Intravenous thrombolysis for large vessel or distal occlusions presenting with mild stroke severity.

BACKGROUND AND PURPOSE: We investigated the effectiveness of intravenous thrombolysis (IVT) in acute ischaemic stroke (AIS) patients with large vessel or distal occlusions and mild neurological deficits, defined as National Institutes of Health Stroke Scale scores < 6 points. METHODS: The primary efficacy outcome was 3-month functional independence (FI) [modified Rankin Scale (mRS) scores 0-2] that was compared between patients with and without IVT treatment. Other efficacy outcomes of interest included 3-month favorable functional outcome (mRS scores 0-1) and mRS score distribution at discharge and at 3 months. The safety outcomes comprised all-cause 3-month mortality, symptomatic intracranial hemorrhage (ICH), asymptomatic ICH and severe systemic bleeding. RESULTS: We evaluated 336 AIS patients with large vessel or distal occlusions and mild stroke severity (mean age 63 ± 15 years, 45% women). Patients treated with IVT (n = 162) had higher FI (85.6% vs. 74.8%, P = 0.027) with lower mRS scores at hospital discharge (P = 0.034) compared with the remaining patients. No differences were detected in any of the safety outcomes including symptomatic ICH, asymptomatic ICH, severe systemic bleeding and 3-month mortality. IVT was associated with higher likelihood of 3-month FI [odds ratio (OR), 2.19; 95% confidence intervals (CI), 1.09-4.42], 3-month favorable functional outcome (OR, 1.99; 95% CI, 1.10-3.57), functional improvement at discharge [common OR (per 1-point decrease in mRS score), 2.94; 95% CI, 1.67-5.26)] and at 3 months (common OR, 1.72; 95% CI, 1.06-2.86) on multivariable logistic regression models adjusting for potential confounders, including mechanical thrombectomy. CONCLUSIONS: Intravenous thrombolysis is independently associated with higher odds of improved discharge and 3-month functional outcomes in AIS patients with large vessel or distal occlusions and mild stroke severity. IVT appears not to increase the risk of systemic or symptomatic intracranial bleeding.

Particle damage sources for fused silica optics and their mitigation on high energy laser systems.

High energy laser systems are ultimately limited by laser-induced damage to their critical components. This is especially true of damage to critical fused silica optics, which grows rapidly upon exposure to additional laser pulses. Much progress has been made in eliminating damage precursors in as-processed fused silica optics (the advanced mitigation process, AMP3), and very high damage resistance has been demonstrated in laboratory studies. However, the full potential of these improvements has not yet been realized in actual laser systems. In this work, we explore the importance of additional damage sources-in particular, particle contamination-for fused silica optics fielded in a high-performance laser environment, the National Ignition Facility (NIF) laser system. We demonstrate that the most dangerous sources of particle contamination in a system-level environment are laser-driven particle sources. In the specific case of the NIF laser, we have identified the two important particle sources which account for nearly all the damage observed on AMP3 optics during full laser operation and present mitigations for these particle sources. Finally, with the elimination of these laser-driven particle sources, we demonstrate essentially damage free operation of AMP3 fused silica for ten large optics (a total of 12,000 cm2 of beam area) for shots from 8.6 J/cm2 to 9.5 J/cm2 of 351 nm light (3 ns Gaussian pulse shapes). Potentially many other pulsed high energy laser systems have similar particle sources, and given the insight provided by this study, their identification and elimination should be possible. The mitigations demonstrated here are currently being employed for all large UV silica optics on the National Ignition Facility.

The protective effect of astrocyte-derived 14,15-epoxyeicosatrienoic acid on hydrogen peroxide-induced cell injury in astrocyte-dopaminergic neuronal cell line co-culture.

Astrocytes perform several functions that are essential for normal neuronal activity. They play a critical role in neuronal survival during ischemia and other degenerative injuries and also modulate neuronal recovery by influencing neurite outgrowth. In this study, we investigated the neuroprotective effects of astrocyte-derived 14,15-epoxyeicosatrienoic acid (14,15-EET), metabolite of arachidonic acid by cytochrome P450 epoxygenases (CYP), against oxidative stress induced by hydrogen peroxide (H(2)O(2)). We found that dopaminergic neuronal cells (N27 cell line) stimulated with two different doses of H(2)O(2) (0.1 and 1mM) for 1h showed decreased cell viability compared to the control group, while astrocytes showed less cell death after stimulation with the same doses of H(2)O(2) for 1h. Dopaminergic neuronal cells (N27 cell line) pretreated with different doses of 14,15-EET (0.1-30 µM, 30 min) before H(2)O(2) stimulation also showed increased cell viability. Furthermore, pre-treatment of the co-cultured cells with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid, an inhibitor of the EET metabolizing enzyme, soluble epoxide hydrolase (sEH), before H(2)O(2) stimulation (1mM, for 1h) increased cell viability. It also increased the endogenous level of 14,15-EET in the media compared to control group. However, pretreatment with the CYP epoxygenase inhibitor miconazole (1-20 µM, 1h) before H(2)O(2) (1mM, 1h) stimulation showed decreased cell viability. Our data suggest that 14,15-EET which is released from astrocytes, enhances cell viability against oxidant-induced injury. Further understanding of the mechanism of 14,15-EET-mediated protection in dopaminergic neurons is imperative, as it could lead to novel therapeutic approaches for treating CNS neuropathologies, such as Parkinson's disease.

Demonstration of high-energy 2 omega (526.5 nm) operation on the National Ignition Facility Laser System.

A single beamline of the National Ignition Facility (NIF) has been operated at a wavelength of 526.5 nm (2 omega) by frequency converting the fundamental 1053 nm (1 omega) wavelength with an 18.2 mm thick type-I potassium dihydrogen phosphate (KDP) second-harmonic generator (SHG) crystal. Second-harmonic energies of up to 17.9 kJ were measured at the final optics focal plane with a conversion efficiency of 82%. For a similarly configured 192-beam NIF, this scales to a total 2 omega energy of 3.4 MJ full NIF equivalent (FNE).

National Ignition Facility laser performance status.

The National Ignition Facility (NIF) is the world's largest laser system. It contains a 192 beam neodymium glass laser that is designed to deliver 1.8 MJ at 500 TW at 351 nm in order to achieve energy gain (ignition) in a deuterium-tritium nuclear fusion target. To meet this goal, laser design criteria include the ability to generate pulses of up to 1.8 MJ total energy, with peak power of 500 TW and temporal pulse shapes spanning 2 orders of magnitude at the third harmonic (351 nm or 3omega) of the laser wavelength. The focal-spot fluence distribution of these pulses is carefully controlled, through a combination of special optics in the 1omega (1053 nm) portion of the laser (continuous phase plates), smoothing by spectral dispersion, and the overlapping of multiple beams with orthogonal polarization (polarization smoothing). We report performance qualification tests of the first eight beams of the NIF laser. Measurements are reported at both 1omega and 3omega, both with and without focal-spot conditioning. When scaled to full 192 beam operation, these results demonstrate, to the best of our knowledge for the first time, that the NIF will meet its laser performance design criteria, and that the NIF can simultaneously meet the temporal pulse shaping, focal-spot conditioning, and peak power requirements for two candidate indirect drive ignition designs.

Room-temperature laser action at 4.34.4 mum in CaGa(2)S(4):Dy(3+).

We report room-temperature mid-IR laser operation in a new low-phonon-frequency nonhygroscopic host crystal, calcium thiogallate (CaGa(2)S(4)) . Laser action at 4.314.38 mum on the Dy(3+)H(11/2)(6)?H(13/2)(6) transition occurred with a maximum slope efficiency of 1.6%.

Quantitative determination of antiviral nucleoside analog in DNA.

A technique for the analysis of the amount of an antiviral nucleoside analog incorporated into DNA, utilizing enzymatic digestion of DNA, followed by high-performance liquid chromatography is described. The cells or tissue samples were treated with perchloric acid to inactivate the nucleases, then digested with pronase in the presence of EDTA. DNA was purified by CsCl centrifugation followed by Sephadex chromatography and treatment with deoxyribonuclease 1 and venom phosphodiesterase. The deoxyribonucleoside monophosphates and the monophosphate of the nucleoside analog liberated from DNA were separated and quantitated by HPLC analysis and measurement of radioactivity. This assay is more sensitive, specific, and precise than the determination of DNA density shift. It is also applicable for nucleoside analogs which do not change the density of DNA either because of their structure or their very small degree of incorporation.