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92 result(s) for "Earn, David J. D"
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A draft genome of Yersinia pestis from victims of the Black Death
Reconstruction of Black Death genome The latest DNA recovery and sequencing technologies have been used to reconstruct the genome of the Yersinia pestis bacterium responsible for the Black Death pandemic of bubonic plague that spread across Europe in the fourteenth century. The genome was pieced together from total DNA extracted from the skeletal remains of four individuals excavated from a large cemetery on the site of the Royal Mint in East Smithfield in London, where more than 2,000 plague victims were buried in 1348 and 1349. The draft genome sequence does not differ substantially from modern Y. pestis strains, providing no answer to the question of why the Black Death was more deadly than modern bubonic plague outbreaks. Technological advances in DNA recovery and sequencing have drastically expanded the scope of genetic analyses of ancient specimens to the extent that full genomic investigations are now feasible and are quickly becoming standard 1 . This trend has important implications for infectious disease research because genomic data from ancient microbes may help to elucidate mechanisms of pathogen evolution and adaptation for emerging and re-emerging infections. Here we report a reconstructed ancient genome of Yersinia pestis at 30-fold average coverage from Black Death victims securely dated to episodes of pestilence-associated mortality in London, England, 1348–1350. Genetic architecture and phylogenetic analysis indicate that the ancient organism is ancestral to most extant strains and sits very close to the ancestral node of all Y. pestis commonly associated with human infection. Temporal estimates suggest that the Black Death of 1347–1351 was the main historical event responsible for the introduction and widespread dissemination of the ancestor to all currently circulating Y. pestis strains pathogenic to humans, and further indicates that contemporary Y. pestis epidemics have their origins in the medieval era. Comparisons against modern genomes reveal no unique derived positions in the medieval organism, indicating that the perceived increased virulence of the disease during the Black Death may not have been due to bacterial phenotype. These findings support the notion that factors other than microbial genetics, such as environment, vector dynamics and host susceptibility, should be at the forefront of epidemiological discussions regarding emerging Y. pestis infections.
Interactions Between the Immune System and Cancer: A Brief Review of Non-spatial Mathematical Models
We briefly review spatially homogeneous mechanistic mathematical models describing the interactions between a malignant tumor and the immune system. We begin with the simplest (single equation) models for tumor growth and proceed to consider greater immunological detail (and correspondingly more equations) in steps. This approach allows us to clarify the necessity for expanding the complexity of models in order to capture the biological mechanisms we wish to understand. We conclude by discussing some unsolved problems in the mathematical modeling of cancer-immune system interactions.
Multiple Transmission Pathways and Disease Dynamics in a Waterborne Pathogen Model
Multiple transmission pathways exist for many waterborne diseases, including cholera, Giardia, Cryptosporidium, and Campylobacter. Theoretical work exploring the effects of multiple transmission pathways on disease dynamics is incomplete. Here, we consider a simple ODE model that extends the classical SIR framework by adding a compartment (W) that tracks pathogen concentration in the water. Infected individuals shed pathogen into the water compartment, and new infections arise both through exposure to contaminated water, as well as by the classical SIR person-person transmission pathway. We compute the basic reproductive number (ℛ₀), epidemic growth rate, and final outbreak size for the resulting “SIWR” model, and examine how these fundamental quantities depend upon the transmission parameters for the different pathways. We prove that the endemic disease equilibrium for the SIWR model is globally stable. We identify the pathogen decay rate in the water compartment as a key parameter determining when the distinction between the different transmission routes in the SIWR model is important. When the decay rate is slow, using an SIR model rather than the SIWR model can lead to under-estimates of the basic reproductive number and over-estimates of the infectious period.
Using artificial intelligence tools to automate data extraction for living evidence syntheses
Living evidence synthesis (LES) involves repeatedly updating a systematic review or meta-analysis at regular intervals to incorporate new evidence into the summary results. It requires a considerable amount of human time investment in the article search, collection, and data extraction phases. Tools exist to automate the retrieval of relevant journal articles, but pulling data out of those articles is currently still a manual process. In this article, we present a proof-of-concept Python program that leverages artificial intelligence (AI) tools (specifically, ChatGPT) to parse a batch of journal articles and extract relevant results, greatly reducing the human time investment in this action without compromising on accuracy. Our program is tested on a set of journal articles that estimate the mean incubation period for COVID-19, an epidemiological parameter of importance for mathematical modelling. We also discuss important limitations related to the total amount of information and rate at which that information can be sent to the AI engine. This work contributes to the ongoing discussion about the use of AI and the role such tools can have in scientific research.
Fast estimation of time-varying infectious disease transmission rates
Compartmental epidemic models have been used extensively to study the historical spread of infectious diseases and to inform strategies for future control. A critical parameter of any such model is the transmission rate. Temporal variation in the transmission rate has a profound influence on disease spread. For this reason, estimation of time-varying transmission rates is an important step in identifying mechanisms that underlie patterns in observed disease incidence and mortality. Here, we present and test fast methods for reconstructing transmission rates from time series of reported incidence. Using simulated data, we quantify the sensitivity of these methods to parameters of the data-generating process and to mis-specification of input parameters by the user. We show that sensitivity to the user's estimate of the initial number of susceptible individuals-considered to be a major limitation of similar methods-can be eliminated by an efficient, \"peak-to-peak\" iterative technique, which we propose. The method of transmission rate estimation that we advocate is extremely fast, for even the longest infectious disease time series that exist. It can be used independently or as a fast way to obtain better starting conditions for computationally expensive methods, such as iterated filtering and generalized profiling.
Targeted enrichment of ancient pathogens yielding the pPCP1 plasmid of Yersinia pestis from victims of the Black Death
Although investigations of medieval plague victims have identified Yersinia pestis as the putative etiologic agent of the pandemic, methodological limitations have prevented large-scale genomic investigations to evaluate changes in the pathogen's virulence over time. We screened over 100 skeletal remains from Black Death victims of the East Smithfield mass burial site (1348–1350, London, England). Recent methods of DNA enrichment coupled with high-throughput DNA sequencing subsequently permitted reconstruction of ten full human mitochondrial genomes (16 kb each) and the full pPCP1 (9.6 kb) virulence-associated plasmid at high coverage. Comparisons of molecular damage profiles between endogenous human and Y. pestis DNA confirmed its authenticity as an ancient pathogen, thus representing the longest contiguous genomic sequence for an ancient pathogen to date. Comparison of our reconstructed plasmid against modern Y. pestis shows identity with several isolates matching the Medievalis biovar; however, our chromosomal sequences indicate the victims were infected with a Y. pestis variant that has not been previously reported. Our data reveal that the Black Death in medieval Europe was caused by a variant of Y. pestis that may no longer exist, and genetic data carried on its pPCP1 plasmid were not responsible for the purported epidemiological differences between ancient and modern forms of Y. pestis infections.
Yersinia pestis and the Plague of Justinian 541–543 AD: a genomic analysis
Yersinia pestis has caused at least three human plague pandemics. The second (Black Death, 14–17th centuries) and third (19–20th centuries) have been genetically characterised, but there is only a limited understanding of the first pandemic, the Plague of Justinian (6–8th centuries). To address this gap, we sequenced and analysed draft genomes of Y pestis obtained from two individuals who died in the first pandemic. Teeth were removed from two individuals (known as A120 and A76) from the early medieval Aschheim-Bajuwarenring cemetery (Aschheim, Bavaria, Germany). We isolated DNA from the teeth using a modified phenol-chloroform method. We screened DNA extracts for the presence of the Y pestis-specific pla gene on the pPCP1 plasmid using primers and standards from an established assay, enriched the DNA, and then sequenced it. We reconstructed draft genomes of the infectious Y pestis strains, compared them with a database of genomes from 131 Y pestis strains from the second and third pandemics, and constructed a maximum likelihood phylogenetic tree. Radiocarbon dating of both individuals (A120 to 533 AD [plus or minus 98 years]; A76 to 504 AD [plus or minus 61 years]) places them in the timeframe of the first pandemic. Our phylogeny contains a novel branch (100% bootstrap at all relevant nodes) leading to the two Justinian samples. This branch has no known contemporary representatives, and thus is either extinct or unsampled in wild rodent reservoirs. The Justinian branch is interleaved between two extant groups, 0.ANT1 and 0.ANT2, and is distant from strains associated with the second and third pandemics. We conclude that the Y pestis lineages that caused the Plague of Justinian and the Black Death 800 years later were independent emergences from rodents into human beings. These results show that rodent species worldwide represent important reservoirs for the repeated emergence of diverse lineages of Y pestis into human populations. McMaster University, Northern Arizona University, Social Sciences and Humanities Research Council of Canada, Canada Research Chairs Program, US Department of Homeland Security, US National Institutes of Health, Australian National Health and Medical Research Council.
Inferring the causes of the three waves of the 1918 influenza pandemic in England and Wales
Past influenza pandemics appear to be characterized by multiple waves of incidence, but the mechanisms that account for this phenomenon remain unclear. We propose a simple epidemic model, which incorporates three factors that might contribute to the generation of multiple waves: (i) schools opening and closing, (ii) temperature changes during the outbreak, and (iii) changes in human behaviour in response to the outbreak. We fit this model to the reported influenza mortality during the 1918 pandemic in 334 UK administrative units and estimate the epidemiological parameters. We then use information criteria to evaluate how well these three factors explain the observed patterns of mortality. Our results indicate that all three factors are important but that behavioural responses had the largest effect. The parameter values that produce the best fit are biologically reasonable and yield epidemiological dynamics that match the observed data well.
From science to politics: COVID-19 information fatigue on YouTube
Objective The COVID-19 pandemic is the first pandemic where social media platforms relayed information on a large scale, enabling an “infodemic” of conflicting information which undermined the global response to the pandemic. Understanding how the information circulated and evolved on social media platforms is essential for planning future public health campaigns. This study investigated what types of themes about COVID-19 were most viewed on YouTube during the first 8 months of the pandemic, and how COVID-19 themes progressed over this period. Methods We analyzed top-viewed YouTube COVID-19-related videos in English from December 1, 2019 to August 16, 2020 with an open inductive content analysis. We coded 536 videos associated with 1.1 billion views across the study period. East Asian countries were the first to report the virus, while most of the top-viewed videos in English were from the US. Videos from straight news outlets dominated the top-viewed videos throughout the outbreak, and public health authorities contributed the fewest. Although straight news was the dominant COVID-19 video source with various types of themes, its viewership per video was similar to that for entertainment news and YouTubers after March. Results We found, first, that collective public attention to the COVID-19 pandemic on YouTube peaked around March 2020, before the outbreak peaked, and flattened afterwards despite a spike in worldwide cases. Second, more videos focused on prevention early on, but videos with political themes increased through time. Third, regarding prevention and control measures, masking received much less attention than lockdown and social distancing in the study period. Conclusion Our study suggests that a transition of focus from science to politics on social media intensified the COVID-19 infodemic and may have weakened mitigation measures during the first waves of the COVID-19 pandemic. It is recommended that authorities should consider co-operating with reputable social media influencers to promote health campaigns and improve health literacy. In addition, given high levels of globalization of social platforms and polarization of users, tailoring communication towards different digital communities is likely to be essential.
Patterns of smallpox mortality in London, England, over three centuries
Smallpox is unique among infectious diseases in the degree to which it devastated human populations, its long history of control interventions, and the fact that it has been successfully eradicated. Mortality from smallpox in London, England was carefully documented, weekly, for nearly 300 years, providing a rare and valuable source for the study of ecology and evolution of infectious disease. We describe and analyze smallpox mortality in London from 1664 to 1930. We digitized the weekly records published in the London Bills of Mortality (LBoM) and the Registrar General’s Weekly Returns (RGWRs). We annotated the resulting time series with a sequence of historical events that might have influenced smallpox dynamics in London. We present a spectral analysis that reveals how periodicities in reported smallpox mortality changed over decades and centuries; many of these changes in epidemic patterns are correlated with changes in control interventions and public health policies. We also examine how the seasonality of reported smallpox mortality changed from the 17th to 20th centuries in London.