Profound hypotony maculopathy in a first episode of bilateral idiopathic acute anterior uveitis

BACKGROUND: We report a case of a HLA-B27 negative patient presenting with severe, bilateral, idiopathic acute anterior uveitis with acute hypotony and hypotony maculopathy as their first uveitic episode. CASE PRESENTATION: Within a week of onset of her first episode of acute anterior uveitis, a 45 year-old Caucasian lady developed profound ocular hypotony with unrecordable intraocular pressures, reduced vision and choroidal folds. All investigations were negative. Uveitic hypotony responded slowly to corticosteroids – intravenous, oral and topical – with normalization of intraocular pressure and resolution of choroidal folds after two months. Anterior uveitis and hypotony have not returned with six months of follow-up. CONCLUSION: Bilateral, profound hypotony maculopathy may present acutely in idiopathic acute anterior uveitis, may be slow to respond to treatment and should be considered as a cause of vision loss in patients with this condition

Are ethnicity, social grade, and social deprivation associated with severity of thyroid-associated ophthalmopathy?

PURPOSE: Previous studies have extensively investigated the pathophysiology, genetics, and lifestyle risk factors of thyroid-associated ophthalmopathy (TAO). The aim of this study was to investigate the independent contribution of ethnic origin, social grade, and level of social deprivation to TAO severity in a large, multiethnic, and urban population. METHODS: Retrospective case note review of all TAO patients seen at Birmingham and Midland Eye Centre, United Kingdom over a 14-year period. Ethnicity (White, Asian, or Black) was recorded, and residence postcode was used to determine social grade (National Readership Survey classification) and level of social deprivation (Index of Multiple Deprivation 2007). TAO severity was defined by European Group on Graves’ Orbitopathy criteria. Moderate-to-severe: necessity for TAO treatment with oral or intravenous steroid, long-term immunosuppressants, or orbital radiotherapy. Sight-threatening: presence of dysthyroid optic neuropathy (DON) or need for urgent orbital decompression surgery. Multivariable logistic regression was performed to measure the independent influence of ethnicity, social grade, and social deprivation on indicators of severe TAO. RESULTS: Lower social grade was significantly associated with increased odds ratio (OR) of TAO patients having severe TAO, including treatment with oral (OR: 2.3 (95% CI 1.1–5.1) p = 0.03) and intravenous steroid (OR: 2.6 (95% CI 1.0–7.0) p = 0.04) and DON (OR: 4.0 (95% CI 1.2–12.7) p = 0.02), compared with those of highest social grade. Similar results were observed for social deprivation. Ethnicity had no independent association with any measure of TAO severity. CONCLUSIONS: In this cohort, lower social grade and higher social deprivation, but not ethnicity, had independent, statistically significant association with more severe TAO

Self-Swabbing for Virological Confirmation of Influenza-Like Illness Among an Internet-Based Cohort in the UK During the 2014-2015 Flu Season: Pilot Study.

BACKGROUND: Routine influenza surveillance, based on laboratory confirmation of viral infection, often fails to estimate the true burden of influenza-like illness (ILI) in the community because those with ILI often manage their own symptoms without visiting a health professional. Internet-based surveillance can complement this traditional surveillance by measuring symptoms and health behavior of a population with minimal time delay. Flusurvey, the UK's largest crowd-sourced platform for surveillance of influenza, collects routine data on more than 6000 voluntary participants and offers real-time estimates of ILI circulation. However, one criticism of this method of surveillance is that it is only able to assess ILI, rather than virologically confirmed influenza. OBJECTIVE: We designed a pilot study to see if it was feasible to ask individuals from the Flusurvey platform to perform a self-swabbing task and to assess whether they were able to collect samples with a suitable viral content to detect an influenza virus in the laboratory. METHODS: Virological swabbing kits were sent to pilot study participants, who then monitored their ILI symptoms over the influenza season (2014-2015) through the Flusurvey platform. If they reported ILI, they were asked to undertake self-swabbing and return the swabs to a Public Health England laboratory for multiplex respiratory virus polymerase chain reaction testing. RESULTS: A total of 700 swab kits were distributed at the start of the study; from these, 66 participants met the definition for ILI and were asked to return samples. In all, 51 samples were received in the laboratory, 18 of which tested positive for a viral cause of ILI (35%). CONCLUSIONS: This demonstrated proof of concept that it is possible to apply self-swabbing for virological laboratory testing to an online cohort study. This pilot does not have significant numbers to validate whether Flusurvey surveillance accurately reflects influenza infection in the community, but highlights that the methodology is feasible. Self-swabbing could be expanded to larger online surveillance activities, such as during the initial stages of a pandemic, to understand community transmission or to better assess interseasonal activity

Human Acid Sphingomyelinase Structures Provide Insight to Molecular Basis of Niemann-Pick Disease

Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and phosphocholine, essential components of myelin in neurons. Genetic alterations in ASM lead to ASM deficiency (ASMD) and have been linked to Niemann–Pick disease types A and B. Olipudase alfa, a recombinant form of human ASM, is being developed as enzyme replacement therapy to treat the non-neurological manifestations of ASMD. Here we present the human ASM holoenzyme and product bound structures encompassing all of the functional domains. The catalytic domain has a metallophosphatase fold, and two zinc ions and one reaction product phosphocholine are identified in a histidine-rich active site. The structures reveal the underlying catalytic mechanism, in which two zinc ions activate a water molecule for nucleophilic attack of the phosphodiester bond. Docking of sphingomyelin provides a model that allows insight into the selectivity of the enzyme and how the ASM domains collaborate to complete hydrolysis. Mapping of known mutations provides a basic understanding on correlations between enzyme dysfunction and phenotypes observed in ASMD patients

X-Rays from NGC 3256: High-Energy Emission in Starburst Galaxies and Their Contribution to the Cosmic X-Ray Background

The infrared-luminous galaxy NGC3256 is a classic example of a merger induced nuclear starburst system. We find here that it is the most X-ray luminous star-forming galaxy yet detected (~10^42 ergs/s). Long-slit optical spectroscopy and a deep, high-resolution ROSAT X-ray image show that the starburst is driving a "superwind" which accounts for ~20% of the observed soft (kT~0.3 keV) X-ray emission. Our model for the broadband X-ray emission of NGC3256 contains two additional components: a warm thermal plasma (kT~0.8 keV) associated with the central starburst, and a hard power-law component with an energy index of ~0.7. We find that the input of mechanical energy from the starburst is more than sufficient to sustain the observed level of emission. We also examine possible origins for the power-law component, concluding that neither a buried AGN nor the expected population of high-mass X-ray binaries can account for this emission. Inverse-Compton scattering, involving the galaxy's copious flux of infrared photons and the relativistic electrons produced by supernovae, is likely to make a substantial contribution to the hard X-ray flux. Such a model is consistent with the observed radio and IR fluxes and the radio and X-ray spectral indices. We explore the role of X-ray-luminous starbursts in the production of the cosmic X-ray background radiation. The number counts and spectral index distribution of the faint radio source population, thought to be dominated by star-forming galaxies, suggest that a significant fraction of the hard X-ray background could arise from starbursts at moderate redshift.Comment: 31 pages (tex, epsf), 8 figures (postscript files), accepted for publication in Part 1 of The Astrophysical Journa

Defining the limits of normal conjunctival fornix anatomy in a healthy South Asian population

PURPOSE: Quantifying the extent of conjunctival fibrosis for documentation of progression in conjunctival scarring disease is a clinical challenge. Measurement of forniceal foreshortening facilitates monitoring of these disorders. This study aims (1) to define the limits of the normal human conjunctival fornices and how these alter with age and (2) to provide normative data for upper and lower fornix depths (FDs) and fornix intercanthal distance (FICD) within a healthy South Asian, racially distinct population. DESIGN: Epidemiologic, cross-sectional study. PARTICIPANTS: A total of 240 subjects with national origins from South Asia, with no known ocular history and normal adnexal and conjunctival examination, aged 20 to 80 years. METHODS: An FICD modification of a custom-designed fornix depth measurer (FDM) was validated and used for measurement of both lower and upper FDs together with FICDs in 480 healthy eyes with no ocular comorbidities. Data were analyzed using repeated-measures analysis of variance and presented as means with 95% confidence intervals (CIs). MAIN OUTCOME MEASURES: Mean lower and upper FDs and FICD for the entire cohort, stratified according to age decade and sex. RESULTS: For this South Asian population, the overall upper and lower FDs were 15.3 mm (95% CI, 14.9–15.6) and 10.9 mm (95% CI, 10.7–11.1), respectively, with FICD defined as 32.9 mm (95% CI, 32.5–33.4) (upper) and 31.7 mm (95% CI, 31.3–32.1) (lower). With increasing age, a progressive reduction of all measured parameters (P < 0.001) was noted, with female subjects having significantly shallower fornices (upper FD, P < 0.001; lower FD, P < 0.001; upper FICD, P = 0.081; and lower FICD, P = 0.015). CONCLUSIONS: This is the first study to define the limits of normal upper FD and FICDs in any population group. Our study demonstrates sex variations and progressive conjunctival shrinkage with age. Although it provides important, objective data for normal forniceal anatomy, further study is recommended in other populations to confirm the generalizability of these data or to enable normal comparative datasets for the assessment of conjunctival scarring disorders among all anthropological groups

Self-swabbing for virological confirmation of influenza like illness (ILI) amongst an internet based cohort in the UK, 2014-5

Background: Routine influenza surveillance, based on laboratory confirmation of viral infection often fails to estimate a true burden of influenza like illness (ILI) in the community due to the fact that those suffering from ILI often manage their own symptoms, without visiting a health professional. Internet based surveillance can complement this traditional health-service-based surveillance by measuring symptoms and health behaviour of a population with minimal time delay. Flusurvey, the UK’s largest crowd-sourced platform for surveillance of influenza, collects routine data on over 6,000 voluntary participants and offers real-time estimates of ILI circulation. However, one criticism of this method of surveillance is that it is only able to assess ILI, rather than virologically confirmed influenza. Objective: We designed a pilot to see if it was feasible to ask individuals from the Flusurvey platform to perform a self-swabbing task, and to assess whether they were able to collect samples with a suitable viral content to be able to identify an influenza virus in the laboratory. Methods: Virological swabbing kits were sent to pilot participants, who then monitored their ILI symptoms over the influenza season (2014-5) through the Flusurvey platform. If they reported ILI, they were asked to undertake the self-swabbing exercise, and return the swabs to Public Health England (PHE) laboratory for multiplex PCR testing. Results: The results showed that samples from 18/51 people who reported ILI tested positive for a virological confirmed infection through multiplex PCR testing. Conclusions: This demonstrated proof of concept that it is possible to apply self-swabbing for virological laboratory testing to an online cohort study. This pilot does not have significant numbers to validate whether Flusurvey surveillance does reflect influenza infection in the community, but it highlights that the methodology is feasible and self-swabbing could be expanded to larger online surveillance activities, such as during the initial stages of a pandemic to understand community transmission or to better assess inter-seasonal activity

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Addressing climate change with behavioral science: a global intervention tournament in 63 countries

Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions’ effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior—several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people’s initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors