The Librarian

published or submitted for publicatio

Formation and Evolution of the Disk System of the Milky Way: [alpha/Fe] Ratios and Kinematics of the SEGUE G-Dwarf Sample

We employ measurements of the [alpha/Fe] ratio derived from low-resolution (R~2000) spectra of 17,277 G-type dwarfs from the SEGUE survey to separate them into likely thin- and thick-disk subsamples. Both subsamples exhibit strong gradients of orbital rotational velocity with metallicity, of opposite signs, -20 to -30 km/s/dex for the thin-disk and +40 to +50 km/s/dex for the thick-disk population. The rotational velocity is uncorrelated with Galactocentric distance for the thin-disk subsample, and exhibits a small trend for the thick-disk subsample. The rotational velocity decreases with distance from the plane for both disk components, with similar slopes (-9.0 {\pm} 1.0 km/s/kpc). Thick-disk stars exhibit a strong trend of orbital eccentricity with metallicity (about -0.2/dex), while the eccentricity does not change with metallicity for the thin-disk subsample. The eccentricity is almost independent of Galactocentric radius for the thin-disk population, while a marginal gradient of the eccentricity with radius exists for the thick-disk population. Both subsamples possess similar positive gradients of eccentricity with distance from the Galactic plane. The shapes of the eccentricity distributions for the thin- and thick-disk populations are independent of distance from the plane, and include no significant numbers of stars with eccentricity above 0.6. Among several contemporary models of disk evolution we consider, radial migration appears to have played an important role in the evolution of the thin-disk population, but possibly less so for the thick disk, relative to the gas-rich merger or disk heating scenarios. We emphasize that more physically realistic models and simulations need to be constructed in order to carry out the detailed quantitative comparisons that our new data enable.Comment: Accepted for publication in ApJ, 18 pages, 12 figures, 2 tables, emulateapj forma

On the alleged duality of the Galactic halo

We examine the kinematics of the Galactic halo based on SDSS/SEGUE data by Carollo et al. (2007, 2010). We find that their claims of a counter-rotating halo are the result of substantial biases in distance estimates (of order 50%): the claimed retrograde component, which makes up only a tiny fraction of the entire sample, prone to contaminations, is identified as the tail of distance overestimates. The strong overestimates also result in a lift in the vertical velocity component, which explains the large altitudes those objects were claimed to reach. Errors are worst for the lowest metallicity stars, which explains the metal-poor nature of the artificial component. We also argue that measurement errors were not properly accounted for and that the use of Gaussian fitting on intrinsically non-Gaussian Galactic components invokes the identification of components that are distorted or even artificial. Our evaluation of the data leads to a revision of the estimated velocity ellipsoids and does not yield any reliable evidence for a counterrotating halo component. If a distinct counterrotating halo component exists it must be far weaker than claimed by Carollo et al. Finally we note that their revised analysis presented in Beers et al. (2011) does not alleviate our main concerns.Comment: 17 pages, 12 figures, submitted to MNRA

Radial Migration in Galactic Thick Discs

We present a study of the extent to which the Sellwood & Binney radial migration of stars is affected by their vertical motion about the midplane. We use both controlled simulations in which only a single spiral mode is excited, as well as slightly more realistic cases with multiple spiral patterns and a bar. We find that rms angular momentum changes are reduced by vertical motion, but rather gradually, and the maximum changes are almost as large for thick disc stars as for those in a thin disc. We find that particles in simulations in which a bar forms suffer slightly larger angular momentum changes than in comparable cases with no bar, but the cumulative effect of multiple spiral events still dominates. We have determined that vertical action, and not vertical energy, is conserved on average during radial migration.Comment: 23 pages, 25 figures, accepted to appear in MNRA

Quantitative Assessment of Whole-Body Tumor Burden in Adult Patients with Neurofibromatosis

Purpose Patients with neurofibromatosis 1 (NF1), NF2, and schwannomatosis are at risk for multiple nerve sheath tumors and premature mortality. Traditional magnetic resonance imaging (MRI) has limited ability to assess disease burden accurately. The aim of this study was to establish an international cohort of patients with quantified whole-body internal tumor burden and to correlate tumor burden with clinical features of disease. Methods We determined the number, volume, and distribution of internal nerve sheath tumors in patients using whole-body MRI (WBMRI) and three-dimensional computerized volumetry. We quantified the distribution of tumor volume across body regions and used unsupervised cluster analysis to group patients based on tumor distribution. We correlated the presence and volume of internal tumors with disease-related and demographic factors. Results WBMRI identified 1286 tumors in 145/247 patients (59%). Schwannomatosis patients had the highest prevalence of tumors (P = 0.03), but NF1 patients had the highest median tumor volume (P = 0.02). Tumor volume was unevenly distributed across body regions with overrepresentation of the head/neck and pelvis. Risk factors for internal nerve sheath tumors included decreasing numbers of café-au-lait macules in NF1 patients (P = 0.003) and history of skeletal abnormalities in NF2 patients (P = 0.09). Risk factors for higher tumor volume included female gender (P = 0.05) and increasing subcutaneous neurofibromas (P = 0.03) in NF1 patients, absence of cutaneous schwannomas in NF2 patients (P = 0.06), and increasing age in schwannomatosis patients (p = 0.10). Conclusion WBMRI provides a comprehensive phenotype of neurofibromatosis patients, identifies distinct anatomic subgroups, and provides the basis for investigating molecular biomarkers that correlate with unique disease manifestations

Quantitative Assessment of Whole-Body Tumor Burden in Adult Patients with Neurofibromatosis

Patients with neurofibromatosis 1 (NF1), NF2, and schwannomatosis are at risk for multiple nerve sheath tumors and premature mortality. Traditional magnetic resonance imaging (MRI) has limited ability to assess disease burden accurately. The aim of this study was to establish an international cohort of patients with quantified whole-body internal tumor burden and to correlate tumor burden with clinical features of disease.We determined the number, volume, and distribution of internal nerve sheath tumors in patients using whole-body MRI (WBMRI) and three-dimensional computerized volumetry. We quantified the distribution of tumor volume across body regions and used unsupervised cluster analysis to group patients based on tumor distribution. We correlated the presence and volume of internal tumors with disease-related and demographic factors.WBMRI identified 1286 tumors in 145/247 patients (59%). Schwannomatosis patients had the highest prevalence of tumors (P = 0.03), but NF1 patients had the highest median tumor volume (P = 0.02). Tumor volume was unevenly distributed across body regions with overrepresentation of the head/neck and pelvis. Risk factors for internal nerve sheath tumors included decreasing numbers of café-au-lait macules in NF1 patients (P = 0.003) and history of skeletal abnormalities in NF2 patients (P = 0.09). Risk factors for higher tumor volume included female gender (P = 0.05) and increasing subcutaneous neurofibromas (P = 0.03) in NF1 patients, absence of cutaneous schwannomas in NF2 patients (P = 0.06), and increasing age in schwannomatosis patients (p = 0.10).WBMRI provides a comprehensive phenotype of neurofibromatosis patients, identifies distinct anatomic subgroups, and provides the basis for investigating molecular biomarkers that correlate with unique disease manifestations

FoxP3+ T regulatory cells in cancer : prognostic biomarkers and therapeutic targets

T Regulatory cells (Tregs) can have both protective and pathological roles. They maintain immune homeostasis and inhibit immune responses in various diseases, including cancer. Proportions of Tregs in the peripheral blood of some cancer patients increase by five-to ten-folds, compared to those in healthy individuals. Tregs contribute to cancer development and progression by suppressing T effector cell functions, thereby compromising tumor killing and promoting tumor growth. Highly immunosuppressive Tregs express upregulated levels of the transcription factor, Forkhead box protein P3 (FoxP3). Elevated levels of FoxP3+ Tregs within the tumor microenvironment (TME) showed a positive correlation with poor prognosis in various cancer patients. Despite the success of immunotherapy, including the use of immune checkpoint inhibitors, a significant proportion of patients show low response rates as a result of primary or acquired resistance against therapy. Some of the mechanisms which underlie the development of therapy resistance are associated with Treg suppressive function. In this review, we describe Treg contribution to cancer development/progression, and the mechanisms of Treg-mediated immunosuppression. We discuss the prognostic significance of FoxP3+ Tregs in different cancers and their potential use as prognostic biomarkers. We also describe potential therapeutic strategies to target Tregs in combination with other types of immunotherapies aiming to overcome tumor resistance and improve clinical outcomes in cancer patients. Overall, understanding the prognostic significance of FoxP3+ Tregs in various cancers and their contribution to therapeutic resistance could help in the development of more effective targeted therapeutic strategies to enhance the clinical outcomes in cancer patients

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Use of ovary culture techniques in reproductive toxicology

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved. Acknowledgements The author's studies in this field are supported by MRC grants G1002118 (NS and RAA) and G110357 (RAA), MR/L010011/1 (PAF), the European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 212885 (PAF) and the Wellcome Trust (080388 to PAF). AS was funded by a BBSRC CASE Studentship co-funded by AstraZeneca.Peer reviewedPublisher PD