Mismatch-based delayed thrombolysis: a meta-analysis

<p><b>Background and Purpose</b>: Clinical benefit from thrombolysis is reduced as stroke onset to treatment time increases. The use of "mismatch" imaging to identify patients for delayed treatment has face validity and has been used in case series and clinical trials. We undertook a meta-analysis of relevant trials to examine whether present evidence supports delayed thrombolysis among patients selected according to mismatch criteria.</p> <p><b>Methods</b>: We collated outcome data for patients who were enrolled after 3 hours of stroke onset in thrombolysis trials and had mismatch on pretreatment imaging. We selected the trials on the basis of a systematic search of the Web of Knowledge. We compared favorable outcome, reperfusion and/or recanalization, mortality, and symptomatic intracerebral hemorrhage between the thrombolyzed and nonthrombolyzed groups of patients and the probability of a favorable outcome among patients with successful reperfusion and clinical findings for 3 to 6 versus 6 to 9 hours from poststroke onset. Results are expressed as adjusted odds ratios (a-ORs) with 95% CIs. Heterogeneity was explored by test statistics for clinical heterogeneity, I2 (inconsistency), and L’Abbé plot.</p> <p><b>Results</b>: We identified articles describing the DIAS, DIAS II, DEDAS, DEFUSE, and EPITHET trials, giving a total of 502 mismatch patients thrombolyzed beyond 3 hours. The combined a-ORs for favorable outcomes were greater for patients who had successful reperfusion (a-OR=5.2; 95% CI, 3 to 9; I2=0%). Favorable clinical outcome was not significantly improved by thrombolysis (a-OR=1.3; 95% CI, 0.8 to 2.0; I2=20.9%). Odds for reperfusion/recanalization were increased among patients who received thrombolytic therapy (a-OR=3.0; 95% CI, 1.6 to 5.8; I2=25.7%). The combined data showed a significant increase in mortality after thrombolysis (a-OR=2.4; 95% CI, 1.2 to 4.9; I2=0%), but this was not confirmed when we excluded data from desmoteplase doses that were abandoned in clinical development (a-OR=1.6; 95% CI, 0.7 to 3.7; I2=0%). Symptomatic intracerebral hemorrhage was significantly increased after thrombolysis (a-OR=6.5; 95% CI, 1.2 to 35.4; I2=0%) but not significant after exclusion of abandoned doses of desmoteplase (a-OR=5.4; 95% CI, 0.9 to 31.8; I2=0%).</p> <p><b>Conclusions</b>: Delayed thrombolysis amongst patients selected according to mismatch imaging is associated with increased reperfusion/recanalization. Recanalization/reperfusion is associated with improved outcomes. However, delayed thrombolysis in mismatch patients was not confirmed to improve clinical outcome, although a useful clinical benefit remains possible. Thrombolysis carries a significant risk of symptomatic intracerebral hemorrhage and possibly increased mortality. Criteria to diagnose mismatch are still evolving. Validation of the mismatch selection paradigm is required with a phase III trial. Pending these results, delayed treatment, even according to mismatch selection, cannot be recommended as part of routine care.</p&gt

Circumbinary disk evolution in the presence of an outer companion star

We consider a hierarchical triple system consisting of an inner eccentric binary with an outer companion. A highly misaligned circumbinary disk around the inner binary is subject to two competing effects: (i) nodal precession about the inner binary eccentricity vector that leads to an increase in misalignment (polar alignment) and (ii) Kozai-Lidov (KL) oscillations of eccentricity and inclination driven by the outer companion that leads to a reduction in the misalignment. The outcome depends upon the ratio of the timescales of these effects. If the inner binary torque dominates, then the disk aligns to a polar orientation. If the outer companion torque dominates, then the disk undergoes KL oscillations. In that case, the highly eccentric and misaligned disk is disrupted and accreted by the inner binary, while some mass is transferred to the outer companion. However, when the torques are similar, the outer parts of the circumbinary disk can undergo large eccentricity oscillations while the inclination remains close to the polar orientation. The range of initial disk inclinations that evolve to a polar orientation is smaller in the presence of the outer companion. Disk breaking is also more likely, at least temporarily, during the polar alignment process. The stellar orbits in HD 98800 have parameters such that polar alignment of the circumbinary disk is expected. In the absence of the gas, solid particles are unstable at much smaller radii than the gas disk inner tidal truncation radius because KL driven eccentricity leads to close encounters with the binary.Comment: Accepted for publication in ApJ

Early professional development in Scotland : teachers in years 2-6. Learning and teaching Scotland

This is the report of work undertaken by the Quality in Education Centre of the University of Strathclyde, in conjunction with colleagues from the Universities of Aberdeen and Glasgow, on behalf of Learning and Teaching Scotland. It explored the continuing professional development (CPD) needs of teachers in years 2-6 of their professional lives

A New Limit on the Antiproton Lifetime

Measurements of the cosmic ray pbar/p ratio are compared to predictions from an inhomogeneous disk-diffusion model of pbar production and propagation within the Galaxy, combined with a calculation of the modulation of the interstellar cosmic ray spectra as the particles propagate through the heliosphere to the Earth. The predictions agree with the observed pbar/p spectrum. Adding a finite pbar lifetime to the model, we obtain the limit tau_pbar > 0.8 Myr (90 % C.L.).Comment: 13 pages, 3 encapsulated Postscript figures, uses AASTeX; accepted by Astrophysical Journal; minor change

The electrophilic fluorination of enol esters using SelectFluor : a polar two-electron process

The reaction of enol esters with SelectFluor is facile and leads to the corresponding α-fluoroketones under mild conditions and, as a result, this route is commonly employed for the synthesis of medicinally important compounds such as fluorinated steroids. However, despite the use of this methodology in synthesis, the mechanism of this reaction and the influence of structure on reactivity are unclear. We present a rigorous mechanistic study of the fluorination of these substrates, informed primarily by detailed and robust kinetic experiments. The results of this study implicate a polar two-electron process via an oxygen-stabilised carbenium species, rather than a single-electron process involving radical intermediates. The structure/reactivity relationships revealed here will assist synthetic chemists in deploying this type of methodology in the syntheses of α-fluoroketone

Instability in the Molecular Dynamics Step of Hybrid Monte Carlo in Dynamical Fermion Lattice QCD Simulations

We investigate instability and reversibility within Hybrid Monte Carlo simulations using a non-perturbatively improved Wilson action. We demonstrate the onset of instability as tolerance parameters and molecular dynamics step sizes are varied. We compare these findings with theoretical expectations and present limits on simulation parameters within which a stable and reversible algorithm is obtained for physically relevant simulations. Results of optimisation experiments with respect to tolerance prarameters are also presented

Instability in the molecular dynamics step of a hybrid Monte Carlo algorithm in dynamical fermion lattice QCD simulations

We investigate instability and reversibility within Hybrid Monte Carlo simulations using a non-perturbatively improved Wilson action. We demonstrate the onset of instability as tolerance parameters and molecular dynamics step sizes are varied. We compare these findings with theoretical expectations and present limits on simulation parameters within which a stable and reversible algorithm is obtained for physically relevant simulations. Results of optimisation experiments with respect to tolerance prarameters are also presented.Comment: RevTeX, Some results here were presented at Vielat 99, Vienna, Austria, Sept 1999 22 Pages, 10 figures, to be submitted to PR

Holonomic quantum computing in symmetry-protected ground states of spin chains

While solid-state devices offer naturally reliable hardware for modern classical computers, thus far quantum information processors resemble vacuum tube computers in being neither reliable nor scalable. Strongly correlated many body states stabilized in topologically ordered matter offer the possibility of naturally fault tolerant computing, but are both challenging to engineer and coherently control and cannot be easily adapted to different physical platforms. We propose an architecture which achieves some of the robustness properties of topological models but with a drastically simpler construction. Quantum information is stored in the symmetry-protected degenerate ground states of spin-1 chains, while quantum gates are performed by adiabatic non-Abelian holonomies using only single-site fields and nearest-neighbor couplings. Gate operations respect the symmetry, and so inherit some protection from noise and disorder from the symmetry-protected ground states.Comment: 19 pages, 4 figures. v2: published versio

Association Between Public Reporting of Outcomes With Procedural Management and Mortality for Patients With Acute Myocardial Infarction

AbstractBackgroundPublic reporting of procedural outcomes may create disincentives to provide percutaneous coronary intervention (PCI) for critically ill patients.ObjectivesThis study evaluated the association between public reporting with procedural management and outcomes among patients with acute myocardial infarction (AMI).MethodsUsing the Nationwide Inpatient Sample, we identified all patients with a primary diagnosis of AMI in states with public reporting (Massachusetts and New York) and regionally comparable states without public reporting (Connecticut, Maine, Maryland, New Hampshire, Rhode Island, and Vermont) between 2005 and 2011. Procedural management and in-hospital outcomes were stratified by public reporting.ResultsAmong 84,121 patients hospitalized with AMI, 57,629 (69%) underwent treatment in a public reporting state. After multivariate adjustment, percutaneous revascularization was performed less often in public reporting states than in nonreporting states (odds ratio [OR]: 0.81, 95% confidence interval [CI]: 0.67 to 0.96), especially among older patients (OR: 0.75, 95% CI: 0.62 to 0.91), those with Medicare insurance (OR: 0.75, 95% CI: 0.62 to 0.91), and those presenting with ST-segment elevation myocardial infarction (OR: 0.63, 95% CI: 0.56 to 0.71) or concomitant cardiac arrest or cardiogenic shock (OR: 0.58, 95% CI: 0.47 to 0.70). Overall, patients with AMI in public reporting states had higher adjusted in-hospital mortality rates (OR: 1.21, 95% CI: 1.06 to 1.37) than those in nonreporting states. This was observed predominantly in patients who did not receive percutaneous revascularization in public reporting states (adjusted OR: 1.30, 95% CI: 1.13 to 1.50), whereas those undergoing the procedure had lower mortality (OR: 0.71, 95% CI: 0.62 to 0.83).ConclusionsPublic reporting is associated with reduced percutaneous revascularization and increased in-hospital mortality among patients with AMI, particularly among patients not selected for PCI

Insights into the mechanism for gold catalysis: behaviour of gold(i) amide complexes in solution

We report the synthesis and activity of new mononuclear and dinuclear gold amide complexes . The dinuclear complexes and were characterised by single crystal X-ray analysis. We also report solution NMR and freezing point depression experiments to rationalise their behaviour in solution and question the de-ligation process invoked in gold catalysis