Does eye examination order for standard automated perimetry matter?

PURPOSE: In spite of faster examination procedures, visual field (VF) results are potentially influenced by fatigue. We use large-scale VF data collected from clinics to test the hypothesis that perimetric fatigue effects are greater in the eye examined second. METHODS: Series of six Humphrey Swedish Interactive Testing Algorithm (SITA) VFs from 6901 patients were retrospectively extracted from a VF database from four different glaucoma clinics. Mean deviation (MD) was compared between first and second tested eyes. A surrogate measure of longitudinal MD variability over time was estimated from errors using linear regression of MD against time then compared between first and second tested eye. RESULTS: Right eye VF was tested consistently first throughout in 6320 (91.6%) patients. Median (interquartile range; IQR) MD in the first tested (right) eye and second tested (left) eye was -2.57 (-6.15, -0.58) dB and -2.70 (-6.34, -0.80) dB respectively (median reduction VF sensitivity of 0.13 dB; p < 0.001). Median (IQR) increase in our surrogate measure of longitudinal MD variability in the second eye tested was 3% (-43%, 50%); this effect was not associated with patient age or rest time between examinations. CONCLUSION: Statistically significant perimetric fatigue effects manifest on average in the second eye tested in routine clinics using Humphrey Field Analyzer SITA examinations. However, the average effects were very small and there was enormous variation among patients. We recommend starting with a right eye examination so that any perimetric fatigue effects, if they exist in an individual, will be as constant as possible from visit to visit

Nucleation at the DNA supercoiling transition

Twisting DNA under a constant applied force reveals a thermally activated transition into a state with a supercoiled structure known as a plectoneme. Using transition state theory, we predict the rate of this plectoneme nucleation to be of order 10^4 Hz. We reconcile this with experiments that have measured hopping rates of order 10 Hz by noting that the viscosity of the bead used to manipulate the DNA limits the measured rate. We find that the intrinsic bending caused by disorder in the base-pair sequence is important for understanding the free energy barrier that governs the transition. Both analytic and numerical methods are used in the calculations. We provide extensive details on the numerical methods for simulating the elastic rod model with and without disorder.Comment: 18 pages, 15 figure

Patients' preferences for the management of non-metastatic prostate cancer: discrete choice experiment

Objective To establish which attributes of conservative treatments for prostate cancer are most important to men. Design Discrete choice experiment. Setting Two London hospitals. Participants 129 men with non-metastatic prostate cancer, mean age 70 years; 69 of 118 (58%) with T stage 1 or 2 cancer at diagnosis. Main outcome measures Men's preferences for, and trade-offs between, the attributes of diarrhoea, hot flushes, ability to maintain an erection, breast swelling or tenderness, physical energy, sex drive, life expectancy, and out of pocket expenses. Results The men's responses to changes in attributes were all statistically significant. When asked to assume a starting life expectancy of five years, the men were willing to make trade-offs between life expectancy and side effects. On average, they were most willing to give up life expectancy to avoid limitations in physical energy (mean three months) and least willing to trade life expectancy to avoid hot flushes (mean 0.6 months to move from a moderate to mild level or from mild to none). Conclusions Men with prostate cancer are willing to participate in a relatively complex exercise that weighs up the advantages and disadvantages of various conservative treatments for their condition. They were willing to trade off some life expectancy to be relieved of the burden of troublesome side effects such as limitations in physical energy

Requirements for Catalysis in Cre Recombinase

Cre recombinase, a member of the tyrosine recombinase (YR) family of site-specific recombinases catalyzes DNA rearrangements using phosphoryl transfer chemistry that is identical to that used by the type IB topoisomerases (TopIBs). In this dissertation, the requirements for YR catalysis and the relationship between the YRs and the TopIBs are explored. I have analyzed the in vivo and in vitro recombination activities of all possible substitutions of the seven active site residues in Cre recombinase. To facilitate the interpretation mutant activities, I also determined the structure of a vanadate transition state mimic for the Cre-loxP reaction that allows for a comparison with similar structures from the related TopIBs. The results demonstrate that active site residues shared by the TopIBs are most sensitive to substitution. Two of the conserved active site residues in YRs have no equivalent in TopIBs. I have concluded that Glu176 and His289 in Cre evolved to have functional roles in site-specific recombination, that are unnecessary for relaxation by TopIB. His289 is not essential for cleavage of DNA, but accelerates water mediated hydrolysis of the 3\u27-phosphotyrosine covalent intermediate. Glu176 serves a structural role in facilitating the activation of Cre for cleavage by helping position the general acid, K201 in the active site. These residues may compensate for activity lost during the evolution of allosteric regulation required for recombination. Examination of two regions involved in protein:protein interactions in the Cre-DNA tetramer complex has led to the characterization of two modes of allosteric regulation. The first involves a C-terminal helix (hN), which binds in the pocket of a neighboring Cre monomer to serve as a regulatory switch by acting as a tether to position the tyrosine nucleophile (Y324). The second regulatory module involves the mobile β2-β3 hairpin carrying the general acid, K201. This hairpin must form synapsis dependent contacts to efficiently position K201 near O5\u27 of the scissile phosphate. Cre has evolved to modulate the positions of critical residues for catalysis, which is an effective and highly sensitive mechanism of regulation of catalysis not shared by TopIBs

Progression from ocular hypertension to visual field loss in the English hospital eye service

Background There are more than one million National Health Service visits in England and Wales each year for patients with glaucoma or ocular hypertension (OHT). With the ageing population and an increase in optometric testing, the economic burden of glaucoma-related visits is predicted to increase. We examined the conversion rates of OHT to primary open-angle glaucoma (POAG) in England and assessed factors associated with risk of conversion. Methods Electronic medical records of 45 309 patients from five regionally different glaucoma clinics in England were retrospectively examined. Conversion to POAG from OHT was defined by deterioration in visual field (two consecutive tests classified as stage 1 or worse as per the glaucoma staging system 2). Cox proportional hazards models were used to examine factors (age, sex, treatment status and baseline intraocular pressure (IOP)) associated with conversion. Results The cumulative risk of conversion to POAG was 17.5% (95% CI 15.4% to 19.6%) at 5 years. Older age (HR 1.35 per decade, 95% CI 1.22 to 1.50, p<0.001) was associated with a higher risk of conversion. IOP-lowering therapy (HR 0.45, 95% CI 0.35 to 0.57, p<0.001) was associated with a lower risk of conversion. Predicted 5-year conversion rates for treated and untreated groups were 14.0% and 26.9%, respectively. Conclusion Less than one-fifth of OHT patients managed in glaucoma clinics in the UK converted to POAG over a 5-year period, suggesting many patients may require less intensive follow-up. Our study provides real-world evidence for the efficacy of current management (including IOP-lowering treatment) at reducing risk of conversion

A Positive-Weight Next-to-Leading-Order Monte Carlo for e+e- Annihilation to Hadrons

We apply the positive-weight Monte Carlo method of Nason for simulating QCD processes accurate to Next-To-Leading Order to the case of e+e- annihilation to hadrons. The method entails the generation of the hardest gluon emission first and then subsequently adding a `truncated' shower before the emission. We have interfaced our result to the Herwig++ shower Monte Carlo program and obtained better results than those obtained with Herwig++ at leading order with a matrix element correction.Comment: 21 pages, 11 figures, 2 tables Reason for replacement: minor corrections, typos and 1 changed referenc

Capacitor-type micrometeoroid detectors

The metal oxide semiconductor (MOS) capacitor micrometeroid detector consists of a thin dielectric capacitor fabricated on a silicon wafer. In operation, the device is charged to a voltage level sufficiently near breakdown that micrometeoroid impacts will cause dielectric deformation or heating and subsequent arc-over at the point of impact. Each detector is capable of recording multiple impacts because of the self-healing characteristics of the device. Support instrumentation requirements consist of a voltage source and pulse counters that monitor the pulse of recharging current following every impact. An investigation has been conducted in which 0.5 to 5 micron diameter carbonized iron spheres traveling at velocities of 4 to 10 Km/sec were impacted on to detectors with either a dielectric thickness of 0.4 or 1.0 micron. This study demonstrated that an ion microprobe tuned to sufficiently high resolution can detect Fe remaining on the detector after the impact. Furthermore, it is also possible to resolve Fe ion images free of mass interferences from Si, for example, giving its spatial distribution after impact. Specifically this technique has shown that significant amounts of impacting particles remain in the crater and near it which can be analyzed for isotopic content. Further testing and calibration could lead to quantitive analysis. This study has shown that the capacitor type micrometeroid detector is capable of not only time and flux measurements but can also be used for isotopic analysis

Transient reflectance of photoexcited Cd\u3csub\u3e3\u3c/sub\u3eAs\u3csub\u3e2\u3c/sub\u3e

We report ultrafast transient-grating measurements of crystals of the three-dimensional Dirac semimetal cadmium arsenide, Cd3As2, at both room temperature and 80 K. After photoexcitation with 1.5-eV photons, charge-carriers relax by two processes, one of duration 500 fs and the other of duration 3.1 ps. By measuring the complex phase of the change in reflectance, we determine that the faster signal corresponds to a decrease in absorption, and the slower signal to a decrease in the light\u27s phase velocity, at the probe energy. We attribute these signals to electrons\u27 filling of phase space, first near the photon energy and later at lower energy. We attribute their decay to cooling by rapid emission of optical phonons, then slower emission of acoustic phonons. We also present evidence that both the electrons and the lattice are strongly heated

Explaining the entropy excess in clusters and groups of galaxies without additional heating

The X-ray luminosity and temperature of clusters and groups of galaxies do not scale in a self-similar manner. This has often been interpreted as a sign that the intracluster medium has been substantially heated by non-gravitational sources. In this paper, we propose a simple model which, instead, uses the properties of galaxy formation to explain the observations. Drawing on available observations, we show that there is evidence that the efficiency of galaxy formation was higher in groups than in clusters. If confirmed, this would deplete the low-entropy gas in groups, increase their central entropy and decrease their X-ray luminosity. A simple, empirical, hydrostatic model appears to match both the luminosity-temperature relation of clusters and properties of their internal structure as well.Comment: 5 pages, 4 figures, accepted in ApJL; added one reference, otherwise unchange