| 1. |
- Beecham, Ashley H, et al.
(author)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Journal article (peer-reviewed)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 2. |
- Adhikari, Subash, et al.
(author)
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A high-stringency blueprint of the human proteome
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Research review (peer-reviewed)abstract
- The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP’s tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases.
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| 3. |
- Berg, Danielle A., et al.
(author)
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The COS Legacy Archive Spectroscopy Survey (CLASSY) Treasury Atlas
- 2022
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In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 261:2
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Journal article (peer-reviewed)abstract
- Far-ultraviolet (FUV; ∼1200–2000 Å) spectra are fundamental to our understanding of star-forming galaxies, providing a unique window on massive stellar populations, chemical evolution, feedback processes, and reionization. The launch of the James Webb Space Telescope will soon usher in a new era, pushing the UV spectroscopic frontier to higher redshifts than ever before; however, its success hinges on a comprehensive understanding of the massive star populations and gas conditions that power the observed UV spectral features. This requires a level of detail that is only possible with a combination of ample wavelength coverage, signal-to-noise, spectral-resolution, and sample diversity that has not yet been achieved by any FUV spectral database. We present the Cosmic Origins Spectrograph Legacy Spectroscopic Survey (CLASSY) treasury and its first high-level science product, the CLASSY atlas. CLASSY builds on the Hubble Space Telescope (HST) archive to construct the first high-quality (S/N1500 Å ≳ 5/resel), high-resolution (R ∼ 15,000) FUV spectral database of 45 nearby (0.002 < z < 0.182) star-forming galaxies. The CLASSY atlas, available to the public via the CLASSY website, is the result of optimally extracting and coadding 170 archival+new spectra from 312 orbits of HST observations. The CLASSY sample covers a broad range of properties including stellar mass (6.2 < log M⋆(M⊙) < 10.1), star formation rate (−2.0 < log SFR (M⊙ yr−1) < +1.6), direct gas-phase metallicity (7.0 < 12+log(O/H) < 8.8), ionization (0.5 < O32 < 38.0), reddening (0.02 < E(B − V) < 0.67), and nebular density (10 < ne (cm−3) < 1120). CLASSY is biased to UV-bright star-forming galaxies, resulting in a sample that is consistent with the z ∼ 0 mass–metallicity relationship, but is offset to higher star formation rates by roughly 2 dex, similar to z ≳ 2 galaxies. This unique set of properties makes the CLASSY atlas the benchmark training set for star-forming galaxies across cosmic time.
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| 4. |
- Binggeli, Christian, 1989-
(author)
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Galaxies in the epoch of reionization : Investigating the high-redshift galaxy population through simulations and observations
- 2021
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Doctoral thesis (other academic/artistic)abstract
- The cosmic reionization is the last major gas phase transition in cosmic history, yet it remains poorly understood. Current constraints indicate that early star-forming galaxies drove the reionization process through producing and releasing large numbers of ionizing photons into the intergalactic medium. However, our understanding of the ionizing escape fraction (fesc) and the general properties of high-redshift galaxies is still limited.In this thesis, simulated galaxies and observations are used to investigate epoch-of-reionization galaxies and to explore methods that can aid future investigations of such objects. Using simulations, we have shown that it may be possible to constrain fesc in epoch-of-reionization galaxies using quite simple diagnostics that should be observable with the upcoming James Webb Space Telescope (JWST). We also show that variations in star formation activity larger than those predicted in our simulations may lead to a possible degeneracy with high fesc. However, auxiliary information obtained with the JWST may allow us to disentangle variations in the star formation activity from high fesc.We compare galaxies from several simulations to the recently spectroscopically confirmed z=9.1096 galaxy MACS1149-JD1. We find that none of the simulations are able to reproduce the large Balmer break observed in MACS1149-JD1, and argue that unless it represents an outlier in the high-redshift galaxy population, this may indicate that the simulations fail to capture some key physics. Finally, we present ALMA observations of the z=7.6637 galaxy z7_GSD_3811. This object remains undetected in several commonly detected FIR emission lines and FIR dust emission. Using SED-fitting and by comparing our observations to models and low-redshift observations, we show that our non-detections could indicate that the object is poor in metals and dust.Our findings could help future observers to further constrain the nature of high-redshift galaxies and their role in reionization.
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| 5. |
- Bonate, Peter L., et al.
(author)
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Training the next generation of pharmacometric modelers : a multisector perspective
- 2023
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In: Journal of Pharmacokinetics and Pharmacodynamics. - : Springer Nature. - 1567-567X .- 1573-8744. ; 51:1, s. 5-31
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Journal article (peer-reviewed)abstract
- The current demand for pharmacometricians outmatches the supply provided by academic institutions and considerable investments are made to develop the competencies of these scientists on-the-job. Even with the observed increase in academic programs related to pharmacometrics, this need is unlikely to change in the foreseeable future, as the demand and scope of pharmacometrics applications keep expanding. Further, the field of pharmacometrics is changing. The field largely started when Lewis Sheiner and Stuart Beal published their seminal papers on population pharmacokinetics in the late 1970’s and early 1980’s and has continued to grow in impact and use since its inception. Physiological-based pharmacokinetics and systems pharmacology have grown rapidly in scope and impact in the last decade and machine learning is just on the horizon. While all these methodologies are categorized as pharmacometrics, no one person can be an expert in everything. So how do you train future pharmacometricians? Leading experts in academia, industry, contract research organizations, clinical medicine, and regulatory gave their opinions on how to best train future pharmacometricians. Their opinions were collected and synthesized to create some general recommendations.
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| 6. |
- Forslund, Tommie, et al.
(author)
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Attachment goes to court : child protection and custody issues
- 2022
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In: Attachment & Human Development. - : Taylor & Francis Group. - 1461-6734 .- 1469-2988. ; 24:1, s. 1-52
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Journal article (peer-reviewed)abstract
- Attachment theory and research are drawn upon in many applied settings, including family courts, but misunderstandings are widespread and sometimes result in misapplications. The aim of this consensus statement is, therefore, to enhance understanding, counter misinformation, and steer family-court utilisation of attachment theory in a supportive, evidence-based direction, especially with regard to child protection and child custody decision-making. The article is divided into two parts. In the first, we address problems related to the use of attachment theory and research in family courts, and discuss reasons for these problems. To this end, we examine family court applications of attachment theory in the current context of the best-interest-of-the-child standard, discuss misunderstandings regarding attachment theory, and identify factors that have hindered accurate implementation. In the second part, we provide recommendations for the application of attachment theory and research. To this end, we set out three attachment principles: the child’s need for familiar, non-abusive caregivers; the value of continuity of good-enough care; and the benefits of networks of attachment relationships. We also discuss the suitability of assessments of attachment quality and caregiving behaviour to inform family court decision-making. We conclude that assessments of caregiver behaviour should take center stage. Although there is dissensus among us regarding the use of assessments of attachment quality to inform child custody and child-protection decisions, such assessments are currently most suitable for targeting and directing supportive interventions. Finally, we provide directions to guide future interdisciplinary research collaboration.
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| 7. |
- Forslund, Tommie, et al.
(author)
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El Apego Va a Juicio: Problemas de Custodia y Protección Infantil : [Attachment goes to court: Child protection and custody issues]
- 2021
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In: Anuario de psicología jurídica. - : Colegio Oficial de la Psicologia de Madrid. - 1133-0740 .- 2174-0542. ; 32:1, s. 115-139
-
Journal article (peer-reviewed)abstract
- Attachment theory and research are drawn upon in many applied settings, including family courts, but misunderstandings are widespread and sometimes result in misapplications. The aim of this consensus statement is, therefore, to enhance understanding, counter misinformation, and steer family-court utilisation of attachment theory in a supportive, evidence-based direction, especially with regard to child protection and child custody decision-making. This article is divided into two parts. In the first part, we address problems related to the use of attachment theory and research in family courts, and discuss reasons for these problems. To this end, we examine family court applications of attachment theory in the current context of the best-interest-of-the-child standard, discuss misunderstandings regarding attachment theory, and identify factors that have hindered accurate implementation. In the second part, we provide recommendations for the application of attachment theory and research. To this end, we set out three attachment principles: the child's need for familiar, non-abusive caregivers; the value of continuity of good-enough care; and the benefits of networks of attachment relationships. We also discuss the suitability of assessments of attachment quality and caregiving behaviour to inform family court decision-making. We conclude that assessments of caregiver behaviour should take center stage. Although there is dissensus among us regarding the use of assessments of attachment quality to inform child custody and child-protection decisions, such assessments are currently most suitable for targeting and directing supportive interventions. Finally, we provide directions to guide future interdisciplinary research collaboration.
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| 8. |
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| 9. |
- Gazagnes, Simon, et al.
(author)
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Interpreting the Si ii and C ii Line Spectra from the COS Legacy Archive Spectroscopic SurveY Using a Virtual Galaxy from a High-resolution Radiation-hydrodynamic Simulation
- 2023
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 952:2
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Journal article (peer-reviewed)abstract
- Observations of low-ionization state metal lines provide crucial insights into the interstellar medium (ISM) of galaxies, yet, disentangling the physical processes responsible for the emerging line profiles is difficult. This work investigates how mock spectra generated using a single galaxy in a radiation-hydrodynamical simulation can help us interpret observations of a real galaxy. We create 22,500 C ii and Si ii spectra from the virtual galaxy at different times and through multiple lines of sight and compare them with the 45 observations of low-redshift star-forming galaxies from the COS Legacy Spectroscopic SurveY (classy). We find that the mock profiles provide accurate replicates of the observations of 38 galaxies with a broad range of stellar masses (106–109M⊙) and metallicities (0.02–0.55 Z⊙). Additionally, we highlight that aperture losses explain the weakness of the fluorescent emission in several classy spectra and must be accounted for when comparing simulations to observations. Overall, we show that the evolution of a single simulated galaxy can produce a large diversity of spectra whose properties are representative of galaxies of comparable or smaller masses. Building upon these results, we explore the origin of the continuum, residual flux, and fluorescent emission in the simulation. We find that these different spectral features all emerge from distinct regions in the galaxy's ISM, and their characteristics can vary as a function of the viewing angle. While these outcomes challenge simplified interpretations of down-the-barrel spectra, our results indicate that high-resolution simulations provide an optimal framework to interpret these observations.
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| 10. |
- James, Bethan L., et al.
(author)
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CLASSY. II. A Technical Overview of the COS Legacy Archive Spectroscopic Survey
- 2022
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In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 262:2
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Journal article (peer-reviewed)abstract
- The COS Legacy Archive Spectroscopic SurveY (CLASSY) is designed to provide the community with a spectral atlas of 45 nearby star-forming galaxies that were chosen to cover similar properties to those seen at high z (z > 6). The prime high-level science product of CLASSY is accurately coadded UV spectra, ranging from ∼1000 to 2000 Å, derived from a combination of archival and new data obtained with HST's Cosmic Origins Spectrograph (COS). This paper details the multistage technical processes of creating this prime data product and the methodologies involved in extracting, reducing, aligning, and coadding far-ultraviolet and near-ultraviolet (NUV) spectra. We provide guidelines on how to successfully utilize COS observations of extended sources, despite COS being optimized for point sources, and best-practice recommendations for the coaddition of UV spectra in general. Moreover, we discuss the effects of our reduction and coaddition techniques in the scientific application of the CLASSY data. In particular, we find that accurately accounting for flux calibration offsets can affect the derived properties of the stellar populations, while customized extractions of NUV spectra for extended sources are essential for correctly diagnosing the metallicity of galaxies via C iii] nebular emission. Despite changes in spectral resolution of up to ∼25% between individual data sets (due to changes in the COS line-spread function), no adverse affects were observed on the difference in velocity width and outflow velocities of isolated absorption lines when measured in the final combined data products, owing in part to our signal-to-noise regime of S/N < 20.
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