Tenofovir-Associated Nephrotoxicity in Two HIV-Infected Adolescent Males

We report two cases of tenofovir (TDF)-associated nephrotoxicity in perinatally HIV-infected adolescents. The first case, a 16-year-old African American male with an absolute CD4+ cell count of 314 cells/mm3, presented with an abrupt rise in serum creatinine leading to irreversible renal failure while on TDF-containing highly active antiretroviral therapy (HAART). While the patient had evidence of underlying kidney disease, the timing of his renal failure indicates that TDF played a central role. The second case, a 16-year-old African-American male with an absolute CD4+ cell count of 895 cells/mm3, presented with rickets and hypophosphatemia while receiving TDF-based HAART. To our knowledge, these cases represent the first reports of TDF-associated irreversible renal failure and rickets in pediatric patients. We believe these cases highlight important and potentially irreversible side effects of this agent and emphasize the need for further studies of the renal safety of TDF in pediatric patients

Financing Direct Democracy: Revisiting the Research on Campaign Spending and Citizen Initiatives

The conventional view in the direct democracy literature is that spending against a measure is more effective than spending in favor of a measure, but the empirical results underlying this conclusion have been questioned by recent research. We argue that the conventional finding is driven by the endogenous nature of campaign spending: initiative proponents spend more when their ballot measure is likely to fail. We address this endogeneity by using an instrumental variables approach to analyze a comprehensive dataset of ballot propositions in California from 1976 to 2004. We find that both support and opposition spending on citizen initiatives have strong, statistically significant, and countervailing effects. We confirm this finding by looking at time series data from early polling on a subset of these measures. Both analyses show that spending in favor of citizen initiatives substantially increases their chances of passage, just as opposition spending decreases this likelihood

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Localizing FRBs through VLBI with the Algonquin Radio Observatory 10 m Telescope

The Canadian Hydrogen Intensity Mapping Experiment (CHIME)/FRB experiment has detected thousands of fast radio bursts (FRBs) due to its sensitivity and wide field of view; however, its low angular resolution prevents it from localizing events to their host galaxies. Very long baseline interferometry (VLBI), triggered by FRB detections from CHIME/FRB will solve the challenge of localization for non-repeating events. Using a refurbished 10 m radio dish at the Algonquin Radio Observatory located in Ontario Canada, we developed a testbed for a VLBI experiment with a theoretical λ/D ≲ 30 mas. We provide an overview of the 10 m system and describe its refurbishment, the data acquisition, and a procedure for fringe fitting that simultaneously estimates the geometric delay used for localization and the dispersive delay from the ionosphere. Using single pulses from the Crab pulsar, we validate the system and localization procedure, and analyze the clock stability between sites, which is critical for coherently delay referencing an FRB event. We find a localization of ∼200 mas is possible with the performance of the current system (single-baseline). Furthermore, for sources with insufficient signal or restricted wideband to simultaneously measure both geometric and ionospheric delays, we show that the differential ionospheric contribution between the two sites must be measured to a precision of 1 × 10-8 pc cm-3 to provide a reasonable localization from a detection in the 400-800 MHz band. Finally we show detection of an FRB observed simultaneously in the CHIME and the Algonquin 10 m telescope, the first non-repeating FRB in this long baseline. This project serves as a testbed for the forthcoming CHIME/FRB Outriggers project

How to Detect an Astrophysical Nanohertz Gravitational-Wave Background

Analysis of pulsar timing data have provided evidence for a stochastic gravitational wave background in the nHz frequency band. The most plausible source of such a background is the superposition of signals from millions of supermassive black hole binaries. The standard statistical techniques used to search for such a background and assess its significance make several simplifying assumptions, namely: i) Gaussianity; ii) isotropy; and most often iii) a power-law spectrum. However, a stochastic background from a finite collection of binaries does not exactly satisfy any of these assumptions. To understand the effect of these assumptions, we test standard analysis techniques on a large collection of realistic simulated datasets. The dataset length, observing schedule, and noise levels were chosen to emulate the NANOGrav 15-year dataset. Simulated signals from millions of binaries drawn from models based on the Illustris cosmological hydrodynamical simulation were added to the data. We find that the standard statistical methods perform remarkably well on these simulated datasets, despite their fundamental assumptions not being strictly met. They are able to achieve a confident detection of the background. However, even for a fixed set of astrophysical parameters, different realizations of the universe result in a large variance in the significance and recovered parameters of the background. We also find that the presence of loud individual binaries can bias the spectral recovery of the background if we do not account for them.Comment: 14 pages, 8 figure

CHIME/FRB Discovery of 25 Repeating Fast Radio Burst Sources

We present the discovery of 25 new repeating fast radio burst (FRB) sources found among CHIME/FRB events detected between 2019 September 30 and 2021 May 1. The sources were found using a new clustering algorithm that looks for multiple events co-located on the sky having similar dispersion measures (DMs). The new repeaters have DMs ranging from $\sim$220 pc cm$^{-3}$ to $\sim$1700 pc cm$^{-3}$, and include sources having exhibited as few as two bursts to as many as twelve. We report a statistically significant difference in both the DM and extragalactic DM (eDM) distributions between repeating and apparently nonrepeating sources, with repeaters having lower mean DM and eDM, and we discuss the implications. We find no clear bimodality between the repetition rates of repeaters and upper limits on repetition from apparently nonrepeating sources after correcting for sensitivity and exposure effects, although some active repeating sources stand out as anomalous. We measure the repeater fraction and find that it tends to an equilibrium of $2.6_{-2.6}^{+2.9}$% over our exposure thus far. We also report on 14 more sources which are promising repeating FRB candidates and which merit follow-up observations for confirmation.Comment: Submitted to ApJ. Comments are welcome and follow-up observations are encouraged

Building a model: developing genomic resources for common milkweed (Asclepias syriaca) with low coverage genome sequencing

<p>Abstract</p> <p>Background</p> <p>Milkweeds (<it>Asclepias </it>L.) have been extensively investigated in diverse areas of evolutionary biology and ecology; however, there are few genetic resources available to facilitate and compliment these studies. This study explored how low coverage genome sequencing of the common milkweed (<it>Asclepias syriaca </it>L.) could be useful in characterizing the genome of a plant without prior genomic information and for development of genomic resources as a step toward further developing <it>A. syriaca </it>as a model in ecology and evolution.</p> <p>Results</p> <p>A 0.5× genome of <it>A. syriaca </it>was produced using Illumina sequencing. A virtually complete chloroplast genome of 158,598 bp was assembled, revealing few repeats and loss of three genes: <it>accD, clpP</it>, and <it>ycf1</it>. A nearly complete rDNA cistron (18S-5.8S-26S; 7,541 bp) and 5S rDNA (120 bp) sequence were obtained. Assessment of polymorphism revealed that the rDNA cistron and 5S rDNA had 0.3% and 26.7% polymorphic sites, respectively. A partial mitochondrial genome sequence (130,764 bp), with identical gene content to tobacco, was also assembled. An initial characterization of repeat content indicated that Ty1/<it>copia</it>-like retroelements are the most common repeat type in the milkweed genome. At least one <it>A. syriaca </it>microread hit 88% of <it>Catharanthus roseus </it>(Apocynaceae) unigenes (median coverage of 0.29×) and 66% of single copy orthologs (COSII) in asterids (median coverage of 0.14×). From this partial characterization of the <it>A. syriaca </it>genome, markers for population genetics (microsatellites) and phylogenetics (low-copy nuclear genes) studies were developed.</p> <p>Conclusions</p> <p>The results highlight the promise of next generation sequencing for development of genomic resources for any organism. Low coverage genome sequencing allows characterization of the high copy fraction of the genome and exploration of the low copy fraction of the genome, which facilitate the development of molecular tools for further study of a target species and its relatives. This study represents a first step in the development of a community resource for further study of plant-insect co-evolution, anti-herbivore defense, floral developmental genetics, reproductive biology, chemical evolution, population genetics, and comparative genomics using milkweeds, and <it>A. syriaca </it>in particular, as ecological and evolutionary models.</p

The NANOGrav 15-year Data Set: Bayesian Limits on Gravitational Waves from Individual Supermassive Black Hole Binaries

Evidence for a low-frequency stochastic gravitational wave background has recently been reported based on analyses of pulsar timing array data. The most likely source of such a background is a population of supermassive black hole binaries, the loudest of which may be individually detected in these datasets. Here we present the search for individual supermassive black hole binaries in the NANOGrav 15-year dataset. We introduce several new techniques, which enhance the efficiency and modeling accuracy of the analysis. The search uncovered weak evidence for two candidate signals, one with a gravitational-wave frequency of $\sim$4 nHz, and another at $\sim$170 nHz. The significance of the low-frequency candidate was greatly diminished when Hellings-Downs correlations were included in the background model. The high-frequency candidate was discounted due to the lack of a plausible host galaxy, the unlikely astrophysical prior odds of finding such a source, and since most of its support comes from a single pulsar with a commensurate binary period. Finding no compelling evidence for signals from individual binary systems, we place upper limits on the strain amplitude of gravitational waves emitted by such systems.Comment: 23 pages, 13 figures, 2 tables. Accepted for publication in Astrophysical Journal Letters as part of Focus on NANOGrav's 15-year Data Set and the Gravitational Wave Background. For questions or comments, please email [email protected]