Testing the Copernican and Cosmological Principles in the local universe with galaxy surveys

Cosmological density fields are assumed to be translational and rotational invariant, avoiding any special point or direction, thus satisfying the Copernican Principle. A spatially inhomogeneous matter distribution can be compatible with the Copernican Principle but not with the stronger version of it, the Cosmological Principle which requires the additional hypothesis of spatial homogeneity. We establish criteria for testing that a given density field, in a finite sample at low redshifts, is statistically and/or spatially homogeneous. The basic question to be considered is whether a distribution is, at different spatial scales, self-averaging. This can be achieved by studying the probability density function of conditional fluctuations. We find that galaxy structures in the SDSS samples, the largest currently available, are spatially inhomogeneous but statistically homogeneous and isotropic up to ~ 100 Mpc/h. Evidences for the breaking of self-averaging are found up to the largest scales probed by the SDSS data. The comparison between the results obtained in volumes of different size allows us to unambiguously conclude that the lack of elf-averaging is induced by finite-size effects due to long-range correlated fluctuations. We finally discuss the relevance of these results from the point of view of cosmological modeling.Comment: 12 pages, 3 figures, accepted for publication in JCA

The complex universe: recent observations and theoretical challenges

The large scale distribution of galaxies in the universe displays a complex pattern of clusters, super-clusters, filaments and voids with sizes limited only by the boundaries of the available samples. A quantitative statistical characterization of these structures shows that galaxy distribution is inhomogeneous in these samples, being characterized by large-amplitude fluctuations of large spatial extension. Over a large range of scales, both the average conditional density and its variance show a nontrivial scaling behavior: at small scales, r<20 Mpc/h, the average (conditional) density scales as 1/r. At larger scales, the density depends only weakly (logarithmically) on the system size and density fluctuations follow the Gumbel distribution of extreme value statistics. These complex behaviors are different from what is expected in a homogeneous distribution with Gaussian fluctuations. The observed density inhomogeneities pose a fundamental challenge to the standard picture of cosmology but it also represent an important opportunity which points to new directions with respect to many cosmological puzzles. Indeed, the fact that matter distribution is not uniform, in the limited range of scales sampled by observations, rises the question of understanding how inhomogeneities affect the large-scale dynamics of the universe. We discuss several attempts which try to model inhomogeneities in cosmology, considering their effects with respect to the role and abundance of dark energy and dark matter.Comment: 30 pages, 10 figure

Light propagation in statistically homogeneous and isotropic universes with general matter content

We derive the relationship of the redshift and the angular diameter distance to the average expansion rate for universes which are statistically homogeneous and isotropic and where the distribution evolves slowly, but which have otherwise arbitrary geometry and matter content. The relevant average expansion rate is selected by the observable redshift and the assumed symmetry properties of the spacetime. We show why light deflection and shear remain small. We write down the evolution equations for the average expansion rate and discuss the validity of the dust approximation.Comment: 42 pages, no figures. v2: Corrected one detail about the angular diameter distance and two typos. No change in result

Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive-stage small cell lung cancer: A multicentre, randomised, double-blind, placebo-controlled Phase II trial

Trilaciclib is an intravenous CDK4/6 inhibitor administered prior to chemotherapy to preserve haematopoietic stem and progenitor cells and immune system function from chemotherapy-induced damage (myelopreservation). The effects of administering trilaciclib prior to carboplatin, etoposide and atezolizumab (E/P/A) were evaluated in a randomised, double-blind, placebo-controlled Phase II study in patients with newly diagnosed extensive-stage small cell lung cancer (ES-SCLC) (NCT03041311). The primary endpoints were duration of severe neutropenia (SN; defined as absolute neutrophil count <0.5 × 109 cells per L) in Cycle 1 and occurrence of SN during the treatment period. Other endpoints were prespecified to assess the effects of trilaciclib on additional measures of myelopreservation, patient-reported outcomes, antitumour efficacy and safety. Fifty-two patients received trilaciclib prior to E/P/A and 53 patients received placebo. Compared to placebo, administration of trilaciclib resulted in statistically significant decreases in the mean duration of SN in Cycle 1 (0 vs 4 days; P < .0001) and occurrence of SN (1.9% vs 49.1%; P < .0001), with additional improvements in red blood cell and platelet measures and health-related quality of life (HRQoL). Trilaciclib was well tolerated, with fewer grade ≥3 adverse events compared with placebo, primarily due to less high-grade haematological toxicity. Antitumour efficacy outcomes were comparable. Administration of trilaciclib vs placebo generated more newly expanded peripheral T-cell clones (P = .019), with significantly greater expansion among patients with an antitumour response to E/P/A (P = .002). Compared with placebo, trilaciclib administered prior to E/P/A improved patients' experience of receiving treatment for ES-SCLC, as shown by reduced myelosuppression, and improved HRQoL and safety profiles

Comparative lesion sequencing provides insights into tumor evolution

We show that the times separating the birth of benign, invasive, and metastatic tumor cells can be determined by analysis of the mutations they have in common. When combined with prior clinical observations, these analyses suggest the following general conclusions about colorectal tumorigenesis: (i) It takes ≈17 years for a large benign tumor to evolve into an advanced cancer but <2 years for cells within that cancer to acquire the ability to metastasize; (ii) it requires few, if any, selective events to transform a highly invasive cancer cell into one with the capacity to metastasize; (iii) the process of cell culture ex vivo does not introduce new clonal mutations into colorectal tumor cell populations; and (iv) the rates at which point mutations develop in advanced cancers are similar to those of normal cells. These results have important implications for understanding human tumor pathogenesis, particularly those associated with metastasis

Repatriating knowledge: variables influencing the “transfer” process

Because of the strategic importance of organizational learning in a global economy, the knowledge that repatriates acquire during international assignments is a valuable resource. Few multinational enterprises, however, actively harvest this knowledge, and little quantitative empirical research on this topic exists to date. We propose an original model and propositions that delineate the facilitative and inhibiting factors affecting repatriate knowledge transfer to work units. We conclude with suggestions for future research and practical implications. Journal of International Business Studies (2009) 40, 181–199; doi:10.1057/palgrave.jibs.8400402