An exponential decline at the bright end of the z=6 galaxy luminosity function

We present the results of a search for the most luminous star-forming galaxies at redshifts z~6 based on CFHT Legacy Survey data. We identify a sample of 40 Lyman break galaxies brighter than magnitude z'=25.3 across an area of almost 4 square degrees. Sensitive spectroscopic observations of seven galaxies provide redshifts for four, of which only two have moderate to strong Lyman alpha emission lines. All four have clear continuum breaks in their spectra. Approximately half of the Lyman break galaxies are spatially resolved in 0.7 arcsec seeing images, indicating larger sizes than lower luminosity galaxies discovered with the Hubble Space Telescope, possibly due to on-going mergers. The stacked optical and infrared photometry is consistent with a galaxy model with stellar mass ~ 10^{10} solar masses. There is strong evidence for substantial dust reddening with a best-fit A_V=0.7 and A_V>0.48 at 2 sigma confidence, in contrast to the typical dust-free galaxies of lower luminosity at this epoch. The spatial extent and spectral energy distribution suggest that the most luminous z~6 galaxies are undergoing merger-induced starbursts. The luminosity function of z=5.9 star-forming galaxies is derived. This agrees well with previous work and shows strong evidence for an exponential decline at the bright end, indicating that the feedback processes which govern the shape of the bright end are occurring effectively at this epoch.Comment: 14 pages, 11 figures, AJ in press, revised to address referee comment

COVID-19 AND THE GLOBAL POLITICAL ECONOMY: Crises in the 21st Century

Covid-19 and the Global Political Economy investigates and explores how far and in what ways the Covid-19 pandemic is challenging, restructuring, and perhaps remaking aspects of the global political economy. Since the 1970s, neoliberal capitalism has been the guiding principle of global development: fiscal discipline, privatisations, deregulation, the liberalisation of trade and investment regimes, and lower corporate and wealth taxation. But, after Covid-19, will these trends continue, particularly when states are continuing to struggle with overcoming the pandemic and violating one of neoliberalism’s key principles: balanced budgets? The pandemic has exposed the fragility of the global political economy, and it can be argued that the intensification of global trade, tourism, and finance over the past 30 years has facilitated the spread of infectious diseases such as Covid-19. Therefore, economies in lockdown, jittery markets, and massive government spending have sparked interest in potentially re-evaluating certain features of the global political economy. This volume brings together leading and upcoming critical scholars in international relations and international political economy to provide novel, timely, and innovative research on how the Covid-19 pandemic is impacting (and will continue to impact) the global economy in important dimensions, including state fiscal policy, monetary policy, the accumulation of debt, health and social reproduction, and the future of austerity and the fate of neoliberalism. This book will be of great interest to students, scholars, and experts in international relations and international political economy, as well as history, anthropology, political science, sociology, cultural studies, economics, development studies, and human geography. Chapter 8 of this book is freely available as a downloadable Open Access PDF at https://www.taylorfrancis.com under a Creative Commons Attribution-Non Commercial-No Derivatives (CC-BY-NC-ND) 4.0 license

Risk of Adverse Drug Events Following the Virtual Addition of COVID-19 Repurposed Drugs to Drug Regimens of Frail Older Adults with Polypharmacy

Determination of the risk–benefit ratio associated with the use of novel coronavirus disease 2019 (COVID-19) repurposed drugs in older adults with polypharmacy is mandatory. Our objective was to develop and validate a strategy to assess risk for adverse drug events (ADE) associated with COVID-19 repurposed drugs using hydroxychloroquine (HCQ) and chloroquine (CQ), alone or in combination with azithromycin (AZ), and the combination lopinavir/ritonavir (LPV/r). These medications were virtually added, one at a time, to drug regimens of 12,383 participants of the Program of All-Inclusive Care for the Elderly. The MedWise Risk Score (MRSTM) was determined from 198,323 drug claims. Results demonstrated that the addition of each repurposed drug caused a rightward shift in the frequency distribution of MRSTM values (p < 0.05); the increase was due to an increase in the drug-induced Long QT Syndrome (LQTS) or CYP450 drug interaction burden risk scores. Increases in LQTS risk observed with HCQ + AZ and CQ + AZ were of the same magnitude as those estimated when terfenadine or terfenadine + AZ, used as positive controls for drug-induced LQTS, were added to drug regimens. The simulation-based strategy performed offers a way to assess risk of ADE for drugs to be used in people with underlying medical comorbidities and polypharmacy at risk of COVID-19 infection without exposing them to these drugs

Comprehensive microRNA analysis across genome-edited colorectal cancer organoid models reveals miR-24 as a candidate regulator of cell survival

Abstract Somatic mutations drive colorectal cancer (CRC) by disrupting gene regulatory mechanisms. Distinct combinations of mutations can result in unique changes to regulatory mechanisms leading to variability in the efficacy of therapeutics. MicroRNAs are important regulators of gene expression, and their activity can be altered by oncogenic mutations. However, it is unknown how distinct combinations of CRC-risk mutations differentially affect microRNAs. Here, using genetically-modified mouse intestinal organoid (enteroid) models, we identify 12 different modules of microRNA expression patterns across different combinations of mutations common in CRC. We also show that miR-24-3p is aberrantly upregulated in genetically-modified mouse enteroids irrespective of mutational context. Furthermore, we identify an enrichment of miR-24-3p predicted targets in downregulated gene lists from various mutational contexts compared to WT. In follow-up experiments, we demonstrate that miR-24-3p promotes CRC cell survival in multiple cell contexts. Our novel characterization of genotype-specific patterns of miRNA expression offer insight into the mechanisms that drive inter-tumor heterogeneity and highlight candidate microRNA therapeutic targets for the advancement of precision medicine for CRC