5,980 research outputs found

    Selecting children for head CT following head injury

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    OBJECTIVE: Indicators for head CT scan defined by the 2007 National Institute for Health and Care Excellence (NICE) guidelines were analysed to identify CT uptake, influential variables and yield. DESIGN: Cross-sectional study. SETTING: Hospital inpatient units: England, Wales, Northern Ireland and the Channel Islands. PATIENTS: Children (3 years were much more likely to have CT than those <3 years (OR 2.35 (95% CI 2.08 to 2.65)). CONCLUSION: Compliance with guidelines and diagnostic yield was variable across age groups, the type of hospital and region where children were admitted. With this pattern of clinical practice the risks of both missing intracranial injury and overuse of CT are considerable

    In vitro FRAP reveals the ATP-dependent nuclear mobilization of the exon junction complex protein SRm160

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    We present a new in vitro system for characterizing the binding and mobility of enhanced green fluorescent protein (EGFP)-labeled nuclear proteins by fluorescence recovery after photobleaching in digitonin-permeabilized cells. This assay reveals that SRm160, a splicing coactivator and component of the exon junction complex (EJC) involved in RNA export, has an adenosine triphosphate (ATP)-dependent mobility. Endogenous SRm160, lacking the EGFP moiety, could also be released from sites at splicing speckled domains by an ATP-dependent mechanism. A second EJC protein, RNPS1, also has an ATP-dependent mobility, but SRm300, a protein that binds to SRm160 and participates with it in RNA splicing, remains immobile after ATP supplementation. This finding suggests that SRm160-containing RNA export, but not splicing, complexes have an ATP-dependent mobility. We propose that RNA export complexes have an ATP-regulated mechanism for release from binding sites at splicing speckled domains. In vitro fluorescence recovery after photobleaching is a powerful tool for identifying cofactors required for nuclear binding and mobility

    Potholes and molehills: bias in the diagnostic performance of diffusion-tensor imaging in concussion

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    PURPOSE: To investigate the extent of bias in a clinical study involving pothole analysis of diffusion-tensor imaging (DTI) data used to quantify white matter lesion load in diseases with a heterogeneous spatial distribution of pathologic findings, such as mild traumatic brain injury (TBI), and create a mathematical model of the bias. MATERIALS AND METHODS: Use of the same reference population to define normal findings and make comparisons with a patient group introduces bias, which potentially inflates reported diagnostic performance. In this institutional review board-approved prospective observational cohort study, DTI data were obtained in 20 patients admitted to the emergency department with mild TBI and in 16 control subjects. Potholes and molehills were defined as clusters of voxels with fractional anisotropy values more than 2 standard deviations below and above the mean of the corresponding voxels in the reference population, respectively. The number and volume of potholes and molehills in the two groups were compared by using a Mann-Whitney U test. RESULTS: Standard analysis showed significantly more potholes in mild TBI than in the control group (102.5 +/- 34.3 vs 50.6 +/- 28.9, P \u3c .001). Repeat analysis by using leave-one-out cross-validation decreased the apparent difference in potholes between groups (mild TBI group, 102.5 +/- 34.3; control group, 93.4 +/- 27.2; P = .369). It was demonstrated that even with 100 subjects, this bias can decrease the voxelwise false-positive rate by more than 30% in the control group. CONCLUSION: The pothole approach to neuroimaging data may introduce bias, which can be minimized by independent training and test groups or cross-validation methods. This bias is sufficient to call into question the previously reported diagnostic performance of DTI for mild TBI

    Trajectories of grief, depression, and posttraumatic stress in disaster-bereaved people

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    Background: Previous latent trajectory studies in adult bereaved people have identified individual differences in reactions postloss. However, prior findings may not reflect the complete picture of distress postloss, because they were focused on depression symptoms following nonviolent death. We examined trajectories of symptom-levels of persistent complex bereavement disorder (PCBD), depression, and posttraumatic stress disorder (PTSD) in a disaster-bereaved sample. We also investigated associations among these trajectories and background and loss-related factors, psychological support, and previous mental health complaints. Methods: Latent class growth modeling was used to identify distinct trajectories of PCBD, depression, and PTSD symptoms in people who lost loved ones in a plane disaster in 2014. Participants (N = 172) completed questionnaires for PCBD, depression, and PTSD at 11, 22, 31, and 42 months postdisaster. Associations among class membership and background and loss-related variables, psychological support, and previous mental health complaints were examined using logistic regression analyses. Results: Two PCBD classes emerged: mild (81.8%) and chronic (18.2%) PCBD. For both depression and PTSD, three classes emerged: mild (85.6% and 85.2%), recovered (8.2% and 4.4%), and chronic trajectory (6.2% and 10.3%). People assigned to the chronic PCBD, depression, or PTSD class were less highly educated than people assigned to the mild/recovered classes. Conclusions: This is the first latent trajectory study that offers insights in individual differences in longitudinal symptom profiles of PCBD, depression, and PTSD in bereaved people. We found support for differential trajectories and predictors across the outcomes

    Binding of ATP to UAP56 is necessary for mRNA export

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    The major-histocompatibility-complex protein UAP56 (BAT1) is a DEAD-box helicase that is deposited on mRNA during splicing. UAP56 is retained on spliced mRNA in an exon junction complex (EJC) or, alternatively, with the TREX complex at the 5\u27 end, where it might facilitate the export of the spliced mRNA to the cytoplasm. Using confocal microscopy, UAP56 was found to be concentrated in RNA-splicing speckled domains of nuclei but was also enriched in adjacent nuclear regions, sites at which most mRNA transcription and splicing occur. At speckled domains, UAP56 was in complexes with the RNA-splicing and -export protein SRm160, and, as measured by FRAP, was in a dynamic binding equilibrium. The application of an in vitro FRAP assay, in which fluorescent nuclear proteins are photobleached in digitonin-extracted cells, revealed that the equilibrium binding of UAP56 in complexes at speckled domains was directly regulated by ATP binding. This was confirmed using a point mutant of UAP56 that did not bind ATP. Point mutation of UAP56 to eliminate ATP binding did not affect RNA splicing, but strongly inhibited the export of mRNA to the cytoplasm

    The State of Short-Term Rentals in Montana

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    Little is known about short term rentals (STRs) as an accommodation choice for pleasure or business in Montana. The goal of this study was to assess the impacts of STRs on hosts and communities in Montana, as well as to better understand the characteristics and motivations of visitors who use STRs. Two independent studies; interviews with city and county officials in Montana, as well as an online travel behavior survey regarding accommodation choices and changes in travel due to the COVID-19 pandemic were conducted. Results suggest that positive STR impacts include increased financial well-being for hosts and more vacation rental opportunities for the guests. In some locations, however, STRs appear to limit housing availability and contribute to increased rent and housing costs

    AmpliTaq DNA polymerase, FS dye-terminator sequencing: Analysis of peak height patterns

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    Taq DNA polymerases in which the phenylalanine is substituted by a tyrosine at position 667 (Taq F667Y) are members of a new class of DNA polymerases that incorporate chain-terminating dideoxyribonucleoside triphosphates (ddNTPs) much more efficiently than the wild-type Taq DNA polymerase. Improved incorporation of ddNTPs into DNA during cycle sequencing using AmpliTaq DNA polymerase, FS (Taq-FS, a member of the Taq F667Y family), and dye-labeled primers results in nearly uniform peak heights in the sequencing trace. This is not the case when dye-labeled ddNTPs are used in Taq-FS cycle sequencing reactions. While the rate of dye-terminator incorporation is more efficient with Taq-FS, the peak pattern is still highly variable and different from that produced by the wild-type enzyme. We have systematically examined pairs of sequence-tagged sites that vary at only a single nucleotide to determine how base changes influence the peak heights of neighboring bases in sequencing traces generated by the Taq-FS dye-terminator chemistry. In 31 of 64 possible 3-base windows (48%), we find that the peak height of a particular base can be predicted by knowing just one or two bases 5\u27 to the base in question. We have also compared and contrasted the peak patterns produced by the Taq-FS enzyme with those previously identified for the wild-type enzyme. Establishing the patterns in peak heights within local sequence contexts can improve the accuracy of base-calling and the identification of polymorphisms/mutations when using the Taq-FS dye-terminator cycle-sequencing chemistry

    The representation of scientific research in the national curriculum and secondary school pupils’ perceptions of research, its function, usefulness and value to their lives

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    Young people’s views on what research is, how it is conducted and whether it is important, influences the decisions they make about their further studies and career choices. In this paper we report the analysis of questionnaire data with a particular focus on pupil perceptions of research in the sciences and of the scientific method. The questionnaire was a 25-item Likert Scale (1-5) distributed to seven collaborating schools. We received 2634 returns from pupils across key stages 3, 4 and 5. We also asked teachers to complete the questionnaire in order to explore how they thought their pupils would respond. We received 54 teacher responses. Statistically significant differences in the responses were identified through a chi-square test on SPSS. As what is being taught influences secondary pupil views on research we also consider how the term ‘research’ appears in the national curriculum for England and Wales and the three main English exam boards. The main theoretical construct that informs our analysis of the questionnaire data and the national curriculum is Angela Brew’s 4-tier descriptor of perceptions of research (domino, trading, layer, journey). We use this framework in order to map what, when and how research is presented to school pupils in England and Wales. We also use this framework in order to highlight and discuss certain pupil views that emerged from the questionnaire data and which indicate areas where curriculum and pedagogy intervention may be necessary: pupils seem less confident in their understanding of research as involving the identification of a research question; and, they often see research as a means to confirm one’s own opinion. They do however understand research as involving the generation of new knowledge and the collection of new data, such as interviews and questionnaires as well as laboratory work, field trips and library searches and they appear relatively confident in their statements about their ability to do research, their school experiences of research and the importance of research in their future career choice

    A three-dimensional culture system recapitulates placental syncytiotrophoblast development and microbial resistance

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    In eutherians, the placenta acts as a barrier and conduit at the maternal-fetal interface. Syncytiotrophoblasts, the multinucleated cells that cover the placental villous tree surfaces of the human placenta, are directly bathed in maternal blood and are formed by the fusion of progenitor cytotrophoblasts that underlie them. Despite their crucial role in fetal protection, many of the events that govern trophoblast fusion and protection from microbial infection are unknown. We describe a three-dimensional (3D)–based culture model using human JEG-3 trophoblast cells that develop syncytiotrophoblast phenotypes when cocultured with human microvascular endothelial cells. JEG-3 cells cultured in this system exhibit enhanced fusogenic activity and morphological and secretory activities strikingly similar to those of primary human syncytiotrophoblasts. RNASeq analyses extend the observed functional similarities to the transcriptome, where we observed significant overlap between syncytiotrophoblast-specific genes and 3D JEG-3 cultures. Furthermore, JEG-3 cells cultured in 3D are resistant to infection by viruses and Toxoplasma gondii, which mimics the high resistance of syncytiotrophoblasts to microbial infections in vivo. Given that this system is genetically manipulatable, it provides a new platform to dissect the mechanisms involved in syncytiotrophoblast development and microbial resistance
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