141 research outputs found
Limited Sampling Strategy to Predict AUC of the CYP3A Phenotyping Probe Midazolam in Adults: Application to Various Assay Techniques
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97211/1/00912700222011418.pd
Delivery of Dark Material to Vesta via Carbonaceous Chondritic Impacts
NASA's Dawn spacecraft observations of asteroid (4) Vesta reveal a surface
with the highest albedo and color variation of any asteroid we have observed so
far. Terrains rich in low albedo dark material (DM) have been identified using
Dawn Framing Camera (FC) 0.75 {\mu}m filter images in several geologic
settings: associated with impact craters (in the ejecta blanket material and/or
on the crater walls and rims); as flow-like deposits or rays commonly
associated with topographic highs; and as dark spots (likely secondary impacts)
nearby impact craters. This DM could be a relic of ancient volcanic activity or
exogenic in origin. We report that the majority of the spectra of DM are
similar to carbonaceous chondrite meteorites mixed with materials indigenous to
Vesta. Using high-resolution seven color images we compared DM color properties
(albedo, band depth) with laboratory measurements of possible analog materials.
Band depth and albedo of DM are identical to those of carbonaceous chondrite
xenolith-rich howardite Mt. Pratt (PRA) 04401. Laboratory mixtures of Murchison
CM2 carbonaceous chondrite and basaltic eucrite Millbillillie also show band
depth and albedo affinity to DM. Modeling of carbonaceous chondrite abundance
in DM (1-6 vol%) is consistent with howardite meteorites. We find no evidence
for large-scale volcanism (exposed dikes/pyroclastic falls) as the source of
DM. Our modeling efforts using impact crater scaling laws and numerical models
of ejecta reaccretion suggest the delivery and emplacement of this DM on Vesta
during the formation of the ~400 km Veneneia basin by a low-velocity (<2
km/sec) carbonaceous impactor. This discovery is important because it
strengthens the long-held idea that primitive bodies are the source of carbon
and probably volatiles in the early Solar System.Comment: Icarus (Accepted) Pages: 58 Figures: 15 Tables:
Study protocol for a type III hybrid effectiveness-implementation trial of strategies to implement firearm safety promotion as a universal suicide prevention strategy in pediatric primary care
BACKGROUND: Insights from behavioral economics, or how individuals\u27 decisions and behaviors are shaped by finite cognitive resources (e.g., time, attention) and mental heuristics, have been underutilized in efforts to increase the use of evidence-based practices in implementation science. Using the example of firearm safety promotion in pediatric primary care, which addresses an evidence-to-practice gap in universal suicide prevention, we aim to determine: is a less costly and more scalable behavioral economic-informed implementation strategy (i.e., Nudge ) powerful enough to change clinician behavior or is a more intensive and expensive facilitation strategy needed to overcome implementation barriers?
METHODS: The Adolescent and child Suicide Prevention in Routine clinical Encounters (ASPIRE) hybrid type III effectiveness-implementation trial uses a longitudinal cluster randomized design. We will test the comparative effectiveness of two implementation strategies to support clinicians\u27 use of an evidence-based firearm safety practice, S.A.F.E. Firearm, in 32 pediatric practices across two health systems. All pediatric practices in the two health systems will receive S.A.F.E. Firearm materials, including training and cable locks. Half of the practices (k = 16) will be randomized to receive Nudge; the other half (k = 16) will be randomized to receive Nudge plus 1 year of facilitation to target additional practice and clinician implementation barriers (Nudge+). The primary implementation outcome is parent-reported clinician fidelity to the S.A.F.E Firearm program. Secondary implementation outcomes include reach and cost. To understand how the implementation strategies work, the primary mechanism to be tested is practice adaptive reserve, a self-report practice-level measure that includes relationship infrastructure, facilitative leadership, sense-making, teamwork, work environment, and culture of learning.
DISCUSSION: The ASPIRE trial will integrate implementation science and behavioral economic approaches to advance our understanding of methods for implementing evidence-based firearm safety promotion practices in pediatric primary care. The study answers a question at the heart of many practice change efforts: which strategies are sufficient to support change, and why? Results of the trial will offer valuable insights into how best to implement evidence-based practices that address sensitive health matters in pediatric primary care.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT04844021 . Registered 14 April 2021
Swift follow-up observations of candidate gravitational-wave transient events
We present the first multi-wavelength follow-up observations of two candidate
gravitational-wave (GW) transient events recorded by LIGO and Virgo in their
2009-2010 science run. The events were selected with low latency by the network
of GW detectors and their candidate sky locations were observed by the Swift
observatory. Image transient detection was used to analyze the collected
electromagnetic data, which were found to be consistent with background.
Off-line analysis of the GW data alone has also established that the selected
GW events show no evidence of an astrophysical origin; one of them is
consistent with background and the other one was a test, part of a "blind
injection challenge". With this work we demonstrate the feasibility of rapid
follow-ups of GW transients and establish the sensitivity improvement joint
electromagnetic and GW observations could bring. This is a first step toward an
electromagnetic follow-up program in the regime of routine detections with the
advanced GW instruments expected within this decade. In that regime
multi-wavelength observations will play a significant role in completing the
astrophysical identification of GW sources. We present the methods and results
from this first combined analysis and discuss its implications in terms of
sensitivity for the present and future instruments.Comment: Submitted for publication 2012 May 25, accepted 2012 October 25,
published 2012 November 21, in ApJS, 203, 28 (
http://stacks.iop.org/0067-0049/203/28 ); 14 pages, 3 figures, 6 tables;
LIGO-P1100038; Science summary at
http://www.ligo.org/science/Publication-S6LVSwift/index.php ; Public access
area to figures, tables at
https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p110003
Search for gravitational waves associated with the InterPlanetary Network short gamma ray bursts
We outline the scientific motivation behind a search for gravitational waves
associated with short gamma ray bursts detected by the InterPlanetary Network
(IPN) during LIGO's fifth science run and Virgo's first science run. The IPN
localisation of short gamma ray bursts is limited to extended error boxes of
different shapes and sizes and a search on these error boxes poses a series of
challenges for data analysis. We will discuss these challenges and outline the
methods to optimise the search over these error boxes.Comment: Methods paper; Proceedings for Eduardo Amaldi 9 Conference on
Gravitational Waves, July 2011, Cardiff, U
A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007
We present the results of the first search for gravitational wave bursts
associated with high energy neutrinos. Together, these messengers could reveal
new, hidden sources that are not observed by conventional photon astronomy,
particularly at high energy. Our search uses neutrinos detected by the
underwater neutrino telescope ANTARES in its 5 line configuration during the
period January - September 2007, which coincided with the fifth and first
science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed
for candidate gravitational-wave signals coincident in time and direction with
the neutrino events. No significant coincident events were observed. We place
limits on the density of joint high energy neutrino - gravitational wave
emission events in the local universe, and compare them with densities of
merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at
http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access
area to figures, tables at
https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000
First Low-Latency LIGO+Virgo Search for Binary Inspirals and their Electromagnetic Counterparts
Aims. The detection and measurement of gravitational-waves from coalescing
neutron-star binary systems is an important science goal for ground-based
gravitational-wave detectors. In addition to emitting gravitational-waves at
frequencies that span the most sensitive bands of the LIGO and Virgo detectors,
these sources are also amongst the most likely to produce an electromagnetic
counterpart to the gravitational-wave emission. A joint detection of the
gravitational-wave and electromagnetic signals would provide a powerful new
probe for astronomy.
Methods. During the period between September 19 and October 20, 2010, the
first low-latency search for gravitational-waves from binary inspirals in LIGO
and Virgo data was conducted. The resulting triggers were sent to
electromagnetic observatories for followup. We describe the generation and
processing of the low-latency gravitational-wave triggers. The results of the
electromagnetic image analysis will be described elsewhere.
Results. Over the course of the science run, three gravitational-wave
triggers passed all of the low-latency selection cuts. Of these, one was
followed up by several of our observational partners. Analysis of the
gravitational-wave data leads to an estimated false alarm rate of once every
6.4 days, falling far short of the requirement for a detection based solely on
gravitational-wave data.Comment: 13 pages, 13 figures. For a repository of data used in the
publication, go to:
http://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=P1100065 Also see the
announcement for this paper on ligo.org at:
http://www.ligo.org/science/Publication-S6CBCLowLatency
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Activation of the hypothalamic-pituitary-adrenal axis by exogenous and endogenous GDF15.
An acute increase in the circulating concentration of glucocorticoid hormones is essential for the survival of severe somatic stresses. Circulating concentrations of GDF15, a hormone that acts in the brain to reduce food intake, are frequently elevated in stressful states. We now report that GDF15 potently activates the hypothalamic-pituitary-adrenal (HPA) axis in mice and rats. A blocking antibody to the GDNF-family receptor α-like receptor completely prevented the corticosterone response to GDF15 administration. In wild-type mice exposed to a range of stressful stimuli, circulating levels of both corticosterone and GDF15 rose acutely. In the case of Escherichia coli or lipopolysaccharide injections, the vigorous proinflammatory cytokine response elicited was sufficient to produce a near-maximal HPA response, regardless of the presence or absence of GDF15. In contrast, the activation of the HPA axis seen in wild-type mice in response to the administration of genotoxic or endoplasmic reticulum toxins, which do not provoke a marked rise in cytokines, was absent in Gdf15 -/- mice. In conclusion, consistent with its proposed role as a sentinel hormone, endogenous GDF15 is required for the activation of the protective HPA response to toxins that do not induce a substantial cytokine response. In the context of efforts to develop GDF15 as an antiobesity therapeutic, these findings identify a biomarker of target engagement and a previously unrecognized pharmacodynamic effect, which will require monitoring in human studies
Anticipated and experienced discrimination amongst people with schizophrenia, bipolar disorder and major depressive disorder: a cross-sectional study.
BACKGROUND: The unfair treatment of individuals with severe mental illness has been linked to poorer physical and mental health outcomes. Additionally, anticipation of discrimination may lead some individuals to avoid participation in particular life areas, leading to greater isolation and social marginalisation. This study aimed to establish the levels and clinical and socio-demographic associations of anticipated and experienced discrimination amongst those diagnosed with a schizophrenia and comparator severe mental illnesses (bipolar and major depressive disorders). METHODS: This study was a cross-sectional analysis of anticipated and experienced discrimination from 202 individuals in South London (47% with schizophrenia, 32% with depression and 20% with bipolar disorder). RESULTS: 93% of the sample anticipated discrimination and 87% of participants had experienced discrimination in at least one area of life in the previous year. There was a significant association between the anticipation and the experience of discrimination. Higher levels of experienced discrimination were reported by those of a mixed ethnicity, and those with higher levels of education. Women anticipated more discrimination than men. Neither diagnosis nor levels of functioning were associated with the extent of discrimination. Clinical symptoms of anxiety, depression and suspiciousness were associated with more experienced and anticipated discrimination respectively. CONCLUSIONS: The unfair treatment of individuals with severe mental illnesses remains unacceptably common. Population level interventions are needed to reduce levels of discrimination and to safeguard individuals. Interventions are also required to assist those with severe mental illness to reduce internalised stigma and social avoidance
Neurocognitive functioning in acute or early HIV infection
We examined neurocognitive functioning among persons with acute or early HIV infection (AEH) and hypothesized that the neurocognitive performance of AEH individuals would be intermediate between HIV seronegatives (HIVâ) and those with chronic HIV infection. Comprehensive neurocognitive testing was accomplished with 39 AEH, 63 chronically HIV infected, and 38 HIVâ participants. All AEH participants were HIV infected for less than 1Â year. Average domain deficit scores were calculated in seven neurocognitive domains. HIVâ, AEH, and chronically HIV infected groups were ranked from best (rank of 1) to worst (rank of 3) in each domain. All participants received detailed substance use, neuromedical, and psychiatric evaluations and HIV infected persons provided information on antiretroviral treatment and completed laboratory evaluations including plasma and CSF viral loads. A nonparametric test of ordered alternatives (Page test), and the appropriate nonparametric follow-up test, was used to evaluate level of neuropsychological (NP) functioning across and between groups. The median duration of infection for the AEH group was 16Â weeks [interquartile range, IQR: 10.3â40.7] as compared to 4.9Â years [2.8â11.1] in the chronic HIV group. A Page test using ranks of average scores in the seven neurocognitive domains showed a significant monotonic trend with the best neurocognitive functioning in the HIVâ group (mean rankâ=â1.43), intermediate neurocognitive functioning in the AEH group (mean rankâ=â1.71), and the worst in the chronically HIV infected (mean rankâ=â2.86; L statisticâ=â94, pâ<â0.01); however, post-hoc testing comparing neurocognitive impairment of each group against each of the other groups showed that the chronically infected group was significantly different from both the HIVâ and AEH groups on neurocognitive performance; the AEH group was statistically indistinguishable from the HIVâ group. Regression models among HIV infected participants were unable to identify significant predictors of neurocognitive performance. Neurocognitive functioning was worst among persons with chronic HIV infection. Although a significant monotonic trend existed and patterns of the data suggest the AEH individuals may fall intermediate to HIVâ and chronic participants, we were not able to statistically confirm this hypothesis
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