotypes. Our findings suggest that the PR + RPE complex is a potential surrogate endpoint for the BCVA in future studies

Accessing parental perspectives to inform the development of parent training in autism in south-eastern Europe

Parent training has been shown to be an important means of supporting families living with autism – but such services are not universally accessible. A multinational project funded by the European Commission has been developed in order to establish such parent training in three south-eastern European countries. To ensure that the training was relevant and appropriate, a survey was carried out in autumn 2015 to ascertain the attitudes of parents of children with autism in Croatia, Cyprus and the Former Yugoslav Republic of Macedonia regarding this issue, and to identify the areas of training that they felt most important. Two hundred and fifty-three surveys were distributed, and 148 were returned, a response rate of 58%. Respondents in the three counties were overwhelmingly positive about parent training, with almost 90% stating that they would like to attend such training. Weekend training sessions were preferred by the majority of respondents. There was wide variation between the three countries with regard to what content was felt important to be included, with parents in the FYR of Macedonia seeking information in the greatest number of areas. Five topics were prioritised by parents across all three countries. These were: • Strategies for enhancing my child’s communication • Strategies on facilitating my child’s interaction with other children • Sensory integration and development • General information on behavioural management strategies • Identifying and/or developing socialisation opportunitie

The spectrum of structural and functional abnormalities in female carriers of pathogenic variants in the RPGR gene

PURPOSE. The purpose of this study was to investigate the phenotype and long-term clinical course of female carriers of RPGR mutations. METHODS. This was a retrospective cohort study of 125 heterozygous RPGR mutation carriers from 49 families. RESULTS. Eighty-three heterozygotes were from retinitis pigmentosa (RP) pedigrees, 37 were from cone-/cone-rod dystrophy (COD/CORD) pedigrees, and 5 heterozygotes were from pedigrees with mixed RP/CORD or unknown diagnosis. Mutations were located in exon 1-14 and in ORF15 in 42 of 125 (34%) and 83 of 125 (66%) subjects, respectively. The mean age at the first examination was 34.4 years (range, 2.1 to 86.0 years). The median follow-up time in heterozygotes with longitudinal data (n = 62) was 12.2 years (range, 1.1 to 52.2 years). Retinal pigmentary changes were present in 73 (58%) individuals. Visual symptoms were reported in 51 (40%) cases. Subjects with both symptoms and pigmentary fundus changes were older than the other heterozygotes (P = 0.01) and had thinner foveal outer retinas (P = 0.006). Complete expression of the RP or CORD phenotype was observed in 29 (23%) heterozygotes, although usually in milder forms than in affected male relatives. Best-corrected visual acuity (BCVA) was <20/40 and <20/400 in at least one eye in 45 of 116 (39%) and 11 of 116 (9%) heterozygotes, respectively. Myopia was observed in 74 of 101 (73%) subjects and was associated with lower BCVA (P = 0.006). Increasing age was associated with lower BCVA (P = 0.002) and decreasing visual field size (P = 0.012; I4e isopter). CONCLUSIONS. RPGR mutations lead to a phenotypic spectrum in female carriers, with myopia as a significantly aggravating factor. Complete disease expression is observed in some individuals, who may benefit from future (gene) therapeutic options

Combining Rational and Biological Factors in Virtual Agent Decision Making

To enhance believability of virtual agents, this paper presents an agent-based modelling approach for decision making, which integrates rational reasoning based on means-end analysis with personal psychological and biological aspects. The agent model developed is a combination of a BDI-model and a utility-based decision model in the context of specific desires and beliefs. The approach is illustrated by addressing the behaviour of violent criminals, thereby creating a model for virtual criminals. Within a number of simulation experiments, the model has been tested in the context of a street robbery scenario. In addition, a user study has been performed, which confirms the fact that the model enhances believability of virtual agents. © 2009 The Author(s)

HET KARTELBELEID VAN DE REGERING

HET KARTELBELEID VAN DE REGERIN