A SIFT approach for analysing failure by delamination and disbonding in composite structures

A strain invariant failure theory (SIFT) has been developed to predict resin failure in damaged and pristine composite structures The finite element (FE) analysis in this work uses shell elements consistent with common practice in the aeronautical industry. The new SIFT is similar in nature to a characteristic length method that requires a matched finite element mesh. It samples the strains in brick elements lofted between two layers of shell elements, each representing half of the damaged laminate in the failure critical zone. Experimental tests involving three laminate materials have been carried out to validate t he modified SIFT approach for notched laminates, including single and multiple level delamination tests, and stiffened panel tests under shear or compression load. These results are summarised in a table. Square and rectangle single delamination tests are presented in more detail and indicate that failure location and load predicted by the modified SIFT approach correlates well with the experimental results

Growth of nanowire arrays from micron-feature templates

Here, we present a two-step annealing procedure to imprint nanofeatures on SiO2 starting from metallic microfeatures. The first annealing transforms the microfeatures into gold nanoparticles and the second imprints these nanoparticles into the SiO2 layer with nanometric control. The resulting nanohole arrays show a high ensemble uniformity. As a potential application, the nanohole mask is used as a selective mask for the Ga self-assisted growth of GaAs nanowires (NWs). Thus, for the first time, a successful implementation of nano-self-imprinting that links high-throughput microlithography with bottom-up NW growth is shown. The beneficial hole morphology of the SiO2 mask promotes high Ga droplet contact angles with the silicon substrate and the formation of single droplets in the mask holes. This droplet predeposition configuration enables a high vertical yield of NWs. Thus, this article describes a new protocol to grow NW devices that combines simultaneously nanosized holes and parallel processing

Safety and outcomes of routine endovascular thrombectomy in large artery occlusion recorded in the SITS Register: An observational study

Background and objective We aimed to evaluate the safety and outcomes of thrombectomy in anterior circulation acute ischaemic stroke recorded in the SITS-International Stroke Thrombectomy Register (SITS-ISTR) and compare them with pooled randomized controlled trials (RCTs) and two national registry studies. Methods We identified centres recording >= 10 consecutive patients in the SITS-ISTR with at least 70% of available modified Rankin Scale (mRS) at 3 months during 2014-2019. We defined large artery occlusion as intracranial internal carotid artery, first and second segment of middle cerebral artery and first segment of anterior cerebral artery. Outcome measures were functional independence (mRS score 0-2) and death at 3 months and symptomatic intracranial haemorrhage (SICH) per modified SITS-MOST. Results Results are presented in the following order: SITS-ISTR, RCTs, MR CLEAN Registry and German Stroke Registry (GSR). Median age was 73, 68, 71 and 75 years; baseline NIHSS score was 16, 17, 16 and 15; prior intravenous thrombolysis was 62%, 83%, 78% and 56%; onset to reperfusion time was 289, 285, 267 and 249 min; successful recanalization (mTICI score 2b or 3) was 86%, 71%, 59% and 83%; functional independence at 3 months was 45.5% (95% CI: 44-47), 46.0% (42-50), 38% (35-41) and 37% (35-41), respectively; death was 19.2% (19-21), 15.3% (12.7-18.4), 29.2% (27-32) and 28.6% (27-31); and SICH was 3.6% (3-4), 4.4% (3.0-6.4), 5.8% (4.7-7.1) and not available. Conclusion Thrombectomy in routine clinical use registered in the SITS-ISTR showed safety and outcomes comparable to RCTs, and better functional outcomes and lower mortality than previous national registry studies.Peer reviewe

Safety and efficacy of sonothrombolysis for acute ischaemic stroke: a multicentre, double-blind, phase 3, randomised controlled trial

Background: Pulsed-wave ultrasound increases the exposure of an intracranial thrombus to alteplase (recombinant tissue plasminogen activator), potentially facilitating early reperfusion. We aimed to ascertain if a novel operator-independent transcranial ultrasound device delivering low-power high-frequency ultrasound could improve functional outcome in patients treated with alteplase after acute ischaemic stroke. Methods: We did a multicentre, double-blind, phase 3, randomised controlled trial (CLOTBUST-ER) at 76 medical centres in 14 countries. We included patients with acute ischaemic stroke (National Institutes of Health Stroke Scale score ≥10) who received intravenous thrombolysis (alteplase bolus) within 3 h of symptom onset in North America and within 4·5 h of symptom onset in all other countries. Participants were randomly allocated (1:1) via an interactive web response system to either active ultrasound (2 MHz pulsed-wave ultrasound for 120 min [sonothrombolysis]; intervention group) or sham ultrasound (control group). Ultrasound was delivered using an operator-independent device, which had to be activated within 30 min of the alteplase bolus. Participants, investigators, and those assessing outcomes were unaware of group assignments. The primary outcome was improvement in the modified Rankin Scale score at 90 days in patients enrolled within 3 h of symptom onset, assessed in the intention-to-treat population as a common odds ratio (cOR) using ordinal logistic regression shift analysis. This trial is registered with ClinicalTrials.gov, number NCT01098981. The trial was stopped early by the funder after the second interim analysis because of futility. Findings: Between August, 2013, and April, 2015, 335 patients were randomly allocated to the intervention group and 341 patients to the control group. Compared with the control group, the adjusted cOR for an improvement in modified Rankin Scale score at 90 days in the intervention group was 1·05 (95% CI 0·77–1·45; p=0·74). 51 (16%) of 317 patients in the intervention group and 44 (13%) of 329 patients in the control group died (unadjusted OR 1·24, 95% CI 0·80–1·92; p=0·37) and 83 (26%) and 79 (24%), respectively, had serious adverse events (1·12, 0·79–1·60; p=0·53). Interpretation: Sonothrombolysis delivered by an operator-independent device to patients treated with alteplase after acute ischaemic stroke was feasible and most likely safe, but no clinical benefit was seen at 90 days. Sonothrombolysis could be further investigated either in randomised trials undertaken in stroke centres that are dependent on patient transfer for endovascular reperfusion therapies or in countries where these treatments cannot yet be offered as the standard of care

Endovascular equipoise shift in a phase III randomized clinical trial of sonothrombolysis for acute ischemic stroke

Background: Results of our recently published phase III randomized clinical trial of ultrasound-enhanced thrombolysis (sonothrombolysis) using an operator-independent, high frequency ultrasound device revealed heterogeneity of patient recruitment among centers. Methods: We performed a post hoc analysis after excluding subjects that were recruited at centers reporting a decline in the balance of randomization between sonothrombolysis and concurrent endovascular trials. Results: From a total of 676 participants randomized in the CLOTBUST-ER trial we identified 52 patients from 7 centers with perceived equipoise shift in favor of endovascular treatment. Post hoc sensitivity analysis in the intention-to-treat population adjusted for age, National Institutes of Health Scale score at baseline, time from stroke onset to tPA bolus and baseline serum glucose showed a significant (p < 0.01) interaction of perceived endovascular equipoise shift on the association between sonothrombolysis and 3 month functional outcome [adjusted common odds ratio (cOR) in centers with perceived endovascular equipoise shift: 0.22, 95% CI 0.06–0.75; p = 0.02; adjusted cOR for centers without endovascular equipoise shift: 1.20, 95% CI 0.89–1.62; p = 0.24)]. After excluding centers with perceived endovascular equipoise shift, patients randomized to sonothrombolysis had higher odds of 3 month functional independence (mRS scores 0–2) compared with patients treated with tPA only (adjusted OR: 1.53; 95% CI 1.01–2.31; p = 0.04). Conclusion: Our experience in CLOTBUST-ER indicates that increasing implementation of endovascular therapies across major academic stroke centers raises significant challenges for clinical trials aiming to test noninterventional or adjuvant reperfusion strategies

Primary stroke prevention worldwide: translating evidence into action

Stroke is the second leading cause of death and the third leading cause of disability worldwide and its burden is increasing rapidly in low-income and middle-income countries, many of which are unable to face the challenges it imposes. In this Health Policy paper on primary stroke prevention, we provide an overview of the current situation regarding primary prevention services, estimate the cost of stroke and stroke prevention, and identify deficiencies in existing guidelines and gaps in primary prevention. We also offer a set of pragmatic solutions for implementation of primary stroke prevention, with an emphasis on the role of governments and population-wide strategies, including task-shifting and sharing and health system re-engineering. Implementation of primary stroke prevention involves patients, health professionals, funders, policy makers, implementation partners, and the entire population along the life course

Rivaroxaban for secondary stroke prevention in patients with embolic strokes of undetermined source : Design of the NAVIGATE ESUS randomized trial

Peer reviewe

Characterization of patients with embolic strokes of undetermined source in the NAVIGATE ESUS randomized trial

Background: The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS. Aims: We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups. Methods: We enrolled 7213 patients at 459 sites in 31 countries. Prespecified subgroups for primary safety and efficacy analyses included age, sex, race, global region, stroke or transient ischemic attack prior to qualifying event, time to randomization, hypertension, and diabetes mellitus. Results: Mean age was 66.9 ± 9.8 years; 24% were under 60 years. Older patients had more hypertension, coronary disease, and cancer. Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infarction. Women comprised 38% of participants and were older than men. Patients from East Asia were oldest whereas those from Latin America were youngest. Patients in the Americas more frequently were on aspirin prior to the qualifying stroke. Acute cortical infarction was more common in the United States, Canada, and Western Europe, whereas prior radiographic infarctions were most common in East Asia. Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke, with earliest enrollments in Asia and Eastern Europe. Conclusions: NAVIGATE-ESUS is the largest randomized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS. The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research

Топическая гипотензивная терапия, предшествующая хирургическому этапу лечения глаукомы

PURPOSE. To analyze specific clinical and epidemiological parameters of patients with primary open-angle glaucoma (POAG) who were admitted for surgical treatment to the ophthalmological hospital of a multi-specialty in-patient medical center in the period of 2021–2022 years.METHODS. The retrospective elective study analyzed data from 95 patients (95 eyes) with different stages of primary open-angle glaucoma (mean age 73 [67; 80] years old) who were hospitalized for surgical treatment of the disease in 2021–2022. In addition to standard ophthalmological examination, several clinical and epidemiologic characteristics were analyzed in detail, including the prevalence of prescriptions for antiglaucoma hypotensive drugs. Comparison of the obtained results with the data of similar procedures performed in the period from 2005 to 2016 was carried out.RESULTS. The number of main comorbid somatic diseases was on average 3 (2; 4), and comparison of conditions by disease stage revealed no significant differences (p>0.05). Mean duration of the disease (according to anamnesis) was 8 (4; 13) years and was longer in comparison with similar results from 2005–2006 presented in a previous study. The period preceding the first surgical intervention was 5 (2; 10) years and was statistically significantly longer in those with moderate stage of POAG (9 [3; 14] years) compared to those with early stage of POAG (4 [3; 5] years, p<0.05) and advanced stage of POAG (6 [0; 10] years, p<0.04). The average number of drugs at the time of hospitalization for surgical treatment has increased significantly in comparison with the data of the early-mid 2000s and amounted to 4 (3; 4) units (stage I glaucoma — 3 [3; 4]; stage II — 4 [3; 4]; stage III — 4 [3; 4] units), with no statistically significant difference (p1,2=0.64; p1,3=0.21; p2,3=0.42, respectively).CONCLUSION. Unwarranted long-term use of a large number of antiglaucoma drugs ("maximal medication therapy adherence") is a significant problem in modern glaucomatology and can evidently affect future prognosis of the disease.ЦЕЛЬ. Проанализировать отдельные клинико-эпидемиологические показатели пациентов с первичной открытоугольной глаукомой (ПОУГ), поступавших на оперативное лечение в офтальмологический стационар многопрофильного медицинского учреждения в течение 2021–2022 гг.МЕТОДЫ. Ретроспективному выборочному обследованию были подвергнуты данные 95 пациентов (95 глаз) с разными стадиями ПОУГ (средний возраст — 73 [67; 80] года), поступавшие для оперативного лечения заболевания. Помимо обследования был проанализирован ряд клинико-эпидемиологических характеристик, включающих, в частности, распространенность назначений антиглаукомных гипотензивных препаратов. Выполнено сравнение с данными аналогичных процедур, установленными в период с 2005 по 2016 гг.РЕЗУЛЬТАТЫ. Количество основных сопутствующих соматических заболеваний составило 3 (2; 4), а сравнение состояний по стадиям болезни не выявило достоверных отличий (р>0,05). Средний срок заболевания составил 8 (4; 13) лет, что при сравнении с аналогичными результатами 2005–2006 гг. было более продолжительным по времени. Период, предшествующий выполнению первого оперативного вмешательства, составил 5 (2; 10) лет, и был статистически достоверно более длительным у лиц с развитой стадией ПОУГ (9 [3; 14] лет), по сравнению с лицами с начальной (4 [3; 5] года, p<0,05) и далекозашедшей стадией (6 [0; 10] лет, p<0,04). Среднее число препаратов на момент госпитализации значительно увеличилось, по сравнению с данными начала-середины 2000-х годов и составило 4 (3; 4) ед. (I ст. глаукомы — 3 [3; 4]; II ст. — 4 [3; 4]; III ст. — 4 [3; 4] ед.), не отличаясь статистически достоверно (р1,2=0,64; р1,3=0,21; р2,3=0,42 соответственно). ЗАКЛЮЧЕНИЕ. Неоправданное продолжительное использование большого количества антиглаукомных препаратов (приверженность к применению максимальной медикаментозной терапии) представляет значимую проблему в современной глаукоматологии и, очевидно, может влиять на прогноз заболевания