Ocular higher-order aberrations and visual performance

Since adaptive optics was first used to correct the monochromatic aberrations of the eye over a decade ago there has been considerable interest in correcting the ocular aberrations beyond defocus and astigmatism. In order to understand the prospective benefits of correcting these higher-order aberrations it is important to study their effect on visual performance. From a clinical perspective it is important to know how different types of aberration can affect visual performance so that wavefront measurements can be better understood. Visual performance is determined by a combination of optical and neural factors. It is important to consider how degradations in the optical quality of the eye can impact the neural processes involved in visual tasks such as object recognition. In this thesis we present a study of the effects of three types of aberration, defocus, coma and secondary astigmatism, on letter recognition and reading performance. In the course of this work we also characterise the repeatability of the Zywave aberrometer, which we used to measure our subjects' ocular wavefronts. We use stimuli that have these aberrations applied in their rendering to examine the differences between these aberrations and how they differ with respect to the visual task. We find that secondary astigmatism causes the largest impairment to both letter recognition and reading performance, followed by defocus. Coma causes comparatively smaller degradations to performance but its effect is different depending on the visual task. We can predict the reduction in performance based on a simple cross-correlation model of letter confusability. The relationship between these predictions and the experimental results are the same for all three aberrations, in the case of single letter recognition. In reading however, the relationship is different for coma. We suggest that coma causes lateral masking effects and may additionally disrupt the planning of eye movements. Coma slows reading, but does not specifically impair word identification whereas defocus and secondary astigmatism do. We attribute disruptions in word identification to the dramatic effects defocus and secondary astigmatism have on the form of a letter

Patterns of sugar-sweetened beverage consumption amongst young people aged 13–15 years during the school day in Scotland

© 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Background There is currently little research regarding sugar-sweetened beverage (SSB) consumption patterns of young people though adolescents are thought to be frequent consumers of these drinks. There is no research regarding the other foods and drinks consumed alongside SSBs by young people. The aim of this paper is to explore the patterns of SSB purchase and consumption amongst young people aged 13–15 years. Methods A purchasing recall questionnaire (PRQ) was administered online in seven case study schools with 535 young people aged 13–15 years. Nutrient composition (kilocalories, fat, saturated fat, sodium and sugar) was also calculated for food/drink purchases. Chi-Square and Wilcoxon-Mann Whitney tests were conducted to examine patterns of SSB consumption and sugar/kilocalories consumption for SSB consumers and non-consumers. Results SSB consumers were significantly more likely to consume a drink at mid-morning break. Fewer consumed food at mid-morning break, ate food before school or ate food at lunchtime, but this was not statistically significant. A higher percentage of SSB consumers consumed ‘unhealthy’ food and drinks in comparison to young people who did not consume a SSB. Both median lunchtime sugar consumption (40.7 g vs 10.2 g) and median sugar as a percentage of Kcals (39% vs 14%) were significantly higher for SSB purchasers in comparison to non-purchasers. Conclusion The analysis highlights that SSB purchasers consume significantly more sugar at lunchtime than non-purchasers. However, both purchasers and non-purchasers exceeded WHO (2015) recommendations that sugar consumption be halved to form no more than 5% of daily energy intake. This study provides new insights for public health stakeholders and schools. Multifaceted and inventive strategies relevant to young people will be required to WHO recommendations.Peer reviewedFinal Published versio

Early Last Interglacial ocean warming drove substantial ice mass loss from Antarctica

The future response of the Antarctic ice sheet to rising temperatures remains highly uncertain. A useful period for assessing the sensitivity of Antarctica to warming is the Last Interglacial (LIG) (129 to 116 ky), which experienced warmer polar temperatures and higher global mean sea level (GMSL) (+6 to 9 m) relative to present day. LIG sea level cannot be fully explained by Greenland Ice Sheet melt (∼2 m), ocean thermal expansion, and melting mountain glaciers (∼1 m), suggesting substantial Antarctic mass loss was initiated by warming of Southern Ocean waters, resulting from a weakening Atlantic meridional overturning circulation in response to North Atlantic surface freshening. Here, we report a blue-ice record of ice sheet and environmental change from the Weddell Sea Embayment at the periphery of the marine-based West Antarctic Ice Sheet (WAIS), which is underlain by major methane hydrate reserves. Constrained by a widespread volcanic horizon and supported by ancient microbial DNA analyses, we provide evidence for substantial mass loss across the Weddell Sea embayment during the LIG, most likely driven by ocean warming and associated with destabilization of subglacial hydrates. Ice sheet modeling supports this interpretation and suggests that millennial-scale warming of the Southern Ocean could have triggered a multimeter rise in global sea levels. Our data indicate that Antarctica is highly vulnerable to projected increases in ocean temperatures and may drive ice–climate feedbacks that further amplify warming

The ethics of ‘Trials within Cohorts’ (TwiCs): 2nd international symposium - London, UK. 7-8 November 2016

On 7-8 th November 2016, 60 people with an interest in the ‘ Trials within Cohorts ’ (TwiCs) approach for randomised controlled trial design met in London. The purpose of this 2 nd TwiCs international symposium was to share perspectives and experiences on ethical aspects of the TwiCs design, discuss how TwiCs relate to the current ethical frame- work, provide a forum in which to discuss and debate ethical issues and identify future directions for conceptual and empirical research. The symposium was supported by the Wellcome Trust and the NIHR CLAHRC Yorkshire and Humber and organised by members of the TwiCs network led by Clare Relton and attended by people from the UK, the Netherlands, Norway, Canada and USA. The two-day sympo- sium enabled an international group to meet and share experiences of the TwiCs design (also known as the ‘ cohort multiple RCT design ’ ), and to discuss plans for future research. Over the two days, invited plenary talks were interspersed by discussions, posters and mini pre- sentations from bioethicists, triallists and health research regulators. Key findings of the symposium were: (1) It is possible to make a compelling case to ethics committees that TwiCs designs are ap- propriate and ethical; (2) The importance of wider considerations around the ethics of inefficient trial designs; and (3) some questions about the ethical requirements for content and timing of informed consent for a study using the TwiCs design need to be decided on a case-by-case basis

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Structure Guided Design and Synthesis of a Pyridazinone Series of Trypanosoma cruzi Proteasome Inhibitors

There is an urgent need for new treatments for Chagas disease, a parasitic infection which mostly impacts South and Central America. We previously reported on the discovery of GSK3494245/DDD01305143, a preclinical candidate for visceral leishmaniasis which acted through inhibition of the Leishmania proteasome. A related analogue, active against Trypanosoma cruzi, showed suboptimal efficacy in an animal model of Chagas disease, so alternative proteasome inhibitors were investigated. Screening a library of phenotypically active analogues against the T. cruzi proteasome identified an active, selective pyridazinone, the development of which is described herein. We obtained a cryo-EM co-structure of proteasome and a key inhibitor and used this to drive optimization of the compounds. Alongside this, optimization of the absorption, distribution, metabolism, and excretion (ADME) properties afforded a suitable compound for mouse efficacy studies. The outcome of these studies is discussed, alongside future plans to further understand the series and its potential to deliver a new treatment for Chagas disease.</p

The Lantern, 2022-2023

The Genie and the Scotsman • Taxi Driver Savior Complex • Midnight Waltz • Eulogy of Caution • Don\u27t cry over spilled milk!! • I am the spider • The Lamb • The Witch and the Shepherd • Nostalgia • In the Summer I Want Light • I Am (Not) • Thanatophobia • We\u27re not children anymore • Hamlet\u27s Fool • Lemon • the last two people in the world • Amongst Chaos (what captivated me) • How About Now, Billy Joel • Bug Trap • Spring, Musser Hall, Room 219 • Time\u27s Denial • A Song of History • A Haiku for You • Hello! My Name Is: • Toilet Humor • Waterfalls • Communion • Shift • Mama Told Me Not To Waste My Life • Writer\u27s Block • Sharp-Tongued Women • Off Trail • Paper Bag Town • Serenity • Landscape of Ursinus Courtyard • Image #07, Affinist designer • Love Birds • Discount Narnia • False Security • Stripes and Illusions • The Burning of Ophelia • Molly\u27s Folly • The Son of Bethany • Meta • Little Blue Sailboats • Grease Trap • Hitchhiking With My Eyes Closed • The Donna of Our Time • The Magic of Cooking • The Closing Shift • A Baptism of Teeth • Dear Beloved • How Kansas Got to Chicago • Anywhere, if you look hard enoughhttps://digitalcommons.ursinus.edu/lantern/1191/thumbnail.jp

Functional antibody and T-cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study (NCT03226886) integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2-positive, 94 were symptomatic and 2 patients died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies, 82% had neutralizing antibodies against WT, whereas neutralizing antibody titers (NAbT) against the Alpha, Beta, and Delta variants were substantially reduced. Whereas S1-reactive antibody levels decreased in 13% of patients, NAbT remained stable up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment-specific, but presented compensatory cellular responses, further supported by clinical. Overall, these findings advance the understanding of the nature and duration of immune response to SARS-CoV-2 in patients with cancer