Background Stroke thrombolysis with alteplase is currently recommended 0-4•5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4•5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.Methods In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4•5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036.
FindingsWe identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1•86, 95% CI 1•15-2•99, p=0•011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9•7, 95% CI 1•23-76•55, p=0•031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1•55, 0•81-2•96, p=0•66).Interpretation Patients with ischaemic stroke 4•5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.
Solution-processed ultra-thin (∼3 nm) zinc tin oxide (ZTO) thin film transistors (TFTs) with a mobility of 8 cm2/Vs are obtained with post spin-coating annealing at only 350 °C. The effect of light illumination (at wavelengths of 405 nm or 532 nm) on the stability of TFT transfer characteristics under various gate bias stress conditions (zero, positive, and negative) is investigated. It is found that the ΔVth (Vthstress 3400 s − stress 0 s) window is significantly positive when ZTO TFTs are under positive bias stress (PBS, ΔVth = 9.98 V) and positive bias illumination stress (λ = 405 nm and ΔVth = 6.96 V), but ΔVth is slightly negative under only light illumination stress (λ = 405 nm and ΔVth = −2.02 V) or negative bias stress (ΔVth = −2.27 V). However, the ΔVth of ZTO TFT under negative bias illumination stress is substantial, and it will efficiently recover the ΔVth caused by PBS. The result is attributed to the photo-ionization and subsequent transition of electronic states of oxygen vacancies (i.e., Vo, Vo+, and Vo++) in ZTO. A detailed mechanism is discussed to better understand the bias stress stability of solution processed ZTO TFTs.
Ultrathin Ru-N and Ru-Ta-N films ͑ϳ15 nm in thickness͒ deposited by reactive sputtering are applied as a diffusion barrier in the Cu/barrier/SiO 2 /Si systems. After film deposition, the samples are tested before and after annealing at 200-900°C in vacuum for 30 min. The sheet resistance examined by four-point probe appraises that the Ru-Ta-N barrier would not fail until annealing at 900°C, as compared to Ru-N, which fails after annealing at 600°C. The depth distribution of elements examined by Auger electron spectroscopy confirms different degrees of Cu diffusion into underlayers for the two systems after annealing at 600°C. Also, the cross-sectional microstructures of the Cu/barrier/SiO 2 /Si samples analyzed by transmission electron microscopy, the crystallinity of barrier films examined by grazing incident angle X-ray diffraction, and the chemical state of barrier characterized by X-ray photoelectron spectroscope might explain the difference in barrier performance for the ultrathin Ru-N and Ru-Ta-N films in the Cu/barrier/SiO 2 /Si multilayered systems.
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