Early-onset, severe retinal dystrophy caused by mutations in the gene encoding retinal pigment epithelium–specific 65-kD protein (RPE65) is associated with poor vision at birth and complete loss of vision in early adulthood. We administered to three young adult patients subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) under the control of a human RPE65 promoter. There were no serious adverse events. There was no clinically significant change in visual acuity or in peripheral visual fields on Goldmann perimetry in any of the three patients. We detected no change in retinal responses on electroretinography. One patient had significant improvement in visual function on microperimetry and on dark-adapted perimetry. This patient also showed improvement in a subjective test of visual mobility. These findings provide support for further clinical studies of this experimental approach in other patients with mutant RPE65. (ClinicalTrials.gov number, NCT00643747.)

Mutations in RPE65 cause Leber’s congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited. We performed a phase 1–2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, and measured visual function over the course of 3 years. Four participants were administered a lower dose of the vector, and 8 were administered a higher dose. In a parallel study in dogs, we investigated the relationship among vector dose, visual function, and electroretinography (ERG) findings. Improvements in retinal sensitivity were evident, to varying extents, in six participants for up to 3 years, peaking at 6 to 12 months after treatment and then declining. No associated improvement in retinal function was detected by means of ERG. Three participants had intraocular inflammation, and two had clinically significant deterioration of visual acuity. The reduction in central retinal thickness varied among participants. In dogs, RPE65 gene therapy with the same vector at lower doses improved vision-guided behavior, but only higher doses resulted in improvements in retinal function that were detectable with the use of ERG. Gene therapy with rAAV2/2 RPE65 vector improved retinal sensitivity, albeit modestly and temporarily. Comparison with the results obtained in the dog model indicates that there is a species difference in the amount of RPE65 required to drive the visual cycle and that the demand for RPE65 in affected persons was not met to the extent required for a durable, robust effect. (Funded by the National Institute for Health Research and others; ClinicalTrials.gov number, NCT00643747.)

Pain-related emotions are a major barrier to effective self rehabilitation in chronic pain. Automated coaching systems capable of detecting these emotions are a potential solution. This paper lays the foundation for the development of such systems by making three contributions. First, through literature reviews, an overview of how pain is expressed in chronic pain and the motivation for detecting it in physical rehabilitation is provided. Second, a fully labelled multimodal dataset (named `EmoPain') containing high resolution multiple-view face videos, head mounted and room audio signals, full body 3D motion capture and electromyographic signals from back muscles is supplied. Natural unconstrained pain related facial expressions and body movement behaviours were elicited from people with chronic pain carrying out physical exercises. Both instructed and non-instructed exercises were considered to reflect traditional scenarios of physiotherapist directed therapy and home-based self-directed therapy. Two sets of labels were assigned: level of pain from facial expressions annotated by eight raters and the occurrence of six pain-related body behaviours segmented by four experts. Third, through exploratory experiments grounded in the data, the factors and challenges in the automated recognition of such expressions and behaviour are described, the paper concludes by discussing potential avenues in the context of these findings also highlighting differences for the two exercise scenarios addressed.

Dwell time is the time that a public transport vehicle remains stopped while transferring passengers. Dwell time depends on the number of boarding and alighting passengers plus other characteristics, such as platform height, door width, fare collection method, internal layout of the vehicle, and occupancy of the vehicle. Traditionally, dwell time has been described as a linear function of the number of passengers boarding and alighting. In this paper, results are presented of dwell time parameters obtained from real-scale experiments made at the Pedestrian Accessibility and Movement Environment Laboratory, University College London. Three variables were controlled: platform height (0, 150, and 300 mm), door width (800 and 1,600 mm), and fare collection method (prepayment outside the vehicle and payment with an electronic card at the entrance of the vehicle). For each value of the variables mentioned above, between 15 and 20 runs were recorded on videotape with four cameras and different views. In total, 300 records of boarding and alighting processes were obtained. Some results indicate that door width has more influence than platform height. For example, it was found that a wider door can reduce the average alighting time by almost 40%, regardless of platform height, and can reduce the average boarding time by 20%. However, for the same door width, a lower platform reduces the average alighting time by only 1% to 9%. More results and analysis are reported in this paper.

The last decade has seen substantial advances in the capacity to record behaviour and neural activity in humans in real-world settings, to simulate real-world situations in laboratory settings and to apply sophisticated analyses to large-scale data. Along with these developments, a growing number of groups has begun to advocate for real-world neuroscience and cognitive science. Here, we review the arguments and the available methods for real-world research and outline an overarching framework that embeds key ideas proposed in the literature integrating them into a cyclic process of ‘bringing the lab to the real world’ (recording behavioural and neural activity in real-world settings) and ‘bringing the real-world to the lab’ (manipulating the environments in which behaviours occur in the laboratory) that combines exploratory and confirmatory research and is interdisciplinary (including those sciences concerned with the natural, built or virtual environment). We highlight the benefits brought by this framework emphasizing the greater potential for novel discovery, theory development and human-centred applications to the environment.