Genomic Analyses across Six Cancer Types Identify Basal-like Breast Cancer as a Unique Molecular Entity

To improve our understanding of the biological relationships among different types of cancer, we have characterized variation in gene expression patterns in a set of 1,707 samples representing 6 human cancer types (breast, ovarian, brain, colorectal, lung adenocarcinoma and squamous cell lung cancer). In the unified dataset, breast tumors of the Basal-like subtype were found to represent a unique molecular entity as any other cancer type, including the rest of breast tumors, while showing striking similarities with squamous cell lung cancers. Moreover, gene signatures tracking various cancer- and stromal-related biological processes such as proliferation, hypoxia and immune activation were found expressed similarly in different proportions of tumors across the various cancer types. These data suggest that clinical trials focusing on tumors with common profiles and/or biomarker expression rather than their tissue of origin are warranted with a special focus on Basal-like breast cancer and squamous cell lung carcinoma

High-resolution hepatitis C virus subtyping using NS5B deep sequencing and phylogeny, an alternative to current methods

HepatitisCvirus(HCV)is classified into seven major genotypesand67 subtypes. Recent studies haveshownthat inHCVgenotype 1-infected patients, response rates to regimens containingdirect-acting antivirals(DAAs)are subtype dependent. Currently available genotypingmethods have limited subtyping accuracy.Wehave evaluated theperformanceof adeep-sequencing-basedHCVsubtyping assay, developed for the 454/GS-Junior platform, in comparisonwith thoseof two commercial assays (VersantHCVgenotype 2.0andAbbott Real-timeHCVGenotype II)andusingdirectNS5Bsequencing as a gold standard (direct sequencing), in 114 clinical specimenspreviously tested by first-generation hybridization assay (82 genotype 1and32 with uninterpretable results). Phylogenetic analysis of deep-sequencing reads matched subtype 1 callingbypopulation Sanger sequencing(69%1b,31%1a) in 81 specimensandidentified amixed-subtype infection (1b/3a/1a) in one sample. Similarly,amongthe 32previously indeterminate specimens, identical genotypeandsubtype results were obtained by directanddeep sequencing in all but four samples with dual infection. In contrast, both VersantHCVGenotype 2.0andAbbott Real-timeHCVGenotype II failed subtype 1 calling in 13 (16%) samples eachandwere unable to identify theHCVgenotype and/or subtype inmore than half of the nongenotype 1 samples.Weconcluded that deep sequencing ismore efficient forHCVsubtyping than currently available methodsandallows qualitative identificationofmixed infectionsandmay bemorehelpfulwith respect to informing treatment strategies withnewDAA-containing regimens across allHCVsubtypesThis study has been supported by CDTI (Centro para el Desarrollo Tecnológico Industrial), Spanish Ministry of Economics and Competitiveness (MINECO), IDI-20110115; MINECO projects SAF 2009-10403; and also by the Spanish Ministry of Health, Instituto de Salud Carlos III (FIS) projects PI10/01505, PI12/01893, and PI13/00456. CIBERehd is funded by the Instituto de Salud Carlos III, Madrid, Spain. Work at CBMSO was supported by grant MINECO-BFU2011-23604, FIPSE, and Fundación Ramón Areces. X. Forns received unrestricted grant support from Roche and has acted as advisor for MSD, Gilead, and Abbvie. M. Alvarez-Tejado, J. Gregori, and J. M. Muñoz work in Roche Diagnostic

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Preliminary study on fluidic actuators. Design modifications

As fluidic actuators have the advantage of lacking moving parts, their use in real applications brings high reliability. This is why, once having overcome their drawbacks, which means being able to provide the appropriate momentum and frequency, they could extensively be used in a wide range of applications. The present paper will present a CFD evaluation of the flow inside a fluidic oscillator. Initially a standard fluidic actuator will be simulated and the results compared with existing experimental data. In a second step, several geometric parameters will be modified; the actuator performance under these new conditions is reported. The paper aims to be an aid for future innovative oscillator designs.Peer ReviewedPostprint (published version

Preliminary study on fluidic actuators. Design modifications

As fluidic actuators have the advantage of lacking moving parts, their use in real applications brings high reliability. This is why, once having overcome their drawbacks, which means being able to provide the appropriate momentum and frequency, they could extensively be used in a wide range of applications. The present paper will present a CFD evaluation of the flow inside a fluidic oscillator. Initially a standard fluidic actuator will be simulated and the results compared with existing experimental data. In a second step, several geometric parameters will be modified; the actuator performance under these new conditions is reported. The paper aims to be an aid for future innovative oscillator designs.Peer Reviewe

Preliminary study on fluidic actuators. Design modifications

As fluidic actuators have the advantage of lacking moving parts, their use in real applications brings high reliability. This is why, once having overcome their drawbacks, which means being able to provide the appropriate momentum and frequency, they could extensively be used in a wide range of applications. The present paper will present a CFD evaluation of the flow inside a fluidic oscillator. Initially a standard fluidic actuator will be simulated and the results compared with existing experimental data. In a second step, several geometric parameters will be modified; the actuator performance under these new conditions is reported. The paper aims to be an aid for future innovative oscillator designs.Peer Reviewe

Research on fluidic amplifiers dimensional modifications via computer simulation (CFD)

When studying active flow control applications, it is already stated that activating the boundary layer via using periodic flow produces better performance than when employing steady blowing or sucking. This is why studying the performance characteristics of devices like fluidic oscillators and zero net mass flow actuators is particularly interesting. In the present paper a particular configuration of fluidic oscillator is carefully analyzed, initially its dynamic performance is compared with experimental results undertaken by previous researchers, then the dimensional internal characteristics are modified in order to obtain how is the dynamic behavior being affected, in a third stage the evaluation of how fluidic oscillators scale is affecting its dynamic performance is also presented. Based on the results obtained it can be concluded that a given actuator working at a given Reynolds number, is capable of producing different frequencies and amplitudes when modifying some dimensional parameters.Peer Reviewe

Research on fluidic amplifiers dimensional modifications via computer simulation (CFD)

When studying active flow control applications, it is already stated that activating the boundary layer via using periodic flow produces better performance than when employing steady blowing or sucking. This is why studying the performance characteristics of devices like fluidic oscillators and zero net mass flow actuators is particularly interesting. In the present paper a particular configuration of fluidic oscillator is carefully analyzed, initially its dynamic performance is compared with experimental results undertaken by previous researchers, then the dimensional internal characteristics are modified in order to obtain how is the dynamic behavior being affected, in a third stage the evaluation of how fluidic oscillators scale is affecting its dynamic performance is also presented. Based on the results obtained it can be concluded that a given actuator working at a given Reynolds number, is capable of producing different frequencies and amplitudes when modifying some dimensional parameters.Peer Reviewe

Fluidic actuator performance variation via internal dimensions modifications

When aimed to modify the downstream vortex shedding of a given bluff body, whether any road vehicle or wing profile, the use of Active Flow Control (AFC) appears to be an efficient technology. Among the different (AFC) methodologies the use of periodic forcing is ment to have better efficiency since it requires less energy to activate the shear layer, the reason behind this efficiency lies on the fact that periodic forcing interacts with the shear layer natural instabilites. In the present paper, one of the devices widely emloyed to generate pulsating flow, is carefully studied via 3D-CFD and using OpenFOAM. Initially the base flow is being determined and compared with previous experimental results, in a second step several internal dimensions of the fluidic actuator are being modified to characterize the output frequency and amplitude variations, among the conclusions obtained it is found that a given fluidic actuator is capable of generating several output frequencies and amplitudes when modifying some internal dimensions while maintaining a constant incoming flow Reynolds number.Postprint (published version