Portable dynamic fundus instrument

A portable diagnostic image analysis instrument is disclosed for retinal funduscopy in which an eye fundus image is optically processed by a lens system to a charge coupled device (CCD) which produces recordable and viewable output data and is simultaneously viewable on an electronic view finder. The fundus image is processed to develop a representation of the vessel or vessels from the output data

Organic-walled tentaculids of Late Devonian (Frasnian) deposits of the Appalachian and Michigan Basins, Laurussia (NY, MI, OH)

This is the first report of organic-walled tentaculid remains from Givetian through Frasnian age deposits of the Michigan and Appalachian Basins in western Laurussia. This adds to the geographic scope of similar finds that have been described from the Frasnian through the Famennian in eastern Laurussia. However, those previous specimens were retrieved through palynological preparations and more closely resemble sheath structures rather than the full forms found herein, which were retrieved through complete maceration with ammonium surfactants

The relationship between transmission time and clustering methods in Mycobacterium tuberculosis epidemiology

YesBackground: Tracking recent transmission is a vital part of controlling widespread pathogens such as Mycobacterium tuberculosis. Multiple methods with specific performance characteristics exist for detecting recent transmission chains, usually by clustering strains based on genotype similarities. With such a large variety of methods available, informed selection of an appropriate approach for determining transmissions within a given setting/time period is difficult. Methods: This study combines whole genome sequence (WGS) data derived from 324 isolates collected 2005–2010 in Kinshasa, Democratic Republic of Congo (DRC), a high endemic setting, with phylodynamics to unveil the timing of transmission events posited by a variety of standard genotyping methods. Clustering data based on Spoligotyping, 24-loci MIRU-VNTR typing, WGS based SNP (Single Nucleotide Polymorphism) and core genome multi locus sequence typing (cgMLST) typing were evaluated. Findings: Our results suggest that clusters based on Spoligotyping could encompass transmission events that occurred almost 200 years prior to sampling while 24-loci-MIRU-VNTR often represented three decades of transmission. Instead, WGS based genotyping applying low SNP or cgMLST allele thresholds allows for determination of recent transmission events, e.g. in timespans of up to 10 years for a 5 SNP/allele cut-off. Interpretation: With the rapid uptake of WGS methods in surveillance and outbreak tracking, the findings obtained in this study can guide the selection of appropriate clustering methods for uncovering relevant transmission chains within a given time-period. For high resolution cluster analyses, WGS-SNP and cgMLST based analyses have similar clustering/timing characteristics even for data obtained from a high incidence setting.ERC grant [INTERRUPTB; no. 311725] to BdJ, FG and CJM; an ERC grant to TS [PhyPD; no. 335529]; an FWO PhD fellowship to PM [grant number 1141217N]; the Leibniz Science Campus EvolLUNG for MM and SN; the German Centre for Infection Research (DZIF) for TAK, MM, CU, PB and SN; a SNF SystemsX grant (TBX) to JP and TS and a Marie Heim-Vögtlin fellowship granted to DK by the Swiss National Science Foundation. The computational resources and services used in this work were provided by the VSC (Flemish Supercomputer Center), funded by the Research Foundation - Flanders (FWO) and the Flemish Government – department EWI

Proton Magnetic Resonance Spectroscopy Lactate/N-Acetylaspartate Within 48 h Predicts Cell Death Following Varied Neuroprotective Interventions in a Piglet Model of Hypoxia–Ischemia With and Without Inflammation-Sensitization

Despite therapeutic hypothermia, survivors of neonatal encephalopathy have high rates of adverse outcome. Early surrogate outcome measures are needed to speed up the translation of neuroprotection trials. Thalamic lactate (Lac)/N-acetylaspartate (NAA) peak area ratio acquired with proton (1H) magnetic resonance spectroscopy (MRS) accurately predicts 2-year neurodevelopmental outcome. We assessed the relationship between MR biomarkers acquired at 24–48 h following injury with cell death and neuroinflammation in a piglet model following various neuroprotective interventions. Sixty-seven piglets with hypoxia–ischemia, hypoxia alone, or lipopolysaccharide (LPS) sensitization were included, and neuroprotective interventions were therapeutic hypothermia, melatonin, and magnesium. MRS and diffusion-weighted imaging (DWI) were acquired at 24 and 48 h. At 48 h, experiments were terminated, and immunohistochemistry was assessed. There was a correlation between Lac/NAA and overall cell death [terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)] [mean Lac/NAA basal ganglia and thalamus (BGT) voxel r = 0.722, white matter (WM) voxel r = 0.784, p < 0.01] and microglial activation [ionized calcium-binding adapter molecule 1 (Iba1)] (BGT r = −0.786, WM r = −0.632, p < 0.01). Correlation with marker of caspase-dependent apoptosis [cleaved caspase 3 (CC3)] was lower (BGT r = −0.636, WM r = −0.495, p < 0.01). Relation between DWI and TUNEL was less robust (mean diffusivity BGT r = −0.615, fractional anisotropy BGT r = 0.523). Overall, Lac/NAA correlated best with cell death and microglial activation. These data align with clinical studies demonstrating Lac/NAA superiority as an outcome predictor in neonatal encephalopathy (NE) and support its use in preclinical and clinical neuroprotection studies

Functional plasticity in the respiratory drive to thoracic motoneurons in the segment above a chronic lateral spinal cord lesion

A previous neurophysiological investigation demonstrated an increase in functional projections of expiratory bulbospinal neurons (EBSNs) in the segment above a chronic lateral thoracic spinal cord lesion which severed their axons. We have now investigated how this plasticity might be manifested in thoracic motoneurons, by measuring their respiratory drive and the connections to them from individual EBSNs. In anesthetized cats, simultaneous recordings were made intracellularly from motoneurons in the segment above a left-side chronic (16 week) lesion of the spinal cord in the rostral part of T8, T9 or T10 and extracellularly from EBSNs in the right caudal medulla, antidromically excited from just above the lesion, but not from below. Spike-triggered averaging was used to measure the connections between pairs of EBSNs and motoneurons. Connections were found to have a very similar distribution to normal and were, if anything (non-significantly), weaker than normal, being present for 42/158 pairs, vs. 55/154 pairs in controls. The expiratory drive in expiratory motoneurons appeared stronger than in controls, but again not significantly so. Thus we conclude that new connections made by the EBSNs following these lesions were made to neurons other than alpha-motoneurons. However, a previously unidentified form of functional plasticity was seen, in that there was a significant increase in the excitation of motoneurons during post-inspiration, being manifest either in increased incidence of expiratory-decrementing respiratory drive potentials, or in an increased amplitude of the post-inspiratory depolarizing phase in inspiratory motoneurons. We suggest that this component arose from spinal cord interneurons

Understanding how Victoria, Australia gained control of its second COVID-19 wave

During 2020, Victoria was the Australian state hardest hit by COVID-19, but was successful in controlling its second wave through aggressive policy interventions. We calibrated a detailed compartmental model of Victoria's second wave to multiple geographically-structured epidemic time-series indicators. We achieved a good fit overall and for individual health services through a combination of time-varying processes, including case detection, population mobility, school closures, physical distancing and face covering usage. Estimates of the risk of death in those aged ≥75 and of hospitalisation were higher than international estimates, reflecting concentration of cases in high-risk settings. We estimated significant effects for each of the calibrated time-varying processes, with estimates for the individual-level effect of physical distancing of 37.4% (95%CrI 7.2-56.4%) and of face coverings of 45.9% (95%CrI 32.9-55.6%). That the multi-faceted interventions led to the dramatic reversal in the epidemic trajectory is supported by our results, with face coverings likely particularly important