Effectiveness of platelet function analysis-guided aspirin and/or clopidogrel therapy in preventing secondary stroke : A systematic review and meta-analysis

Antiplatelet medications such as aspirin and clopidogrel are used following thrombotic stroke or transient ischemic attack (TIA) to prevent a recurrent stroke. However, the antiplatelet treatments fail frequently, and patients experience recurrent stroke. One approach to lower the rates of recurrence may be the individualized antiplatelet therapies (antiplatelet therapy modification (ATM)) based on the results of platelet function analysis (PFA). This review was undertaken to gather and analyze the evidence about the effectiveness of such approaches. We searched Medline, CINAHL, Embase, Web of Science, and Cochrane databases up to 7 January 2020. Two observational studies involving 1136 patients were included. The overall effects of PFA-based ATM on recurrent strokes (odds ratio (OR) 1.05; 95% confidence interval (CI) 0.69 to 1.58), any bleeding risk (OR 1.39; 95% CI 0.92 to 2.10) or death hazard from any cause (OR 1.19; 95% CI 0.62 to 2.29) were not significantly different from the standard antiplatelet therapy without ATM. The two studies showed opposite effects of PFA-guided ATM on the recurrent strokes in aspirin non-responders, leading to an insignificant difference in the subgroup meta-analysis (OR 1.59; 95% CI 0.07 to 33.77), while the rates of any bleeding events (OR 1.04; 95% CI 0.49 to 2.17) or death from any cause (OR 1.17; 95% CI 0.41 to 3.35) were not significantly different between aspirin non-responders with ATM and those without ATM. There is a need for large, randomized controlled trials which account for potential confounders such as ischemic stroke subtypes, technical variations in the testing protocols, patient adherence to therapy and pharmacogenetic differences

The Effect of Galactic Properties on the Escape Fraction of Ionizing Photons

The escape fraction, fesc, of ionizing photons from early galaxies is a crucial parameter for determining whether the observed galaxies at z > 6 are able to reionize the high-redshift intergalactic medium. Previous attempts to measure fesc have found a wide range of values, varying from less than 0.01 to nearly 1. Rather than finding a single value of fesc, we clarify through modeling how internal properties of galaxies affect fesc through the density and distribution of neutral hydrogen within the galaxy, along with the rate of ionizing photons production. We find that the escape fraction depends sensitively on the covering factor of clumps, along with the density of the clumped and interclump medium. One must therefore be cautious when dealing with an inhomogeneous medium. Fewer, high-density clumps lead to a greater escape fraction than more numerous low-density clumps. When more ionizing photons are produced in a starburst, fesc increases, as photons escape more readily from the gas layers. Large variations in the predicted escape fraction, caused by differences in the hydrogen distribution, may explain the large observed differences in fesc among galaxies. Values of fesc must also be consistent with the reionization history. High-mass galaxies alone are unable to reionize the universe, because fesc > 1 would be required. Small galaxies are needed to achieve reionization, with greater mean escape fraction in the past.Comment: 27 pages, 8 figures. Accepted to ApJ. v2: Improvements based on referee's comment

WISE/NEOWISE observations of Active Bodies in the Main Belt

We report results based on mid-infrared photometry of 5 active main belt objects (AMBOs) detected by the Wide-field Infrared Survey Explorer (WISE) spacecraft. Four of these bodies, P/2010 R2 (La Sagra), 133P/Elst-Pizarro, (596) Scheila, and 176P/LINEAR, showed no signs of activity at the time of the observations, allowing the WISE detections to place firm constraints on their diameters and albedos. Geometric albedos were in the range of a few percent, and on the order of other measured comet nuclei. P/2010 A2 was observed on April 2-3, 2010, three months after its peak activity. Photometry of the coma at 12 and 22 {\mu}m combined with ground-based visible-wavelength measurements provides constraints on the dust particle mass distribution (PMD), dlogn/dlogm, yielding power-law slope values of {\alpha} = -0.5 +/- 0.1. This PMD is considerably more shallow than that found for other comets, in particular inbound particle fluence during the Stardust encounter of comet 81P/Wild 2. It is similar to the PMD seen for 9P/Tempel 1 in the immediate aftermath of the Deep Impact experiment. Upper limits for CO2 & CO production are also provided for each AMBO and compared with revised production numbers for WISE observations of 103P/Hartley 2.Comment: 32 Pages, including 5 Figure

A Kinetic Analysis of The Inhibition of FOX-4 β-Lactamase, A Plasmid-Mediated AmpC Cephalosporinase, By Monocyclic β-lactams and Carbapenems

Abstract: Objectives: Class C β-lactamases are prevalent among Enterobacteriaceae; however, these enzymes are resistant to inactivation by commercially available β-lactamase inhibitors. In order to find novel scaffolds to inhibit class C β-lactamases, the comparative efficacy of monocyclic β-lactam antibiotics (aztreonam and the siderophore monosulfactam BAL30072), the bridged monobactam β-lactamase inhibitor BAL29880, and carbapenems (imipenem, meropenem, doripenem and ertapenem) were tested in kinetic assays against FOX-4, a plasmid-mediated class C β-lactamase (pmAmpC). Methods: The FOX-4 β-lactamase was purified. Steady-state kinetics, electrospray ionization mass spectrometry (ESI-MS) and ultraviolet difference (UVD) spectroscopy were conducted using the β-lactam scaffolds described. Results: The Ki values for the monocyclic β-lactams against FOX-4 β-lactamase were 0.04 ± 0.01 μM (aztreonam) and 0.66 ± 0.03 μM (BAL30072), and the Ki value for the bridged monobactam BAL29880 was 8.9 ± 0.5 μM. For carbapenems, the Ki values ranged from 0.27 ± 0.05 μM (ertapenem) to 2.3 ± 0.3 μM (imipenem). ESI-MS demonstrated the formation of stable covalent adducts when the monocyclic β-lactams and carbapenems were reacted with FOX-4 β-lactamase. UVD spectroscopy suggested the appearance of different chromophoric intermediates. Conclusions: Monocyclic β-lactam and carbapenem antibiotics are effective mechanism-based inhibitors of FOX-4 β-lactamase, a clinically important pmAmpC, and provide stimulus for the development of new inhibitors to inactivate plasmidic and chromosomal class C β-lactamases

A dynamic model of the eye nystagmus response to high magnetic fields

It was recently shown that high magnetic fields evoke nystagmus in human subjects with functioning vestibular systems. The proposed mechanism involves interaction between ionic currents in the endolymph of the vestibular labyrinth and the static magnetic field. This results in a Lorentz force that causes endolymph flow to deflect the cupulae of the semi-circular canals to evoke a vestibular-ocular reflex (VOR). This should be analogous to stimulation by angular acceleration or caloric irrigation. We made measurements of nystagmus slow-phase velocities in healthy adults experiencing variable magnetic field profiles of up to 7 Tesla while supine on a bed that could be moved smoothly into the bore of an MRI machine. The horizontal slow-phase velocity data were reliably modelled by a linear transfer function incorporating a low-pass term and a high-pass adaptation term. The adaptation time constant was estimated at 39.3 s from long-exposure trials. When constrained to this value, the low-pass time constant was estimated at 13.6 3.6 s (to 95% confidence) from both short and long exposure trials. This confidence interval overlaps with values obtained previously using angular acceleration and caloric stimulation. Hence it is compatible with endolymph flow causing a cupular deflection and therefore supports the hypothesis that the Lorentz force is a likely transduction mechanism of the magnetic-field evoked VOR

The NEOWISE-Discovered Comet Population and the CO+CO_2 production rates

The 163 comets observed during the WISE/NEOWISE prime mission represent the largest infrared survey to date of comets, providing constraints on dust, nucleus size, and CO + CO_2 production. We present detailed analyses of the WISE/NEOWISE comet discoveries, and discuss observations of the active comets showing 4.6 μm band excess. We find a possible relation between dust and CO + CO_2 production, as well as possible differences in the sizes of long and short period comet nuclei

Implications of MMP9 for Blood Brain Barrier Disruption and Hemorrhagic Transformation Following Ischemic Stroke.

Numerous studies have documented increases in matrix metalloproteinases (MMPs), specifically MMP-9 levels following stroke, with such perturbations associated with disruption of the blood brain barrier (BBB), increased risk of hemorrhagic complications, and worsened outcome. Despite this, controversy remains as to which cells release MMP-9 at the normal and pathological BBB, with even less clarity in the context of stroke. This may be further complicated by the influence of tissue plasminogen activator (tPA) treatment. The aim of the present review is to examine the relationship between neutrophils, MMP-9 and tPA following ischemic stroke to elucidate which cells are responsible for the increases in MMP-9 and resultant barrier changes and hemorrhage observed following stroke

A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.

Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing complaint in childhood (discovery cohort) and in 84 probands with recessive retinal disease (replication cohort). Detailed phenotyping, including retinal imaging and audiological assessment, was performed in individuals with two likely disease-causing USH2A variants. Further genetic testing, including screening for a deep-intronic disease-causing variant and large deletions/duplications, was performed in those with one likely disease-causing change. Overall, 23 of 186 probands (discovery cohort) were found to harbour two likely disease-causing variants in USH2A. Some of these variants were predominantly associated with nonsyndromic retinal degeneration ('retinal disease-specific'); these included the common c.2276 G>T, p.(Cys759Phe) mutation and five additional variants: c.2802 T>G, p.(Cys934Trp); c.10073 G>A, p.(Cys3358Tyr); c.11156 G>A, p.(Arg3719His); c.12295-3 T>A; and c.12575 G>A, p.(Arg4192His). An allelic hierarchy was observed in the discovery cohort and confirmed in the replication cohort. In nonsyndromic USH2A disease, retinopathy was consistent with retinitis pigmentosa and the audiological phenotype was variable. USH2A retinopathy is a common cause of nonsyndromic recessive retinal degeneration and has a different mutational spectrum to that observed in Usher syndrome. The following model is proposed: the presence of at least one 'retinal disease-specific' USH2A allele in a patient with USH2A-related disease results in the preservation of normal hearing. Careful genotype-phenotype studies such as this will become increasingly important, especially now that high-throughput sequencing is widely used in the clinical setting.European Journal of Human Genetics advance online publication, 4 February 2015; doi:10.1038/ejhg.2014.283

Effects of the sources of reionization on 21-cm redshift-space distortions

The observed 21 cm signal from the epoch of reionization will be distorted along the line of sight by the peculiar velocities of matter particles. These redshift-space distortions will affect the contrast in the signal and will also make it anisotropic. This anisotropy contains information about the cross-correlation between the matter density field and the neutral hydrogen field, and could thus potentially be used to extract information about the sources of reionization. In this paper, we study a collection of simulated reionization scenarios assuming different models for the sources of reionization. We show that the 21 cm anisotropy is best measured by the quadrupole moment of the power spectrum. We find that, unless the properties of the reionization sources are extreme in some way, the quadrupole moment evolves very predictably as a function of global neutral fraction. This predictability implies that redshift-space distortions are not a very sensitive tool for distinguishing between reionization sources. However, the quadrupole moment can be used as a model-independent probe for constraining the reionization history. We show that such measurements can be done to some extent by first-generation instruments such as LOFAR, while the SKA should be able to measure the reionization history using the quadrupole moment of the power spectrum to great accuracy