SARS-CoV-2 is a SARS-like coronavirus of likely zoonotic origin first identified in December 2019 in Wuhan, the capital of China's Hubei province. The virus has since spread globally, resulting in ...the currently ongoing COVID-19 pandemic. The first whole genome sequence was published on January 5 2020, and thousands of genomes have been sequenced since this date. This resource allows unprecedented insights into the past demography of SARS-CoV-2 but also monitoring of how the virus is adapting to its novel human host, providing information to direct drug and vaccine design. We curated a dataset of 7666 public genome assemblies and analysed the emergence of genomic diversity over time. Our results are in line with previous estimates and point to all sequences sharing a common ancestor towards the end of 2019, supporting this as the period when SARS-CoV-2 jumped into its human host. Due to extensive transmission, the genetic diversity of the virus in several countries recapitulates a large fraction of its worldwide genetic diversity. We identify regions of the SARS-CoV-2 genome that have remained largely invariant to date, and others that have already accumulated diversity. By focusing on mutations which have emerged independently multiple times (homoplasies), we identify 198 filtered recurrent mutations in the SARS-CoV-2 genome. Nearly 80% of the recurrent mutations produced non-synonymous changes at the protein level, suggesting possible ongoing adaptation of SARS-CoV-2. Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. We additionally provide an interactive user-friendly web-application to query the alignment of the 7666 SARS-CoV-2 genomes.
•Phylogenetic estimates support that the COVID-2 pandemic started sometimes around 6 October 2019 – 11 December 2019.•The diversity of SARS-CoV-2 strains in many countries recapitulates its entire global diversity.•198 sites in the SARS-CoV-2 genome appear to have already undergone recurrent, independent mutations.•Detected recurrent mutations may indicate ongoing adaptation of SARS-CoV-2 to its novel human host.•Monitoring the build-up of genetic diversity in SARS-CoV-2 has potential to inform on targets for drugs and vaccines.
To obtain prevalence estimates of age-related macular degeneration (AMD; late, geographic atrophy, neovascular) by age and gender amongst populations of European ancestry taking into account study ...design and time trends.
Systematic review of population-based studies published by September 2010 with quantitative estimates of geographic atrophy (GA), neovascular (NV), and late AMD prevalence. Studies were identified by a literature search of MEDLINE (from 1950), EMBASE (from 1980), and Web of Science (from 1980) databases.
Data from 25 published studies (57 173 subjects: 455 with GA, 464 with NVAMD, and 1571 with late AMD).
Bayesian meta-regression of the log odds of AMD with age, gender, and year of study allowing for differences in study design characteristics, to estimate prevalences of AMD (late, GA, NVAMD) along with 95% credible intervals (CrI).
Log odds and prevalence of AMD.
There was considerable heterogeneity in prevalence rates between studies; for late AMD, 20% of the variability in prevalence rates was explained by differences in age and 50% by study characteristics. The prevalence of AMD increased exponentially with age (odds ratio OR, 4.2 per decade; 95% CrI, 3.8-4.6), which did not differ by gender. There was some evidence to suggest higher risk of NVAMD in women compared with men (OR, 1.2; 95% CrI, 1.0-1.5). Compared with studies using fundus imaging and international classification systems, studies using fundus imaging with alternative classifications were more likely (OR, 2.7; 95% CrI, 1.1-2.8), and studies using alternative classifications without fundus imaging most likely to diagnose late AMD (OR, 2.9; 95% CrI, 1.3-7.8). There was no good evidence of trends in AMD prevalence over time. Estimated prevalence of late AMD is 1.4% (95% CrI, 1.0%-2.0%) at 70 years of age, rising to 5.6% (95% CrI, 3.9%-7.7%) at age 80 and 20% (95% CrI, 14%-27%) at age 90.
Studies using recognized classifications systems with fundus photography reported the lowest prevalences of AMD taking account of age and gender, and were stable over time, with a potentially higher risk of NVAMD for women. These prevalence estimates can be used to guide health service provision in populations of European ancestry.
Yttria-stabilized tetragonal zirconia polycrystal has been used as a dental biomaterial for several decades because the fracture toughness and bend strength are increased by a stress-induced ...transformation-toughening mechanism. However, its esthetics are compromised by its poor translucency and grayish-white appearance.
The purpose of the present systematic review was to assess information on the mechanical, chemical, and optical requirements of monolithic zirconia dental restorations.
The following databases (2010 to 2015) were electronically searched: ProQuest, EMBASE, SciFinder, MRS Online Proceedings Library, Medline, Compendex, and Journal of the American Ceramic Society. The search was limited to English-language publications, in vitro studies, experimental reports, and modeling studies.
The data from 57 studies were considered in order to review the intrinsic and extrinsic characteristics of zirconia and their effects on the optical properties.
The materials and microstructural issues relevant to the esthetics and long-term stability of zirconia have been considered in terms of monolithic restorations, while there also are restorations specifically for esthetic applications. Although zirconia-toughened lithium silicate offers the best esthetic outcomes, transformation-toughened zirconia offers the best mechanical properties and long-term stability; cubic stabilized zirconia offers a potential compromise. The properties of these materials can be altered to some extent through the appropriate application of intrinsic (such as, annealing) and extrinsic (such as, shade-matching) parameters.
Systematic review of published population based surveys to examine the relationship between primary open angle glaucoma (POAG) prevalence and demographic factors. A literature search identified ...population-based studies with quantitative estimates of POAG prevalence (to October 2014). Multilevel binomial logistic regression of log-odds of POAG was used to examine the effect of age and gender among populations of different geographical and ethnic origins, adjusting for study design factors. Eighty-one studies were included (37 countries, 216 214 participants, 5266 POAG cases). Black populations showed highest POAG prevalence, with 5.2% (95% credible interval (CrI) 3.7%, 7.2%) at 60 years, rising to 12.2% (95% CrI 8.9% to 16.6%) at 80 years. Increase in POAG prevalence per decade of age was greatest among Hispanics (2.31, 95% CrI 2.12, 2.52) and White populations (1.99, 95% CrI 1.86, 2.12), and lowest in East and South Asians (1.48, 95% CrI 1.39, 1.57; 1.56, 95% CrI 1.31, 1.88, respectively). Men were more likely to have POAG than women (1.30, 95% CrI 1.22, 1.41). Older studies had lower POAG prevalence, which was related to the inclusion of intraocular pressure in the glaucoma definition. Studies with visual field data on all participants had a higher POAG prevalence than those with visual field data on a subset. Globally 57.5 million people (95% CI 46.4 to 73.1 million) were affected by POAG in 2015, rising to 65.5 million (95% CrI 52.8, 83.2 million) by 2020. This systematic review provides the most precise estimates of POAG prevalence and shows omitting routine visual field assessment in population surveys may have affected case ascertainment. Our findings will be useful to future studies and healthcare planning.
This paper presents a new supervised method for segmentation of blood vessels in retinal photographs. This method uses an ensemble system of bagged and boosted decision trees and utilizes a feature ...vector based on the orientation analysis of gradient vector field, morphological transformation, line strength measures, and Gabor filter responses. The feature vector encodes information to handle the healthy as well as the pathological retinal image. The method is evaluated on the publicly available DRIVE and STARE databases, frequently used for this purpose and also on a new public retinal vessel reference dataset CHASE_DB1 which is a subset of retinal images of multiethnic children from the Child Heart and Health Study in England (CHASE) dataset. The performance of the ensemble system is evaluated in detail and the incurred accuracy, speed, robustness, and simplicity make the algorithm a suitable tool for automated retinal image analysis.
We use magnetic field and ion moment data from the MFI and SWE instruments on board the Wind spacecraft to study the nature of solar wind turbulence at ion-kinetic scales. We analyze the spectral ...properties of magnetic field fluctuations between 0.1 and 5.4 Hz during 2012 using an automated routine, computing high-resolution 92 s power and magnetic helicity spectra. To ensure the spectral features are physical, we make the first in-flight measurement of the MFI "noise-floor" using tail-lobe crossings of the Earth's magnetosphere during early 2004. We utilize Taylor's hypothesis to Doppler-shift into the spacecraft frequency frame, finding that the spectral break observed at these frequencies is best associated with the proton cyclotron resonance scale, 1/kc, rather than the proton inertial length, di, or proton gyroscale, i. This agreement is strongest when we consider periods where , and is consistent with a spectral break at di for and at i for . We also find that the coherent magnetic helicity signature observed at these frequencies is bounded at low frequencies by 1/kc, and its absolute value reaches a maximum at i. These results hold in both slow and fast wind streams, but with a better correlation in the more Alfvénic fast wind where the helicity signature is strongest. We conclude that these findings are consistent with proton cyclotron resonance as an important mechanism for dissipation of turbulent energy in the solar wind, occurring at least half the time in our selected interval. However, we do not rule out additional mechanisms.
Abstract
BACKGROUND: Blister aneurysms of the supraclinoid internal carotid artery (ICA) are challenging lesions with high intraoperative rupture rates and significant morbidity. An optimal treatment ...strategy for these aneurysms has not been established.
OBJECTIVE: To analyze treatment strategy, operative techniques, and outcomes in a consecutive 17-year series of ICA blister aneurysms treated microsurgically.
METHODS: Seventeen patients underwent blister aneurysm treatment with direct clipping, bypass and trapping, or clip-reinforced wrapping.
RESULTS: Twelve aneurysms (71%) were treated with direct surgical clipping. Three patients required bypass: 1 superficial temporal artery to middle cerebral artery bypass, 1 external carotid artery to middle cerebral artery bypass, and 1 ICA to middle cerebral artery bypass. One patient was treated with clip-reinforced wrapping. Initial treatment strategy was enacted 71% of the time. Intraoperative rupture occurred in 7 patients (41%), doubling the rate of a poor outcome (57% vs 30% for patients with and without intraoperative rupture, respectively). Severe vasospasm developed in 9 of 16 patients (56%). Twelve patients (65%) were improved or unchanged after treatment, and 10 patients (59%) had good outcomes (modified Rankin Scale scores of 1 or 2).
CONCLUSION: ICA blister aneurysms can be cautiously explored and treated with direct clipping as the first-line technique in the majority of cases. Complete trapping of the parent artery with temporary clips and placing permanent clip blades along normal arterial walls enables clipping that avoids intraoperative aneurysm rupture. Trapping/bypass is used as the second-line treatment, maintaining a low threshold for bypass with extensive or friable pathology of the carotid wall and in patients with incomplete circles of Willis.
SARS-CoV-2, the causative agent of the COVID-19 pandemic, can infect a wide range of mammals. Since its spread in humans, secondary host jumps of SARS-CoV-2 from humans to multiple domestic and wild ...populations of mammals have been documented. Understanding the extent of adaptation to these animal hosts is critical for assessing the threat that the spillback of animal-adapted SARS-CoV-2 into humans poses. We compare the genomic landscapes of SARS-CoV-2 isolated from animal species to that in humans, profiling the mutational biases indicative of potentially different selective pressures in animals. We focus on viral genomes isolated from mink (Neovison vison) and white-tailed deer (Odocoileus virginianus) for which multiple independent outbreaks driven by onward animal-to-animal transmission have been reported. We identify five candidate mutations for animal-specific adaptation in mink (NSP9_G37E, Spike_F486L, Spike_N501T, Spike_Y453F, ORF3a_L219V), and one in deer (NSP3a_L1035F), though they appear to confer a minimal advantage for human-to-human transmission. No considerable changes to the mutation rate or evolutionary trajectory of SARS-CoV-2 has resulted from circulation in mink and deer thus far. Our findings suggest that minimal adaptation was required for onward transmission in mink and deer following human-to-animal spillover, highlighting the 'generalist' nature of SARS-CoV-2 as a mammalian pathogen.
To evaluate the test performance of the QUARTZ (QUantitative Analysis of Retinal vessel Topology and siZe) software in detecting retinal features from retinal images captured by health care ...professionals in a Danish high street optician chain, compared with test performance from other large population studies (i.e., UK Biobank) where retinal images were captured by non-experts.
The dataset FOREVERP (Finding Ophthalmic Risk and Evaluating the Value of Eye exams and their predictive Reliability, Pilot) contains retinal images obtained from a Danish high street optician chain. The QUARTZ algorithm utilizes both image processing and machine learning methods to determine retinal image quality, vessel segmentation, vessel width, vessel classification (arterioles or venules), and optic disc localization. Outcomes were evaluated by metrics including sensitivity, specificity, and accuracy and compared to human expert ground truths.
QUARTZ's performance was evaluated on a subset of 3,682 images from the FOREVERP database. 80.55% of the FOREVERP images were labelled as being of adequate quality compared to 71.53% of UK Biobank images, with a vessel segmentation sensitivity of 74.64% and specificity of 98.41% (FOREVERP) compared with a sensitivity of 69.12% and specificity of 98.88% (UK Biobank). The mean (± standard deviation) vessel width of the ground truth was 16.21 (4.73) pixels compared to that predicted by QUARTZ of 17.01 (4.49) pixels, resulting in a difference of -0.8 (1.96) pixels. The differences were stable across a range of vessels. The detection rate for optic disc localisation was similar for the two datasets.
QUARTZ showed high performance when evaluated on the FOREVERP dataset, and demonstrated robustness across datasets, providing validity to direct comparisons and pooling of retinal feature measures across data sources.
Reconstructing the phylogenetic relationships that unite all lineages (the tree of life) is a grand challenge. The paucity of homologous character data across disparately related lineages currently ...renders direct phylogenetic inference untenable. To reconstruct a comprehensive tree of life, we therefore synthesized published phylogenies, together with taxonomic classifications for taxa never incorporated into a phylogeny.We present a draft tree containing 2.3 million tips—the Open Tree of Life. Realization of this tree required the assembly of two additional community resources: (i) a comprehensive global reference taxonomy and (ii) a database of published phylogenetic trees mapped to this taxonomy. Our open source framework facilitates community comment and contribution, enabling the tree to be continuously updated when new phylogenetic and taxonomic data become digitally available. Although data coverage and phylogenetic conflict across the Open Tree of Life illuminate gaps in both the underlying data available for phylogenetic reconstruction and the publication of trees as digital objects, the tree provides a compelling starting point for community contribution. This comprehensive tree will fuel fundamental research on the nature of biological diversity, ultimately providing up-to-date phylogenies for downstream applications in comparative biology, ecology, conservation biology, climate change, agriculture, and genomics.
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