233 research outputs found

    Tumor-educated platelets: From RNA to diagnosis

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    Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

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    The B0B^0-Bˉ0\bar B^0 oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives Δmd=0.493±0.012(stat)±0.009(syst)\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)} ps1^{-1}.Comment: 7 pages, 1 figure, submitted to Physical Review Letter

    Past and present distribution, densities and movements of blue whales <i>Balaenoptera musculus</i> in the Southern Hemisphere and northern Indian Ocean

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    1Blue whale locations in the Southern Hemisphere and northern Indian Ocean were obtained from catches (303 239), sightings (4383 records of =8058 whales), strandings (103), Discovery marks (2191) and recoveries (95), and acoustic recordings.2Sighting surveys included 7 480 450 km of effort plus 14 676 days with unmeasured effort. Groups usually consisted of solitary whales (65.2%) or pairs (24.6%); larger feeding aggregations of unassociated individuals were only rarely observed. Sighting rates (groups per 1000 km from many platform types) varied by four orders of magnitude and were lowest in the waters of Brazil, South Africa, the eastern tropical Pacific, Antarctica and South Georgia; higher in the Subantarctic and Peru; and highest around Indonesia, Sri Lanka, Chile, southern Australia and south of Madagascar.3Blue whales avoid the oligotrophic central gyres of the Indian, Pacific and Atlantic Oceans, but are more common where phytoplankton densities are high, and where there are dynamic oceanographic processes like upwelling and frontal meandering.4Compared with historical catches, the Antarctic (‘true’) subspecies is exceedingly rare and usually concentrated closer to the summer pack ice. In summer they are found throughout the Antarctic; in winter they migrate to southern Africa (although recent sightings there are rare) and to other northerly locations (based on acoustics), although some overwinter in the Antarctic.5Pygmy blue whales are found around the Indian Ocean and from southern Australia to New Zealand. At least four groupings are evident: northern Indian Ocean, from Madagascar to the Subantarctic, Indonesia to western and southern Australia, and from New Zealand northwards to the equator. Sighting rates are typically much higher than for Antarctic blue whales.6South-east Pacific blue whales have a discrete distribution and high sighting rates compared with the Antarctic. Further work is needed to clarify their subspecific status given their distinctive genetics, acoustics and length frequencies.7Antarctic blue whales numbered 1700 (95% Bayesian interval 860–2900) in 1996 (less than 1% of original levels), but are increasing at 7.3% per annum (95% Bayesian interval 1.4–11.6%). The status of other populations in the Southern Hemisphere and northern Indian Ocean is unknown because few abundance estimates are available, but higher recent sighting rates suggest that they are less depleted than Antarctic blue whales.</li

    Study Protocol for Better Evidence for Selecting Transplant Fluids (BEST-Fluids): a pragmatic, registry-based, multi-center, double-blind, randomized controlled trial evaluating the effect of intravenous fluid therapy with Plasma-Lyte 148 versus 0.9% saline on delayed graft function in deceased donor kidney transplantation

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    BACKGROUND: Delayed graft function, the requirement for dialysis due to poor kidney function post-transplant, is a frequent complication of deceased donor kidney transplantation and is associated with inferior outcomes and higher costs. Intravenous fluids given during and after transplantation may affect the risk of poor kidney function after transplant. The most commonly used fluid, isotonic sodium chloride (0.9% saline), contains a high chloride concentration, which may be associated with acute kidney injury, and could increase the risk of delayed graft function. Whether using a balanced, low-chloride fluid instead of 0.9% saline is safe and improves kidney function after deceased donor kidney transplantation is unknown. METHODS: BEST-Fluids is an investigator-initiated, pragmatic, registry-based, multi-center, double-blind, randomized controlled trial. The primary objective is to compare the effect of intravenous Plasma-Lyte 148 (Plasmalyte), a balanced, low-chloride solution, with the effect of 0.9% saline on the incidence of delayed graft function in deceased donor kidney transplant recipients. From January 2018 onwards, 800 participants admitted for deceased donor kidney transplantation will be recruited over 3 years in Australia and New Zealand. Participants are randomized 1:1 to either intravenous Plasmalyte or 0.9% saline peri-operatively and until 48 h post-transplant, or until fluid is no longer required; whichever comes first. Follow up is for 1 year. The primary outcome is the incidence of delayed graft function, defined as dialysis in the first 7 days post-transplant. Secondary outcomes include early kidney transplant function (composite of dialysis duration and rate of improvement in graft function when dialysis is not required), hyperkalemia, mortality, graft survival, graft function, quality of life, healthcare resource use, and cost-effectiveness. Participants are enrolled, randomized, and followed up using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. DISCUSSION: If using Plasmalyte instead of 0.9% saline is effective at reducing delayed graft function and improves other clinical outcomes in deceased donor kidney transplantation, this simple, inexpensive change to using a balanced low-chloride intravenous fluid at the time of transplantation could be easily implemented in the vast majority of transplant settings worldwide. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12617000358347. Registered on 8 March 2017. ClinicalTrials.gov: NCT03829488. Registered on 4 February 2019.Michael G. Collins, Magid A. Fahim, Elaine M. Pascoe, Kathryn B. Dansie, Carmel M. Hawley, Philip A. Clayton, Kirsten Howard, David W. Johnson, Colin J. McArthur, Rachael C. McConnochie, Peter F. Mount, Donna Reidlinger, Laura Robison, Julie Varghese, Liza A. Vergara, Laurence Weinberg, Steven J. Chadban, and for the BEST-Fluids Investigators and the Australasian Kidney Trials Networ

    Glioblastomas exploit truncated O - linked glycans for local and distant immune modulation via the macrophage galactose-type lectin

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    Glioblastoma is the most aggressive brain malignancy, for which immunotherapy has failed to prolong survival. Glioblastoma-associated immune infiltrates are dominated by tumor-associated macrophages and microglia (TAMs), which are key mediators of immune suppression and resistance to immunotherapy. We and others demonstrated aberrant expression of glycans in different cancer types. These tumor-associated glycans trigger inhibitory signaling in TAMs through glycan-binding receptors. We investigated the glioblastoma glycocalyx as a tumor-intrinsic immune suppressor. We detected increased expression of both tumor-associated truncated O-linked glycans and their receptor, macrophage galactose-type lectin (MGL), on CD163+ TAMs in glioblastoma patient-derived tumor tissues. In an immunocompetent orthotopic glioma mouse model overexpressing truncated O-linked glycans (MGL ligands), high-dimensional mass cytometry revealed a wide heterogeneity of infiltrating myeloid cells with increased infiltration of PD-L1+ TAMs as well as distant alterations in the bone marrow (BM). Our results demonstrate that glioblastomas exploit cell surface O-linked glycans for local and distant immune modulation.</p

    Conformational dynamics and internal friction in homopolymer globules: equilibrium vs. non-equilibrium simulations

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    We study the conformational dynamics within homopolymer globules by solvent-implicit Brownian dynamics simulations. A strong dependence of the internal chain dynamics on the Lennard-Jones cohesion strength ε and the globule size N [subscript G] is observed. We find two distinct dynamical regimes: a liquid-like regime (for ε ε[subscript s] with slow internal dynamics. The cohesion strength ε[subscript s] of this freezing transition depends on N G . Equilibrium simulations, where we investigate the diffusional chain dynamics within the globule, are compared with non-equilibrium simulations, where we unfold the globule by pulling the chain ends with prescribed velocity (encompassing low enough velocities so that the linear-response, viscous regime is reached). From both simulation protocols we derive the internal viscosity within the globule. In the liquid-like regime the internal friction increases continuously with ε and scales extensive in N [subscript G] . This suggests an internal friction scenario where the entire chain (or an extensive fraction thereof) takes part in conformational reorganization of the globular structure.American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowshi

    MIGHTEE : total intensity radio continuum imaging and the COSMOS/XMM-LSS Early Science fields

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    Please read abstract in the article.The UK Science and Technology Facilities Council; the South African Radio Astronomy Observatory; the Leverhulme Trust through an Early Career Research Fellowship; the South African Research Chairs Initiative of the Department of Science and Technology; the National Research Foundation; the Science and Technology Foundation (FCT, Portugal); the UK STFC ; the South African Research Chairs Initiative of the Department of Science and Innovation; the Bundesministerium für Bildung und Forschung (BMBF); the Italian Ministry of Foreign Affairs and International Cooperation; the South African Department of Science and Technology’s National Research Foundation (DST-NRF).https://academic.oup.com/mnrashj2022Physic

    Platelet RNA sequencing for cancer screening in patients with unprovoked venous thromboembolism: a prospective cohort study

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    BackgroundPlatelet RNA sequencing has been shown to accurately detect cancer in previous studies.ObjectivesTo compare the diagnostic accuracy of platelet RNA sequencing with standard-of-care limited cancer screening in patients with unprovoked venous thromboembolism (VTE).MethodsPatients aged ≥40 years with unprovoked VTE were recruited at 13 centers and followed for 12 months for cancer. Participants underwent standard-of-care limited cancer screening, and platelet RNA sequencing analysis was performed centrally at study end for cases and selected controls. Sensitivity and specificity were calculated, using the predefined primary positivity threshold of 0.54 for platelet RNA sequencing aiming at 86% test sensitivity, and an additional predefined threshold of 0.89 aiming at 99% test specificity.ResultsA total of 476 participants were enrolled, of whom 25 (5.3%) were diagnosed with cancer during 12-month follow-up. For each cancer patient, 3 cancer-free patients were randomly selected for the analysis. The sensitivity of limited screening was 72% (95% CI, 52-86) at a specificity of 91% (95% CI, 82-95). The area under the receiver operator characteristic for platelet RNA sequencing was 0.54 (95% CI, 0.41-0.66). At the primary positivity threshold, all patients had a positive test, for a sensitivity estimated at 100% (95% CI, 87-99) and a specificity of 8% (95% CI, 3.7-16.4). At the secondary threshold, sensitivity was 68% (95% CI, 48-83; p value compared with limited screening 0.71) at a specificity of 36% (95% CI, 26-47).ConclusionPlatelet RNA sequencing had poor diagnostic accuracy for detecting occult cancer in patients with unprovoked VTE with the current algorithm.Thrombosis and Hemostasi

    Obesity, Ethnicity, and Risk of Critical Care, Mechanical Ventilation, and Mortality in Patients Admitted to Hospital with COVID-19: Analysis of the ISARIC CCP-UK Cohort

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    A search for the decay B+K+ννˉB^+ \to K^+ \nu \bar{\nu}

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    We search for the rare flavor-changing neutral-current decay B+K+ννˉB^+ \to K^+ \nu \bar{\nu} in a data sample of 82 fb1^{-1} collected with the {\sl BABAR} detector at the PEP-II B-factory. Signal events are selected by examining the properties of the system recoiling against either a reconstructed hadronic or semileptonic charged-B decay. Using these two independent samples we obtain a combined limit of B(B+K+ννˉ)<5.2×105{\mathcal B}(B^+ \to K^+ \nu \bar{\nu})<5.2 \times 10^{-5} at the 90% confidence level. In addition, by selecting for pions rather than kaons, we obtain a limit of B(B+π+ννˉ)<1.0×104{\mathcal B}(B^+ \to \pi^+ \nu \bar{\nu})<1.0 \times 10^{-4} using only the hadronic B reconstruction method.Comment: 7 pages, 8 postscript figures, submitted to Phys. Rev. Let
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