34 research outputs found
Efficacy of face coverings in reducing transmission of COVID-19:Calculations based on models of droplet capture
In the COVID--19 pandemic, among the more controversial issues is the use of
masks and face coverings. Much of the concern boils down to the question --
just how effective are face coverings? One means to address this question is to
review our understanding of the physical mechanisms by which masks and
coverings operate -- steric interception, inertial impaction, diffusion and
electrostatic capture. We enquire as to what extent these can be used to
predict the efficacy of coverings. We combine the predictions of the models of
these mechanisms which exist in the filtration literature and compare the
predictions with recent experiments and lattice Boltzmann simulations, and find
reasonable agreement with the former and good agreement with the latter.
Building on these results, we explore the parameter space for woven cotton
fabrics to show that three-layered cloth masks can be constructed with
comparable filtration performance to surgical masks under ideal conditions.
Reusable cloth masks thus present an environmentally friendly alternative to
surgical masks so long as the face seal is adequate enough to minimise leakage.Comment: 26 pages (13 + references, 10 pages supplementary), 10 figures (8 in
main text, 2 in SI); accepted version, to appear in Physics of Fluids'
special issue "Flow and the Virus
How effective are face coverings in reducing transmission of COVID-19?
In the COVID-19 pandemic, among the more controversial issues is the use of
face coverings. To address this we show that the underlying physics ensures
particles with diameters & 1 m are efficiently filtered out by a simple
cotton or surgical mask. For particles in the submicron range the efficiency
depends on the material properties of the masks, though generally the
filtration efficiency in this regime varies between 30 to 60 % and
multi-layered cotton masks are expected to be comparable to surgical masks.
Respiratory droplets are conventionally divided into coarse droplets (> 5-10
m) responsible for droplet transmission and aerosols (< 5-10 m)
responsible for airborne transmission. Masks are thus expected to be highly
effective at preventing droplet transmission, with their effectiveness limited
only by the mask fit, compliance and appropriate usage. By contrast, knowledge
of the size distribution of bioaerosols and the likelihood that they contain
virus is essential to understanding their effectiveness in preventing airborne
transmission. We argue from literature data on SARS-CoV-2 viral loads that the
finest aerosols (< 1 m) are unlikely to contain even a single virion in
the majority of cases; we thus expect masks to be effective at reducing the
risk of airborne transmission in most settings.Comment: 5 pages + references, 3 figure
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Transcriptional Landscape of the Prenatal Human Brain
Summary The anatomical and functional architecture of the human brain is largely determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and postmitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and human-expanded outer subventricular zones. Both germinal and postmitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in frontal lobe. Finally, many neurodevelopmental disorder and human evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE Δ4 allele
Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease
We identified rare coding variants associated with Alzheimerâs disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1Ă10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5Ă10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38Ă10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56Ă10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55Ă10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development
A novel Alzheimer disease locus located near the gene encoding tau protein
This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAPOE Δ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE Δ4+ (10 352 cases and 9207 controls) and APOE Δ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE Δ4 status. Suggestive associations (P<1 Ă 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE Δ4+: 1250 cases and 536 controls; APOE Δ4-: 718 cases and 1699 controls). Among APOE Δ4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 Ă 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE Δ4+ subjects (CR1 and CLU) or APOE Δ4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 Ă 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (Pâ€1.3 Ă 10-8), frontal cortex (Pâ€1.3 Ă 10-9) and temporal cortex (Pâ€1.2 Ă 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 Ă 10-6) and temporal cortex (P=2.6 Ă 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE Δ4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted