Relationship between visual dysfunction and retinal changes in patients with multiple sclerosis.

Aim To evaluate structural changes in the retina and their correlation with visual dysfunction in patients with multiple sclerosis. Methods Patients with multiple sclerosis (n = 84) and healthy controls (n = 84) underwent structural eval- uation of the retinal nerve fiber layer, and macular and ganglion cell layer thicknesses using Spectral domain optical coherence tomography (SD-OCT). All subjects underwent high and low contrast visual acuity, color vision (using the Farnsworth and L ´Anthony desaturated D15 color tests), and contrast sensitivity vision using the Pelli Robson chart and CSV 1000E test. Results Macular, retinal nerve fiber layer, and ganglion cell layer thinning was observed in multiple sclerosis patients compared to healthy controls (p<0.05). High- and low-contrast visual acu- ity and contrast sensitivity vision at four different spatial frequencies were significantly reduced in comparison with healthy subjects (p<0.05). Macular, retinal nerve fiber layer and ganglion cell layer measurements correlated with high and low contrast visual acuity, and contrast sensitivity vision. Contrast sensitivity vision was the functional parameter that most strongly correlated with the structural measurements in multiple sclerosis and was associ- ated with ganglion cell layer measurements. The L ´Anthony color vision score (age-cor- rected color confusion index) was associated with macular measurements. Conclusions Patients with multiple sclerosis had visual dysfunction that correlated with structural changes evaluated by SD-OCT. Macular and ganglion cell layer measurements may be good indicators of visual impairment in multiple sclerosis patients

Retinal and Optic Nerve Degeneration in Patients with Multiple Sclerosis Followed up for 5 Years

Purpose: To quantify retinal nerve fiber layer (RNFL) changes in patients with multiple sclerosis (MS) and healthy controls with a 5-year follow-up and to analyze correlations between disability progression and RNFL degeneration. Design: Observational and longitudinal study. Participants: One hundred patients with relapsing-remitting MS and 50 healthy controls. Methods: All participants underwent a complete ophthalmic and electrophysiologic exploration and were re-evaluated annually for 5 years. Main Outcome Measures: Visual acuity (Snellen chart), color vision (Ishihara pseudoisochromatic plates), visual field examination, optical coherence tomography (OCT), scanning laser polarimetry (SLP), and visual evoked potentials. Expanded Disability Status Scale (EDSS) scores, disease duration, treatments, prior optic neuritis episodes, and quality of life (QOL; based on the 54-item Multiple Sclerosis Quality of Life Scale score). Results: Optical coherence tomography (OCT) revealed changes in all RNFL thicknesses in both groups. In the MS group, changes were detected in average thickness and in the mean deviation using the GDx-VCC nerve fiber analyzer (Laser Diagnostic Technologies, San Diego, CA) and in the P100 latency of visual evoked potentials; no changes were detected in visual acuity, color vision, or visual fields. Optical coherence tomography showed greater differences in the inferior and temporal RNFL thicknesses in both groups. In MS patients only, OCT revealed a moderate correlation between the increase in EDSS and temporal and superior RNFL thinning. Temporal RNFL thinning based on OCT results was correlated moderately with decreased QOL. Conclusions: Multiple sclerosis patients exhibit a progressive axonal loss in the optic nerve fiber layer. Retinal nerve fiber layer thinning based on OCT results is a useful marker for assessing MS progression and correlates with increased disability and reduced QOL

Diagnostic capability of a linear discriminant function applied to a novel Spectralis OCT glaucoma-detection protocol

Background Bruch membrane opening–minimum rim width (BMO–MRW) assessment offers a new diagnostic use in glaucoma patients of the Glaucoma Module Premium Edition (GMPE) available for the Spectralis optical coherence tomography (OCT) system. The objective of our research was to evaluate the diagnostic benefits of examining BMO–MRW and peripapillary retinal nerve fibre layer (pRNFL) readings acquired with Spectralis OCT to distinguish between healthy and mild glaucoma patients, comparing those readings with the standard pRNFL application. Moreover, we investigated whether using a particular combination of BMO–MRW and pRNFL parameters with a linear discriminant function (LDF) could further enhance glaucoma diagnosis. Methods One hundred thirty-six eyes from 136 individuals were incorporated into this observational, prospective cross-sectional study: 68 mild primary open-angle glaucoma (POAG) patients according to the Hodapp-Parrish-Anderson criteria (mean deviation between 0 and?-?6?dB) and 68 healthy control subjects selected by Propensity Score Matching. MRW and pRNFL thickness around the disc (diameters: 3.5?mm, 4.1?mm, and 4.7?mm) were obtained using the BMO–MRW protocol, and pRNFL thickness at 3.5?mm was obtained with the standard glaucoma application. The group data were contrasted. One sample was chosen at random to develop the LDF (teaching set: 34 healthy subjects and 34 POAG patients) using a combination of MRW and pRNFL parameters (acquired with the BMO–MRW protocol); the other sample provided a test of how the LDF performed on an independent group (validating set: 34 healthy subjects and 34 POAG patients). The receiver operating curves (ROCs) were plotted for every measurement and contrasted with the proposed LDF. The OCT parameters with the best area under the receiver operating characteristic curve (AUC) were determined. Results Global MRW and pRNFL thicknesses were significantly thinner in the POAG group (p?<? 0.001). The BMO–MRW parameters showed good diagnostic accuracy; the largest AUCs reached 0.875 for the LDF and 0.879 for global RNFL thickness using the standard glaucoma application. There were no statistical differences between the AUCs calculated. Conclusions BMO–MRW parameters show a strong capability to differentiate between mild glaucoma and control eyes. Our LDF based on the new BMO–MRW OCT protocol did not perform better than isolated parameters

Beyond the required LISA free-fall performance: new LISA pathfinder results down to 20 μHz

In the months since the publication of the first results, the noise performance of LISA Pathfinder has improved because of reduced Brownian noise due to the continued decrease in pressure around the test masses, from a better correction of noninertial effects, and from a better calibration of the electrostatic force actuation. In addition, the availability of numerous long noise measurement runs, during which no perturbation is purposely applied to the test masses, has allowed the measurement of noise with good statistics down to 20  μHz. The Letter presents the measured differential acceleration noise figure, which is at (1.74±0.05)  fm s^{-2}/sqrt[Hz] above 2 mHz and (6±1)×10  fm s^{-2}/sqrt[Hz] at 20  μHz, and discusses the physical sources for the measured noise. This performance provides an experimental benchmark demonstrating the ability to realize the low-frequency science potential of the LISA mission, recently selected by the European Space Agency

Sub-femto-g free fall for space-based gravitational wave observatories: LISA pathfinder results

We report the first results of the LISA Pathfinder in-flight experiment. The results demonstrate that two free-falling reference test masses, such as those needed for a space-based gravitational wave observatory like LISA, can be put in free fall with a relative acceleration noise with a square root of the power spectral density of 5.2 ± 0.1 fm s−2/√Hz or (0.54 ± 0.01) × 10−15 g/√Hz, with g the standard gravity, for frequencies between 0.7 and 20 mHz. This value is lower than the LISA Pathfinder requirement by more than a factor 5 and within a factor 1.25 of the requirement for the LISA mission, and is compatible with Brownian noise from viscous damping due to the residual gas surrounding the test masses. Above 60 mHz the acceleration noise is dominated by interferometer displacement readout noise at a level of (34.8 ± 0.3) fm/√Hz, about 2 orders of magnitude better than requirements. At f ≤ 0.5 mHz we observe a low-frequency tail that stays below 12 fm s−2/√Hz down to 0.1 mHz. This performance would allow for a space-based gravitational wave observatory with a sensitivity close to what was originally foreseen for LISA

Micrometeoroid Events in LISA Pathfinder

The zodiacal dust complex, a population of dust and small particles that pervades the Solar System, provides important insight into the formation and dynamics of planets, comets, asteroids, and other bodies. Here we present a new set of data obtained using a novel technique: direct measurements of momentum transfer to a spacecraft from individual particle impacts. This technique is made possible by the extreme precision of the instruments flown on the LISA Pathfinder spacecraft, a technology demonstrator for a future space-based gravitational wave observatory that operated near the first Sun-Earth Lagrange point from early 2016 through Summer of 2017. Using a simple model of the impacts and knowledge of the control system, we show that it is possible to detect impacts and measure properties such as the transferred momentum (related to the particle's mass and velocity), direction of travel, and location of impact on the spacecraft. In this paper, we present the results of a systematic search for impacts during 4348 hours of Pathfinder data. We report a total of 54 candidates with momenta ranging from 0.2$\,\mu\textrm{Ns}$ to 230$\,\mu\textrm{Ns}$. We furthermore make a comparison of these candidates with models of micrometeoroid populations in the inner solar system including those resulting from Jupiter-family comets, Oort-cloud comets, Hailey-type comets, and Asteroids. We find that our measured population is consistent with a population dominated by Jupiter-family comets with some evidence for a smaller contribution from Hailey-type comets. This is in agreement with consensus models of the zodiacal dust complex in the momentum range sampled by LISA Pathfinder.Comment: 22 pages, 14 figures, accepted in Ap

Differential epigenetic reprogramming in response to specific endocrine therapies promotes cholesterol biosynthesis and cellular invasion

Endocrine therapies target the activation of the oestrogen receptor alpha (ERα) via distinct mechanisms, but it is not clear whether breast cancer cells can adapt to treatment using drug-specific mechanisms. Here we demonstrate that resistance emerges via drug-specific epigenetic reprogramming. Resistant cells display a spectrum of phenotypical changes with invasive phenotypes evolving in lines resistant to the aromatase inhibitor (AI). Orthogonal genomics analysis of reprogrammed regulatory regions identifies individual drug-induced epigenetic states involving large topologically associating domains (TADs) and the activation of super-enhancers. AI-resistant cells activate endogenous cholesterol biosynthesis (CB) through stable epigenetic activation in vitro and in vivo. Mechanistically, CB sparks the constitutive activation of oestrogen receptors alpha (ERα) in AI-resistant cells, partly via the biosynthesis of 27-hydroxycholesterol. By targeting CB using statins, ERα binding is reduced and cell invasion is prevented. Epigenomic-led stratification can predict resistance to AI in a subset of ERα-positive patients

A single-oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve outcomes in the COVID-19 disease: the COVID-VIT-D—a randomised multicentre international clinical trial

BACKGROUND: Vitamin D status has been implicated in COVID-19 disease. The objective of the COVID-VIT-D trial was to investigate if an oral bolus of cholecalciferol (100,000 IU) administered at hospital admission influences the outcomes of moderate-severe COVID-19 disease. In the same cohort, the association between baseline serum calcidiol levels with the same outcomes was also analysed. METHODS: The COVID-VIT-D is a multicentre, international, randomised, open label, clinical trial conducted throughout 1 year. Patients older than 18 years with moderate-severe COVID-19 disease requiring hospitalisation were included. At admission, patients were randomised 1:1 to receive a single oral bolus of cholecalciferol (n=274) or nothing (n=269). Patients were followed from admission to discharge or death. Length of hospitalisation, admission to intensive care unit (ICU) and mortality were assessed. RESULTS: In the randomised trial, comorbidities, biomarkers, symptoms and drugs used did not differ between groups. Median serum calcidiol in the cholecalciferol and control groups were 17.0 vs. 16.1 ng/mL at admission and 29.0 vs. 16.4 ng/mL at discharge, respectively. The median length of hospitalisation (10.0 [95%CI 9.0-10.5] vs. 9.5 [95%CI 9.0-10.5] days), admission to ICU (17.2% [95%CI 13.0-22.3] vs. 16.4% [95%CI 12.3-21.4]) and death rate (8.0% [95%CI 5.2-12.1] vs. 5.6% [95%CI 3.3-9.2]) did not differ between the cholecalciferol and control group. In the cohort analyses, the highest serum calcidiol category at admission (>25ng/mL) was associated with lower percentage of pulmonary involvement and better outcomes. CONCLUSIONS: The randomised clinical trial showed the administration of an oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve the outcomes of the COVID-19 disease. A cohort analysis showed that serum calcidiol at hospital admission was associated with outcomes. TRIAL REGISTRATION: COVID-VIT-D trial was authorised by the Spanish Agency for Medicines and Health products (AEMPS) and registered in European Union Drug Regulating Authorities Clinical Trials (EudraCT 2020-002274-28) and in ClinicalTrials.gov ( NCT04552951 )