Don't know, can't know: Embracing deeper uncertainties when analysing risks

This article is available open access through the publisher’s website at the link below. Copyright @ 2011 The Royal Society.Numerous types of uncertainty arise when using formal models in the analysis of risks. Uncertainty is best seen as a relation, allowing a clear separation of the object, source and ‘owner’ of the uncertainty, and we argue that all expressions of uncertainty are constructed from judgements based on possibly inadequate assumptions, and are therefore contingent. We consider a five-level structure for assessing and communicating uncertainties, distinguishing three within-model levels—event, parameter and model uncertainty—and two extra-model levels concerning acknowledged and unknown inadequacies in the modelling process, including possible disagreements about the framing of the problem. We consider the forms of expression of uncertainty within the five levels, providing numerous examples of the way in which inadequacies in understanding are handled, and examining criticisms of the attempts taken by the Intergovernmental Panel on Climate Change to separate the likelihood of events from the confidence in the science. Expressing our confidence in the adequacy of the modelling process requires an assessment of the quality of the underlying evidence, and we draw on a scale that is widely used within evidence-based medicine. We conclude that the contingent nature of risk-modelling needs to be explicitly acknowledged in advice given to policy-makers, and that unconditional expressions of uncertainty remain an aspiration

Trade-off between angular and spatial resolutions in in vivo fiber tractography

Tractography is becoming an increasingly popular method to reconstruct white matter connections in vivo. The diffusion MRI data that tractography is based on requires a high angular resolution to resolve crossing fibers whereas high spatial resolution is required to distinguish kissing from crossing fibers. However, scan time increases with increasing spatial and angular resolutions, which can become infeasible in clinical settings. Here we investigated the trade-off between spatial and angular resolutions to determine which of these factors is most worth investing scan time in. We created a unique diffusion MRI dataset with 1.0mm isotropic resolution and a high angular resolution (100 directions) using an advanced 3D diffusion-weighted multi-slab EPI acquisition. This dataset was reconstructed to create subsets of lower angular (75, 50, and 25 directions) and lower spatial (1.5, 2.0, and 2.5mm) resolution. Using all subsets, we investigated the effects of angular and spatial resolutions in three fiber bundles-the corticospinal tract, arcuate fasciculus and corpus callosum-by analyzing the volumetric bundle overlap and anatomical correspondence between tracts. Our results indicate that the subsets of 25 and 50 directions provided inferior tract reconstructions compared with the datasets with 75 and 100 directions. Datasets with spatial resolutions of 1.0, 1.5, and 2.0mm were comparable, while the lowest resolution (2.5mm) datasets had discernible inferior quality. In conclusion, we found that angular resolution appeared to be more influential than spatial resolution in improving tractography results. Spatial resolutions higher than 2.0mm only appear to benefit multi-fiber tractography methods if this is not at the cost of decreased angular resolution

The Airn lncRNA does not require any DNA elements within its locus to silence distant imprinted genes

Long non-coding (lnc) RNAs are numerous and found throughout the mammalian genome, and many are thought to be involved in the regulation of gene expression. However, the majority remain relatively uncharacterised and of uncertain function making the use of model systems to uncover their mode of action valuable. Imprinted lncRNAs target and recruit epigenetic silencing factors to a cluster of imprinted genes on the same chromosome, making them one of the best characterized lncRNAs for silencing distant genes in cis. In this study we examined silencing of the distant imprinted gene Slc22a3 by the lncRNA Airn in the Igf2r imprinted cluster in mouse. Previously we proposed that imprinted lncRNAs may silence distant imprinted genes by disrupting promoter-enhancer interactions by being transcribed through the enhancer, which we called the enhancer interference hypothesis. Here we tested this hypothesis by first using allele-specific chromosome conformation capture (3C) to detect interactions between the Slc22a3 promoter and the locus of the Airn lncRNA that silences it on the paternal chromosome. In agreement with the model, we found interactions enriched on the maternal allele across the entire Airn gene consistent with multiple enhancer-promoter interactions. Therefore, to test the enhancer interference hypothesis we devised an approach to delete the entire Airn gene. However, the deletion showed that there are no essential enhancers for Slc22a2, Pde10a and Slc22a3 within the Airn gene, strongly indicating that the Airn RNA rather than its transcription is responsible for silencing distant imprinted genes. Furthermore, we found that silent imprinted genes were covered with large blocks of H3K27me3 on the repressed paternal allele. Therefore we propose an alternative hypothesis whereby the chromosome interactions may initially guide the lncRNA to target imprinted promoters and recruit repressive chromatin, and that these interactions are lost once silencing is established

Relationship among research collaboration, number of documents and number of citations. A case study in Spanish computer science production in 2000-2009.

This paper analyzes the relationship among research collaboration, number of documents and number of citations of computer science research activity. It analyzes the number of documents and citations and how they vary by number of authors. They are also analyzed (according to author set cardinality) under different circumstances, that is, when documents are written in different types of collaboration, when documents are published in different document types, when documents are published in different computer science subdisciplines, and, finally, when documents are published by journals with different impact factor quartiles. To investigate the above relationships, this paper analyzes the publications listed in the Web of Science and produced by active Spanish university professors between 2000 and 2009, working in the computer science field. Analyzing all documents, we show that the highest percentage of documents are published by three authors, whereas single-authored documents account for the lowest percentage. By number of citations, there is no positive association between the author cardinality and citation impact. Statistical tests show that documents written by two authors receive more citations per document and year than documents published by more authors. In contrast, results do not show statistically significant differences between documents published by two authors and one author. The research findings suggest that international collaboration results on average in publications with higher citation rates than national and institutional collaborations. We also find differences regarding citation rates between journals and conferences, across different computer science subdisciplines and journal quartiles as expected. Finally, our impression is that the collaborative level (number of authors per document) will increase in the coming years, and documents published by three or four authors will be the trend in computer science literature

A holistic multi-methodology for sustainable renovation

A review of the barriers for building renovation has revealed a lack of methodologies, which can promote sustainability objectives and assist various stakeholders during the design stage of building renovation/retrofitting projects. The purpose of this paper is to develop a Holistic Multi-methodology for Sustainable Renovation, which aims to deal with complexity of renovation projects. It provides a framework through which to involve the different stakeholders in the design process to improve group learning and group decision-making, and hence make the building renovation design process more robust and efficient. Therefore, the paper discusses the essence of multifaceted barriers in building renovation regarding cultural changes and technological/physical changes. The outcome is a proposal for a multi-methodology framework, which is developed by introducing, evaluating and mixing methods from Soft Systems Methodologies (SSM) with Multiple Criteria Decision Making (MCDM). The potential of applying the proposed methodology in renovation projects is demonstrated through a case study

Three dimensional three component whole heart cardiovascular magnetic resonance velocity mapping: comparison of flow measurements from 3D and 2D acquisitions

<p>Abstract</p> <p>Background</p> <p>Two-dimensional, unidirectionally encoded, cardiovascular magnetic resonance (CMR) velocity mapping is an established technique for the quantification of blood flow in large vessels. However, it requires an operator to correctly align the planes of acquisition. If all three directional components of velocity are measured for each voxel of a 3D volume through the phases of the cardiac cycle, blood flow through any chosen plane can potentially be calculated retrospectively. The initial acquisition is then more time consuming but relatively operator independent.</p> <p>Aims</p> <p>To compare the curves and volumes of flow derived from conventional 2D and comprehensive 3D flow acquisitions in a steady state flow model, and in vivo through planes transecting the ascending aorta and pulmonary trunk in 10 healthy volunteers.</p> <p>Methods</p> <p>Using a 1.5 T Phillips Intera CMR system, 3D acquisitions used an anisotropic 3D segmented k-space phase contrast gradient echo sequence with a short EPI readout, with prospective ECG and diaphragm navigator gating. The 2D acquisitions used segmented k-space phase contrast with prospective ECG and diaphragm navigator gating. Quantitative flow analyses were performed retrospectively with dedicated software for both the in vivo and in vitro acquisitions.</p> <p>Results</p> <p>Analysis of in vitro data found the 3D technique to have overestimated the continuous flow rate by approximately 5% across the entire applied flow range. In vivo, the 2D and the 3D techniques yielded similar volumetric flow curves and measurements. Aortic flow: (mean ± SD), 2D = 89.5 ± 13.5 ml & 3D = 92.7 ± 17.5 ml. Pulmonary flow: 2D = 98.8 ± 18.4 ml & 3D = 94.9 ± 19.0 ml). Each in vivo 3D acquisition took about 8 minutes or more.</p> <p>Conclusion</p> <p>Flow measurements derived from the 3D and 2D acquisitions were comparable. Although time consuming, comprehensive 3D velocity acquisition could be relatively operator independent, and could potentially yield information on flow through several retrospectively chosen planes, for example in patients with congenital or valvular heart disease.</p