Averaging Robertson-Walker Cosmologies

The cosmological backreaction arises when one directly averages the Einstein equations to recover an effective Robertson-Walker cosmology, rather than assuming a background a priori. While usually discussed in the context of dark energy, strictly speaking any cosmological model should be recovered from such a procedure. We apply the Buchert averaging formalism to linear Robertson-Walker universes containing matter, radiation and dark energy and evaluate numerically the discrepancies between the assumed and the averaged behaviour, finding the largest deviations for an Einstein-de Sitter universe, increasing rapidly with Hubble rate to a 0.01% effect for h=0.701. For the LCDM concordance model, the backreaction is of the order of Omega_eff~4x10^-6, with those for dark energy models being within a factor of two or three. The impacts at recombination are of the order of 10^-8 and those in deep radiation domination asymptote to a constant value. While the effective equations of state of the backreactions in Einstein-de Sitter, concordance and quintessence models are generally dust-like, a backreaction with an equation of state w_eff<-1/3 can be found for strongly phantom models.Comment: 18 pages, 11 figures, ReVTeX. Updated to version accepted by JCA

High-redshift post-reionization cosmology with 21cm intensity mapping

We investigate the possibility of performing cosmological studies in the redshift range 2.5<z<5 through suitable extensions of existing and upcoming radio-telescopes like CHIME, HIRAX and FAST. We use the Fisher matrix technique to forecast the bounds that those instruments can place on the growth rate, the BAO distance scale parameters, the sum of the neutrino masses and the number of relativistic degrees of freedom at decoupling, Neff. We point out that quantities that depend on the amplitude of the 21cm power spectrum, like f\u3c38, are completely degenerate with \u3a9HI and bHI, and propose several strategies to independently constrain them through cross-correlations with other probes. Assuming 5% priors on \u3a9HI and bHI, kmax=0.2 h Mpc-1 and the primary beam wedge, we find that a HIRAX extension can constrain, within bins of \u394 z=0.1: 1) the value of f\u3c38 at 4%, 2) the value of DA and H at 1%. In combination with data from Euclid-like galaxy surveys and CMB S4, the sum of the neutrino masses can be constrained with an error equal to 23 meV (1\u3c3), while Neff can be constrained within 0.02 (1\u3c3). We derive similar constraints for the extensions of the other instruments. We study in detail the dependence of our results on the instrument, amplitude of the HI bias, the foreground wedge coverage, the nonlinear scale used in the analysis, uncertainties in the theoretical modeling and the priors on bHI and \u3a9HI. We conclude that 21cm intensity mapping surveys operating in this redshift range can provide extremely competitive constraints on key cosmological parameters

Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study

A41 Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study In: Addiction Science & Clinical Practice 2017, 12(Suppl 1): A4

An integrated model of organisational innovation and firm performance: generation, persistence and complementarity

Our paper encompasses an integral view of organizational innovation (OI), covering from the generation of OI to the effect of OI on firm performance, tackling the gap identified by Damanpour et al. (2009) about the lack of studies that comprehensively study OI. We empirically test this question using data from the Spanish Technological Innovation Panel (PITEC, 2016) carried out in the years 2008-2013, focusing on a sample of 3,795 manufacturing firms. The results provide empirical evidence that confirms OI as an innovation capability. We conclude that innovation capabilities operate through a reciprocity and complementarity relation, where technological, product and process, innovations and OI are all determining factors of one another. Last, our paper explores the effect of OI on firm performance, expanding the current analysis of the effect of process and product innovation on firm performanc

Evolutionary characterization of lung adenocarcinoma morphology in TRACERx

Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions in predominantly high-grade pattern tumors exhibited higher proliferation and lower clonal diversity, potentially reflecting large recent subclonal expansions. Co-occurrence of truncal loss of chromosomes 3p and 3q was enriched in predominantly low-/mid-grade tumors, while purely undifferentiated solid-pattern tumors had a higher frequency of truncal arm or focal 3q gains and SMARCA4 gene alterations compared with mixed-pattern tumors with a solid component, suggesting distinct evolutionary trajectories. Clonal evolution analysis revealed that tumors tend to evolve toward higher-grade patterns. The presence of micropapillary pattern and ‘tumor spread through air spaces’ were associated with intrathoracic recurrence, in contrast to the presence of solid/cribriform patterns, necrosis and preoperative circulating tumor DNA detection, which were associated with extra-thoracic recurrence. These data provide insights into the relationship between LUAD morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk

The evolution of lung cancer and impact of subclonal selection in TRACERx

Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource