Reply to: ''Network-based discovery of gene signature for vascular invasion prediction in HCC''

To the Editor:Liu and colleagues raise some issues regarding our recently pub-lished study [1] to which we would like to make the followingcomments. We acknowledge the limitations that a gene-expres-sion-based biomarker could have, and that our signature is notunique. Certainly, previous attempts to find such a signature havebeen published in the past [2]. We also know that, as in othergene expression studies, potential bias could occur. In fact,reported prognostic signatures are often not reproducible, inmost of the cases due to suboptimal study design, small samplesizes, and also because many of them have been based on retro-spectively collected tissue samples [3]. Even after taking intoaccount these sources of bias or inconsistencies, it so happensthat only a small minority of the reported signatures truly retainprognostic significance. In fact, our recent outcome analysisincluding 22 gene signatures with prognostic significance inHCC (18 from the tumor, and four from the non-tumoral adjacenttissue) showed that only two signatures retained independentprognostic value [4].In our work, we select a training cohort based upon a homo-geneous etiology to minimize the risk of molecular heterogene-ity and to identify a clean and distinct signature. Patients withHCV-related HCC were selected, since this is the most commonetiology in the Western countries. Then, we validate the signa-ture in an independent multi-etiologic cohort of patients andthe accuracy remained stable when an etiology-dependent sub-group analysis was performed [1]. The study was aimed at pro-viding a gene-set to ease the preoperative diagnosis of vascularinvasion, but was not designed for defining outcome prediction.Nonetheless, we have data indicating that the presence of a vas-cular invasion signature correlates with poor outcome, since thesignature was found to be associated with early recurrence(p = 0.057), and was enriched in patients sharing signatures ofpoor prognosis [4].Even considering that the question posed is simple (to identifya gene-signature capturing vascular invasion) the characteristicsof patients, sample collection, sampling issues, technical varia-tion, validation of results, and bioinformatics approaches are cer-tainly heterogeneous, and thus the results might vary. In mostinstances, however, the different signatures seem to be able tocapture common oncogenic mechanisms, as reflected by theircapacity to adequately allocate patients into a poor or good prog-nosis group [5]. By applying a different methodological approach(weighted gene co-expression network analysis) to our data, Liuet al. provide a 9-gene signature with similar accuracy and nooverlap with our 35-gene signature. The method applied is basedon systems biology to find clusters of highly correlated genesacross microarray samples, identify hubs of each module and cor-relate them with clinical traits [6]. This analysis is based on thehypothesis that information on signaling pathways is crucial tounderstand how genes are connected to each other and how theyinfluence cellular functions in both normal and cancer conditions.This result further underlines the need for integrating the vastamount of available data and the development of powerful bioin-formatics resources (annotation, methodologies, technical plat-forms, etc.).A more relevant question is when can our signature-alone orin combination with tumor size- be translated into clinical prac-tice. Strict rules have been proposed recently by Simon and col-leagues [7]. Following this proposal, the EASL-EORTC guidelineson management of HCC have outlined a list of requirements inorder to adopt molecular signatures in the clinical practice [8],which are as follows:1. First, the signature should be generated in the setting of ran-domized studies or in case of cohort studies, it should followthe training/validation approach.2. The signature should retain independent prognostic valuewhen tested along known clinico-pathological variables.3. The results should be confirmed by independent investigatorsin a separate set of samples.Thus, according to these rules, in order to implement our sig-nature in the decision-making process, for instance in the waitinglist of liver transplantation, it should be validated by independentinvestigators in a novel set of samples. Ideally, the signature hasto be reproduced in a device, which should give similar results.Only then, data is ready for acceptance in guidelines. It is a longpath, but the only one for translation of genomic results into ourpractice.Conflict of interestThe authors declared that they do not have anything to discloseregarding funding or conflict of interest with respect to thismanuscript.Reference

The discourse of Olympic security 2012 : London 2012

This paper uses a combination of CDA and CL to investigate the discursive realization of the security operation for the 2012 London Olympic Games. Drawing on Didier Bigo’s (2008) conceptualisation of the ‘banopticon’, it address two questions: what distinctive linguistic features are used in documents relating to security for London 2012; and, how is Olympic security realized as a discursive practice in these documents? Findings suggest that the documents indeed realized key banoptic features of the banopticon: exceptionalism, exclusion and prediction, as well as what we call ‘pedagogisation’. Claims were made for the exceptional scale of the Olympic events; predictive technologies were proposed to assess the threat from terrorism; and documentary evidence suggests that access to Olympic venues was being constituted to resemble transit through national boundarie

Integrative model of behavioural intention: the influence of environmental concern and condition factors on food waste separation

Purpose This paper positions environmental concern as the antecedent of attitude, subjective norm and perceived behavioural control. It also sets to expand the theory of planned behaviour by including two condition factors: favourable situation and facility availability on the intention to separate food waste at source. Design/methodology/approach The study collects data by using self-administered questionnaires on 682 respondents in Malaysia. Structural equation modelling is employed to test the conceptual model and the proposed hypotheses. Findings The results show that environmental concern positively influences attitude and subjective norms, which, in turn, influences food waste separation intention. Favourable situation and facility availability are found to influence the separation intention. Originality/value This study is one of the earliest studies to investigate residents’ intention to participate in food waste separation at a source that employs the expanded theory of planned behaviour with environmental concern and condition factors

Data on experimental investigation of Methyl Ester Sulphonate and nanopolystyrene for rheology improvement and filtration loss control of water-based drilling fluid

Data presented in this article focused on the application of Methyl Ester Sulphonate (MES) surfactant and nanopolystyrene in water based drilling fluid. Data from rheology study using Bingham and Power law models showed that the synergy of MES and nanopolystyrene improved the formulated drilling fluid. Filtration study under LPLT and HPHT conditions showed that MES and nanopolystyrene drilling fluid reduced filtration loss by 50.7% at LPLT and 61.1% at HPHT conditions. These filtration data were validated by filter cake permeability and scanning electron microscope images

18-02 Investigating and Prioritizing Factors for Quantifying Bikeability

Bikeability is an important element that must be considered in planning bicycle facilities. The resource constraints make it imperative for the planners and engineers to be able to identify and shortlist important factors that promote cyclists’ friendly environment. The current study utilized the Analytical Hierarchy Process (AHP), a multiple criteria decision analysis technique, to rank the relative importance of bikeability factors for on-road bicycle facilities. AHP is the most applied multiple criteria decision analysis technique due to its ability to convert subjective judgment to a numerical value which can easily be incorporated in the decision-making process. A survey was administered to experienced cyclists and experts (i.e. planners and engineers), who were asked to rank the relative importance of one factor over the other when assessing the bikeability of on-road designated bike lanes, shared lanes, off-road bicycle facilities, intersections and bicycle infrastructure network. While this report documents summary results for other facilities studies, it gives detailed analysis results for on-road designated bike lanes since they had sufficient responses from the survey. Out of 21 factors that were investigated, the presence and enforcement of passing distance laws was ranked as the most important factor to consider when assessing the bikeability of on-road bicycle facilities. Other important factors, in descending order of importance, were bike lane marking, presence of on-street parking, bike lane type, presence of roadside hazards, motor vehicle speed, presence of paved shoulders and motor vehicle volume, among others. The results from this research form a basis for the factors deemed important by cyclists, planners and designers when assessing the bikeability of on-road bicycle lanes

A High Diffusive Model for Nanomaterials

Considerable attention is today devoted to the engineering of films widely used in photocatalytic, solar energy converters, photochemical and photoelectrochemical cells, dye-sensitized solar cells (DSSCs), to optimize electronic time response following photogeneration. However, the precise nature of transport processes in these systems has remained unresolved. To investigate such aspects of carrier dynamics, we have suggested a model for the calculation of correlation functions, expressed as the Fourier transform of the frequency-dependent complex conductivity σ(ω). Results are presented for the velocity correlation functions, the mean square deviation of position and the diffusion coefficient in systems, like TiO2 and doped Si, of large interest in present devices. Fast diffusion occurs in short time intervals of the order of few collision times. Consequences for efficiency of this fast response are discussed in relation to nanostructured devices

Translating '–omics' results into precision medicine for hepatocellular carcinoma

A large-scale comprehensive analysis of hepatocellular carcinoma (HCC) based on the integration of six distinct data platforms has pinpointed novel oncogenic processes and prognostic subgroups. These findings confirm previously identified molecular subclasses and fuel the need for a clear strategy of precision medicine in HCC