Launched in June 2008, the Fermi Gamma-ray Telescope includes a pair conversion detector designed for the 20
MeV to
∼
300
GeV
gamma-ray sky study, the Large Area Telescope (LAT). Operating in all-sky ...survey mode, its excellent sensitivity and angular resolution will allow either to discover or constrain a signal coming through the annihilation of dark matter particles. Predicted by cold dark matter scenarios as the largest clumps, dwarf spheroidal galaxies are amongst the most attractive targets for indirect search of dark matter by gamma-ray experiments. We present here an overview of the Fermi LAT Dark Matter and New Physics Working Group efforts in the searches of gamma-ray fluxes coming from WIMP pair annihilations in dwarf spheroidal galaxies.
An accurate injury severity measurement is essential for the evaluation of pediatric trauma care and outcome research. The traditional Injury Severity Score (ISS) does not consider the differential ...risks of the Abbreviated Injury Scale (AIS) from different body regions nor is it pediatric specific. The objective of this study was to develop a weighted ISS (wISS) system for pediatric blunt trauma patients with better predictive power than ISS.
Based on the association between mortality and AIS from each of the six ISS body regions, we generated different weights for the component AIS scores used in the calculation of ISS. The weights and wISS were generated using the National Trauma Data Bank. The Nationwide Emergency Department Sample (NEDS) was used to validate our main results. Pediatric blunt trauma patients younger than 16 years were included, and mortality was the outcome. Discrimination (areas under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, negative predictive value, concordance) and calibration (Hosmer-Lemeshow statistic) were compared between the wISS and ISS.
The areas under the receiver operating characteristic curves from the wISS and ISS are 0.88 versus 0.86 in ISS of 1 to 74 and 0.77 versus 0.64 in ISS of 25 to 74 (p < 0.0001). The wISS showed higher specificity, positive predictive value, negative predictive value, and concordance when they were compared at similar levels of sensitivity. The wISS had better calibration (smaller Hosmer-Lemeshow statistic) than the ISS (11.6 vs. 19.7 for ISS = 1-74 and 10.9 vs. 12.6 for ISS = 25-74). The wISS showed even better discrimination with the Nationwide Emergency Department Sample.
By weighting the AIS from different body regions, the wISS had significantly better predictive power for mortality than the ISS, especially in critically injured children.
Prognostic/epidemiological, level IV.
The γ-ray emission above $250 \mathrm{GeV}$ from the BL Lac object Markarian 421 was observed by the CAT Cherenkov imaging telescope between December, 1996, and June, 2000. In 1998, the source ...produced a series of small flares, making it the second extragalactic source detected by CAT. The time-averaged differential spectrum has been measured from 0.3 to $5 \mathrm{TeV}$, which is well fitted with a power law: $\frac{\mathrm{d}\phi}{\mathrm{d}E}\varpropto E_{\mathrm{TeV}}^{-2.88\pm0.12^\mathrm{stat}\pm0.06^\mathrm{syst}}$. In 2000, the source showed an unprecedented activity, with variability time-scales as short as one hour, as for instance observed during the night between 4 and 5 February. The 2000 time-averaged spectrum measured is compatible with that of 1998, but some indication of a spectral curvature is found between 0.3 and $5 \mathrm{TeV}$. The possibility of $\mathrm{TeV}$ spectral hardening during flares is also discussed, and the results are compared to those obtained on the other $\mathrm{TeV}$ BL Lac, Markarian 501.
The occurrence of postconcussive symptoms (PCS) following mild traumatic brain injury (TBI) in children may depend on cognitive reserve capacity. This prospective, longitudinal study examined whether ...the relationship between mild TBI and PCS is moderated by cognitive ability, which served as a proxy for cognitive reserve. Participants included 182 children with mild TBI and 99 children with orthopedic injuries (OI), ranging from 8 to 15 years of age when injured. Mild TBI were classified as complicated (n = 32) or uncomplicated (n = 150) depending on whether they were associated with trauma-related intracranial abnormalities on magnetic resonance imaging. PCS were assessed initially within 3 weeks of injury, and again at 1, 3, and 12 months post injury. The initial assessment also included standardized tests of children's cognitive skills and retrospective parent ratings of pre-injury symptoms. Hierarchical linear modeling indicated that ratings of PCS were moderated jointly by cognitive ability and injury severity. Children of lower cognitive ability with a complicated mild TBI were especially prone to cognitive symptoms across time according to parents and to high acute levels of PCS according to children's self-ratings. Cognitive reserve is an important moderator of the outcomes of mild TBI in children and adolescents.
Abstract
Objective
This article describes the method of integrating a manual pediatric emergency department sepsis screening process into the electronic health record that leverages existing ...clinical documentation and keeps providers in their current, routine clinical workflows.
Methods
Criteria in the manual pediatric emergency department sepsis screening tool were mapped to standard documentation routinely entered in the electronic health record. Data elements were extracted and scored from the medical history, medication record, vital signs, and physical assessments. Scores that met a predefined sepsis risk threshold triggered interruptive system alerts which notified emergency department staff to perform sepsis huddles and consider appropriate interventions. Statistical comparison of the new electronic tool to the manual process was completed by a two-tail paired
t
-test.
Results
The performance of the pediatric electronic sepsis screening tool was evaluated by comparing flowsheet row documentation of the manual, sepsis alert process against the interruptive system alert instance of the electronic sepsis screening tool. In an 8-week testing period, the automated pediatric electronic sepsis screening tool identified 100% of patients flagged by the manual process (
n
= 29), on average, 68 minutes earlier.
Conclusion
Integrating a manual sepsis screening tool into the electronic health record automated identification of pediatric sepsis screening in a busy emergency department. The electronic sepsis screening tool is as accurate as a manual process and would alert bedside clinicians significantly earlier in the emergency department course. Deployment of this electronic tool has the capability to improve timely sepsis detection and management of patients at risk for sepsis without requiring additional documentation by providers.
To assess whether postconcussive symptoms (PCS) can be used to discriminate injury severity among children with mild traumatic brain injury (TBI).
One hundred eighty-six children with mild TBI, ...divided into high and low injury severity depending on whether the injury was associated with a loss of consciousness (LOC), and a comparison group of 99 children with orthopedic injuries (OI), all aged 8 to 15 years at the time of injury.
Parent-rated frequency and severity of PCS at initial assessment within 2 weeks postinjury and again at 3 and 12 months postinjury.
Ratings of PCS obtained at the initial and 3-month assessments differentiated children with mild TBI from OI, although only ratings at the initial assessment discriminated among all 3 groups. Somatic PCS accounted for most of the discriminatory power.
Overall, the accuracy of group classification was relatively modest, with a large proportion of misclassifications of children in the mild-TBI groups. Although children with mild TBI have more PCS than children with OI, PCS do not permit sufficiently accurate discrimination of mild TBI and injury severity to warrant diagnostic decisions at this time.
A search query consisting of two aromatic centers and two cationic centers was defined based on previously identified small molecule inhibitors of the botulinum neurotoxin serotype A light chain ...(BoNT/A LC) and used to mine the National Cancer Institute Open Repository. Ten small molecule hits were identified, and upon testing, three demonstrated inhibitory activity. Of these, one was structurally unique, possessing a rigid diazachrysene scaffold. The steric limitations of the diazachrysene imposed a separation between the overlaps of previously identified inhibitors, revealing an extended binding mode. As a result, the pharmacophore for BoNT/A LC inhibition has been modified to encompass three zones. To demonstrate the utility of this model, a novel three‐zone inhibitor was mined and its activity was confirmed.
Three‐dimensional database mining employing an internally consistent search query identified a novel botulinum neurotoxin serotype A metalloprotease inhibitor chemotype. This inhibitor served as the basis for uniting different structural classes of previously identified inhibitors in a three‐zone pharmacophore. Subsequently, this model was used to identify a novel three‐zone inhibitor.
Botulinum neurotoxins (BoNTs) comprise seven distinct serotypes that inhibit the release of neurotransmitter across neuromuscular junctions, resulting in potentially fatal flaccid paralysis. BoNT ...serotype A (BoNT/A), which targets synaptosomal-associated protein of 25kDa (SNAP-25), is particularly long-lived within neurons and requires a longer time for recovery of neuromuscular function. There are currently no treatments available to counteract BoNT/A after it has entered the neuronal cytosol. In this study, we examined the ability of small molecule non-peptidic inhibitors (SMNPIs) to prevent SNAP-25 cleavage post-intoxication of neurons. The progressive cleavage of SNAP-25 observed over 5 h following 1 h BoNT/A intoxication was prevented by addition of SMNPIs. In contrast, anti-BoNT/A neutralizing antibodies that strongly inhibited SNAP-25 cleavage when added during intoxication were completely ineffective when added post-intoxication. Although Bafilomycin A1, which blocks entry of BoNT/A into the cytosol by preventing endosomal acidification, inhibited SNAP-25 cleavage post-intoxication, the degree of inhibition was significantly reduced versus addition both during and after intoxication. Post-intoxication application of SMNPIs, on the other hand, was nearly as effective as application both during and after intoxication. Taken together, the results indicate that competitive SMNPIs of BoNT/A light chain can be effective within neurons post-intoxication.
ABSTRACT We present the third Fermi Large Area Telescope (LAT) source catalog (3FGL) of sources in the 100 MeV-300 GeV range. Based on the first 4 yr of science data from the Fermi Gamma-ray Space ...Telescope mission, it is the deepest yet in this energy range. Relative to the Second Fermi LAT catalog, the 3FGL catalog incorporates twice as much data, as well as a number of analysis improvements, including improved calibrations at the event reconstruction level, an updated model for Galactic diffuse γ-ray emission, a refined procedure for source detection, and improved methods for associating LAT sources with potential counterparts at other wavelengths. The 3FGL catalog includes 3033 sources above significance, with source location regions, spectral properties, and monthly light curves for each. Of these, 78 are flagged as potentially being due to imperfections in the model for Galactic diffuse emission. Twenty-five sources are modeled explicitly as spatially extended, and overall 238 sources are considered as identified based on angular extent or correlated variability (periodic or otherwise) observed at other wavelengths. For 1010 sources we have not found plausible counterparts at other wavelengths. More than 1100 of the identified or associated sources are active galaxies of the blazar class; several other classes of non-blazar active galaxies are also represented in the 3FGL. Pulsars represent the largest Galactic source class. From source counts of Galactic sources we estimate that the contribution of unresolved sources to the Galactic diffuse emission is ∼3% at 1 GeV.
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