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Metagenomics for neurological infections — expanding our imagination
Over the past two decades, the diagnosis rate for patients with encephalitis has remained poor despite advances in pathogen-specific testing such as PCR and antigen assays. Metagenomic next-generation sequencing (mNGS) of RNA and DNA extracted from cerebrospinal fluid and brain tissue now offers another strategy for diagnosing neurological infections. Given that mNGS simultaneously assays for a wide range of infectious agents in an unbiased manner, it can identify pathogens that were not part of a neurologist’s initial differential diagnosis either because of the rarity of the infection, because the microorganism has not been previously associated with a clinical phenotype or because it is a newly discovered organism. This Review discusses the technical advantages and pitfalls of cerebrospinal fluid mNGS in the context of patients with neuroinflammatory syndromes, including encephalitis, meningitis and myelitis. We also speculate on how mNGS testing potentially fits into current diagnostic testing algorithms given data on mNGS test performance, cost and turnaround time. Finally, the Review highlights future directions for mNGS technology and other hypothesis-free testing methodologies that are in development.This Review discusses the advantages and pitfalls of metagenomic next-generation sequencing (mNGS) in patients with encephalitis, meningitis and myelitis. The authors outline data on mNGS test performance, cost and turnaround time and highlight future directions for mNGS technology.
Journal Article
The roots of peace
By focusing on peace, Glowacki provides a fresh perspective on warfare. Why did humans evolve peace? Other animals aggregate peacefully when resources are not economically defendable. The human capacity for peace may arise from two key factors: Multilevel societies and psychology shaped by within-group exchanges, which may have begun when tools enabled hominins to extract foods, including tubers and roots.
Journal Article
Resisting extractivism : Peruvian gold, everyday violence, and the politics of attention
\"Through an ethnographic and systematic comparison of four gold mining conflicts in Peru, Resisting Extractivism presents an account of subtle and routine forms of violence, analyzing how meaning making practices render certain types of damage and suffering noticeable while occluding others. The book thus builds a ground-up theory of violence-how it is framed, how it impacts people's lived experiences, and how it can be confronted\"-- Provided by publisher.
BOOK
Rapid Turnover of Long Noncoding RNAs and the Evolution of Gene Expression
A large proportion of functional sequence within mammalian genomes falls outside protein-coding exons and can be transcribed into long RNAs. However, the roles in mammalian biology of long noncoding RNA (lncRNA) are not well understood. Few lncRNAs have experimentally determined roles, with some of these being lineage-specific. Determining the extent by which transcription of lncRNA loci is retained or lost across multiple evolutionary lineages is essential if we are to understand their contribution to mammalian biology and to lineage-specific traits. Here, we experimentally investigated the conservation of lncRNA expression among closely related rodent species, allowing the evolution of DNA sequence to be uncoupled from evolution of transcript expression. We generated total RNA (RNAseq) and H3K4me3-bound (ChIPseq) DNA data, and combined both to construct catalogues of transcripts expressed in the adult liver of Mus musculus domesticus (C57BL/6J), Mus musculus castaneus, and Rattus norvegicus. We estimated the rate of transcriptional turnover of lncRNAs and investigated the effects of their lineage-specific birth or death. LncRNA transcription showed considerably greater gain and loss during rodent evolution, compared with protein-coding genes. Nucleotide substitution rates were found to mirror the in vivo transcriptional conservation of intergenic lncRNAs between rodents: only the sequences of noncoding loci with conserved transcription were constrained. Finally, we found that lineage-specific intergenic lncRNAs appear to be associated with modestly elevated expression of genomically neighbouring protein-coding genes. Our findings show that nearly half of intergenic lncRNA loci have been gained or lost since the last common ancestor of mouse and rat, and they predict that such rapid transcriptional turnover contributes to the evolution of tissue- and lineage-specific gene expression.
Journal Article
Black ships : illustrated Japanese history--The Americans arrive
\"On the 14th of July, 1853, the USS Plymouth, Mississippi, Saratoga, and Susquehanna sailed into Yokosuka, Japan. The mysterious 'Black Ships' had arrived. In this stirring account of a pivotal moment in modern Japanese history, award-winning author and illustrator team Sean Michael Wilson and Akiko Shimojima tell the story of the four American 'Black Ships' that arrived in Japan in 1853 under the command of Commodore Perry to force Japan to open up to trade. The book compellingly portrays the apprehension and confusion of the Japanese people witnessing the Black Ships steaming into view over the horizon; the anxious response of the samurai; the cat-and-mouse game that ensued; the protracted negotiations; and the eventual agreement signed on March 31st, 1854, as the Treaty of Kanagawa. Historically accurate and with an easy-to-read visual format, Black Ships conveys the personalities of the key figures in the drama: on one side, Commodore Perry and his captains, and on the other, Shogunate officials Abe Masahiro and Hayashi Akira. Wilson and Shimojima vividly capture the atmosphere of threat and change that pervaded Japan during Bakumatsu, the final years of the Edo period, as the feudal Tokugawa shogunate took its last breaths and gave way to the new Meiji government\"-- Provided by publisher.
Book
Bayesian approach to inverse problems: an application to NNPDF closure testing
We discuss the Bayesian approach to the solution of inverse problems and apply the formalism to analyse the closure tests performed by the NNPDF collaboration. Starting from a comparison with the approach that is currently used for the determination of parton distributions (PDFs), we discuss some analytical results that can be obtained for linear problems and use these results as a guidance for more complicated non-linear problems. We show that, in the case of Gaussian distributions, the posterior probability density of the parametrized PDFs is fully determined by the results of the NNPDF fitting procedure. Building on the insight that we obtain from the analytical results, we introduce new estimators to assess the statistical faithfulness of the fit results in closure tests. These estimators are defined in data space, and can be studied analytically using the Bayesian formalism in a linear model in order to clarify their meaning. Finally we present results from a number of closure tests performed with current NNPDF methodologies. These further tests allow us to validate the NNPDF4.0 methodology and provide a quantitative comparison of the NNPDF4.0 and NNPDF3.1 methodologies. As PDFs determinations move into precision territory, the need for a careful validation of the methodology becomes increasingly important: the error bar has become the focal point of contemporary PDFs determinations. In this perspective, theoretical assumptions and other sources of error are best formulated and analysed in the Bayesian framework, which provides an ideal language to address the precision and the accuracy of current fits.
Journal Article
The Satsuma Rebellion : the last stand of the samurai
In graphic novel format, \"portrays the bloody uprising of 1877, when Satsuma rebels, led by the infamous Saigo Takamori, fought enforced modernization by the Meiji Japanese government. Their crushing defeat by the imperial army ended their power once and for all and ushered in an era of modern technology and Western military methods\"--Back cover.
Book
Access to pathology and laboratory medicine services: a crucial gap
As global efforts accelerate to implement the Sustainable Development Goals and, in particular, universal health coverage, access to high-quality and timely pathology and laboratory medicine (PALM) services will be needed to support health-care systems that are tasked with achieving these goals. This access will be most challenging to achieve in low-income and middle-income countries (LMICs), which have a disproportionately large share of the global burden of disease but a disproportionately low share of global health-care resources, particularly PALM services. In this first in a Series of three papers on PALM in LMICs, we describe the crucial and central roles of PALM services in the accurate diagnosis and detection of disease, informing prognosis and guiding treatment, contributing to disease screening, public health surveillance and disease registries, and supporting medical-legal systems. We also describe how, even though data are sparse, these services are of both insufficient scope and inadequate quality to play their key role in health-care systems in LMICs. Lastly, we identify four key barriers to the provision of optimal PALM services in resource-limited settings: insufficient human resources or workforce capacity, inadequate education and training, inadequate infrastructure, and insufficient quality, standards, and accreditation.
Journal Article