A RE-EXAMINATION OF EVENT STUDIES APPLIED TO CHALLENGED HORIZONTAL MERGERS

A growing body of empirical studies have been interpreted as support for a laissez-faire policy towards mergers. These "event studies" examine the reaction of stock market prices of firms that announce an agreement to merge. The type ~f reaction reveals whether a merger is motivated by a desire for market power or purely to improve market efficiency. In this paper, a version of the capital asset pricing model (CAPM) is applied to determine if abnormal returns are earned by rivals of 22 pairs of firms whose attempted horizontal mergers were challenged by the federal antitrust agencies. At most eight, and possibly only five, of the cases were found to be motivated by efficiency in seeking merger, and at most six, and possibly only one, were motivated by market power; the rest were inconclusive. The event-study technique is highly flawed for the study of business-regulation effects. Numerous unrealistic assumptions, inappropriate data constraints, and questionable interpretations hamper .the application of this technique to policy analysis.Industrial Organization,

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

A RE-EXAMINATION OF EVENT STUDIES APPLIED TO CHALLENGED HORIZONTAL MERGERS

A growing body of empirical studies have been interpreted as support for a laissez-faire policy towards mergers. These "event studies" examine the reaction of stock market prices of firms that announce an agreement to merge. The type ~f reaction reveals whether a merger is motivated by a desire for market power or purely to improve market efficiency. In this paper, a version of the capital asset pricing model (CAPM) is applied to determine if abnormal returns are earned by rivals of 22 pairs of firms whose attempted horizontal mergers were challenged by the federal antitrust agencies. At most eight, and possibly only five, of the cases were found to be motivated by efficiency in seeking merger, and at most six, and possibly only one, were motivated by market power; the rest were inconclusive. The event-study technique is highly flawed for the study of business-regulation effects. Numerous unrealistic assumptions, inappropriate data constraints, and questionable interpretations hamper .the application of this technique to policy analysis

Multiwavelength view of SPT-CL J2106-5844

Context. SPT-CL J2106-5844 is among the most massive galaxy clusters at z > 1 yet discovered. While initially used in cosmological tests to assess the compatibility with Λ Cold Dark Matter cosmology of such a massive virialized object at this redshift, more recent studies indicate SPT-CL J2106-5844 is undergoing a major merger and is not an isolated system with a singular, well-defined halo. Aims. We use sensitive, high spatial resolution measurements from the Atacama Large Millimeter/Submillimeter Array (ALMA) and Atacama Compact Array (ACA) of the thermal Sunyaev-Zeldovich (SZ) effect to reconstruct the pressure distribution of the intracluster medium in this system. These measurements are coupled with radio observations from the pilot survey for the Evolutionary Map of the Universe, using the Australian Square Kilometre Array Pathfinder (ASKAP), and the Australia Telescope Compact Array (ATCA) to search for diffuse nonthermal emission. Further, to better constrain the thermodynamic structure of the cluster, we complement our analysis with reprocessed archival Chandra observations. Methods. We jointly fit the ALMA and ACA SZ data in uv-space using a Bayesian forward modeling technique. The ASKAP and low-frequency ATCA data are processed and imaged to specifically highlight any potential diffuse radio emission. Results. In the ALMA and ACA SZ data, we reliably identify at high significance two main gas components associated with the mass clumps inferred from weak lensing. Our statistical test excludes at the ∼9.9σ level the possibility of describing the system with a single SZ component. While the components had been more difficult to identify in the X-ray data alone, we find that the bimodal gas distribution is supported by the X-ray hardness distribution. The EMU radio observations reveal a diffuse radio structure ∼400 kpc in projected extent along the northwest-southeast direction, indicative of strong activity from the active galactic nucleus within the brightest cluster galaxy. Interestingly, a putative optical star-forming filamentary structure detected in the HST image is in an excellent alignment with the radio structure, albeit on a smaller scale

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease