Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

BACKGROUND: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain. METHODS: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group). The primary efficacy outcome was functional status as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days after randomization. The primary safety outcome was any serious adverse event. RESULTS: A total of 2404 patients (mean age, 70 years) in China underwent randomization and provided consent for the trial: 1205 in the intervention group and 1199 in the usual-care group. The median time between symptom onset and randomization was 61 minutes (interquartile range, 41 to 93), and the mean blood pressure at randomization was 178/98 mm Hg. Stroke was subsequently confirmed by imaging in 2240 patients, of whom 1041 (46.5%) had a hemorrhagic stroke. At the time of patients' arrival at the hospital, the mean systolic blood pressure in the intervention group was 159 mm Hg, as compared with 170 mm Hg in the usual-care group. Overall, there was no difference in functional outcome between the two groups (common odds ratio, 1.00; 95% confidence interval [CI], 0.87 to 1.15), and the incidence of serious adverse events was similar in the two groups. Prehospital reduction of blood pressure was associated with a decrease in the odds of a poor functional outcome among patients with hemorrhagic stroke (common odds ratio, 0.75; 95% CI, 0.60 to 0.92) but an increase among patients with cerebral ischemia (common odds ratio, 1.30; 95% CI, 1.06 to 1.60). CONCLUSIONS: In this trial, prehospital blood-pressure reduction did not improve functional outcomes in a cohort of patients with undifferentiated acute stroke, of whom 46.5% subsequently received a diagnosis of hemorrhagic stroke. (Funded by the National Health and Medical Research Council of Australia and others; INTERACT4 ClinicalTrials.gov number, NCT03790800; Chinese Trial Registry number, ChiCTR1900020534.).

Adversarial Decision-Making for Moving Target Defense: A Multi-Agent Markov Game and Reinforcement Learning Approach.

Reinforcement learning has shown a great ability and has defeated human beings in the field of real-time strategy games. In recent years, reinforcement learning has been used in cyberspace to carry out automated and intelligent attacks. Traditional defense methods are not enough to deal with this problem, so it is necessary to design defense agents to counter intelligent attacks. The interaction between the attack agent and the defense agent can be modeled as a multi-agent Markov game. In this paper, an adversarial decision-making approach that combines the Bayesian Strong Stackelberg and the WoLF algorithms was proposed to obtain the equilibrium point of multi-agent Markov games. With this method, the defense agent can obtain the adversarial decision-making strategy as well as continuously adjust the strategy in cyberspace. As verified in experiments, the defense agent should attach importance to short-term rewards in the process of a real-time game between the attack agent and the defense agent. The proposed approach can obtain the largest rewards for defense agent compared with the classic Nash-Q and URS-Q algorithms. In addition, the proposed approach adjusts the action selection probability dynamically, so that the decision entropy of optimal action gradually decreases.

IKN-CF: An Approach to Identify Key Nodes in Inter-Domain Routing Systems Based on Cascading Failures.

Inter-domain routing systems is an important complex network in the Internet. Research on the vulnerability of inter-domain routing network nodes is of great support to the stable operation of the Internet. For the problem of node vulnerability, we proposed a method for identifying key nodes in inter-domain routing systems based on cascading failures (IKN-CF). Firstly, we analyzed the topology of inter-domain routing network and proposed an optimal valid path discovery algorithm considering business relationships. Then, the reason and propagation mechanism of cascading failure in the inter-domain routing network were analyzed, and we proposed two cascading indicators, which can approximate the impact of node failure on the network. After that, we established a key node identification model based on improved entropy weight TOPSIS (EWT), and the key node sequence in the network can be obtained through EWT calculation. We compared the existing three methods in two real inter-domain routing networks. The results indicate that the ranking results of IKN-CF are high accuracy, strong stability, and wide applicability. The accuracy of the top 100 nodes of the ranking result can reach 83.6%, which is at least 12.8% higher than the average accuracy of the existing three methods.

The effect of perceived social support during early pregnancy on depressive symptoms at 6 weeks postpartum: a prospective study.

BACKGROUND: Postpartum depression was associated with maternal suffering and diminished functioning, increased risk of marital conflict as well as adverse child outcomes. Perceived social support during pregnancy was associated with postpartum depression among women. However, its causal relationship remains unclear. Therefore, we prospectively evaluate the association between perceived social support during early pregnancy and postpartum depressive symptoms. METHODS: We prospectively examined whether perceived social support during early pregnancy affected depressive symptoms at 6 weeks postpartum in a cohort of 3310 women. Perceived social support and postpartum depression were assessed by ENRICHD Social Support Instrument (ESSI) and the postpartum Edinburgh Postpartum Depression Scale (EPDS), respectively. Prevalence of postpartum depressive symptoms was 11.4% (EPDS cutoff≥10). As a test of heterogeneity of association in subpopulations, logistic regression models were performed to analyze the association between social support and postpartum depressive symptoms in strata which were defined by the potential confounder candidates. After multiple imputation, multivariable logistic regression was performed to assess the effect of social support on postpartum symptoms in individual items and total score. Two models were built. Model I adjusted for the variables associated with social support or postpartum depression and changed the association estimates by ≥10%. Model II adjusted for all variables that may be related to social support or postpartum depression. RESULTS: Significant associations between low perceived social support and postpartum depressive symptoms was found(Model I odds ratio: 1.63, 95% confidence interval: 1.15, 2.30; Model II odds ratio: 1.77, 95% confidence interval: 1.24-2.52). Stratified analyses showed that there was little evidence of heterogeneity of association in subpopulations by basic characteristics of participants. CONCLUSIONS: These findings suggest that early intervention may be able to help protect against depression symptoms at 6 weeks postpartum.

[The clinical characteristics of patients with posterior circulation ischemic stroke].

OBJECTIVE: To describe the clinical features of patients with posterior circulation ischemic stroke. METHODS: 216 patients with posterior circulation ischemic stroke admitted in our department during 2004-2006 were analyzed retrospectively. All patients were undertaken MRI on admission and responsible lesions were identified at the posterior circulation territories. The patients' clinical symptoms and signs were evaluated and the relationships between lesion locations and clinical characteristics were analyzed. RESULTS: The common symptoms of posterior circulation ischemic stroke were unilateral limb weakness (81.9%), speech difficulty (46.3%), dizziness (33.8%), and unilateral limb numbness (31.0%). The common signs of posterior circulation ischemic stroke were unilateral limb weakness (81.9%), central facial or lingual palsy (61.1%), dysarthria (46.3%), unilateral limb sensory loss (31.0%), and ataxia (30.1%). The incidence of crossed paralysis was low (2.8%). Isolated vertigo was rare (1.4%). Predominant clinical features such as bulbar paralysis, unconsciousness, visual disorder and amnesia can help to localize the lesions. Typical brainstem syndromes had topographic meanings. CONCLUSIONS: The clinical features of patients with posterior circulation ischemic stroke were complex. Predominant symptoms can help to diagnose the posterior circulation ischemic stroke.

Identification of chaperones in a MPP+-induced and ATRA/TPA-differentiated SH-SY5Y cell PD model.

Parkinson's disease (PD) is characterized by the pathological accumulation of misfolded proteins. Molecular chaperones assist in the proper folding of proteins and removal of irreversibly misfolded proteins. This study aims to identify potential chaperones associated with protein misfolding and accumulation in PD. ATRA/TPA-differentiated SH-SY5Y cells were treated with 1 mM of MPP+ for 48 hours. Proteins were analyzed by 2D-DIGE followed by MALDI-ToF MS. The treatment of differentiated SH-SY5Y cells by MPP+ led to the unambiguous identification of 10 protein spots, which corresponds to six proteins. Among these six proteins, four were chaperone proteins including nucleophosmin (NPM1), chaperonin-containing TCP-1 subunit 2 (CCT2 or CCTß), heat shock 90 kDa protein 1 beta (HSP90AB1 or HSP90-ß), and tyrosin3/tryptopha5-monoxygenase activation protein, zeta polypeptide (14-3-3ζ, gene symbol: Ywhaz). To our knowledge, this is the first report that linked the upregulation of chaperones after MPP+ treatment with SH-SY5Y cells. However, the NPM1 protein was identified for the first time in the PD model. The upregulation of four chaperone proteins provided evidence that these chaperones have a complementary effect on protein misfolding in the pathogenesis of PD, and hold promise as a good therapeutic target for PD treatment.