SrTiO3—Glimpses of an Inexhaustible Source of Novel Solid State Phenomena

The purpose of this selective review is primarily to demonstrate the large versatility of the insulating quantum paraelectric perovskite SrTiO3 explained in “Introduction” part, and “Routes of SrTiO3 toward ferroelectricity and other collective states” part. Apart from ferroelectricity under various boundary conditions, it exhibits regular electronic and superconductivity via doping or external fields and is capable of displaying diverse coupled states. “Magnetoelectric multiglass (Sr,Mn)TiO3” part, deals with mesoscopic physics of the solid solution SrTiO3:Mn2+. It is at the origin of both polar and spin cluster glass forming and is altogether a novel multiferroic system. Independent transitions at different glass temperatures, power law dynamic criticality, divergent third-order susceptibilities, and higher order magneto-electric interactions are convincing fingerprints

Towards the genetic basis of cerebral venous thrombosis-the BEAST Consortium: a study protocol.

INTRODUCTION: Cerebral venous thrombosis (CVT) is a rare cerebrovascular condition accounting for <1% of all stroke cases and mainly affects young adults. Its genetic aetiology is not clearly elucidated. METHODS AND ANALYSIS: To better understand the genetic basis of CVT, we have established an international biobank of CVT cases, Biorepository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) which aims to recruit highly phenotyped cases initially of European descent and later from other populations. To date we have recruited 745 CVT cases from 12 research centres. As an initial step, the consortium plans to undertake a genome-wide association analysis of CVT using the Illumina Infinium HumanCoreExome BeadChip to assess the association and impact of common and low-frequency genetic variants on CVT risk by using a case-control study design. Replication will be performed to confirm putative findings. Furthermore, we aim to identify interactions of genetic variants with several environmental and comorbidity factors which will likely contribute to improve the understanding of the biological mechanisms underlying this complex disease. ETHICS AND DISSEMINATION: BEAST meets all ethical standards set by local institutional review boards for each of the participating sites. The research outcomes will be published in international peer-reviewed open-access journals with high impact and visibility. The results will be presented at national and international meetings to highlight the contributions into improving the understanding of the mechanisms underlying this uncommon but important disease. This international DNA repository will become an important resource for investigators in the field of haematological and vascular disorders

Coma in adult cerebral venous thrombosis:The BEAST study

Background and purpose: Coma is an independent predictor of poor clinical outcomes in cerebral venous thrombosis (CVT). We aimed to describe the association of age, sex, and radiological characteristics of adult coma patients with CVT. Methods: We used data from the international, multicentre prospective observational BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. Only positively associated variables with coma with &lt;10% missing data in univariate analysis were considered for the multivariate logistic regression model. Results: Of the 596 adult patients with CVT (75.7% women), 53 (8.9%) patients suffered coma. Despite being a female-predominant disease, the prevalence of coma was higher among men than women (13.1% vs. 7.5%, p = 0.04). Transverse sinus thrombosis was least likely to be associated with coma (23.9% vs. 73.3%, p &lt; 0.001). The prevalence of superior sagittal sinus thrombosis was higher among men than women in the coma sample (73.6% vs. 37.5%, p = 0.01). Men were significantly older than women, with a median (interquartile range) age of 51 (38.5–60) versus 40 (33–47) years in the coma (p = 0.04) and 44.5 (34–58) versus 37 (29–48) years in the non-coma sample (p &lt; 0.001), respectively. Furthermore, an age-and superior sagittal sinus-adjusted multivariate logistic regression model found male sex (odds ratio = 1.8, 95% confidence interval [CI] = 1.0–3.4, p = 0.04 to be an independent predictor of coma in CVT, with an area under the receiver operating characteristic curve of 0.61 (95% CI = 0.52–0.68, p = 0.01). Conclusions: Although CVT is a female-predominant disease, men were older and nearly twice as likely to suffer from coma than women

Genome-Wide Association Study Identifies First Locus Associated with Susceptibility to Cerebral Venous Thrombosis

Objective Cerebral venous thrombosis (CVT) is an uncommon form of stroke affecting mostly young individuals. Although genetic factors are thought to play a role in this cerebrovascular condition, its genetic etiology is not well understood. Methods A genome-wide association study was performed to identify genetic variants influencing susceptibility to CVT. A 2-stage genome-wide study was undertaken in 882 Europeans diagnosed with CVT and 1,205 ethnicity-matched control subjects divided into discovery and independent replication datasets. Results In the overall case-control cohort, we identified highly significant associations with 37 single nucleotide polymorphisms (SNPs) within the 9q34.2 region. The strongest association was with rs8176645 (combined p = 9.15 x 10(-24); odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.76-2.31). The discovery set findings were validated across an independent European cohort. Genetic risk score for this 9q34.2 region increases CVT risk by a pooled estimate OR = 2.65 (95% CI = 2.21-3.20, p = 2.00 x 10(-16)). SNPs within this region were in strong linkage disequilibrium (LD) with coding regions of the ABO gene. The ABO blood group was determined using allele combination of SNPs rs8176746 and rs8176645. Blood groups A, B, or AB, were at 2.85 times (95% CI = 2.32-3.52, p = 2.00 x 10(-16)) increased risk of CVT compared with individuals with blood group O. Interpretation We present the first chromosomal region to robustly associate with a genetic susceptibility to CVT. This region more than doubles the likelihood of CVT, a risk greater than any previously identified thrombophilia genetic risk marker. That the identified variant is in strong LD with the coding region of the ABO gene with differences in blood group prevalence provides important new insights into the pathophysiology of CVT. ANN NEUROL 2021Peer reviewe

Towards the genetic basis of cerebral venous thrombosis-the BEAST Consortium : a study protocol

Introduction: Cerebral venous thrombosis (CVT) is a rare cerebrovascular condition accounting for <1% of all stroke cases and mainly affects young adults. Its genetic aetiology is not clearly elucidated. Methods and analysis: To better understand the genetic basis of CVT, we have established an international biobank of CVT cases, Biorepository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) which aims to recruit highly phenotyped cases initially of European descent and later from other populations. To date we have recruited 745 CVT cases from 12 research centres. As an initial step, the consortium plans to undertake a genome-wide association analysis of CVT using the Illumina Infinium HumanCoreExome BeadChip to assess the association and impact of common and low-frequency genetic variants on CVT risk by using a case-control study design. Replication will be performed to confirm putative findings. Furthermore, we aim to identify interactions of genetic variants with several environmental and comorbidity factors which will likely contribute to improve the understanding of the biological mechanisms underlying this complex disease. Ethics and dissemination: BEAST meets all ethical standards set by local institutional review boards for each of the participating sites. The research outcomes will be published in international peer-reviewed open-access journals with high impact and visibility. The results will be presented at national and international meetings to highlight the contributions into improving the understanding of the mechanisms underlying this uncommon but important disease. This international DNA repository will become an important resource for investigators in the field of haematological and vascular disorders.Peer reviewe

Coma in adult cerebral venous thrombosis: The BEAST study

Background and purpose: Coma is an independent predictor of poor clinical outcomes in cerebral venous thrombosis (CVT). We aimed to describe the association of age, sex, and radiological characteristics of adult coma patients with CVT. Methods: We used data from the international, multicentre prospective observational BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. Only positively associated variables with coma with <10% missing data in univariate analysis were considered for the multivariate logistic regression model. Results: Of the 596 adult patients with CVT (75.7% women), 53 (8.9%) patients suffered coma. Despite being a female-predominant disease, the prevalence of coma was higher among men than women (13.1% vs. 7.5%, p = 0.04). Transverse sinus thrombosis was least likely to be associated with coma (23.9% vs. 73.3%, p < 0.001). The prevalence of superior sagittal sinus thrombosis was higher among men than women in the coma sample (73.6% vs. 37.5%, p = 0.01). Men were significantly older than women, with a median (interquartile range) age of 51 (38.5–60) versus 40 (33–47) years in the coma (p = 0.04) and 44.5 (34–58) versus 37 (29–48) years in the non-coma sample (p < 0.001), respectively. Furthermore, an age- and superior sagittal sinus-adjusted multivariate logistic regression model found male sex (odds ratio = 1.8, 95% confidence interval [CI] = 1.0–3.4, p = 0.04) to be an independent predictor of coma in CVT, with an area under the receiver operating characteristic curve of 0.61 (95% CI = 0.52–0.68, p = 0.01). Conclusions: Although CVT is a female-predominant disease, men were older and nearly twice as likely to suffer from coma than women

Genetic analysis of <i>Echinococcus granulosus</i> from humans and pigs in Poland, Slovakia and Ukraine: a multicenter study

Mitochondrial ND1 gene sequences were obtained from 56 isolates of E. granulosus from pigs collected in Central and East Europe (Poland, Slovakia and Ukraine) and from 5 isolates of E. granulosus from humans collected in Poland. No differences have been found between isolates from all pigs and between those from pigs and humans; all sequences were identical or very similar to the published sequence of the G7 strain. Additionally, 21 clones of the ITS1 rDNA obtained from 5 isolates of E. granulosus collected from pigs in 3 countries and 1 human isolate from Poland, were sequenced. Our data do not confirm the existence of specific G9 strain of E. granulosus in humans (Scott et al. 1997). Moreover, high sequence divergence found between and within the isolates indicates a strong polymorphism of ITS rDNA copies making use of this gene for identification of E. granulosus strains and reconstruction of their phylogenetic relationships questionable

Understanding Physician and Patient Preferences for Thrombolysis in Ischemic Stroke Eligible for Endovascular Thrombectomy

Background In light of evidence from recent trials that endovascular thrombectomy (EVT) alone may potentially be noninferior to combined treatment, that is, with intravenous thrombolysis (IVT) with alteplase and EVT, we sought to understand physician and patient preferences around this issue. Methods We conducted a 2‐stage mixed methods study that included a structured, international, web‐based cross‐sectional survey among stroke physicians, and a focus group involving stroke survivors and caregivers. Demographic information was collected from all participants. The survey offered multiple choice questions and options to respond via free text which was analyzed quantitatively. The focus group was conducted online and analyzed qualitatively using a grounded theory approach. Results A total of 225 physicians (67% men) from 44 countries completed the survey. Most participants (70%) were between 31 and 50 years of age. Survey results showed that in current practice, 90% respondents would offer IVT to patients with large vessel occlusion stroke eligible for both IVT and EVT. When asked if their practice would change in light of recent trials, 63% responded no. When asked about the appropriate timing for IVT in the setting of large vessel occlusion stroke with EVT availability, 56% preferred to administer IVT immediately, 21% were willing to defer the decision for 30 minutes from groin puncture, and 8% were willing to defer for 60 minutes from groin puncture to assess if reperfusion was achieved with EVT. A total of 61% participants would choose to use tenecteplase over alteplase as the preferred drug for IVT if both drugs are backed by evidence. The focus group identified a need to better understand patient characteristics that may benefit from EVT‐only or combined strategies. The focus group also identified the need for more data to inform physician decision making. Conclusions Most physicians surveyed prefer IVT before EVT in patients with acute ischemic stroke attributable to large vessel occlusion, although there was some uncertainty around this issue. The need for further studies, including data on IVT with tenecteplase and among various patient subgroups to inform decision making, was apparent from both the survey and the patient focus group

AcT Trial: Protocol for a Pragmatic Registry‐Linked Randomized Clinical Trial

Background Intravenous thrombolysis with alteplase is widely used in patients with acute ischemic stroke presenting early after symptom onset. Recent phase II trials have suggested that intravenous tenecteplase may be safer and associated with higher early reperfusion rates as compared with alteplase. This study investigates whether intravenous tenecteplase is noninferior to intravenous alteplase for the treatment of acute ischemic stroke. Methods This is a pragmatic, registry‐linked, prospective, randomized (1:1) controlled, open‐label parallel group clinical trial (AcT [Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke]) with blinded end point assessment of 1600 patients to test if intravenous tenecteplase (0.25 mg/kg body weight, maximum dose 25 mg) is noninferior to intravenous alteplase (0.9 mg/kg body weight; maximum dose, 90 mg) in patients with acute ischemic stroke eligible for intravenous thrombolysis in clinical routine. Patients are recruited from comprehensive and primary stroke centers and enrolled using deferral of consent. The proposed sample has at least 90% power with a noninferiority margin of 5%, assuming incidence of the 90‐day modified Rankin Scale score of 0 to 1 is 38% in the tenecteplase and 35% in the alteplase groups, and a loss to follow‐up rate <5%. Results The blinded primary end point is the proportion of subjects achieving a 90‐day modified Rankin Scale score of 0 to 1. Key safety outcomes include 24‐hour symptomatic intracerebral hemorrhage and 90‐day all‐cause mortality. All serious adverse events within a 24‐hour period will be reported and coded using the Medical Dictionary for Regulatory Activities. Outcomes are collected either centrally (primary, key secondary, and safety end points) or through ongoing Canadian stroke registries. The primary analysis is a simple unadjusted comparison of proportions. Conclusions Results from the trial will provide real‐world evidence of the effectiveness of intravenous tenecteplase versus alteplase in patients with acute ischemic stroke presenting early after stroke onset