2,460 research outputs found
Revisions to user costs for the Federal Reserve Bank of St. Louis monetary services indices
This analysis discusses recent changes to the user cost figures that are computed as part of the Federal Reserve Bank of St. Louis monetary services indices (MSI). The authors first introduce an alternative splicing procedure, robust to differences in scale between series, for those price subindices which, individually, have a time span shorter than the overall MSI but are spliced to span the entire period. They then correct an error in the calculation of user costs for money market mutual funds that caused these funds' user costs to be based, for a considerable period of time, on the last-reported value for one input data series. Finally, the authors also restore the yield-curve adjustment for composite assets, which they removed from published data during 2004 as they explored the unusual behavior of the user cost data for small-denomination time deposits.Federal Reserve Bank of St. Louis ; Monetary theory
TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy
Significance
Alzheimer’s disease (AD) is the most common cause of dementia and is a major public health problem for which there is currently no disease-modifying treatment. There is an urgent need for greater understanding of the molecular mechanisms underlying neurodegeneration in patients to create better therapeutic options. Recently, genetic studies uncovered novel AD risk variants in the microglial receptor, triggering receptor expressed on myeloid cells 2 (TREM2). Previous studies suggested that loss of TREM2 function worsens amyloid-β (Aβ) plaque-related toxicity. In contrast, we observe TREM2 deficiency mitigates neuroinflammation and protects against brain atrophy in the context of tau pathology. These findings indicate dual roles for TREM2 and microglia in the context of amyloid versus tau pathology, which are important to consider for potential treatments targeting TREM2.</jats:p
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Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study.
BackgroundEnrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors.MethodsIn a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies.Measurements and main resultsAn admission sTNFR1 concentration > 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration > 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level > 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor.ConclusionsThresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials
The White Dwarf Cooling Sequence of NGC6397
We present the results of a deep Hubble Space Telescope (HST) exposure of the
nearby globular cluster NGC6397, focussing attention on the cluster's white
dwarf cooling sequence. This sequence is shown to extend over 5 magnitudes in
depth, with an apparent cutoff at magnitude F814W=27.6. We demonstrate, using
both artificial star tests and the detectability of background galaxies at
fainter magnitudes, that the cutoff is real and represents the truncation of
the white dwarf luminosity function in this cluster. We perform a detailed
comparison between cooling models and the observed distribution of white dwarfs
in colour and magnitude, taking into account uncertainties in distance,
extinction, white dwarf mass, progenitor lifetimes, binarity and cooling model
uncertainties. After marginalising over these variables, we obtain values for
the cluster distance modulus and age of \mu_0 = 12.02 \pm 0.06 and T_c = 11.47
\pm 0.47Gyr (95% confidence limits). Our inferred distance and white dwarf
initial-final mass relations are in good agreement with other independent
determinations, and the cluster age is consistent with, but more precise than,
prior determinations made using the main sequence turnoff method. In
particular, within the context of the currently accepted \Lambda CDM
cosmological model, this age places the formation of NGC6397 at a redshift z=3,
at a time when the cosmological star formation rate was approaching its peak.Comment: 56 pages, 30 figure
Cell-specific activity-dependent fractionation of layer 2/3→5B excitatory signaling in mouse auditory cortex
© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Journal of Neuroscience 35 (2015): 3112-3123, doi:10.1523/JNEUROSCI.0836-14.2015.Auditory cortex (AC) layer 5B (L5B) contains both corticocollicular neurons, a type of pyramidal-tract neuron projecting to the inferior colliculus, and corticocallosal neurons, a type of intratelencephalic neuron projecting to contralateral AC. Although it is known that these neuronal types have distinct roles in auditory processing and different response properties to sound, the synaptic and intrinsic mechanisms shaping their input–output functions remain less understood. Here, we recorded in brain slices of mouse AC from retrogradely labeled corticocollicular and neighboring corticocallosal neurons in L5B. Corticocollicular neurons had, on average, lower input resistance, greater hyperpolarization-activated current (Ih), depolarized resting membrane potential, faster action potentials, initial spike doublets, and less spike-frequency adaptation. In paired recordings between single L2/3 and labeled L5B neurons, the probabilities of connection, amplitude, latency, rise time, and decay time constant of the unitary EPSC were not different for L2/3→corticocollicular and L2/3→corticocallosal connections. However, short trains of unitary EPSCs showed no synaptic depression in L2/3→corticocollicular connections, but substantial depression in L2/3→corticocallosal connections. Synaptic potentials in L2/3→corticocollicular connections decayed faster and showed less temporal summation, consistent with increased Ih in corticocollicular neurons, whereas synaptic potentials in L2/3→corticocallosal connections showed more temporal summation. Extracellular L2/3 stimulation at two different rates resulted in spiking in L5B neurons; for corticocallosal neurons the spike rate was frequency dependent, but for corticocollicular neurons it was not. Together, these findings identify cell-specific intrinsic and synaptic mechanisms that divide intracortical synaptic excitation from L2/3 to L5B into two functionally distinct pathways with different input–output functions.This work was supported by National Institutes of Health grants DC013272 (T.T. and G.M.G.S.), DC007905 (T.T.), NS061963 (G.M.G.S), R03DC012585 (J.W.M.), T32DC011499 (C.T.A.), and F32DC013734 (C.T.A), and by the Albert and Ellen Grass Faculty Award (T.T. and G.M.G.S.) and Charles Evans Foundation Award (T.T. and G.M.G.S.).2015-08-1
Deep ACS Imaging in the Globular Cluster NGC 6397: The Cluster Color Magnitude Diagram and Luminosity Function
We present the CMD from deep HST imaging in the globular cluster NGC 6397.
The ACS was used for 126 orbits to image a single field in two colors (F814W,
F606W) 5 arcmin SE of the cluster center. The field observed overlaps that of
archival WFPC2 data from 1994 and 1997 which were used to proper motion (PM)
clean the data. Applying the PM corrections produces a remarkably clean CMD
which reveals a number of features never seen before in a globular cluster CMD.
In our field, the main sequence stars appeared to terminate close to the
location in the CMD of the hydrogen-burning limit predicted by two independent
sets of stellar evolution models. The faintest observed main sequence stars are
about a magnitude fainter than the least luminous metal-poor field halo stars
known, suggesting that the lowest luminosity halo stars still await discovery.
At the bright end the data extend beyond the main sequence turnoff to well up
the giant branch. A populous white dwarf cooling sequence is also seen in the
cluster CMD. The most dramatic features of the cooling sequence are its turn to
the blue at faint magnitudes as well as an apparent truncation near F814W = 28.
The cluster luminosity and mass functions were derived, stretching from the
turn off down to the hydrogen-burning limit. It was well modeled with either a
very flat power-law or a lognormal function. In order to interpret these fits
more fully we compared them with similar functions in the cluster core and with
a full N-body model of NGC 6397 finding satisfactory agreement between the
model predictions and the data. This exercise demonstrates the important role
and the effect that dynamics has played in altering the cluster IMF.Comment: 43 pages including 4 tables and 12 diagrams. Figures 2 and 3 have
been bitmapped. Accepted for publication in the Astronomical Journa
Subjective Cognitive Decline Higher Among Sexual and Gender Minorities in the United States, 2015–2018
Introduction: Subjective cognitive decline (SCD) represents self-reported problems with memory, a possible early sign of dementia. Little is known about SCD among sexual and gender minority (SGM) adults who identify as lesbian, gay, bisexual, and/or transgender or gender non-binary. Methods: Data were weighted to represent population estimates from 25 states’ 2015–2018 Behavioral Risk Factor Surveillance System to describe SCD in adults ≥ 45 years by SGM status. Logistic regression tested associations between demographic and health conditions. Results: SCD prevalence was higher in SGM (15.7%; 95% confidence interval [CI]:13.1–18.2) than in non-SGM adults (10.5%; 95% CI:10.1–10.9; P \u3c .0001). SGM adults with SCD were also more likely to report functional limitations due to SCD than non-SGM adults with SCD, 60.8% versus 47.8%, P =.0048. Differences in SCD by SGM status were attenuated after accounting for depression. Discussion: Higher prevalence of SCD in SGM adults highlights the importance of ensuring inclusive screenings, interventions, care services, and resources for SGM adults
Deep ACS Imaging in the Globular Cluster NGC6397: Dynamical Models
We present N-body models to complement deep imaging of the metal-poor
core-collapsed cluster NGC6397 obtained with the Hubble Space Telescope. All
simulations include stellar and binary evolution in-step with the stellar
dynamics and account for the tidal field of the Galaxy. We focus on the results
of a simulation that began with 100000 objects (stars and binaries), 5%
primordial binaries and Population II metallicity. After 16 Gyr of evolution
the model cluster has about 20% of the stars remaining and has reached
core-collapse. We compare the color-magnitude diagrams of the model at this age
for the central region and an outer region corresponding to the observed field
of NGC6397 (about 2-3 half-light radii from the cluster centre). This
demonstrates that the white dwarf population in the outer region has suffered
little modification from dynamical processes - contamination of the luminosity
function by binaries and white dwarfs with non-standard evolution histories is
minimal and should not significantly affect measurement of the cluster age. We
also show that the binary fraction of main-sequence stars observed in the
NGC6397 field can be taken as representative of the primordial binary fraction
of the cluster. For the mass function of the main-sequence stars we find that
although this has been altered significantly by dynamics over the cluster
lifetime, especially in the central and outer regions, that the position of the
observed field is close to optimal for recovering the initial mass function of
the cluster stars (below the current turn-off mass). More generally we look at
how the mass function changes with radius in a dynamically evolved stellar
cluster and suggest where the best radial position to observe the initial mass
function is for clusters of any age.Comment: 34 pages, 11 figures, submitted to AJ, companion paper to 0708.403
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