Background: A range of case fatality ratio (CFR) estimates for COVID-19 have been produced that differ substantially in magnitude. Methods:We used individual-case data from mainland China and cases detected outside mainland China to estimate the time between onset of symptoms and outcome (death or discharge from hospital). We next obtained age-stratified estimates of the CFR by relating the aggregate distribution of cases by dates of onset to the observed cumulative deaths in China, assuming a constant attack rate by age and adjusting for the demography of the population, and age-and location-based underascertainment. We additionally estimated the CFR from individual line-list data on 1,334 cases identified outside mainland China. We used data on the PCR prevalence in international residents repatriated from China at the end of January 2020 to obtain age-stratified estimates of the infection fatality ratio (IFR). Using data on age-stratified severity in a subset of 3,665 cases from China, we estimated the proportion of infections that will likely require hospitalisation. Findings:We estimate the mean duration from onset-of-symptoms to death to be 17.8 days (95% credible interval, crI 16.9-19.2 days) and from onset-of-symptoms to hospital discharge to be 22.6 days (95% crI 21.1-24.4 days). We estimate a crude CFR of 3.67% (95% crI 3.56%-3.80%) in cases from mainland China. Adjusting for demography and under-ascertainment of milder cases in Wuhan relative to the rest of China, we obtain a best estimate of the CFR in China of 1.38% (95% crI 1.23%-1.53%) with substantially higher values in older ages. Our estimate of the CFR from international cases stratified by age (under 60 / 60 and above) are consistent with these estimates from China. We obtain an overall IFR estimate for China of 0.66% (0.39%-1.33%), again with an increasing profile with age.Interpretation: These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and demonstrate a strong age-gradient in risk.

11Bird strike can cause serious risks to the safety of air travel. In this paper, the aim is to improve 12 design by determining deformation and damage mechanisms of laminated glass windows when 13 subjected to high velocity soft impacts. To achieve this, laboratory-scale impact experiments 14 using bird substitute materials were performed in the velocity range of 100-180 m s -1 . An 15 important step forward is that high-speed 3D Digital Image Correlation (DIC) has effectively 16 been employed to extract the full-field deformation and strain on the back surface of the 17 specimens during impact. The finite element simulations were performed in Abaqus/explicit 18 using Eulerian approach and were able to represent successfully the experiments. 19

The polytypism of SiC, phase transformation of ZrB 2 and the interfaces between SiC and ZrB 2 were investigated using high resolution TEM in a hot pressed 10 vol.%SiC-ZrB 2 composite. In most cases, no grain boundary interphases between hexagonal ZrB 2 and 6H-SiC phases were observed with SiC being both inter-and intragranular. Occasionally, 6H-SiC transformed into 3C and 15R and hexagonal ZrB 2 transformed into cubic ZrB. High resolution TEM showed no grain boundary interphases in most regions. Energy dispersive X-ray spectroscopy and electron energy-loss spectroscopy analyses showed the presence of oxygen throughout the sample. The phase transformation of SiC and ZrB 2 , and the interphase formation between SiC and ZrB 2 grains are discussed.

No abstract

No abstract

Cornelia de Lange Syndrome (CdLS) is a human developmental disorder caused by mutations that compromise the function of cohesin, a major regulator of 3D genome organization. Cognitive impairment is a universal and as yet unexplained feature of CdLS. We characterized the transcriptional profile of cortical neurons from CdLS patients and found deregulation of hundreds of genes enriched for neuronal functions related to synaptic transmission, signalling processes, learning and behaviour. Inducible proteolytic cleavage of cohesin disrupted 3-D genome organization and transcriptional control in post-mitotic cortical mouse neurons. The genes affected belonged to similar gene ontology classes and showed significant numerical overlap with those deregulated in CdLS. Interestingly, gene expression was largely rescued by subsequent reconstitution of cohesin function. These experiments show that cohesin is continuously required for neuronal gene expression and provide a tractable approach for addressing mechanisms of neuronal dysfunction in CdLS.

-Background: Docosahexaenoic acid (DHA) has been the dominant acyl component of the membrane phosphoglycerides in neural signaling systems since the origin of the eukaryotes. In this paper, we propose, this extreme conservation, is explained by its special electrical properties. Based on the Pauli Exclusion Principle we offer an explanation on how its six methylene interrupted double-bonds provide a special arrangement of π-electrons that offer an absolute control for the precision of the energy of the signal. Precision is not explained by standard concepts of ion movement or synaptic strengthening by enhanced protein synthesis. Yet precision is essential to visual acuity, truthful recall and the exercise of a dedicated neural pathway. Concept: Synaptic membranes have been shown to actively incorporate DHA with a high degree of selectivity. During a learning process, this biomagnification will increase the proportion of membrane DHA with two consequential neuronal and synaptic enhancements which build into a David Marr type model of the real world: DHA induced gene expression resulting in enhanced protein synthesis; increased density of π-electrons which could provide memory blocks and provide for the preferential flow of a current in neural pathways. Proposal: Both the above imply memory from synaptic strengthening. We propose memory is achieved by the activation of neuronal synaptic activation with synaptic turnover resulting in enhanced membrane DHA, which in turn induces gene expression, protein synthesis and π-electron density. Repetition amplifies the process activating synapses, which form a matrix representing the memory. The electro-chemical potentials then fire the electrons as electromagnetic waves via the six methylene interrupted double bonds. These allow transmission at a specific energy level based on their quantum mechanical properties providing the precision required for faithful recall. It is difficult to conceive of protein synthesis alone providing for precision. Using the principle of the dual properties of photons and electrons we develop the idea of complex wave patterns representing the visual or auditory fields. These are likely to be noncomputable. We suggest that harmonization of the electromagnetic waves can result in cohesion explaining recall and associations. The cohesion of electromagnetic flow leads to a surge above the resting level, which is recognized by the brain as, demonstrated in artificial, electrical stimulus during neurosurgery.Keywords: chaos theory / docosahexaenoic acid / π-electrons / signal precision / quantum mechanics / memory / cognition / perception Résumé -Une théorie sur le rôle des électrons π de l'acide docosahexaénoïque dans la fonction cérébrale. Les six doubles liaisons interrompues par un groupe méthylène et la précision de la signalisation neuronale. Introduction : Depuis l'origine des eucaryotes, l'acide docosahexaénoïque (DHA) est l'acide gras majoritaire des phosphoglycérides des membranes dans les systèmes neuronaux de signalisation. Dans ...

-In Part I, we discuss the background to views on brain function and our thesis that it is conducted by π-electrons which perform sensory reception, memory, action, cognition and consciousness. Our thesis is consistent with the classical views of ion movement and synaptic protein strengthening. However, protein based views contain no element of precision for the signal. Precision is essential for true signal transduction of sensory input and the faithful execution of learnt neural pathways. In Part II, we incorporate these principles to discuss the mechanism whereby electron function adds precision of signal energy to the process through the Pauli Exclusion Principle. The Huxley-Hodgkin (HH) account of neural function describes the movement of sodium, potassium and calcium ions to create electrochemical potentials across membranes with well-established mathematical and experimental support. To explain learning, consciousness and perception, others have claimed brain function depends on protein synthesis or RNA coding. Some consider super position and collapse as the computational mechanism. This however is fragile with no mechanism described to protect from natural collapse and decoherence at the temperatures of the brain. A novel approach was adopted by Penrose and Hammeroff who describe consciousness as a function of ʻobjective reduction' (ʻOR') of the quantum state. This orchestrated OR activity (ʻOrch OR') is taken to result in moments of conscious awareness and/or choice (Hameroff S, Penrose R. 2014 Consciousness in the universe: a review of the ʻOrch OR' theory. Phys Life Rev 11(1): 39-78. Doi: 10.1016/j.plrev.2013.08.002. Epub 2013. Orch-OR operates in principle in protein tubules of neurons. This concept is non-computational and has received much attention with a convincing advocacy and its share of criticism. The advocacy includes the fossil record of organisms that emerged throughout the first Cambrian period with onset roughly 540 million years ago (mya). They had essential degrees of microtubular arrays in skeletal size, complexity and capability for quantum isolation. Attractive as this hypothesis maybe we point out that the brain is predominantly made of lipid not protein. We suggest that both protein and RNA in the brain would more likely been required to serve the extraordinary energy requirements for the brain. Early photosynthetic systems such as the dinoflagellates are rich in docosahexaenoic acid (DHA) including di-DHA phosphoglycerides as also in contemporary mammalian photoreceptors. We wish to discuss in Part II, quantum mechanical properties of the π-electrons of DHA suggestive of a mechanism for the depolarization of the receptor membrane at a precise energy levels as required for vision and neural signalling (Crawford MA, Broadhurst CL, Guest M et al., 2013. A quantum theory for the irreplaceable role of docosahexaenoic acid in neural cell signalling throughout evolution. Prostaglandins Leukot Essent Fatty Acids (PLEFA) 88(1): 5-13. Doi: 10.1016/j.plefa.2012.08.005. PMID: 2320...