Safety and tolerability of NXY-059 for acute intracerebral hemorrhage: the CHANT trial

<p><b>Background and Purpose:</b> NXY-059 is a free radical-trapping neuroprotectant developed for use in acute ischemic stroke. To facilitate prompt administration of treatment, potentially before neuroimaging, we investigated the safety of NXY-059 in patients with intracerebral hemorrhage (ICH).</p> <p><b>Methods:</b> We randomized 607 patients within 6 hours of acute ICH to receive 2270 mg intravenous NXY-059 over 1 hour and then up to 960 mg/h over 71 hours, or matching placebo, in addition to standard care. The primary outcome was safety: the mortality and the frequency of adverse events, and the change from baseline for a variety of serum, imaging, and electrophysiological measurements. We also studied the overall distribution of disability scores on the modified Rankin Scale (mRS) and the Barthel index.</p> <p><b>Results:</b> We treated 300 patients with NXY-059 and 303 with placebo. Treatment groups were well matched for prognostic variables including Glasgow Coma Scale, risk factors, and age. The mean National Institute of Health Stroke Scale score on admission was 14 in both groups. The baseline hemorrhage volume was 22.4±20.1 mL in the NXY-059 group and 23.3±22.8 mL in the placebo group (mean±SD). Most hemorrhages were related to hypertension or anticoagulant use. Mortality was similar in both groups: 20.3% for NXY-059 and 19.8% for placebo-treated patients. The proportion of patients who experienced an adverse event was the same for both groups, whereas for serious adverse events the proportion was slightly higher in the NXY-059 group. However, no pattern emerged to indicate a safety concern. Serum potassium fell transiently in both groups, lower in the NXY-059 group. There were no differences in 3-month function, disability, or neurological deficit scores. The odds ratio for an improved outcome in 3-month mRS scores in the NXY-059 group was 1.01 (95% CI 0.75, 1.35).</p> <p><b>Conclusions:</b> NXY-059 given within 6 hours of acute ICH has a good safety and tolerability profile, with no adverse effect on important clinical outcomes.</p&gt

Noninvasive Brain Stimulation and Noninvasive Peripheral Stimulation for Neglect Syndrome Following Acquired Brain Injury

OBJECTIVE: Hemispatial neglect is a frequent condition usually following nondominant hemispheric brain injury. It strongly affects rehabilitation strategies and everyday life activities. It is associated with behavioral and cognitive disability with a strong impact on patient's life. METHODS: We reviewed the published literature on the use of noninvasive brain stimulation, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), and of noninvasive peripheral muscle stimulation, as therapeutic strategies for rehabilitation of neglect after acquired brain injury, such as in stroke or in traumatic injuries. The studies were grouped as controlled or uncontrolled studies in each stimulation techniques. RESULTS: Thirty-four studies were identified and 16 on rTMS, 10 on tDCS, and 8 on vibration. All studies were conducted in adult patients who suffered a stroke, except for one that was conducted in a patient suffering traumatic acquired brain injury and another that was conducted in a patient with brain tumor. In spite of significant variability in treatment protocols, patients' features and assessment of neglect, improvement was reported in almost all studies with no side-effects. CONCLUSIONS: Noninvasive brain stimulation and neuromuscular vibration are promising therapeutic neuromodulatory approaches for neglect. Further randomized-controlled studies are needed to corroborate their effectiveness as separate and combined techniques

BER-Adaptive RMLSA Algorithm for Wide-Area Flexible Optical Networks

Wide-area optical networks face significant transmission challenges due to the relentless growth of bandwidth demands experienced nowadays. Network operators must consider the relationship between modulation format and maximum reach for each connection request due to the accumulation of physical layer impairments in optical fiber links, to guarantee a minimum quality of service (QoS) and quality of transmission (QoT) to all connection requests. In this work, we present a BER-adaptive solution to solve the routing, modulation format, and spectrum assignment (RMLSA) problem for wide-area elastic optical networks. Our main goal is to maximize successful connection requests in wide-area networks while choosing modulation formats with the highest efficiency possible. Consequently, our technique uses an adaptive bit-error-rate (BER) threshold to achieve communication with the best QoT in the most efficient manner, using the strictest BER value and the modulation format with the smallest bandwidth possible. Additionally, the proposed algorithm relies on 3R regeneration devices to enable long-distances communications if transparent communication cannot be achieved. We assessed our method through simulations for various network conditions, such as the number of regenerators per node, traffic load per user, and BER threshold values. In a scenario without regenerators, the BER-Adaptive algorithm performs similarly to the most relaxed fixed BER threshold studied in blocking probability. However, it ensures a higher QoT to most of the connection requests. The proposed algorithm thrives with the use of regenerators, showing the best performance among the studied solutions, enabling long-distance communications with a high QoT and low blocking probability

Multivariable analysis of outcome predictors and adjustment of main outcome results to baseline data profile in randomized controlled trials: Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST)

<p><b>Background and Purpose:</b> The Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST) unadjusted results demonstrated that intravenous alteplase is well tolerated and that the effects were comparable with those seen in randomized, controlled trials (RCTs) when used in routine clinical practice within 3 hours of ischemic stroke onset. We aimed to identify outcome predictors and adjust the outcomes of the SITS-MOST to the baseline characteristics of RCTs.</p> <p><b>Methods:</b> The study population was SITS-MOST (n=6483) and pooled RCTs (n=464) patients treated with intravenous alteplase within 3 hours of stroke onset. Multivariable, backward stepwise regression analyses (until P≤0.10) were performed to identify the outcome predictors for SITS-MOST. Variables appearing either in the final multivariable model or differing (P<0.10) between SITS-MOST and RCTs were included in the prediction model for the adjustment of outcomes. Main outcome measures were symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale deterioration ≥1 within 7 days with any hemorrhage (RCT definition), mortality, and independency as defined by modified Rankin Score of 0 to 2 at 3 months.</p> <p><b>Results:</b> The adjusted proportion of symptomatic intracerebral hemorrhage for SITS-MOST was 8.5% (95% CI, 7.9 to 9.0) versus 8.6% (6.3 to 11.6) for pooled RCTs; mortality was 15.5% (14.7 to 16.2) versus 17.3% (14.1 to 21.1); and independency was 50.4% (49.6 to 51.2) versus 50.1% (44.5 to 54.7), respectively. In the multivariable analysis, older age, high blood glucose, high National Institutes of Health Stroke Scale score, and current infarction on imaging scans were related to poor outcome in all parameters. Systolic blood pressure, atrial fibrillation, and weight were additional predictors of symptomatic intracerebral hemorrhage. Current smokers had a lower rate of symptomatic intracerebral hemorrhage. Disability before current stroke (modified Rankin Score 2 to 5), diastolic blood pressure, antiplatelet other than aspirin, congestive heart failure, patients treated in new centers, and male sex were related to high mortality at 3 months.</p> <p><b>Conclusions:</b> The adjusted outcomes from SITS-MOST were almost identical to those in relevant RCTs and reinforce the conclusion drawn previously in the unadjusted analysis. We identified several important outcome predictors to better identify patients suitable for thrombolysis.</p&gt

Evidence of Critical Behavior in the Disassembly of Nuclei with A ~ 36

A wide variety of observables indicate that maximal fluctuations in the disassembly of hot nuclei with A ~ 36 occur at an excitation energy of 5.6 +- 0.5 MeV/u and temperature of 8.3 +- 0.5 MeV. Associated with this point of maximal fluctuations are a number of quantitative indicators of apparent critical behavior. The associated caloric curve does not appear to show a flattening such as that seen for heavier systems. This suggests that, in contrast to similar signals seen for liquid-gas transitions in heavier nuclei, the observed behavior in these very light nuclei is associated with a transition much closer to the critical point.Comment: v2: Major changes, new model calculations, new figure

Critical Behavior in Light Nuclear Systems: Experimental Aspects

An extensive experimental survey of the features of the disassembly of a small quasi-projectile system with $A \sim$ 36, produced in the reactions of 47 MeV/nucleon $^{40}$Ar + $^{27}$Al, $^{48}$Ti and $^{58}$Ni, has been carried out. Nuclei in the excitation energy range of 1-9 MeV/u have been investigated employing a new method to reconstruct the quasi-projectile source. At an excitation energy $\sim$ 5.6 MeV/nucleon many observables indicate the presence of maximal fluctuations in the de-excitation processes. The fragment topological structure shows that the rank sorted fragments obey Zipf's law at the point of largest fluctuations providing another indication of a liquid gas phase transition. The caloric curve for this system shows a monotonic increase of temperature with excitation energy and no apparent plateau. The temperature at the point of maximal fluctuations is $8.3 \pm 0.5$ MeV. Taking this temperature as the critical temperature and employing the caloric curve information we have extracted the critical exponents $\beta$, $\gamma$ and $\sigma$ from the data. Their values are also consistent with the values of the universality class of the liquid gas phase transition. Taken together, this body of evidence strongly suggests a phase change in an equilibrated mesoscopic system at, or extremely close to, the critical point.Comment: Physical Review C, in press; some discussions about the validity of excitation energy in peripheral collisions have been added; 24 pages and 32 figures; longer abstract in the preprin

Towards the critical behavior for the light nuclei by NIMROD detector

The critical behavior for the light nuclei with A$\sim 36$ has been investigated experimentally by the NIMROD multi-detectors. The wide variety of observables indicate the critical point has been reached in the disassembly of hot nuclei at an excitation energy of 5.6$\pm$0.5 MeV/u.Comment: 4 pages, 2 figures; Proceeding of 18th Nuclear Physics Division Conference of the Euro. Phys. Society (NPDC18) "Phase transitions in strongly interacting matter", Prague, 23.8.-29.8. 2004. To be published in Nuclear Physics

Properties of the Initial Participant Matter Interaction Zone in Near Fermi-Energy Heavy Ion Collisions

The sizes, temperatures and free neutron to proton ratios of the initial interaction zones produced in the collisions of 40 MeV/nucleon $^{40}$Ar + $^{112}$Sn and 55 MeV/nucleon$^{27}$Al + $^{124}$Sn are derived using total detected neutron plus charged particle multiplicity as a measure of the impact parameter range and number of participant nucleons. The size of the initial interaction zone, determined from a coalescence model analysis, increases significantly with decreasing impact parameter. The temperatures and free neutron to proton ratios in the interaction zones are relatively similar for different impact parameter ranges and evolve in a similar fashion.Comment: 7 pages, 8 figure

Tracing the Evolution of Temperature in Near Fermi Energy Heavy Ion Collisions

The kinetic energy variation of emitted light clusters has been employed as a clock to explore the time evolution of the temperature for thermalizing composite systems produced in the reactions of 26A, 35A and 47A MeV $^{64}$Zn with $^{58}$Ni, $^{92}$Mo and $^{197}$Au. For each system investigated, the double isotope ratio temperature curve exhibits a high maximum apparent temperature, in the range of 10-25 MeV, at high ejectile velocity. These maximum values increase with increasing projectile energy and decrease with increasing target mass. The time at which the maximum in the temperature curve is reached ranges from 80 to 130 fm/c after contact. For each different target, the subsequent cooling curves for all three projectile energies are quite similar. Temperatures comparable to those of limiting temperature systematics are reached 30 to 40 fm/c after the times corresponding to the maxima, at a time when AMD-V transport model calculations predict entry into the final evaporative or fragmentation stage of de-excitation of the hot composite systems. Evidence for the establishment of thermal and chemical equilibrium is discussed.Comment: 9 pages, 5 figure

A Ghoshal-like Test of Equilibration in Near-Fermi-Energy Heavy Ion Collisions

Calorimetric and coalescence techniques have been employed to probe equilibration for hot nuclei produced in heavy ion collisions of 35 to 55 MeV/u projectiles with medium mass targets. Entrance channel mass asymmetries and energies were selected in order that very hot composite nuclei of similar mass and excitation would remain after early stage pre-equilibrium particle emission. Inter-comparison of the properties and de-excitation patterns for these different systems provides evidence for the production of hot nuclei with decay patterns relatively independent of the specific entrance channel.Comment: 7 pages, 2 figure