223 research outputs found

    Likelihood-ratio ranking of gravitational-wave candidates in a non-Gaussian background

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    We describe a general approach to detection of transient gravitational-wave signals in the presence of non-Gaussian background noise. We prove that under quite general conditions, the ratio of the likelihood of observed data to contain a signal to the likelihood of it being a noise fluctuation provides optimal ranking for the candidate events found in an experiment. The likelihood-ratio ranking allows us to combine different kinds of data into a single analysis. We apply the general framework to the problem of unifying the results of independent experiments and the problem of accounting for non-Gaussian artifacts in the searches for gravitational waves from compact binary coalescence in LIGO data. We show analytically and confirm through simulations that in both cases the likelihood ratio statistic results in an improved analysis.Comment: 10 pages, 6 figure

    Analysis of Chlamydia pneumoniae and AD-like Pathology in the Brains of BALB/c Mice Following Direct Intra-cranial Infection

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    Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disorder and the most common form of dementia. The pathology in the central nervous system (CNS) impairs memory and cognition, hindering the capabilities and the quality of life of the individual. This project continues studying the role of infection and Alzheimer’s disease, as previous studies in this laboratory have done, and contributes to the overall understanding of the possible causes of this disease. In this study, BALB/c mice were infected, via direct intracranial injection, with a respiratory isolate (AR-39) of Chlamydia pneumoniae. Their brains were analyzed at 7 and 14 days post-infection, via immunohistochemistry, for the presence of C. pneumoniae, amyloid deposits and activated glial cells. The goal of this project was to measure the location and degree of C. pneumoniae burden, amyloid deposition and glial cell activation in the CNS following direct intracranial injection and to compare this data with results obtained from previous studies in this laboratory. We hypothesized that C. pneumoniae antigen and activated inflammatory cells will be observed in the infected mouse brains following direct intracranial injection and Aβ deposition will be observed in areas where inflammation occurs. C. pneumoniae, amyloid deposits and activated glial cells were detected in the brains following direct intracranial infection with C. pneumoniae. In infected mice there was an approximate 3.5-fold increase of C. pneumoniae antigen burden compared to uninfected mice at day 7 and there was an approximate 5.5-fold increase of C. pneumoniae antigen burden compared to uninfected mice at day 14. The burden of C. pneumoniae antigen, in the infected mice, increased 1.009-fold (no change) from day 7 to day 14 post-infection. The amyloid burden in infected mice increased approximately 3-fold compared to uninfected mice at day 7 and increased greater than10-fold compared to uninfected mice at day 14. The burden of amyloid, in the infected mice, increased 7-fold from day 7 to 14. From 7 to 14 days post-infection the C. pneumoniae and amyloid deposits located near the injection site spread distally from this location to other regions of the brain. Global activation of glia was observed in the CNS of infected mice at both 7 and 14 days post-infection. This data confirms that C. pneumoniae is capable of establishing an infection in the CNS. Although deposits were observed, the lack of a substantial amount of amyloid deposits suggested that the generation of deposits may require longer than 14 days following C. pneumoniae infection. As early as 7 days post-infection, inflammation is observed in response to the presence of C. pneumoniae and/or soluble amyloid in the CNS and the contribution of both infection with C. pneumoniae and the presence of soluble amyloid elicit the inflammatory response that presumably precedes and contributes to amyloid depositionhttps://digitalcommons.pcom.edu/posters/1003/thumbnail.jp

    A novel research definition of bladder health in women and girls: Implications for research and public health promotion

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    BACKGROUND:Bladder health in women and girls is poorly understood, in part, due to absence of a definition for clinical or research purposes. This article describes the process used by a National Institutes of Health funded transdisciplinary research team (The Prevention of Lower Urinary Tract Symptoms [PLUS] Consortium) to develop a definition of bladder health. METHODS:The PLUS Consortium identified currently accepted lower urinary tract symptoms (LUTS) and outlined elements of storage and emptying functions of the bladder. Consistent with the World Health Organization's definition of health, PLUS concluded that absence of LUTS was insufficient and emphasizes the bladder's ability to adapt to short-term physical, psychosocial, and environmental challenges for the final definition. Definitions for subjective experiences and objective measures of bladder dysfunction and health were drafted. An additional bioregulatory function to protect against infection, neoplasia, chemical, or biologic threats was proposed. RESULTS:PLUS proposes that bladder health be defined as: "A complete state of physical, mental, and social well-being related to bladder function and not merely the absence of LUTS. Healthy bladder function permits daily activities, adapts to short-term physical or environmental stressors, and allows optimal well-being (e.g., travel, exercise, social, occupational, or other activities)." Definitions for each element of bladder function are reported with suggested subjective and objective measures. CONCLUSIONS:PLUS used a comprehensive transdisciplinary process to develop a bladder health definition. This will inform instrument development for evaluation of bladder health promotion and prevention of LUTS in research and public health initiatives

    Census of the Local Universe (CLU) Narrow-Band Survey I: Galaxy Catalogs from Preliminary Fields

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    We present the Census of the Local Universe (CLU) narrow-band survey to search for emission-line (\ha) galaxies. CLU-\ha~has imaged \approx3π\pi of the sky (26,470~deg2^2) with 4 narrow-band filters that probe a distance out to 200~Mpc. We have obtained spectroscopic follow-up for galaxy candidates in 14 preliminary fields (101.6~deg2^2) to characterize the limits and completeness of the survey. In these preliminary fields, CLU can identify emission lines down to an \ha~flux limit of 101410^{-14}~erg s1 cm2\rm{erg~s^{-1}~cm^{-2}} at 90\% completeness, and recovers 83\% (67\%) of the \ha~flux from catalogued galaxies in our search volume at the Σ\Sigma=2.5 (Σ\Sigma=5) color excess levels. The contamination from galaxies with no emission lines is 61\% (12\%) for Σ\Sigma=2.5 (Σ\Sigma=5). Also, in the regions of overlap between our preliminary fields and previous emission-line surveys, we recover the majority of the galaxies found in previous surveys and identify an additional \approx300 galaxies. In total, we find 90 galaxies with no previous distance information, several of which are interesting objects: 7 blue compact dwarfs, 1 green pea, and a Seyfert galaxy; we also identified a known planetary nebula. These objects show that the CLU-\ha~survey can be a discovery machine for objects in our own Galaxy and extreme galaxies out to intermediate redshifts. However, the majority of the CLU-\ha~galaxies identified in this work show properties consistent with normal star-forming galaxies. CLU-\ha~galaxies with new redshifts will be added to existing galaxy catalogs to focus the search for the electromagnetic counterpart to gravitational wave events.Comment: 28 pages, 22 figures, 4 tables (Accepted to ApJ

    Individual Response to Risk As a Function of Normative Social Pressure: A Pilot Study of Seat Belt Use

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    The authors attempt to clarify some of the variables that influence whether people act appropriately when a Risk is substantial and subject to individual control. They do so by reporting results of a pilot study of seat belt use. Also, the authors believe their approach to be generalizable to problems such as encouraging people to test for radon, to use condoms to prevent AIDS or to quit smoking

    Critical Period After Stroke Study (CPASS): A phase II clinical trial testing an optimal time for motor recovery after stroke in humans

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    Restoration of human brain function after injury is a signal challenge for translational neuroscience. Rodent stroke recovery studies identify an optimal or sensitive period for intensive motor training after stroke: near-full recovery is attained if task-specific motor training occurs during this sensitive window. We extended these findings to adult humans with stroke in a randomized controlled trial applying the essential elements of rodent motor training paradigms to humans. Stroke patients were adaptively randomized to begin 20 extra hours of self-selected, task-specific motor therapy at ≤30 d (acute), 2 to 3 mo (subacute), or ≥6 mo (chronic) after stroke, compared with controls receiving standard motor rehabilitation. Upper extremity (UE) impairment assessed by the Action Research Arm Test (ARAT) was measured at up to five time points. The primary outcome measure was ARAT recovery over 1 y after stroke. By 1 y we found significantly increased UE motor function in the subacute group compared with controls (ARAT difference = +6.87 ± 2.63, P = 0.009). The acute group compared with controls showed smaller but significant improvement (ARAT difference = +5.25 ± 2.59 points, P = 0.043). The chronic group showed no significant improvement compared with controls (ARAT = +2.41 ± 2.25, P = 0.29). Thus task-specific motor intervention was most effective within the first 2 to 3 mo after stroke. The similarity to rodent model treatment outcomes suggests that other rodent findings may be translatable to human brain recovery. These results provide empirical evidence of a sensitive period for motor recovery in humans

    Converging on bladder health through design thinking: From an ecology of influence to a focused set of research questions

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    Lower urinary tract symptoms affect a substantial number of women in the United States (U.S.) and globally. In 2015, the Prevention of Lower Urinary tract Symptoms in women (PLUS) Research Consortium was funded to establish the scientific basis for prevention efforts by (1) understanding healthy bladder function and (2) identifying risk and protective factors for bladder health in women across the lifecourse. This transdisciplinary consortium generated a list of over 600 candidate risk and protective factors for bladder health in women and girls and refined and prioritized these into 29 focused research questions to inform a national longitudinal observational study in the U.S. This paper describes that process using design thinking, a human-centered set of principles and strategies by which innovations are developed, as a framework. Design thinking is an iterative process consisting of five stages: Empathizing with end-users of innovations, Defining core principles girding the work, Ideation of all possible solutions, and rapid-cycle Prototyping and Testing of solutions. Lessons learned are offered to inform future prevention science research endeavors that might benefit from such an approach

    Using paired serology and surveillance data to quantify dengue transmission and control during a large outbreak in Fiji.

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    Dengue is a major health burden, but it can be challenging to examine transmission and evaluate control measures because outbreaks depend on multiple factors, including human population structure, prior immunity and climate. We combined population-representative paired sera collected before and after the 2013/14 dengue-3 outbreak in Fiji with surveillance data to determine how such factors influence transmission and control in island settings. Our results suggested the 10-19 year-old age group had the highest risk of infection, but we did not find strong evidence that other demographic or environmental risk factors were linked to seroconversion. A mathematical model jointly fitted to surveillance and serological data suggested that herd immunity and seasonally varying transmission could not explain observed dynamics. However, the model showed evidence of an additional reduction in transmission coinciding with a vector clean-up campaign, which may have contributed to the decline in cases in the later stages of the outbreak

    Src Inhibition Blocks c-Myc Translation and Glucose Metabolism to Prevent the Development of Breast Cancer

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    Preventing breast cancer will require the development of targeted strategies that can effectively block disease progression. Tamoxifen and aromatase inhibitors are effective in addressing estrogen receptor–positive (ER+) breast cancer development, but estrogen receptor–negative (ER−) breast cancer remains an unmet challenge due to gaps in pathobiologic understanding. In this study, we used reverse-phase protein array to identify activation of Src kinase as an early signaling alteration in premalignant breast lesions of women who did not respond to tamoxifen, a widely used ER antagonist for hormonal therapy of breast cancer. Src kinase blockade with the small-molecule inhibitor saracatinib prevented the disorganized three-dimensional growth of ER− mammary epithelial cells in vitro and delayed the development of premalignant lesions and tumors in vivo in mouse models developing HER2+ and ER− mammary tumors, extending tumor-free and overall survival. Mechanistic investigations revealed that Src blockade reduced glucose metabolism as a result of an inhibition in ERK1/2–MNK1–eIF4E–mediated cap-dependent translation of c-Myc and transcription of the glucose transporter GLUT1, thereby limiting energy available for cell growth. Taken together, our results provide a sound rationale to target Src pathways in premalignant breast lesions to limit the development of breast cancers
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