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In discussing Browning’s revisionary attempt to re-write The Cenci, this chapter focuses on four points. Firstly, it looks at the polarization of characters into good and evil. Secondly, it explores the idea of casuistry and a ‘case’ as a moral problematic that traditionally required casuistic thinking. Shelley situates the story in such terms, but without being able to reach a clear resolution, he resorts to sympathy, which readers are invited to feel with the victim-turned-aggressor. Thirdly, it describes how Browning resolves this moral dilemma by introducing the rescue theme. Finally, it argues that The Cenci is a historical play in both senses of the word: it is based on a historical event, but it also represents the historicity of the time in which Shelley composed the play. Unlike Shelley, who was only able to envision the independence of Italy obliquely, Browning was able to conceive of it more optimistically.

This chapter examines Browning’s views on art by teasing out his aesthetics and poetics in the two painter/art poems as well as in his letters and ‘Essay’. ‘Fra Lippo Lippi’, for example, can be interpreted partly as Browning’s approval of the naturalism or realism that succeeded the idealism of Fra Angelico and Giotto, thereby breaking from the widely held view that Lippi’s art was inferior to that of his predecessors. In ‘Old Pictures of Florence’, medieval architecture, such as Giotto’s unfinished bell-tower, exemplifies a Christian worldview that emphasizes the significance of incompletion or imperfection as opposed to the perfected art of ancient Greece. This chapter argues that Browning’s aesthetic preference had an individual motivating factor, deriving from a deeply personal decision to move away from, and hence displace, the poetic influence of Shelley.

The Introduction suggests a new way of integrating the ‘biographical’ and the ‘literary’ as suggested by Julie Carlson. It also takes on board the collaborative nature of the relationship of the Shelleys as recently examined by Anna Mercer, and builds on the dialogic relationship of the Brownings first established through the examination of their correspondence by Daniel Karlin. When discussing the relationships between texts, it is useful to discriminate between ‘influence’ and ‘intertextuality.’ This Introduction addresses the latter in relation to the burgeoning scholarship on “echoes” and “allusions” across Romantic and Victorian literature (e.g., book-length studies by Mark Sandy, Richard Cronin and Lucy Newlyn). By utilizing the strategic insights which they offer and building on Romantic historicism, the book aims to assimilate ‘historical consciousness’ into the notion of ‘influence.’

The two texts dealt with in this chapter explore the political strife that tore apart the city-states of medieval Italy. In their treatment of history, each attempts to (re)politicize their dramatis personae and to exploit history for their own ends, in order to proselytise on behalf of the democratic cause. The texts also concern the emotional or intellectual trauma of the writers: Valperga is about the interiority of emotional life, which reflects that of Mary Shelley. Sordello, by contrast, might be seen as a textualized rite of passage that documents and inscribes Browning’s becoming a poet in his own right. The liberties taken by Browning with historical facts also enable him to respond to Mary Shelley’s gendered argument of masculine egoism. In terms of politics, Mary Shelley remains firmly entrenched in Shelleyan Romanticism whereas Browning goes beyond a Romantic transformation of society to intimate a more practical and necessarily gradual means of changing society.

In elucidating Shelleyan influence on Browning, this chapter singles out Shelley’s last, unfinished poem, ‘The Triumph of Life’, as being comparable to Fifine on two grounds: the use of dream vision, and the underlying dramatic situation of being torn between passion for one’s wife and for another woman (with the former less obvious than the latter). Fifine is a statement about Romanticism as Browning had first encountered it through his immersion in Shelley’s works, which were then partly discarded but partly assimilated, as first argued by John Woolford. Browning acknowledges his debt to the Romantics, and in particular Shelley, regarding the visionary nature of his work, but also as a man with complicated emotional life, which Browning initially perhaps could not understand but came around to appreciating, as he was to undergo such experiences himself.

The two texts dealt with in this chapter offer a compelling example of Mary Shelley’s influence on Browning’s textual practice. If one considers Browning’s own inscription in the poem, of Paracelsus’s will to serve mankind and his lack of Love (which becomes apparent when encountering a Shelleyan figure who embodies Love), its closeness to Frankenstein becomes immediately apparent. There are other similarities to note: the structure of the two plots—the protagonists’ respective success followed by their downfall and finally their realization as to the cause of their failure—is almost identical. The manner in which ‘Prometheanism’ (a notion that is clearly manifest in Frankenstein) is at once condemned and—in a qualified manner—endorsed in Paracelsus draws attention to the possible influence of Frankenstein for its subtle and nuanced treatment of the subject-matter.

The three sections that make up this chapter trace Shelleyan resonance/influence in Elizabeth Barrett’s writings, from her early works to her later poem, Casa Guidi Windows. Section One focuses on Barrett’s The Battle of Marathon, Prometheus Bound and The Seraphim. In Section Two, a comparison between Shelley’s “The Triumph of Life” and Barrett’s “A Vision of Poets” is undertaken. One can read Barrett’s “Vision” as a corrective to Shelley’s pessimism concerning the role of poets as they figure in his last poem. Section Three examines Casa Guidi Windows, as it utilizes some Shelleyan ideas and motifs, which derive largely from his Defence of Poetry. The chapter argues that Barrett’s use of the seasonal trope, as dramatized in Shelley’s ‘Ode to the West Wind’, deserves further attention. Finally, in order to provide a reading that deviates from the conventional interpretation, Isobel Armstrong’s formulation of the ‘radical aesthetic’ is deployed.

This book is about the intertextual relationships between the works of the Shelleys and the Brownings. While a lot of research has been done on the relationship between Percy Bysshe Shelley and Robert Browning, virtually nothing has been said about the links between Mary Shelley and Robert Browning, and very little on the connections between the Shelleys and Elizabeth Barrett Browning. The book seeks to address this blind spot by focusing on three areas in particular: firstly, the way that Browning’s later poems reflect back on and re-engage with Shelley’s work; second, Mary Shelley’s influence on Browning’s early poems; and third, Shelley’s presence in and influence on Elizabeth Barrett Browning’s writing. In mapping out the various ways in which texts relate to other texts, the book also identifies a number of important thematic threads that run throughout the work of all four writers. These include theories of history and historical consciousness, providing a further dimension to the question of ‘influence.’ They also include ideas about exile, gender, liberal politics and cultural heritage, central to almost all the texts discussed here, as the Shelleys and the Brownings, in different ways and in varying contexts, tried to negotiate the possibility of a more tolerant and resilient social, political and cultural environment.

International audience; BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. FINDINGS: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I(2)=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [\textless1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). INTERPRETATION: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. FUNDING: None.

Background and Purpose— As a prespecified post hoc analysis of the J-STARS (Japan Statin Treatment Against Recurrent Stroke) Echo Study, the 5-year stroke recurrence rate according to the baseline mean carotid intima-media thickness (IMT) with and without pravastatin treatment was investigated. Methods— Patients were randomly assigned to receive pravastatin 10 mg/day (pravastatin group) or control group (nonstatin treatment; 1:1) for 5 years. Baseline mean IMT of the common carotid artery was measured by ultrasonography. Cox proportional hazards models were used to investigate whether the stroke (any ischemic stroke, atherothrombotic brain infarction, or lacunar infarction) recurrence rate was different according to tertiles of baseline mean IMT. Results— A total of 793 patients, including 388 in the pravastatin group and 405 in the control group, were investigated. In the control group, Cox proportional hazards models showed that participants in the highest tertile IMT group (≥0.931 mm) had a higher rate of atherothrombotic brain infarction than those in the lowest tertile IMT group (P value=0.045). Conclusions— Long-term pravastatin administration may prevent the occurrence of atherothrombotic brain infarction in noncardioembolic infarction patients with the highest tertile IMT. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00361530.

Background Anticoagulation therapy, particularly subcutaneous heparin therapy, is recommended for cancer-associated thrombosis. However, not starting or discontinuing anticoagulation was not rare. The aim of the present study was to examine the practical issues related to anticoagulation therapy and effects of subcutaneous heparin therapy for cancer-associated stroke. Methods Patients with cancer-associated stroke in our stroke center between October 2014 and August 2017 who were diagnosed as having acute ischemic stroke based on diffusion-weighted imaging were retrospectively enrolled. Baseline clinical characteristics, heparin injection, reasons for no subcutaneous heparin therapy, and clinical outcomes were collected. Results A total of 59 patients with cancer-associated stroke (75 ± 10 years old, male 42%) were enrolled. Lung cancer was the most frequently observed cancer (n = 17, 29%), followed by gastric cancer (n = 8, 14%) and pancreatic cancer (n = 8, 14%). Of the 19 patients (32%) who underwent subcutaneous heparin therapy, it was discontinued in 9 (47%), mainly because of patients’ medical conditions (deterioration of cancer or hemorrhagic complication). Ten patients with long-term subcutaneous heparin therapy did not have stroke recurrence. In contrast, among nine patients who discontinued subcutaneous heparin therapy, three (33%) had recurrence of ischemic stroke. Of the 40 patients without subcutaneous heparin therapy, the main reasons for no subcutaneous heparin therapy were the patients’ medical conditions (n = 22, 55%). Conclusions Although subcutaneous heparin therapy was given to only one third of cancer-associated stroke patients, long-term subcutaneous heparin therapy might prevent recurrence of cancer-associated stroke.

Background and Purpose: We determined to identify patients with unknown onset stroke who could have favorable 90-day outcomes after low-dose thrombolysis from the THAWS (Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes With Alteplase at 0.6 mg/kg) database. Methods: This was a subanalysis of an investigator-initiated, multicenter, randomized, open-label, blinded–end point trial. Patients with stroke with a time last-known-well >4.5 hours who showed a mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg intravenously or standard medical treatment. The patients were dichotomized by ischemic core size or National Institutes of Health Stroke Scale score, and the effects of assigned treatments were compared in each group. The efficacy outcome was favorable outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. Results: The median DWI-Alberta Stroke Program Early CT Score (ASPECTS) was 9, and the median ischemic core volume was 2.5 mL. Both favorable outcome (47.1% versus 48.3%) and any intracranial hemorrhage (26% versus 14%) at 22 to 36 hours were comparable between the 68 thrombolyzed patients and the 58 control patients. There was a significant treatment-by-cohort interaction for favorable outcome between dichotomized patients by ASPECTS on DWI ( P =0.026) and core volume ( P =0.035). Favorable outcome was more common in the alteplase group than in the control group in patients with DWI-ASPECTS 5 to 8 (RR, 4.75 [95% CI, 1.33–30.2]), although not in patients with DWI-ASPECTS 9 to 10. Favorable outcome tended to be more common in the alteplase group than in the control group in patients with core volume >6.4 mL (RR, 6.15 [95% CI, 0.87–43.64]), although not in patients with volume ≤6.4 mL. The frequency of any intracranial hemorrhage did not differ significantly between the 2 treatment groups in any dichotomized patients. Conclusions: Patients developing unknown onset stroke with DWI-ASPECTS 5 to 8 showed favorable outcomes more commonly after low-dose thrombolysis than after standard treatment. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT02002325. URL: https://www.umin.ac.jp/ctr ; Unique Identifier: UMIN000011630.

Using near-infrared spectroscopy, we examined changes in the concentration of oxygenated hemoglobin ([oxy-Hb]) in the frontal lobe during a verbal fluency task in 20 patients with schizophrenia (10 patients each receiving olanzapine [OLZ] and risperidone [RIS]) and 10 healthy controls. We found that [oxy-Hb] levels in the prefrontal region were higher in the patients receiving OLZ than in those receiving RIS. These results suggest that antipsychotic drugs have different effects on cerebral hemodynamic patterns, which may reflect frontal lobe function. Further studies with a larger sample size are needed to verify our preliminary findings.

Aims: There may be ethnic differences in carotid atherosclerosis and its contributing factors between Asian and other populations. The purpose of this study was to examine intima-media complex thickness (IMT) of the carotid artery and associated clinical factors in Japanese stroke patients with hyperlipidemia from a cohort of the Japan Statin Treatment Against Recurrent Stroke Echo Study. Methods: Patients with hyperlipidemia, not on statins, who developed noncardioembolic ischemic stroke were included in this study. Mean IMT and maximum IMT of the distal wall of the common carotid artery were centrally measured using carotid ultrasonography. Significant factors related to mean IMT and maximum IMT were examined using multivariable analysis. Results: In 793 studied patients, mean IMT was 0.89 ± 0.15 mm and maximum IMT was 1.19 ± 0.32 mm. Age (per 10 years, parameter estimate = 0.044, p < 0.001), smoking (0.022, p = 0.004), category of blood pressure (0.022, p = 0.006), HDL cholesterol (per 10 mg/dl, −0.009, p = 0.008), and diabetes mellitus (0.033, p = 0.010) were independently associated with mean IMT. Age (per 10 years, 0.076, p < 0.001), smoking (0.053, p = 0.001), HDL cholesterol (−0.016, p = 0.036), and diabetes mellitus (0.084, p = 0.002) were independently associated with maximum IMT. Conclusion: Baseline mean and maximum values of carotid IMT in Japanese noncardioembolic stroke patients with hyperlipidemia were 0.89 ± 0.15 mm and 1.19 ± 0.32 mm, respectively, which were similar to those previously reported from Western countries. Age, smoking, hypertension, HDL cholesterol, and diabetes mellitus were associated with mean IMT, and those, except for hypertension, were associated with maximum IMT.

Supplemental Digital Content is available in the text., Background and Purpose— The effect of statins on progression of carotid intima–media complex thickness (IMT) has been shown exclusively in nonstroke Western patients. This study aimed to determine the effect of low-dose pravastatin on carotid IMT in Japanese patients with noncardioembolic ischemic stroke. Methods— This is a substudy of the J-STARS trial (Japan Statin Treatment Against Recurrent Stroke), a multicenter, randomized, open-label, parallel-group trial to examine whether pravastatin reduces stroke recurrence. Patients were randomized to receive pravastatin (10 mg daily, usual dose in Japan; pravastatin group) or not to receive any statins (control group). The primary outcome was IMT change of the common carotid artery for a 5-year observation period. IMT change was compared using mixed-effects models for repeated measures. Results— Of 864 patients registered in this substudy, 71 without baseline ultrasonography were excluded, and 388 were randomly assigned to the pravastatin group and 405 to the control group. Baseline characteristics were not significantly different, except National Institutes of Health Stroke Scale scores (median, 0 [interquartile range, 0–2] versus 1 [interquartile range, 0–2]; P=0.019) between the 2 groups. Baseline IMT (mean±SD) was 0.887±0.155 mm in the pravastatin group and 0.887±0.152 mm in the control group (P=0.99). The annual change in the IMT at 5-year visit was significantly reduced in the pravastatin group as compared with that in the control group (0.021±0.116 versus 0.040±0.118 mm; P=0.010). Conclusions— The usual Japanese dose of pravastatin significantly reduced the progression of carotid IMT at 5 years in patients with noncardioembolic stroke. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00361530.

The clinical course of schizophrenia is characterized by recurrence and chronicity and has a large burden on society. Nevertheless, diagnosis of schizophrenia is based only on distinctive symptoms and the disease course. Near-infrared spectroscopy (NIRS) is a useful method for measuring changes in the hemoglobin concentration in the cortical surface area and reflects brain function. We measured NIRS four times during the clinical course in a patient with first-episode schizophrenia. A 17-year-old woman admitted to our hospital because of hallucinations, delusions and appetite loss. After treatment with low-dose antipsychotics, NIRS findings showed a prompt increase in the cerebral blood volume in the frontal region. On the basis of the clinical course of this patient, we introduce a new point of view, namely, that NIRS findings may be useful as a state marker that indicates the severity of schizophrenia in some cases.

Stroke is one of the major causes of maternal death. This study aimed to analyze the maternal and fetal outcomes of stroke occurred during pregnancy and puerperium.We conducted a retrospective analysis of patients admitted to our perinatology center between 1982 and 2012 with a diagnosis of acute cerebral stroke during pregnancy or within 6 weeks postpartum.Thirty-four patients were registered and all the patients had never been diagnosed as stroke nor detected cerebrovascular abnormalities before the current pregnancies. They were divided into 8 ischemic strokes (ISs) and 26 intracranial hemorrhage group. In the hemorrhage group, there was a spontaneous abortion and two patients chose artificial abortions to avoid rehemorrhage, and there were another three intrauterine fetal deaths (IUFDs) in the acute stage of maternal stroke. More patients in hemorrhage group delivered in preterm than in IS group for the treatment of stroke, 10/23 (43%)Hemorrhagic stroke was more common etiology of stroke related to pregnancy than IS in this study. Intensive and multidisciplinary care was needed especially in hemorrhagic stroke related to pregnancy as in the hemorrhagic stroke the fetal survival rate was lower, and maternal conscious levels at the onset of the stroke and neurological outcomes in the chronic stage were worse than IS.

Dengue virus (DENV) is the causative agent of dengue fever (DF), dengue haemorrhagic fever (DHF), and dengue shock syndrome (DSS) and continues to be a public health problem in the tropical and subtropical areas. However, there is currently no antiviral treatment for DENV infection. In this study, our aim was to develop a stable reporter replicon cell system that supports constant viral RNA replication in cultured cells. The isolated replicon cells exhibited high levels of luciferase activity in the culture supernatant concomitant with expression of virus-encoded NS1, NS3 and NS5 proteins in the cells. The NS1, NS3 proteins and dsRNA were detected in the replicon cells by immunofluorescence analysis. Furthermore, the anti-DENV inhibitors ribavirin and bromocriptine significantly reduced the luciferase activity in a dose-dependent manner. High-throughput screening with a compound library using the stably-transfected replicon cells showed a Z' factor value of 0.57. Our screening yielded several candidates including one compound that has already shown anti-DENV activity. Taken together, our results demonstrate that this DENV subgenomic replicon cell system expressing a secretory luciferase gene can be useful for the high-throughput screening of anti-DENV compounds and the analysis of the replication mechanism of the DENV RNA.

Objective:\ud It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary prevention should be managed.\ud \ud Methods:\ud We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OACprior ) with those without prior oral anticoagulation (OACnaive ). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OACchanged ) with those who continued the same anticoagulation as secondary prevention (OACunchanged ). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine-Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).\ud \ud Results:\ud We included 5,413 patients (median age = 78 years [interquartile range (IQR) = 71-84 years]; 5,136 [96.7%] had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 [IQR = 2-12]). The median CHA2 DS2 -Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) was 5 (IQR = 4-6) and was similar for OACprior (n = 1,195) and OACnaive (n = 4,119, p = 0.103). During 6,128 patient-years of follow-up, 289 patients had AIS (4.7% per year, 95% CI = 4.2-5.3%). OACprior was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2-2.3, p = 0.005). OACchanged (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7-2.1, p = 0.415) compared with OACunchanged (n = 585).\ud \ud Interpretation:\ud Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA2 DS2 -Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high-risk patient group.

Background We aimed to clarify associations between prior anticoagulation and short‐ or long‐term clinical outcomes in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Methods and Results A total of 1189 ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation who were hospitalized within 7 days after onset were analyzed. Of these, 813 patients (68.4%) received no prior anticoagulation, 310 (26.1%) received prior warfarin treatment with an international normalized ratio ( INR ) INR ≥2 on admission, and the remaining 38 (3.2%) received prior direct oral anticoagulant treatment. Prior warfarin treatment was associated with a lower risk of death or disability at 3 months compared with no prior anticoagulation ( INR P =0.001; INR ≥2: adjusted odds ratio: 0.40; 95% CI, 0.16–0.97; P =0.043) but was not associated with a lower risk of death or disability at 2 years. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years compared with no prior anticoagulation (adjusted hazard ratio: 2.94; 95% CI, 1.20–6.15; P =0.021). Conclusions Prior warfarin treatment was associated with a lower risk of death or disability at 3 months but was not associated with a lower risk of death or disability at 2 years in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01581502.

Dengue virus (DENV) is the most prevalent human arthropod-borne virus and causes severe problems worldwide, mainly in tropical and sub-tropical regions. However, there is no specific antiviral drug against DENV infection. We and others recently reported that stearoyl-CoA desaturase-1 (SCD1) inhibitor showed potent suppression of hepatitis C virus replication. In this study, we examined the impact of SCD1 on DENV replication. We found that SCD1 inhibitors (MK8245 and #1716) dramatically suppressed DENV replication in a dose-dependent manner without cytotoxicity. This anti-DENV efficacy was observed against all four DENV serotypes and other flaviviruses, including Zika virus and Japanese encephalitis virus. A subgenomic replicon system of DENV was used to confirm that SCD1 inhibitor suppressed viral RNA replication. Interestingly, exogenous supplementation of unsaturated fatty acids resulted in recovery of the DENV titer even in the presence of SCD1 inhibitor, suggesting that fatty acid biosynthesis contributes to DENV genome replication. These findings indicate that SCD1 is a novel host factor required for DENV replication, and SCD1 inhibitor is a potential candidate for treating dengue fever.

This essay argues that Browning’s ‘most metaphysical and boldest’ poem after Sordello, Fifine at the Fair, is also a poem in which Percy Shelley’s influence can be detected. I have argued elsewhere for the influence of Shelley on Browning in Sordello and Browning returned to address issues that Shelley raised in ‘The Triumph of Life’ in Fifine. Although it is often thought that Browning moved away from Shelley after discovering the Harriet letters, I argue that he worked out his attitude towards Shelley in Fifine through the concepts of ‘falsehood’ and ‘truth’. As for his engagement with Romanticism, Browning criticizes the condescending attitude that the speaker–narrator takes in ‘The Triumph’ towards the people to embrace humanity in its flawed state. He also engages with the moral dilemma that was central to ‘The Triumph’ by working out the protagonist’s relationship with two female figures – Elvire and Fifine. As a result, the essay concludes that Fifine can be seen as a direct response to Shelley’s ‘...

Background and Purpose: In patients with emergent large vessel occlusion (ELVO), fluid-attenuated inversion recovery (FLAIR) hyperintense vessel (FHV) has been linked to cerebral hypoperfusion. However, the association between FHV and infarction lesion after successful recanalization by endovascular thrombectomy (ET) remains unknown. In this study, we investigated the relationship baseline FHV and baseline or post-ET diffusion weighted imaging (DWI) positive lesions. Methods: From April 2012 to August 2016, fifty-nine patients were received ET for ELVO of the anterior circulation. We included twenty-five patients of them who obtained successful (Thrombolysis In Cerebral Infarction score 2b/3) recanalization of ICA or M1 occlusion. All patients had DWI before and after ET and FLAIR before ET. Infarct lesions and FHV were evaluated in seven cortical lesions which divided according to cortical area of Alberta Stroke Program Early CT (ASPECT) scoring (I, M1-M6). The association between baseline or post-ET DWI positive and baseline FHV was analyzed in each one hundred seventy-five lesions. Results: DWI positive lesions were present in 65/171 (37%) and 108/175 (62%) lesions on baseline and post-ET DWI, respectively. FHV was present in 89/175 (51%) lesions on baseline FLAIR. Baseline DWI positive lesion was significantly higher at FHV positive lesion than FHV negative lesion (FHV (+) vs. FHV (-): 56% vs. 17%, p Conclusion: Baseline FHV positive lesions have already been infarcted before ET and likely to become infarction after successful recanalization compared to FHV negative lesion. Because FHV positive lesion became infarct despite early successful recanalization, FHV seemed to suggest severe hypoperfusion.

Background and Purpose: Modified Rankin scale (mRS) score at 3-month after onset is widely used as clinical outcomes in stroke patients. Functional Independence Measure (FIM) is a valid tool to estimate the level of ADL. However, there were few studies whether FIM score in acute stroke patients can predict clinical outcomes at 3-month. Our aim is to reveal that FIM scores of acute stroke patients can predict favorable outcome (mRS 0-1 at 3-month). Method: We used data from a prospectively collected observational registry in single stroke center between January 2016 and March 2017. Baseline NIHSS score, acute FIM score (=within 3 days from admission to the stroke unit), discharge FIM score (=at discharge from the stroke unit), and mRS score (before stroke, at 3-month) were collected. The relationship between discharge FIM score and mRS score at 3-month were examined using Spearman’s rank correlation test. Logistic regression analyses were used to reveal the predictors of favorable outcome. Results: Of 678 patients were admitted to our stroke center due to acute stroke, 410 patients whose clinical data could be obtained (60%; mean age, 74±13 years; male, 57%; the median of length of hospital stay, 21 days; 75% with ischemic stroke) were enrolled. The median of the baseline NIHSS score, acute and discharge FIM scores were 5 (interquartile range [IQR], 2-16), 53 (IQR 22-83), and 86 (IQR 32-119), respectively. Discharge FIM score strongly correlated with mRS score at 3 month (ρ=-0.86; p Conclusions: FIM score at discharge from the stroke unit can predict favorable clinical outcome at three months. Our results can help stroke physicians to expect stroke patients’ status in the chronic phase.

Background and purpose: Functional Independence Measure (FIM) is a valid tool to estimate the level of ADL. However, there were few studies whether FIM score in acute stroke patients is associated with the short-term outcome. Our aim is to reveal whether FIM scores within 3 days from admission to a stroke unit can predict the short-term good outcome (discharge directly to home). Method: We used data from a prospectively collected observational registry in a single stroke center between January 2016 and March 2017. Baseline NIHSS score, acute FIM score (= within 3 days from admission to the stroke unit), discharge FIM score (= at discharge from the stroke unit) were collected. FIM efficiency was calculated from (discharge FIM - acute FIM)/ the length of hospital stay. Logistic regression analysis was used to determine the independent predictors of discharge directly to home. Results: Of 678 patients were admitted to our stroke center due to acute stroke, 410 patients whose clinical data could be obtained (60%; mean age, 74±13 years; male, 57%; the median of length of hospital stay, 21 days; 75% with ischemic stroke) were enrolled. The median of the baseline NIHSS score, acute FIM score, and FIM efficiency were 5 (interquartile range [IQR], 2-16), 53 (IQR 22-83), and 0.88 (IQR 0.10-1.73), respectively. In univariate logistic regression analysis, male sex, acute ischemic stroke, baseline NIHSS score, acute FIM score, discharge FIM score, the length of hospital stay, and FIM efficiency were associated with discharge directly to home. In multivariate logistic regression analysis, acute FIM score (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.03-1.06; p71, with a sensitivity of 72%, specificity of 88%, and an area under the curve of 0.86 (p Conclusions: FIM scores within 3 days from admission to a stroke unit can predict discharge directly to home, which can help stroke physicians to expect the short-term outcomes.

Introduction: Early stroke risk in patients with transient ischemic attack (TIA) due to small vessel occlusion (SVO) is underestimated. We assessed whether TIA patients due to SVO are at a higher early stroke risk, using the data of a prospective, multicenter, observational registration study in Japan (PROMISE-TIA registry). Methods: The study subjects were 1,320 TIA patients (470 women, 69±12 years, median ABCD2 score 5) within 7 days of onset. The primary outcome was recurrent stroke within 30 days after TIA. SVO-TIA was defined as having lacunar TIA syndrome without cardiac source of embolism or large artery stenosis, as the exact determination of TIA due to SVO is difficult. Lacunar TIA syndrome was defined as unilateral weakness or sensory disturbance of at least two of three body parts (face, arm, and leg) in the absence of cortical dysfunction. Predictors for 30-day recurrent stroke were estimated using a Cox proportional hazards model. Results: Recurrent stroke within 30 days after TIA was observed in 61 patients (4.6%). In multivariable analysis, SVO-TIA (hazard ratio, 1.87; 95%CI, 1.11-3.11), higher systolic blood pressure at presentation (hazard ratio, 1.18 (per 10mmHg increase); 95%CI, 1.08-1.28) and presentation within 3 hours after onset (hazard ratio, 2.25; 95%CI, 1.30-4.10) were independently associated with recurrent stroke. Furthermore, SVO-TIA with an evidence of subcortical or brainstem infarcts on diffusion weighted imaging (definite TIA due to SVO) was a stronger predictor for recurrent stroke (hazard ratio, 3.63; 95%CI, 1.59-7.23). The presence of cardiac source of embolism and symptomatic large artery steno-occlusion were not significant predictors. Conclusions: The data from a Japanese large TIA registry suggested that patients with TIA due to SVO were at a higher risk of early recurrent stroke.

Depression is implicated as a risk factor for the recurrence of inflammatory bowel disease (IBD). Near-infrared spectroscopy (NIRS) and brain-derived neurotrophic factor (BDNF) are useful tools for evaluation of brain activity and a depressive state, respectively. The aim of this study was to clarify the association between brain activity or depressive symptoms and IBD using NIRS and BDNF. This study included 36 ulcerative colitis (UC) patients, 32 Crohn’s disease (CD) patients, and 17 healthy controls (HC). Center for Epidemiologic Studies Depression Scale (CES-D) scores were determined, NIRS was performed, and serum BDNF levels were measured in all subjects. NIRS showed that the mean oxygenated hemoglobin concentration was significantly lower in the frontal lobe in the UC group than in the HC group (HC 167 ± 106 vs. UC 83.1 ± 85.3, p

Background Patients with transient ischemic attack (TIA) without large-artery disease (LAD) or atrial fibrillation (AF) on admission may be at higher risk of stroke than previously thought. The aim of this study was to investigate early stroke risk and its predictors in such patients. Methods We studied 410 TIA patients admitted to our institute within 48 hours of onset. Urgent etiological workup revealed that 210 patients had neither symptomatic LAD nor AF. The outcome measure was the stroke occurrence within 7 days after admission. Results Stroke occurred within 7 days in 15 patients, 7.1% of patients without LAD or AF and 6.5% of those with LAD or AF, showing no statistical difference between the 2 groups. Twelve of the 15 patients were diagnosed with small-vessel disease as the stroke etiology. In multivariable regression analysis, motor lacunar symptoms (odds ratio [OR], 5.7; 95% confidence interval [CI], 1.4-41.1), high systolic blood pressure on admission of 183 mm Hg or greater (OR, 15.3; 95% CI, 3.8-80.2), and positive diffusion-weighted imaging findings (OR, 6.1; 95% CI, 1.6-28.1) were independent predictors for the stroke occurrence within 7 days in patients without LAD or AF. Conclusions TIA patients should be cautiously managed, even when neither LAD nor AF are identified by urgent workup. Clinical findings as motor lacunar symptom or high admission blood pressure, besides diffusion-weighted imaging findings, may be helpful to predict early stroke in such patients.

DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) is the planned Japanese space gravitational wave antenna, aiming to detect gravitational waves from astrophysically and cosmologically significant sources mainly between 0.1 Hz and 10 Hz and thus to open a new window for gravitational wave astronomy and for the universe. DECIGO will consists of three drag-free spacecraft arranged in an equilateral triangle with 1000 km arm lengths whose relative displacements are measured by a differential Fabry-Perot interferometer, and four units of triangular Fabry-Perot interferometers are arranged on heliocentric orbit around the sun. DECIGO is vary ambitious mission, we plan to launch DECIGO in era of 2030s after precursor satellite mission, B-DECIGO. B-DECIGO is essentially smaller version of DECIGO: B-DECIGO consists of three spacecraft arranged in an triangle with 100 km arm lengths orbiting 2000 km above the surface of the earth. It is hoped that the launch date will be late 2020s for the present..

A resin-supported peptide with an N-terminal primary amino group was developed as a primary aminocatalyst and used in the asymmetric Michael addition of nitromethane to α,β-unsaturated ketones. These peptides with helical motifs, that is, polyleucine and a repeated Leu-Leu-Aib (Aib=2-aminoisobutyric acid) sequence, efficiently catalyzed the reaction. The introduction of two tryptophan residues at the N-terminus of the helical peptides improved the enantioselectivity of the reaction, and using the catalysts in aqueous media enhanced the reaction rate. The versatility of the optimum catalyst with the (Trp)2-(Leu-Leu-Aib)3 sequence was demonstrated by applying it to other organocatalytic reactions such as the Michael addition of malonates to α,β-unsaturated ketones and a three-component, sequential reaction with methacrolein.

Background Atrial fibrillation impairs left atrial appendage function and the thrombus formation in the left atrial appendage is a major cause of cardioembolic stroke. Aims To evaluate the association between the volume of the left atrial appendage measured by real-time three-dimensional transesophageal echocardiography and presence of paroxysmal atrial fibrillation in patients with cerebral infarction or transient ischemic attack. Methods Real-time three-dimensional transesophageal echocardiography was performed to measure left atrial appendage end-diastolic and end-systolic volumes to calculate left atrial appendage ejection fraction. Patients with normal sinus rhythm at the time of real-time three-dimensional transesophageal echocardiography were divided into groups with and without paroxysmal atrial fibrillation. Volumetric data were corrected with the body surface area. Results Of 146 patients registered, 102 (29 women, 72·2 ± 10·7 years) were normal sinus rhythm at the examination. In 23 patients with paroxysmal atrial fibrillation, left atrial appendage end-diastolic volume (4·78 ± 3·00 ml/m2 vs. 3·14 ± 2·04 ml/m2, P = 0·003) and end-systolic volume (3·10 ± 2·47 ml/m2 vs. 1·39 ± 1·56 ml/m2, P < 0·001) were larger and left atrial appendage ejection fraction (37·3 ±19·1% vs. 57·1 ± 17·5%, P < 0·001) was lower than in the other 79 patients without paroxysmal atrial fibrillation. The optimal cutoff for left atrial appendage peak flow velocity to predict paroxysmal atrial fibrillation was 39·0 cm/s (sensitivity, 54·6%; specificity, 89·7%; c-statistic, 0·762). The cutoffs for left atrial appendage end-diastolic volume, end-systolic volume, and ejection fraction were 4·52 ml/m2 (sensitivity, 47·8%; specificity, 82·3%; c-statistic, 0·694), 1·26 ml/m2 (sensitivity, 91·3%; specificity, 60·3%; c-statistic, 0·806), and 47·9% (sensitivity, 78·3%; specificity, 74·7%; c-statistic, 0·774), respectively. In multivariate analysis, all these parameters were independently associated with paroxysmal atrial fibrillation after adjusting for sex, age, diabetes mellitus, and previous stroke. Conclusions Left atrial appendage volumetric analysis by real-time three-dimensional transesophageal echocardiography is a promising method for detecting paroxysmal atrial fibrillation in acute cerebral infarction or transient ischemic attack.

DECi-hertz Interferometer Gravitational-wave Observatory (DECIGO) is a future Japanese space gravitational-wave antenna. The most important objective of DECIGO, among various sciences to be aimed at, is to detect gravitational waves coming from the inflation of the universe. DECIGO consists of four clusters of spacecraft, and each cluster consists of three spacecraft with three Fabry–Perot Michelson interferometers. As a pathfinder mission of DECIGO, B-DECIGO will be launched, hopefully in the 2020s, to demonstrate technologies necessary for DECIGO as well as to lead to fruitful multimessenger astronomy. B-DECIGO is a small-scale or simpler version of DECIGO with the sensitivity slightly worse than that of DECIGO, yet good enough to provide frequent detection of gravitational waves., ファイル公開：2020/09/01

This article examines Robert Browning’s aesthetics, and argues for the influence of Leigh Hunt. It breaks away from the predominant view that the young Browning was influenced solely by Shelley. The article does not refute Shelley’s presence in Browning’s works, but rather complements it by suggesting that Browning owed much to other Romantics such as Hunt in his grounding of poetic principles. Browning’s critical attitude toward the Romantics such as Wordsworth, Shelley, and Byron is offset by his eager engagement with Hunt’s works. Browning embraces the real as opposed to the ideal, and his depiction of everyday life aligns him with Hunt’s preference for the more tangible aspects of life. It also notes Browning’s distance from Wordsworth, whose depiction of nature in solitude contrasts with Hunt’s urban sociability. I take as an example Browning’s ‘Fra Lippo Lippi’, which not only closely follows passages from Hunt’s Letters from Pisa and Letters from Genoa, but also emulates his aesthetics.