Understanding State Preferences With Text As Data: Introducing the UN General Debate Corpus

Every year at the United Nations, member states deliver statements during the General Debate discussing major issues in world politics. These speeches provide invaluable information on governments’ perspectives and preferences on a wide range of issues, but have largely been overlooked in the study of international politics. This paper introduces a new dataset consisting of over 7,300 country statements from 1970-2014. We demonstrate how the UN General Debate Corpus (UNGDC) can be used to derive country positions on different policy dimensions using text analytic methods. The paper provides applications of these estimates, demonstrating the contribution the UNGDC can make to the study of international politics

Mangarara Formation: exhumed remnants of a middle Miocene, temperate carbonate, submarine channel-fan system on the eastern margin of Taranaki Basin, New Zealand

The middle Miocene Mangarara Formation is a thin (1–60 m), laterally discontinuous unit of moderately to highly calcareous (40–90%) facies of sandy to pure limestone, bioclastic sandstone, and conglomerate that crops out in a few valleys in North Taranaki across the transition from King Country Basin into offshore Taranaki Basin. The unit occurs within hemipelagic (slope) mudstone of Manganui Formation, is stratigraphically associated with redeposited sandstone of Moki Formation, and is overlain by redeposited volcaniclastic sandstone of Mohakatino Formation. The calcareous facies of the Mangarara Formation are interpreted to be mainly mass-emplaced deposits having channelised and sheet-like geometries, sedimentary structures supportive of redeposition, mixed environment fossil associations, and stratigraphic enclosure within bathyal mudrocks and flysch. The carbonate component of the deposits consists mainly of bivalves, larger benthic foraminifers (especially Amphistegina), coralline red algae including rhodoliths (Lithothamnion and Mesophyllum), and bryozoans, a warm-temperate, shallow marine skeletal association. While sediment derivation was partly from an eastern contemporary shelf, the bulk of the skeletal carbonate is inferred to have been sourced from shoal carbonate factories around and upon isolated basement highs (Patea-Tongaporutu High) to the south. The Mangarara sediments were redeposited within slope gullies and broad open submarine channels and lobes in the vicinity of the channel-lobe transition zone of a submarine fan system. Different phases of sediment transport and deposition (lateral-accretion and aggradation stages) are identified in the channel infilling. Dual fan systems likely co-existed, one dominating and predominantly siliciclastic in nature (Moki Formation), and the other infrequent and involving the temperate calcareous deposits of Mangarara Formation. The Mangarara Formation is an outcrop analogue for middle Miocene-age carbonate slope-fan deposits elsewhere in subsurface Taranaki Basin, New Zealand

Using palaeoenvironmental DNA to reconstruct past environments: progress and prospects

Palaeoenvironmental DNA (PalEnDNA) is defined as ancient DNA (aDNA) originating from disseminated genetic material within palaeoenvironmental samples. Sources of PalEnDNA include marine and lake sediments, peat, loess, till, ice, permafrost, palaeosols, coprolites, preserved gut contents, dental calculus, tephras, and soils as well as deposits in caves/rockshelters and at archaeological sites. PalEnDNA analysis provides a relatively new tool for Quaternary and archaeological sciences and its applications have included palaeoenvironmental and palaeodietary reconstructions, testing hypotheses regarding megafaunal extinctions, human–environment interactions, taxonomic studies and studies of DNA damage. Because PalEnDNA samples comprise markedly different materials, and represent wide-ranging depositional and taphonomic contexts, various issues must be addressed to achieve robust, reproducible findings. Such issues include climatic and temporal limitations, the biological origin and state (free versus bound) of PalEnDNA, stratigraphic reliability, sterile sampling, ability to distinguish modern from aDNA signals, DNA damage and PCR amplification, DNA extraction methods, and taxonomic resolution. In this review, we provide a non-specialist introduction to the use of PalEnDNA for Quaternary and archaeological researchers, assess attributes and limitations of this palaeoenvironmental tool, and discuss future prospects of using PalEnDNA to reconstruct past environments

Epigenetics as a mechanism driving polygenic clinical drug resistance

Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance

European admixture on the Micronesian island of Kosrae: lessons from complete genetic information

The architecture of natural variation present in a contemporary population is a result of multiple population genetic forces, including population bottleneck and expansion, selection, drift, and admixture. We seek to untangle the contribution of admixture to genetic diversity on the Micronesian island of Kosrae. Toward this goal, we used a complete genetic approach by combining a dense genome-wide map of 100 000 single-nucleotide polymorphisms (SNPs) with data from uniparental markers from the mitochondrial genome and the nonrecombining portion of the Y chromosome. These markers were typed in ∼3200 individuals from Kosrae, representing 80% of the adult population of the island. We developed novel software that uses SNP data to delineate ancestry for individual segments of the genome. Through this analysis, we determined that 39% of Kosraens have some European ancestry. However, the vast majority of admixed individuals (77%) have European alleles spanning less than 10% of their genomes. Data from uniparental markers show most of this admixture to be male, introduced in the late nineteenth century. Furthermore, pedigree analysis shows that the majority of European admixture on Kosrae is because of the contribution of one individual. This approach shows the benefit of combining information from autosomal and uniparental polymorphisms and provides new methodology for determining ancestry in a population

A cognitive forcing tool to mitigate cognitive bias:A randomised control trial

Abstract Background Cognitive bias is an important source of diagnostic error yet is a challenging area to understand and teach. Our aim was to determine whether a cognitive forcing tool can reduce the rates of error in clinical decision making. A secondary objective was to understand the process by which this effect might occur. Methods We hypothesised that using a cognitive forcing tool would reduce diagnostic error rates. To test this hypothesis, a novel online case-based approach was used to conduct a single blinded randomized clinical trial conducted from January 2017 to September 2018. In addition, a qualitative series of “think aloud” interviews were conducted with 20 doctors from a UK teaching hospital in 2018. The primary outcome was the diagnostic error rate when solving bias inducing clinical vignettes. A volunteer sample of medical professionals from across the UK, Republic of Ireland and North America. They ranged in seniority from medical student to Attending Physician. Results Seventy six participants were included in the study. The data showed doctors of all grades routinely made errors related to cognitive bias. There was no difference in error rates between groups (mean 2.8 cases correct in intervention vs 3.1 in control group, 95% CI -0.94 – 0.45 P = 0.49). The qualitative protocol revealed that the cognitive forcing strategy was well received and a produced a subjectively positive impact on doctors’ accuracy and thoughtfulness in clinical cases. Conclusions The quantitative data failed to show an improvement in accuracy despite a positive qualitative experience. There is insufficient evidence to recommend this tool in clinical practice, however the qualitative data suggests such an approach has some merit and face validity to users

The Epstein-Barr Virus G-Protein-Coupled Receptor Contributes to Immune Evasion by Targeting MHC Class I Molecules for Degradation

Epstein-Barr virus (EBV) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. Recent evidence indicates that an important component of the persistence strategy involves active interference with the MHC class I antigen processing pathway during the lytic replication cycle. We have now identified a novel role for the lytic cycle gene, BILF1, which encodes a glycoprotein with the properties of a constitutive signaling G-protein-coupled receptor (GPCR). BILF1 reduced the levels of MHC class I at the cell surface and inhibited CD8+ T cell recognition of endogenous target antigens. The underlying mechanism involves physical association of BILF1 with MHC class I molecules, an increased turnover from the cell surface, and enhanced degradation via lysosomal proteases. The BILF1 protein of the closely related CeHV15 c1-herpesvirus of the Rhesus Old World primate (80% amino acid sequence identity) downregulated surface MHC class I similarly to EBV BILF1. Amongst the human herpesviruses, the GPCR encoded by the ORF74 of the KSHV c2-herpesvirus is most closely related to EBV BILF1 (15% amino acid sequence identity) but did not affect levels of surface MHC class I. An engineered mutant of BILF1 that was unable to activate G protein signaling pathways retained the ability to downregulate MHC class I, indicating that the immune-modulating and GPCR-signaling properties are two distinct functions of BILF1. These findings extend our understanding of the normal biology of an important human pathogen. The discovery of a third EBV lytic cycle gene that cooperates to interfere with MHC class I antigen processing underscores the importance of the need for EBV to be able to evade CD8+ T cell responses during the lytic replication cycle, at a time when such a large number of potential viral targets are expressed

Automatic Diagnosis of Pathological Myopia from Heterogeneous Biomedical Data

10.1371/journal.pone.0065736PLoS ONE86

The implications of climate change for the water environment in England

This paper reviews the implications of climate change for the water environment and its management in England. There is a large literature, but most studies have looked at flow volumes or nutrients and none have considered explicitly the implications of climate change for the delivery of water management objectives. Studies have been undertaken in a small number of locations. Studies have used observations from the past to infer future changes, and have used numerical simulation models with climate change scenarios. The literature indicates that climate change poses risks to the delivery of water management objectives, but that these risks depend on local catchment and water body conditions. Climate change affects the status of water bodies, and it affects the effectiveness of measures to manage the water environment and meet policy objectives. The future impact of climate change on the water environment and its management is uncertain. Impacts are dependent on changes in the duration of dry spells and frequency of ‘flushing’ events, which are highly uncertain and not included in current climate scenarios. There is a good qualitative understanding of ways in which systems may change, but interactions between components of the water environment are poorly understood. Predictive models are only available for some components, and model parametric and structural uncertainty has not been evaluated. The impacts of climate change depend on other pressures on the water environment in a catchment, and also on the management interventions that are undertaken to achieve water management objectives. The paper has also developed a series of consistent conceptual models describing the implications of climate change for pressures on the water environment, based around the source-pathway-receptor concept. They provide a framework for a systematic assessment across catchments and pressures of the implications of climate change for the water environment and its management