Summary More than 50 years after its initial description, transient global amnesia (TGA) remains one of the most enigmatic syndromes in clinical neurology. Recent MRI data suggest that a transient ...perturbation of hippocampal function is the functional correlate of TGA because focal diffusion lesions can be selectively detected in the CA1 field of the hippocampal cornu ammonis. Although various factors, such as migraine, focal ischaemia, venous flow abnormalities, and epileptic phenomena, have been suggested to be involved in the pathophysiology of TGA, the factors triggering the emergence of these lesions are still elusive. Recent data suggest that the vulnerability of CA1 neurons to metabolic stress plays a pivotal part in the pathophysiological cascade, leading to an impairment of hippocampal function during TGA. In this Review, we discuss clinical aspects, new imaging findings, and recent clinical–epidemiological data with regard to the phenotype, functional anatomy, and putative cellular mechanisms of TGA.
Trials have evaluated the use of clopidogrel and aspirin to prevent stroke after an ischemic stroke or transient ischemic attack (TIA). In a previous trial, ticagrelor was not better than aspirin in ...preventing vascular events or death after stroke or TIA. The effect of the combination of ticagrelor and aspirin on prevention of stroke has not been well studied.
We conducted a randomized, placebo-controlled, double-blind trial involving patients who had had a mild-to-moderate acute noncardioembolic ischemic stroke, with a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less (range, 0 to 42, with higher scores indicating more severe stroke), or TIA and who were not undergoing thrombolysis or thrombectomy. The patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive a 30-day regimen of either ticagrelor (180-mg loading dose followed by 90 mg twice daily) plus aspirin (300 to 325 mg on the first day followed by 75 to 100 mg daily) or matching placebo plus aspirin. The primary outcome was a composite of stroke or death within 30 days. Secondary outcomes were first subsequent ischemic stroke and the incidence of disability within 30 days. The primary safety outcome was severe bleeding.
A total of 11,016 patients underwent randomization (5523 in the ticagrelor-aspirin group and 5493 in the aspirin group). A primary-outcome event occurred in 303 patients (5.5%) in the ticagrelor-aspirin group and in 362 patients (6.6%) in the aspirin group (hazard ratio, 0.83; 95% confidence interval CI, 0.71 to 0.96; P = 0.02). Ischemic stroke occurred in 276 patients (5.0%) in the ticagrelor-aspirin group and in 345 patients (6.3%) in the aspirin group (hazard ratio, 0.79; 95% CI, 0.68 to 0.93; P = 0.004). The incidence of disability did not differ significantly between the two groups. Severe bleeding occurred in 28 patients (0.5%) in the ticagrelor-aspirin group and in 7 patients (0.1%) in the aspirin group (P = 0.001).
Among patients with a mild-to-moderate acute noncardioembolic ischemic stroke (NIHSS score ≤5) or TIA who were not undergoing intravenous or endovascular thrombolysis, the risk of the composite of stroke or death within 30 days was lower with ticagrelor-aspirin than with aspirin alone, but the incidence of disability did not differ significantly between the two groups. Severe bleeding was more frequent with ticagrelor. (Funded by AstraZeneca; THALES ClinicalTrial.gov number, NCT03354429.).
Abstract The most common way to discover extragalactic fast transients, which fade within a few nights in the optical, is via follow-up of gamma-ray burst and gravitational-wave triggers. However, ...wide-field surveys have the potential to identify rapidly fading transients independently of such external triggers. The volumetric survey speed of the Zwicky Transient Facility (ZTF) makes it sensitive to objects as faint and fast fading as kilonovae, the optical counterparts to binary neutron star mergers, out to almost 200 Mpc. We introduce an open-source software infrastructure, the ZTF REaltime Search and Triggering, ZTFReST , designed to identify kilonovae and fast transients in ZTF data. Using the ZTF alert stream combined with forced point-spread-function photometry, we have implemented automated candidate ranking based on their photometric evolution and fitting to kilonova models. Automated triggering, with a human in the loop for monitoring, of follow-up systems has also been implemented. In 13 months of science validation, we found several extragalactic fast transients independently of any external trigger, including two supernovae with post-shock cooling emission, two known afterglows with an associated gamma-ray burst (ZTF20abbiixp, ZTF20abwysqy), two known afterglows without any known gamma-ray counterpart (ZTF20aajnksq, ZTF21aaeyldq), and three new fast-declining sources (ZTF20abtxwfx, ZTF20acozryr, ZTF21aagwbjr) that are likely associated with GRB200817A, GRB201103B, and GRB210204A. However, we have not found any objects that appear to be kilonovae. We constrain the rate of GW170817-like kilonovae to R < 900 Gpc −3 yr −1 (95% confidence). A framework such as ZTFReST could become a prime tool for kilonova and fast-transient discovery with the Vera Rubin Observatory.
The myelin sheaths wrapped around axons by oligodendrocytes are crucial for brain function. In ischaemia myelin is damaged in a Ca(2+)-dependent manner, abolishing action potential propagation. This ...has been attributed to glutamate release activating Ca(2+)-permeable N-methyl-D-aspartate (NMDA) receptors. Surprisingly, we now show that NMDA does not raise the intracellular Ca(2+) concentration (Ca(2+)i) in mature oligodendrocytes and that, although ischaemia evokes a glutamate-triggered membrane current, this is generated by a rise of extracellular K(+) and decrease of membrane K(+) conductance. Nevertheless, ischaemia raises oligodendrocyte Ca(2+)i, Mg(2+)i and H(+)i, and buffering intracellular pH reduces the Ca(2+)i and Mg(2+)i increases, showing that these are evoked by the rise of H(+)i. The H(+)-gated Ca(2+)i elevation is mediated by channels with characteristics of TRPA1, being inhibited by ruthenium red, isopentenyl pyrophosphate, HC-030031, A967079 or TRPA1 knockout. TRPA1 block reduces myelin damage in ischaemia. These data suggest that TRPA1-containing ion channels could be a therapeutic target in white matter ischaemia.
In this paper, an adaptive trajectory tracking control algorithm for underactuated unmanned surface vessels (USVs) with guaranteed transient performance is proposed. To meet the realistic dynamical ...model of USVs, we consider that the mass and damping matrices are not diagonal and the input saturation problem. Neural networks (NNs) are employed to approximate the unknown external disturbances and uncertain hydrodynamics of USVs. Moreover, both full-state feedback control and output feedback control are presented, and the unmeasurable velocities of the output feedback controller are estimated via high-gain observer. Unlike the conventional control methods, we employ the error transformation function to guarantee the transient tracking performance. Both simulation and experimental results are carried out to validate the superior performance via comparing with traditional potential integral control approaches.
The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for ...low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied.
In this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes.
A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P = 0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups.
After an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target ClinicalTrials.gov number, NCT01252875.).
Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. ...However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk.
We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602.
The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69–0·77) with a calibration slope of 0·94 (0·81–1·06) for the intracranial haemorrhage model and 0·63 (0·62–0·65) with a calibration slope of 0·97 (0·87–1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models.
The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted.
British Heart Foundation and Stroke Association.
When adjusting the transmission power of the dual-bridge series resonant converter (DBSRC) under the phase-shift modulation, significant step changes in phase-shift angles may occur. These changes ...stimulate a long-time oscillation process in the resonant tank with a large amplitude appearing in inductor current and capacitor voltage. During this transient process, the converter's dynamic performance deteriorates considerably, and the circuit components may experience severe overvoltage and overcurrent. In view of that, this paper develops a transient process calculation model (TPCM) for the DBSRC using the fundamental harmonic approximation to analyze the oscillations during the transient process. Subsequently, the peak capacitor voltage, the peak inductor current, and the settling time during the transient process are estimated. Further, based on the TPCM, this paper proposes a control method to make the converter reach a steady state after one switching cycle, thus avoiding the risk of overvoltage and overcurrent and greatly improving the dynamic performance of the converter. Finally, the results of the theoretical analysis and the proposed control method are verified by simulations and experiments.
With an increase in the ageing population, there is a rise in the burden of cardiovascular disease. Age and Ageing have compiled collections of their key cardiovascular themed papers. The first Age ...and Ageing Cardiovascular Collection focussed on blood pressure, coronary heart disease and heart failure. In this second collection, publications since 2011 were selected with emphasis on atrial fibrillation, transient ischaemic attack (TIA) and stroke. The prevalence of TIA and stroke increases as people get older. In this commentary we summarise studies published in Age and Ageing that bring to the fore the need for a multidisciplinary, person-centred approach to care, conscientious identification of risk factors and their management and prevention strategies, which will inform policy ultimately reducing the burden of cost placed by stroke care on healthcare financing. Read the latest Cardiovascular Collection here.
Abstract We present Hubble Space Telescope ultraviolet and infrared observations of eight fast radio burst (FRB) host galaxies with subarcsecond localizations, including the hosts of three known ...repeating FRBs. We quantify their spatial distributions and locations with respect to their host galaxy light distributions, finding that they occur at moderate host-normalized offsets of 1.4 r e (0.6, 2.1 r e ; 68% interval) and on fainter regions of their hosts in terms of IR light but overall trace the radial distribution of IR light in their galaxies. The FRBs in our tested distribution do not clearly trace the distributions of any other transient population with known progenitors and are statistically distinct from the locations of LGRBs, H-poor SLSNe, SGRBs, and Ca-rich transients. We further find that most FRBs are not in regions of elevated local star formation rates and stellar mass surface densities in comparison to the mean global values of their hosts. We also place upper limits on the IR flux at the FRB positions of m IR ≳ 24.8–27.6 AB mag, constraining both satellite and background galaxies to luminosities well below the host luminosity of FRB 121102. We find that 5/8 FRB hosts exhibit clear spiral arm features in IR light, and that the positions of all well-localized FRBs located in such hosts are consistent with their spiral arms, although not on their brightest regions. Our results do not strongly support the primary progenitor channel of FRBs being connected with either the most massive (stripped-envelope) stars or events that require kicks and long delay times (neutron star mergers).
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