COMAP Early Science: VIII. A Joint Stacking Analysis with eBOSS Quasars

We present a new upper limit on the cosmic molecular gas density at z = 2.4 − 3.4 obtained using the first year of observations from the CO Mapping Array Project (COMAP). COMAP data cubes are stacked on the 3D positions of 243 quasars selected from the Extended Baryon Oscillation SpectroscopicSurvey (eBOSS) catalog, yielding a 95% upper limit for flux from CO(1-0) line emission of 0.129 Jykm/s. Depending on the balance of the emission between the quasar host and its environment, this value can be interpreted as an average CO line luminosity L′CO of eBOSS quasars of ≤ 1.26 × 1011 K km pc2s−1, or an average molecular gas density ρH2 in regions of the universe containing a quasar of ≤ 1.52 × 108 M⊙ cMpc−3. The L′ CO upper limit falls among CO line luminosities obtained fromindividually-targeted quasars in the COMAP redshift range, and the ρH2 value is comparable to upper limits obtained from other Line Intensity Mapping (LIM) surveys and their joint analyses. Further, we forecast the values obtainable with the COMAP/eBOSS stack after the full 5-year COMAP Pathfinder survey. We predict that a detection is probable with this method, depending on the CO properties of the quasar sample. Based on the achieved sensitivity, we believe that this technique of stacking LIM data on the positions of traditional galaxy or quasar catalogs is extremely promising, both asa technique for investigating large galaxy catalogs efficiently at high redshift and as a technique for bolstering the sensitivity of LIM experiments, even with a fraction of their total expected survey data

COMAP Early Science: VIII. A Joint Stacking Analysis with eBOSS Quasars

We present a new upper limit on the cosmic molecular gas density at $z=2.4-3.4$ obtained using the first year of observations from the CO Mapping Array Project (COMAP). COMAP data cubes are stacked on the 3D positions of 282 quasars selected from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS) catalog, yielding a 95% upper limit for flux from CO(1-0) line emission of 0.210 Jy km/s. Depending on the assumptions made, this value can be interpreted as either an average CO line luminosity $L'_\mathrm{CO}$ of eBOSS quasars of $\leq 7.30\times10^{10}$ K km pc$^2$ s$^{-1}$, or an average molecular gas density $\rho_\mathrm{H_2}$ in regions of the universe containing a quasar of $\leq 2.02\times10^8$ M$_\odot$ cMpc$^{-3}$. The $L'_\mathrm{CO}$ upper limit falls among CO line luminosities obtained from individually-targeted quasars in the COMAP redshift range, and the $\rho_\mathrm{H_2}$ value is comparable to upper limits obtained from other Line Intensity Mapping (LIM) surveys and their joint analyses. Further, we forecast the values obtainable with the COMAP/eBOSS stack after the full 5-year COMAP Pathfinder survey. We predict that a detection is probable with this method, depending on the CO properties of the quasar sample. Based on these achieved sensitivities, we believe that this technique of stacking LIM data on the positions of traditional galaxy or quasar catalogs is extremely promising, both as a technique for investigating large galaxy catalogs efficiently at high redshift and as a technique for bolstering the sensitivity of LIM experiments, even with a fraction of their total expected survey data.Comment: 15 pages, 8 figures. To be submitted to Ap

PIK3CA Mutations Frequently Coexist with RAS and BRAF Mutations in Patients with Advanced Cancers

Oncogenic mutations of PIK3CA, RAS (KRAS, NRAS), and BRAF have been identified in various malignancies, and activate the PI3K/AKT/mTOR and RAS/RAF/MEK pathways, respectively. Both pathways are critical drivers of tumorigenesis.Tumor tissues from 504 patients with diverse cancers referred to the Clinical Center for Targeted Therapy at MD Anderson Cancer Center starting in October 2008 were analyzed for PIK3CA, RAS (KRAS, NRAS), and BRAF mutations using polymerase chain reaction-based DNA sequencing.PIK3CA mutations were found in 54 (11%) of 504 patients tested; KRAS in 69 (19%) of 367; NRAS in 19 (8%) of 225; and BRAF in 31 (9%) of 361 patients. PIK3CA mutations were most frequent in squamous cervical (5/14, 36%), uterine (7/28, 25%), breast (6/29, 21%), and colorectal cancers (18/105, 17%); KRAS in pancreatic (5/9, 56%), colorectal (49/97, 51%), and uterine cancers (3/20, 15%); NRAS in melanoma (12/40, 30%), and uterine cancer (2/11, 18%); BRAF in melanoma (23/52, 44%), and colorectal cancer (5/88, 6%). Regardless of histology, KRAS mutations were found in 38% of patients with PIK3CA mutations compared to 16% of patients with wild-type (wt)PIK3CA (p = 0.001). In total, RAS (KRAS, NRAS) or BRAF mutations were found in 47% of patients with PIK3CA mutations vs. 24% of patients wtPIK3CA (p = 0.001). PIK3CA mutations were found in 28% of patients with KRAS mutations compared to 10% with wtKRAS (p = 0.001) and in 20% of patients with RAS (KRAS, NRAS) or BRAF mutations compared to 8% with wtRAS (KRAS, NRAS) or wtBRAF (p = 0.001).PIK3CA, RAS (KRAS, NRAS), and BRAF mutations are frequent in diverse tumors. In a wide variety of tumors, PIK3CA mutations coexist with RAS (KRAS, NRAS) and BRAF mutations

COMAP Early Science: V. Constraints and Forecasts at z∼3z \sim 3

We present the current state of models for the $z\sim3$ carbon monoxide (CO) line-intensity signal targeted by the CO Mapping Array Project (COMAP) Pathfinder in the context of its early science results. Our fiducial model, relating dark matter halo properties to CO luminosities, informs parameter priors with empirical models of the galaxy-halo connection and previous CO(1-0) observations. The Pathfinder early science data spanning wavenumbers $k=0.051$-$0.62\,$Mpc$^{-1}$ represent the first direct 3D constraint on the clustering component of the CO(1-0) power spectrum. Our 95% upper limit on the redshift-space clustering amplitude $A_{\rm clust}\lesssim70\,\mu$K$^2$ greatly improves on the indirect upper limit of $420\,\mu$K$^2$ reported from the CO Power Spectrum Survey (COPSS) measurement at $k\sim1\,$Mpc$^{-1}$. The COMAP limit excludes a subset of models from previous literature, and constrains interpretation of the COPSS results, demonstrating the complementary nature of COMAP and interferometric CO surveys. Using line bias expectations from our priors, we also constrain the squared mean line intensity-bias product, $\langle{Tb}\rangle^2\lesssim50\,\mu$K$^2$, and the cosmic molecular gas density, $\rho_\text{H2}<2.5\times10^8\,M_\odot\,$Mpc$^{-3}$ (95% upper limits). Based on early instrument performance and our current CO signal estimates, we forecast that the five-year Pathfinder campaign will detect the CO power spectrum with overall signal-to-noise of 9-17. Between then and now, we also expect to detect the CO-galaxy cross-spectrum using overlapping galaxy survey data, enabling enhanced inferences of cosmic star-formation and galaxy-evolution history.Comment: Paper 5 of 7 in series. 17 pages + appendix and bibliography (30 pages total); 15 figures, 6 tables; accepted for publication in ApJ; v3 reflects the accepted version with minor changes and additions to tex

COMAP Early Science: III. CO Data Processing

We describe the first season COMAP analysis pipeline that converts raw detector readouts to calibrated sky maps. This pipeline implements four main steps: gain calibration, filtering, data selection, and map-making. Absolute gain calibration relies on a combination of instrumental and astrophysical sources, while relative gain calibration exploits real-time total-power variations. High efficiency filtering is achieved through spectroscopic common-mode rejection within and across receivers, resulting in nearly uncorrelated white noise within single-frequency channels. Consequently, near-optimal but biased maps are produced by binning the filtered time stream into pixelized maps; the corresponding signal bias transfer function is estimated through simulations. Data selection is performed automatically through a series of goodness-of-fit statistics, including $\chi^2$ and multi-scale correlation tests. Applying this pipeline to the first-season COMAP data, we produce a dataset with very low levels of correlated noise. We find that one of our two scanning strategies (the Lissajous type) is sensitive to residual instrumental systematics. As a result, we no longer use this type of scan and exclude data taken this way from our Season 1 power spectrum estimates. We perform a careful analysis of our data processing and observing efficiencies and take account of planned improvements to estimate our future performance. Power spectrum results derived from the first-season COMAP maps are presented and discussed in companion papers.Comment: Paper 3 of 7 in series. 26 pages, 23 figures, submitted to Ap

COMAP Early Science: IV. Power Spectrum Methodology and Results

We present the power spectrum methodology used for the first-season COMAP analysis, and assess the quality of the current data set. The main results are derived through the Feed-feed Pseudo-Cross-Spectrum (FPXS) method, which is a robust estimator with respect to both noise modeling errors and experimental systematics. We use effective transfer functions to take into account the effects of instrumental beam smoothing and various filter operations applied during the low-level data processing. The power spectra estimated in this way have allowed us to identify a systematic error associated with one of our two scanning strategies, believed to be due to residual ground or atmospheric contamination. We omit these data from our analysis and no longer use this scanning technique for observations. We present the power spectra from our first season of observing and demonstrate that the uncertainties are integrating as expected for uncorrelated noise, with any residual systematics suppressed to a level below the noise. Using the FPXS method, and combining data on scales $k=0.051-0.62 \,\mathrm{Mpc}^{-1}$ we estimate $P_\mathrm{CO}(k) = -2.7 \pm 1.7 \times 10^4\mu\textrm{K}^2\mathrm{Mpc}^3$, the first direct 3D constraint on the clustering component of the CO(1-0) power spectrum in the literature.Comment: Paper 4 of 7 in series. 18 pages, 11 figures, as accepted in Ap

COMAP Early Science: VI. A First Look at the COMAP Galactic Plane Survey

We present early results from the COMAP Galactic Plane Survey conducted between June 2019 and April 2021, spanning $20^\circ<\ell<40^\circ$ in Galactic longitude and |b|<1.\!\!^{\circ}5 in Galactic latitude with an angular resolution of $4.5^{\prime}$. The full survey will span $\ell \sim 20^{\circ}$- $220^{\circ}$ and will be the first large-scale radio continuum survey at $30$ GHz with sub-degree resolution. We present initial results from the first part of the survey, including diffuse emission and spectral energy distributions (SEDs) of HII regions and supernova remnants. Using low and high frequency surveys to constrain free-free and thermal dust emission contributions, we find evidence of excess flux density at $30\,$GHz in six regions that we interpret as anomalous microwave emission. Furthermore we model UCHII contributions using data from the $5\,$GHz CORNISH catalogue and reject this as the cause of the $30\,$GHz excess. Six known supernova remnants (SNR) are detected at $30\,$GHz, and we measure spectral indices consistent with the literature or show evidence of steepening. The flux density of the SNR W44 at $30\,$GHz is consistent with a power-law extrapolation from lower frequencies with no indication of spectral steepening in contrast with recent results from the Sardinia Radio Telescope. We also extract five hydrogen radio recombination lines to map the warm ionized gas, which can be used to estimate electron temperatures or to constrain continuum free-free emission. The full COMAP Galactic plane survey, to be released in 2023/2024, will be an invaluable resource for Galactic astrophysics.Comment: Paper 6 of 7 in series. 28 pages, 10 figures, submitted to Ap

COMAP Early Science: VII. Prospects for CO Intensity Mapping at Reionization

We introduce COMAP-EoR, the next generation of the Carbon Monoxide Mapping Array Project aimed at extending CO intensity mapping to the Epoch of Reionization. COMAP-EoR supplements the existing 30 GHz COMAP Pathfinder with two additional 30 GHz instruments and a new 16 GHz receiver. This combination of frequencies will be able to simultaneously map CO(1--0) and CO(2--1) at reionization redshifts ($z\sim5-8$) in addition to providing a significant boost to the $z\sim3$ sensitivity of the Pathfinder. We examine a set of existing models of the EoR CO signal, and find power spectra spanning several orders of magnitude, highlighting our extreme ignorance about this period of cosmic history and the value of the COMAP-EoR measurement. We carry out the most detailed forecast to date of an intensity mapping cross-correlation, and find that five out of the six models we consider yield signal to noise ratios (S/N) $\gtrsim20$ for COMAP-EoR, with the brightest reaching a S/N above 400. We show that, for these models, COMAP-EoR can make a detailed measurement of the cosmic molecular gas history from $z\sim2-8$, as well as probe the population of faint, star-forming galaxies predicted by these models to be undetectable by traditional surveys. We show that, for the single model that does not predict numerous faint emitters, a COMAP-EoR-type measurement is required to rule out their existence. We briefly explore prospects for a third-generation Expanded Reionization Array (COMAP-ERA) capable of detecting the faintest models and characterizing the brightest signals in extreme detail.Comment: Paper 7 of 7 in series. 19 pages, 10 figures, to be submitted to Ap

Effects of oral anticoagulation in people with atrial fibrillation after spontaneous intracranial haemorrhage (COCROACH): prospective, individual participant data meta-analysis of randomised trials

Background - The safety and efficacy of oral anticoagulation for prevention of major adverse cardiovascular events in people with atrial fibrillation and spontaneous intracranial haemorrhage are uncertain. We planned to estimate the effects of starting versus avoiding oral anticoagulation in people with spontaneous intracranial haemorrhage and atrial fibrillation. Methods - In this prospective meta-analysis, we searched bibliographic databases and trial registries using the strategies of a Cochrane systematic review (CD012144) on June 23, 2023. We included clinical trials if they were registered, randomised, and included participants with spontaneous intracranial haemorrhage and atrial fibrillation who were assigned to either start long-term use of any oral anticoagulant agent or avoid oral anticoagulation (ie, placebo, open control, another antithrombotic agent, or another intervention for the prevention of major adverse cardiovascular events). We assessed eligible trials using the Cochrane Risk of Bias tool. We sought data for individual participants who had not opted out of data sharing from chief investigators of completed trials, pending completion of ongoing trials in 2028. The primary outcome was any stroke or cardiovascular death. We used individual participant data to construct a Cox regression model of the time to the first occurrence of outcome events during follow-up in the intention-to-treat dataset supplied by each trial, followed by meta-analysis using a fixed-effect inverse-variance model to generate a pooled estimate of the hazard ratio (HR) with 95% CI. This study is registered with PROSPERO, CRD42021246133. Findings - We identified four eligible trials; three were restricted to participants with atrial fibrillation and intracranial haemorrhage (SoSTART [NCT03153150], with 203 participants) or intracerebral haemorrhage (APACHE-AF [NCT02565693], with 101 participants, and NASPAF-ICH [NCT02998905], with 30 participants), and one included a subgroup of participants with previous intracranial haemorrhage (ELDERCARE-AF [NCT02801669], with 80 participants). After excluding two participants who opted out of data sharing, we included 412 participants (310 [75%] aged 75 years or older, 249 [60%] with CHA2DS2-VASc score ≤4, and 163 [40%] with CHA2DS2-VASc score >4). The intervention was a direct oral anticoagulant in 209 (99%) of 212 participants who were assigned to start oral anticoagulation, and the comparator was antiplatelet monotherapy in 67 (33%) of 200 participants assigned to avoid oral anticoagulation. The primary outcome of any stroke or cardiovascular death occurred in 29 (14%) of 212 participants who started oral anticoagulation versus 43 (22%) of 200 who avoided oral anticoagulation (pooled HR 0·68 [95% CI 0·42–1·10]; I2=0%). Oral anticoagulation reduced the risk of ischaemic major adverse cardiovascular events (nine [4%] of 212 vs 38 [19%] of 200; pooled HR 0·27 [95% CI 0·13–0·56]; I2=0%). There was no significant increase in haemorrhagic major adverse cardiovascular events (15 [7%] of 212 vs nine [5%] of 200; pooled HR 1·80 [95% CI 0·77–4·21]; I2=0%), death from any cause (38 [18%] of 212 vs 29 [15%] of 200; 1·29 [0·78–2·11]; I2=50%), or death or dependence after 1 year (78 [53%] of 147 vs 74 [51%] of 145; pooled odds ratio 1·12 [95% CI 0·70–1·79]; I2=0%). Interpretation - For people with atrial fibrillation and intracranial haemorrhage, oral anticoagulation had uncertain effects on the risk of any stroke or cardiovascular death (both overall and in subgroups), haemorrhagic major adverse cardiovascular events, and functional outcome. Oral anticoagulation reduced the risk of ischaemic major adverse cardiovascular events, which can inform clinical practice. These findings should encourage recruitment to, and completion of, ongoing trials. Funding - British Heart Foundation

COMAP Early Science: II. Pathfinder Instrument

Line intensity mapping (LIM) is a new technique for tracing the global properties of galaxies over cosmic time. Detection of the very faint signals from redshifted carbon monoxide (CO), a tracer of star formation, pushes the limits of what is feasible with a total-power instrument. The CO Mapping Project (COMAP) Pathfinder is a first-generation instrument aiming to prove the concept and develop the technology for future experiments, as well as delivering early science products. With 19 receiver channels in a hexagonal focal plane arrangement on a 10.4 m antenna, and an instantaneous 26-34 GHz frequency range with 2 MHz resolution, it is ideally suited to measuring CO($J$=1-0) from $z\sim3$. In this paper we discuss strategies for designing and building the Pathfinder and the challenges that were encountered. The design of the instrument prioritized LIM requirements over those of ancillary science. After a couple of years of operation, the instrument is well understood, and the first year of data is already yielding useful science results. Experience with this Pathfinder will drive the design of the next generations of experiments.Comment: Paper 2 of 7 in series. 27 pages, 28 figures, submitted to Ap