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Patients with pre-stroke disability, defined as a modified Rankin Scale (mRS) ≥3, were excluded from most trials of endovascular thrombectomy (EVT) for acute stroke. We sought to evaluate the prognostic factors associated with favorable outcome in stroke patients with known disability undergoing EVT, and the impact of successful reperfusion.Consecutive acute stroke patients with pre-stroke disability, undergoing EVT, were retrospectively collected between 2016 to 2019 from a Canadian cohort and a multicenter French cohort (Endovascular Treatment in Ischemic Stroke registry-ETIS). Favorable outcome was defined as an mRS equal to pre-stroke mRS. Patients achieving successful reperfusion (defined as a modified Thrombolysis in Cerebral Infarction score of 2b/3) were compared with patients without successful reperfusion to determine if successful EVT was associated with better functional outcomes.Among 6220 patients treated with EVT, 280 (4.5%) patients with a pre-stroke mRS ≥3 were included. Sixty-one patients (21.8%) had a favorable outcome and 146 (52.1%) died at 3 months. Patients with successful reperfusion had a higher proportion of favorable 90-day mRS (27.6% versus 19.6%, p = 0.025) and a lower mortality (48.3% versus 69.6%, p = 0.008) than patients without successful reperfusion. After adjusting for baseline prognostic factors, successful reperfusion defined by TICI ≥2b was associated with favorable functional outcome (OR 3.16 CI95% [1.11-11.5]; p 0.048).In patients with pre-stroke disability, successful reperfusion is associated with a greater proportion of favorable outcome and lower mortality.

Background and purpose: First pass effect (FPE), the occurrence of complete reperfusion after one pass with no rescue attempt during endovascular therapy (EVT), is associated with the best clinical outcome after an acute ischemic stroke (AIS). Previous studies evaluating FPE occurrence according to EVT technical strategies, occlusion locations, or thrombus composition have provided controversial results. Here, we performed a correlation analysis between FPE occurrence and AIS thrombus cellular composition, as assessed using quantitative biochemical assays. Patients and methods: Homogenates of AIS thrombi from 250 patients were prepared by mechanical grinding. Platelet, red blood cell (RBC), and leukocyte contents of AIS thrombi were respectively estimated by quantification of GP (glycoprotein) VI, heme, and DNA in thrombus homogenates. FPE was defined as a modified Thrombolysis in Cerebral Infraction (mTICI) score of 2C or 3 after a single EVT device pass. Results: AIS thrombi successfully removed after a single pass were poorer in GPVI (0.098 ± 0.023 vs 0.111 ± 0.024 ng/mg, p Discussion and conclusion: Thrombus platelet content may hamper thrombus removal by EVT. This result suggests that adjunctive therapies or functionalization of retrieval devices targeting platelets may improve EVT efficacy.

Despite continuous improvement and growing knowledge in the endovascular therapy of large vessel occlusion stroke (LVOS), mechanical thrombectomy (MT) still fails to obtain satisfying intracranial recanalization in 10% to 15% of cases. However, little is known regarding clinical and radiological outcomes among this singularly underexplored subpopulation undergoing failed MT. We aimed to investigate the outcome after failed MT and identify predictive factors of favorable outcome despite recanalization failure.We conducted a retrospective analysis of consecutive patients prospectively included in the ongoing observational multicenter Endovascular Treatment in Ischemic Stroke registry from January 2015 to September 2020. Patients presenting with anterior circulation LVOS treated with MT but experiencing failed intracranial recanalization defined as final modified Thrombolysis In Cerebral Infarction (mTICI) score of 0, 1 and 2a were included. Clinical and radiological outcomes were assessed along with the exploration of predictive factors of Day-90 favorable outcome.The study population comprised 533 patients. Mean age was 68.8 ± 16 years, and median admission National Institutes of Health Stroke Scale (NIHSS) and Alberta Stroke Program Early Computed Tomography Score (ASPECTS) were 17 (IQR 12-21) and 7 (IQR 5-8), respectively. Favorable outcomes were observed in 85 patients (18.2%) and 186 died (39.0%). The rate of symptomatic intracranial hemorrhage was 14.1%. In multivariable analysis, younger age (odds ratio [OR] 0.96, 95% CI 0.94-0.98, p lt; 0.001), a lower admission NIHSS (OR 0.87, 95% CI 0.83-0.91, p lt; 0.001), a lower number of MT passes (OR 0.77, 95% CI 0.77-0.87, p lt; 0.001), a lower delta ASPECTS between initial and Day-1 imaging (OR 0.83, 95% CI 0.71-0.98, p = 0.026) and stroke etiology [significant difference among etiological subtypes (p = 0.024) with a tendency toward more favorable outcomes for dissection (OR 2.01, 95% CI 0.71-5.67)] were significantly associated with a 90-day favorable outcome.In this large retrospective analysis of a multicenter registry, we quantified the poor outcome after MT failure. We also identified factors associated with favorable outcome despite recanalization failure that might influence therapeutic management.

Resistance to fibrinolysis, levels of procoagulant/antifibrinolytic neutrophil extracellular traps (NETs), and the severity of acute ischemic stroke (AIS) are increased by COVID-19. Whether NETs are components of AIS thrombi from COVID-19 patients and whether COVID-19 impacts the susceptibility of these thrombi to thrombolytic treatments remain unknown, however.We aimed to characterize AIS thrombi from COVID-19 patients by immunohistology and to compare their response to thrombolysis to that of AIS thrombi from non-COVID-19 patients.For this monocentric cohort study, 14 thrombi from COVID-19 AIS patients and 16 thrombi from non-COVID-19 patients, all recovered by endovascular therapy, were analyzed by immunohistology or subjected to ex vivo thrombolysis by tissue-type plasminogen (tPA)/plasminogen.COVID-19 AIS thrombi were rich in neutrophils and contained NETs, but not spike protein. Thrombolysis assays revealed a mean resistance profile to tPA/plasminogen of COVID-19 AIS thrombi similar to that of non-COVID-19 AIS thrombi. The addition of DNase 1 successfully improved thrombolysis by potentiating fibrinolysis irrespective of COVID-19 status. Levels of neutrophil, NETs, and platelet markers in lysis supernatants were comparable between AIS thrombi from non-COVID-19 and COVID-19 patients.These results show that COVID-19 does not impact NETs content or worsen fibrinolysis resistance of AIS thrombi, a therapeutic hurdle that could be overcome by DNase 1 even in the context of SARS-CoV-2 infection.

Background and Purpose: In the settings of thrombectomy, the first-pass effect (FPE), defined by a complete recanalization after one pass with no rescue therapy, has been shown to be associated with an improved outcome. As this phenomenon has been predominantly described in anterior circulation strokes, we aimed to study the prevalence, outcomes, and predictors of FPE in patients with a basilar artery occlusion. Methods: From a prospective multicentric registry, we collected the data of all consecutive basilar artery occlusion patients who underwent thrombectomy and compared the outcomes of patients who achieved FPE and those who did not. We also compared FPE patients with those who achieved a complete recanalization with >1 pass. Finally, a multivariate analysis was performed to determine the predictors of FPE. Results: Data from 280 patients were analyzed in our study, including 84 of 280 patients (30%) with an atheromatous etiology. An FPE was achieved in 93 patients (33.2%), with a significantly higher proportion of good outcomes (modified Rankin Scale score 0-2 at 3 months) and lower mortality than non-FPE patients. An FPE was also associated with improved outcomes compared with patients who went on to have full recanalization with >1 pass. Contact aspiration as first-line strategy was a strong predictor of FPE, whereas baseline antiplatelets and atheromatous etiology were negative predictors. Conclusions: In our study, an FPE was achieved in approximately one-third of patients with a basilar artery occlusion and was associated with improved outcomes. More research is needed to improve devices and techniques to increase the incidence of FPE. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03776877.

Background: Management of extracranial internal carotid artery steno-occlusive lesion during endovascular therapy remains debated. Stent occlusion within 24 hours of endovascular therapy is a frequent event after acute carotid artery stenting, and we currently lack large population results. We investigated the incidence, predictors, and clinical impact of stent occlusion after acute carotid artery stenting in current clinical practice. Methods: Patients treated by endovascular therapy with acute carotid artery stenting between 2015 and 2019 in 5 large-volume endovascular-capable centers were retrospectively analyzed. Patients were separated in 2 groups according to the stent patency at 24 hours after carotid artery stenting. We compared baseline characteristics, treatment modalities, and clinical outcome depending on 24-hour stent patency. Primary end point was favorable outcome, defined as a modified Rankin Scale score 0–2 at 3 months. Results: A stent occlusion was observed in 47/225 patients (20.9%). Patients with stent patency had a lower baseline National Institutes of Health Stroke Scale (median [interquartile range]: 13 [7–17] versus 18 [12–21]) and had more often stroke of atherothrombotic origin (77.0% versus 53.2%). A higher stent patency rate was found for patients treated with P2Y 12 antagonists at the acute phase (odds ratio [OR]‚ 2.95 [95% CI‚ 1.10–7.91]; P =0.026) and treated with angioplasty (OR‚ 2.42 [95% CI‚ 1.24–4.67]; P =0.008). A better intracranial angiographic reperfusion was observed in patients with 24-hour stent patency compared with patients without stent patency (OR‚ 8.38 [95% CI‚ 3.07–22.78]; P P P =0.009). Conclusions: One out of 5 patients treated with carotid artery stenting during endovascular therapy presented a stent occlusion within 24 hours. This event was associated with worse functional outcome. Stroke etiology, P2Y 12 antagonist administration, quality of intracranial reperfusion, and angioplasty were associated with 24-hour stent patency.

In sequence similarity search applications such as read mapping, it is desired that seeds match between a read and reference in regions with mutations or read errors (seed sensitivity).K-mers are likely the most well-known and used seed construct in bioinformatics, and many studies on,e.g., spacedk-mers aim to improve sensitivity overk-mers. Spacedk-mers are highly sensitive when substitutions largely dominate the mutation rate but quickly deteriorate when indels are present. Recently, we developed a pseudo-random seeding construct, strobemers, which were empirically demonstrated to have high sensitivity also at high indel rates. However, the study lacked a deeper understanding of why. In this study, we demonstrate that a seed’s entropy (randomness) is a good predictor for seed sensitivity. We propose a model to estimate the entropy of a seed and find that seeds with high entropy, according to our model, in most cases have high match sensitivity. We also present three new strobemer seed constructs, mixedstrobes, altstrobes, and multistrobes. We use both simulated and biological data to demonstrate that our new seed constructs improve sequence-matching sensitivity to other strobemers. We implement strobemers into minimap2 and observe slightly faster alignment time and higher accuracy than usingk-mers at various error rates.Our discovered seed randomness-sensitivity relationship explains why some seeds perform better than others, and the relationship provides a framework for designing even more sensitive seeds. In addition, we show that the three new seed constructs are practically useful. Finally, in cases where our entropy model does not predict the observed sensitivity well, we explain why and how to improve the model in future work.

BackgroundDespite constant improvements in recent years, sufficient reperfusion after mechanical thrombectomy (MT) is not reached in up to 15% of patients with large vessel occlusion stroke (LVOS). The outcome of patients with unsuccessful reperfusion after MT especially after intravenous thrombolysis (IVT) use is not known. We investigated the influence of initial IVT in this particular group of patients with failed intracranial recanalization.MethodsWe conducted a retrospective analysis of the Endovascular Treatment in Ischemic Stroke (ETIS) registry from January 2015 to December 2019. Patients presenting with LVOS of the anterior circulation and final modified Thrombolysis in Cerebral Infarction score (mTICI) of 0, 1 or 2a were included. Posterior circulation, isolated cervical carotid occlusions and successful reperfusions (mTICI 2b, 2c or 3) were excluded. The primary endpoint was favorable outcome (modified Rankin Scale score of 0–2) after 3 months. Secondary endpoints were safety outcomes including mortality, any intracranial hemorrhage (ICH), parenchymal hematoma (PH) and symptomatic intracranial hemorrhage (sICH) rates.ResultsAmong 5076 patients with LVOS treated with MT, 524 patients with insufficient recanalization met inclusion criteria, of which 242 received IVT and 282 did not. Functional outcome was improved in the MT+IVT group compared with the MT alone group, although the difference did not reach statistical significance (23.0% vs 12.9%; adjusted OR=1.82; 95% CI 0.98 to 3.38; p=0.058). However, 3 month mRS shift analysis showed a significant benefit of IVT (adjusted OR=1.68; 95% CI 1.56 to 6.54). ICH and sICH rates were similar in both groups, although PH rate was higher in the MT+IVT group (adjusted OR=3.20; 95% CI 1.56 to 6.54).ConclusionsAmong patients with LVOS in the anterior circulation and unsuccessful MT, IVT was associated with improved functional outcome even after unsuccessful MT. Despite recent trials questioning the place of IVT in the LVOS reperfusion strategy, these findings emphasize a subgroup of patients still benefiting from IVT.

More than 40% of endovascular therapy (EVT) fail to achieve complete reperfusion of the territory of the occluded artery in patients with acute ischemic stroke (AIS). Understanding factors influencing EVT could help overcome its limitations. Our objective was to study the impact of thrombus cell composition on EVT procedures, using a simulation system for modeling thrombus-induced large vessel occlusion (LVO) in flow conditions. In an open comparative trial, we analyzed the behavior of size-standardized platelet-rich and red blood cells (RBC)-rich thrombi during simulated stent retriever-mediated EVT procedures. Sixteen simulated EVT procedures were performed (8 RBC- vs. 8 platelet-rich thrombi). Platelet-rich thrombi were associated with a higher number of stent retriever passes (p = 0.03) and a longer procedure duration (p = 0.02) compared to RBC-rich thrombi. Conversely, RBC-rich thrombi released more embolic fragments than platelet-rich thrombi (p = 0.004). Both RBC-rich and platelet-rich thrombi underwent drastic compaction after being injected into the in vitro circulation model, and histologic analyses showed that these EVT-retrieved thrombi displayed features comparable to those previously observed in thrombi from patients with AIS patients having LVO, including a marked structural dichotomy between RBC- and platelet-rich areas. Our results show that the injection of in vitro-produced thrombi in artificial cerebrovascular arterial networks is suitable for testing recanalization efficacy and the risk of embolization of EVT devices and strategies in association with thrombus cell composition.

Background and Purpose: Approximately half of the patients with acute ischemic stroke due to anterior circulation large vessel occlusion do not achieve functional independence despite successful reperfusion. We aimed to determine influence of reperfusion strategy (bridging therapy, intravenous thrombolysis alone, or mechanical thrombectomy alone) on clinical outcomes in this population. Methods: From ongoing, prospective, multicenter, observational Endovascular Treatment in Ischemic Stroke registry in France, all patients with anterior circulation large vessel occlusion who achieved successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b-3) following reperfusion therapy were included. Primary end point was favorable outcome, defined as 90-day modified Rankin Scale score ≤2. Patient groups were compared using those treated with bridging therapy as reference. Differences in baseline characteristics were reduced after propensity score-matching, with a maximum absolute standardized difference of 14% for occlusion site. Results: Among 1872 patients included, 970 (51.8%) received bridging therapy, 128 (6.8%) received intravenous thrombolysis alone, and the remaining 774 (41.4%) received MT alone. The rate of favorable outcome was comparable between groups. Excellent outcome (90-day modified Rankin Scale score 0–1) was achieved more frequently in the bridging therapy group compared with the MT alone (odds ratio after propensity score-matching, 0.70 [95% CI, 0.50–0.96]). Regarding safety outcomes, hemorrhagic complications were similar between the groups, but 90-day mortality was significantly higher in the MT alone group compared with the bridging therapy group (odds ratio, 1.60 [95% CI, 1.09–2.37]). Conclusions: This real-world observational study of patients with anterior circulation large vessel occlusion demonstrated a similar rate of favorable outcome following successful reperfusion with different therapeutic strategies. However, our results suggest that bridging therapy compared with MT alone is significantly associated with excellent clinical outcome and lower mortality. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03776877.

Background and Purpose: The influence of prior antiplatelet therapy (APT) uses on the outcomes of patients with acute ischemic stroke treated with endovascular therapy is unclear. We compared procedural and clinical outcomes of endovascular therapy in patients on APT or not before stroke onset. Methods: We analyzed 2 groups from the ongoing prospective multicenter Endovascular Treatment in Ischemic Stroke registry in France: patients on prior APT (APT+) and patients without prior APT (APT−) treated by endovascular therapy, with and without intravenous thrombolysis. Multilevel mixed-effects logistic models including center as random effect were used to compare angiographic (rates of reperfusion at the end of procedure, procedural complications) and clinical (favorable and excellent outcome, 90-day all-cause mortality, and hemorrhagic complications) outcomes according to APT subgroups. Comparisons were adjusted for prespecified confounders (age, admission National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score, intravenous thrombolysis, and time from onset to puncture), as well as for meaningful baseline between-group differences. Results: A total of 2939 patients were analyzed, of whom 877 (29.8%) were on prior APT. Patients with prior APT were older, had more frequent vascular risk factors, cardioembolic stroke mechanism, and prestroke disability. Rates of complete reperfusion (37.9% in the APT− group versus 42.7 % in the APT+ group; aOR, 1.09 [95% CI, 0.88–1.34]; P =0.41) and periprocedural complication (16.9% versus 13.3%; aOR, 0.90 [95% CI, 0.7–1.2]; P =0.66) did not differ between the two groups. Symptomatic intracerebral hemorrhage (aOR, 0.93 [95% CI, 0.63–1.37]; P =0.73), 3 months favorable clinical outcome (modified Rankin Scale score of 0–2; aOR, 0.98 [95% CI, 0.77–1.25]; P =0.89), and mortality (aOR, 0.95 [95% CI, 0.72–1.26]; P =0.76) at 90 days did not differ between the groups. Conclusions: Prior APT does not influence angiographic and functional outcomes following endovascular therapy and should not be taken into account for acute revascularization strategies.

BackgroundThe Safety and Efficacy of Intensive Blood Pressure Lowering after Successful Endovascular Therapy in Acute Ischaemic Stroke (BP TARGET) trial demonstrated no benefit from intensive systolic blood pressure (SBP) treatment after successful reperfusion with endovascular therapy. However, it remains unknown if the response to blood pressure treatment is modified by other factors.ObjectiveTo carry out a post hoc analysis of the BP TARGET trial data to determine if the response to blood pressure treatment is modified by factors such as age, history of hypertension, recanalization status, location of occlusion, diabetes, hyperglycemia, or pretreatment with intravenous thrombolysis.MethodsThis is a post hoc analysis of the BP TARGET trial. Patients were divided into groups based on age, diabetes, blood glucose, site of occlusion, history of hypertension, and pretreatment with intravenous thrombolysis. The primary outcome was any intraparenchymal hemorrhage.Results318 patients were included. Diabetes modified the treatment effect on favorable functional outcome (Pheteogenity=0.041). There was a trend towards benefit from intensive SBP treatment in diabetic patients (OR=2.81; 95% CI 0.88 to 8.88; p=0.08) but not in non-diabetic patients (OR=0.75; 95% 0.45 to 126; p 0.28). Age, location of occlusion, admission SBP, pretreatment with intravenous thrombolysis, and history of hypertension did not modify the effect of intensive SBP treatment on any of the outcomes.ConclusionThe effect of SBP lowering treatment was not modified by age, location of occlusion history of hypertension, intravenous thrombolysis, and admission SBP. Diabetes modified the effect of intensive SBP lowering treatment, and there was a trend towards benefit from intensive SBP treatment in diabetic patients. This finding is hypothesis generating and requires further validation.

Background and Purpose: Identification of acute ischemic stroke (AIS) cause is crucial for guidance of secondary prevention. Previous studies have yielded inconsistent results regarding possible correlations between AIS cause and thrombus composition, as assessed by semiquantitative histological analysis. Here, we performed a correlation analysis between AIS cause and AIS thrombus cellular composition and content, as assessed using quantitative biochemical assays. Methods: Homogenates of 250 patients with AIS thrombi were prepared by mechanical grinding. Platelet, red blood cell, and leukocyte content of AIS thrombi were estimated by quantification of GP (glycoprotein) VI, heme, and DNA in thrombus homogenates. AIS cause was defined as cardioembolic, noncardioembolic, or embolic stroke of undetermined source, according to the TOAST classification (Trial of ORG 10172 in Acute Stroke Treatment). Results: Cardioembolic thrombi were richer in DNA (35.8 versus 13.8 ng/mg, P P =0.045) than noncardioembolic ones. The area under the receiver operating characteristic curve of DNA content to discriminate cardioembolic thrombi from noncardioembolic was 0.72 (95% CI, 0.63–0.81). With a threshold of 44.7 ng DNA/mg thrombus, 47% of thrombi from undetermined cause would be classified as cardioembolic with a specificity of 90%. Conclusions: Thrombus DNA content may provide an accurate biomarker for identification of cardioembolic thrombi in patients with AIS with embolic stroke of undetermined source. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03268668.

BackgroundIt is unknown whether collateral status modifies the effect of pretreatment intravenous thrombolysis (IVT) on the outcomes of patients with large vessel occlusions treated with endovascular therapy (EVT). We aimed to assess whether collateral status modifies the effect of IVT on the outcomes of EVT in clinical practice.MethodsWe used data from the ongoing prospective multicentric Endovascular Treatment in Ischemic Stroke (ETIS) Registry in France. Patients with anterior circulation proximal large vessel occlusions treated with EVT within 6 hours of symptom onset were enrolled. Patients were divided into two groups based on pretreatment with IVT. The two groups were matched based on baseline characteristics. We tested the interaction between collateral status and IVT in unadjusted and adjusted models.ResultsA total of 1589 patients were enrolled in the study, of whom 55% received IVT. Using a propensity score matching method, 724 no IVT patients were matched to 549 IVT patients. In propensity score weighted analysis, IVT was associated with higher odds of early neurological improvement (OR 1.74; 95% CI 1.33 to 2.26), favorable functional outcome (OR 1.66; 95% CI 1.23 to 2.24), excellent functional outcome (OR 2.04; 95% CI 1.47 to 2.83), and successful reperfusion (OR 2.18; 95% CI 1.51 to 3.16). IVT was not associated with mortality or hemorrhagic complications. There was no interaction between collateral status and IVT association with any of the outcomes.ConclusionsCollateral status does not modify the effect of pretreatment IVT on the efficacy and safety outcomes of EVT.

A Ti2AlC MAX phase material was deposited on Zircaloy-4 substrate using the cold spray process, with the goal of enhancing the accident tolerance of zirconium-alloy fuel cladding in light water reactors. The samples were annealed up to 923 K to study the intermetallic phase formation between the coating and Zircaloy-4 substrate. Three interface compounds, ZrAl2, ZrAl, and Zr3Al, were identified and the activation energy of the interfacial intermetallic compound growth was determined. The radiation response of the coating material and interfacial intermetallic compounds after 3.5 MeV Zr2+ ion irradiation was investigated by transmission electron microscopy and nanoindentation. Ion irradiation disrupted the nanolamellar structure of the Ti2AlC coating while amorphization was observed some of the intermetallic compounds. Nanoindentation revealed overall hardening of the Ti2AlC coating and Zr3Al phase, with no significant change observed in the ZrAl2 and ZrAl phases.

A novel fabrication method of oxide dispersion strengthened (ODS) steel cladding tubes for advanced fast reactors has been investigated using the cold spray powder-based materials deposition process. Cold spraying has the potential advantage for rapidly fabricating ODS cladding tubes in comparison with the conventional multi-step extrusion process. A gas atomized spherical 14YWT (Fe-14%Cr, 3%W, 0.4%Ti, 0.2%Y, 0.01%O) powder was sprayed on a rotating cylindrical 6061-T6 aluminum mandrel using nitrogen as the propellant gas. The powder lacked the oxygen content needed to precipitate the nanoclusters in ODS steel, therefore this work was intended to serve as a proof-of-concept study to demonstrate that free-standing steel cladding tubes with prototypical ODS composition could be manufactured using the cold spray process. The spray process produced an approximately 1-mm thick, dense 14YWT deposit on the aluminum-alloy tube. After surface polishing of the 14YWT deposit to obtain desired cladding thickness and surface roughness, the aluminum-alloy mandrel was dissolved in an alkaline medium to leave behind a free-standing ODS tube. The as-fabricated cladding tube was annealed at 1000 °C for 1 h in an argon atmosphere to improve the overall mechanical properties of the cladding. Keywords: Oxide dispersion strengthened steel, 14YWT powder, Cold spray process, ODS tube manufacturing

The cold spray materials deposition process has been investigated for manufacturing oxide dispersion-strengthened (ODS) steel fuel cladding tubes. Gas-atomized 14YWT ODS steel powder was used as the feedstock material. A parametric investigation of the cold spray process involving substrate materials of various hardnesses, gas preheat temperatures, and carrier gas compositions was performed to achieve the highest quality deposit. The high-velocity impact of the powder on the substrate led to dissolution of discrete oxide nanoparticles, which subsequently reprecipitated during postdeposition annealing at high temperatures. The tubes were manufactured by deposition on an Al-alloy mandrel substrate and subsequent chemical dissolution of the substrate. A 204-mm-long and 1-mm-thick ODS steel cladding tube was successfully manufactured. The grain growth and distribution of oxide nanoparticles in ferritic steel matrix were identified at elevated temperatures. Overall, the cold spray process holds considerable promise for rapid, cost-effective manufacturing of ODS steel cladding tubes.

The development of a cold spray process for the deposition of chromium (Cr) coatings on zirconium-alloys is presented with the goal of improving the accident tolerance of light water reactor (LWR) fuel cladding tubes. The cold spray parameters and feedstock powders were varied to attain the desired coating properties such as thickness, microstructure, and oxidation resistance, on both Zircaloy-4 flat specimens and Optimized ZIRLO™ cladding tubes. The coated samples were tested at temperatures up to 1300 °C in air to investigate the oxidation performance and inter-diffusion between the Cr coatings and the underlying zirconium-alloy substrate. To simulate the performance of the coatings under normal LWR operating conditions, the coated samples were also tested in a steam autoclave at 400 °C and 10.3 MPa. Microstructures, phases, and hardnesses of the feedstock powders and as-deposited coatings were examined, and oxidation and inter-diffusion profiles were quantified in post-oxidation test samples. Overall, cold sprayed Cr coatings show significant promise for enhancing the accident tolerance of zirconium-alloy fuel cladding in LWRs both in terms of performance and cost-effective manufacturability.

FeCrAl has been proposed as a coating layer to enhance accident tolerance of Zircaloy-4 fuel cladding. In this study, we systematically examined the diffusion kinetics and interface compound formation of the spray-coated FeCrAl and Zircaloy-4 substrate. After vacuum annealing at 923 K, 963 K, and 998 K for various time periods, a mixed Zr2Fe phase and Zr3Fe formed at the interface. The formation energies of these two phases were found to be 65 kJ/mol and 58 kJ/mol for Zr2Fe and Zr3Fe, respectively. Bending tests of cantilevers prepared by a focused ion beam technique showed good interface bonding between the coating layer and the substrate. Nanoindentation and micropillar compression tests in the cross-section of polished samples show different mechanical responses of each phase. The substrate exhibited the lowest hardness and most ductile deformation under compression, while interfacial Zr2Fe and Zr3Fe possessed the highest hardness and brittle failure.

The first in-situ ion irradiation and transmission electron microscopy (TEM) of cold spray deposited Cr coatings was performed at the Intermediate Voltage Electron Microscope (IVEM) facility at Argonne National Laboratory for preliminary investigation into the radiation damage tolerance of these materials for use in accident tolerance fuel cladding. The severely plastically deformed microstructure of the cold spray deposited Cr delayed the onset and growth of radiation induced defects when compared to an annealed coating simulating bulk Cr. Evidence to support this conclusion was based on defect density and defect size measurements of TEM images obtained at different irradiation intervals.

To evaluate outcomes of thrombectomy in patients with a basilar artery occlusion (BAO) and mild symptoms, defined by an initial National Institutes of Health Stroke Scale (NIHSS) score ≤6.We performed a retrospective analysis of a multicenter prospective cohort of consecutive patients with acute ischemic stroke with BAO who underwent thrombectomy. We compared baseline and procedural characteristics, as well as outcomes between patients with BAO with an NIHSS score ≤6 and6. Multivariate analyses were performed to determine baseline and procedural predictors of good outcome (modified Rankin Scale score 0-2) among patients with an NIHSS score ≤6.A total of 269 patients were included: 50 (19%) had an initial NIHSS score ≤6 and 219 (81%) had an NIHSS score6. Patients with mild strokes (NIHSS score ≤6) had better outcomes (68% of modified Rankin Scale score 0-2 vs. 27% for NIHSS score6; P0.0001), lower mortality (14% vs. 48; P0.0001) and fewer parenchymal hematomas at day 1 (0% vs. 10%; P = 0.016). A multivariate analysis identified the following predictors for good outcome among patients with BAO with an NIHSS score ≤6: younger age, fewer passes, a cardioembolic cause, and the absence of need for angioplasty/stenting.Thrombectomy seems to be safer and more effective for mild BAO strokes with NIHSS score ≤6 than for more severe patients. Even although thrombectomy showed high rates of recanalization, a substantial proportion (32%) nevertheless had a poor long-term clinical outcome. The number of passes, patient's age, and stroke cause seem to be predictors of clinical outcome.

Background and Purpose: Acute ischemic stroke and large vessel occlusion can be concurrent with the coronavirus disease 2019 (COVID-19) infection. Outcomes after mechanical thrombectomy (MT) for large vessel occlusion in patients with COVID-19 are substantially unknown. Our aim was to study early outcomes after MT in patients with COVID-19. Methods: Multicenter, European, cohort study involving 34 stroke centers in France, Italy, Spain, and Belgium. Data were collected between March 1, 2020 and May 5, 2020. Consecutive laboratory-confirmed COVID-19 cases with large vessel occlusion, who were treated with MT, were included. Primary investigated outcome: 30-day mortality. Secondary outcomes: early neurological improvement (National Institutes of Health Stroke Scale improvement ≥8 points or 24 hours National Institutes of Health Stroke Scale 0–1), successful reperfusion (modified Thrombolysis in Cerebral Infarction grade ≥2b), and symptomatic intracranial hemorrhage. Results: We evaluated 93 patients with COVID-19 with large vessel occlusion who underwent MT (median age, 71 years [interquartile range, 59–79]; 63 men [67.7%]). Median pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were 17 (interquartile range, 11–21) and 8 (interquartile range, 7–9), respectively. Anterior circulation acute ischemic stroke represented 93.5% of cases. The rate modified Thrombolysis in Cerebral Infarction 2b to 3 was 79.6% (74 patients [95% CI, 71.3–87.8]). Thirty-day mortality was 29% (27 patients [95% CI, 20–39.4]). Early neurological improvement was 19.5% (17 patients [95% CI, 11.8–29.5]), and symptomatic intracranial hemorrhage was 5.4% (5 patients [95% CI, 1.7–12.1]). Patients who died at 30 days exhibited significantly lower lymphocyte count, higher levels of aspartate, and LDH (lactate dehydrogenase). After adjustment for age, initial National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and successful reperfusion, these biological markers remained associated with increased odds of 30-day mortality (adjusted odds ratio of 2.70 [95% CI, 1.21–5.98] per SD-log decrease in lymphocyte count, 2.66 [95% CI, 1.22–5.77] per SD-log increase in aspartate, and 4.30 [95% CI, 1.43–12.91] per SD-log increase in LDH). Conclusions: The 29% rate of 30-day mortality after MT among patients with COVID-19 is not negligible. Abnormalities of lymphocyte count, LDH and aspartate may depict a patient’s profiles with poorer outcomes after MT. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT04406090.

The performance and safety of human robot interaction (HRI) can be improved by using subject-specific movement prediction. Typical models include biomechanical (parametric) or black-box (non-parametric) models. The current work aims to investigate the benefits and drawbacks of these approaches by comparing elbow-joint torque predictions based on electromyography signals of the elbow flexors and extensors. To this end, a parameterized biomechanical model is compared to a non-parametric (Gaussian-process) approach. Both models showed adequate results in predicting the elbow-joint torques. While the non-parametric model requires minimal modeling effort, the parameterized biomechanical model can lead to deeper insight of the underlying subject specific musculoskeletal system.

Background and Purpose: Although the efficacy of endovascular treatment (EVT) in patients with anterior circulation ischemic stroke (AIS) is well documented, early neurological deterioration after EVT remains a serious issue associated with poor outcome. Besides obvious causes, such as lack of reperfusion, procedural complications, or parenchymal hemorrhage, early neurological deterioration may remain unexplained (UnEND). Our aim was to investigate predictors of UnEND after EVT in patients with AIS. Methods: Patients who underwent EVT for AIS, with an initial National Institutes of Health Stroke Scale score >5, Alberta Stroke Program Early CT Score ≥6, and included in a multicenter prospective observational registry were analyzed. Predictors of UnEND, defined as ≥4-point increase in the National Institutes of Health Stroke Scale score between baseline and day 1 after EVT, were determined via center-adjusted analyses. Results: Among the 1925 included in the analysis, 128 UnEND (6.6%) were recorded. In multivariate analysis, predictors of UnEND were diabetes mellitus (odds ratio [OR], 2.17 [95% CI, 1.32–3.56]), prestroke modified Rankin Scale score ≥2 (OR, 2.22 [95% CI, 1.09–4.55]), general anesthesia (OR, 2.55 [95% CI, 1.51–4.30]), admission systolic blood pressure (OR, 1.10 [95% CI, 1.01–1.20]), age (OR, 1.38 [95% CI, 1.14–1.67]), number of passes (OR, 1.16 [95% CI, 1.04–1.28]), direct admission or not to a comprehensive stroke center (OR, 0.49 [95% CI, 0.30–0.81]), and initial National Institutes of Health Stroke Scale score (OR, 0.65 [95% CI, 0.52–0.81]). Conclusions: Severely impaired AIS patients with nonmodifiable factors are more likely to develop UnEND. Some modifiable predictors of UnEND such as the number of EVT passes could be the object of improvement in AIS management.

Handling flexible, one-dimensional objects like tubes, cables, strings or ropes usually requires to quickly predict the dynamic behavior of the object. Tasks of robotic arms manipulating flexible one-dimensional objects often take place on a workspace with a flat surface. Here, the dynamic behavior of the bending, flexible object is governed by friction between the object and the surface. In this paper, we formulate a model based on differential geometry that predicts the dynamic behavior of an elastic one-dimensional object on a 2D workspace with friction. Orientation and position of one end of the object are prescribed by the gripper movement. We present algorithmic and numeric optimizations of the computation and provide details on our parallel implementation which achieves real-time performance. We showcase different features of the model and validate the modeling approach by comparison with experiments.

In this paper, we present a novel approach to the approximate solution of elliptic partial differential equations on compact submanifolds of $\mathbb {R}^{d}$ , particularly compact surfaces and the surface equation ${\Delta }_{\mathbb {M}} u - \lambda u=f$ . In the course of this, we reconsider differential operators on such submanifolds to deduce suitable penalty based functionals. These functionals are based on the residual of the equation in an integral representation, extended by a penalty on the first-order normal derivative. The general framework we develop is accompanied by error analysis and exemplified by numerical examples employing tensor product B-splines.

Energy minimization is one of the properties that make univariate splines so favorable in many problems of approximation and estimation; interpolation in and extrapolation from sparse data sites and smoothing of noisy data in particular. In this paper, we present a novel approach to approximate energy minimization on certain classes of submanifolds that gives rise to new methods for extrapolation and smoothing on submanifolds. To accomplish this, we minimize intrinsic functionals approximately by minimising a suitable extrinsic formulation of the functional augmented by a penalty on the first order normal derivative. The general framework we develop is accompanied by error analysis and exemplified by tensor product B-splines.

Background and Purpose: The efficiency of prehospital care chain response and the adequacy of hospital resources are challenged amid the coronavirus disease 2019 (COVID-19) outbreak, with suspected consequences for patients with ischemic stroke eligible for mechanical thrombectomy (MT). Methods: We conducted a prospective national-level data collection of patients treated with MT, ranging 45 days across epidemic containment measures instatement, and of patients treated during the same calendar period in 2019. The primary end point was the variation of patients receiving MT during the epidemic period. Secondary end points included care delays between onset, imaging, and groin puncture. To analyze the primary end point, we used a Poisson regression model. We then analyzed the correlation between the number of MTs and the number of COVID-19 cases hospitalizations, using the Pearson correlation coefficient (compared with the null value). Results: A total of 1513 patients were included at 32 centers, in all French administrative regions. There was a 21% significant decrease (0.79; [95%CI, 0.76–0.82]; P P P R 2 −0.51; P =0.04). Patients treated during the COVID outbreak were less likely to receive intravenous thrombolysis and to have unwitnessed strokes (both P Conclusions: Our study showed a significant decrease in patients treated with MTs during the first stages of the COVID epidemic in France and alarming indicators of lengthened care delays. These findings prompt immediate consideration of local and regional stroke networks preparedness in the varying contexts of COVID-19 pandemic evolution.

Here, we investigate the coupled thermomechanical fracture mechanisms of coated nuclear fuel claddings at Light Water Reactor (LWR) operating temperatures. These coated claddings are a highly attractive, near-term solution that address the demands for accident-tolerant fuel systems that provide greater oxidation resistance. However, the fracture mechanisms of these coatings, which may create channels for oxidation ingression, must be fully understood prior to implementation. Thus, high-temperature expanding plug experiments were conducted on coated cladding specimens at a temperature of 315 °C, consistent with the operating environment of LWRs. In-situ thermomechanical deformation was measured with stereo digital image correlation during heating and mechanical testing to separately resolve contributions of thermal and mechanical strain. Image correlation, supported by acoustic emissions (AE) detection, was also leveraged to track cracking activity during loading. Coating fracture was found to initiate at total hoop strains of 0.34%. The thermal deformation of the coated claddings was investigated via finite element simulations, revealing a bidirectional stress-state within the coating with axial and circumferential strains of 0.026 and 0.031%. This bidirectional stress-state was attributed with the generation of off-axis fracture pattern within the coating as identified via post-experiment scanning electron microscopy. Thus, this study unveiled critical, coupled thermomechanical mechanisms governing the coating fracture of coated claddings at LWR temperatures.

Annealing of attrition-milled, electrolytically produced chromium powder has been investigated to improve cold spray coating deposition efficiency of pure chromium on Zr-alloy substrate for light water reactors with the goal of enhancing high-temperature oxidation resistance. The annealing heat treatment at 800 °C for 5 h induced microstructural transitions in the powder such as the development of equiaxed grains and strain relaxation, both associated with a measured decrease in nano-hardness. Deposition efficiency of the annealed powder was about three times more than the as-received electrolytic Cr powder. In addition, the utilization of the annealed powder reduced substrate deformation effects. A qualitative explanation of the effects powder microstructure on the cold spray deposition process in terms of the resulting coating microstructures and deposition efficiencies has been introduced. Finally, high-temperature exposure tests indicated that oxidation resistance of these Cr coatings was comparable to that previously reported for those produced using gas-atomized Cr powder. This study suggests that annealing of electrolytic Cr powder is a practical and economically favorable pathway to produce oxidation-resistant cold spray Cr coatings. More generally, use of the widely available electrolytic and mechanically milled powder vastly opens scope of cold spray deposition process, where atomized powders may not be either available or challenging to produce.

The cold spray process has been investigated for the deposition of FeCrAl coatings on optimized ZIRLO™ fuel cladding tubes in order to enhance oxidation resistance at high temperatures (>1000 °C) that would be encountered in loss of coolant accident (LOCA) scenarios. The FeCrAl alloy provides excellent oxidation resistance, however Fe forms a eutectic with Zr at temperatures as low as 928 °C resulting in massive inter-diffusion and associated melting. Therefore, a Mo interlayer coating was developed also using the cold spray process to serve as a diffusion barrier between the Fe-based coating and the Zr-alloy substrate. To achieve a combination of desired properties for the dual-layered coating-substrate, an optimization study of spray parameters such as propellant gas pre-heat temperature, helical spray speed, and the number of spray passes was conducted. This parametric study was aimed at achieving dense coatings with desired thickness and coverage of the substrate, and good adhesion of the Mo interlayer coating with subsequent top FeCrAl coating and the Zr-alloy substrate. The optimal FeCrAl-Mo coating protected the Zr-alloy cladding tubes from oxidation at high temperatures of 1200 °C, while at the same time preventing diffusion-induced eutectic melting in the substrate.

BackgroundStudies have suggested that collateral status modifies the effect of successful reperfusion on functional outcome after endovascular therapy (EVT). We aimed to assess the association between collateral status and EVT outcomes and to investigate whether collateral status modified the effect of successful reperfusion on EVT outcomes.MethodsWe used data from the ongoing, prospective, multicenter Endovascular Treatment in Ischemic Stroke (ETIS) Registry. Collaterals were graded according to the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) guidelines. Patients were divided into two groups based on angiographic collateral status: poor (grade 0–2) versus good (grade 3–4) collaterals.ResultsAmong 2020 patients included in the study, 959 (47%) had good collaterals. Good collaterals were associated with favorable outcome (90-day modified Rankin Scale (mRS) 0–2) (OR 1.5, 95% CI 1.19 to 1.88). Probability of good outcome decreased with increased time from onset to reperfusion in both good and poor collateral groups. Successful reperfusion was associated with higher odds of favorable outcome in good collaterals (OR 6.01, 95% CI 3.27 to 11.04) and poor collaterals (OR 5.65, 95% CI 3.32 to 9.63) with no significant interaction. Similarly, successful reperfusion was associated with higher odds of excellent outcome (90-day mRS 0–1) and lower odds of mortality in both groups with no significant interaction. The benefit of successful reperfusion decreased with time from onset in both groups, but the curve was steeper in the poor collateral group.ConclusionsCollateral status predicted functional outcome after EVT. However, collateral status on the pretreatment angiogram did not decrease the clinical benefit of successful reperfusion.

The cold spray coating process has been developed at the University of Wisconsin-Madison for the deposition of oxidation-resistant coatings on zirconium alloy light water reactor fuel cladding with the goal of improving accident tolerance during loss of coolant scenarios. Coatings of metallic (Cr), alloy (FeCrAl), and ceramic (Ti2AlC) materials were successfully deposited on zirconium alloy flats and cladding tube sections by optimizing the powder size, gas preheat temperature, pressure and composition, and other process parameters. The coatings were dense and exhibited excellent adhesion to the substrate. Evaluation of the samples after high-temperature oxidation tests at temperatures up to 1300°C showed that the cold spray coatings significantly mitigate oxidation kinetics because of the formation of thin passive oxide layers on the surface. The results of the study indicate that the cold spray coating process is a viable near-term option for developing accident-tolerant zirconium alloy fuel cladding.