2,288 research outputs found

    Exoplanets and SETI

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    The discovery of exoplanets has both focused and expanded the search for extraterrestrial intelligence. The consideration of Earth as an exoplanet, the knowledge of the orbital parameters of individual exoplanets, and our new understanding of the prevalence of exoplanets throughout the galaxy have all altered the search strategies of communication SETI efforts, by inspiring new "Schelling points" (i.e. optimal search strategies for beacons). Future efforts to characterize individual planets photometrically and spectroscopically, with imaging and via transit, will also allow for searches for a variety of technosignatures on their surfaces, in their atmospheres, and in orbit around them. In the near-term, searches for new planetary systems might even turn up free-floating megastructures.Comment: 9 page invited review. v2 adds some references and v3 has other minor additions and modification

    Organizational factors and depression management in community-based primary care settings

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    Abstract Background Evidence-based quality improvement models for depression have not been fully implemented in routine primary care settings. To date, few studies have examined the organizational factors associated with depression management in real-world primary care practice. To successfully implement quality improvement models for depression, there must be a better understanding of the relevant organizational structure and processes of the primary care setting. The objective of this study is to describe these organizational features of routine primary care practice, and the organization of depression care, using survey questions derived from an evidence-based framework. Methods We used this framework to implement a survey of 27 practices comprised of 49 unique offices within a large primary care practice network in western Pennsylvania. Survey questions addressed practice structure (e.g., human resources, leadership, information technology (IT) infrastructure, and external incentives) and process features (e.g., staff performance, degree of integrated depression care, and IT performance). Results The results of our survey demonstrated substantial variation across the practice network of organizational factors pertinent to implementation of evidence-based depression management. Notably, quality improvement capability and IT infrastructure were widespread, but specific application to depression care differed between practices, as did coordination and communication tasks surrounding depression treatment. Conclusions The primary care practices in the network that we surveyed are at differing stages in their organization and implementation of evidence-based depression management. Practical surveys such as this may serve to better direct implementation of these quality improvement strategies for depression by improving understanding of the organizational barriers and facilitators that exist within both practices and practice networks. In addition, survey information can inform efforts of individual primary care practices in customizing intervention strategies to improve depression management.http://deepblue.lib.umich.edu/bitstream/2027.42/78269/1/1748-5908-4-84.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/2/1748-5908-4-84-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/3/1748-5908-4-84.pdfPeer Reviewe

    Interleukin-1β sequesters hypoxia inducible factor 2α to the primary cilium.

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    BACKGROUND: The primary cilium coordinates signalling in development, health and disease. Previously we have shown that the cilium is essential for the anabolic response to loading and the inflammatory response to interleukin-1β (IL-1β). We have also shown the primary cilium elongates in response to IL-1β exposure. Both anabolic phenotype and inflammatory pathology are proposed to be dependent on hypoxia-inducible factor 2 alpha (HIF-2α). The present study tests the hypothesis that an association exists between the primary cilium and HIFs in inflammatory signalling. RESULTS: Here we show, in articular chondrocytes, that IL-1β-induces primary cilia elongation with alterations to cilia trafficking of arl13b. This elongation is associated with a transient increase in HIF-2α expression and accumulation in the primary cilium. Prolyl hydroxylase inhibition results in primary cilia elongation also associated with accumulation of HIF-2α in the ciliary base and axoneme. This recruitment and the associated cilia elongation is not inhibited by blockade of HIFα transcription activity or rescue of basal HIF-2α expression. Hypomorphic mutation to intraflagellar transport protein IFT88 results in limited ciliogenesis. This is associated with increased HIF-2α expression and inhibited response to prolyl hydroxylase inhibition. CONCLUSIONS: These findings suggest that ciliary sequestration of HIF-2α provides negative regulation of HIF-2α expression and potentially activity. This study indicates, for the first time, that the primary cilium regulates HIF signalling during inflammation

    The Songbird Neurogenomics (SoNG) Initiative: Community-based tools and strategies for study of brain gene function and evolution

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    BACKGROUND: Songbirds hold great promise for biomedical, environmental and evolutionary research. A complete draft sequence of the zebra finch genome is imminent, yet a need remains for application of genomic resources within a research community traditionally focused on ethology and neurobiological methods. In response, we developed a core set of genomic tools and a novel collaborative strategy to probe gene expression in diverse songbird species and natural contexts. RESULTS: We end-sequenced cDNAs from zebra finch brain and incorporated additional sequences from community sources into a database of 86,784 high quality reads. These assembled into 31,658 non-redundant contigs and singletons, which we annotated via BLAST search of chicken and human databases. The results are publicly available in the ESTIMA:Songbird database. We produced a spotted cDNA microarray with 20,160 addresses representing 17,214 non-redundant products of an estimated 11,500–15,000 genes, validating it by analysis of immediate-early gene (zenk) gene activation following song exposure and by demonstrating effective cross hybridization to genomic DNAs of other songbird species in the Passerida Parvorder. Our assembly was also used in the design of the "Lund-zfa" Affymetrix array representing ~22,000 non-redundant sequences. When the two arrays were hybridized to cDNAs from the same set of male and female zebra finch brain samples, both arrays detected a common set of regulated transcripts with a Pearson correlation coefficient of 0.895. To stimulate use of these resources by the songbird research community and to maintain consistent technical standards, we devised a "Community Collaboration" mechanism whereby individual birdsong researchers develop experiments and provide tissues, but a single individual in the community is responsible for all RNA extractions, labelling and microarray hybridizations. CONCLUSION: Immediately, these results set the foundation for a coordinated set of 25 planned experiments by 16 research groups probing fundamental links between genome, brain, evolution and behavior in songbirds. Energetic application of genomic resources to research using songbirds should help illuminate how complex neural and behavioral traits emerge and evolve

    Expression of Regulatory Platelet MicroRNAs in Patients with Sickle Cell Disease

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    Background: Increased platelet activation in sickle cell disease (SCD) contributes to a state of hypercoagulability and confers a risk of thromboembolic complications. The role for post-transcriptional regulation of the platelet transcriptome by microRNAs (miRNAs) in SCD has not been previously explored. This is the first study to determine whether platelets from SCD exhibit an altered miRNA expression profile. Methods and Findings: We analyzed the expression of miRNAs isolated from platelets from a primary cohort (SCD = 19, controls = 10) and a validation cohort (SCD = 7, controls = 7) by hybridizing to the Agilent miRNA microarrays. A dramatic difference in miRNA expression profiles between patients and controls was noted in both cohorts separately. A total of 40 differentially expressed platelet miRNAs were identified as common in both cohorts (p-value 0.05, fold change>2) with 24 miRNAs downregulated. Interestingly, 14 of the 24 downregulated miRNAs were members of three families - miR-329, miR-376 and miR-154 - which localized to the epigenetically regulated, maternally imprinted chromosome 14q32 region. We validated the downregulated miRNAs, miR-376a and miR-409-3p, and an upregulated miR-1225-3p using qRT-PCR. Over-expression of the miR-1225-3p in the Meg01 cells was followed by mRNA expression profiling to identify mRNA targets. This resulted in significant transcriptional repression of 1605 transcripts. A combinatorial approach using Meg01 mRNA expression profiles following miR-1225-3p overexpression, a computational prediction analysis of miRNA target sequences and a previously published set of differentially expressed platelet transcripts from SCD patients, identified three novel platelet mRNA targets: PBXIP1, PLAGL2 and PHF20L1. Conclusions: We have identified significant differences in functionally active platelet miRNAs in patients with SCD as compared to controls. These data provide an important inventory of differentially expressed miRNAs in SCD patients and an experimental framework for future studies of miRNAs as regulators of biological pathways in platelets. © 2013 Jain et al

    Maintenance of response with atypical antipsychotics in the treatment of schizophrenia: a post-hoc analysis of 5 double-blind, randomized clinical trials

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    <p>Abstract</p> <p>Background</p> <p>How long an antipsychotic is effective in maintaining response is important in choosing the correct treatment for people with schizophrenia. This post-hoc analysis describes maintenance of response over 24 or 28 weeks in people treated for schizophrenia with olanzapine, risperidone, quetiapine, ziprasidone, or aripiprazole.</p> <p>Methods</p> <p>This was a post-hoc analysis using data from 5 double-blind, randomized, comparative trials of 24 or 28 weeks duration in which olanzapine was compared to risperidone (1 study; N = 339), quetiapine (1 study; N = 346), ziprasidone (2 studies; N = 548 and 394) or aripiprazole (1 study; N = 566) for treatment of schizophrenia. For each study, time to loss of response in patients who met criteria for response at Week 8 and the proportion of patients who lost response following Week 8 were compared by treatment group. The number needed to treat (NNT) with olanzapine rather than comparator to avoid loss of one additional responder over 24 or 28 weeks of treatment was calculated for each study.</p> <p>Results</p> <p>Time maintained in response was significantly longer (p < .05) for olanzapine compared to risperidone, quetiapine, and ziprasidone. Olanzapine did not significantly differ from aripiprazole. The proportion of patients who lost response was significantly lower for olanzapine versus risperidone, quetiapine, and ziprasidone (p < .05). NNTs to avoid one additional patient with loss of response with olanzapine versus risperidone, quetiapine and ziprasidone were favourable, ranging from 5 to 9.</p> <p>Conclusion</p> <p>During 24 and 28 weeks of treatment, the antipsychotics studied differed in the time that treated patients with schizophrenia remained in response and the proportion of patients who lost response. Olanzapine treatment resulted in a consistent and statistically significant advantage in maintenance of response compared to treatment with risperidone, quetiapine and ziprasidone; but not compared to treatment with aripiprazole.</p

    Academic Performance and Behavioral Patterns

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    Identifying the factors that influence academic performance is an essential part of educational research. Previous studies have documented the importance of personality traits, class attendance, and social network structure. Because most of these analyses were based on a single behavioral aspect and/or small sample sizes, there is currently no quantification of the interplay of these factors. Here, we study the academic performance among a cohort of 538 undergraduate students forming a single, densely connected social network. Our work is based on data collected using smartphones, which the students used as their primary phones for two years. The availability of multi-channel data from a single population allows us to directly compare the explanatory power of individual and social characteristics. We find that the most informative indicators of performance are based on social ties and that network indicators result in better model performance than individual characteristics (including both personality and class attendance). We confirm earlier findings that class attendance is the most important predictor among individual characteristics. Finally, our results suggest the presence of strong homophily and/or peer effects among university students

    Fabrication and Properties of Porphyrin Nano- and Micro-particles with Novel Morphology

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    New types of porphyrin nano- and micro-particles composed of J- and H-heteroaggregates were prepared by electrostatic self-assembly of two oppositely charged porphyrins, tetrakis(4-trimethylammoniophenyl)porphyrin (H2TAPP4+) and tetrakis(4-sulfonatophenyl)porphyrin cobalt(II) (CoTPPS4−), in aqueous solutions. Transmission electron microscopy (TEM) images showed novel morphology and size distribution of porphyrin particles fabricated under different experimental conditions. The assembly process of the nano- and micro-particles was monitored by UV–Vis spectra. Fluorescence spectra and UV–Vis spectra provided optical information on the formation of the nano- and micro-particles. Cyclic voltammograms of the porphyrin particles indicated that the electron gain and loss of the H2TAPP4+ion were restrained, and the electron transfer of the CoTPPS4−ion was promoted in the J- and H-type porphyrin heteroaggregates within the particles. The stability and constitution of the nano- and micro-particles were confirmed by UV-light irradiation, heat-treatment, and pH and ionic strength changes. Photoelectrochemical measurements showed that the photoelectron transfer of TiO2modified with the particles was more efficient than that of TiO2sensitized by either monomers. The photoelectronic and photocatalytic properties of the products indicated that the pyramidal or spherical configuration of the nano- and micro-particles was favorable for the absorption and transfer of the energy. It can be found that TiO2sensitized by the porphyrin nano- and micro-particles exhibits significant improvement in energy conversion and photocatalytic activity with reference to pure TiO2

    Potential for early warning of viral influenza activity in the community by monitoring clinical diagnoses of influenza in hospital emergency departments

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    <p>Abstract</p> <p>Background</p> <p>Although syndromic surveillance systems are gaining acceptance as useful tools in public health, doubts remain about whether the anticipated early warning benefits exist. Many assessments of this question do not adequately account for the confounding effects of autocorrelation and trend when comparing surveillance time series and few compare the syndromic data stream against a continuous laboratory-based standard. We used time series methods to assess whether monitoring of daily counts of Emergency Department (ED) visits assigned a clinical diagnosis of influenza could offer earlier warning of increased incidence of viral influenza in the population compared with surveillance of daily counts of positive influenza test results from laboratories.</p> <p>Methods</p> <p>For the five-year period 2001 to 2005, time series were assembled of ED visits assigned a provisional ED diagnosis of influenza and of laboratory-confirmed influenza cases in New South Wales (NSW), Australia. Poisson regression models were fitted to both time series to minimise the confounding effects of trend and autocorrelation and to control for other calendar influences. To assess the relative timeliness of the two series, cross-correlation analysis was performed on the model residuals. Modelling and cross-correlation analysis were repeated for each individual year.</p> <p>Results</p> <p>Using the full five-year time series, short-term changes in the ED time series were estimated to precede changes in the laboratory series by three days. For individual years, the estimate was between three and 18 days. The time advantage estimated for the individual years 2003–2005 was consistently between three and four days.</p> <p>Conclusion</p> <p>Monitoring time series of ED visits clinically diagnosed with influenza could potentially provide three days early warning compared with surveillance of laboratory-confirmed influenza. When current laboratory processing and reporting delays are taken into account this time advantage is even greater.</p

    The Seroprevalence and Seroincidence of Enterovirus71 Infection in Infants and Children in Ho Chi Minh City, Viet Nam

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    Enterovirus 71 (EV71)-associated hand, foot and mouth disease has emerged as a serious public health problem in South East Asia over the last decade. To better understand the prevalence of EV71 infection, we determined EV71 seroprevalence and seroincidence amongst healthy infants and children in Ho Chi Minh City, Viet Nam. In a cohort of 200 newborns, 55% of cord blood samples contained EV71 neutralizing antibodies and these decayed to undetectable levels by 6 months of age in 98% of infants. The EV71 neutralizing antibody seroconversion rate was 5.6% in the first year and 14% in the second year of life. In children 5–15 yrs of age, seroprevalence of EV71 neutralizing antibodies was 84% and in cord blood it was 55%. Taken together, these data suggest EV71 force of infection is high and highlights the need for more research into its epidemiology and pathogenesis in high disease burden countries
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