123 research outputs found

    Peer Smoking, Other Peer Attributes, and Adolescent Cigarette Smoking: A Social Network Analysis

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    Peer attributes other than smoking have received little attention in the research on adolescent smoking, even though the developmental literature suggests the importance of multiple dimensions of adolescent friendships and peer relations. Social network analysis was used to measure the structure of peer relations (i.e., indicators of having friends, friendship quality, and status among peers) and peer smoking (i.e., friend and school smoking). We used three-level hierarchical growth models to examine the contribution of each time varying peer variable to individual trajectories of smoking from age 11 to 17 while controlling for the other variables and we tested interactions between the peer structure and peer smoking variables. Data were collected over five waves of assessment from a longitudinal sample of 6,579 students in three school districts. Findings suggest a greater complexity in the peer context of smoking than previously recognized

    Hospital Costs Related to Early Extubation after Infant Cardiac Surgery

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    Background The Pediatric Heart Network Collaborative Learning Study (PHN CLS) increased early extubation rates after infant Tetralogy of Fallot (TOF) and coarctation (CoA) repair across participating sites by implementing a clinical practice guideline (CPG). The impact of the CPG on hospital costs has not been studied. Methods PHN CLS clinical data were linked to cost data from Children’s Hospital Association by matching on indirect identifiers. Hospital costs were evaluated across active and control sites in the pre- and post-CPG periods using generalized linear mixed effects models. A difference-in-difference approach was used to assess whether changes in cost observed in active sites were beyond secular trends in control sites. Results Data were successfully linked on 410/428 (96%) of eligible patients from 4 active and 4 control sites. Mean adjusted cost/case for TOF repair was significantly reduced in the post-CPG period at active sites (42,833vs.42,833 vs. 56,304, p<0.01) and unchanged at control sites (47,007vs.47,007 vs. 46,476, p=0.91), with an overall cost reduction of 27% in active vs. control sites (p=0.03). Specific categories of cost reduced in the TOF cohort included clinical (-66%, p<0.01), pharmacy (-46%, p=0.04), lab (-44%, p<0.01), and imaging (-32%, p<0.01). There was no change in costs for CoA repair at active or control sites. Conclusions The early extubation CPG was associated with a reduction in hospital costs for infants undergoing repair of TOF, but not CoA repair. This CPG represents an opportunity to both optimize clinical outcome and reduce costs for certain infant cardiac surgeries

    The Social Ecology of Adolescent Alcohol Misuse

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    A conceptual framework based on social ecology, social learning, and social control theories guided identification of social contexts, contextual attributes, and joint effects that contribute to development of adolescent alcohol misuse. Modeling of alcohol use, suggested by social learning theory, and indicators of the social bond, suggested by social control theory, were examined in the family, peer, school, and neighborhood contexts. Interactions between alcohol modeling and social bond indicators were tested within and between contexts. Data were from a longitudinal study of 6,544 students, 1,663 of their parents, and the U.S. Census. All contexts were uniquely implicated in development of alcohol misuse from ages 11 through 17 years and most alcohol modeling effects were contingent on attributes of social bonds

    The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway

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    Mutations in AIPL1 cause the inherited blindness Leber congenital amaurosis (LCA). AIPL1 has previously been shown to interact with NUB1, which facilitates the proteasomal degradation of proteins modified with the ubiquitin-like protein FAT10. Here we report that AIPL1 binds non-covalently to free FAT10 and FAT10ylated proteins and can form a ternary complex with FAT10 and NUB1. In addition, AIPL1 antagonised the NUB1-mediated degradation of the model FAT10 conjugate, FAT10-DHFR, and pathogenic mutations of AIPL1 were defective in inhibiting this degradation. While all AIPL1 mutants tested still bound FAT10-DHFR, there was a close correlation between the ability of the mutants to interact with NUB1 and their ability to prevent NUB1-mediated degradation. Interestingly, AIPL1 also co-immunoprecipitated the E1 activating enzyme for FAT10, UBA6, suggesting AIPL1 may have a role in directly regulating the FAT10 conjugation machinery. These studies are the first to implicate FAT10 in retinal cell biology and LCA pathogenesis, and reveal a new role of AIPL1 in regulating the FAT10 pathway

    Low Frequency (100-600 MHz) Searches with Axion Cavity Haloscopes

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    We investigate reentrant and dielectric loaded cavities for the purpose of extending the range of axion cavity haloscopes to lower masses, below the range where the Axion Dark Matter eXperiment (ADMX) has already searched. Reentrant and dielectric loaded cavities were simulated numerically to calculate and optimize their form factors and quality factors. A prototype reentrant cavity was built and its measured properties were compared with the simulations. We estimate the sensitivity of axion dark matter searches using reentrant and dielectric loaded cavities inserted in the existing ADMX magnet at the University of Washington and a large magnet being installed at Fermilab.Comment: 33 pages, 24 figure

    Assessing mechanical integrity of spinal fusion by in situ endochondral osteoinduction in the murine model

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    <p>Abstract</p> <p>Background</p> <p>Historically, radiographs, micro-computed tomography (micro-CT) exams, palpation and histology have been used to assess fusions in a mouse spine. The objective of this study was to develop a faster, cheaper, reproducible test to directly quantify the mechanical integrity of spinal fusions in mice.</p> <p>Methods</p> <p>Fusions were induced in ten mice spine using a previously described technique of in situ endochondral ossification, harvested with soft tissue, and cast in radiolucent alginate material for handling. Using a validated software package and a customized mechanical apparatus that flexed and extended the spinal column, the amount of intervertebral motion between adjacent vertebral discs was determined with static flexed and extended lateral spine radiographs. Micro-CT images of the same were also blindly reviewed for fusion.</p> <p>Results</p> <p>Mean intervertebral motion between control, non-fused, spinal vertebral discs was 6.1 ± 0.2° during spine flexion/extension. In fusion samples, adjacent vertebrae with less than 3.5° intervertebral motion had fusions documented by micro-CT inspection.</p> <p>Conclusions</p> <p>Measuring the amount of intervertebral rotation between vertebrae during spine flexion/extension is a relatively simple, cheap (<$100), clinically relevant, and fast test for assessing the mechanical success of spinal fusion in mice that compared favorably to the standard, micro-CT.</p

    Search for the Cosmic Axion Background with ADMX

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    We report the first result of a direct search for a Cosmic axion{\it axion} Background CaaB - a relativistic background of axions that is not dark matter - performed with the axion haloscope, the Axion Dark Matter eXperiment (ADMX). Conventional haloscope analyses search for a signal with a narrow bandwidth, as predicted for dark matter, whereas the CaaB will be broad. We introduce a novel analysis strategy, which searches for a CaaB induced daily modulation in the power measured by the haloscope. Using this, we repurpose data collected to search for dark matter to set a limit on the axion photon coupling of the CaaB originating from dark matter decay in the 800-995 MHz frequency range. We find that the present sensitivity is limited by fluctuations in the cavity readout as the instrument scans across dark matter masses. Nevertheless, we demonstrate that these challenges can be surmounted with the use of superconducting qubits as single photon counters, and allow ADMX to operate as a telescope searching for axions emerging from the decay of dark matter. The daily modulation analysis technique we introduce can be deployed for various broadband RF signals, such as other forms of a CaaB or even high-frequency gravitational waves.Comment: 9 pages, 4 figure

    Non-Virialized Axion Search Sensitive to Doppler Effects in the Milky Way Halo

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    The Axion Dark Matter eXperiment (ADMX) has previously excluded Dine-Fischler-Srednicki-Zhitnisky (DFSZ) axions between 680-790 MHz under the assumption that the dark matter is described by the isothermal halo model. However, the precise nature of the velocity distribution of dark matter is still unknown, and alternative models have been proposed. We report the results of a non-virialized axion search over the mass range 2.81-3.31 {\mu}eV, corresponding to the frequency range 680-800 MHz. This analysis marks the most sensitive search for non-virialized axions sensitive to Doppler effects in the Milky Way Halo to date. Accounting for frequency shifts due to the detector's motion through the Galaxy, we exclude cold flow relic axions with a velocity dispersion of order 10^-7 c with 95% confidence

    Transcriptional profiling of the effects of 25-hydroxycholesterol on human hepatocyte metabolism and the antiviral state it conveys against the hepatitis C virus

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    <p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) infection is a global health problem. A number of studies have implicated a direct role of cellular lipid metabolism in the HCV life cycle and inhibitors of the mevalonate pathway have been demonstrated to result in an antiviral state within the host cell. Transcriptome profiling was conducted on Huh-7 human hepatoma cells bearing subgenomic HCV replicons with and without treatment with 25-hydroxycholesterol (25-HC), an inhibitor of the mevalonate pathway that alters lipid metabolism, to assess metabolic determinants of pro- and antiviral states within the host cell. These data were compared with gene expression profiles from HCV-infected chimpanzees.</p> <p>Results</p> <p>Transcriptome profiling of Huh-7 cells treated with 25-HC gave 47 downregulated genes, 16 of which are clearly related to the mevalonate pathway. Fewer genes were observed to be upregulated (22) in the presence of 25-HC and 5 genes were uniquely upregulated in the HCV replicon bearing cells. Comparison of these gene expression profiles with data collected during the initial rise in viremia in 4 previously characterized HCV-infected chimpanzees yielded 54 overlapping genes, 4 of which showed interesting differential regulation at the mRNA level in both systems. These genes are PROX1, INSIG-1, NK4, and UBD. The expression of these genes was perturbed with siRNAs and with overexpression vectors in HCV replicon cells, and the effect on HCV replication and translation was assessed. Both PROX1 and NK4 regulated HCV replication in conjunction with an antiviral state induced by 25-hydroxycholesterol.</p> <p>Conclusion</p> <p>Treatment of Huh-7 cells bearing HCV replicons with 25-HC leads to the downregulation of many key genes involved in the mevalonate pathway leading to an antiviral state within the host cell. Furthermore, dysregulation of a larger subset of genes not directly related to the mevalonate pathway occurs both in 25-HC-treated HCV replicon harbouring cells as well as during the initial rise in viremia in infected chimpanzees. Functional studies of 3 of these genes demonstrates that they do not directly act as antiviral gene products but that they indirectly contribute to the antiviral state in the host cell. These genes may also represent novel biomarkers for HCV infection, since they demonstrate an outcome-specific expression profile.</p
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