LC-MS analysis to determine the biodistribution of a polymer coated ilomastat ocular implant

Ilomastat is a matrix metalloproteinase inhibitor (MMPi) that has shown the potential to inhibit scarring (fibrosis) by mediating healing after injury or surgery. A long lasting ocular implantable pharmaceutical formulation of ilomastat is being developed to mediate the healing process to prevent scarring after glaucoma filtration surgery. The ilomastat implant was coated with water permeable and biocompatible phosphoryl choline polymer (PC1059) displayed extended slow release of ilomastat in vitro and in vivo. The ocular distribution of ilomastat from the implant in rabbits at day 30 post surgery was determined by the extraction of ilomastat and its internal standard marimastat from the ocular tissues, plasma, aqueous humour and vitreous fluid followed by capillary-flow liquid chromatography (cap-LC), the column effluent was directed into a triple quadrupole mass spectrometer operating in product scan mode. The lower limits of quantification (LLOQs) were 0.3 pg/μL for ocular fluids and plasma, and 3 pg/mg for ocular tissues. The extraction recoveries were 90-95% for ilomastat and its internal standard from ocular tissues. Ilomastat was found in ocular fluids and tissues at day 30 after surgery. The level of ilomastat was 18 times higher in the aqueous humour than vitreous humour. The concentration ranking of ilomastat in the ocular tissues was sclera > bleb conjunctiva > conjunctiva (rest of the eye) > cornea. Mass spectrometry analysis to confirm the presence of ilomastat in the ocular tissues and fluids at day 30 post-surgery establishes the extended release of ilomastat can be achieved in vivo, which is crucial information for optimisation of the ilomastat coated implant

Acute suprachoroidal haemorrhage post-tenecteplase thrombolysis for myocardial infarction: management considerations

We report a case of a 63-year-old man who received intravenous tenecteplase as thrombolytic therapy for an inferior ST elevation myocardial infarction. Three hours later he complained of blurred vision in the right eye and on examination had sustained a suprachoroidal haemorrhage. With conservative treatment the haemorrhage resolved, leading to a normalisation of visual acuity. To the authors’ knowledge, no case reports exist of this rare complication following intravenous tenecteplase. We discuss implications for further thrombolysis and anticoagulation

Shorter axial length and increased astigmatic refractive error are associated with socio-economic deprivation in an adult UK cohort

Purpose: to evaluate whether socio-economic deprivation is associated with ocular axial length and refractive error in a British cohort.Methods: the study population consisted of 7,652 individuals who provided data to the prospective cataract database at Portsmouth Eye unit, UK over a 4 year period (January 2004 to June 2008). Indices of multiple deprivation (IMD) scores measuring both social and economic domains for each patient’s locality were calculated. The association of these measures of deprivation with axial length and refractive error (astigmatic and spherical) were evaluated using regression analyses after adjusting for age and sex.Results: socio-economically deprived areas (higher IMD scores) were inversely associated with axial lengths and astigmatic refraction. After controlling for age and sex, an inverse linear association was observed between axial length and IMD scores (-0.24mm in highest quintile compared to lowest; 95% confidence intervals: -0.33 to -0.15) and between astigmatic refraction and IMD scores (-0.12 dioptres in highest quintile compared to lowest; 95% confidence intervals: -0.21 to -0.03). There was no association between spherical refraction and IMD scores.Conclusions: axial length and astigmatic refraction were inversely associated with socio-economic deprivation in this population. Identification of the environmental exposures involved may identify reversible risk factors for impaired vision<br/

Characterizing Flocculated Mineral Sediments with Acoustic Backscatter, Using Solid and Hybrid Scattering Models

This study investigated the performance of an acoustic backscatter system (ABS) for the in situ particle characterization of complex wastes. Two sediments were used: a fine, milled calcite that was flocculated with anionic polyacrylamide and naturally flocculated pond sludge. Particles were initially measured independently by light-based techniques to gain size, the coefficient of variation (COV), and fractal dimensions. For acoustic experiments, a bespoke, high-fidelity ABS was employed with 1, 2.25, and 5 MHz probes and a recirculating mixing tank. Initially, the concentration independent attenuation and backscatter coefficients were measured for each system using a robust calibration procedure at multiple concentrations. Comparisons of the total scattering cross-section (χ) and form function (f) were made between the experimental data and two semiempirical models: a Solid Scattering model and a Hybrid model (where the effects of bound fluid are incorporated). Experimental data compared more closely to the Solid Scattering model, as it was assumed scattering was dominated by small, bound “flocculi” rather than the macroscopic structure. However, if the COV was used as a fit parameter, the hybrid model could give equally accurate fits for a range of input aggregate sizes, highlighting that important size and structure information can be gained from the acoustic models if there is some a priori system data. Additionally, dual-frequency inversions were undertaken to measure concentration profiles for various frequency pairs. Here, the lowest frequency pair gave the best performance (with accurate measurements in the range of 2–35 g·L–1) as interparticle scattering was lowest

Open data from the first and second observing runs of Advanced LIGO and Advanced Virgo

Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software

Search for intermediate-mass black hole binaries in the third observing run of Advanced LIGO and Advanced Virgo

International audienceIntermediate-mass black holes (IMBHs) span the approximate mass range 100−105 M⊙, between black holes (BHs) that formed by stellar collapse and the supermassive BHs at the centers of galaxies. Mergers of IMBH binaries are the most energetic gravitational-wave sources accessible by the terrestrial detector network. Searches of the first two observing runs of Advanced LIGO and Advanced Virgo did not yield any significant IMBH binary signals. In the third observing run (O3), the increased network sensitivity enabled the detection of GW190521, a signal consistent with a binary merger of mass ∼150 M⊙ providing direct evidence of IMBH formation. Here, we report on a dedicated search of O3 data for further IMBH binary mergers, combining both modeled (matched filter) and model-independent search methods. We find some marginal candidates, but none are sufficiently significant to indicate detection of further IMBH mergers. We quantify the sensitivity of the individual search methods and of the combined search using a suite of IMBH binary signals obtained via numerical relativity, including the effects of spins misaligned with the binary orbital axis, and present the resulting upper limits on astrophysical merger rates. Our most stringent limit is for equal mass and aligned spin BH binary of total mass 200 M⊙ and effective aligned spin 0.8 at 0.056 Gpc−3 yr−1 (90% confidence), a factor of 3.5 more constraining than previous LIGO-Virgo limits. We also update the estimated rate of mergers similar to GW190521 to 0.08 Gpc−3 yr−1.Key words: gravitational waves / stars: black holes / black hole physicsCorresponding author: W. Del Pozzo, e-mail: [email protected]† Deceased, August 2020