59 research outputs found
Nucleoside reverse-transcriptase inhibitor dosing errors in an outpatient HIV clinic in the electronic medical record era
Information on antiretroviral dosing errors among health care providers for outpatient human immunodeficiency virus (HIV)-infected patients is lacking. We evaluated factors associated with nucleoside reverse-transcriptase inhibitor dosing errors in a university-based HIV clinic using an electronic medical record. Overall, older age, minority race or ethnicity, and didanosine use were related to such errors. Impaired renal function was more common in older patients and racial or ethnic minorities and, in conjunction with fixed-dose combination drugs, contributed to the higher rates of errors in nucleoside reverse-transcriptase inhibitor dosing. Understanding the factors related to nucleoside reverse-transcriptase inhibitor dosing errors is an important step in the building of preventive tools
Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans
The electrocardiographic QRS duration, a measure of ventricular depolarization and conduction, is associated with cardiovascular mortality. While single nucleotide polymorphisms (SNPs) associated with QRS duration have been identified at 22 loci in populations of European descent, the genetic architecture of QRS duration in non-European populations is largely unknown. We therefore performed a genome-wide association study (GWAS) meta-analysis of QRS duration in 13,031 African Americans from ten cohorts and a transethnic GWAS meta-analysis with additional results from populations of European descent. In the African American GWAS, a single genome-wide significant SNP association was identified (rs3922844, P = 4 × 10−14) in intron 16 of SCN5A, a voltage-gated cardiac sodium channel gene. The QRS-prolonging rs3922844 C allele was also associated with decreased SCN5A RNA expression in human atrial tissue (P = 1.1 × 10−4). High density genotyping revealed that the SCN5A association region in African Americans was confined to intron 16. Transethnic GWAS meta-analysis identified novel SNP associations on chromosome 18 in MYL12A (rs1662342, P = 4.9 × 10−8) and chromosome 1 near CD1E and SPTA1 (rs7547997, P = 7.9 × 10−9). The 22 QRS loci previously identified in populations of European descent were enriched for significant SNP associations with QRS duration in African Americans (P = 9.9 × 10−7), and index SNP associations in or near SCN5A, SCN10A, CDKN1A, NFIA, HAND1, TBX5 and SETBP1 replicated in African Americans. In summary, rs3922844 was associated with QRS duration and SCN5A expression, two novel QRS loci were identified using transethnic meta-analysis, and a significant proportion of QRS–SNP associations discovered in populations of European descent were transferable to African Americans when adequate power was achieved
The Atacama Cosmology Telescope: A Measurement of the DR6 CMB Lensing Power Spectrum and its Implications for Structure Growth
We present new measurements of cosmic microwave background (CMB) lensing over
sq. deg. of the sky. These lensing measurements are derived from the
Atacama Cosmology Telescope (ACT) Data Release 6 (DR6) CMB dataset, which
consists of five seasons of ACT CMB temperature and polarization observations.
We determine the amplitude of the CMB lensing power spectrum at
precision ( significance) using a novel pipeline that minimizes
sensitivity to foregrounds and to noise properties. To ensure our results are
robust, we analyze an extensive set of null tests, consistency tests, and
systematic error estimates and employ a blinded analysis framework. The
baseline spectrum is well fit by a lensing amplitude of
relative to the Planck 2018 CMB power spectra
best-fit CDM model and relative to
the best-fit model. From our lensing power
spectrum measurement, we derive constraints on the parameter combination
of
from ACT DR6 CMB lensing alone and
when combining ACT DR6 and Planck NPIPE
CMB lensing power spectra. These results are in excellent agreement with
CDM model constraints from Planck or
CMB power spectrum measurements. Our lensing measurements from redshifts
-- are thus fully consistent with CDM structure growth
predictions based on CMB anisotropies probing primarily . We find no
evidence for a suppression of the amplitude of cosmic structure at low
redshiftsComment: 45+21 pages, 50 figures. Prepared for submission to ApJ. Also see
companion papers Madhavacheril et al and MacCrann et a
The Atacama Cosmology Telescope: High-resolution component-separated maps across one-third of the sky
Observations of the millimeter sky contain valuable information on a number
of signals, including the blackbody cosmic microwave background (CMB), Galactic
emissions, and the Compton- distortion due to the thermal Sunyaev-Zel'dovich
(tSZ) effect. Extracting new insight into cosmological and astrophysical
questions often requires combining multi-wavelength observations to spectrally
isolate one component. In this work, we present a new arcminute-resolution
Compton- map, which traces out the line-of-sight-integrated electron
pressure, as well as maps of the CMB in intensity and E-mode polarization,
across a third of the sky (around 13,000 sq.~deg.). We produce these through a
joint analysis of data from the Atacama Cosmology Telescope (ACT) Data Release
4 and 6 at frequencies of roughly 93, 148, and 225 GHz, together with data from
the \textit{Planck} satellite at frequencies between 30 GHz and 545 GHz. We
present detailed verification of an internal linear combination pipeline
implemented in a needlet frame that allows us to efficiently suppress Galactic
contamination and account for spatial variations in the ACT instrument noise.
These maps provide a significant advance, in noise levels and resolution, over
the existing \textit{Planck} component-separated maps and will enable a host of
science goals including studies of cluster and galaxy astrophysics, inferences
of the cosmic velocity field, primordial non-Gaussianity searches, and
gravitational lensing reconstruction of the CMB.Comment: The Compton-y map and associated products will be made publicly
available upon publication of the paper. The CMB T and E mode maps will be
made available when the DR6 maps are made publi
The Atacama Cosmology Telescope: DR6 Gravitational Lensing Map and Cosmological Parameters
We present cosmological constraints from a gravitational lensing mass map
covering 9400 sq. deg. reconstructed from CMB measurements made by the Atacama
Cosmology Telescope (ACT) from 2017 to 2021. In combination with BAO
measurements (from SDSS and 6dF), we obtain the amplitude of matter
fluctuations at 1.8% precision,
and the Hubble
constant at
1.6% precision. A joint constraint with CMB lensing measured by the Planck
satellite yields even more precise values: ,
and . These measurements agree
well with CDM-model extrapolations from the CMB anisotropies measured
by Planck. To compare these constraints to those from the KiDS, DES, and HSC
galaxy surveys, we revisit those data sets with a uniform set of assumptions,
and find from all three surveys are lower than that from ACT+Planck
lensing by varying levels ranging from 1.7-2.1. These results motivate
further measurements and comparison, not just between the CMB anisotropies and
galaxy lensing, but also between CMB lensing probing on
mostly-linear scales and galaxy lensing at on smaller scales. We
combine our CMB lensing measurements with CMB anisotropies to constrain
extensions of CDM, limiting the sum of the neutrino masses to eV (95% c.l.), for example. Our results provide independent
confirmation that the universe is spatially flat, conforms with general
relativity, and is described remarkably well by the CDM model, while
paving a promising path for neutrino physics with gravitational lensing from
upcoming ground-based CMB surveys.Comment: 30 pages, 16 figures, prepared for submission to ApJ. Cosmological
likelihood data is here:
https://lambda.gsfc.nasa.gov/product/act/actadv_prod_table.html ; likelihood
software is here: https://github.com/ACTCollaboration/act_dr6_lenslike . Also
see companion papers Qu et al and MacCrann et al. Mass maps will be released
when papers are publishe
Multi-ethnic genome-wide association study for atrial fibrillation
Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF
CMB-S4: Forecasting Constraints on Primordial Gravitational Waves
CMB-S4---the next-generation ground-based cosmic microwave background (CMB)
experiment---is set to significantly advance the sensitivity of CMB
measurements and enhance our understanding of the origin and evolution of the
Universe, from the highest energies at the dawn of time through the growth of
structure to the present day. Among the science cases pursued with CMB-S4, the
quest for detecting primordial gravitational waves is a central driver of the
experimental design. This work details the development of a forecasting
framework that includes a power-spectrum-based semi-analytic projection tool,
targeted explicitly towards optimizing constraints on the tensor-to-scalar
ratio, , in the presence of Galactic foregrounds and gravitational lensing
of the CMB. This framework is unique in its direct use of information from the
achieved performance of current Stage 2--3 CMB experiments to robustly forecast
the science reach of upcoming CMB-polarization endeavors. The methodology
allows for rapid iteration over experimental configurations and offers a
flexible way to optimize the design of future experiments given a desired
scientific goal. To form a closed-loop process, we couple this semi-analytic
tool with map-based validation studies, which allow for the injection of
additional complexity and verification of our forecasts with several
independent analysis methods. We document multiple rounds of forecasts for
CMB-S4 using this process and the resulting establishment of the current
reference design of the primordial gravitational-wave component of the Stage-4
experiment, optimized to achieve our science goals of detecting primordial
gravitational waves for at greater than , or, in the
absence of a detection, of reaching an upper limit of at CL.Comment: 24 pages, 8 figures, 9 tables, submitted to ApJ. arXiv admin note:
text overlap with arXiv:1907.0447
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