431 research outputs found

    Taking AIM at serious illness: implementing an access to investigational medicines expanded access program

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    When seriously ill patients have exhausted all treatment options available as part of usual care, the use of investigational agents may be warranted. Food and Drug Administration’s (FDA) Expanded Access (EA) pathway provides a mechanism for these patient’s physicians to pursue use of an investigational agent outside of a clinical trial when trial enrollment is not a feasible option. Though FDA has recently implemented processes to significantly streamline the regulatory portion of the process, the overall pathway has several time-consuming components including communication with the pharmaceutical company and the associated institutional requirements for EA use (contracting, Institutional Review Board [IRB], pharmacy, billing). Here, we present our experience building infrastructure at the Vanderbilt University Medical Center (VUMC) to support physicians and patients in pursuing EA, called the Access to Investigational Medicines (AIM) Platform, aligning the needs and responsibilities of institutional stakeholders and streamlining to ensure efficiency and regulatory compliance. Since its launch, the AIM team has experienced steady growth, supporting 40 EA cases for drugs/biologics, including both single patient cases and intermediate-size EA protocols in the emergent and non-emergent setting. As the EA pathway is a complex process that requires expert facilitation, we propose prioritizing EA support infrastructure at major academic medical centers as an essential regulatory knowledge function

    Galaxy Zoo: Are Bars Responsible for the Feeding of Active Galactic Nuclei at 0.2 < z < 1.0?

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    We present a new study investigating whether active galactic nuclei (AGN) beyond the local universe are preferentially fed via large-scale bars. Our investigation combines data from Chandra and Galaxy Zoo: Hubble (GZH) in the AEGIS, COSMOS, and GOODS-S surveys to create samples of face-on, disc galaxies at 0.2 < z < 1.0. We use a novel method to robustly compare a sample of 120 AGN host galaxies, defined to have 10^42 erg/s < L_X < 10^44 erg/s, with inactive control galaxies matched in stellar mass, rest-frame colour, size, Sersic index, and redshift. Using the GZH bar classifications of each sample, we demonstrate that AGN hosts show no statistically significant enhancement in bar fraction or average bar likelihood compared to closely-matched inactive galaxies. In detail, we find that the AGN bar fraction cannot be enhanced above the control bar fraction by more than a factor of two, at 99.7% confidence. We similarly find no significant difference in the AGN fraction among barred and non-barred galaxies. Thus we find no compelling evidence that large-scale bars directly fuel AGN at 0.2<z<1.0. This result, coupled with previous results at z=0, implies that moderate-luminosity AGN have not been preferentially fed by large-scale bars since z=1. Furthermore, given the low bar fractions at z>1, our findings suggest that large-scale bars have likely never directly been a dominant fueling mechanism for supermassive black hole growth.Comment: 13 pages, 5 figures, 2 tables, accepted by MNRA

    Genetic epidemiology of pelvic organ prolapse: a systematic review

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    Given current evidence supporting a genetic predisposition for pelvic organ prolapse (POP), we conducted a systematic review of published literature on the genetic epidemiology of POP. Inclusion criteria were linkage studies, candidate gene association and genome-wide association studies (GWAS) in adult women published in English and indexed in PubMed through December 2012, with no limit on date of publication. Methodology adhered to the PRISMA guidelines. Data were systematically extracted by two reviewers and graded by the Venice criteria for studies of genetic associations. A meta-analysis was performed on all single nucleotide polymorphisms (SNPs) evaluated by two or more studies with similar methodology. The meta-analysis suggests that collagen type 3 alpha 1 (COL3A1) rs1800255 genotype AA is associated with POP, OR 4.79 (95% CI 1.91 to 11.98, p= 0.001) compared to the reference genotype GG in populations of Asian and Dutch women. There was little evidence of heterogeneity for rs1800255 (p-value for heterogeneity= 0.94; proportion of variance due to heterogeneity, I2= 0.00%). There was insufficient evidence to determine whether other SNPs evaluated by two or more papers were associated with POP. An association with POP was seen in individual studies for estrogen receptor alpha (ER-α) rs2228480 GA, COL3A1 exon 31, chromosome 9q21 (HLOD score 3.41) as well as six SNPs identified by a GWAS. Overall, individual studies were of small sample size and often of poor quality. Future studies would benefit from more rigorous study design as outlined in the Venice recommendations

    The K2 M67 Study: A Curiously Young Star in an Eclipsing Binary in an Old Open Cluster

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    We present an analysis of a slightly eccentric (e=0.05e=0.05), partially eclipsing long-period (P=69.73P = 69.73 d) main sequence binary system (WOCS 12009, Sanders 1247) in the benchmark old open cluster M67. Using Kepler K2 and ground-based photometry along with a large set of new and reanalyzed spectra, we derived highly precise masses (1.111±0.0151.111\pm0.015 and 0.748±0.005M⊙0.748\pm0.005 M_\odot) and radii (1.071±0.008±0.0031.071\pm0.008\pm0.003 and 0.713±0.019±0.026R⊙0.713\pm0.019\pm0.026 R_\odot, with statistical and systematic error estimates) for the stars. The radius of the secondary star is in agreement with theory. The primary, however, is approximately 15%15\% smaller than reasonable isochrones for the cluster predict. Our best explanation is that the primary star was produced from the merger of two stars, as this can also account for the non-detection of photospheric lithium and its higher temperature relative to other cluster main sequence stars at the same VV magnitude. To understand the dynamical characteristics (low measured rotational line broadening of the primary star and the low eccentricity of the current binary orbit), we believe that the most probable (but not the only) explanation is the tidal evolution of a close binary within a primordial triple system (possibly after a period of Kozai-Lidov oscillations), leading to merger approximately 1Gyr ago. This star appears to be a future blue straggler that is being revealed as the cluster ages and the most massive main sequence stars die out.Comment: 33 pages, 11 figures, accepted to AJ, photometry files will be available with the electronic journal articl

    Galaxy Zoo: Are bars responsible for the feeding of active galactic nuclei at 0.2<z<1.0?

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    We present a new study investigating whether active galactic nuclei (AGN) beyond the local universe are preferentially fed via large-scale bars. Our investigation combines data from Chandra and Galaxy Zoo: Hubble (GZH) in the AEGIS (All-wavelength Extended Groth strip International Survey), COSMOS (Cosmological Evolution Survey), and (Great Observatories Origins Deep Survey-South) GOODS-S surveys to create samples of face-on, disc galaxies at 0.21, our findings suggest that large-scale bars have likely never directly been a dominant fuelling mechanism for supermassive black hole growt

    Galaxy Zoo: Are Bars Responsible for the Feeding of Active Galactic Nuclei at 0.2 \u3c \u3cem\u3ez\u3c/em\u3e \u3c 1.0?

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    We present a new study investigating whether active galactic nuclei (AGN) beyond the local universe are preferentially fed via large-scale bars. Our investigation combines data from Chandra and Galaxy Zoo: Hubble (GZH) in the AEGIS (All-wavelength Extended Groth strip International Survey), COSMOS (Cosmological Evolution Survey), and (Great Observatories Origins Deep Survey-South) GOODS-S surveys to create samples of face-on, disc galaxies at 0.2 \u3c z \u3c 1.0. We use a novel method to robustly compare a sample of 120 AGN host galaxies, defined to have 1042 erg s−1 \u3c LX \u3c 1044 erg s−1, with inactive control galaxies matched in stellar mass, rest-frame colour, size, Sérsic index, and redshift. Using the GZH bar classifications of each sample, we demonstrate that AGN hosts show no statistically significant enhancement in bar fraction or average bar likelihood compared to closely-matched inactive galaxies. In detail, we find that the AGN bar fraction cannot be enhanced above the control bar fraction by more than a factor of 2, at 99.7 per cent confidence. We similarly find no significant difference in the AGN fraction among barred and non-barred galaxies. Thus we find no compelling evidence that large-scale bars directly fuel AGN at 0.2 \u3c z \u3c 1.0. This result, coupled with previous results at z = 0, implies that moderate-luminosity AGN have not been preferentially fed by large-scale bars since z = 1. Furthermore, given the low bar fractions at z \u3e 1, our findings suggest that large-scale bars have likely never directly been a dominant fuelling mechanism for supermassive black hole growth
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