Utility and uncorrected refractive error

Purpose: To investigate utility (a preference-based quality of life [QoL] measure) associated with uncorrected refractive error (URE). Design: Cross-sectional study. Participants: A cohort of 341 consecutive patients 40 to 65 years of age with refractive error and no ocular disease impairing vision worse than 20/25 (0.1 logarithm of the minimum angle of resolution [logMAR] units) in the better eye. Without vision correction, 30 had no vision impairment, 65 had only distance vision impairment (DVI), 97 had only near vision impairment (NVI), 112 had moderate amounts of both distance and near vision impairment (DNVI), and 37 had severe impairment (distance or near worse than 20/200 [>1.0 logMAR]) in the better eye. Methods: All participants underwent a comprehensive eye examination with refraction, aided and unaided visual acuity (VA) at 6 m and 40 cm, and ocular health assessment. Utilities were elicited for a number of scenarios using a standardized, face-to-face time trade-off (TTO) interview method. Main Outcome Measures: The main outcome measure was TTO utility for the participant's own uncorrected vision state. Utilities ranged from 0 to 1, where 0 = death and 1 = perfect vision, and were scaled to account for comorbidities so that 1 = perfect health (adjusted utility). Results: Unaided VA was 0.50±0.24 logMAR at distance in the DVI group, 0.43±0.17 logMAR at near in the NVI group, and 0.72±0.36 and 0.56±0.29 at distance and near, respectively, in the DNVI group. Adjusted utilities for the 3 groups were 0.82±0.16 in the DVI group, 0.81±0.17 in the NVI group, and 0.68±0.25 in the DNVI group. The DVI and NVI group utilities (adjusted and unadjusted) did not differ significantly (P = 0.73 and P = 0.77, respectively). The DNVI utility was significantly worse than that of the DVI and NVI groups (adjusted and unadjusted, P<0.01). Conclusions: The URE is associated with measurable reductions in utility (and therefore QoL). Reductions are similar regardless of whether near or distance vision is impaired, but worse when both are impaired. The results underscore the significance of the effect of URE on QoL, particularly with respect to uncorrected presbyopia, which has been a relatively neglected area in research and policy. The utility figures in this study can be used as inputs for cost-effectiveness studies relating to URE to assist resource allocation decisions. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2013 American Academy of Ophthalmology

Old Drugs To Treat Resistant Bugs: Methicillin-Resistant Staphylococcus aureus Isolates with mecC Are Susceptible to a Combination of Penicillin and Clavulanic Acid.

β-Lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA) is mediated by the expression of an alternative penicillin-binding protein 2a (PBP2a) (encoded by mecA) with a low affinity for β-lactam antibiotics. Recently, a novel variant of mecA, known as mecC, was identified in MRSA isolates from both humans and animals. In this study, we demonstrate that mecC-encoded PBP2c does not mediate resistance to penicillin. Rather, broad-spectrum β-lactam resistance in MRSA strains carrying mecC (mecC-MRSA strains) is mediated by a combination of both PBP2c and the distinct β-lactamase encoded by the blaZ gene of strain LGA251 (blaZLGA251), which is part of mecC-encoding staphylococcal cassette chromosome mec (SCCmec) type XI. We further demonstrate that mecC-MRSA strains are susceptible to the combination of penicillin and the β-lactam inhibitor clavulanic acid in vitro and that the same combination is effective in vivo for the treatment of experimental mecC-MRSA infection in wax moth larvae. Thus, we demonstrate how the distinct biological differences between mecA- and mecC-encoded PBP2a and PBP2c have the potential to be exploited as a novel approach for the treatment of mecC-MRSA infections.This work was supported by a Medical Research Council (MRC) Partnership Grant (G1001787/1) held between the Department of Veterinary Medicine, University of Cambridge (M. A. H.), the School of Clinical Medicine, University of Cambridge (S. J. P.), the Moredun Research Institute (R. N. Z.) and the Wellcome Trust Sanger Institute (J. P. and S. J. P.).This is the author accepted manuscript. The final version is available from American Society for Microbiology via http://dx.doi.org/10.1128/AAC.01469-1

Novel mutations in penicillin-binding protein genes in clinical Staphylococcus aureus isolates that are methicillin resistant on susceptibility testing, but lack the mec gene.

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is an important global health problem. MRSA resistance to β-lactam antibiotics is mediated by the mecA or mecC genes, which encode an alternative penicillin-binding protein (PBP) 2a that has a low affinity to β-lactam antibiotics. Detection of mec genes or PBP2a is regarded as the gold standard for the diagnosis of MRSA. We identified four MRSA isolates that lacked mecA or mecC genes, but were still phenotypically resistant to pencillinase-resistant β-lactam antibiotics. METHODS: The four human S. aureus isolates were investigated by whole genome sequencing and a range of phenotypic assays. RESULTS: We identified a number of amino acid substitutions present in the endogenous PBPs 1, 2 and 3 that were found in the resistant isolates but were absent in closely related susceptible isolates and which may be the basis of resistance. Of particular interest are three identical amino acid substitutions in PBPs 1, 2 and 3, occurring independently in isolates from at least two separate multilocus sequence types. Two different non-conservative substitutions were also present in the same amino acid of PBP1 in two isolates from two different sequence types. CONCLUSIONS: This work suggests that phenotypically resistant MRSA could be misdiagnosed using molecular methods alone and provides evidence of alternative mechanisms for β-lactam resistance in MRSA that may need to be considered by diagnostic laboratories

Novel mutations in penicillin-binding protein genes in clinical Staphylococcus aureus isolates that are methicillin resistant on susceptibility testing, but lack the mec gene.

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is an important global health problem. MRSA resistance to β-lactam antibiotics is mediated by the mecA or mecC genes, which encode an alternative penicillin binding protein (PBP)2a that has a low affinity to β-lactam antibiotics. Detection of mec genes or PBP2a is regarded as the gold standard for the diagnosis of MRSA.We identified four MRSA isolates that lacked mecA or mecC genes, but were still phenotypically resistant to encillinase-resistant β-lactam antibiotics. Methods: The four human S. aureus isolates were investigated by whole genome sequencing and a range of phenotypic assays. Results: We identified a number of amino acid substitutions present in the endogenous PBPs 1, 2 and 3 that were found in the resistant isolates but were absent in closely related susceptible isolates and which maybe the basis of resistance. Of particular interest are three identical amino acid substitutions in PBPs 1, 2 and 3, occurring independently in isolates from at least two separate multilocus sequence types. Two different non-conservative substitutions were also present in the same amino acid of PBP1 in two isolates from two different sequence types. Conclusions: This work suggests that phenotypically resistant MRSA could be misdiagnosed using molecular methods alone and provides evidence of alternative mechanisms for β-lactam resistance in MRSA that may need to be considered by diagnostic laboratories

Serratamolide is a hemolytic factor produced by Serratia marcescens

Serratia marcescens is a common contaminant of contact lens cases and lenses. Hemolytic factors of S. marcescens contribute to the virulence of this opportunistic bacterial pathogen. We took advantage of an observed hyper-hemolytic phenotype of crp mutants to investigate mechanisms of hemolysis. A genetic screen revealed that swrW is necessary for the hyper-hemolysis phenotype of crp mutants. The swrW gene is required for biosynthesis of the biosurfactant serratamolide, previously shown to be a broad-spectrum antibiotic and to contribute to swarming motility. Multicopy expression of swrW or mutation of the hexS transcription factor gene, a known inhibitor of swrW expression, led to an increase in hemolysis. Surfactant zones and expression from an swrW-transcriptional reporter were elevated in a crp mutant compared to the wild type. Purified serratamolide was hemolytic to sheep and murine red blood cells and cytotoxic to human airway and corneal limbal epithelial cells in vitro. The swrW gene was found in the majority of contact lens isolates tested. Genetic and biochemical analysis implicate the biosurfactant serratamolide as a hemolysin. This novel hemolysin may contribute to irritation and infections associated with contact lens use. © 2012 Shanks et al

Training the brain to overcome the effect of aging on the human eye

Presbyopia, from the Greek for aging eye, is, like death and taxes, inevitable. Presbyopia causes near vision to degrade with age, affecting virtually everyone over the age of 50. Presbyopia has multiple negative effects on the quality of vision and the quality of life, due to limitations on daily activities – in particular, reading. In addition presbyopia results in reduced near visual acuity, reduced contrast sensitivity, and slower processing speed. Currently available solutions, such as optical corrections, are not ideal for all daily activities. Here we show that perceptual learning (repeated practice on a demanding visual task) results in improved visual performance in presbyopes, enabling them to overcome and/or delay some of the disabilities imposed by the aging eye. This improvement was achieved without changing the optical characteristics of the eye. The results suggest that the aging brain retains enough plasticity to overcome the natural biological deterioration with age

Rapid assessment of visual impairment (RAVI) in marine fishing communities in South India - study protocol and main findings

<p>Abstract</p> <p>Background</p> <p>Reliable data are a pre-requisite for planning eye care services. Though conventional cross sectional studies provide reliable information, they are resource intensive. A novel rapid assessment method was used to investigate the prevalence and causes of visual impairment and presbyopia in subjects aged 40 years and older. This paper describes the detailed methodology and study procedures of Rapid Assessment of Visual Impairment (RAVI) project.</p> <p>Methods</p> <p>A population-based cross-sectional study was conducted using cluster random sampling in the coastal region of Prakasam district of Andhra Pradesh in India, predominantly inhabited by fishing communities. Unaided, aided and pinhole visual acuity (VA) was assessed using a Snellen chart at a distance of 6 meters. The VA was re-assessed using a pinhole, if VA was < 6/12 in either eye. Near vision was assessed using N notation chart binocularly. Visual impairment was defined as presenting VA < 6/18 in the better eye. Presbyopia is defined as binocular near vision worse than N8 in subjects with binocular distance VA of 6/18 or better.</p> <p>Results</p> <p>The data collection was completed in <12 weeks using two teams each consisting of one paramedical ophthalmic personnel and two community eye health workers. The prevalence of visual impairment was 30% (95% CI, 27.6-32.2). This included 111 (7.1%; 95% CI, 5.8-8.4) individuals with blindness. Cataract was the leading cause of visual impairment followed by uncorrected refractive errors. The prevalence of blindness according to WHO definition (presenting VA < 3/60 in the better eye) was 2.7% (95% CI, 1.9-3.5).</p> <p>Conclusion</p> <p>There is a high prevalence of visual impairment in marine fishing communities in Prakasam district in India. The data from this rapid assessment survey can now be used as a baseline to start eye care services in this region. The rapid assessment methodology (RAVI) reported in this paper is robust, quick and has the potential to be replicated in other areas.</p

Pattern of reading eye movements during monovision contact lens wear in presbyopes

Monovision can be used as a method to correct presbyopia with contact lenses (CL) but its effect on reading behavior is still poorly understood. In this study eye movements (EM) were recorded in fifteen presbyopic participants, naïve to monovision, whilst they read arrays of words, non-words, and text passages to assess whether monovision affected their reading. Three conditions were compared, using daily disposable CLs: baseline (near correction in both eyes), conventional monovision (distance correction in the dominant eye, near correction in the non-dominant eye), and crossed monovision (the reversal of conventional monovision). Behavioral measures (reading speed and accuracy) and EM parameters (single fixation duration, number of fixations, dwell time per item, percentage of regressions, and percentage of skipped items) were analyzed. When reading passages, no differences in behavioral and EM measures were seen in any comparison of the three conditions. The number of fixations and dwell time significantly increased for both monovision and crossed monovision with respect to baseline only with word and non-word arrays. It appears that monovision did not appreciably alter visual processing when reading meaningful texts but some limited stress of the EM pattern was observed only with arrays of unrelated or meaningless items under monovision, which require the reader to have more in-depth controlled visual processing

Gender Differences in Publication Output: Towards an Unbiased Metric of Research Performance

We examined the publication records of a cohort of 168 life scientists in the field of ecology and evolutionary biology to assess gender differences in research performance. Clear discrepancies in publication rate between men and women appear very early in their careers and this has consequences for the subsequent citation of their work. We show that a recently proposed index designed to rank scientists fairly is in fact strongly biased against female researchers, and advocate a modified index to assess men and women on a more equitable basis