661 research outputs found
Controlling Level of Unconsciousness by Titrating Propofol with Deep Reinforcement Learning
Reinforcement Learning (RL) can be used to fit a mapping from patient state
to a medication regimen. Prior studies have used deterministic and value-based
tabular learning to learn a propofol dose from an observed anesthetic state.
Deep RL replaces the table with a deep neural network and has been used to
learn medication regimens from registry databases. Here we perform the first
application of deep RL to closed-loop control of anesthetic dosing in a
simulated environment. We use the cross-entropy method to train a deep neural
network to map an observed anesthetic state to a probability of infusing a
fixed propofol dosage. During testing, we implement a deterministic policy that
transforms the probability of infusion to a continuous infusion rate. The model
is trained and tested on simulated pharmacokinetic/pharmacodynamic models with
randomized parameters to ensure robustness to patient variability. The deep RL
agent significantly outperformed a proportional-integral-derivative controller
(median absolute performance error 1.7% +/- 0.6 and 3.4% +/- 1.2). Modeling
continuous input variables instead of a table affords more robust pattern
recognition and utilizes our prior domain knowledge. Deep RL learned a smooth
policy with a natural interpretation to data scientists and anesthesia care
providers alike.Comment: International Conference on Artificial Intelligence in Medicine 202
Stellar Population Diagnostics of Elliptical Galaxy Formation
Major progress has been achieved in recent years in mapping the properties of
passively-evolving, early-type galaxies (ETG) from the local universe all the
way to redshift ~2. Here, age and metallicity estimates for local cluster and
field ETGs are reviewed as based on color-magnitude, color-sigma, and
fundamental plane relations, as well as on spectral-line indices diagnostics.
The results of applying the same tools at high redshifts are then discussed,
and their consistency with the low-redshift results is assessed. Most low- as
well as high-redshift (z~1) observations consistently indicate 1) a formation
redshift z>~3 for the bulk of stars in cluster ETGs, with their counterparts in
low-density environments being on average ~1-2 Gyr younger, i.e., formed at
z>~1.5-2, 2) the duration of the major star formation phase anticorrelates with
galaxy mass, and the oldest stellar populations are found in the most massive
galaxies. With increasing redshift there is evidence for a decrease in the
number density of ETGs, especially of the less massive ones, whereas existing
data appear to suggest that most of the most-massive ETGs were already fully
assembled at z~1. Beyond this redshift, the space density of ETGs starts
dropping significantly, and as ETGs disappear, a population of massive,
strongly clustered, starburst galaxies progressively becomes more and more
prominent, which makes them the likely progenitors to ETGs.Comment: To appear on Annual Review of Astronomy & Astrophysics, Vol. 44
(2006). 46 pages with 16 figures. Replaced version includes updated
references, few typos less, and replaces Fig. 11 and Fig. 16 which had been
skrewed u
CD69 is a TGF-β/1α,25-dihydroxyvitamin D3 target gene in monocytes
CD69 is a transmembrane lectin that can be expressed on most hematopoietic cells. In monocytes, it has been functionally linked to the 5-lipoxygenase pathway in which the leukotrienes, a class of highly potent inflammatory mediators, are produced. However, regarding CD69 gene expression and its regulatory mechanisms in monocytes, only scarce data are available. Here, we report that CD69 mRNA expression, analogous to that of 5-lipoxygenase, is induced by the physiologic stimuli transforming growth factor-β (TGF-β) and 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) in monocytic cells. Comparison with T- and B-cell lines showed that the effect was specific for monocytes. CD69 expression levels were increased in a concentration-dependent manner, and kinetic analysis revealed a rapid onset of mRNA expression, indicating that CD69 is a primary TGF-β/1α,25(OH)2D3 target gene. PCR analysis of different regions of the CD69 mRNA revealed that de novo transcription was initiated and proximal and distal parts were induced concomitantly. In common with 5-lipoxygenase, no activation of 0.7 kb or ~2.3 kb promoter fragments by TGF-β and 1α,25(OH)2D3 could be observed in transient reporter assays for CD69. Analysis of mRNA stability using a transcription inhibitor and a 3′UTR reporter construct showed that TGF-β and 1α,25(OH)2D3 do not influence CD69 mRNA stability. Functional knockdown of Smad3 clearly demonstrated that upregulation of CD69 mRNA, in contrast to 5-LO, depends on Smad3. Comparative studies with different inhibitors for mitogen activated protein kinases (MAPKs) revealed that MAPK signalling is involved in CD69 gene regulation, whereas 5-lipoxygenase gene expression was only partly affected. Mechanistically, we found evidence that CD69 gene upregulation depends on TAK1-mediated p38 activation. In summary, our data indicate that CD69 gene expression, conforming with 5-lipoxygenase, is regulated monocyte-specifically by the physiologic stimuli TGF-β and 1α,25(OH)2D3 on mRNA level, although different mechanisms account for the upregulation of each gene
Preoperative diagnosis of obscure gastrointestinal bleeding due to a GIST of the jejunum: a case report
Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms affecting the digestive tract or nearby structures within the abdomen. We present a case of a 66-year-old female patient who presented with obscure anemia due to gastrointestinal bleeding and underwent exploratory laparotomy during which a large GIST of the small intestine was discovered. Examining the preoperative results of video capsule endoscopy, computed tomography, and angiography and comparing them with the operative findings we discuss which of these investigations plays the most important role in the detection and localization of GIST. A sort review of the literature is also conducted on these rare mesenchymal tumours
The fitness of African malaria vectors in the presence and limitation of host behaviour
<p>Background
Host responses are important sources of selection upon the host species range of ectoparasites and phytophagous insects. However little is known about the role of host responses in defining the host species range of malaria vectors. This study aimed to estimate the relative importance of host behaviour to the feeding success and fitness of African malaria vectors, and assess its ability to predict their known host species preferences in nature.</p>
<p>Methods
Paired evaluations of the feeding success and fitness of African vectors Anopheles arabiensis and Anopheles gambiae s.s in the presence and limitation of host behaviour were conducted in a semi-field system (SFS) at Ifakara Health Institute, Tanzania. In one set of trials, mosquitoes were released within the SFS and allowed to forage overnight on a host that was free to exhibit natural behaviour in response to insect biting. In the other, mosquitoes were allowed to feed directly on from the skin surface of immobile hosts. The feeding success and subsequent fitness of vectors under these conditions were investigated on 6 host types (humans, calves, chickens, cows, dogs and goats) to assess whether physical movements of preferred host species (cattle for An. arabiensis, humans for An. gambiae s.s.) were less effective at preventing mosquito bites than those of common alternatives.</p>
<p>Results
Anopheles arabiensis generally had greater feeding success when applied directly to host skin than when foraging on unrestricted hosts (in five of six host species). However, An. gambiae s.s obtained blood meals from free and restrained hosts with similar success from most host types (four out of six). Overall, the blood meal size, oviposition rate, fecundity and post-feeding survival of mosquito vectors were significantly higher after feeding on hosts free to exhibit behaviour, than those who were immobilized during feeding trials.</p>
<p>Conclusions
Allowing hosts to move freely during exposure to mosquitoes was associated with moderate reductions in mosquito feeding success, but no detrimental impact to the subsequent fitness of mosquitoes that were able to feed upon them. This suggests that physical defensive behaviours exhibited by common host species including humans do not impose substantial fitness costs on African malaria vectors.</p>
Search for gamma-ray emission from magnetars with the Fermi Large Area Telescope
We report on the search for 0.1-10 GeV emission from magnetars in 17 months
of Fermi Large Area Telescope (LAT) observations. No significant evidence for
gamma-ray emission from any of the currently-known magnetars is found. The most
stringent upper limits to date on their persistent emission in the Fermi-LAT
energy range are estimated between ~10^{-12}-10^{-10} erg/s/cm2, depending on
the source. We also searched for gamma-ray pulsations and possible outbursts,
also with no significant detection. The upper limits derived support the
presence of a cut-off at an energy below a few MeV in the persistent emission
of magnetars. They also show the likely need for a revision of current models
of outer gap emission from strongly magnetized pulsars, which, in some
realizations, predict detectable GeV emission from magnetars at flux levels
exceeding the upper limits identified here using the Fermi-LAT observations.Comment: ApJ Letters in press; Corresponding authors: Caliandro G. A., Hadasch
D., Rea N., Burnett
Detection of Gamma-Ray Emission from the Starburst Galaxies M82 and NGC 253 with the Large Area Telescope on Fermi
We report the detection of high-energy gamma-ray emission from two starburst
galaxies using data obtained with the Large Area Telescope on board the Fermi
Gamma-ray Space Telescope. Steady point-like emission above 200 MeV has been
detected at significance levels of 6.8 sigma and 4.8 sigma respectively, from
sources positionally coincident with locations of the starburst galaxies M82
and NGC 253. The total fluxes of the sources are consistent with gamma-ray
emission originating from the interaction of cosmic rays with local
interstellar gas and radiation fields and constitute evidence for a link
between massive star formation and gamma-ray emission in star-forming galaxies.Comment: Submitted to ApJ Letter
Fermi Gamma-ray Imaging of a Radio Galaxy
The Fermi Gamma-ray Space Telescope has detected the gamma-ray glow emanating
from the giant radio lobes of the radio galaxy Centaurus A. The resolved
gamma-ray image shows the lobes clearly separated from the central active
source. In contrast to all other active galaxies detected so far in high-energy
gamma-rays, the lobe flux constitutes a considerable portion (>1/2) of the
total source emission. The gamma-ray emission from the lobes is interpreted as
inverse Compton scattered relic radiation from the cosmic microwave background
(CMB), with additional contribution at higher energies from the
infrared-to-optical extragalactic background light (EBL). These measurements
provide gamma-ray constraints on the magnetic field and particle energy content
in radio galaxy lobes, and a promising method to probe the cosmic relic photon
fields.Comment: 27 pages, includes Supplementary Online Material; corresponding
authors: C.C. Cheung, Y. Fukazawa, J. Knodlseder, L. Stawar
Fermi Large Area Telescope observations of PSR J1836+5925
The discovery of the gamma-ray pulsar PSR J1836+5925, powering the formerly
unidentified EGRET source 3EG J1835+5918, was one of the early accomplishments
of the Fermi Large Area Telescope (LAT). Sitting 25 degrees off the Galactic
plane, PSR J1836+5925 is a 173 ms pulsar with a characteristic age of 1.8
million years, a spindown luminosity of 1.1 erg s, and a
large off-peak emission component, making it quite unusual among the known
gamma-ray pulsar population. We present an analysis of one year of LAT data,
including an updated timing solution, detailed spectral results and a long-term
light curve showing no indication of variability. No evidence for a surrounding
pulsar wind nebula is seen and the spectral characteristics of the off-peak
emission indicate it is likely magnetospheric. Analysis of recent XMM
observations of the X-ray counterpart yields a detailed characterization of its
spectrum, which, like Geminga, is consistent with that of a neutron star
showing evidence for both magnetospheric and thermal emission.Comment: Accepted to Astrophysical Journa
The pathogenesis of low pathogenicity H7 avian influenza viruses in chickens, ducks and turkeys
<p>Abstract</p> <p>Background</p> <p>Avian influenza (AI) viruses infect numerous avian species, and low pathogenicity (LP) AI viruses of the H7 subtype are typically reported to produce mild or subclinical infections in both wild aquatic birds and domestic poultry. However relatively little work has been done to compare LPAI viruses from different avian species for their ability to cause disease in domestic poultry under the same conditions. In this study twelve H7 LPAI virus isolates from North America were each evaluated for their comparative pathogenesis in chickens, ducks, and turkeys.</p> <p>Results</p> <p>All 12 isolates were able to infect all three species at a dose of 10<sup>6 </sup>50% egg infectious doses based on seroconversion, although not all animals seroconverted with each isolate-species combination. The severity of disease varied among isolate and species combinations, but there was a consistent trend for clinical disease to be most severe in turkeys where all 12 isolates induced disease, and mortality was observed in turkeys exposed to 9 of the 12 viruses. Turkeys also shed virus by the oral and cloacal routes at significantly higher titers than either ducks or chickens at numerous time points. Only 3 isolates induced observable clinical disease in ducks and only 6 isolates induced disease in chickens, which was generally very mild and did not result in mortality. Full genome sequence was completed for all 12 isolates and some isolates did have features consistent with adaptation to poultry (e.g. NA stalk deletions), however none of these features correlated with disease severity.</p> <p>Conclusions</p> <p>The data suggests that turkeys may be more susceptible to clinical disease from the H7 LPAI viruses included in this study than either chickens or ducks. However the severity of disease and degree of virus shed was not clearly correlated with any isolate or group of isolates, but relied on specific species and isolate combinations.</p
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