A DSEL for Studying and Explaining Causation

We present a domain-specific embedded language (DSEL) in Haskell that supports the philosophical study and practical explanation of causation. The language provides constructs for modeling situations comprised of events and functions for reliably determining the complex causal relationships that emerge between these events. It enables the creation of visual explanations of these causal relationships and a means to systematically generate alternative, related scenarios, along with corresponding outcomes and causes. The DSEL is based on neuron diagrams, a visual notation that is well established in practice and has been successfully employed for causation explanation and research. In addition to its immediate applicability by users of neuron diagrams, the DSEL is extensible, allowing causation experts to extend the notation to introduce special-purpose causation constructs. The DSEL also extends the notation of neuron diagrams to operate over non-boolean values, improving its expressiveness and offering new possibilities for causation research and its applications.Comment: In Proceedings DSL 2011, arXiv:1109.032

Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children

This article is made available for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing.BACKGROUND: Despite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant mortality. Therefore, we aimed to develop a highly sensitive metagenomic next-generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children. METHODS: We collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 children's hospitals from 2014-2016. Samples underwent mechanical homogenization, parallel RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the National Center for Biotechnology Information nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort. RESULTS: We identified a rich cross-domain pulmonary microbiome that contained bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median, 0.61; interquartile range [IQR], 0.33-0.72 vs median, 0.96; IQR, 0.94-0.96; P < .001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (P < .001). CONCLUSIONS: An optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease

Real Potential

There\u27s a student in my philosophy class who has real potential. I might express this thought in any of the following ways: She is potentially a philosopher ; She is a potential philosopher ; She has the potential to be a philosopher. The first way uses a cognate of potential as an adverb to modify is. The second ways uses potential as an adjective to modify philosopher. However, the third way uses potential as a noun to refer to something that the student has. What kind of thing is this potential? One worry about even asking this question is that this nominalization of the adjective potential suggests a metaphysical picture that is an artifact of language. This is even more strongly suggested by the less ambiguous nominalization potentiality. Once we have the term potentiality, we have a new kind of entity to countenance, and questions about its nature arise. One might argue, just because we use the word potentiality, we should not think that it refers to a thing that someone can have. There is something disingenuous about such an argument. It proceeds as if the adverbial and adjectival uses of potential are unproblematic, and questions only arise with the nominalization. But it is not obvious what it means to potentially be something, or what it means to be a potential something. To say that someone is potentially a philosopher is to talk about a way of being that falls short of actuality. And a potential philosopher is not a kind of philosopher at all. So what is it? Each of the three above formulations is a modal claim. If there is anything philosophical puzzling about a potentiality claim, it is not going to go away by translating it into an equivalent modal claim. In this chapter I defend the existence of potentialities against anti-realist arguments, and make a proposal as to their nature. The proposal, in short, is that potentialities are properties, specifically dispositions, though more needs to be said about properties and dispositions. I will do this in Part I. In Part II, I will address two lines of argument against potentialities: that they are reducible, and that they are causally inert

Optical Atomic Clock Comparison through Turbulent Air

We use frequency comb-based optical two-way time-frequency transfer (O-TWTFT) to measure the optical frequency ratio of state-of-the-art ytterbium and strontium optical atomic clocks separated by a 1.5 km open-air link. Our free-space measurement is compared to a simultaneous measurement acquired via a noise-cancelled fiber link. Despite non-stationary, ps-level time-of-flight variations in the free-space link, ratio measurements obtained from the two links, averaged over 30.5 hours across six days, agree to $6\times10^{-19}$, showing that O-TWTFT can support free-space atomic clock comparisons below the $10^{-18}$ level

Structural and functional annotation of the porcine immunome

Background: The domestic pig is known as an excellent model for human immunology and the two species share many pathogens. Susceptibility to infectious disease is one of the major constraints on swine performance, yet the structure and function of genes comprising the pig immunome are not well-characterized. The completion of the pig genome provides the opportunity to annotate the pig immunome, and compare and contrast pig and human immune systems.[br/] Results: The Immune Response Annotation Group (IRAG) used computational curation and manual annotation of the swine genome assembly 10.2 (Sscrofa10.2) to refine the currently available automated annotation of 1,369 immunity-related genes through sequence-based comparison to genes in other species. Within these genes, we annotated 3,472 transcripts. Annotation provided evidence for gene expansions in several immune response families, and identified artiodactyl-specific expansions in the cathelicidin and type 1 Interferon families. We found gene duplications for 18 genes, including 13 immune response genes and five non-immune response genes discovered in the annotation process. Manual annotation provided evidence for many new alternative splice variants and 8 gene duplications. Over 1,100 transcripts without porcine sequence evidence were detected using cross-species annotation. We used a functional approach to discover and accurately annotate porcine immune response genes. A co-expression clustering analysis of transcriptomic data from selected experimental infections or immune stimulations of blood, macrophages or lymph nodes identified a large cluster of genes that exhibited a correlated positive response upon infection across multiple pathogens or immune stimuli. Interestingly, this gene cluster (cluster 4) is enriched for known general human immune response genes, yet contains many un-annotated porcine genes. A phylogenetic analysis of the encoded proteins of cluster 4 genes showed that 15% exhibited an accelerated evolution as compared to 4.1% across the entire genome.[br/] Conclusions: This extensive annotation dramatically extends the genome-based knowledge of the molecular genetics and structure of a major portion of the porcine immunome. Our complementary functional approach using co-expression during immune response has provided new putative immune response annotation for over 500 porcine genes. Our phylogenetic analysis of this core immunome cluster confirms rapid evolutionary change in this set of genes, and that, as in other species, such genes are important components of the pig’s adaptation to pathogen challenge over evolutionary time. These comprehensive and integrated analyses increase the value of the porcine genome sequence and provide important tools for global analyses and data-mining of the porcine immune response

Strange reading: Keith Windschuttle on race, Asia and White Australia

In his recently published book, The White Australia Policy, Keith Windschuttle accuses academic historians of errors of fact and judgement in their accounts of white Australia. This article examines these claims of exaggeration and distortion with particular reference to the nature and meaning of race, racism and representations of Asia in Australian history. The article rejects Winschuttle\u27s sweeping claim that academic historians have sought to make Australia appear a much more racist society than the historical record would suggest.<br /

Between Commerce and Empire: David Hume, Colonial Slavery, and Commercial Incivility

Eighteenth-century Enlightenment thought has recently been reclaimed as a robust, albeit short-lived, cosmopolitan critique of European imperialism. This essay complicates this interpretation through a study of David Hume’s reflections on commerce, empire and slavery. I argue that while Hume condemned the colonial system of monopoly, war and conquest, his strictures against empire did not extend to colonial slavery in the Atlantic. This was because colonial slavery represented a manifestly uncivil institution when judged by enlightened metropolitan sensibilities, yet also a decisively commercial institution pivotal to the eighteenth-century global economy. Confronted by the paradoxical ‘commercial incivility’ of modern slavery, Hume opted for disavowing the link between slavery and commerce, and confined his criticism of slavery to its ancient, feudal and Asiatic incarnations. I contend that Hume’s disavowal of the commercial barbarism of the Atlantic economy is part of a broader ideological effort to separate the idea of commerce from its imperial origins and posit it as the liberal antithesis of empire. The implications of analysis, I conclude, go beyond the eighteenth-century debates over commerce and empire, and more generally pertain to the contradictory entwinement of liberalism and capitalism

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead