| 1. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 2. |
- Coughlin, Michael W., et al.
(författare)
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GROWTH on S190425z : Searching Thousands of Square Degrees to Identify an Optical or Infrared Counterpart to a Binary Neutron Star Merger with the Zwicky Transient Facility and Palomar Gattini-IR
- 2019
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 885:1
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Tidskriftsartikel (refereegranskat)abstract
- The third observing run by LVC has brought the discovery of many compact binary coalescences. Following the detection of the first binary neutron star merger in this run (LIGO/Virgo S190425z), we performed a dedicated follow-up campaign with the Zwicky Transient Facility (ZTF) and Palomar Gattini-IR telescopes. The initial skymap of this single-detector gravitational wave (GW) trigger spanned most of the sky observable from Palomar Observatory. Covering 8000 deg(2) of the initial skymap over the next two nights, corresponding to 46% integrated probability, ZTF system achieved a depth of 21 m(AB) in g- and r-bands. Palomar Gattini-IR covered 2200 square degrees in J-band to a depth of 15.5 mag, including 32% integrated probability based on the initial skymap. The revised skymap issued the following day reduced these numbers to 21% for the ZTF and 19% for Palomar Gattini-IR. We narrowed 338,646 ZTF transient ?alerts? over the first two nights of observations to 15 candidate counterparts. Two candidates, ZTF19aarykkb and ZTF19aarzaod, were particularly compelling given that their location, distance, and age were consistent with the GW event, and their early optical light curves were photometrically consistent with that of kilonovae. These two candidates were spectroscopically classified as young core-collapse supernovae. The remaining candidates were ruled out as supernovae. Palomar Gattini-IR did not identify any viable candidates with multiple detections only after merger time. We demonstrate that even with single-detector GW events localized to thousands of square degrees, systematic kilonova discovery is feasible.
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| 3. |
- Bellm, Eric C., et al.
(författare)
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The Zwicky Transient Facility : System Overview, Performance, and First Results
- 2019
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:995
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Tidskriftsartikel (refereegranskat)abstract
- The Zwicky Transient Facility (ZTF) is a new optical time-domain survey that uses the Palomar 48 inch Schmidt telescope. A custom-built wide-field camera provides a 47 deg(2) field of view and 8 s readout time, yielding more than an order of magnitude improvement in survey speed relative to its predecessor survey, the Palomar Transient Factory. We describe the design and implementation of the camera and observing system. The ZTF data system at the Infrared Processing and Analysis Center provides near-real-time reduction to identify moving and varying objects. We outline the analysis pipelines, data products, and associated archive. Finally, we present on-sky performance analysis and first scientific results from commissioning and the early survey. ZTF's public alert stream will serve as a useful precursor for that of the Large Synoptic Survey Telescope.
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| 4. |
- Ho, Anna Y. Q., et al.
(författare)
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Evidence for Late-stage Eruptive Mass Loss in the Progenitor to SN2018gep, a Broad-lined Ic Supernova : Pre-explosion Emission and a Rapidly Rising Luminous Transient
- 2019
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 887:2
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Tidskriftsartikel (refereegranskat)abstract
- We present detailed observations of ZTF18abukavn (SN2018gep), discovered in high-cadence data from the Zwicky Transient Facility as a rapidly rising (1.4 +/- 0.1 mag hr(-1)) and luminous (M-g,M- peak = -20 mag) transient. It is spectroscopically classified as a broad-lined stripped-envelope supernova (Ic-BL SN). The high peak luminosity (L-bol greater than or similar to 3 x 10(44) erg s(-1)), the short rise time (t(rise) = 3 days in g band), and the blue colors at peak (g-r similar to -0.4) all resemble the high-redshift Ic-BL iPTF16asu, as well as several other unclassified fast transients. The early discovery of SN2018gep (within an hour of shock breakout) enabled an intensive spectroscopic campaign, including the highest-temperature (T-eff greater than or similar to 40,000 K) spectra of a stripped-envelope SN. A retrospective search revealed luminous (M-g similar to M-r approximate to -14 mag) emission in the days to weeks before explosion, the first definitive detection of precursor emission for a Ic-BL. We find a limit on the isotropic gamma-ray energy release E-gamma,E- iso < 4.9 x 10(48) erg, a limit on X-ray emission L-X < 10(40) erg s(-1), and a limit on radio emission nu L-v less than or similar to 10(37) erg s(-1). Taken together, we find that the early (< 10 days) data are best explained by shock breakout in a massive shell of dense circumstellar material (0.02 M-circle dot) at large radii (3 x 10(14) cm) that was ejected in eruptive pre-explosion mass-loss episodes. The late-time (> 10 days) light curve requires an additional energy source, which could be the radioactive decay of Ni-56.
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| 5. |
- Yao, Yuhan, et al.
(författare)
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ZTF Early Observations of Type Ia Supernovae. I. Properties of the 2018 Sample
- 2019
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 886:2
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Tidskriftsartikel (refereegranskat)abstract
- Early-time observations of Type Ia supernovae (SNe Ia) are essential to constrain the properties of their progenitors. In this paper, we present high-quality light curves of 127 SNe Ia discovered by the Zwicky Transient Facility (ZTF) in 2018. We describe our method to perform forced point-spread function photometry, which can be applied to other types of extragalactic transients. With a planned cadence of six observations per night (three g + three r), all of the 127 SNe Ia are detected in both g and r bands more than 10 days (in the rest frame) prior to the epoch of g-band maximum light. The redshifts of these objects range from z = 0.0181 to 0.165; the median redshift is 0.074. Among the 127 SNe, 50 are detected at least 14 days prior to maximum light (in the rest frame), with a subset of nine objects being detected more than 17 days before g-band peak. This is the largest sample of young SNe Ia collected to date; it can be used to study the shape and color evolution of the rising light curves in unprecedented detail. We discuss six peculiar events in this sample: one 02cx-like event ZTF18abclfee (SN 2018crl), one Ia-CSM SN ZTF18aaykjei (SN 2018cxk), and four objects with possible super-Chandrasekhar mass progenitors: ZTF18abhpgje (SN 2018eul), ZTF18abdpvnd (SN 2018dvf), ZTF18aawpcel (SN 2018cir), and ZTF18abddmrf (SN 2018dsx).
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| 6. |
- Coughlin, Michael W., et al.
(författare)
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2900 Square Degree Search for the Optical Counterpart of Short Gamma-Ray Burst GRB 180523B with the Zwicky Transient Facility
- 2019
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:998
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Tidskriftsartikel (refereegranskat)abstract
- There is significant interest in the models for production of short gamma-ray bursts (GRBs). Until now, the number of known short GRBs with multi-wavelength afterglows has been small. While the Fermi GRB Monitor detects many GRBs relative to the Neil Gehrels Swift Observatory, the large localization regions makes the search for counterparts difficult. With the Zwicky Transient Facility (ZTF) recently achieving first light, it is now fruitful to use its combination of depth (m(AB) similar to 20.6), field of view (approximate to 47 square degrees), and survey cadence (every similar to 3 days) to perform Target of Opportunity observations. We demonstrate this capability on GRB 180523B, which was recently announced by the Fermi GRB Monitor as a short GRB. ZTF imaged approximate to 2900 square degrees of the localization region, resulting in the coverage of 61.6% of the enclosed probability over two nights to a depth of m(AB) similar to 20.5. We characterized 14 previously unidentified transients, and none were found to be consistent with a short GRB counterpart. This search with the ZTF shows it is an efficient camera for searching for coarsely localized short GRB and gravitational-wave counterparts, allowing for a sensitive search with minimal interruption to its nominal cadence.
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| 7. |
- Andreoni, Igor, et al.
(författare)
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GROWTH on S190510g : DECam Observation Planning and Follow-up of a Distant Binary Neutron Star Merger Candidate
- 2019
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 881:1
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Tidskriftsartikel (refereegranskat)abstract
- The first two months of the third Advanced LIGO and Virgo observing run (2019 April-May) showed that distant gravitational-wave (GW) events can now be readily detected. Three candidate mergers containing neutron stars (NS) were reported in a span of 15 days, all likely located more than 100 Mpc away. However, distant events such as the three new NS mergers are likely to be coarsely localized, which highlights the importance of facilities and scheduling systems that enable deep observations over hundreds to thousands of square degrees to detect the electromagnetic counterparts. On 2019 May 10 02: 59:39.292 UT the GW candidate S190510g was discovered and initially classified as a binary neutron star (BNS) merger with 98% probability. The GW event was localized within an area of 3462 deg(2), later refined to 1166 deg(2) (90%) at a distance of 227 +/- 92 Mpc. We triggered Target-of-Opportunity observations with the Dark Energy Camera (DECam), a wide-field optical imager mounted at the prime focus of the 4 m Blanco Telescope at Cerro Tololo Inter-American Observatory in Chile. This Letter describes our DECam observations and our real-time analysis results, focusing in particular on the design and implementation of the observing strategy. Within 24 hr of the merger time, we observed 65% of the total enclosed probability of the final skymap with an observing efficiency of 94%. We identified and publicly announced 13 candidate counterparts. S190510g was reclassified 1.7 days after the merger, after our observations were completed, with a BNS merger probability reduced from 98% to 42% in favor of a terrestrial classification.
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| 8. |
- Ghaneh, Paula, et al.
(författare)
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The Impact of Positive Resection Margins on Survival and Recurrence Following Resection and Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma
- 2019
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Ingår i: Annals of Surgery. - 0003-4932 .- 1528-1140. ; 269:3, s. 520-529
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Tidskriftsartikel (refereegranskat)abstract
- Objective and Background: Local and distant disease recurrence are frequently observed following pancreatic cancer resection, but an improved understanding of resection margin assessment is required to aid tailored therapiesMethods: Analyses were carried out to assess the association between clinical characteristics and margin involvement as well as the effects of individual margin involvement on site of recurrence and overall and recurrence-free survival using individual patient data from the European Study Group for Pancreatic Cancer (ESPAC)-3 randomized controlled trial.Results: There were 1151 patients, of whom 505 (43.9%) had an RI resection. The median and 95% confidence interval (CI) overall survival was 24.9 (22.9-27.2) months for 646 (56.1%) patients with resection margin negative R0 >1 mm) tumors, 25.4 (21.6 30.4) months for 146 (12.7%) patients with RI <1 mm positive resection margins, and 18.7 (17.2-21.1) months for 359 (31.2%) patients with R1-direct positive margins (P < 0.001). In multivariable analysis, overall R 1-direct tumor margins, poor tumor differentiation, positive lymph node status, WHO performance status ≥ 1, maximum tumor size, and RI-direct posterior resection margin were all independently significantly associated with reduced overall and recurrence-free survival. Competing risks analysis showed that overall R1-direct positive resection margin status, positive lymph node status. WHO performance status 1, and R1-direct positive superior mesenteric/medial margin resection status were all significantly associated with local recurrence.Conclusions: RI-direct resections were associated with significantly reduced overall and recurrence-free survival following pancreatic cancer resection. Resection margin involvement was also associated with an increased risk for local recurrence.
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| 9. |
- Goldstein, Daniel A., et al.
(författare)
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Rates and Properties of Supernovae Strongly Gravitationally Lensed by Elliptical Galaxies in Time-domain Imaging Surveys
- 2019
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 243:1
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Tidskriftsartikel (refereegranskat)abstract
- Supernovae that are strongly gravitationally lensed (gLSNe) by elliptical galaxies are powerful probes of astrophysics and cosmology that will be discovered systematically by wide-field, high-cadence imaging surveys such as the Zwicky Transient Facility (ZTF) and the Large Synoptic Survey Telescope (LSST). Here we use pixel-level simulations that include observing strategy, target selection, supernova properties, and dust to forecast the rates and properties of gLSNe that ZTF and LSST will find. Applying the resolution-insensitive discovery strategy of Goldstein et al., we forecast that ZTF (LSST) can discover 0.02 (0.79) 91bg-like, 0.17 (5.92) 91T-like, 1.22 (47.84) Type Ia, 2.76 (88.51) Type IIP, 0.31 (12.78) Type IIL, and 0.36 (15.43) Type Ib/c gLSNe per year, with uncertainties dominated by uncertainties in the supernova rate. We also forecast that the surveys can discover at least 3.75 (209.32) Type IIn gLSNe per year, for a total of at least 8.60 (380.60) gLSNe per year under fiducial observing strategies. ZTF gLSNe have a median z(s) = 0.9, z(l) = 0.35, vertical bar mu(tot)vertical bar = 30, Delta t(max) = 10 days, min (theta) = 0 ''.25, and N-img = 4. LSST gLSNe are less compact and less magnified, with a median z(s) = 1.0, z(l) = 0.4, vertical bar mu(tot)vertical bar = 6, Delta t(max) = 25 days, min(theta) = 0 ''.6, and N-img = 2. We develop a model of the supernova-host galaxy connection and find that the vast majority of gLSN host galaxies will be multiply imaged, enabling detailed constraints on lens models with sufficiently deep high-resolution imaging taken after the supernova has faded. We release the results of our simulations as catalogs at http://portal.nersc.gov/project/astro250/glsne/.
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| 10. |
- Goldstein, Sarah A., et al.
(författare)
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Characteristics and Outcomes of Atrial Fibrillation in Patients With Thyroid Disease (from the ARISTOTLE Trial)
- 2019
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 124:9, s. 1406-1412
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Tidskriftsartikel (refereegranskat)abstract
- Whether patients with atrial fibrillation (AF) and thyroid disease are clinically distinct from those with AF and no thyroid disease is unknown. Furthermore, the effectiveness of anticoagulation for prevention of AF-related thromboembolic events in patients with thyroid disease has not been adequately studied. Patients enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation, which compared apixaban with warfarin in patients with AF (n = 18,201), were categorized by thyroid disease history at randomization (hypothyroidism, hyperthyroidism, and no thyroid disease). Adjusted hazard ratios derived from Cox models were used to compare outcomes by thyroid disease history. Associations between randomized treatment and outcomes by thyroid disease history were examined using Cox models with interaction terms. A total of 18,021/18,201 (99%) patients had available thyroid disease history at randomization: 1,656 (9%) had hypothyroidism, 321 (2%) had hyperthyroidism, and 16,044 (89%) had no thyroid disease. When compared with those without a history of thyroid disease, patients with hypo- or hyperthyroidism were more likely to be female (60.4% vs 32.1%; 52.0% vs 32.1%; both p < 0.0001). Patients with hypothyroidism were older (73 vs 70 years, p < 0.0001) and more likely to have had previous falls (8.7% vs 4.3%, p < 0.0001). There was no difference in clinical outcomes by thyroid disease history. The benefit of apixaban compared with warfarin was similar regardless of thyroid disease history (interaction p > 0.10). In conclusion, despite differences in baseline characteristics of patients with and without thyroid disease, their clinical outcomes were similar. The benefit of apixban compared with warfarin was preserved regardless of thyroid disease history.
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