Multisystem imaging manifestations of covid-19, part 1: Viral pathogenesis and pulmonary and vascular system complications

© RSNA, 2020. Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in coronavirus disease 2019 (COVID-19), which was declared an official pandemic by the World Health Organization on March 11, 2020. The infection has been reported in most countries around the world. As of August 2020, there have been over 21 million cases of COVID-19 reported worldwide, with over 800 000 COVID-19–associated deaths. It has become appar-ent that although COVID-19 predominantly affects the respiratory system, many other organ systems can also be involved. Imaging plays an essential role in the diagnosis of all manifestations of the disease, as well as its related complications, and proper utilization and interpretation of imaging examinations is crucial. With the growing global COVID-19 outbreak, a comprehensive understanding of the diagnostic imaging hallmarks, imaging features, multi-systemic involvement, and evolution of imaging findings is essential for effective patient management and treatment. To date, only a few articles have been published that comprehensively describe the multisystemic imaging manifestations of COVID-19. The authors provide an inclusive system-by-system image-based review of this life-threatening and rapidly spreading infection. In part 1 of this article, the authors discuss general aspects of the disease, with an emphasis on virology, the pathophysiology of the virus, and clinical presentation of the disease. The key imaging features of the varied pathologic manifestations of this infection that involve the pulmonary and peripheral and central vascular systems are also described. Part 2 will focus on key imaging features of COVID-19 that involve the cardiac, neurologic, abdominal, dermatologic and ocular, and musculoskeletal systems, as well as pediatric and pregnancy-related manifestations of the virus. Vascular complications pertinent to each system will be also be discussed in part 2

Bone Marrow-Derived Microglia-Based Neurturin Delivery Protects Against Dopaminergic Neurodegeneration in a Mouse Model of Parkinson\u27s Disease

Although neurotrophic factors have long been recognized as potent agents for protecting against neuronal degeneration, clinical success in treating Parkinson\u27s disease and other neurodegenerative disorders has been hindered by difficulties in delivery of trophic factors across the blood brain barrier (BBB). Bone marrow hematopoietic stem cell-based gene therapy is emerging as a promising tool for overcoming drug delivery problems, as myeloid cells can cross the BBB and are recruited in large numbers to sites of neurodegeneration, where they become activated microglia that can secrete trophic factors. We tested the efficacy of bone marrow-derived microglial delivery of neurturin (NTN) in protecting dopaminergic neurons against neurotoxin-induced death in mice. Bone marrow cells were transduced ex vivo with lentivirus expressing the NTN gene driven by a synthetic macrophage-specific promoter. Infected bone marrow cells were then collected and transplanted into recipient animals. Eight weeks after transplantation, the mice were injected with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropuridine (MPTP) for seven days to induce dopaminergic neurodegeneration. Microglia-mediated NTN delivery dramatically ameliorated MPTP-induced degeneration of tyrosine hydroxylase (TH)-positive neurons of the substantia nigra and their terminals in the striatum. Microglia-mediated NTN delivery also induced significant recovery of synaptic marker staining in the striatum of MPTP-treated animals. Functionally, NTN treatment restored MPTP-induced decline in general activity, rearing behavior, and food intake. Thus, bone marrow-derived microglia can serve as cellular vehicles for sustained delivery of neurotrophic factors capable of mitigating dopaminergic injury

The Origin of the Universe as Revealed Through the Polarization of the Cosmic Microwave Background

Modern cosmology has sharpened questions posed for millennia about the origin of our cosmic habitat. The age-old questions have been transformed into two pressing issues primed for attack in the coming decade: How did the Universe begin? and What physical laws govern the Universe at the highest energies? The clearest window onto these questions is the pattern of polarization in the Cosmic Microwave Background (CMB), which is uniquely sensitive to primordial gravity waves. A detection of the special pattern produced by gravity waves would be not only an unprecedented discovery, but also a direct probe of physics at the earliest observable instants of our Universe. Experiments which map CMB polarization over the coming decade will lead us on our first steps towards answering these age-old questions.Comment: Science White Paper submitted to the US Astro2010 Decadal Survey. Full list of 212 author available at http://cmbpol.uchicago.ed

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

More than smell - COVID-19 is associated with severe impairment of smell, taste, and chemesthesis

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± standard deviation), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms. © 2020 The Author(s) 2020. Published by Oxford University Press. All rights reserved

Merwehaven New Ferry Station

The Hyperbody graduation studio is set to be an endeavor to integrate research with the final design product. The “computational” nature of the whole process serves as both an opportunity and challenge to develop a design methodology out of analyzing the complexity of current social and climatic context and using these presets as “intrigues” to drive the form-finding process, as well as the performance of the project. This personal project is located in a somehow “extreme” situation: the fact that the surrounding urban context will no longer be existed provides a tricky setup for context research. Moreover, the multi-functional requirements, especially the restricted ones regarding ferry operation, are in the other way around of significant research importance. Consequently, the research process focuses on “creating” an urban context and “illustrating” the inner programme relationship. Computational tools are in crucial status at this stage. It is fair to say this project, at research level, indicates what the Hyperbody graduation studio is searching for in the sense of producing a research outcome to guide the afterwards design, in both urban and architectural level. In practical or social level, this project is definitely an experimental one. However, the purpose of this kind of academic projects is to develop future possibilities of built environment, and research projects could reflect the certain social trend at that time as well as vertically inheriting past wisdoms throughout the history of architecture. If we would call this project “a mat building in digital age”, which exactly indicates the current emerging technology to be influencing the architectural occupation and the whole urban development, meantime referring to the old ideals of integrating urban and architectural scale by designing horizontally spanned building network, we are actually revealing the relationship between this project and wider social context.HyperbodyArchitectureArchitecture and The Built Environmen

Composite Anderson acceleration method with two window sizes and optimized damping

In this article, we propose and analyze a set of fully nonstationary Anderson acceleration (AA) algorithms with two window sizes and optimized damping. Although AA has been used for decades to speed up nonlinear solvers in many applications, most authors are simply using and analyzing the stationary version of AA (sAA) with fixed window size and a constant damping factor. The behavior and potential of the nonstationary version of AA methods remain an open question. Most efficient linear solvers however use composable algorithmic components. Similar ideas can be used for AA to solve nonlinear systems. Thus in the present work, to develop nonstationary AA algorithms, we first propose a systematic way to dynamically alternate the window size (Formula presented.) by the multiplicative composite combination, which means we apply sAA((Formula presented.)) in the outer loop and apply sAA((Formula presented.)) in the inner loop. By doing this, significant gains can be achieved. Second, to make AA to be a fully nonstationary algorithm, we need to combine these strategies with our recent work on the nonstationary AA algorithm with optimized damping (AAoptD), which is another important direction of producing nonstationary AA and nice performance gains have been observed. Moreover, we also investigate the rate of convergence of these nonstationary AA methods under suitable assumptions. Finally, our numerical results show that some of these proposed nonstationary AA algorithms converge faster than the stationary sAA method and they may significantly reduce the storage and time to find the solution in many cases.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Numerical AnalysisDelft Institute of Applied Mathematic

Development of a Two-Scale Turbulence Model and Its Applications

The use of second order closure turbulence model in predicting turbulent flows is known to be more successful than the classical mixing length model. However, it is found that if the turbulence constants are not altered or modified, the second order closure turbulence model is unable to predict satisfactorily f or some flows such as round jet and wake flows. In order to improve the predictability of the second order closure model, the present work proposes to consider two turbulent scales in the modelling of turbulent flows. One of these scales is based on using the turbulent kinetic energy, k, and its dissipation rate, epsilon, to characterize the large energy containing eddies. The other scale is based on the dissipation rate and the kinematic viscosity, nie, to characterize the small energy dissipating eddies. The second scale is based on the well known Kolmogorov hypothesis that dissipation of turbulent kinetic energy occurs primarily at small eddies. The turbulence model derived based on the concept of two different scales is called the two-scale turbulence model. The existing turbulence model which is modelled based on the one-scale concept of k and epsilon is called the one-scale turbulence model. The two-scale turbulence model is then applied to predict turbulent free shear flows and recirculating flows. The calculations were done in three parts. The first test case was nonbuoyant free shear flows which included round and plane jets in stagnant and moving streams, plane wakes and mixing layer. In the second part, the model was tested for plane and round buoyant jets having different Froude numbers. Finally, some results were obtained for recirculating flows, namely, backward facing step and flow past an obstruction. It is shown in the present study that the two-scale turbulence model performs significantly better than the one-scale turbulence model in all the cases concerned. The prediction capability of the two-scale turbulence model is shown since one does not need to alter or modify the turbulence constants as in the case of the one-scale turbulence model