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

Matrix Quantization of Turbulence

Based on our recent work on Quantum Nambu Mechanics \cite{af2}, we provide an explicit quantization of the Lorenz chaotic attractor through the introduction of Non-commutative phase space coordinates as Hermitian $N \times N$ matrices in $R^{3}$. For the volume preserving part, they satisfy the commutation relations induced by one of the two Nambu Hamiltonians, the second one generating a unique time evolution. Dissipation is incorporated quantum mechanically in a self-consistent way having the correct classical limit without the introduction of external degrees of freedom. Due to its volume phase space contraction it violates the quantum commutation relations. We demonstrate that the Heisenberg-Nambu evolution equations for the Matrix Lorenz system develop fast decoherence to N independent Lorenz attractors. On the other hand there is a weak dissipation regime, where the quantum mechanical properties of the volume preserving non-dissipative sector survive for long times.Comment: 14 pages, Based on invited talks delivered at: Fifth Aegean Summer School, "From Gravity to Thermal Gauge theories and the AdS/CFT Correspondance", September 2009, Milos, Greece; the Intern. Conference on Dynamics and Complexity, Thessaloniki, Greece, 12 July 2010; Workshop on "AdS4/CFT3 and the Holographic States of Matter", Galileo Galilei Institute, Firenze, Italy, 30 October 201

Scaling and synchronization in a ring of diffusively coupled nonlinear oscillators

Chaos synchronization in a ring of diffusively coupled nonlinear oscillators driven by an external identical oscillator is studied. Based on numerical simulations we show that by introducing additional couplings at $(mN_c+1)$-th oscillators in the ring, where $m$ is an integer and $N_c$ is the maximum number of synchronized oscillators in the ring with a single coupling, the maximum number of oscillators that can be synchronized can be increased considerably beyond the limit restricted by size instability. We also demonstrate that there exists an exponential relation between the number of oscillators that can support stable synchronization in the ring with the external drive and the critical coupling strength $\epsilon_c$ with a scaling exponent $\gamma$. The critical coupling strength is calculated by numerically estimating the synchronization error and is also confirmed from the conditional Lyapunov exponents (CLEs) of the coupled systems. We find that the same scaling relation exists for $m$ couplings between the drive and the ring. Further, we have examined the robustness of the synchronous states against Gaussian white noise and found that the synchronization error exhibits a power-law decay as a function of the noise intensity indicating the existence of both noise-enhanced and noise-induced synchronizations depending on the value of the coupling strength $\epsilon$. In addition, we have found that $\epsilon_c$ shows an exponential decay as a function of the number of additional couplings. These results are demonstrated using the paradigmatic models of R\"ossler and Lorenz oscillators.Comment: Accepted for Publication in Physical Review

Direct transition to high-dimensional chaos through a global bifurcation

In the present work we report on a genuine route by which a high-dimensional (with d>4) chaotic attractor is created directly, i.e., without a low-dimensional chaotic attractor as an intermediate step. The high-dimensional chaotic set is created in a heteroclinic global bifurcation that yields an infinite number of unstable tori.The mechanism is illustrated using a system constructed by coupling three Lorenz oscillators. So, the route presented here can be considered a prototype for high-dimensional chaotic behavior just as the Lorenz model is for low-dimensional chaos.Comment: 7 page

Auditing service delivery in glaucoma clinics using visual field records: A feasibility study

© 2019 Author(s). Objective This study aimed to demonstrate that large-scale visual field (VF) data can be extracted from electronic medical records (EMRs) and to assess the feasibility of calculating metrics from these data that could be used to audit aspects of service delivery of glaucoma care. Method and analysis Humphrey visual field analyser (HFA) data were extracted from Medisoft EMRs from five regionally different clinics in England in November 2015, resulting in 602 439 records from 73 994 people. Target patients were defined as people in glaucoma clinics with measurable and sustained VF loss in at least one eye (HFA mean deviation (MD) outside normal limits ≥2 VFs). Metrics for VF reliability, stage of VF loss at presentation, speed of MD loss, predicted loss of sight years (bilateral VF impairment) and frequency of VFs were calculated. Results One-third of people (34.8%) in the EMRs had measurable and repeatable VF loss and were subject to analyses (n=25 760 patients). Median (IQR) age and presenting MD in these patients were 71 (61, 78) years and -6 (-10, -4) dB, respectively. In 19 264 patients with >4 years follow-up, median (IQR) MD loss was -0.2 (-0.8, 0.3) dB/year and median (IQR) intervals between VF examinations was 11 (8, 16) months. Metrics predicting loss of sight years and reliability of examinations varied between centres (p<0.001). Conclusion This study illustrates the feasibility of assessing aspects of health service delivery in glaucoma clinics through analysis of VF databases. Proposed metrics could be useful for blindness prevention from glaucoma in secondary care centres

Bacillus Calmette-Guérin Induces PD-L1 Expression on Antigen-Presenting Cells via Autocrine and Paracrine Interleukin-STAT3 Circuits

Bacillus Calmette-Guérin (BCG) is the only licensed vaccine for tuberculosis (TB), and is also used as an immunotherapy for bladder cancer and other malignancies due to its immunostimulatory properties. Mycobacteria spp., however, are well known for their numerous immune evasion mechanisms that limit the true potential of their therapeutic use. One such major mechanism is the induction of programmed death ligand-1 (PD-L1), which mitigates adaptive immune responses. Here, we sought to unravel the molecular pathways behind PD-L1 up-regulation on antigen-presenting cells (APCs) by BCG. We found that infection of APCs with BCG induced PD-L1 up-regulation, but that this did not depend on direct infection, suggesting a soluble mediator for this effect. BCG induced potent quantities of IL-6 and IL-10, and the downstream transcription factor STAT3 was hyper-phosphorylated. Intracellular analyses revealed that levels of PD-L1 molecules were associated with the STAT3 phosphorylation state, suggesting a causal link. Neutralisation of the IL-6 or IL-10 cytokine receptors dampened STAT3 phosphorylation and BCG-mediated up-regulation of PD-L1 on APCs. Pharmacological inhibition of STAT3 achieved the same effect, confirming an autocrine-paracrine cytokine loop as a mechanism for BCG-mediated up-regulation of PD-L1. Finally, an in vivo immunisation model showed that BCG vaccination under PD-L1 blockade could enhance antigen-specific memory CD4 T-cell responses. These novel findings could lead to refinement of BCG as both a vaccine for infectious disease and as a cancer immunotherapy

Turbulent and Transitional Modeling of Drag on Oceanographic Measurement Devices

Computational fluid dynamic techniques have been applied to the determination of drag on oceanographic devices (expendable bathythermographs). Such devices, which are used to monitor changes in ocean heat content, provide information that is dependent on their drag coefficient. Inaccuracies in drag calculations can impact the estimation of ocean heating associated with global warming. Traditionally, ocean-heating information was based on experimental correlations which related the depth of the device to the fall time. The relation of time-depth is provided by a fall-rate equation (FRE). It is known that FRE depths are reasonably accurate for ocean environments that match the experiments from which the correlations were developed. For other situations, use of the FRE may lead to depth errors that preclude XBTs as accurate oceanographic devices. Here, a CFD approach has been taken which provides drag coefficients that are used to predict depths independent of an FRE

Analysis of the shearing instability in nonlinear convection and magnetoconvection

Numerical experiments on two-dimensional convection with or without a vertical magnetic field reveal a bewildering variety of periodic and aperiodic oscillations. Steady rolls can develop a shearing instability, in which rolls turning over in one direction grow at the expense of rolls turning over in the other, resulting in a net shear across the layer. As the temperature difference across the fluid is increased, two-dimensional pulsating waves occur, in which the direction of shear alternates. We analyse the nonlinear dynamics of this behaviour by first constructing appropriate low-order sets of ordinary differential equations, which show the same behaviour, and then analysing the global bifurcations that lead to these oscillations by constructing one-dimensional return maps. We compare the behaviour of the partial differential equations, the models and the maps in systematic two-parameter studies of both the magnetic and the non-magnetic cases, emphasising how the symmetries of periodic solutions change as a result of global bifurcations. Much of the interesting behaviour is associated with a discontinuous change in the leading direction of a fixed point at a global bifurcation; this change occurs when the magnetic field is introduced