Cerebrospinal fluid levels of extracellular heat shock protein 72: A potential biomarker for bacterial meningitis in children

Extracellular heat shock protein 72 (Hsp72) is an endogenous danger signal and potential biomarker for critical illness in children. We hypothesized that elevated levels of extracellular Hsp72 in the cerebrospinal fluid (CSF) of children with suspected meningitis could predict bacterial meningitis. We measured extracellular Hsp72 levels in the CSF of 31 critically ill children with suspected meningitis via a commercially available enzyme-linked immunosorbent assay. Fourteen had bacterial meningitis based on CSF pleocytosis and bacterial growth in either blood or CSF culture. Seventeen children with negative cultures comprised the control group. CSF Hsp72 was significantly elevated in children with bacterial meningitis compared to controls. Importantly, CSF Hsp72 levels did not correlate with the CSF white blood cell count. On receiver operator characteristic analysis, using a cut-off of 8.1 ng/mL, CSF Hsp72 has a sensitivity of 79% and a specificity of 94% for predicting bacterial meningitis. We therefore conclude that CSF extracellular Hsp72 levels are elevated in critically ill children with bacterial meningitis versus controls. Hsp72 potentially offers clinicians improved diagnostic information in distinguishing bacterial meningitis from other processes

Magnetic field waves at Uranus

The proposed research efforts funded by the UDAP grant to the BRI involve the study of magnetic field waves associated with the Uranian bow shock. This is a collaborative venture bringing together investigators at the BRI, Southwest Research Institute (SwRI), and Goddard Space Flight Center (GSFC). In addition, other collaborations have been formed with investigators granted UDAP funds for similar studies and with investigators affiliated with other Voyager experiments. These investigations and the corresponding collaborations are included in the report. The proposed effort as originally conceived included an examination of waves downstream from the shock within the magnetosheath. However, the observations of unexpected complexity and diversity within the upstream region have necessitated that we confine our efforts to those observations recorded upstream of the bow shock on the inbound and outbound legs of the encounter by the Voyager 2 spacecraft

Past approaches and future directions for targeting tumor hypoxia in squamous cell carcinomas of the head and neck

AbstractRecurrent squamous cell carcinoma of the head and neck (SCCHN) carries a poor prognosis. Tumor hypoxia (TH) has been implicated as one of many factors contributing to SCCHN recurrence. TH leads to radiation resistance by reversing radiation-induced DNA damage. Effective strategies to overcome TH may improve outcomes in patients with SCCHN. We searched the English literature on PubMed and reviewed the reference sections of key articles related to TH (publications spanning from the early 1900s to the present). We summarized the underlying theory of TH in SCCHN, methods for quantifying it, and the numerous therapies developed to modulate it. We included articles that set the foundation of TH as a theory and the most relevant articles published within the last 15 years related to TH quantification and therapeutic targeting. Despite extensive research, targeting TH in SCCHN has not become a part of routine clinical practice in North America, and we analyze the pitfalls in hypoxia research that have led to this failure. We propose that future studies should test a combined approach of targeting the immune system in addition to cellular pathways rendered aberrant in TH and should include development of novel surrogate markers of TH and/or TH imaging

Generalized genetic association study with samples of related individuals

Genetic association study is an essential step to discover genetic factors that are associated with a complex trait of interest. In this paper we present a novel generalized quasi-likelihood score (GQLS) test that is suitable for a study with either a quantitative trait or a binary trait. We use a logistic regression model to link the phenotypic value of the trait to the distribution of allelic frequencies. In our model, the allele frequencies are treated as a response and the trait is treated as a covariate that allows us to leave the distribution of the trait values unspecified. Simulation studies indicate that our method is generally more powerful in comparison with the family-based association test (FBAT) and controls the type I error at the desired levels. We apply our method to analyze data on Holstein cattle for an estimated breeding value phenotype, and to analyze data from the Collaborative Study of the Genetics of Alcoholism for alcohol dependence. The results show a good portion of significant SNPs and regions consistent with previous reports in the literature, and also reveal new significant SNPs and regions that are associated with the complex trait of interest.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS465 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Abundance recovery error analysis using simulated AVIRIS data

Measurement noise and imperfect atmospheric correction translate directly into errors in the determination of the surficial abundance of materials from imaging spectrometer data. The effects of errors on abundance recovery were investigated previously using Monte Carlo simulation methods by Sabol et. al. The drawback of the Monte Carlo approach is that thousands of trials are needed to develop good statistics on the probable error in abundance recovery. This computational burden invariably limits the number of scenarios of interest that can practically be investigated. A more efficient approach is based on covariance analysis. The covariance analysis approach expresses errors in abundance as a function of noise in the spectral measurements and provides a closed form result eliminating the need for multiple trials. Monte Carlo simulation and covariance analysis are used to predict confidence limits for abundance recovery for a scenario which is modeled as being derived from Airborne Visible/Infrared Imaging Spectrometer (AVIRIS)

Comparison of total body water estimates from O-18 and bioelectrical response prediction equations

Identification of an indirect, rapid means to measure total body water (TBW) during space flight may aid in quantifying hydration status and assist in countermeasure development. Bioelectrical response testing and hydrostatic weighing were performed on 27 subjects who ingested O-18, a naturally occurring isotope of oxygen, to measure true TBW. TBW estimates from three bioelectrical response prediction equations and fat-free mass (FFM) were compared to TBW measured from O-18. A repeated measures MANOVA with post-hoc Dunnett's Test indicated a significant (p less than 0.05) difference between TBW estimates from two of the three bioelectrical response prediction equations and O-18. TBW estimates from FFM and the Kushner & Schoeller (1986) equation yielded results that were similar to those given by O-18. Strong correlations existed between each prediction method and O-18; however, standard errors, identified through regression analyses, were higher for the bioelectrical response prediction equations compared to those derived from FFM. These findings suggest (1) the Kushner & Schoeller (1986) equation may provide a valid measure of TBW, (2) other TBW prediction equations need to be identified that have variability similar to that of FFM, and (3) bioelectrical estimates of TBW may prove valuable in quantifying hydration status during space flight

Early affective changes and increased connectivity in preclinical Alzheimer's disease.

IntroductionAffective changes precede cognitive decline in mild Alzheimer's disease and may relate to increased connectivity in a "salience network" attuned to emotionally significant stimuli. The trajectory of affective changes in preclinical Alzheimer's disease, and its relationship to this network, is unknown.MethodsOne hundred one cognitively normal older adults received longitudinal assessments of affective symptoms, then amyloid-PET. We hypothesized amyloid-positive individuals would show enhanced emotional reactivity associated with salience network connectivity. We tested whether increased global connectivity in key regions significantly related to affective changes.ResultsIn participants later found to be amyloid positive, emotional reactivity increased with age, and interpersonal warmth declined in women. These individuals showed higher global connectivity within the right insula and superior temporal sulcus; higher superior temporal sulcus connectivity predicted increasing emotional reactivity and decreasing interpersonal warmth.ConclusionsAffective changes should be considered an early preclinical feature of Alzheimer's disease. These changes may relate to higher functional connectivity in regions critical for social-emotional processing

Extended X-ray emission in the IC 2497 - Hanny's Voorwerp system: energy injection in the gas around a fading AGN

We present deep Chandra X-ray observations of the core of IC 2497, the galaxy associated with Hanny's Voorwerp and hosting a fading AGN. We find extended soft X-ray emission from hot gas around the low intrinsic luminosity (unobscured) AGN ($L_{\rm bol} \sim 10^{42}-10^{44}$ erg s$^{-1}$). The temperature structure in the hot gas suggests the presence of a bubble or cavity around the fading AGN (\mbox{E_{\rm bub}} \sim 10^{54} - 10^{55} erg). A possible scenario is that this bubble is inflated by the fading AGN, which after changing accretion state is now in a kinetic mode. Other possibilities are that the bubble has been inflated by the past luminous quasar ($L_{\rm bol} \sim 10^{46}$ erg s$^{-1}$), or that the temperature gradient is an indication of a shock front from a superwind driven by the AGN. We discuss the possible scenarios and the implications for the AGN-host galaxy interaction, as well as an analogy between AGN and X-ray binaries lifecycles. We conclude that the AGN could inject mechanical energy into the host galaxy at the end of its lifecycle, and thus provide a source for mechanical feedback, in a similar way as observed for X-ray binaries.Comment: 9 pages, 5 figures, accepted for publication in MNRA

Local structures of free-standing AlₓGa₁ˍₓN thin films studied by extended x-ray absorption fine structure

Local structural information for the first two atomic shells surrounding Ga atoms in free standing AlₓGa₁ˍₓN alloy films has been obtained by extended x-ray absorption fine structure spectroscopy. For an AlN mole fraction ranging from 0 to 0.6, we found that the first shell Ga–N bond length had only a weak composition dependence, roughly one quarter of that predicted by Vegard’s Law. In the second shell, the Ga–Ga bond length was significantly longer than that of Ga–Al (Δ∼0.04–0.065 Å). A bond-type specific composition dependence was observed for the second shell cation–cation distances. While the composition dependence of the Ga–Ga bond length is ∼70% of that predicted by Vegard’s Law, the Ga–Al bond length was essentially composition independent. These results suggested that local strain in AlₓGa₁ˍₓN was also accommodated by lattice distortion in the Al cation sublattice.This work was supported by the Director, Office of Science, Of- fice of Basic Energy Sciences, Materials Science Division of the U.S. Department of Energy under Contract No. DE-AC03-76SF00098. The LLO work was performed at the UC Berkeley Integrated Materials Laboratory which was supported in part by the National Science Foundation. C.J.G. and M.C.R. were supported by the Australian Synchrotron Research Program, funded by the Commonwealth of Australia via the Major National Research Facilities Program. SSRL was supported by the Office of Basic Energy Sciences of the U.S. Department of Energy