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Background Flow diversion has revolutionized the management of wide‐necked intracranial aneurysms (IAs). We aimed to assess the effectiveness and safety of the new generation 64‐wire Surpass Evolve for the treatment of unruptured small/medium‐sized IAs. Methods and Results This is a subanalysis from the SEASE (Safety and Effectiveness Assessment of the Surpass Evolve) registry, an observational cohort study including 15 academic institutions in North America and Europe between July 2020 and October 2022. Patients with wide‐necked saccular IAs, measuring

Background The presence of an incorporated branch as well as its anatomical relationship to the intracranial aneurysms (IAs) and the parent artery may affect the occlusion outcome following flow diversion. This study evaluated the safety and effectiveness of the cobalt‐chromium Surpass Evolve (Stryker), a 64‐wire flow diversion device for the treatment of IAs with incorporated branches. Methods This subanalysis uses data from the SEASE (Safety and Effectiveness Assessment of Surpass Evolve) registry to retrieve data related to IAs with incorporated branches. Those IAs were classified by a core lab into 4 categories based on their anatomical relationship to the parent artery and branch: (A) sidewall anatomic, (B) sidewall hemodynamic, (C) neck branch, and (D) dome branch. We compared the outcomes based on their incorporated branch's relation to the dome (A–C versus D). Results This study included 67 patients and IAs. Most IAs were in the posterior communicating artery (46.3%), with a median size of 4.35 mm. Age, sex, comorbidities, baseline functional‐status, and IA features were similar between the 2 groups. Among those, 53 (79.1%) had branches emerging from the dome, and 14 (20.9%) had branches originating from other locations (A = 7, B = 2, and C = 5). At a median imaging follow‐up of 10.5 months, complete occlusion was lower in IAs with a branch from the sac compared with those with the neck (60.8% versus 92.9%; P = 0.026), with an overall occlusion of 67.7%. Thromboembolic and hemorrhagic complications, as well as retreatment, were reported in 1.6% and 3.1% of cases, respectively, with no significant differences between groups. Conclusion Our analysis underscores the influence of branch origin on occlusion rates, with the neck‐originating branch demonstrating higher occlusion rates. These insights emphasize the role of anatomical considerations in treatment strategies, follow‐up timelines, and designing future clinical trials. Further studies are warranted to explore these variations across different flow diversion technologies.

Abstract Understanding the interaction between Mars and the solar wind is crucial for comprehending the atmospheric evolution and climate change on Mars. To gain a comprehensive understanding of the Martian plasma environment, global numerical simulations are essential in addition to spacecraft observations. However, there are still discrepancies among different simulation models. This study investigates how these discrepancies stem from the considered physical processes and numerical implementations. We compare two global multispecies MHD models: the “Sun model” based on the BATS‐R‐US code and the “Sakata model” based on a newly developed multifluid model MAESTRO. By employing the same typical upstream conditions and the same neutral atmosphere for current Mars, along with similar numerical implementations such as inner boundary conditions, we obtain simulation results that exhibit unprecedented agreement between the two models. The dayside results are nearly identical, especially along the subsolar line, indicating the robustness of MHD models to predict dayside interaction under given upstream conditions and ionosphere assumptions. The escape rates of planetary ions are also in good agreement. However, discrepancies remain in the terminator and nightside regions. Detailed numerical implementations, including inner boundary conditions, magnetic field divergence control methods, and radial resolutions, are shown to influence certain aspects of the results greatly, such as magnetotail configuration and ion diffusion.

Background Flow diversion (FD) has emerged as an effective treatment option for intracranial aneurysms. However, there is limited evidence regarding its safety and efficacy specifically for distal and small‐artery aneurysms of the posterior circulation. This study aimed to investigate the outcomes of FD for aneurysms arising from the posterior inferior cerebellar artery, anterior inferior cerebellar artery, superior cerebellar artery, and the P2 and P3 segments of the posterior cerebral artery. Methods This is a subanalysis of the Post‐FD (Posterior Circulation Aneurysms Treated With Flow Diversion) registry, highlighting distal aneurysms in the posterior inferior cerebellar artery, anterior inferior cerebellar artery, superior cerebellar artery, and the P2 and P3 segments of the posterior cerebral artery treated with FD. Aneurysm characteristics and patient outcomes were described for the total series, and a more focused analysis comparing fusiform/dissecting versus saccular aneurysms was performed. The primary treatment outcome was complete aneurysm occlusion (Raymond–Roy class 1). Primary safety outcome was major ischemic/hemorrhagic stroke following FD. Secondary outcomes included functional outcome, aneurysm retreatment, and in‐stent stenosis. Results Overall, 36 patients with 36 aneurysms were treated with FD, with a median age of 60.0 years (interquartile range [IQR], 52.8—65.3 years). Of those, 13 were fusiform/dissecting, while 23 were saccular aneurysms. Complete occlusion was achieved in 78.1% for all aneurysms at a median follow‐up of 14.0 months (IQR, 9.3–48.6 months). There was a nonsignificant trend in rates of complete occlusion between fusiform/dissecting (91.7%) and saccular aneurysms (70%; P = 0.151). Major stroke was reported in 2 cases (5.6%) and in‐stent stenosis in 4 (11.1%), and retreatment was required for 4 aneurysms (11.4%) There was no difference in rates of major stroke, in‐stent stenosis, or retreatment between fusiform/dissecting and saccular aneurysms. Conclusion This study suggests the safety and feasibility of FD for distal aneurysms of the posterior circulation, particularly fusiform/dissecting aneurysms. Further larger‐scale studies are warranted to confirm these findings.

Gaussian Processes (GP) have become popular machine learning methods for kernel based learning on datasets with complicated covariance structures. In this paper, we present a novel extension to the GP framework using a contaminated normal likelihood function to better account for heteroscedastic variance and outlier noise. We propose a scalable inference algorithm based on the Sparse Variational Gaussian Process (SVGP) method for fitting sparse Gaussian process regression models with contaminated normal noise on large datasets. We examine an application to geomagnetic ground perturbations, where the state-of-art prediction model is based on neural networks. We show that our approach yields shorter predictions intervals for similar coverage and accuracy when compared to an artificial dense neural network baseline.

Background The rate of underlying ruptured aneurysms, complications, and their relevance to outcomes in “benign” perimesencephalic subarachnoid hemorrhage are not well known and underreported. Methods Retrospective analysis of patients with perimesencephalic subarachnoid hemorrhage from a large tertiary care center (2007–2022). Results Eighty‐one patients were included with mean age of 55.5 ± 10.3 years. An underlying ruptured aneurysm was diagnosed in 5 patients (6.2%); 3 (60%) had negative computed tomography angiography and they were detected only in digital subtraction angiography (2 on initial digital subtraction angiography and 1 on follow‐up digital subtraction angiography). The most common complication was vasospasm in 25/81 patients (31%), and the majority 21/25 (84%) were asymptomatic. Symptomatic vasospasm occurred at a significantly higher rate among patients with underlying aneurysm (40% versus 2.6%; P = 0.01). Hydrocephalus occurred in 10% of patients, all within 1 day, but at a higher rate in the aneurysmal group (40% versus 8%; P = 0.07). A total of 88% of patients had modified Rankin scale score 0–2 at discharge, but at a significantly higher rate in nonaneurysmal patients (91% versus 40%; P = 0.01). An underlying aneurysm, hydrocephalus, and symptomatic vasospasm were associated with poor functional status (odds ratio [OR] = 14.7 [2.1–104]; P = 0.007, OR = 22.6 [4.2–123.5]; P

Parker Solar Probe observations reveal that the near-Sun space is almost filled with magnetic switchbacks (“switchbacks” hereinafter), which may be a major contributor to the heating and acceleration of solar wind. Here, for the first time, we develop an analytic model of an axisymmetric switchback with uniform magnetic field strength. In this model, three parameters control the geometry of the switchback: height (length along the background magnetic field), width (thickness along radial direction perpendicular to the background field), and the radial distance from the center of switchback to the central axis, which is a proxy of the size of the switchback along the third dimension. We carry out 3D magnetohydrodynamic simulations to investigate the dynamic evolution of the switchback. Comparing simulations conducted with compressible and incompressible codes, we verify that compressibility, i.e., parametric decay instability, is necessary for destabilizing the switchback. Our simulations also reveal that the geometry of the switchback significantly affects how fast the switchback destabilizes. The most stable switchbacks are 2D-like (planar) structures with large aspect ratios (length to width), consistent with the observations. We show that when plasma beta ( β ) is smaller than one, the switchback is more stable as β increases. However, when β is greater than 1, the switchback becomes very unstable as the pattern of the growing compressive fluctuations changes. Our results may explain some of the observational features of switchbacks, including the large aspect ratios and nearly constant occurrence rates in the inner heliosphere.

ImportanceStroke-to-recanalization time is a strong predictor of outcomes in anterior circulation large-vessel occlusion (LVO). The authors aimed to evaluate functional outcomes in early (

Introduction Flow diversion (FD) has emerged as an effective treatment option for intracranial aneurysms (IAs). However, there is limited evidence regarding its safety and efficacy specifically for distal aneurysms of the posterior circulation including posterior inferior cerebellar artery (PICA), anterior inferior cerebellar artery (AICA), superior cerebellar artery (SCA), and the P2 and P3 segment of the posterior cerebral artery (PCA). This study aimed to investigate the outcomes of FD for these aneurysms. Methods A retrospective analysis of a multicentric observational registry was performed between 2014 and 2022. Patients harboring distal aneurysms of the posterior circulation including the PICA, AICA, SCA, and PCA P2‐3 treated with FD were included. Aneurysms characteristics and outcomes were calculated for the total series and a comparison was performed between fusiform/dissecting versus saccular aneurysms. The primary outcome was complete occlusion at last imaging follow up which was defined as per the Raymond Roy occlusion scale. Additional outcomes included the retreatment rate, and thromboembolic and hemorrhagic complications Results Overall, 36 patients with 36 aneurysms were treated with FD with a median age in years of 60.0 (interquartile range [IQR]: 52.8‐65.3 years). Of those, 13 were fusiform/dissecting while 23 were saccular IAs. Complete occlusion was achieved in 78.1% for all IAs at a median follow‐up of 14.0 months (IQR: 9.3‐48.6 months). There was no significant difference in rates of complete occlusion between fusiform/dissecting (91.7%) and saccular aneurysms (70%, p=0.151). Thromboembolic and hemorrhagic complications were observed in four cases (11.1%), and retreatment was required for four IAs (11.4%). There was no significant difference in rates of thromboembolic and hemorrhagic complications, or retreatment between fusiform/dissecting and saccular IAs Conclusion This study suggests the safety and efficacy of FD for distal aneurysms of the posterior circulation. Further larger‐scale studies are warranted to confirm these findings and to explore the long‐term safety and efficacy of FD in this specific aneurysm population.

Introduction Mechanical thrombectomy using stent retrievers and aspiration techniques has emerged as the standard of care for patients with acute ischemic stroke (AIS) secondary to emergent large vessel occlusion (LVO). This study intended to collect real‐world clinical evidence on the safety and effectiveness of endovascular treatment of AIS using the SOFIA Flow Plus 6F aspiration catheter. The primary endpoint was the proportion of subjects achieving mTICI ≥2b. Secondary endpoints included good functional outcomes (mRS 0‐2) at Day 90, revascularization time, first line and first pass mTICI ≥2b, occurrence of procedure‐related SAEs, vasospasm involving the accessed vascular tree, embolization to new territories (ENTs), symptomatic intracerebral hemorrhage (sICH) within 24 hours and mortality at Day 90. Methods SOFAST was a prospective, multicenter, single‐arm, observational post‐market study. The enrolled subjects were ≥21 and ≤85 years with large vessel (ICA or MCA) proximal occlusion, pre‐morbid mRS ≤1, baseline NIHSS ≥5, and for whom groin puncture was within 8 hours of symptom onset. A total of 108 patients were enrolled and treated using aspiration thrombectomy with SOFIA 6F as the first line treatment device. Patients were followed at 24 hours, 7 days/discharge, and 90 days post‐procedure. Cerebral angiography was performed pre‐ and post‐procedure. Clinical assessments included the NIHSS and mRS scales. All neurological, device‐related, and procedure‐related AEs and deaths were adjudicated by independent medical reviewers. Angiographic and other imaging data was adjudicated by an independent core laboratory. Results A total of 108 subjects were enrolled (mean age 62.7 years, 50% men) with a median NIHSS of 15.5. Of 108 subjects, 97.2% (105/108), 85.2% (92/108) and 55.6% (60/108) achieved mTICI ≥2b, ≥2c and =3 revascularization, respectively. With first line aspiration using SOFIA 6F, 87.0%, 79.6% and 52.8% achieved mTICI ≥2b, ≥2c and =3 revascularization, respectively. Median number of passes was one (range 1‐3). First pass rate of mTICI 2c or 3 using SOFIA 6F was 70.4%, of which 50.9% patients achieved mTICI score of 3. Mean duration from groin puncture to initial clot contact was 13.0 min and to successful revascularization was 17.9 min. Good functional outcome was achieved in 66.7% (72/108) of subjects at Day 90 (mRS 0‐2), procedure‐related SAEs occurred in 2.8% (3/108) of subjects and sICH in 0.9% (1/108) of subjects within 24 hours. Procedural vasospasm was recorded in in 9.3% (10/108) of subjects, and mortality in 7.4% (8/108) subjects at Day 90 (none related to the study device). No ENTs occurred. Conclusion In SOFAST study, mTICI ≥2b revascularization was achieved in the majority of patients at the end of all procedures (97.2%) and with first line treatment (87.0%) with a large fraction of these subjects achieving mTICI ≥2c following the first SOFIA 6F pass (70.4%). Durations from groin puncture to clot contact and successful revascularization were relatively short. The study presented high rates of good functional outcome at Day 90 and low rates of safety events. In summary, the study provides encouraging evidence of the safety and effectiveness of the SOFIA 6F device for aspiration thrombectomy in acute ischemic stroke subjects.

Abstract Background Cerebral infection with the protozoan Toxoplasma gondii (T. gondii) is responsible for inflammation of the central nervous system (CNS) contributing to subtle neuronal alterations. Albeit essential for brain parasite control, continuous microglia activation and recruitment of peripheral immune cells entail distinct neuronal impairment upon infection-induced neuroinflammation. PACAP is an endogenous neuropeptide known to inhibit inflammation and promote neuronal survival. Since PACAP is actively transported into the CNS, we aimed to assess the impact of PACAP on the T. gondii-induced neuroinflammation and subsequent effects on neuronal homeostasis. Methods Exogenous PACAP was administered intraperitoneally in the chronic stage of T. gondii infection, and brains were isolated for histopathological analysis and determination of pathogen levels. Immune cells from the brain, blood, and spleen were analyzed by flow cytometry, and the further production of inflammatory mediators was investigated by intracellular protein staining as well as expression levels by RT-qPCR. Neuronal and synaptic alterations were assessed on the transcriptional and protein level, focusing on neurotrophins, neurotrophin-receptors and signature synaptic markers. Results Here, we reveal that PACAP administration reduced the inflammatory foci and the number of apoptotic cells in the brain parenchyma and restrained the activation of microglia and recruitment of monocytes. The neuropeptide reduced the expression of inflammatory mediators such as IFN-γ, IL-6, iNOS, and IL-1β. Moreover, PACAP diminished IFN-γ production by recruited CD4+ T cells in the CNS. Importantly, PACAP promoted neuronal health via increased expression of the neurotrophin BDNF and reduction of p75NTR, a receptor related to neuronal cell death. In addition, PACAP administration was associated with increased expression of transporters involved in glutamatergic and GABAergic signaling that are particularly affected during cerebral toxoplasmosis. Conclusions Together, our findings unravel the beneficial effects of exogenous PACAP treatment upon infection-induced neuroinflammation, highlighting the potential implication of neuropeptides to promote neuronal survival and minimize synaptic prejudice.

Most stars generate winds and move through the interstellar medium that surrounds them. This movement creates a cocoon formed by the deflection of these winds that envelops and protects the stars. We call these “cocoons” astrospheres. The Sun has its own cocoon, the heliosphere. The heliosphere is an immense shield that protects the Solar System from harsh, galactic radiation. The radiation that enters the heliosphere affects life on Earth as well as human space exploration. Galactic cosmic rays are the dominant source of radiation and principal hazard affecting space missions within our Solar System. Current global heliosphere models do not successfully predict the radiation environment at all locations or under different solar conditions. To understand the heliosphere’s shielding properties, we need to understand its structure and large-scale dynamics. A fortunate confluence of missions has provided the scientific community with a treasury of heliospheric data. However, fundamental features remain unknown. The vision of the Solar wind with Hydrogen Ion charge Exchange and Large-Scale Dynamics (SHIELD) DRIVE Science Center is to understand the nature and structure of the heliosphere. Through four integrated research thrusts leading to the global model, SHIELD will: 1) determine the global nature of the heliosphere; 2) determine how pickup ions evolve from “cradle to grave” and affect heliospheric processes; 3) establish how the heliosphere interacts with and influences the Local Interstellar Medium (LISM); and 4) establish how cosmic rays are filtered by and transported through the heliosphere. The key deliverable is a comprehensive, self-consistent, global model of the heliosphere that explains data from all relevant in situ and remote observations and predicts the radiation environment. SHIELD will develop a “digital twin” of the heliosphere capable of: (a) predicting how changing solar and LISM conditions affect life on Earth, (b) understanding the radiation environment to support long-duration space travel, and (c) contributing toward finding life elsewhere in the Galaxy. SHIELD also will train the next-generation of heliophysicists, a diverse community fluent in team science and skilled working in highly transdisciplinary collaborative environments.

The charge exchange between the interstellar medium and the solar wind plasma is crucial for determining the structures of the heliosphere. Since both the neutral-ion and neutral–neutral collision mean free paths are either comparable to or larger than the size of the heliosphere, the neutral phase space distribution can deviate far away from the Maxwellian distribution. A kinetic description for the neutrals is crucial for accurately modeling the heliosphere. It is computationally challenging to run three-dimensional time-dependent kinetic simulations due to the large number of macroparticles. In this paper, we present the new highly efficient Solar Wind with Hydrogen Ion Exchange and Large-scale Dynamics-2 model with a kinetic model of neutrals and a magnetohydrodynamic model for the ions and electrons. To improve the simulation efficiency, we implement adaptive mesh refinement and particle splitting and merging algorithms for the neutral particles to reduce the particle number that is required for an accurate simulation. We present several tests to verify and demonstrate the capabilities of the model.

Ly α absorption profiles have been used to detect astrospheres and heliospheric absorption from the hydrogen wall and heliotail. Using magnetohydrodynamic models of the heliosphere, we can compare simulated to observed Ly α profiles to probe the neutral hydrogen within and near the heliosphere. There is an ongoing controversy whether the heliosphere has a long “comet-like” tail or a short “croissant-like” tail. Here we present the first Ly α absorption investigation using a croissant-like heliosphere. With identical boundary conditions we compare the BU model, which presents a croissant-like tail, and the Moscow model, which presents a comet-like tail. The BU and Moscow models present nearly identical Ly α profiles toward nose targets ( α Cen and 36 Oph). Differences in Ly α profiles are shown toward the tail target (HD 35296). Despite the shortened heliotail of the croissant model, significant downwind heliosheath absorption is seen, just 5% shallower and shifted by 4 km s ^−1 . This implies that an extended tail model is not required to reproduce the heliosheath Ly α absorption observations. Finer observation gratings may be able to resolve this shift. Additionally, when using higher interstellar medium (ISM) neutral and plasma densities and lower magnetic field (∣ B _LISM ∣ = 3.2 μ G, α _BV ≈ 40°) than in the Moscow model, we find better agreement with observed Ly α profiles. None of the models presented show agreement in all directions simultaneously. Furthermore, we show that for the ISM conditions with the least certainty ( n _p,LISM , n _H,LISM , T _LISM , B _LISM ), B _LISM has the most significant effect on the structure of the hydrogen wall and Ly α profiles.

Introduction Large vessel occlusion (LVO) is estimated to account for up to 39% of all ischemic strokes with 62% of them resulting in post‐ischemic stroke dependency and 96% of all post‐ischemic stroke mortality. Advanced imaging modalities and efficient stroke systems of care have resulted in faster reperfusion times. There is however limited data on the outcomes of thrombectomy as a function of age. We present a retrospective analysis on thrombectomy in younger (age 18–49 years) versus older (age >50 years) patients. Methods Retrospective single center study with population being identified using our procedural database and “SlicerDicer” tool on EPIC from 2017–2021. Patients who underwent mechanical thrombectomy were divided into 2 groups based on age. Younger group consists of patients between the ages 18–49 while older group is 50 and over. Primary outcome of the study was to identify good clinical outcome as defined by mRS of 0–2 in both groups. Secondary outcomes included rate of favorable reperfusion defined by TICI 2b‐3, symptomatic ICH and mortality rate. Results > We have identified 48 patients between the age of 18–49 and 436 over the age of 50. > We found that median groin puncture to repercussion time was lower in younger population (32 v/s 69 mins; p = 0.0044) > The median groin puncture to first pass time was lower in younger population (22 v/s 43; p = 0.056), but it failed to show statistical significance. > Younger compared to older patients had better clinical outcomes (mRS 0–2) at 77.1% v/s 32.3% (p< 0.0001) and higher rates of favorable repercussion (TICI 2b‐3) at 93.7% v/s 72.9% (p = 0.0016) > The older group required more passes to achieve recanalization (4 or more passes: 4.3% v/s 16.2%; p = 0.035) > Mortality rate was significantly less in the younger population (8.3% v/s 22.1%; p = 0.026) Conclusions Younger patients had better clinical outcomes than their older counterparts after mechanical thrombectomy in our analysis. Other than younger age, higher rates of favorable repercussion, earlier recanalization, and less passes to recanalization were seen in association with better observed outcomes.

Introduction Rescue stenting may be considered during mechanical thrombectomy (MT) if a newly recanalized intracranial vessel keeps re‐occluding, or recanalization is not achieved with conventional thrombectomy methods. There are multiple published case series with mixed results on safety and efficacy of this approach, and there are no available randomized trials. We aimed to compare the outcomes of rescue intracranial stenting with unsuccessful/poor reperfusion after MT. Methods Retrospective review of ischemic stroke patients who underwent MT from 2016–2021. Emergent intracranial stent patients were selected and compared with those who had poor/unsuccessful post‐procedural reperfusion (TICI 0–2a). Initial ASPECT score, NIHSS, number of passes, and MT method (aspiration vs stentriever) were recorded. Complications (intracranial hemorrhage, vessel perforation, groin or retroperitoneal hematoma, or distal embolization), final infarct size, 90‐day mRS, and mortality were analyzed. Results Sixteen patients underwent emergent intracranial stenting. Of the 89patients with failed MT, 34 had TICI 2a, 11 had TICI 1, and 44 had TICI 0 reperfusion. All 16 stenting patients achieved TICI 2B‐3 grade recanalization. Pre‐procedure ASPECT score was similar between both groups. Six patients had either intracranial vertebral or basilar artery stenting, and 10 had either intracranial ICA or MCA stenting. Patients with posterior compared to anterior circulation involvement were more likely to receive stenting (50% vs 11%, p = 0.003). There were no differences in the stenting versus non‐stenting group in 24‐hour post intervention NIHSS, post‐procedural complications, intracranial hemorrhage, infarct size, and mortality (75% vs 67%). The stenting group had better functional independence (mRS 0–2) at 90 days (33% vs 11%, p = 0.04). There were no outcome differences in anterior compared to posterior circulation stenting. Conclusions Rescue stenting was more often seen with posterior circulation strokes. In patients with failed or unsuccessful reperfusion after conventional MT, emergent stenting achieved better 90‐day functional independence without increasing rates of complications, intracranial hemorrhage, or mortality.

Introduction Perimesencephalic subarachnoid hemorrhage (PMSAH) is characterized by bleeding centered in the basal cisterns anterior to the midbrain and pons without intraparenchymal or overt intraventricular extension. The term “benign” is often attached, because typically no source of bleeding is identified on high‐resolution vascular imaging, and recovery if often uncomplicated. Rarely, however, PMSAH can be secondary to ruptured vertebrobasilar aneurysms, and outcomes of these patients is underreported. Methods Retrospective analysis of patients with PMSAH to determine the rate of underlying ruptured aneurysm or vascular abnormality, associated complications, and outcomes. Age, sex, vascular risk factors, presenting symptoms, Hunt and Hess grade, modified Fisher grade, rate of underlying ruptured aneurysm, vasospasm, re‐bleed, hydrocephalus, and modified Rankin scale (mRS) were collected. Primary outcome was good functional status at discharge (mRS 0–2), reported as odds ratio (OR) with 95% confidence interval (CI). Results A total of 74 patients with PMSAH between 2007 and 2022 were identified. Mean age was 55.5± 10 years, and 60% were male. Hypertension and smoking were reported in 57% and 35% of patients, respectively. The most common presenting symptom was thunderclap headache in 89% of patients. Median (IQR) ofHunt and Hess grade was 2 (1‐2), and modified Fisher grade was 3 (1‐3). An underlying ruptured aneurysm was found in 3 patients (4%); two of which were in the vertebrobasilar system and one in the posterior communicating artery. Most common complications in this cohort was vasospasm in 28%, followed by hydrocephalus in 11%. Among patients with aneurysmal bleed, vasospasm and hydrocephalus occurred in 66% of patients each, compared to 8.5% and 27%, respectively in patients with non‐aneurysmal PMSAH. Re‐bleeding occurred only in one patient (1.3%); which occurred in a patient with non‐aneurysmal source of hemorrhage. A total of 88% of patients in our cohort had a favorable functional outcome (mRS 0–2) at discharge. An underlying ruptured aneurysm and acute hydrocephalus were associated with poor functional status(OR = 18.3, [1.5–228], P < 0.024), and OR = 25.8, [4.5–149], P < 0.001), respectively. However, vasospasm was noted to be asymptomatic in most cases (90%) and was not associated with unfavorable outcomes (OR = 0.75, [0.14–3.9], P < 0.73). Conclusions “Benign” PMSAH pattern was associated with a ruptured aneurysm in 4% of patients in our cohort.An underlying aneurysm and acute hydrocephalus were associated with poor outcomes. However, vasospasm was incidental and was not associated with unfavorable outcomes in patients with PMSAH.

Introduction Limited data is available regarding comparative outcomes amongst FDA‐approved devices for mechanical thrombectomy (MT). The objective of this study is to assess procedural efficacy, clinical outcomes, and safety of currently available stent retriever devices when used during first pass thrombectomy for acute ischemic stroke. Methods A retrospective analysis was performed on all patients who underwent MT for large vessel occlusion (LVO) at a single comprehensive stroke center between January 2016 and January 2022. All patients who underwent MT with a stent retriever (Solitaire, Embotrap, Trevo) during first pass were included in the analysis. Primary efficacy and safety outcomes included time to recanalization, attainment of first‐pass effect (FPE), recanalization TICI score, 90‐day modified Rankin scale (mRS), and incidence of hemorrhagic transformation. One‐way ANOVA was used to compare median time to recanalization amongst cohorts. Chi‐squared test was used to compare frequencies of outcome measures amongst cohorts. Results During the study period, 234 patients underwent MT for LVO with use of stent retriever device during the first pass. In these cases, the type of stent retriever utilized was Solitaire (n = 163), Embotrap (n = 45), or Trevo (n = 26). There were no significant differences between cohorts in terms of age, gender, ethnicity, initial NIH stroke scale, or level of occlusion, or comorbidities. No significant differences were observed between cohorts for any primary outcome measures. The median time to recanalization was 53 min [Solitaire], 49 min [Embotrap], 63 min [Trevo] (p = 0.17). First‐pass effect was attained in 28.6% [Solitaire], 38.4% [Embotrap], 26.9% [Trevo] (p = 0.41). TICI 2b or greater recanalization was attained in 80.3% [Solitaire], 88.9% [Embotrap], 84.6% [Trevo] (p = 0.38). 90‐day mRS of 0–2 was observed in 36.6% [Solitaire], 38.9% [Embotrap], 34.8% [Trevo] (p = 0.95). Hemorrhagic transformation was observed in 45.9% [Solitaire], 36.8% [Embotrap], 34.6% [Trevo] (p = 0.40). Conclusions The type of stent retriever chosen for first pass thrombectomy did not predict procedural efficacy, clinical outcomes, or safety in our single center analysis.

Collisionless magnetic reconnection typically requires kinetic treatment that is, in general, computationally expensive compared to fluid-based models. In this study, we use the magnetohydrodynamics with an adaptively embedded particle-in-cell (MHD-AEPIC) model to study the interaction of two magnetic flux ropes. This innovative model embeds one or more adaptive PIC regions into a global MHD simulation domain such that the kinetic treatment is only applied in regions where the kinetic physics is prominent. We compare the simulation results among three cases: (1) MHD with adaptively embedded PIC regions, (2) MHD with statically (or fixed) embedded PIC regions, and (3) a full PIC simulation. The comparison yields good agreement when analyzing their reconnection rates and magnetic island separations as well as the ion pressure tensor elements and ion agyrotropy. In order to reach good agreement among the three cases, large adaptive PIC regions are needed within the MHD domain, which indicates that the magnetic island coalescence problem is highly kinetic in nature, where the coupling between the macro-scale MHD and micro-scale kinetic physics is important.

Background Endovascular management of wide‐necked bifurcation aneurysms poses a therapeutic challenge, as coiling often requires the use of multiple adjunctive stent constructs to achieve successful embolization without compromising parent vessel integrity. The Neuroform Atlas Stent System is a novel low‐profile, intraluminal remodeling device. The study aims to investigate the safety and efficacy of Y‐stent–assisted coiling configuration constructs using the next generation stent for aneurysm coil embolization. Methods Subjects undergoing Y‐stent–assisted coiling in the ATLAS IDE (Safety and Effectiveness of the Treatment of Wide Neck, Saccular Intracranial Aneurysms with the Neuroform Atlas Stent System Investigational Device Exception) trial were identified for subgroup analysis. Enrollment in the trial was not stratified on the basis of the procedural stenting technique used. The primary efficacy end point was complete aneurysm occlusion (Raymond–Roy class 1) on 12‐month angiography, in the absence of re‐treatment or parent artery stenosis (>50%) at the target location. The primary safety end point was any major stroke or ipsilateral stroke or neurological death within 12 months. Adjudication of the primary end points was performed by an independent imaging core laboratory and the clinical events committee. Results A total of 60 subjects were identified. The mean age was 59, and 28.3% were men. The median aneurysm size was 6.7 mm, with a median neck size of 4.3 mm. Frequently reported aneurysm locations included the basilar apex (56.7%), anterior communicating artery (20.0%), and middle cerebral artery bifurcation (11.7%). The composite primary efficacy end point was achieved in 81.1% of subjects. Overall, 1.7% of subjects experienced a primary safety endpoint of major ipsilateral stroke or neurological death. Conclusion In the ATLAS IDE aneurysm cohort premarket approval study, Y‐stent–assisted coiling with Neuroform demonstrated high rates of complete aneurysm occlusion at 12 months, with low rates of morbidity.

We present results of 131 geomagnetic storm simulations using the University of Michigan Space Weather Modeling Framework Geospace configuration. We compare the geomagnetic indices derived from the simulation with those observed, and use 2D cuts in the noon-midnight planes to compare the magnetopause locations with empirical models. We identify the location of the current sheet center and look at the plasma parameters to deduce tail dynamics. We show that the simulation produces geomagnetic index distributions similar to those observed, and that their relationship to the solar wind driver is similar to that observed. While the magnitudes of the Dst and polar cap potentials are close to those observed, the simulated AL index is consistently underestimated. Analysis of the magnetopause position reveals that the subsolar position agrees well with an empirical model, but that the tail flaring in the simulation is much smaller than that in the empirical model. The magnetotail and ring currents are closely correlated with the Dst index, and reveal a strong contribution of the tail current beyond 8 RE to the Dst index during the storm main phase.

Magnetic switchbacks are rapid high-amplitude reversals of the radial magnetic field in the solar wind that do not involve a heliospheric current sheet crossing. First seen sporadically in the 1970s in Mariner and Helios data, switchbacks were later observed by the Ulysses spacecraft beyond 1 au and have been recently discovered to be a typical component of solar wind fluctuations in the inner heliosphere by the Parker Solar Probe spacecraft. While switchbacks are now well understood to be spherically polarized Alfvén waves thanks to Parker Solar Probe observations, their formation has been an intriguing and unsolved puzzle. Here we provide a simple yet predictive theory for the formation of these magnetic reversals: the switchbacks are produced by the distortion and twisting of circularly polarized Alfvén waves by a transversely varying radial wave propagation velocity. We provide an analytic expression for the magnetic field variation, establish the necessary and sufficient conditions for the formation of switchbacks, and show that the proposed mechanism works in a realistic solar wind scenario. We also show that the theoretical predictions are in excellent agreement with observations, and the high-amplitude radial oscillations are strongly correlated with the shear of the wave propagation speed. The correlation coefficient is around 0.3–0.5 for both encounter 1 and encounter 12. The probability of this being a lucky coincidence is essentially zero with p -values below 0.1%.

We explore the performance of the Alfvén Wave Solar atmosphere Model with near-real-time (NRT) synoptic maps of the photospheric vector magnetic field. These maps, produced by assimilating data from the Helioseismic Magnetic Imager (HMI) on board the Solar Dynamics Observatory, use a different method developed at the National Solar Observatory (NSO) to provide a near contemporaneous source of data to drive numerical models. Here, we apply these NSO-HMI-NRT maps to simulate three full Carrington rotations: 2107.69 (centered on the 2011 March 7 20:12 CME event), 2123.5 (centered on 2012 May 11), and 2219.12 (centered on the 2019 July 2 solar eclipse), which together cover various activity levels for solar cycle 24. We show the simulation results, which reproduce both extreme ultraviolet emission from the low corona while simultaneously matching in situ observations at 1 au as well as quantify the total unsigned open magnetic flux from these maps.

Coupling between the solar wind and magnetosphere can be expressed in terms of energy transfer through the separating boundary known as the magnetopause. Geospace simulation is performed using the Space Weather Modeling Framework (SWMF) of a multi-ICME impact event on February 18–20, 2014 in order to study the energy transfer through the magnetopause during storm conditions. The magnetopause boundary is identified using a modified plasma β and fully closed field line criteria to a downstream distance of −20Re. Observations from Geotail, Themis, and Cluster are used as well as the Shue 1998 model to verify the simulation field data results and magnetopause boundary location. Once the boundary is identified, energy transfer is calculated in terms of total energy flux K, Poynting flux S, and hydrodynamic flux H. Surface motion effects are considered and the regional distribution of energy transfer on the magnetopause surface is explored in terms of dayside X>0, flank X

BACKGROUND:PACAP and VIP are closely related neuropeptides with wide distribution and potent effect in the vasculature. We previously reported vasomotor activity in peripheral vasculature of male wild type (WT) and PACAP-deficient (KO) mice. However, female vascular responses are still unexplored. We hypothesized that PACAP-like activity is maintained in female PACAP KO mice and the mechanism through which it is regulated differs from that of male PACAP KO animals. METHODS:We investigated the vasomotor effects of VIP and PACAP isoforms and their selective blockers in WT and PACAP KO female mice in carotid and femoral arteries. The expression and level of different PACAP receptors in the vessels were measured by RT-PCR and Western blot. RESULTS:In both carotid and femoral arteries of WT mice, PACAP1-38, PACAP1-27 or VIP induced relaxation, without pronounced differences between them. Reduced relaxation was recorded only in the carotid arteries of KO mice as compared to their WT controls. The specific VPAC1R antagonist completely blocked the PACAP/VIP-induced relaxation in both arteries of all mice, while PAC1R antagonist affected relaxation only in their femoral arteries. CONCLUSION:In female WT mice, VPAC1 receptors appear to play a dominant role in PACAP-induced vasorelaxation both in carotid and in femoral arteries. In the PACAP KO group PAC1R activation exerts vasorelaxation in the femoral arteries but in carotid arteries there is no significant effect of the activation of this receptor. In the background of this regional difference, decreased PAC1R and increased VPAC1R availability in the carotid arteries was found.

The neuropeptide Pituitary adenylate cyclase-activating polypeptide (PACAP) plays pivotal roles in immunity and inflammation. So far, potential immune-modulatory properties of PACAP have not been investigated in experimental ileitis.Mice were perorally infected with Toxoplasma (T.) gondii to induce acute ileitis (day 0) and treated daily with synthetic PACAP38 from day 1 to 6 post infection (p.i.; prophylaxis) or from day 4 to 6 p.i. (therapy). Whereas placebo-treated control mice suffered from acute ileitis at day 7 p.i. and succumbed to infection, intestinal immunopathology was ameliorated following PACAP prophylaxis. PACAP-treated mice exhibited increased abundance of small intestinal FOXP3+ cells, but lower numbers of ileal T lymphocytes, neutrophils, monocytes and macrophages, which was accompanied by less ileal expression of pro-inflammatory cytokines such as IL-23p19, IL-22, IFN-γ, and MCP-1. Furthermore, PACAP-treated mice displayed higher anti-inflammatory IL-4 concentrations in mesenteric lymph nodes and liver and higher systemic anti-inflammatory IL-10 levels in spleen and serum as compared to control animals at day 7 p.i. Remarkably, PACAP-mediated anti-inflammatory effects could also be observed in extra-intestinal compartments as indicated by reduced pro-inflammatory mediator levels in spleen (TNF-α, nitric oxide) and liver (TNF-α, IFN-γ, MCP-1, IL-6) and less severe histopathological sequelae in lungs and kidneys following prophylactic PACAP treatment. Strikingly, PACAP prolonged survival of T. gondii infected mice in a time-of-treatment dependent manner.Synthetic PACAP ameliorates acute small intestinal inflammation and extra-intestinal sequelae by down-regulating Th1-type immunopathology, reducing oxidative stress and up-regulating anti-inflammatory cytokine responses. These findings provide novel potential treatment options of inflammatory bowel diseases.

Pituitary adenylate cyclase activating polypeptide (PACAP) has neuroprotective effects in different neuronal and retinal injuries. Retinal ischemia can be effectively modelled by permanent bilateral common carotid artery occlusion (BCCAO), which causes chronic hypoperfusion-induced degeneration in the entire rat retina. The retinoprotective effect of PACAP 1-38 and VIP is well-established in ischemic retinopathy. However, little is known about the effects of related peptides and PACAP fragments in ischemic retinopathy. The aim of the present study was to investigate the potential retinoprotective effects of different PACAP fragments (PACAP 4-13, 4-22, 6-10, 6-15, 11-15, and 20-31) and related peptides (secretin, glucagon) in BCCAO-induced ischemic retinopathy. Wistar rats (3-4 months old) were used in the experiment. After performing BCCAO, the right eyes of the animals were treated with PACAP fragments or related peptides intravitreal (100 pM), while the left eyes were injected with saline serving as control eyes. Sham-operated (without BCCAO) rats received the same treatment. Routine histology was performed 2 weeks after the surgery; cells were counted and the thickness of retinal layers was compared. Our results revealed significant neuroprotection by PACAP 1-38 but did not reveal retinoprotective effect of the PACAP fragments or related peptides. These results suggest that PACAP 1-38 has the greatest efficacy in ischemic retinopathy.

A large amount of short interfering RNA (vsiRNA) is generated from plant viruses during infection, but the function, structure and biogenesis of these is not understood. We profiled vsiRNAs using two different high-throughput sequencing platforms and also developed a hybridisation based array approach. The profiles obtained through the Solexa platform and by hybridisation were very similar to each other but different from the 454 profile. Both deep sequencing techniques revealed a strong bias in vsiRNAs for the positive strand of the virus and identified regions on the viral genome that produced vsiRNA in much higher abundance than other regions. The hybridisation approach also showed that the position of highly abundant vsiRNAs was the same in different plant species and in the absence of RDR6. We used the Terminator 5'-Phosphate-Dependent Exonuclease to study the 5' end of vsiRNAs and showed that a perfect control duplex was not digested by the enzyme without denaturation and that the efficiency of the Terminator was strongly affected by the concentration of the substrate. We found that most vsiRNAs have 5' monophosphates, which was also confirmed by profiling short RNA libraries following either direct ligation of adapters to the 5' end of short RNAs or after replacing any potential 5' ends with monophosphates. The Terminator experiments also showed that vsiRNAs were not perfect duplexes. Using a sensor construct we also found that regions from the viral genome that were complementary to non-abundant vsiRNAs were targeted in planta just as efficiently as regions recognised by abundant vsiRNAs. Different high-throughput sequencing techniques have different reproducible sequence bias and generate different profiles of short RNAs. The Terminator exonuclease does not process double stranded RNA, and because short RNAs can quickly re-anneal at high concentration, this assay can be misleading if the substrate is not denatured and not analysed in a dilution series. The sequence profiles and Terminator digests suggest that CymRSV siRNAs are produced from the structured positive strand rather than from perfect double stranded RNA or by RNA dependent RNA polymerase.