| 1. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 2. |
- Abazajian, Kevork, et al.
(author)
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CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
- 2022
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
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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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| 3. |
- Gaziano, Liam, et al.
(author)
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Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19
- 2021
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In: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 27:4
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Journal article (peer-reviewed)abstract
- Large-scale Mendelian randomization and colocalization analyses using gene expression and soluble protein data for 1,263 actionable druggable genes, which encode protein targets for approved drugs or drugs in clinical development, identify IFNAR2 and ACE2 as the most promising therapeutic targets for early management of COVID-19. Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs or in clinical phase of drug development. Using summary statistics from the Host Genetics Initiative and the Million Veteran Program, we studied 7,554 patients hospitalized with COVID-19 and >1 million controls. We found significant Mendelian randomization results for three proteins (ACE2, P = 1.6 x 10(-6); IFNAR2, P = 9.8 x 10(-11) and IL-10RB, P = 2.3 x 10(-14)) using cis-expression quantitative trait loci genetic instruments that also had strong evidence for colocalization with COVID-19 hospitalization. To disentangle the shared expression quantitative trait loci signal for IL10RB and IFNAR2, we conducted phenome-wide association scans and pathway enrichment analysis, which suggested that IFNAR2 is more likely to play a role in COVID-19 hospitalization. Our findings prioritize trials of drugs targeting IFNAR2 and ACE2 for early management of COVID-19.
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| 7. |
- Bonetti, A, et al.
(author)
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RADICL-seq identifies general and cell type-specific principles of genome-wide RNA-chromatin interactions
- 2020
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 1018-
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Journal article (peer-reviewed)abstract
- Mammalian genomes encode tens of thousands of noncoding RNAs. Most noncoding transcripts exhibit nuclear localization and several have been shown to play a role in the regulation of gene expression and chromatin remodeling. To investigate the function of such RNAs, methods to massively map the genomic interacting sites of multiple transcripts have been developed; however, these methods have some limitations. Here, we introduce RNA And DNA Interacting Complexes Ligated and sequenced (RADICL-seq), a technology that maps genome-wide RNA–chromatin interactions in intact nuclei. RADICL-seq is a proximity ligation-based methodology that reduces the bias for nascent transcription, while increasing genomic coverage and unique mapping rate efficiency compared with existing methods. RADICL-seq identifies distinct patterns of genome occupancy for different classes of transcripts as well as cell type–specific RNA-chromatin interactions, and highlights the role of transcription in the establishment of chromatin structure.
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| 8. |
- Hellgren, Margareta, 1955, et al.
(author)
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The burden of poor glycaemic control in people with newly diagnosed type 2 diabetes in Sweden: A health economic modelling analysis based on nationwide data
- 2021
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In: Diabetes, obesity and metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 23:7, s. 1604-1613
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Journal article (peer-reviewed)abstract
- Aim To evaluate the economic and clinical burden associated with poor glycaemic control in Sweden, in people with type 2 diabetes (T2D) initiating first-line glucose-lowering therapy. Materials and Methods Population data were obtained from Swedish national registers. Immediate glycaemic control was compared with delays in achieving control of 1 and 3 years, with outcomes projected over 3, 10 and 50 years in the validated IQVIA CORE Diabetes Model. Glycaemic control was defined as glycated haemoglobin (HbA1c) targets of 52, 48 and 42 mmol/mol, as recommended in Swedish guidelines, according to age and disease duration. Costs (expressed in 2019 Swedish krona [SEK]) were accounted from a Swedish societal perspective. Results Immediate glycaemic control was associated with population-level cost savings of up to SEK 279 million and SEK 673 million versus delays of 1 and 3 years, respectively, as well as small population-level life expectancy benefits of up to 1305 and 2590 life years gained. Reduced levels of burden were a result of lower incidence and delayed time to onset of diabetes-related complications. Conclusions Even in people with T2D initiating first-line glucose-lowering therapy, the economic burden of poor glycaemic control in Sweden is substantial, but could be reduced by early and effective treatment to achieve glycaemic targets.
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