Acting on incidental findings in research imaging

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Single-field inflation constraints from CMB and SDSS data

We present constraints on canonical single-field inflation derived from WMAP five year, ACBAR, QUAD, BICEP data combined with the halo power spectrum from SDSS LRG7. Models with a non-scale-invariant spectrum and a red tilt n_s < 1 are now preferred over the Harrison-Zel'dovich model (n_s = 1, tensor-to-scalar ratio r = 0) at high significance. Assuming no running of the spectral indices, we derive constraints on the parameters (n_s, r) and compare our results with the predictions of simple inflationary models. The marginalised credible intervals read n_s = 0.962^{+0.028}_{-0.026} and r < 0.17 (at 95% confidence level). Interestingly, the 68% c.l. contours favour mainly models with a convex potential in the observable region, but the quadratic potential model remains inside the 95% c.l. contours. We demonstrate that these results are robust to changes in the datasets considered and in the theoretical assumptions made. We then consider a non-vanishing running of the spectral indices by employing different methods, non-parametric but approximate, or parametric but exact. With our combination of CMB and LSS data, running models are preferred over power-law models only by a Delta chi^2 ~ 5.8, allowing inflationary stages producing a sizable negative running -0.063^{+0.061}_{-0.049} and larger tensor-scalar ratio r < 0.33 at the 95% c.l. This requires large values of the third derivative of the inflaton potential within the observable range. We derive bounds on this derivative under the assumption that the inflaton potential can be approximated as a third order polynomial within the observable range.Comment: 32 pages, 7 figures. v2: additional references, some typos corrected, passed to JCAP style. v3: minor changes, matches published versio

Cosmological parameters constraints from galaxy cluster mass function measurements in combination with other cosmological data

We present the cosmological parameters constraints obtained from the combination of galaxy cluster mass function measurements (Vikhlinin et al., 2009a,b) with new cosmological data obtained during last three years: updated measurements of cosmic microwave background anisotropy with Wilkinson Microwave Anisotropy Probe (WMAP) observatory, and at smaller angular scales with South Pole Telescope (SPT), new Hubble constant measurements, baryon acoustic oscillations and supernovae Type Ia observations. New constraints on total neutrino mass and effective number of neutrino species are obtained. In models with free number of massive neutrinos the constraints on these parameters are notably less strong, and all considered cosmological data are consistent with non-zero total neutrino mass \Sigma m_\nu \approx 0.4 eV and larger than standard effective number of neutrino species, N_eff \approx 4. These constraints are compared to the results of neutrino oscillations searches at short baselines. The updated dark energy equation of state parameters constraints are presented. We show that taking in account systematic uncertainties, current cluster mass function data provide similarly powerful constraints on dark energy equation of state, as compared to the constraints from supernovae Type Ia observations.Comment: Accepted for publication in Astronomy Letter

State-of-the-art analytical methods of viral infections in human lung organoids

Human-based organ models can provide strong predictive value to investigate the tropism, virulence, and replication kinetics of viral pathogens. Currently, such models have received widespread attention in the study of SARS-CoV-2 causing the COVID-19 pandemic. Applicable to a large set of organoid models and viruses, we provide a step-by-step work instruction for the infection of human alveolar-like organoids with SARS-CoV-2 in this protocol collection. We also prepared a detailed description on state-of-the-art methodologies to assess the infection impact and the analysis of relevant host factors in organoids. This protocol collection consists of five different sets of protocols. Set 1 describes the protein extraction from human alveolar-like organoids and the determination of protein expression of angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) and FURIN as exemplary host factors of SARS-CoV-2. Set 2 provides detailed guidance on the extraction of RNA from human alveolar-like organoids and the subsequent qPCR to quantify the expression level of ACE2, TMPRSS2, and FURIN as host factors of SARS-CoV-2 on the mRNA level. Protocol set 3 contains an in-depth explanation on how to infect human alveolar-like organoids with SARS-CoV-2 and how to quantify the viral replication by plaque assay and viral E gene-based RT-qPCR. Set 4 provides a step-by-step protocol for the isolation of single cells from infected human alveolar-like organoids for further processing in single-cell RNA sequencing or flow cytometry. Set 5 presents a detailed protocol on how to perform the fixation of human alveolar-like organoids and guides through all steps of immunohistochemistry and in situ hybridization to visualize SARS-CoV-2 and its host factors. The infection and all subsequent analytical methods have been successfully validated by biological replications with human alveolar-like organoids based on material from different donors

''Sex changes'? Paradigm shifts in 'sex' and 'gender' following the gender recognition act?'

Gender transformations are normatively understood as somatic, based on surgical reassignment, where the sexed body is aligned with the gender identity of the individual through genital surgery - hence the common lexicon 'sex change surgery'. We suggest that the UK Gender Recognition Act 2004 challenges what constitutes a 'sex change' through the Act's definitions and also the conditions within which legal 'recognition' is permitted. The sex/gender distinction, (where sex normatively refers to the sexed body, and gender, to social identity) is demobilised both literally and legally. This paper discusses the history of medico-socio-legal definitions of sex have been developed through decision making processes when courts have been faced with people with gender variance and , in particular, the implications of the Gender Recognition Act for our contemporary legal understanding of sex. We ask, and attempt to answer, has 'sex' changed

Human alveolar progenitors generate dual lineage bronchioalveolar organoids

Mechanisms of epithelial renewal in the alveolar compartment remain incompletely understood. To this end, we aimed to characterize alveolar progenitors. Single-cell RNA-sequencing (scRNA-seq) analysis of the HTII-280(+)/EpCAM(+) population from adult human lung revealed subclusters enriched for adult stem cell signature (ASCS) genes. We found that alveolar progenitors in organoid culture in vitro show phenotypic lineage plasticity as they can yield alveolar or bronchial cell-type progeny. The direction of the differentiation is dependent on the presence of the GSK-3β inhibitor, CHIR99021. By RNA-seq profiling of GSK-3β knockdown organoids we identified additional candidate target genes of the inhibitor, among others FOXM1 and EGF. This gives evidence of Wnt pathway independent regulatory mechanisms of alveolar specification. Following influenza A virus (IAV) infection organoids showed a similar response as lung tissue explants which confirms their suitability for studies of sequelae of pathogen-host interaction

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe