Verteporfin photodynamic therapy cohort study:report 1: effectiveness and factors influencing outcomes

Purpose - To compare the visual outcomes after verteporfin photodynamic therapy (VPDT) administered in routine clinical practice with those observed in the Treatment of Age-related macular degeneration with Photodynamic therapy (TAP) trials and to quantify the effects of clinically important baseline covariates on outcome. Design - A prospective longitudinal study of patients treated with VPDT in 45 ophthalmology departments in the United Kingdom with expertise in the management of neovascular age-related macular degeneration (nAMD). Participants - Patients with wholly or predominantly classic choroidal neovascularization (CNV) of any cause with a visual acuity =20/200 in the eye to be treated. Methods - Refracted best-corrected visual acuity (BCVA) and contrast sensitivity were measured in VPDT-treated eyes at baseline and subsequent visits. Eyes were retreated at 3 months if CNV was judged to be active. Baseline angiograms were graded to quantify the percentages of classic and occult CNV. Treated eyes were categorized as eligible or ineligible for TAP, or unclassifiable. Main Outcome Measures - Best-corrected visual acuity and contrast sensitivity during 1 year of follow-up after initial treatment. Results - A total of 7748 treated patients were recruited. Data from 4043 patients with a diagnosis of nAMD were used in the present analysis. Reading center determination of lesion type showed that 87% were predominantly classic CNV. Eyes received 2.4 treatments in year 1 and 0.4 treatments in year 2. Deterioration of BCVA over 1 year was similar to that observed in the VPDT arms of the TAP trials and was not influenced by TAP eligibility classification. Best-corrected visual acuity deteriorated more quickly in current smokers; with increasing proportion of classic CNV, increasing age, and better baseline BCVA; and when the fellow eye was the better eye.

Channel estimation and compensation in chromatic dispersion limited optical fast OFDM systems

We experimentally investigate the channel estimation and compensation in a chromatic dispersion (CD) limited 20Gbit/s optical fast orthogonal frequency division multiplexing (F-OFDM) system with up to 840km transmission. It is shown that symmetric extension based guard interval (GI) is required to enable CD compensation using one-tap equalizers. As few as one optical F-OFDM symbol with four and six pilot tones per symbol can achieve near-optimal channel estimation and compensation performance for 600km and 840km respectively.

Perception while watching movies:effects of physical screen size and scene type

Over the last decade, television screens and display monitors have increased in size considerably, but has this improved our televisual experience? Our working hypothesis was that the audiences adopt a general strategy that “bigger is better.” However, as our visual perceptions do not tap directly into basic retinal image properties such as retinal image size (C. A. Burbeck, 1987), we wondered whether object size itself might be an important factor. To test this, we needed a task that would tap into the subjective experiences of participants watching a movie on different-sized displays with the same retinal subtense. Our participants used a line bisection task to self-report their level of “presence” (i.e., their involvement with the movie) at several target locations that were probed in a 45-min section of the movie “The Good, The Bad, and The Ugly.” Measures of pupil dilation and reaction time to the probes were also obtained. In Experiment 1, we found that subjective ratings of presence increased with physical screen size, supporting our hypothesis. Face scenes also produced higher presence scores than landscape scenes for both screen sizes. In Experiment 2, reaction time and pupil dilation results showed the same trends as the presence ratings and pupil dilation correlated with presence ratings, providing some validation of the method. Overall, the results suggest that real-time measures of subjective presence might be a valuable tool for measuring audience experience for different types of (i) display and (ii) audiovisual material.

Role of copper in reducing hospital environment contamination

The environment may act as a reservoir for pathogens that cause healthcare-associated infections (HCAIs). Approaches to reducing environmental microbial contamination in addition to cleaning are thus worthy of consideration. Copper is well recognised as having antimicrobial activity but this property has not been applied to the clinical setting. We explored its use in a novel cross-over study on an acute medical ward. A toilet seat, set of tap handles and a ward entrance door push plate each containing copper were sampled for the presence of micro-organisms and compared to equivalent standard, non-copper-containing items on the same ward. Items were sampled once weekly for 10 weeks at 07:00 and 17:00. After five weeks, the copper-containing and non-copper-containing items were interchanged. The total aerobic microbial counts per cm2 including the presence of ‘indicator micro-organisms’ were determined. Median numbers of microorganisms harboured by the copper-containing items were between 90% and 100% lower than their control equivalents at both 07:00 and 17:00. This reached statistical significance for each item with one exception. Based on the median total aerobic cfu counts from the study period, five out of ten control sample points and zero out of ten copper points failed proposed benchmark values of a total aerobic count of <5 cfu/cm2. All indicator micro-organisms were only isolated from control items with the exception of one item during one week. The use of copper-containing materials for surfaces in the hospital environment may therefore be a valuable adjunct for the prevention of HCAIs and requires further evaluation.

Small Ubiquitin-related Modifier (SUMO)-1 promotes glycolysis in hypoxia

Under conditions of hypoxia, most eukaryotic cells undergo a shift in metabolic strategy, which involves increased flux through the glycolytic pathway. Although this is critical for bioenergetic homeostasis, the underlying mechanisms have remained incompletely understood. Here, we report that the induction of hypoxia-induced glycolysis is retained in cells when gene transcription or protein synthesis are inhibited suggesting the involvement of additional post-translational mechanisms. Post-translational protein modification by the small ubiquitin related modifier-1 (SUMO-1) is induced in hypoxia and mass spectrometric analysis using yeast cells expressing tap-tagged Smt3 (the yeast homolog of mammalian SUMO) revealed hypoxia-dependent modification of a number of key glycolytic enzymes. Overexpression of SUMO-1 in mammalian cancer cells resulted in increased hypoxia-induced glycolysis and resistance to hypoxia-dependent ATP depletion. Supporting this, non-transformed cells also demonstrated increased glucose uptake upon SUMO-1 overexpression. Conversely, cells overexpressing the de-SUMOylating enzyme SENP-2 failed to demonstrate hypoxia-induced glycolysis. SUMO-1 overexpressing cells demonstrated focal clustering of glycolytic enzymes in response to hypoxia leading us to hypothesize a role for SUMOylation in promoting spatial re-organization of the glycolytic pathway. In summary, we hypothesize that SUMO modification of key metabolic enzymes plays an important role in shifting cellular metabolic strategies toward increased flux through the glycolytic pathway during periods of hypoxic stress. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

Speech and non-speech stimuli in the prediction of early reading skills:the influence of processing demands and response-type

Purpose: Both phonological (speech) and auditory (non-speech) stimuli have been shown to predict early reading skills. However, previous studies have failed to control for the level of processing required by tasks administered across the two levels of stimuli. For example, phonological tasks typically tap explicit awareness e.g., phoneme deletion, while auditory tasks usually measure implicit awareness e.g., frequency discrimination. Therefore, the stronger predictive power of speech tasks may be due to their higher processing demands, rather than the nature of the stimuli. Method: The present study uses novel tasks that control for level of processing (isolation, repetition and deletion) across speech (phonemes and nonwords) and non-speech (tones) stimuli. 800 beginning readers at the onset of literacy tuition (mean age 4 years and 7 months) were assessed on the above tasks as well as word reading and letter-knowledge in the first part of a three time-point longitudinal study. Results: Time 1 results reveal a significantly higher association between letter-sound knowledge and all of the speech compared to non-speech tasks. Performance was better for phoneme than tone stimuli, and worse for deletion than isolation and repetition across all stimuli. Conclusions: Results are consistent with phonological accounts of reading and suggest that level of processing required by the task is less important than stimuli type in predicting the earliest stage of reading.

Are dyslexics' visual deficits limited to measures of dorsal stream function?

We tested the hypothesis that the differences in performance between developmental dyslexics and controls on visual tasks are specific for the detection of dynamic stimuli. We found that dyslexics were less sensitive than controls to coherent motion in dynamic random dot displays. However, their sensitivity to control measures of static visual form coherence was not significantly different from that of controls. This dissociation of dyslexics' performance on measures that are suggested to tap the sensitivity of different extrastriate visual areas provides evidence for an impairment specific to the detection of dynamic properties of global stimuli, perhaps resulting from selective deficits in dorsal stream functions. © 2001 Lippincott Williams & Wilkins.

Encoding order and developmental dyslexia:a family of skills predicting different orthographic components

We investigated order encoding in developmental dyslexia using a task that presented nonalphanumeric visual characters either simultaneously or sequentially—to tap spatial and temporal order encoding, respectively—and asked participants to reproduce their order. Dyslexic participants performed poorly in the sequential condition, but normally in the simultaneous condition, except for positions most susceptible to interference. These results are novel in demonstrating a selective difficulty with temporal order encoding in a dyslexic group. We also tested the associations between our order reconstruction tasks and: (a) lexical learning and phonological tasks; and (b) different reading and spelling tasks. Correlations were extensive when the whole group of participants was considered together. When dyslexics and controls were considered separately, different patterns of association emerged between orthographic tasks on the one side and tasks tapping order encoding, phonological processing, and written learning on the other. These results indicate that different skills support different aspects of orthographic processing and are impaired to different degrees in individuals with dyslexia. Therefore, developmental dyslexia is not caused by a single impairment, but by a family of deficits loosely related to difficulties with order. Understanding the contribution of these different deficits will be crucial to deepen our understanding of this disorder.

EpiJen:a server for multistep T cell epitope prediction

Background - The main processing pathway for MHC class I ligands involves degradation of proteins by the proteasome, followed by transport of products by the transporter associated with antigen processing (TAP) to the endoplasmic reticulum (ER), where peptides are bound by MHC class I molecules, and then presented on the cell surface by MHCs. The whole process is modeled here using an integrated approach, which we call EpiJen. EpiJen is based on quantitative matrices, derived by the additive method, and applied successively to select epitopes. EpiJen is available free online. Results - To identify epitopes, a source protein is passed through four steps: proteasome cleavage, TAP transport, MHC binding and epitope selection. At each stage, different proportions of non-epitopes are eliminated. The final set of peptides represents no more than 5% of the whole protein sequence and will contain 85% of the true epitopes, as indicated by external validation. Compared to other integrated methods (NetCTL, WAPP and SMM), EpiJen performs best, predicting 61 of the 99 HIV epitopes used in this study. Conclusion - EpiJen is a reliable multi-step algorithm for T cell epitope prediction, which belongs to the next generation of in silico T cell epitope identification methods. These methods aim to reduce subsequent experimental work by improving the success rate of epitope prediction.

Transporter associated with antigen processing preselection of peptides binding to the MHC:a bioinformatic evaluation

TAP is responsible for the transit of peptides from the cytosol to the lumen of the endoplasmic reticulum. In an immunological context, this event is followed by the binding of peptides to MHC molecules before export to the cell surface and recognition by T cells. Because TAP transport precedes MHC binding, TAP preferences may make a significant contribution to epitope selection. To assess the impact of this preselection, we have developed a scoring function for TAP affinity prediction using the additive method, have used it to analyze and extend the TAP binding motif, and have evaluated how well this model acts as a preselection step in predicting MHC binding peptides. To distinguish between MHC alleles that are exclusively dependent on TAP and those exhibiting only a partial dependence on TAP, two sets of MHC binding peptides were examined: HLA-A*0201 was selected as a representative of partially TAP-dependent HLA alleles, and HLA-A*0301 represented fully TAP-dependent HLA alleles. TAP preselection has a greater impact on TAP-dependent alleles than on TAP-independent alleles. The reduction in the number of nonbinders varied from 10% (TAP-independent) to 33% (TAP-dependent), suggesting that TAP preselection is an important component in the successful in silico prediction of T cell epitopes.

Channel estimation and compensation in chromatic dispersion limited optical fast OFDM systems

We experimentally investigate the channel estimation and compensation in a chromatic dispersion (CD) limited 20Gbit/s optical fast orthogonal frequency division multiplexing (F-OFDM) system with up to 840km transmission. It is shown that symmetric extension based guard interval (GI) is required to enable CD compensation using one-tap equalizers. As few as one optical F-OFDM symbol with four and six pilot tones per symbol can achieve near-optimal channel estimation and compensation performance for 600km and 840km respectively.

JenPep : a novel computational information resource for immunobiology and vaccinology

JenPep is a relational database containing a compendium of thermodynamic binding data for the interaction of peptides with a range of important immunological molecules:  the major histocompatibility complex, TAP transporter, and T cell receptor. The database also includes annotated lists of B cell and T cell epitopes. Version 2.0 of the database is implemented in a bespoke postgreSQL database system and is fully searchable online via a perl/HTML interface (URL:  http://www.jenner.ac.uk/JenPep).

Genetic Algorithm Approach for Solving the Task Assignment Problem

This research was partially supported by the Serbian Ministry of Science and Ecology under project 144007. The authors are grateful to Ivana Ljubić for help in testing and to Vladimir Filipović for useful suggestions and comments.

Why do doctored images distort memory?

Doctored images can cause people to believe in and remember experiences that never occurred, yet the underlying mechanism(s) responsible are not well understood. How does compelling false evidence distort autobiographical memory? Subjects were filmed observing and copying a Research Assistant performing simple actions, then they returned 2 days later for a memory test. Before taking the test, subjects viewed video-clips of simple actions, including actions that they neither observed nor performed earlier. We varied the format of the video-clips between-subjects to tap into the source-monitoring mechanisms responsible for the 'doctored-evidence effect.' The distribution of belief and memory distortions across conditions suggests that at least two mechanisms are involved: doctored images create an illusion of familiarity, and also enhance the perceived credibility of false suggestions. These findings offer insight into how external evidence influences source-monitoring. © 2009 Elsevier Inc. All rights reserved.

International session at the BCLA conference

Full text: It seems a long time ago now since we were at the BCLA conference. The excellent FIFA World Cup in Brazil kept us occupied over the summer as well as Formula 1, Wimbledon, Tour de France, Commonwealth Games and of course exam paper marking! The BCLA conference this year was held in Birmingham at the International Convention Centre which again proved to be a great venue. The number of attendees overall was up on previous years, and at a record high of 1500 people. Amongst the highlights at this year's annual conference was the live surgery link where Professor Sunil Shah demonstrated the differences in technique between traditional phacoemulsification cataract surgery and femtosecond assisted phacoemulsification cataract surgery. Dr. Raquel Gil Cazorla, a research optometrist at Aston University, assisted in the procedure including calibrating the femtosecond laser. Another highlight for me was the session that I chaired, which was the international session organised by IACLE (International Association of CL Educators). There was a talk by Mirjam van Tilborg about dry eye prevalence in the Netherlands and how it was managed by medical general practitioners (GPs) or optometrists. It was interesting to know that there are only 2 schools of optometry there and currently under 1000 registered optometrists there. It also seems that GPs were more likely to blame CL as the cause for dry eye whereas optometrists who had a fuller range of tests were better at solving the issue. The next part of the session included the presentation of 5 selected posters from around the world. The posters were also displayed in the main poster area but were selected to be presented here as they had international relevance. The posters were: 1. Motivators and Barriers for Contact Lens Recommendation and Wear by Nilesh Thite (India) 2. Contact lens hygiene among Saudi wearers by Dr. Ali Masmaly (Saudi) 3. Trends of contact lens prescribing and patterns of contact lens practice in Jordan by Dr. Mera Haddad (Jordan) 4. Contact Lens Behaviour in Greece by Dr. Dimitra Makrynioti (Greece) 5. How practitioners inform ametropes about the benefits of contact lenses and overcome the potential barriers: an Italian survey, by Dr. Fabrizio Zeri (Italy) It was interesting to learn about CL practice in different parts, for example the CL wearing population ration in Saudi Arabia is around 1:2 Male:Female (similar to other parts of the world) and although the sale of CL is restricted to registered practitioners there are many unregistered outlets, like clothing stores, that flout the rules. In Jordan some older practitioners will still advise patients to use tap water or even saliva! But thankfully the newer generation of practitioners have been educated not to advise this. In Greece one of the concerns was that some practitioners may advise patients to use disposable lenses for longer than they should and again it seems to be the practitioners with inadequate education that would do this. In India it was found that cost was one barrier to using contact lenses but also some practitioners felt that they shouldn’t offer CLs due to cost too. In Italy sensitive eyes and CL care and maintenance were the barriers to CL wear but the motivators were vision and comfort and aesthetics. Finally the international session ended with the IACLE travel award and educator awards presented by IACLE president Shehzad Naroo and BCLA President Andrew Yorke. The travel award went to Wang Ling, Jinling Institute of Technology, Nanjing, China. There were 3 regional Contact Lens Educator of the Year Awards sponsored by Coopervision and presented by Dr. J.C. Aragorn of Coopervision. 1. Asia Pacific Region – Dr. Rajeswari Mahadevan of Sankara Nethralaya Medical Research Foundation, Chennai, India 2. Americas Region – Dr. Sergio Garcia of University of La Salle, Bogotá and the University Santo Tomás, Bucaramanga, Colombia 3. Europe/Africa – Middle East Region: Dr. Eef van der Worp, affiliated with the University of Maastricht, the Netherlands The posters above were just a small selection of those displayed at this year's BCLA conference. If you missed the BCLA conference then you can see the abstracts for all posters and talks in a virtual issue of CLAE very soon. The poster competition was kindly sponsored by Elsevier. The poster winner this year was: Joan Gispets – Corneal and Anterior Chamber Parameters in Keratoconus The 3 runners up were: Debby Yeung – Scleral Lens Central Corneal Clearance Assessment with Biomicroscopy Sarah L. Smith – Subjective Grading of Lid Margin Staining Heiko Pult – Impact of Soft Contact Lenses on Lid Parallel Conjunctival Folds My final two highlights are a little more personal. Firstly, I was awarded Honorary Life Fellowship of the BCLA for my work with the Journal, and I would like to thank the BCLA, Elsevier, the editorial board of CLAE, the reviewers and the authors for their support of my role. My final highlight from the BCLA conference this year was the final presentation of the conference – the BCLA Gold Medal award. The recipient this year was Professor Philip Morgan with his talk ‘Changing the world with contact lenses’. Phil was the person who advised me to go to my first BCLA conference in 1994 (funnily he didn’t attend himself as he was busy getting married!) and now 20 years later he was being honoured with the accolade of being the BCLA Gold Medallist. The date of his BCLA medal addressed was shared with his father's birthday so a double celebration for Phil. Well done to outgoing BCLA President Andy Yorke and his team at the BCLA (including Nick Rumney, Cheryl Donnelly, Sarah Greenwood and Amir Khan) on an excellent conference. And finally welcome to new President Susan Bowers. Copyright © 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.