73 research outputs found

    Curt Flood at Bat against Baseball\u27s Reserve Clause

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    Considering the favorable legal position and the stand that the reserve system is essential to the preservation of the game, the owners are reluctant to allow any changes in the system. Thus, the Flood suit affords the Player\u27s Association the most effective means, short of a costly strike, to force a change in the system

    Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial: study protocol for a multicentre international trial of cardiac output-guided fluid therapy with low-dose inotrope infusion compared with usual care in patients undergoing major elective gastrointestinal surgery.

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    INTRODUCTION: Postoperative morbidity and mortality in older patients with comorbidities undergoing gastrointestinal surgery are a major burden on healthcare systems. Infections after surgery are common in such patients, prolonging hospitalisation and reducing postoperative short-term and long-term survival. Optimal management of perioperative intravenous fluids and inotropic drugs may reduce infection rates and improve outcomes from surgery. Previous small trials of cardiac-output-guided haemodynamic therapy algorithms suggested a modest reduction in postoperative morbidity. A large definitive trial is needed to confirm or refute this and inform widespread clinical practice. METHODS: The Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial is a multicentre, international, parallel group, open, randomised controlled trial. 2502 high-risk patients undergoing major elective gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intravenous fluid combined with low-dose inotrope infusion, or usual care. The trial intervention will be carried out during and for 4 hours after surgery. The primary outcome is postoperative infection of Clavien-Dindo grade II or higher within 30 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation; however, outcome assessors will be blinded when feasible. Participant recruitment started in January 2017 and is scheduled to last 3 years, within 50 hospitals worldwide. ETHICS/DISSEMINATION: The OPTIMISE II trial has been approved by the UK National Research Ethics Service and has been approved by responsible ethics committees in all participating countries. The findings will be disseminated through publication in a widely accessible peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: ISRCTN39653756.The OPTIMISE II trial is supported by Edwards Lifesciences (Irvine, CA) and the UK National Institute for Health Research through RMP’s NIHR Professorship

    Narrow microtunnel technology for the isolation and precise identification of axonal communication among distinct hippocampal subregion networks.

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    Communication between different sub regions of the hippocampus is fundamental to learning and memory. However accurate knowledge about information transfer between sub regions from access to the activity in individual axons is lacking. MEMS devices with microtunnels connecting two sub networks have begun to approach this problem but the commonly used 10 μm wide tunnels frequently measure signals from multiple axons. To reduce this complexity, we compared polydimethylsiloxane (PDMS) microtunnel devices each with a separate tunnel width of 2.5, 5 or 10 μm bridging two wells aligned over a multi electrode array (MEA). Primary rat neurons were grown in the chambers with neurons from the dentate gyrus on one side and hippocampal CA3 on the other. After 2-3 weeks of culture, spontaneous activity in the axons inside the tunnels was recorded. We report electrophysiological, exploratory data analysis for feature clustering and visual evidence to support the expectation that 2.5 μm wide tunnels have fewer axons per tunnel and therefore more clearly delineated signals than 10 or 5 μm wide tunnels. Several measures indicated that fewer axons per electrode enabled more accurate detection of spikes. A clustering analysis comparing the variations of spike height and width for different tunnel widths revealed tighter clusters representing unique spikes with less height and width variation when measured in narrow tunnels. Wider tunnels tended toward more diffuse clusters from a continuum of spike heights and widths. Standard deviations for multiple cluster measures, such as Average Dissimilarity, Silhouette Value (S) and Separation Factor (average dissimilarity/S value), support a conclusion that 2.5 μm wide tunnels containing fewer axons enable more precise determination of individual action potential peaks, their propagation direction, timing, and information transfer between sub networks

    Tighter clusters of spike waveforms classified by spike height and width in narrow 2.5 μm compared to 10 μm wide tunnels.

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    <p>(A) 2.5 μm wide tunnel with four tight clusters, putatively from four different axons in one 2.5 μm wide tunnel. X marks the medoid of each cluster. Total spikes in each cluster: C1- 313, C2- 271, C3- 278, C4- 1138. (B-E) Tight alignment of the waveforms of each cluster of the first 100 spikes shown for clarity. (F) 10 μm tunnel of a diffuse cluster of spike waveforms difficult to separetely classify. (G) First 100 spikes out of 2212 are shown, which are aligned poorly. (H) Forced clustering of data from (F) failed to show discrete waveforms. (I, J and K) show poor classification in first 100 waveforms of each “cluster”. (L) Note that the composite of I, J and K produced a continuum of waveform heights and widths.</p

    Microtunnel and MEA assembly with burst examples.

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    <p>(A) Tunnel widths of either 2.5, 5 or 10 μm were created in PDMS devices separating two chambers. The number of tunnels was adjusted for equal volume. (B) The devices were aligned over the 2 middle rows of an MEA (inter-electrode spacing 200 μm). (C) Bursts in different tunnel widths 2.5, 5 and 10 μm, with spike peaks represented by black circles. Mean and S.E. of spikes per electrode are shown. Note more uniform heights of higher amplitude in the 2.5 μm wide tunnels.</p
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