Design of the Intravenous Magnesium Efficacy in Acute Stroke (IMAGES) trial

The Intravenous Magnesium Efficacy in Acute Stroke (IMAGES) trial is a multicentre,randomised, placebo-controlled trial of magnesium sulphate (MgSO4) funded by the UK Medical Research Council. When complete, it will be the largest single neuroprotective study undertaken to date. Conscious patients presenting within 12 h of acute stroke with limb weakness are eligible. The primary outcome measure is combined death and disability as measured using the Barthel Index at 90-day follow up. By randomizing 2700 patients, the study will have 84% power to detect a 5.5% absolute reduction in the primary end-point. By April 2000, 86 centres were participating, with representation in Canada, USA, Europe, South America, Singapore and Australia. So far, 1206 patients have been randomised, of whom 37% were treated within 6 h. Overall 3-month mortality was 20% and the primary outcome event rate was 43%. The study is ongoing and centres worldwide are encouraged to participate

Chemical structure matching using correlation matrix memories

This paper describes the application of the Relaxation By Elimination (RBE) method to matching the 3D structure of molecules in chemical databases within the frame work of binary correlation matrix memories. The paper illustrates that, when combined with distributed representations, the method maps well onto these networks, allowing high performance implementation in parallel systems. It outlines the motivation, the neural architecture, the RBE method and presents some results of matching small molecules against a database of 100,000 models

Using historical lesion volume data in the design of a new phase II clinical trial in acute stroke

<p><b>Background and Purpose:</b> Clinical research into the treatment of acute stroke is complicated, is costly, and has often been unsuccessful. Developments in imaging technology based on computed tomography and magnetic resonance imaging scans offer opportunities for screening experimental therapies during phase II testing so as to deliver only the most promising interventions to phase III. We discuss the design and the appropriate sample size for phase II studies in stroke based on lesion volume.</p> <p><b>Methods:</b> Determination of the relation between analyses of lesion volumes and of neurologic outcomes is illustrated using data from placebo trial patients from the Virtual International Stroke Trials Archive. The size of an effect on lesion volume that would lead to a clinically relevant treatment effect in terms of a measure, such as modified Rankin score (mRS), is found. The sample size to detect that magnitude of effect on lesion volume is then calculated. Simulation is used to evaluate different criteria for proceeding from phase II to phase III.</p> <p><b>Results:</b> The odds ratios for mRS correspond roughly to the square root of odds ratios for lesion volume, implying that for equivalent power specifications, sample sizes based on lesion volumes should be about one fourth of those based on mRS. Relaxation of power requirements, appropriate for phase II, lead to further sample size reductions. For example, a phase III trial comparing a novel treatment with placebo with a total sample size of 1518 patients might be motivated from a phase II trial of 126 patients comparing the same 2 treatment arms.</p> <p><b>Discussion:</b> Definitive phase III trials in stroke should aim to demonstrate significant effects of treatment on clinical outcomes. However, more direct outcomes such as lesion volume can be useful in phase II for determining whether such phase III trials should be undertaken in the first place.</p&gt

Probing the superconducting ground state of ZrIrSi: A μ\muSR study

The superconducting ground state of newly reported ZrIrSi is probed by means of $\mu$SR technique along with resistivity measurement. The occurrence of superconductivity at $T_\mathrm{C}$ = 1.7 K is confirmed by resistivity measurement. ZF-$\mu$SR study revealed that below $T_\mathrm{C}$, there is no spontaneous magnetic field in the superconducting state, indicates TRS is preserved in case of ZrIrSi. From TF-$\mu$SR measurement, we have estimated the superfluid density as a function of temperature, which is described by an isotropic $s-$wave model with a superconducting gap $2\Delta(0)/k_\mathrm{B}T_\mathrm{C}$ = 5.1, indicates the presence of strong spin-orbit coupling. {\it Ab-initio} electronic structure calculation indicates that there are four bands passing through the Fermi level, forming four Fermi surface pockets. We find that the low-energy bands are dominated by the $4d$-orbitals of transition metal Zr, with substantially lesser weight from the $5d$-orbitals of the Ir-atoms.Comment: 6 pages, 4 figure

Investigation of Superconducting Gap Structure in HfIrSi using muon spin relaxation/rotation

Appearance of strong spin-orbit coupling (SOC) is apparent in ternary equiatomic compounds with 5$d$-electrons due to the large atomic radii of transition metals. SOC plays a significant role in the emergence of unconventional superconductivity. Here we examined the superconducting state of HfIrSi using magnetization, specific heat, zero and transverse-field (ZF/TF) muon spin relaxation/rotation ($\mu$SR) measurements. Superconductivity is observed at $T_\mathrm{C}$ = 3.6 K as revealed by specific heat and magnetization measurements. From the TF$-\mu$SR analysis it is clear that superfluid density well described by an isotropic BCS type $s$-wave gap structure. Furthermore, from TF$-\mu$SR data we have also estimated the superconducting carrier density $n_\mathrm{s}$ = 6.6 $\times$10$^{26}$m$^{-3}$, London penetration depth $\lambda_{L}(0)$ = 259.59 nm and effective mass $m^{*}$ = 1.57 $m_{e}$. Our zero-field muon spin relaxation data indicate no clear sign of spontaneous internal field below $T_\mathrm{C}$, which implies that the time-reversal symmetry is preserved in HfIrSi. Theoretical investigation suggests Hf and Ir atoms hybridize strongly along the $c$-axis of the lattice, which is responsible for the strong three-dimensionality of this system which screens the Coulomb interaction. As a result despite the presence of correlated $d$-electrons in this system, the correlation effect is weakened, promoting electron-phonon coupling to gain importance.Comment: 8 pages, 4 figure

Comparative study of the centrosymmetric and non-centrosymmetric superconducting phases of Re3W using muon-spin spectroscopy and heat capacity measurements

We compare the low-temperature electronic properties of the centrosymmetric (CS) and non-centrosymmetric (NCS) phases of Re3W using muon-spin spectroscopy and heat capacity measurements. The zero-field muSR results indicate that time-reversal symmetry is preserved for both structures of Re3W. Transverse-field muon spin rotation has been used to study the temperature dependence of the penetration depth lambda(T) in the mixed state. For both phases of Re3W, lambda(T) can be explained using a single-gap s-wave BCS model. The magnetic penetration depth at zero temperature, lambda(0), is 164(7) and 418(6) nm for the centrosymmetric and the non-centrosymmetric phases of Re3W respectively. Low-temperature specific heat data also provide evidence for an s-wave gap-symmetry for the two phases of Re3W. Both the muSR and heat capacity data show that the CS material has a higher Tc and a larger superconducting gap Delta(0) at 0 K than the NCS compound. The ratio Delta(0)/kBTc indicates that both phases of Re3W should be considered as strong-coupling superconductors.Comment: 7 pages, to appear in Physical Review

Structure and superconductivity of two different phases of Re3W

Two superconducting phases of Re(3)W have been found with different physical properties. One phase crystallizes in a noncentrosymmetric cubic (alpha-Mn) structure and has a superconducting transition temperature T(c) of 7.8 K. The other phase has a hexagonal centrosymmetric structure and is superconducting with a T(c) of 9.4 K. Switching between the two phases is possible by annealing the sample or remelting it. The properties of both phases of Re(3)W have been characterized by powder neutron diffraction, magnetization, and resistivity measurements. The temperature dependences of the lower and upper critical fields have been measured for both phases. These are used to determine the penetration depths and the coherence lengths for these systems

Non-equilibrium excitation of methanol in Galactic molecular clouds: multi-transitional observations at 2 mm

We observed 14 methanol transitions near lambda=2 mm in Galactic star-forming regions. Broad, quasi-thermal J(0)-J(-1)E methanol lines near 157 GHz were detected toward 73 sources. Together with the 6(-1)-5(0)E and 5(-2)-6(-1)E lines at 133 GHz and the 7(1)-7(0)E line at 165 GHz, they were used to study the methanol excitation. In the majority of the observed objects, the Class I 6(-1)-5(0)E transition is inverted, and the Class II 5(-2)-6(-1)E and 6(0)-6(-1)E transitions are overcooled. This is exactly as predicted by models of low gain Class I masers. The absence of the inversion of Class II transitions 5(-2)-6(-1)E and 6(0)-6(-1)E means that quasi-thermal methanol emission in all objects arises in areas without a strong radiation field, which is required for the inversion.Comment: 23 pages paper (uses aasms4.sty), 12 pages tables (uses apjpt4.sty), 10 Jpeg figures, submitted to the ApJ

Nodal superconducting gap structure in the quasi-one-dimensional Cs2_2Cr3_3As3_3 investigated using μ\muSR measurements

The superconducting ground state of the newly discovered superconductor Cs$_2$Cr$_3$As$_3$ with a quasi-one-dimensional crystal structure ($T_{\bf c}\sim$ 2.1(1) K) has been investigated using magnetization and muon-spin relaxation or rotation ($\mu$SR), both zero-field (ZF) and transverse-field (TF), measurements. Our ZF $\mu$SR measurements reveal the presence of spin fluctuations below 4 K and the ZF relaxation rate ($\lambda$) shows enhancement below $T_{\bf c}\sim$ 2.1 K, which might indicate that the superconducting state is unconventional. This observation suggests that the electrons are paired via unconventional channels such as spin fluctuations, as proposed on the basis of theoretical models. Our analysis of the TF $\mu$SR results shows that the temperature dependence of the superfluid density is fitted better with a nodal gap structure than an isotropic s-wave model for the superconducting gap. The observation of a nodal gap in Cs$_2$Cr$_3$As$_3$ is consistent with that observed in the isostructural K$_2$Cr$_3$As$_3$ compound through TF $\mu$SR measurements. Furthermore, from our TF $\mu$SR study we have estimated the magnetic penetration depth $\lambda_{\mathrm{L}}$$(0)$ = 954 nm, superconducting carrier density $n_s = 4.98 \times 10^{26}~$m$^{-3}$, and carrier's effective-mass enhancement $m^*$ = 1.61m$_{e}$.Comment: 7 pages, 4 figures. arXiv admin note: substantial text overlap with arXiv:1505.0574

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