Stakeholder perspectives of a pilot multicomponent delirium prevention intervention for adult patients with advanced cancer in palliative care units: A behaviour change theory-based qualitative study.

BACKGROUND: Theory-based and qualitative evaluations in pilot trials of complex clinical interventions help to understand quantitative results, as well as inform the feasibility and design of subsequent effectiveness and implementation trials. AIM: To explore patient, family, clinician and volunteer ('stakeholder') perspectives of the feasibility and acceptability of a multicomponent non-pharmacological delirium prevention intervention for adult patients with advanced cancer in four Australian palliative care units that participated in a phase II trial, the 'PRESERVE pilot study'. DESIGN: A trial-embedded qualitative study via semi-structured interviews and directed content analysis using Michie's Behaviour Change Wheel and the Theoretical Domains Framework. SETTING/PARTICIPANTS: Thirty-nine people involved in the trial: nurses (n = 17), physicians (n = 6), patients (n = 6), family caregivers (n = 4), physiotherapists (n = 3), a social worker, a pastoral care worker and a volunteer. RESULTS: Participants' perspectives aligned with the 'capability', 'opportunity' and 'motivation' domains of the applied frameworks. Of seven themes, three were around the alignment of the delirium prevention intervention with palliative care (intervention was considered routine care; intervention aligned with the compassionate and collaborative culture of palliative care; and differing views of palliative care priorities influenced perspectives of the intervention) and four were about study processes more directly related to adherence to the intervention (shared knowledge increased engagement with the intervention; impact of the intervention checklist on attention, delivery and documentation of the delirium prevention strategies; clinical roles and responsibilities; and addressing environmental barriers to delirium prevention). CONCLUSION: This theory-informed qualitative study identified multiple influences on the delivery and documentation of a pilot multicomponent non-pharmacological delirium prevention intervention in four palliative care units. Findings inform future definitive studies of delirium prevention in palliative care.Australian New Zealand Clinical Trials Registry, ACTRN12617001070325; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373168.

A Multicomponent Nonpharmacological Intervention to Prevent Delirium for Hospitalized People with Advanced Cancer: A Phase II Cluster Randomized Waitlist Controlled Trial (The PRESERVE Pilot Study).

Background: Delirium is a common debilitating complication of advanced cancer. Objective: To determine if a multicomponent nonpharmacological delirium prevention intervention was feasible for adult patients with advanced cancer, before a phase III (efficacy) trial. Design: Phase II (feasibility) cluster randomized controlled trial. All sites implemented delirium screening and diagnostic assessment. Strategies within sleep, vision and hearing, hydration, orientation, mobility, and family domains were delivered to enrolled patients at intervention site admission days 1-7. Control sites then implemented the intervention ("waitlist sites"). Setting: Four Australian palliative care units. Measurements: The primary outcome was adherence, with an a priori endpoint of at least 60% patients achieving full adherence. Secondary outcomes were interdisciplinary care delivery, delirium measures, and adverse events, analyzed descriptively and inferentially. Results: Sixty-five enrolled patients (25 control, 20 intervention, and 20 waitlist) had 98% delirium screens and 75% diagnostic assessments completed. Nurses (67%), physicians (16%), allied health (8.4%), family (7%), patients (1%), and volunteers (0.5%) delivered the intervention. There was full adherence for 5% patients at intervention sites, partial for 25%. Both full and partial adherence were higher at waitlist sites: 25% and 45%, respectively. One-third of control site patients (32%) became delirious within seven days of admission compared to one-fifth (20%) at both intervention and waitlist sites (p = 0.5). Mean (standard deviation) Delirium Rating Scale-Revised-1998 scores were 16.8 + 12.0 control sites versus 18.4 + 8.2 (p = 0.6) intervention and 18.7 + 7.8 (p = 0.5) waitlist sites. The intervention caused no adverse events. Conclusion: The intervention requires modification for optimal adherence in a phase III trial.

ENVIRONMENTS and EOL: identification of Environment Ontology terms in text and the annotation of the Encyclopedia of Life.

UNLABELLED: The association of organisms to their environments is a key issue in exploring biodiversity patterns. This knowledge has traditionally been scattered, but textual descriptions of taxa and their habitats are now being consolidated in centralized resources. However, structured annotations are needed to facilitate large-scale analyses. Therefore, we developed ENVIRONMENTS, a fast dictionary-based tagger capable of identifying Environment Ontology (ENVO) terms in text. We evaluate the accuracy of the tagger on a new manually curated corpus of 600 Encyclopedia of Life (EOL) species pages. We use the tagger to associate taxa with environments by tagging EOL text content monthly, and integrate the results into the EOL to disseminate them to a broad audience of users. AVAILABILITY AND IMPLEMENTATION: The software and the corpus are available under the open-source BSD and the CC-BY-NC-SA 3.0 licenses, respectively, at http://environments.hcmr.gr.

The Encyclopedia of Life v2: Providing Global Access to Knowledge About Life on Earth.

The Encyclopedia of Life (EOL, http://eol.org) aims to provide unprecedented global access to a broad range of information about life on Earth. It currently contains 3.5 million distinct pages for taxa and provides content for 1.3 million of those pages. The content is primarily contributed by EOL content partners (providers) that have a more limited geographic, taxonomic or topical scope. EOL aggregates these data and automatically integrates them based on associated scientific names and other classification information. EOL also provides interfaces for curation and direct content addition. All materials in EOL are either in the public domain or licensed under a Creative Commons license. In addition to the web interface, EOL is also accessible through an Application Programming Interface. In this paper, we review recent developments added for Version 2 of the web site and subsequent releases through Version 2.2, which have made EOL more engaging, personal, accessible and internationalizable. We outline the core features and technical architecture of the system. We summarize milestones achieved so far by EOL to present results of the current system implementation and establish benchmarks upon which to judge future improvements. We have shown that it is possible to successfully integrate large amounts of descriptive biodiversity data from diverse sources into a robust, standards-based, dynamic, and scalable infrastructure. Increasing global participation and the emergence of EOL-powered applications demonstrate that EOL is becoming a significant resource for anyone interested in biological diversity.

Knowledge extraction and semantic annotation of text from the encyclopedia of life.

Numerous digitization and ontological initiatives have focused on translating biological knowledge from narrative text to machine-readable formats. In this paper, we describe two workflows for knowledge extraction and semantic annotation of text data objects featured in an online biodiversity aggregator, the Encyclopedia of Life. One workflow tags text with DBpedia URIs based on keywords. Another workflow finds taxon names in text using GNRD for the purpose of building a species association network. Both workflows work well: the annotation workflow has an F1 Score of 0.941 and the association algorithm has an F1 Score of 0.885. Existing text annotators such as Terminizer and DBpedia Spotlight performed well, but require some optimization to be useful in the ecology and evolution domain. Important future work includes scaling up and improving accuracy through the use of distributional semantics.

A decadal view of biodiversity informatics: challenges and priorities.

Biodiversity informatics plays a central enabling role in the research community's efforts to address scientific conservation and sustainability issues. Great strides have been made in the past decade establishing a framework for sharing data, where taxonomy and systematics has been perceived as the most prominent discipline involved. To some extent this is inevitable, given the use of species names as the pivot around which information is organised. To address the urgent questions around conservation, land-use, environmental change, sustainability, food security and ecosystem services that are facing Governments worldwide, we need to understand how the ecosystem works. So, we need a systems approach to understanding biodiversity that moves significantly beyond taxonomy and species observations. Such an approach needs to look at the whole system to address species interactions, both with their environment and with other species.It is clear that some barriers to progress are sociological, basically persuading people to use the technological solutions that are already available. This is best addressed by developing more effective systems that deliver immediate benefit to the user, hiding the majority of the technology behind simple user interfaces. An infrastructure should be a space in which activities take place and, as such, should be effectively invisible.This community consultation paper positions the role of biodiversity informatics, for the next decade, presenting the actions needed to link the various biodiversity infrastructures invisibly and to facilitate understanding that can support both business and policy-makers. The community considers the goal in biodiversity informatics to be full integration of the biodiversity research community, including citizens' science, through a commonly-shared, sustainable e-infrastructure across all sub-disciplines that reliably serves science and society alike.

A large-scale, higher-level, molecular phylogenetic study of the insect order Lepidoptera (moths and butterflies).

BACKGROUND: Higher-level relationships within the Lepidoptera, and particularly within the species-rich subclade Ditrysia, are generally not well understood, although recent studies have yielded progress. We present the most comprehensive molecular analysis of lepidopteran phylogeny to date, focusing on relationships among superfamilies. METHODOLOGY PRINCIPAL FINDINGS: 483 taxa spanning 115 of 124 families were sampled for 19 protein-coding nuclear genes, from which maximum likelihood tree estimates and bootstrap percentages were obtained using GARLI. Assessment of heuristic search effectiveness showed that better trees and higher bootstrap percentages probably remain to be discovered even after 1000 or more search replicates, but further search proved impractical even with grid computing. Other analyses explored the effects of sampling nonsynonymous change only versus partitioned and unpartitioned total nucleotide change; deletion of rogue taxa; and compositional heterogeneity. Relationships among the non-ditrysian lineages previously inferred from morphology were largely confirmed, plus some new ones, with strong support. Robust support was also found for divergences among non-apoditrysian lineages of Ditrysia, but only rarely so within Apoditrysia. Paraphyly for Tineoidea is strongly supported by analysis of nonsynonymous-only signal; conflicting, strong support for tineoid monophyly when synonymous signal was added back is shown to result from compositional heterogeneity. CONCLUSIONS SIGNIFICANCE: Support for among-superfamily relationships outside the Apoditrysia is now generally strong. Comparable support is mostly lacking within Apoditrysia, but dramatically increased bootstrap percentages for some nodes after rogue taxon removal, and concordance with other evidence, strongly suggest that our picture of apoditrysian phylogeny is approximately correct. This study highlights the challenge of finding optimal topologies when analyzing hundreds of taxa. It also shows that some nodes get strong support only when analysis is restricted to nonsynonymous change, while total change is necessary for strong support of others. Thus, multiple types of analyses will be necessary to fully resolve lepidopteran phylogeny.

Evolutionary informatics: unifying knowledge about the diversity of life.

The accelerating growth of data and knowledge in evolutionary biology is indisputable. Despite this rapid progress, information remains scattered, poorly documented and in formats that impede discovery and integration. A grand challenge is the creation of a linked system of all evolutionary data, information and knowledge organized around Darwin's ever-growing Tree of Life. Such a system, accommodating topological disagreement where necessary, would consolidate taxon names, phenotypic and geographical distributional data across clades, and serve as an integrated community resource. The field of evolutionary informatics, reviewed here for the first time, has matured into a robust discipline that is developing the conceptual, infrastructure and community frameworks for meeting this grand challenge.

RCN4GSC Workshop Report: Managing Data at the Interface of Biodiversity and (Meta)Genomics, March 2011.

Building on the planning efforts of the RCN4GSC project, a workshop was convened in San Diego to bring together experts from genomics and metagenomics, biodiversity, ecology, and bioinformatics with the charge to identify potential for positive interactions and progress, especially building on successes at establishing data standards by the GSC and by the biodiversity and ecological communities. Until recently, the contribution of microbial life to the biomass and biodiversity of the biosphere was largely overlooked (because it was resistant to systematic study). Now, emerging genomic and metagenomic tools are making investigation possible. Initial research findings suggest that major advances are in the offing. Although different research communities share some overlapping concepts and traditions, they differ significantly in sampling approaches, vocabularies and workflows. Likewise, their definitions of 'fitness for use' for data differ significantly, as this concept stems from the specific research questions of most importance in the different fields. Nevertheless, there is little doubt that there is much to be gained from greater coordination and integration. As a first step toward interoperability of the information systems used by the different communities, participants agreed to conduct a case study on two of the leading data standards from the two formerly disparate fields: (a) GSC's standard checklists for genomics and metagenomics and (b) TDWG's Darwin Core standard, used primarily in taxonomy and systematic biology.

Can deliberately incomplete gene sample augmentation improve a phylogeny estimate for the advanced moths and butterflies (Hexapoda: Lepidoptera)?

This paper addresses the question of whether one can economically improve the robustness of a molecular phylogeny estimate by increasing gene sampling in only a subset of taxa, without having the analysis invalidated by artifacts arising from large blocks of missing data. Our case study stems from an ongoing effort to resolve poorly understood deeper relationships in the large clade Ditrysia ( > 150,000 species) of the insect order Lepidoptera (butterflies and moths). Seeking to remedy the overall weak support for deeper divergences in an initial study based on five nuclear genes (6.6 kb) in 123 exemplars, we nearly tripled the total gene sample (to 26 genes, 18.4 kb) but only in a third (41) of the taxa. The resulting partially augmented data matrix (45% intentionally missing data) consistently increased bootstrap support for groupings previously identified in the five-gene (nearly) complete matrix, while introducing no contradictory groupings of the kind that missing data have been predicted to produce. Our results add to growing evidence that data sets differing substantially in gene and taxon sampling can often be safely and profitably combined. The strongest overall support for nodes above the family level came from including all nucleotide changes, while partitioning sites into sets undergoing mostly nonsynonymous versus mostly synonymous change. In contrast, support for the deepest node for which any persuasive molecular evidence has yet emerged (78-85% bootstrap) was weak or nonexistent unless synonymous change was entirely excluded, a result plausibly attributed to compositional heterogeneity. This node (Gelechioidea + Apoditrysia), tentatively proposed by previous authors on the basis of four morphological synapomorphies, is the first major subset of ditrysian superfamilies to receive strong statistical support in any phylogenetic study. A "more-genes-only" data set (41 taxa×26 genes) also gave strong signal for a second deep grouping (Macrolepidoptera) that was obscured, but not strongly contradicted, in more taxon-rich analyses.

Semantic tagging of and semantic enhancements to systematics papers: ZooKeys working examples.

The concept of semantic tagging and its potential for semantic enhancements to taxonomic papers is outlined and illustrated by four exemplar papers published in the present issue of ZooKeys. The four papers were created in different ways: (i) written in Microsoft Word and submitted as non-tagged manuscript (doi: 10.3897/zookeys.50.504); (ii) generated from Scratchpads and submitted as XML-tagged manuscripts (doi: 10.3897/zookeys.50.505 and doi: 10.3897/zookeys.50.506); (iii) generated from an author's database (doi: 10.3897/zookeys.50.485) and submitted as XML-tagged manuscript. XML tagging and semantic enhancements were implemented during the editorial process of ZooKeys using the Pensoft Mark Up Tool (PMT), specially designed for this purpose. The XML schema used was TaxPub, an extension to the Document Type Definitions (DTD) of the US National Library of Medicine Journal Archiving and Interchange Tag Suite (NLM). The following innovative methods of tagging, layout, publishing and disseminating the content were tested and implemented within the ZooKeys editorial workflow: (1) highly automated, fine-grained XML tagging based on TaxPub; (2) final XML output of the paper validated against the NLM DTD for archiving in PubMedCentral; (3) bibliographic metadata embedded in the PDF through XMP (Extensible Metadata Platform); (4) PDF uploaded after publication to the Biodiversity Heritage Library (BHL); (5) taxon treatments supplied through XML to Plazi; (6) semantically enhanced HTML version of the paper encompassing numerous internal and external links and linkouts, such as: (i) vizualisation of main tag elements within the text (e.g., taxon names, taxon treatments, localities, etc.); (ii) internal cross-linking between paper sections, citations, references, tables, and figures; (iii) mapping of localities listed in the whole paper or within separate taxon treatments; (v) taxon names autotagged, dynamically mapped and linked through the Pensoft Taxon Profile (PTP) to large international database services and indexers such as Global Biodiversity Information Facility (GBIF), National Center for Biotechnology Information (NCBI), Barcode of Life (BOLD), Encyclopedia of Life (EOL), ZooBank, Wikipedia, Wikispecies, Wikimedia, and others; (vi) GenBank accession numbers autotagged and linked to NCBI; (vii) external links of taxon names to references in PubMed, Google Scholar, Biodiversity Heritage Library and other sources. With the launching of the working example, ZooKeys becomes the first taxonomic journal to provide a complete XML-based editorial, publication and dissemination workflow implemented as a routine and cost-efficient practice. It is anticipated that XML-based workflow will also soon be implemented in botany through PhytoKeys, a forthcoming partner journal of ZooKeys. The semantic markup and enhancements are expected to greatly extend and accelerate the way taxonomic information is published, disseminated and used.

Toward reconstructing the evolution of advanced moths and butterflies (Lepidoptera: Ditrysia): an initial molecular study.

BACKGROUND: In the mega-diverse insect order Lepidoptera (butterflies and moths; 165,000 described species), deeper relationships are little understood within the clade Ditrysia, to which 98% of the species belong. To begin addressing this problem, we tested the ability of five protein-coding nuclear genes (6.7 kb total), and character subsets therein, to resolve relationships among 123 species representing 27 (of 33) superfamilies and 55 (of 100) families of Ditrysia under maximum likelihood analysis. RESULTS: Our trees show broad concordance with previous morphological hypotheses of ditrysian phylogeny, although most relationships among superfamilies are weakly supported. There are also notable surprises, such as a consistently closer relationship of Pyraloidea than of butterflies to most Macrolepidoptera. Monophyly is significantly rejected by one or more character sets for the putative clades Macrolepidoptera as currently defined (P < 0.05) and Macrolepidoptera excluding Noctuoidea and Bombycoidea sensu lato (P < or = 0.005), and nearly so for the superfamily Drepanoidea as currently defined (P < 0.08). Superfamilies are typically recovered or nearly so, but usually without strong support. Relationships within superfamilies and families, however, are often robustly resolved. We provide some of the first strong molecular evidence on deeper splits within Pyraloidea, Tortricoidea, Geometroidea, Noctuoidea and others.Separate analyses of mostly synonymous versus non-synonymous character sets revealed notable differences (though not strong conflict), including a marked influence of compositional heterogeneity on apparent signal in the third codon position (nt3). As available model partitioning methods cannot correct for this variation, we assessed overall phylogeny resolution through separate examination of trees from each character set. Exploration of "tree space" with GARLI, using grid computing, showed that hundreds of searches are typically needed to find the best-feasible phylogeny estimate for these data. CONCLUSION: Our results (a) corroborate the broad outlines of the current working phylogenetic hypothesis for Ditrysia, (b) demonstrate that some prominent features of that hypothesis, including the position of the butterflies, need revision, and (c) resolve the majority of family and subfamily relationships within superfamilies as thus far sampled. Much further gene and taxon sampling will be needed, however, to strongly resolve individual deeper nodes.

TreePlus: interactive exploration of networks with enhanced tree layouts.

Despite extensive research, it is still difficult to produce effective interactive layouts for large graphs. Dense layout and occlusion make food webs, ontologies, and social networks difficult to understand and interact with. We propose a new interactive Visual Analytics component called TreePlus that is based on a tree-style layout. TreePlus reveals the missing graph structure with visualization and interaction while maintaining good readability. To support exploration of the local structure of the graph and gathering of information from the extensive reading of labels, we use a guiding metaphor of "Plant a seed and watch it grow." It allows users to start with a node and expand the graph as needed, which complements the classic overview techniques that can be effective at (but often limited to) revealing clusters. We describe our design goals, describe the interface, and report on a controlled user study with 28 participants comparing TreePlus with a traditional graph interface for six tasks. In general, the advantage of TreePlus over the traditional interface increased as the density of the displayed data increased. Participants also reported higher levels of confidence in their answers with TreePlus and most of them preferred TreePlus.

Visualizations for taxonomic and phylogenetic trees.

MOTIVATION: Despite substantial efforts to develop and populate the back-ends of biological databases, front-ends to these systems often rely on taxonomic expertise. This research applies techniques from human-computer interaction research to the biodiversity domain. RESULTS: We developed an interactive node-link tool, TaxonTree, illustrating the value of a carefully designed interaction model, animation, and integrated searching and browsing towards retrieval of biological names and other information. Users tested the tool using a new, large integrated dataset of animal names with phylogenetic-based and classification-based tree structures. These techniques also translated well for a tool, DoubleTree, to allow comparison of trees using coupled interaction. Our approaches will be useful not only for biological data but as general portal interfaces.

Phylogeny of magpies (genus Pica) inferred from mtDNA data.

We investigated the phylogenetic relationships of species and subspecies of the cosmopolitan genus Pica using 813 bp of the mitochondrial genome (including portions of 16s rDNA, tRNA-Leu, and ND1). The phylogenetic relationships within the genus Pica revealed in our molecular analyses can be summarized as follows: (1). the Korean magpie (Pica pica sericea) appears basal within the genus Pica; (2). the European magpie (Pica pica pica) shows a close relationship to the Kamchatkan magpie (Pica pica camtschatica); (3). two North American species (Pica hudsonia and Pica nuttalli) shows a sister-group relationship; (4). most importantly, the European+Kamchatkan clade appears more closely related to the North American clade than to Korean magpies. Based on these results and genetic distance data, it is possible that members of an ancestral magpie lineage in East Asia initially moved north to form Kamchatkan magpies and then crossed the Bering land bridge to found North American taxa. At a later date, a group might have split off from Kamchatkan magpies and migrated west to form the Eurasian subspecies. The divergence between the two North American taxa appears to have happened no later than the divergence of Eurasian subspecies and both processes appear to have been relatively rapid. Rather than the formation of P. hudsonia by re-colonization from an Asian magpie ancestor, as suggested by, our data suggest a shared ancestry between P. hudsonia and P. nuttalli. Based on the above findings, including phylogenetic placement of P. hudsonia and P. nuttalli as nested within the larger Pica pica clade, and the lack of evidence suggesting reproductive isolation within the genus Pica, we believe that the current classification may be inaccurate. A more conservative classification would recognize one monophyletic species (i.e., P. pica) and treat P. nuttalli and P. hudsonia as subspecies (i.e., P. p. nuttalli and P. p. hudsonia). More extensive studies on the population genetics and biogeography of magpies should be conducted to better inform any taxonomic decisions.