935 research outputs found

    Geographical variations in the correlates of blood donor turnout rates: An investigation of Canadian metropolitan areas

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    <p>Abstract</p> <p>Background</p> <p>Like other countries, Canada's population is aging, and the implications of this demographic change need to be better understood from the perspective of blood supply. Analysis of donor data will help to identify systematic patterns of donation and its correlates.</p> <p>Data</p> <p>Geo-coded blood donor and donor clinic data are provided by Canadian Blood Services. Blood donor data is provided for the fiscal year 2006-2007 indicating the total number of donors for each Canadian postal code, excluding the province of Québec. Potential correlates of blood donation are selected based on social and economic characteristics, as well as descriptors of city size and geographical location in the urban hierarchy measures of accessibility, and capacity of donor clinics.</p> <p>Methods</p> <p>Data is aggregated to <it>n </it>= 3,746 census tracts in 40 Census Metropolitan Areas (CMA) across the country. The number of donors per population in a census tract is regressed against the set of potential donation correlates. Autocorrelation is tested for and results adjusted to provide parsimonious models.</p> <p>Results</p> <p>A number of factors are found to influence donation across the country, including the proportion of younger residents, English ability, proportion of people with immigrant status, higher education, and a population-based measure of accessibility.</p> <p>Conclusion</p> <p>While a number of correlates of blood donation are observed across Canada, important contextual effects across metropolitan areas are highlighted. The paper concludes by looking at policy options that are aimed toward further understanding donor behaviour.</p

    Molecular details of quinolone–DNA interactions: solution structure of an unusually stable DNA duplex with covalently linked nalidixic acid residues and non-covalent complexes derived from it

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    Quinolones are antibacterial drugs that are thought to bind preferentially to disturbed regions of DNA. They do not fall into the classical categories of intercalators, groove binders or electrostatic binders to the backbone. We solved the 3D structure of the DNA duplex (ACGCGU-NA)(2), where NA denotes a nalidixic acid residue covalently linked to the 2′-position of 2′-amino-2′-deoxyuridine, by NMR and restrained torsion angle molecular dynamics (MD). In the complex, the quinolones stack on G:C base pairs of the core tetramer and disrupt the terminal A:U base pair. The displaced dA residues can stack on the quinolones, while the uracil rings bind in the minor groove. The duplex-bridging interactions of the drugs and the contacts of the displaced nucleotides explain the high UV-melting temperature for d(ACGCGU-NA)(2) of up to 53°C. Further, non-covalently linked complexes between quinolones and DNA of the sequence ACGCGT can be generated via MD using constraints obtained for d(ACGCGU-NA)(2). This is demonstrated for unconjugated nalidixic acid and its 6-fluoro derivative. The well-ordered and tightly packed structures thus obtained are compatible with a published model for the quinolone–DNA complex in the active site of gyrases

    Maximum Upper Esophageal Sphincter (UES) Admittance: A Non-Specific Marker of UES Dysfunction

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    This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving'.© 2015 John Wiley & Sons LtdBackground Assessment of upper esophageal sphincter (UES) motility is challenging, as functionally, UES relaxation and opening are distinct. We studied novel parameters, UES admittance (inverse of nadir impedance), and 0.2-s integrated relaxation pressure (IRP), in patients with cricopharyngeal bar (CPB) and motor neuron disease (MND), as predictors of UES dysfunction. Methods Sixty-six healthy subjects (n = 50 controls 20–80 years; n = 16 elderly >80 years), 11 patients with CPB (51–83 years) and 16 with MND (58–91 years) were studied using pharyngeal high-resolution impedance manometry. Subjects received 5 × 5 mL liquid (L) and viscous (V) boluses. Admittance and IRP were compared by age and between groups. A p < 0.05 was considered significant. Key Results In healthy subjects, admittance was reduced (L: p = 0.005 and V: p = 0.04) and the IRP higher with liquids (p = 0.02) in older age. Admittance was reduced in MND compared to both healthy groups (Young: p < 0.0001 for both, Elderly L: p < 0.0001 and V: p = 0.009) and CPB with liquid (p = 0.001). Only liquid showed a higher IRP in MND patients compared to controls (p = 0.03), but was similar to healthy elderly and CPB patients. Only admittance differentiated younger controls from CPB (L: p = 0.0002 and V: p < 0.0001), with no differences in either parameter between CPB and elderly subjects. Conclusions & Inferences The effects of aging and pathology were better discriminated by UES maximum admittance, demonstrating greater statistical confidence across bolus consistencies as compared to 0.2-s IRP. Maximum admittance may be a clinically useful determinate of UES dysfunction

    Effect of n-3 long chain polyunsaturated fatty acid supplementation in pregnancy on infants' allergies in first year of life: randomised controlled trial

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    Objective: To determine whether dietary n-3 long chain polyunsaturated fatty acid (LCPUFA) supplementation of pregnant women with a fetus at high risk of allergic disease reduces immunoglobulin E associated eczema or food allergy at 1 year of age. Design: Follow-up of infants at high hereditary risk of allergic disease in the Docosahexaenoic Acid to Optimise Mother Infant Outcome (DOMInO) randomised controlled trial. Setting: Adelaide, South Australia. Participants: 706 infants at high hereditary risk of developing allergic disease whose mothers were participating in the DOMInO trial. Interventions: The intervention group (n=368) was randomly allocated to receive fish oil capsules (providing 900 mg of n-3 LCPUFA daily) from 21 weeks’ gestation until birth; the control group (n=338) received matched vegetable oil capsules without n-3 LCPUFA. Main outcome measure: Immunoglobulin E associated allergic disease (eczema or food allergy with sensitisation) at 1 year of age. Results: No differences were seen in the overall percentage of infants with immunoglobulin E associated allergic disease between the n-3 LCPUFA and control groups (32/368 (9%) v 43/338 (13%); unadjusted relative risk 0.68, 95% confidence interval 0.43 to 1.05, P=0.08; adjusted relative risk 0.70, 0.45 to 1.09, P=0.12), although the percentage of infants diagnosed as having atopic eczema (that is, eczema with associated sensitisation) was lower in the n-3 LCPUFA group (26/368 (7%) v 39/338 (12%); unadjusted relative risk 0.61, 0.38 to 0.98, P=0.04; adjusted relative risk 0.64, 0.40 to 1.02, P=0.06). Fewer infants were sensitised to egg in the n-3 LCPUFA group (34/368 (9%) v 52/338 (15%); unadjusted relative risk 0.61, 0.40 to 0.91, P=0.02; adjusted relative risk 0.62, 0.41 to 0.93, P=0.02), but no difference between groups in immunoglobulin E associated food allergy was seen. Conclusion: n-3 LCPUFA supplementation in pregnancy did not reduce the overall incidence of immunoglobulin E associated allergies in the first year of life, although atopic eczema and egg sensitisation were lower. Longer term follow-up is needed to determine if supplementation has an effect on respiratory allergic diseases and aeroallergen sensitisation in childhood.D J Palmer, T Sullivan, M S Gold, S L Prescott, R Heddle, R A Gibson, M Makride

    Virus-Templated Near-Amorphous Iron Oxide Nanotubes

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    © 2016 American Chemical Society. We present a simple synthesis of iron oxide nanotubes, grown under very mild conditions from a solution containing Fe(II) and Fe(III), on rod-shaped tobacco mosaic virus templates. Their well-defined shape and surface chemistry suggest that these robust bionanoparticles are a versatile platform for synthesis of small, thin mineral tubes, which was achieved efficiently. Various characterization tools were used to explore the iron oxide in detail: Electron microscopy (SEM, TEM), magnetometry (SQUID-VSM), diffraction (XRD, TEM-SAED), electron spectroscopies (EELS, EDX, XPS), and X-ray absorption (XANES with EXAFS analysis). They allowed determination of the structure, crystallinity, magnetic properties, and composition of the tubes. The protein surface of the viral templates was crucial to nucleate iron oxide, exhibiting analogies to biomineralization in natural compartments such as ferritin cages

    Healthcare provider's perceptions of bleeding in patients with acute leukaemia undergoing induction chemotherapy: A qualitative study

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    Background: Bleeding is a primary outcome for many transfusion‐related trials in acute leukaemia (AL) patients, typically graded using the World Health Organisation (WHO) bleeding scale (clinically significant bleed (CSB) is ≥grade 2). This composite outcome fails to differentiate minor bleeds that may not be significant, poorly represents the total burden of bleeding and lacks input from healthcare providers (HCPs) and patients. As part of a multi‐step project to create a better bleeding tool for trials, our objective was to identify HCPs' perspectives on the components of CSB in AL patients. Study Design and Methods: Using qualitative description, we interviewed 19 physicians and nurses who care for AL patients undergoing induction chemotherapy. Participants were recruited from professional organisations, networks and social media. An inductive approach to conventional content analysis was used. Results: HCPs identified features of CSB as the anatomical site of bleeding, amount of bleeding, need for intervention and changes in vital signs. Using these characteristics, bleeding events were categorised into three groups: clinically significant, could evolve into a CSB and not clinically significant. HCPs considered the patient's condition, bleeding history and clinical intuitions when deciding whether a bleed could escalate into serious bleeding. Discussion: Using data from HCPs, we categorised bleeds as clinically significant, could evolve into a CSB, and not significant. A study of patients' perspectives on the importance of different kinds of bleeding is the next step to creating a bleeding definition that is informed by evidence, clinicians and patients

    Phage Orf family recombinases:conservation of activities and involvement of the central channel in DNA binding

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    Genetic and biochemical evidence suggests that λ Orf is a recombination mediator, promoting nucleation of either bacterial RecA or phage Redβ recombinases onto single-stranded DNA (ssDNA) bound by SSB protein. We have identified a diverse family of Orf proteins that includes representatives implicated in DNA base flipping and those fused to an HNH endonuclease domain. To confirm a functional relationship with the Orf family, a distantly-related homolog, YbcN, from Escherichia coli cryptic prophage DLP12 was purified and characterized. As with its λ relative, YbcN showed a preference for binding ssDNA over duplex. Neither Orf nor YbcN displayed a significant preference for duplex DNA containing mismatches or 1-3 nucleotide bulges. YbcN also bound E. coli SSB, although unlike Orf, it failed to associate with an SSB mutant lacking the flexible C-terminal tail involved in coordinating heterologous protein-protein interactions. Residues conserved in the Orf family that flank the central cavity in the λ Orf crystal structure were targeted for mutagenesis to help determine the mode of DNA binding. Several of these mutant proteins showed significant defects in DNA binding consistent with the central aperture being important for substrate recognition. The widespread conservation of Orf-like proteins highlights the importance of targeting SSB coated ssDNA during lambdoid phage recombination

    Comment on the narrow structure reported by Amaryan et al

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    The CLAS Collaboration provides a comment on the physics interpretation of the results presented in a paper published by M. Amaryan et al. regarding the possible observation of a narrow structure in the mass spectrum of a photoproduction experiment.Comment: to be published in Physical Review
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