10 research outputs found

    Mask wearing in community settings reduces SARS-CoV-2 transmission

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    The effectiveness of mask wearing at controlling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been unclear. While masks are known to substantially reduce disease transmission in healthcare settings [D. K. Chu et al., Lancet 395, 1973–1987 (2020); J. Howard et al., Proc. Natl. Acad. Sci. U.S.A. 118, e2014564118 (2021); Y. Cheng et al., Science eabg6296 (2021)], studies in community settings report inconsistent results [H. M. Ollila et al., medRxiv (2020); J. Brainard et al., Eurosurveillance 25, 2000725 (2020); T. Jefferson et al., Cochrane Database Syst. Rev. 11, CD006207 (2020)]. Most such studies focus on how masks impact transmission, by analyzing how effective government mask mandates are. However, we find that widespread voluntary mask wearing, and other data limitations, make mandate effectiveness a poor proxy for mask-wearing effectiveness. We directly analyze the effect of mask wearing on SARS-CoV-2 transmission, drawing on several datasets covering 92 regions on six continents, including the largest survey of wearing behavior ([Formula: see text] 20 million) [F. Kreuter et al., https://gisumd.github.io/COVID-19-API-Documentation (2020)]. Using a Bayesian hierarchical model, we estimate the effect of mask wearing on transmission, by linking reported wearing levels to reported cases in each region, while adjusting for mobility and nonpharmaceutical interventions (NPIs), such as bans on large gatherings. Our estimates imply that the mean observed level of mask wearing corresponds to a 19% decrease in the reproduction number R. We also assess the robustness of our results in 60 tests spanning 20 sensitivity analyses. In light of these results, policy makers can effectively reduce transmission by intervening to increase mask wearing

    Introducing improved structural properties and salt dependence into a coarse-grained model of DNA

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    We introduce an extended version of oxDNA, a coarse-grained model of deoxyribonucleic acid (DNA) designed to capture the thermodynamic, structural, and mechanical properties of single- and double-stranded DNA. By including explicit major and minor grooves and by slightly modifying the coaxial stacking and backbone-backbone interactions, we improve the ability of the model to treat large (kilobase-pair) structures, such as DNA origami, which are sensitive to these geometric features. Further, we extend the model, which was previously parameterised to just one salt concentration ([Na +] = 0.5M), so that it can be used for a range of salt concentrations including those corresponding to physiological conditions. Finally, we use new experimental data to parameterise the oxDNA potential so that consecutive adenine bases stack with a different strength to consecutive thymine bases, a feature which allows a more accurate treatment of systems where the flexibility of single-stranded regions is important. We illustrate the new possibilities opened up by the updated model, oxDNA2, by presenting results from simulations of the structure of large DNA objects and by using the model to investigate some salt-dependent properties of DNA

    Understanding the effectiveness of government interventions against the resurgence of COVID-19 in Europe.

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    Funder: European and Developing Countries Clinical Trials Partnership (EDCTP); doi: https://doi.org/10.13039/501100001713Funder: MRC Centre for Global Infectious Disease Analysis (MR/R015600/1), jointly funded by the U.K. Medical Research Council (MRC) and the U.K. Foreign, Commonwealth and Development Office (FCDO), under the MRC/FCDO Concordat agreement. Community Jameel. The UK Research and Innovation (MR/V038109/1), the Academy of Medical Sciences Springboard Award (SBF004/1080), The MRC (MR/R015600/1), The BMGF (OPP1197730), Imperial College Healthcare NHS Trust- BRC Funding (RDA02), The Novo Nordisk Young Investigator Award (NNF20OC0059309) and The NIHR Health Protection Research Unit in Modelling Methodology. S. Bhatt thanks Microsoft AI for Health and Amazon AWS for computational credits.Funder: EA FundsFunder: University of Oxford (Oxford University); doi: https://doi.org/10.13039/501100000769Funder: DeepMindFunder: OpenPhilanthropyFunder: UKRI Centre for Doctoral Training in Interactive Artificial Intelligence (EP/S022937/1)Funder: Augustinus Fonden (Augustinus Foundation); doi: https://doi.org/10.13039/501100004954Funder: Knud Højgaards Fond (Knud Højgaard Fund); doi: https://doi.org/10.13039/501100009938Funder: Kai Lange og Gunhild Kai Langes Fond (Kai Lange and Gunhild Kai Lange Foundation); doi: https://doi.org/10.13039/501100008206Funder: Aage og Johanne Louis-Hansens Fond (Aage and Johanne Louis-Hansen Foundation); doi: https://doi.org/10.13039/501100010344Funder: William Demant FoundationFunder: Boehringer Ingelheim Fonds (Stiftung für medizinische Grundlagenforschung); doi: https://doi.org/10.13039/501100001645Funder: Imperial College COVID-19 Research FundFunder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289European governments use non-pharmaceutical interventions (NPIs) to control resurging waves of COVID-19. However, they only have outdated estimates for how effective individual NPIs were in the first wave. We estimate the effectiveness of 17 NPIs in Europe's second wave from subnational case and death data by introducing a flexible hierarchical Bayesian transmission model and collecting the largest dataset of NPI implementation dates across Europe. Business closures, educational institution closures, and gathering bans reduced transmission, but reduced it less than they did in the first wave. This difference is likely due to organisational safety measures and individual protective behaviours-such as distancing-which made various areas of public life safer and thereby reduced the effect of closing them. Specifically, we find smaller effects for closing educational institutions, suggesting that stringent safety measures made schools safer compared to the first wave. Second-wave estimates outperform previous estimates at predicting transmission in Europe's third wave

    Direct Simulation of the Self-Assembly of a Small DNA Origami

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    By using oxDNA, a coarse-grained nucleotide-level model of DNA, we are able to directly simulate the self-assembly of a small 384-base-pair origami from single-stranded scaffold and staple strands in solution. In general, we see attachment of new staple strands occurring in parallel, but with cooperativity evident for the binding of the second domain of a staple if the adjacent junction is already partially formed. For a system with exactly one copy of each staple strand, we observe a complete assembly pathway in an intermediate temperature window; at low temperatures successful assembly is prevented by misbonding while at higher temperature the free-energy barriers to assembly become too large for assembly on our simulation time scales. For high-concentration systems involving a large staple strand excess, we never see complete assembly because there are invariably instances where two copies of the same staple both bind to the scaffold, creating a kinetic trap that prevents the complete binding of either staple. This mutual staple blocking could also lead to aggregates of partially formed origamis in real systems, and helps to rationalize certain successful origami design strategies.By using oxDNA, a coarse-grained nucleotide-level model of DNA, we are able to directly simulate the self-assembly of a small 384-base-pair origami from single-stranded scaffold and staple strands in solution. In general, we see attachment of new staple strands occurring in parallel, but with cooperativity evident for the binding of the second domain of a staple if the adjacent junction is already partially formed. For a system with exactly one copy of each staple strand, we observe a complete assembly pathway in an intermediate temperature window; at low temperatures successful assembly is prevented by misbonding while at higher temperature the free-energy barriers to assembly become too large for assembly on our simulation time scales. For high-concentration systems involving a large staple strand excess, we never see complete assembly because there are invariably instances where two copies of the same staple both bind to the scaffold, creating a kinetic trap that prevents the complete binding of either staple. This mutual staple blocking could also lead to aggregates of partially formed origamis in real systems, and helps to rationalize certain successful origami design strategies

    Coarse-graining DNA for simulations of DNA nanotechnology

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    To simulate long time and length scale processes involving DNA it is necessary to use a coarse-grained description. Here we provide an overview of different approaches to such coarse-graining, focussing on those at the nucleotide level that allow the self-assembly processes associated with DNA nanotechnology to be studied. OxDNA, our recently-developed coarse-grained DNA model, is particularly suited to this task, and has opened up this field to systematic study by simulations. We illustrate some of the range of DNA nanotechnology systems to which the model is being applied, as well as the insights it can provide into fundamental biophysical properties of DNA

    A dataset of non-pharmaceutical interventions on SARS-CoV-2 in Europe.

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    During the second half of 2020, many European governments responded to the resurging transmission of SARS-CoV-2 with wide-ranging non-pharmaceutical interventions (NPIs). These efforts were often highly targeted at the regional level and included fine-grained NPIs. This paper describes a new dataset designed for the accurate recording of NPIs in Europe's second wave to allow precise modelling of NPI effectiveness. The dataset includes interventions from 114 regions in 7 European countries during the period from the 1st August 2020 to the 9th January 2021. The paper includes NPI definitions tailored to the second wave following an exploratory data collection. Each entry has been extensively validated by semi-independent double entry, comparison with existing datasets, and, when necessary, discussion with local epidemiologists. The dataset has considerable potential for use in disentangling the effectiveness of NPIs and comparing the impact of interventions across different phases of the pandemic
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