Collectives of diagnostic biomarkers identify high-risk subpopulations of hematuria patients: exploiting heterogeneity in large-scale biomarker data

Background: Ineffective risk stratification can delay diagnosis of serious disease in patients with hematuria. We applied a systems biology approach to analyze clinical, demographic and biomarker measurements (n = 29) collected from 157 hematuric patients: 80 urothelial cancer (UC) and 77 controls with confounding pathologies.

Methods: On the basis of biomarkers, we conducted agglomerative hierarchical clustering to identify patient and biomarker clusters. We then explored the relationship between the patient clusters and clinical characteristics using Chi-square analyses. We determined classification errors and areas under the receiver operating curve of Random Forest Classifiers (RFC) for patient subpopulations using the biomarker clusters to reduce the dimensionality of the data.

Results: Agglomerative clustering identified five patient clusters and seven biomarker clusters. Final diagnoses categories were non-randomly distributed across the five patient clusters. In addition, two of the patient clusters were enriched with patients with ‘low cancer-risk’ characteristics. The biomarkers which contributed to the diagnostic classifiers for these two patient clusters were similar. In contrast, three of the patient clusters were significantly enriched with patients harboring ‘high cancer-risk” characteristics including proteinuria, aggressive pathological stage and grade, and malignant cytology. Patients in these three clusters included controls, that is, patients with other serious disease and patients with cancers other than UC. Biomarkers which contributed to the diagnostic classifiers for the largest ‘high cancer- risk’ cluster were different than those contributing to the classifiers for the ‘low cancer-risk’ clusters. Biomarkers which contributed to subpopulations that were split according to smoking status, gender and medication were different.

Conclusions: The systems biology approach applied in this study allowed the hematuric patients to cluster naturally on the basis of the heterogeneity within their biomarker data, into five distinct risk subpopulations. Our findings highlight an approach with the promise to unlock the potential of biomarkers. This will be especially valuable in the field of diagnostic bladder cancer where biomarkers are urgently required. Clinicians could interpret risk classification scores in the context of clinical parameters at the time of triage. This could reduce cystoscopies and enable priority diagnosis of aggressive diseases, leading to improved patient outcomes at reduced costs. © 2013 Emmert-Streib et al; licensee BioMed Central Ltd.

Stated choices and benefit estimates in the context of traffic calming schemes:Utility maximization, regret minimization, or both?

This paper proposes a discrete mixture model which assigns individuals, up to a probability, to either a class of random utility (RU) maximizers or a class of random regret (RR) minimizers, on the basis of their sequence of observed choices. Our proposed model advances the state of the art of RU-RR mixture models by (i) adding and simultaneously estimating a membership model which predicts the probability of belonging to a RU or RR class; (ii) adding a layer of random taste heterogeneity within each behavioural class; and (iii) deriving a welfare measure associated with the RU-RR mixture model and consistent with referendum-voting, which is the adequate mechanism of provision for such local public goods. The context of our empirical application is a stated choice experiment concerning traffic calming schemes. We find that the random parameter RU-RR mixture model not only outperforms its fixed coefficient counterpart in terms of fit-as expected-but also in terms of plausibility of membership determinants of behavioural class. In line with psychological theories of regret, we find that, compared to respondents who are familiar with the choice context (i.e. the traffic calming scheme), unfamiliar respondents are more likely to be regret minimizers than utility maximizers. © 2014 Elsevier Ltd.

The CACTOS Vision of Context-Aware Cloud Topology Optimization and Simulation

Recent advances in hardware development coupled with the rapid adoption and broad applicability of cloud computing have introduced widespread heterogeneity in data centers, significantly complicating the management of cloud applications and data center resources. This paper presents the CACTOS approach to cloud infrastructure automation and optimization, which addresses heterogeneity through a combination of in-depth analysis of application behavior with insights from commercial cloud providers. The aim of the approach is threefold: to model applications and data center resources, to simulate applications and resources for planning and operation, and to optimize application deployment and resource use in an autonomic manner. The approach is based on case studies from the areas of business analytics, enterprise applications, and scientific computing.

Andrew Marvell's Latin Poetry: From Text to Context (356pp.)

David Norbrook, Review of English Studies 56 (Sept. 2005), 675-6.
‘We have waited a long time for a study of Marvell’s Latin poetry; fortunately, Estelle Haan’s monograph generously makes good the loss ... One of her most intriguing suggestions … is that Marvell may have presented paired poems like ‘Ros’ and ‘On a Drop of Dew’, and the poems to the obligingly named Dr Witty, to his student Maria Fairfax as his own patterns for the pedagogical practice of double translation. Perhaps the most original parts of the book, however, move beyond the familiar canon to cover the generic range of the Latin verse. Haan offers a very full contextualization of the early Horatian Ode to Charles I in seventeenth-century exercises in parodia. In a rewarding reading of the poem to Dr Ingelo she shows how Marvell deploys the language of Ovid’s Tristia to present Sweden as a place of shivering exile, only to subvert this model with a neo-Virgilian celebration of Christina as a virtuous, city-building Dido. She draws extensively on historical as well as literary sources to offer very detailed contextualizations of the poem to Maniban and ‘Scaevola Scotto-Britannus’... This monograph opens up many new ways into the Latin verse, not least because it is rounded off with new texts and prose translations of the Latin poems. These make a substantial contribution in their own right. They are the best and most accurate translations to date (those in Smith’s edition having some lapses); they avoid poeticisms but bring out the structure of the poems' wordplay very clearly. This book brings us a lot closer to seeing Marvell whole.'

A 'ruin of all space, shattered glass and toppling masonry': Joyce's Orientalism in the Context of 11 September 2001 and 1922

Chapters 3 and 15 of Joyce's Ulysses exhibit glimpses of three dreams, fantasies and eventual nightmares linked to the figure of 'Haroun al Raschid.' Historically speaking, the latter was a powerful Caliph of Baghdad, a medieval potentate about whom many of the most memorable of The Thousand and One Nights or The Arabian Nights' Entertainments were once and then again spun as tales of pleasure. Joyce seizes upon the figure of 'Haroun al Raschid' as a fictive measure to articulate the 'orientalist' fantasies of Stephen Dedalus and Leopold Bloom. However, this evocative figure of Near Eastern history, of fabulous narrative and the progressively converging fantasies of two modern European literary characters is riddled with paradox. Such material provides Joyce a perceptive and proleptic sense of the paradoxes and brutal historical contradictions through which Western and Eastern dreams of theocratic nationalism, ethnic zealotry, colonial rebellion and Zionism are to be played out. W. B. Yeats' poem 'The Gift of Harun al-Raschid', written in 1923, the year after the book publication of Ulysses, provides both a fitting foil and a significant socio-historical point of reference for Joyce's own figurative use of the Caliph of Baghdad.