The Atacama Cosmology Telescope: the stellar content of galaxy clusters selected using the Sunyaev-Zel'dovich effect

We present a first measurement of the stellar mass component of galaxy clusters selected via the Sunyaev-Zel'dovich (SZ) effect, using 3.6 um and 4.5 um photometry from the Spitzer Space Telescope. Our sample consists of 14 clusters detected by the Atacama Cosmology Telescope (ACT), which span the redshift range 0.27 < z < 1.07 (median z = 0.50), and have dynamical mass measurements, accurate to about 30 per cent, with median M500 = 6.9 x 10^{14} MSun. We measure the 3.6 um and 4.5 um galaxy luminosity functions, finding the characteristic magnitude (m*) and faint-end slope (alpha) to be similar to those for IR-selected cluster samples. We perform the first measurements of the scaling of SZ-observables (Y500 and y0) with both brightest cluster galaxy (BCG) stellar mass and total cluster stellar mass (M500star). We find a significant correlation between BCG stellar mass and Y500 (E(z)^{-2/3} DA^2 Y500 ~ M*^{1.2 +/- 0.6}), although we are not able to obtain a strong constraint on the slope of the relation due to the small sample size. Additionally, we obtain E(z)^{-2/3} DA^2 Y500 ~ M500star^{1.0 +/- 0.6} for the scaling with total stellar mass. The mass fraction in stars spans the range 0.006-0.034, with the second ranked cluster in terms of dynamical mass (ACT-CL J0237-4939) having an unusually low total stellar mass and the lowest stellar mass fraction. For the five clusters with gas mass measurements available in the literature, we see no evidence for a shortfall of baryons relative to the cosmic mean value.Comment: Accepted for publication in MNRAS; 12 pages, 10 figure

The Primary PE and School Sport Premium

Central to London’s successful bid to host the 2012 Olympic and Paralympic Games, was the Government’s commitment to improve competitive sport and the sporting habits of young people (Ofsted, 2014). On the 12th March 2013, the then Prime Minister, David Cameron, announced that Primary Schools in England would receive funding worth £150 million per year to create a sustainable infrastructure for long-lasting change and improve the provision of physical education (PE) and sport across all state maintained primary schools. Speaking at the time, he said: ‘We can create a culture in our schools that encourages all children to be active and enjoy sport.’ He added: ‘The Olympic and Paralympic Games marked an incredible year for this country and I will always be proud that we showed the world what Britain can do. I want to ensure the Games count for the future too and that means capitalising on the inspiration young people took from what they saw during those summer months.’: https://www.bbc.co.uk/sport/21808982 Six years on, and with a total investment now of over £1.2 billion, the Primary PE and Sport Premium (here onwards referred to as the PESS Premium) has been a defining feature of the London 2012 legacy. Invariably funding streams at this level do not last forever or in the same format, which raises significant questions about what impact the funding has had on young people since 2013. We believe that a significant investment from Government merits debate and accountability at the highest possible level and that it should acknowledge where the opportunities and shortcomings of such a policy have left us. During the years of austerity, mounting concerns have arisen over the present and long term state of children’s health and the need for the debate to be heard is now imperative. To date there has been little critical appraisal of the PESS Premium funding. This report aims to begin a necessary process and in doing so, brings together evidence from across the sector to consider the future of the PESS Premium post 2018. During the course of the report, we outline and underpin the holistic value and importance of PE for every child. We examine the historic status and funding of PE and Sport and the nature and increasing diversity of the workforce. How has the PESS Premium funding impacted the way in which the subject is regarded and the ability of those tasked with delivering it to discharge their responsibilities? We have uncovered an abiding uncertainty about the nature of the PESS Premium itself; the ways in which it may be spent and its effect on an increasing divide between PE specialists, generalists and externally contracted coaches. Will its legacy be to have established a secure foundation for lifelong physical activity, sport and education – or is it, in effect, another temporarily seductive mirage, leaving PE precisely where it has become accustomed to be; regularly sidelined, delivered largely by those who are not qualified teachers and perpetuating the status quo for the children who already belong to groups that are perceived to be at a disadvantage? The PESS Premium funding is a significant sum and these questions deserve answers. This report is therefore our contribution to an essential debate, containing practical suggestions that we hope will be of use to policy makers. We invite all who care about the physical and mental health and emotional wellbeing of children to join the discussion

Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma

Abstract: The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy

A comparative analysis of whole genome sequencing of esophageal adenocarcinoma pre- and post-chemotherapy

The scientific community has avoided using tissue samples from patients that have been exposed to systemic chemotherapy to infer the genomic landscape of a given cancer. Esophageal adenocarcinoma is a heterogeneous, chemoresistant tumor for which the availability and size of pretreatment endoscopic samples are limiting. This study compares whole-genome sequencing data obtained from chemo-naive and chemo-treated samples. The quality of whole-genomic sequencing data is comparable across all samples regardless of chemotherapy status. Inclusion of samples collected post-chemotherapy increased the proportion of late-stage tumors. When comparing matched pre- and post-chemotherapy samples from 10 cases, the mutational signatures, copy number, and SNV mutational profiles reflect the expected heterogeneity in this disease. Analysis of SNVs in relation to allele-specific copy-number changes pinpoints the common ancestor to a point prior to chemotherapy. For cases in which pre- and post-chemotherapy samples do show substantial differences, the timing of the divergence is near-synchronous with endoreduplication. Comparison across a large prospective cohort (62 treatment-naive, 58 chemotherapy-treated samples) reveals no significant differences in the overall mutation rate, mutation signatures, specific recurrent point mutations, or copy-number events in respect to chemotherapy status. In conclusion, whole-genome sequencing of samples obtained following neoadjuvant chemotherapy is representative of the genomic landscape of esophageal adenocarcinoma. Excluding these samples reduces the material available for cataloging and introduces a bias toward the earlier stages of cancer.This study was partly funded by a project grant from Cancer Research UK. R.C.F. is funded by an NIHR Professorship and receives core funding from the Medical Research Council and infrastructure support from the Biomedical Research Centre and the Experimental Cancer Medicine Centre. We acknowledge the support of The University of Cambridge, Cancer Research UK (C14303/A17197) and Hutchison Whampoa Limited

Democracy Does Not Cause Growth:The Importance of Endogeneity Arguments

This article challenges recent findings that democracy has sizable effects on economic growth. As extensive political science research indicates that economic turmoil is responsible for causing or facilitating many democratic transitions, the paper focuses on this endogeneity concern. Using a worldwide survey of 165 country-specific democracy experts conducted for this study, the paper separates democratic transitions into those occurring for reasons related to economic turmoil, here called endogenous, and those grounded in reasons more exogenous to economic growth. The behavior of economic growth following these more exogenous democratizations strongly indicates that democracy does not cause growth. Consequently, the common positive association between democracy and economic growth is driven by endogenous democratization episodes (i.e., due to faulty identification)

A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex.

Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain1-3. With the proliferation of multi-omics datasets, a major challenge is to validate and integrate results into a biological understanding of cell-type organization. Here we generated transcriptomes and epigenomes from more than 500,000 individual cells in the mouse primary motor cortex, a structure that has an evolutionarily conserved role in locomotion. We developed computational and statistical methods to integrate multimodal data and quantitatively validate cell-type reproducibility. The resulting reference atlas-containing over 56 neuronal cell types that are highly replicable across analysis methods, sequencing technologies and modalities-is a comprehensive molecular and genomic account of the diverse neuronal and non-neuronal cell types in the mouse primary motor cortex. The atlas includes a population of excitatory neurons that resemble pyramidal cells in layer 4 in other cortical regions4. We further discovered thousands of concordant marker genes and gene regulatory elements for these cell types. Our results highlight the complex molecular regulation of cell types in the brain and will directly enable the design of reagents to target specific cell types in the mouse primary motor cortex for functional analysis