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Search: WFRF:(Harrington Richard) > (2020-2023)

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1.
  • Abazajian, Kevork, et al. (author)
  • CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
  • 2022
  • In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
  • Journal article (peer-reviewed)abstract
    • 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. 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 semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, 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 semianalytic 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 r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
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2.
  • Batra, Gorav, et al. (author)
  • Biomarker-Based Prediction of Recurrent Ischemic Events in Patients With Acute Coronary Syndromes
  • 2022
  • In: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 80:18, s. 1735-1747
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: In patients with acute coronary syndrome (ACS), there is residual and variable risk of recurrent ischemic events.OBJECTIVES: This study aimed to develop biomarker-based prediction models for 1-year risk of cardiovascular (CV) death and myocardial infarction (MI) in patients with ACS undergoing percutaneous coronary intervention.METHODS: We included 10,713 patients from the PLATO (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome) trial in the development cohort and externally validated in 3,508 patients from the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trial. Variables contributing to risk of CV death/MI were assessed using Cox regression models, and a score was derived using subsets of variables approximating the full model.RESULTS: There were 632 and 190 episodes of CV death/MI in the development and validation cohorts. The most important predictors of CV death/MI were the biomarkers, growth differentiation factor 15, and N-terminal pro-B-type natriuretic peptide, which had greater prognostic value than all candidate variables. The final model included 8 items: age (A), biomarkers (B) (growth differentiation factor 15 and N-terminal pro-B-type natriuretic peptide), and clinical variables (C) (extent of coronary artery disease, previous vascular disease, Killip class, ACS type, P2Y12 inhibitor). The model, named ABC-ACS ischemia, was well calibrated and showed good discriminatory ability for 1-year risk of CV death/MI with C-indices of 0.71 and 0.72 in the development and validation cohorts, respectively. For CV death, the score performed better, with C-indices of 0.80 and 0.84 in the development and validation cohorts, respectively.CONCLUSIONS: An 8-item score for the prediction of CV death/MI was developed and validated for patients with ACS undergoing percutaneous coronary intervention. The ABC-ACS ischemia score showed good calibration and discrimination and might be useful for risk prediction and decision support in patients with ACS. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872; Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Participants With Acute Coronary Syndrome [TRACER]; NCT00527943)
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3.
  • Mueller, Stefanie H., et al. (author)
  • Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry
  • 2023
  • In: Genome Medicine. - : BioMed Central (BMC). - 1756-994X. ; 15
  • Journal article (peer-reviewed)abstract
    • Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 x 10(-6)) and AC058822.1 (P = 1.47 x 10(-4)), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C.Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 x 10(-5)), demonstrating the importance of diversifying study cohorts.
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4.
  • Otto, Friederike E.L., et al. (author)
  • Causality and the fate of climate litigation : The role of the social superstructure narrative
  • 2022
  • In: Global Policy. - : Wiley. - 1758-5880 .- 1758-5899. ; 13:5, s. 736-750
  • Journal article (peer-reviewed)abstract
    • Climate litigation has become a strategic tool to push for climate justice, including compensation for losses caused by climate change. Many cases rely on the establishment of a causal relationship between the defendants' emission of greenhouse gases (GHG) and the plaintiffs' losses. All decided cases seeking compensation for a concrete climate related impact have been unsuccessful (thus far). Legal scholars as well as social and natural scientists have looked at individual cases and evidence of these unsuccessful claims, aiming to identify legal and scientific hurdles. Based on previous research where we analysed specific cases, we step back from a case-specific analysis in this article and identify the social context in which law and science operate and intersect. We assert that without a general understanding of the urgency of climate change and the scientifically proven fact that climate change impacts the present, and that it is possible to attribute individual losses to human-caused climate change, the fate and future of climate litigation focusing on losses and damages will continue to encounter major obstacles in courts. This is despite the increasingly sophisticated strategies of litigants; the positive outcome of some strategic litigation and improvements in the field of climate science, all of which would be expected to sway for a successful future of the fight against climate change.
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6.
  • Otto, Friederike E L, et al. (author)
  • Toward an Inventory of the Impacts of Human-Induced Climate Change
  • 2020
  • In: Bulletin of the American Meteorological Society. - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 101:11
  • Journal article (peer-reviewed)abstract
    • Current levels of global warming (Haustein et al. 2017) have already intensified heat waves, droughts, and floods, with many recent events exhibiting evidence of being exacerbated by anthropogenic climate change (e.g., Herring et al. 2016, 2018). Recent improvements in understanding demonstrate that half a degree of additional warming will have further severe impacts (Masson-Delmotte et al. 2018). In the context of this rapid and damaging change, there is a clear need to quantify and address both the losses and damages from impacts we have not adapted to today, as well as to adapt to those that will emerge in the next few decades. To do this, it is essential to understand the impacts of man-made climate change on the scales that climate adaptation decisions are made. Drivers of disasters, ultimately responsible for much loss and damage, are unfolding in an ever-changing socioeconomic context, which also alters exposure and vulnerability. While various case studies exist (discussed below), there is to date no comprehensive or comparable database quantifying anthropogenic contributions to climate change loss and damage. We suggest that this needs to change.
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7.
  • Windhorst, Rogier A., et al. (author)
  • JWST PEARLS. Prime extragalactic areas for reionization and lensing science : project overview and first results
  • 2023
  • In: Astronomical Journal. - : Institute of Physics (IOP). - 0004-6256 .- 1538-3881. ; 165:1
  • Journal article (peer-reviewed)abstract
    • We give an overview and describe the rationale, methods, and first results from NIRCam images of the JWST “Prime Extragalactic Areas for Reionization and Lensing Science” (PEARLS) project. PEARLS uses up to eight NIRCam filters to survey several prime extragalactic survey areas: two fields at the North Ecliptic Pole (NEP); seven gravitationally lensing clusters; two high redshift protoclusters; and the iconic backlit VV 191 galaxy system to map its dust attenuation. PEARLS also includes NIRISS spectra for one of the NEP fields and NIRSpec spectra of two high-redshift quasars. The main goal of PEARLS is to study the epoch of galaxy assembly, active galactic nucleus (AGN) growth, and First Light. Five fields—the JWST NEP Time-Domain Field (TDF), IRAC Dark Field, and three lensing clusters—will be observed in up to four epochs over a year. The cadence and sensitivity of the imaging data are ideally suited to find faint variable objects such as weak AGN, high-redshift supernovae, and cluster caustic transits. Both NEP fields have sightlines through our Galaxy, providing significant numbers of very faint brown dwarfs whose proper motions can be studied. Observations from the first spoke in the NEP TDF are public. This paper presents our first PEARLS observations, their NIRCam data reduction and analysis, our first object catalogs, the 0.9–4.5 μm galaxy counts and Integrated Galaxy Light. We assess the JWST sky brightness in 13 NIRCam filters, yielding our first constraints to diffuse light at 0.9–4.5 μm. PEARLS is designed to be of lasting benefit to the community.
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