Nick Tyler

Bio: Nick Tyler is an academic researcher from University College London. The author has contributed to research in topics: Population & Public transport. The author has an hindex of 20, co-authored 135 publications receiving 4049 citations. Previous affiliations of Nick Tyler include University College London Hospitals NHS Foundation Trust.

Effect of gene therapy on visual function in Leber's congenital amaurosis.

Abstract: Early-onset, severe retinal dystrophy caused by mutations in the gene encoding reti- nal pigment epithelium-specific 65-kDa protein (RPE65) is associated with poor vi- sion 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 Gold- mann perimetry in any of the three patients. We detected no change in retinal re- sponses 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.)

Long-Term Effect of Gene Therapy on Leber’s Congenital Amaurosis

Abstract: BackgroundMutations 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. MethodsWe 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. ResultsImprovements 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 d...

The Automatic Detection of Chronic Pain-Related Expression: Requirements, Challenges and the Multimodal EmoPain Dataset

Abstract: 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.

Influence of Platform Height, Door Width, and Fare Collection on Bus Dwell Time: Laboratory Evidence for Santiago de Chile

Abstract: 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, 3...

The Design and Analysis of Experiments

Abstract: THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON

Bruno Latour, The pasteurization of France , trans. Alan Sheridan and John Law, Cambridge, Mass., and London, Harvard University Press, 1988, 8vo, pp. 273, £23.95. - Georges Canguilhem, Ideology and rationality in the history of the life sciences , trans. Arthur Goldhammer, Cambridge, Mass., and London, The MIT Press, 1988, 8vo, pp. xi, 160, £17.95.

Abstract: BRUNO LATOUR, The pasteurization of France, trans. Alan Sheridan and John Law, Cambridge, Mass., and London, Harvard University Press, 1988, 8vo, pp. 273, £23.95. GEORGES CANGUILHEM, Ideology and rationality in the history of the life sciences, trans. Arthur Goldhammer, Cambridge, Mass., and London, The MIT Press, 1988, 8vo, pp. xi, 160, £17.95. Bruno Latour has written a wonderfully funny book about himself. It is difficult, however, to summarize a text committed to the view that \"Nothing is, by itself, either reducible or irreducible to anything else\", (p. 158). In Latour's opinion, the common view that sociologists of knowledge and scientists are opposed is incorrect. Both groups, according to Latour, are the authors of identical mistakes: reductionism and, relatedly, attempting to conjoin (in the instance of the sociologist) science and society, or (in the instance of the scientist) keeping them apart. For Latour, there are only forces or resistances which different groups encounter and attempt to conquer by forming alliances. These groups, however, are not simply the actors of conventional sociology. They include, for example, microbes, the discovery of the Pasteurians, with which they have populated our world and which we must now take notice of in any encounter or war in which we engage. War is a fundamental metaphor for Latour, since in a war or a battle clashes of armies are later called the \"victory\" of a Napoleon or a Kutuzov. Likewise, he argues, the Pasteurization of France can be viewed as a battle, with its field and its myriad contestants, in which opposing sides attempted to mould and coerce various forces of resistance. Strangely, he points out, the outcome of this huge battle, the labour and struggle of these masses, we attribute to the scientific genius of Pasteur. Pasteur's genius, however, says Latour, lay not in science (for this could be yet another way of making science and society distinct) but as strategist. Pasteur was able to cross disciplinary lines, recruiting allies to laboratory science by persuading them that they were recruiting him. This was possible because, like the armies in battle, they had already done the work of the general. Thus Pasteur's microbiology, which might conventionally be seen as a whole new science, can also be construed as a brilliant reformulation of all that preceded it and made it possible. Hygienists seized on the work of the Pasteurians and the two rapidly became powerful allies because \"The time that they [the hygienists] had made was now working for them\" (p. 52). French physicians, on the other hand, resisted recruitment, since for them it meant enslavement. Finally, however, they recruited the Pasteurians to their enterprise. Pasteurian public health was turned into a triumph of medicine. It is impossible to read this book and not substitute Latour for Pasteur. At the head of his own army, increasingly enlarged by the recruitment of allies, Latour now presents us, in his own language, with something we have made, or at least made possible. The cynic might say, using the old jibe against sociologists, that Latour has explained to us in his own language everything we knew anyway. Retorting thus, however, would be to unselfconsciously make an ally of Latour and miss the point by a narrow margin that might as well be a million miles. Latour says all this much more clearly (and certainly more wittily) than any review. Read it, but beware; in spite of Latour's strictures about irreducibility, the text is not what it seems. This is a recruitment brochure: Bruno needs you. Among the many historians whom Latour convicts by quotation of mistaking the general for the army, Pasteur for all the forces at work in French society, is Georges Canguilhem. Latour uses two quotes from Canguilhem, both taken from the original French version of Ideology and rationality in the life sciences, first published in 1977. Reading Canguilhem after Latour induces a feeling akin to culture shock. Astonishingly, Canguilhem seems almost Anglo-American. Anyone familiar with Canguilhem's epistemological universe would hardly be surprised to discover that Latour finds in it perspectives different from his own. After all, Canguilhem remains committed to the epistemologically distinct entity science or, better still, sciences. Likewise he employs distinctions between science and ideology, as in Spencerian ideology and Darwinian science, which will seem familiar, possibly jaded to English-reading eyes. His text is liberally seeded with unLatourian expressions, including injunctions to distinguish \"between ideology and science\" (p. 39), lamentations that eighteenth-century medicine \"squandered its energy in the erection of systems\" (p. 53), rejoicing that physiology \"liberated itself' from classical anatomy (p. 54), and regret that \"Stahl's influence ... seriously impeded experimental

Adeno-associated virus vector as a platform for gene therapy delivery

Abstract: Adeno-associated virus (AAV) vectors are the leading platform for gene delivery for the treatment of a variety of human diseases. Recent advances in developing clinically desirable AAV capsids, optimizing genome designs and harnessing revolutionary biotechnologies have contributed substantially to the growth of the gene therapy field. Preclinical and clinical successes in AAV-mediated gene replacement, gene silencing and gene editing have helped AAV gain popularity as the ideal therapeutic vector, with two AAV-based therapeutics gaining regulatory approval in Europe or the United States. Continued study of AAV biology and increased understanding of the associated therapeutic challenges and limitations will build the foundation for future clinical success.