192 research outputs found

    Machine learning in transfusion medicine: A scoping review

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    A great sporting nation? Sport participation in New Zealand youth

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    Sport is a key avenue to promote regular physical activity and health inyoung people. The study aim was to describe sport participation in NewZealand young people. A national cross-sectional survey of young peopleaged 5–24 years (n=2,503) was conducted. Use of time, demographicand anthropometric data were analysed for participants aged 10–18years (n=1,308) to identify patterns of sport participation. Overall, 894(68%) participants reported engaging in sport. Average daily participationwas 48 minutes of sport and 153 minutes of moderate-vigorous physicalactivity; sport participation therefore accounted for 31% of moderatevigorousphysical activity by time. Sport participation was higher inmales than females, in younger (10–14 years) than older (15–18 years)participants, and in Pacific young people than in other ethnic groups.Pacific youth reported the highest participation in team-based sports butthe lowest participation in individual-based sports. There were gender,age and ethnic differences in the most popular sports. Overall, sportparticipation contributed considerably to daily physical activity. Femaleswere particularly ‘at-risk’ for lower sport participation, and may benefit from targeted intervention. The popularity of sports differed among demographic groups, suggesting it is important to ensure a range of sports are accessible to young people

    On the Comparison of AGN with GRMHD Simulations: II. M87

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    Horizon-scale observations of the jetted active galactic nucleus M87 are compared with simulations spanning a broad range of dissipation mechanisms and plasma content in three-dimensional general relativistic flows around spinning black holes. Observations of synchrotron radiation from radio to X-ray frequencies can be compared with simulations by adding prescriptions specifying the relativistic electron-plus-positron distribution function and associated radiative transfer coefficients. A suite of time-varying simulations with various spins and plasma magnetizations is chosen to represent distinct possibilities for the M87 jet/accretion flow/black hole (JAB) system. We then input turbulent heating and equipartition-based emission prescriptions (and piecewise combinations thereof) in the time-dependent 3D simulations, in which jet morphology, polarization and variation are "observed" and compared with real observations so as to try to infer the rules that govern the polarized emissivity. The models in this paper support a magnetically arrested disk (MAD) with several possible spin/emission model combinations supplying the jet in M87, whose inner jet and black hole shadow have been observed down to the photon ring at 230 GHz by the Event Horizon Telescope (EHT). We also show that some MAD cases that are dominated by intrinsic circular polarization have near-linear V/I dependence on unpaired electron or positron content while SANE polarization exhibits markedly greater positron-dependent Faraday effects -- future probes of the SANE/MAD dichotomy and plasma content with the EHT. This is the second work in a series also applying the "observing" simulations methodology to near-horizon regions of supermassive black holes in Sgr A* and 3C 279.Comment: 25 pages, 27 figures, submitted to MNRA

    The Distal Cytoplasmic Tail Of The Influenza A M2 Protein Dynamically Extends From The Membrane

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    The influenza A M2 protein is a multifunctional membrane-associated homotetramer that orchestrates several essential events in the viral infection cycle. The monomeric subunits of the M2 homotetramer consist of an N-terminal ectodomain, a transmembrane domain, and a C-terminal cytoplasmic domain. The transmembrane domain forms a four-helix proton channel that promotes uncoating of virions upon host cell entry. The membrane-proximal region of the C-terminal domain forms a surface-associated amphipathic helix necessary for viral budding. The structure of the remaining ~34 residues of the distal cytoplasmic tail has yet to be fully characterized despite the functional significance of this region for influenza infectivity. Here, we extend structural and dynamic studies of the poorly characterized M2 cytoplasmic tail. We used SDSL-EPR to collect site-specific information on the mobility, solvent accessibility, and conformational properties of residues 61–70 of the full-length, cell-expressed M2 protein reconstituted into liposomes. Our analysis is consistent with the predominant population of the C-terminal tail dynamically extending away from the membranes surface into the aqueous medium. These findings provide insight into the hypothesis that the C-terminal domain serves as a sensor that regulates how M2 protein participates in critical events in the viral infection cycle

    FOXP2-positive diffuse large B-cell lymphomas exhibit a poor response to R-CHOP therapy and distinct biological signatures.

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    FOXP2 shares partially overlapping normal tissue expression and functionality with FOXP1; an established diffuse large B-cell lymphoma (DLBCL) oncogene and marker of poor prognosis. FOXP2 is expressed in the plasma cell malignancy multiple myeloma but has not been studied in DLBCL, where a poor prognosis activated B-cell (ABC)-like subtype display partially blocked plasma cell differentiation. FOXP2 protein expression was detected in ABC-DLBCL cell lines, and in primary DLBCL samples tumoral FOXP2 protein expression was detected in both germinal center B-cell-like (GCB) and non-GCB DLBCL. In biopsies from DLBCL patients treated with immunochemotherapy (R-CHOP), ≥ 20% nuclear tumoral FOXP2-positivity (n = 24/158) correlated with significantly inferior overall survival (OS: P = 0.0017) and progression-free survival (PFS: P = 0.0096). This remained significant in multivariate analysis against either the international prognostic index score or the non-GCB DLBCL phenotype (P < 0.05 for both OS and PFS). Expression of BLIMP1, a marker of plasmacytic differentiation that is commonly inactivated in ABC-DLBCL, did not correlate with patient outcome or FOXP2 expression in this series. Increased frequency of FOXP2 expression significantly correlated with FOXP1-positivity (P = 0.0187), and FOXP1 co-immunoprecipitated FOXP2 from ABC-DLBCL cells indicating that these proteins can co-localize in a multi-protein complex. FOXP2-positive DLBCL had reduced expression of HIP1R (P = 0.0348), which is directly repressed by FOXP1, and exhibited distinct patterns of gene expression. Specifically in ABC-DLBCL these were associated with lower expression of immune response and T-cell receptor signaling pathways. Further studies are warranted to investigate the potential functional cooperativity between FOXP1 and FOXP2 in repressing immune responses during the pathogenesis of high-risk DLBCL

    Release of miR-29 Target Laminin C2 Improves Skin Repair

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    miRNAs are small noncoding RNAs that regulate mRNA targets in a cell-specific manner. miR-29 is expressed in murine and human skin, where it may regulate functions in skin repair. Cutaneous wound healing model in miR-29a/b1 gene knockout mice was used to identify miR-29 targets in the wound matrix, where angiogenesis and maturation of provisional granulation tissue was enhanced in response to genetic deletion of miR-29. Consistently, antisense-mediated inhibition of miR-29 promoted angiogenesis in vitro by autocrine and paracrine mechanisms. These processes are likely mediated by miR-29 target mRNAs released upon removal of miR-29 to improve cell–matrix adhesion. One of these, laminin (Lam)-c2 (also known as laminin γ2), was strongly up-regulated during skin repair in the wound matrix of knockout mice. Unexpectedly, Lamc2 was deposited in the basal membrane of endothelial cells in blood vessels forming in the granulation tissue of knockout mice. New blood vessels showed punctate interactions between Lamc2 and integrin α6 (Itga6) along the length of the proto-vessels, suggesting that greater levels of Lamc2 may contribute to the adhesion of endothelial cells, thus assisting angiogenesis within the wound. These findings may be of translational relevance, as LAMC2 was deposited at the leading edge in human wounds, where it formed a basal membrane for endothelial cells and assisted neovascularization. These results suggest a link between LAMC2, improved angiogenesis, and re-epithelialization

    Glycaemic outcomes in people living with diabetes under 65 and over 65 years old using an intermittently scanned continuous glucose monitoring system

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    OBJECTIVE: Intermittently scanned continuous glucose monitoring (isCGM) has revolutionised the care of people with diabetes but its uptake and benefits in older adults are not well known. We examined the impact of isCGM (Freestyle Libre, FSL) on glycaemic outcomes in younger (⩽65 years) and older adults (>65 years) with diabetes. DESIGN AND METHODS: In total, 2260 adult patients registered on the Libreview account at University Hospitals Birmingham NHS Foundation Trust, UK, were included. Inclusion criteria: all patients with type 1 and type 2 diabetes aged >18 years, use of isCGM >6 months, scanning at least 6 times/day. Demographics, diabetes history and glycaemic outcomes (time in range (TIR), time above range and time below range (TBR), estimated HbA1c, HbA1c at start and at end of study) were collected by accessing electronic patient records and Libreview. Outcomes were compared between age groups ⩽65 or >65 years old. RESULTS: Most patients were of Caucasian ethnicity (⩽65 years 68%, >65 years 73%) and had type 1 diabetes. Mean duration of diabetes was 19.5 years (range 0-65 years) and 34.5 years (range 0-79 years) for ⩽65 and >65 years, respectively. Only a quarter of those ⩽65 years achieved (219/943; 23.2%) their age specific TIR target compared to 69% (78/113) of those >65 years cohort, while 70.1% (663/946) of ⩽65 years and 40.7% (46/113) of >65 years achieved their age-specific TBR target. When the less strict ⩽65 years TBR target was applied, 75% (85/113) of >65 years cohort achieved this. CONCLUSION: FSL use was associated with improved glycaemic outcomes across all age groups. Individualised targets may be needed to improve TBR in those aged >65 years
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