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- Ashley-Koch, AE, et al.
(författare)
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Genome-wide association study identifies four pan-ancestry loci for suicidal ideation in the Million Veteran Program
- 2023
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 19:3, s. e1010623-
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Tidskriftsartikel (refereegranskat)abstract
- Suicidal ideation (SI) often precedes and predicts suicide attempt and death, is the most common suicidal phenotype and is over-represented in veterans. The genetic architecture of SI in the absence of suicide attempt (SA) is unknown, yet believed to have distinct and overlapping risk with other suicidal behaviors. We performed the first GWAS of SI without SA in the Million Veteran Program (MVP), identifying 99,814 SI cases from electronic health records without a history of SA or suicide death (SD) and 512,567 controls without SI, SA or SD. GWAS was performed separately in the four largest ancestry groups, controlling for sex, age and genetic substructure. Ancestry-specific results were combined via meta-analysis to identify pan-ancestry loci. Four genome-wide significant (GWS) loci were identified in the pan-ancestry meta-analysis with loci on chromosomes 6 and 9 associated with suicide attempt in an independent sample. Pan-ancestry gene-based analysis identified GWS associations with DRD2, DCC, FBXL19, BCL7C, CTF1, ANNK1, and EXD3. Gene-set analysis implicated synaptic and startle response pathways (q’s<0.05). European ancestry (EA) analysis identified GWS loci on chromosomes 6 and 9, as well as GWS gene associations in EXD3, DRD2, and DCC. No other ancestry-specific GWS results were identified, underscoring the need to increase representation of diverse individuals. The genetic correlation of SI and SA within MVP was high (rG = 0.87; p = 1.09e-50), as well as with post-traumatic stress disorder (PTSD; rG = 0.78; p = 1.98e-95) and major depressive disorder (MDD; rG = 0.78; p = 8.33e-83). Conditional analysis on PTSD and MDD attenuated most pan-ancestry and EA GWS signals for SI without SA to nominal significance, with the exception of EXD3 which remained GWS. Our novel findings support a polygenic and complex architecture for SI without SA which is largely shared with SA and overlaps with psychiatric conditions frequently comorbid with suicidal behaviors.
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- Badrzadeh, B, et al.
(författare)
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The Need or Enhanced Power System Modelling Techniques and Simulation Tools
- 2020
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Ingår i: CIGRE SCIENCE & ENGINEERING. - 2426-1335. ; 17:Febr, s. 30-46
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Tidskriftsartikel (refereegranskat)abstract
- The transition to a clean energy future requires thorough understanding of increasingly complex interactions between conventional generation, network equipment, variable renewable generation technologies (centralised and distributed), and demand response. Secure and reliable operation under such complex interactions requires the use of more advanced power system modelling and simulation tools and techniques. Conventional tools and techniques are reaching their limits to support such paradigm shifts. This paper provides an overview of commonly used and emerging power system simulation tools and techniques. Applications of these tools ranging from real-time power system operation to long-term planning are also discussed. Various approaches to gain confidence in the accuracy and applicability of the simulation models are presented. The paper then discusses emerging trends in simulation tools and techniques primarily stemming from the transition to a power system with increased penetration of inverter-based resources as these are used in variable renewable energy technologies.
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- Bessell, Michael S., et al.
(författare)
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Nucleosynthesis in a Primordial Supernova : Carbon and Oxygen Abundances in SMSS J031300.36-670839.3
- 2015
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 806:1
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Tidskriftsartikel (refereegranskat)abstract
- SMSS J031300.36-670839.3 (hereafter SM0313-6708) is a sub-giant halo star, with no detectable Fe lines and large overabundances of C and Mg relative to Ca. We obtained Very Large Telescope-Ultraviolet and Visual Echelle Spectrograph (UVES) spectra extending to 3060 angstrom showing strong OH A-X band lines enabling an oxygen abundance to be derived. The OH A-X band lines in SM0313-6708 are much stronger than the CH C-X band lines. Spectrum synthesis fits indicate an [O/C] ratio of 0.02 +/- 0.175. Our high signal-to-noise ratio UVES data also enabled us to lower the Fe abundance limit to [Fe/H](< 3D >,NLTE) < -7.52 (3 sigma). These data support our previous suggestion that the star formed from the iron-poor ejecta of a single massive star Population III supernova.
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- Gidal, B. E., et al.
(författare)
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Exposure-safety and efficacy response relationships and population pharmacokinetics of eslicarbazepine acetate
- 2018
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314. ; 138:3, s. 203-211
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesEslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) for focal-onset seizures (FOS). Pharmacokinetic (PK) and pharmacodynamic (PD) models were developed to assess dose selection, identify significant AED drug interactions, and quantitate relationships between exposure and safety and efficacy outcomes from Phase 3 trials of adjunctive ESL. MethodsEslicarbazepine (the primary active metabolite of ESL) population PK was evaluated using data from 1351 subjects enrolled in 14 studies (11 Phase 1 and three Phase 3 studies) after multiple oral doses ranging from 400 to 1200mg. Population PK and PD models related individual eslicarbazepine exposures to safety outcomes and efficacy responses. ResultsEslicarbazepine PK was described by a one-compartment model with linear absorption and elimination. The probability of a treatment-emergent adverse event (TEAE; dizziness, headache, or somnolence) was higher with an initial dose of ESL 800mg than with an initial dose of ESL 400mg QD. Body weight, sex, region, and baseline use of carbamazepine (CBZ) or lamotrigine were also found to influence the probability of TEAEs. Eslicarbazepine exposure influenced serum sodium concentration, standardized seizure frequency, and probability of response; better efficacy outcomes were predicted in patients not from Western Europe (WE; vs WE patients) and those not taking CBZ (vs taking CBZ) at baseline. ConclusionsPharmacokinetic and PK/PD modeling were implemented during the development of ESL for adjunctive treatment of FOS in adults. This quantitative approach supported decision-making during the development of ESL, and contributed to dosing recommendations and labeling information related to drug interactions.
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- Jacobson, Heather R., et al.
(författare)
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High-Resolution Spectroscopic Study of Extremely Metal-Poor Star Candidates from the Skymapper Survey
- 2015
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 807:2
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Tidskriftsartikel (refereegranskat)abstract
- The SkyMapper Southern Sky Survey is carrying out a search for the most metal-poor stars in the Galaxy. It identifies candidates by way of its unique filter set which allows for estimation of stellar atmospheric parameters. The set includes a narrow filter centered on the Ca II K 3933 angstrom line, enabling a robust estimate of stellar metallicity. Promising candidates are then confirmed with spectroscopy. We present the analysis of Magellan Inamori Kyocera Echelle high-resolution spectroscopy of 122 metal-poor stars found by SkyMapper in the first two years of commissioning observations. Forty-one stars have [Fe/H] <= -3.0. Nine have [Fe/H] <= -3.5, with three at [Fe/H] similar to -4. A 1D LTE abundance analysis of the elements Li, C, Na, Mg, Al, Si, Ca, Sc, Ti, Cr, Mn, Co, Ni, Zn, Sr, Ba, and Eu shows these stars have [X/Fe] ratios typical of other halo stars. One star with low [X/Fe] values appears to be "Fe-enhanced," while another star has an extremely large [Sr/Ba] ratio: >2. Only one other star is known to have a comparable value. Seven stars are "CEMP-no" stars ([C/Fe] > 0.7, [Ba/Fe] < 0). 21 stars exhibit mild r-process element enhancements (0.3 <= [Eu/Fe] < 1.0), while four stars have [Eu/Fe] >= 1.0. These results demonstrate the ability to identify extremely metal-poor stars from SkyMapper photometry, pointing to increased sample sizes and a better characterization of the metal-poor tail of the halo metallicity distribution function in the future.
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