35 research outputs found
A primate model of severe malarial anaemia: a comparative pathogenesis study.
Severe malarial anaemia (SMA) is the most common life-threatening complication of Plasmodium falciparum infection in African children. SMA is characterised by haemolysis and inadequate erythropoiesis, and is associated with dysregulated inflammatory responses and reduced complement regulatory protein levels (including CD35). However, a deeper mechanistic understanding of the pathogenesis requires improved animal models. In this comparative study of two closely related macaque species, we interrogated potential causal factors for their differential and temporal relationships to onset of SMA. We found that rhesus macaques inoculated with blood-stage Plasmodium coatneyi developed SMA within 2 weeks, with no other severe outcomes, whereas infected cynomolgus macaques experienced only mild/ moderate anaemia. The abrupt drop in haematocrit in rhesus was accompanied by consumption of haptoglobin (haemolysis) and poor reticulocyte production. Rhesus developed a greater inflammatory response than cynomolgus macaques, and had lower baseline levels of CD35 on red blood cells (RBCs) leading to a significant reduction in the proportion of CD35+ RBCs during infection. Overall, severe anaemia in rhesus macaques infected with P. coatneyi has similar features to SMA in children. Our comparisons are consistent with an association of low baseline CD35 levels on RBCs and of early inflammatory responses with the pathogenesis of SMA
Clinician perception of care at the end of life in a quaternary neonatal intensive care unit
IntroductionCare for neonates at the end of life (EOL) is often challenging for families and medical teams alike, performed suboptimally, and requires an experienced and compassionate clinician. Much literature exists on adult and pediatric EOL care, but limited studies examine the neonatal process.MethodsWe aimed to describe clinicians' experiences around EOL care in a single quaternary neonatal intensive care unit as we implemented a standard guideline using the Pediatric Intensive Care Unit-Quality of Dying and Death 20 tool.ResultsSurveys were completed by 205 multidisciplinary clinicians over three time periods and included 18 infants at EOL. While most responses were high, a meaningful minority were below goal (<8 on 0–10 scale) for troubling symptom management, conflict between parents and staff, family access to resources, and parent preparation of symptoms. Comparison between Epochs revealed improvement in one symptom management and four communication categories. Satisfaction scores related to education around EOL were better in later Epochs. Neonatal Pain, Agitation, and Sedation Scale scores were low, with few outliers.DiscussionThese findings can guide those aiming to improve processes around neonatal EOL by identifying areas with the greatest challenges (e.g., conflict management) and areas that need further study (e.g., pain management around death)
The Allen Telescope Array Pi GHz Sky Survey I. Survey Description and Static Catalog Results for the Bootes Field
The Pi GHz Sky Survey (PiGSS) is a key project of the Allen Telescope Array.
PiGSS is a 3.1 GHz survey of radio continuum emission in the extragalactic sky
with an emphasis on synoptic observations that measure the static and
time-variable properties of the sky. During the 2.5-year campaign, PiGSS will
twice observe ~250,000 radio sources in the 10,000 deg^2 region of the sky with
b > 30 deg to an rms sensitivity of ~1 mJy. Additionally, sub-regions of the
sky will be observed multiple times to characterize variability on time scales
of days to years. We present here observations of a 10 deg^2 region in the
Bootes constellation overlapping the NOAO Deep Wide Field Survey field. The
PiGSS image was constructed from 75 daily observations distributed over a
4-month period and has an rms flux density between 200 and 250 microJy. This
represents a deeper image by a factor of 4 to 8 than we will achieve over the
entire 10,000 deg^2. We provide flux densities, source sizes, and spectral
indices for the 425 sources detected in the image. We identify ~100$ new flat
spectrum radio sources; we project that when completed PiGSS will identify 10^4
flat spectrum sources. We identify one source that is a possible transient
radio source. This survey provides new limits on faint radio transients and
variables with characteristic durations of months.Comment: Accepted for publication in ApJ; revision submitted with extraneous
figure remove
The Allen Telescope Array Twenty-centimeter Survey - A 690-Square-Degree, 12-Epoch Radio Dataset - I: Catalog and Long-Duration Transient Statistics
We present the Allen Telescope Array Twenty-centimeter Survey (ATATS), a
multi-epoch (12 visits), 690 square degree radio image and catalog at 1.4GHz.
The survey is designed to detect rare, very bright transients as well as to
verify the capabilities of the ATA to form large mosaics. The combined image
using data from all 12 ATATS epochs has RMS noise sigma = 3.94mJy / beam and
dynamic range 180, with a circular beam of 150 arcsec FWHM. It contains 4408
sources to a limiting sensitivity of S = 20 mJy / beam. We compare the catalog
generated from this 12-epoch combined image to the NRAO VLA Sky Survey (NVSS),
a legacy survey at the same frequency, and find that we can measure source
positions to better than ~20 arcsec. For sources above the ATATS completeness
limit, the median flux density is 97% of the median value for matched NVSS
sources, indicative of an accurate overall flux calibration. We examine the
effects of source confusion due to the effects of differing resolution between
ATATS and NVSS on our ability to compare flux densities. We detect no
transients at flux densities greater than 40 mJy in comparison with NVSS, and
place a 2-sigma upper limit on the transient rate for such sources of 0.004 per
square degree. These results suggest that the > 1 Jy transients reported by
Matsumura et al. (2009) may not be true transients, but rather variable sources
at their flux density threshold.Comment: 41 pages, 19 figures, ApJ accepted; corrected minor typo in Table
The Allen Telescope Array Pi GHz Sky Survey I. Survey Description and Static Catalog Results for the Bootes Field
The Pi GHz Sky Survey (PiGSS) is a key project of the Allen Telescope Array.
PiGSS is a 3.1 GHz survey of radio continuum emission in the extragalactic sky
with an emphasis on synoptic observations that measure the static and
time-variable properties of the sky. During the 2.5-year campaign, PiGSS will
twice observe ~250,000 radio sources in the 10,000 deg^2 region of the sky with
b > 30 deg to an rms sensitivity of ~1 mJy. Additionally, sub-regions of the
sky will be observed multiple times to characterize variability on time scales
of days to years. We present here observations of a 10 deg^2 region in the
Bootes constellation overlapping the NOAO Deep Wide Field Survey field. The
PiGSS image was constructed from 75 daily observations distributed over a
4-month period and has an rms flux density between 200 and 250 microJy. This
represents a deeper image by a factor of 4 to 8 than we will achieve over the
entire 10,000 deg^2. We provide flux densities, source sizes, and spectral
indices for the 425 sources detected in the image. We identify ~100$ new flat
spectrum radio sources; we project that when completed PiGSS will identify 10^4
flat spectrum sources. We identify one source that is a possible transient
radio source. This survey provides new limits on faint radio transients and
variables with characteristic durations of months.Comment: Accepted for publication in ApJ; revision submitted with extraneous
figure remove
Observing the Evolution of the Universe
How did the universe evolve? The fine angular scale (l>1000) temperature and
polarization anisotropies in the CMB are a Rosetta stone for understanding the
evolution of the universe. Through detailed measurements one may address
everything from the physics of the birth of the universe to the history of star
formation and the process by which galaxies formed. One may in addition track
the evolution of the dark energy and discover the net neutrino mass.
We are at the dawn of a new era in which hundreds of square degrees of sky
can be mapped with arcminute resolution and sensitivities measured in
microKelvin. Acquiring these data requires the use of special purpose
telescopes such as the Atacama Cosmology Telescope (ACT), located in Chile, and
the South Pole Telescope (SPT). These new telescopes are outfitted with a new
generation of custom mm-wave kilo-pixel arrays. Additional instruments are in
the planning stages.Comment: Science White Paper submitted to the US Astro2010 Decadal Survey.
Full list of 177 author available at http://cmbpol.uchicago.ed
Synaptic Depression Via Mglur1 Positive Allosteric Modulation Suppresses Cue-Induced Cocaine Craving
Cue-induced cocaine craving is a major cause of relapse in abstinent addicts. In rats, cue-induced craving progressively intensifies (incubates) during withdrawal from extended-access cocaine self-administration. After ~1 month of withdrawal, incubated craving is mediated by Ca(2+)-permeable AMPA receptors (CP-AMPARs) that accumulate in the nucleus accumbens (NAc). We found that decreased mGluR1 surface expression in the NAc preceded and enabled CP-AMPAR accumulation. Thus, restoring mGluR1 transmission by administering repeated injections of an mGluR1 positive allosteric modulator (PAM) prevented CP-AMPAR accumulation and incubation, whereas blocking mGluR1 transmission at even earlier withdrawal times accelerated CP-AMPAR accumulation. In studies conducted after prolonged withdrawal, when CP-AMPAR levels and cue-induced craving are high, we found that systemic administration of an mGluR1 PAM attenuated the expression of incubated craving by reducing CP-AMPAR transmission in the NAc to control levels. These results suggest a strategy in which recovering addicts could use a systemically active compound to protect against cue-induced relapse
Consensus guidelines for the use and interpretation of angiogenesis assays
The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference
Apathy and risk of probable incident dementia among community-dwelling older adults.
ObjectiveTo evaluate the association between baseline apathy and probable incident dementia in a population-based sample of community-dwelling older adults.MethodsWe studied 2,018 white and black community-dwelling older adults from the Health, Aging, and Body Composition (Health ABC) study. We measured apathy at year 6 (our study baseline) with the modified Apathy Evaluation Scale and divided participants into tertiles based on low, moderate, or severe apathy symptoms. Incident dementia was ascertained over 9 years by dementia medication use, hospital records, or clinically relevant cognitive decline on global cognition. We examined the association between apathy and probable incident dementia using a Cox proportional hazards model adjusting for demographics, cardiovascular risk factors, APOE4 status, and depressed mood. We also evaluated the association between the apathy group and cognitive change (as measured by the modified Mini-Mental State Examination and Digit Symbol Substitution Test over 5 years) using linear mixed effects models.ResultsOver 9 years of follow-up, 381 participants developed probable dementia. Severe apathy was associated with an increased risk of dementia compared to low apathy (25% vs 14%) in unadjusted (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.5-2.5) and adjusted models (HR 1.7, 95% CI 1.3-2.2). Greater apathy was associated with worse cognitive score at baseline, but not rate of change over time.ConclusionIn a diverse cohort of community-dwelling adults, apathy was associated with increased risk of developing probable dementia. This study provides novel evidence for apathy as a prodrome of dementia