"Sudden Drop" in Blood Pressure is Associated With Recanalization After Thrombolysis.

We aim to investigate whether the phenomenon of "sudden drop" in blood pressure (BP) within the first 2 hours is associated with vessel recanalization.We retrospectively examined clinical and imaging data from a consecutive series of patients with stroke with large vessel occlusion treated with intravenous thrombolysis (IVT). BP was monitored every 15 minutes during the first 2 hours, then every 30 minutes for 6 hours, and then every hour for 16 hours.We observed the phenomenon of "sudden drop" in systolic BP (≥20 mm Hg) in 82 (50.9%) patients in the first 2 hours and vessel recanalization in 87 (54.0%) patients 24 hours after treatment. This phenomenon was independently associated with recanalization (odds ratio 2.100; 95% confidence interval: 1.085-4.062; P = 0.028) after adjusting for the history of atrial fibrillation, coronary heart disease, and hypertension.The phenomenon of "sudden drop" in systolic BP with 20 mm Hg or greater between 2 continuous measurements within the first 2 hours is associated with recanalization after IVT in patients with large vessel occlusion, especially for middle cerebral artery occlusion

Experimental Study of Silty Clay Plane Strain Tri-axial Test under RTC Path and Modified Cam-clay Model

The character of geomaterials is affected by stress path remarkably. Under different stress paths, the stress-strain characteristics of geomaterials are difference. For the unloading path in existing engineering situation, the physical parameters and constitutive model is usually determined by loading test. The path to uninstall the actual project conditions which may be a larger error. Therefore, this work proceeding from the actual project, deep excavation of the lateral unloading condition is analysed. The tests of CTC path and RTC path on silty clay in Huangshi city of china by multi-path tri-axial plane strain are carried on in the geotechnical Engineering Laboratory of Huangshi Institute of Technology. Then, the phenomenon under the two stress paths are compared with each other and describing the differences between them. The mechanical properties in the RTC stress path is analyzed mainly. Based on the Cam-Clay model framework, then derived this material yield equation based on Cam-clay model, Laiding the foundation for the numerical analysis

Reliability Analysis of High Rise Building Considering Wind Load Uncertainty

In engineering structures, the safety problems are always depending on the respond of structures to different types of load. The safety assessment of a high rise building is highly depending on the analysis of environmental load. Many codes and practices have proposed many requirements for engineers in the design works. These include safety factors, limitations on damage, maximum deflections and so on. When violations in these requirements occur, the structure is believed to be dangerous. But once the problem becomes complicated such as multiple unknown loads in one building, it requires reliability analysis in the design. It must take care of all the assumptions and uncertainties in the structural design. In probabilistic assessment, any input variable is considered as an uncertainty. However, the traditional way to deal with these problems may have problems when uncertainties are large. Many probabilistic safety measures need to be reconsidered in engineering work. This paper, we will provide reliability analysis on a high rise building with consideration of wind load. All the most commonly applied reliability methods are been utilized in this analysis and compared base on the performance. The statistical influences including correlation and distribution type are also discussed in the same reliability problem

Association Between Cortical Superficial Siderosis and Dementia in Patients With Cognitive Impairment: A Meta-Analysis

Background: It remains unclear whether cortical superficial siderosis (cSS) is associated with dementia and its subtypes. We thus performed a meta-analysis to evaluate the relationship between dementia and cSS.Methods: We searched EMBASE, PubMed, and Web of Science for relevant studies assessing risk of dementia and prevalence of cSS in patients with cognitive impairment. Fixed-effects and random-effects models were performed.Results: Seven eligible studies including 3,218 patients with definite cognitive impairment were pooled in meta-analysis. The prevalence of cSS was 3.4%. The pooled analysis demonstrates odds ratio for cSS and dementia to be 1.60 (95% CI 1.04–2.44; p = 0.031). Subgroup analysis further indicated a significant association between cSS and Alzheimer's disease (AD) (OR = 2.01, 95% CI 1.34–3.02; p < 0.001), but not non-AD dementia (OR = 0.700, 95% CI 0.435–1.128; p = 0.143).Conclusions: Our meta-analysis of available published data demonstrates an increased prevalence of dementia in the subjects with pre-existing cSS, especially for AD. These findings suggest cSS to be a candidate imaging indicator for AD. Further longitudinal research is needed to investigate the clinical relevance

Snf2h Primes UL Neuron Production

Alterations in the homeostasis of either cortical progenitor pool, namely the apically located radial glial (RG) cells or the basal intermediate progenitors (IPCs) can severely impair cortical neuron production. Such changes are reflected by microcephaly and are often associated with cognitive defects. Genes encoding epigenetic regulators are a frequent cause of intellectual disability and many have been shown to regulate progenitor cell growth, including our inactivation of the Smarca1 gene encoding Snf2l, which is one of two ISWI mammalian orthologs. Loss of the Snf2l protein resulted in dysregulation of Foxg1 and IPC proliferation leading to macrocephaly. Here we show that inactivation of the closely related Smarca5 gene encoding the Snf2h chromatin remodeler is necessary for embryonic IPC expansion and subsequent specification of callosal projection neurons. Telencephalon-specific Smarca5 cKO embryos have impaired cell cycle kinetics and increased cell death, resulting in fewer Tbr2+ and FoxG1+ IPCs by mid-neurogenesis. These deficits give rise to adult mice with a dramatic reduction in Satb2C upper layer neurons, and partial agenesis of the corpus callosum. Mice survive into adulthood but molecularly display reduced expression of the clustered protocadherin genes that may further contribute to altered dendritic arborization and a hyperactive behavioral phenotype. Our studies provide novel insight into the developmental function of Snf2h-dependent chromatin remodeling processes during brain development

A new mouse model of ATR-X syndrome carrying a common patient mutation exhibits neurological and morphological defects

ATRX is a chromatin remodelling ATPase that is involved in transcriptional regulation, DNA damage repair and heterochromatin maintenance. It has been widely studied for its role in ALT-positive cancers, but its role in neurological function remains elusive. Hypomorphic mutations in the X-linked ATRX gene cause a rare form of intellectual disability combined with alpha-thalassemia called ATR-X syndrome in hemizygous males. Clinical features also include facial dysmorphism, microcephaly, short stature, musculoskeletal defects and genital abnormalities. Since complete deletion of ATRX in mice results in early embryonic lethality, the field has largely relied on conditional knockout models to assess the role of ATRX in multiple tissues. Given that null alleles are not found in patients, a more patient-relevant model was needed. Here, we have produced and characterised the first patient mutation knock-in model of ATR-X syndrome, carrying the most common causative mutation, R246C. This is one of a cluster of missense mutations located in the chromatin binding domain and disrupts its function. The knock-in mice recapitulate several aspects of the patient disorder, including craniofacial defects, microcephaly, reduced body size and impaired neurological function. They provide a powerful model for understanding the molecular mechanisms underlying ATR-X syndrome and for testing potential therapeutic strategies

The Naturally Occurring YMDD Mutation among Patients Chronically Infected HBV and Untreated with Lamivudine: A Systematic Review and Meta-Analysis

Background: Several recent reports have demonstrated that tyrosine (Y)-methionine (M)-aspartic acid (D)-aspartic acid (D) (YMDD) motif mutations can naturally occur in chronic HBV patients without antiviral treatment such as lamivudine therapy. This paper aims to assess the overall spontaneous incidence and related risk factors of YMDD-motif mutations among lamivudine-naïve chronic HBV carriers, so as to provide some clue for clinical treatment of hepatitis B. Methodology/Principal Findings: Chinese and English literatures were searched for studies reporting natural YMDD mutations among untreated chronic HBV patients from 2001 to 2010. The incidence estimates were summarized and analyzed by meta-analyses. Forty-seven eligible articles from eight countries were selected in this review (13 in English and 34 in Chinese). The pooled incidence of YMDD-motif mutation among untreated chronic HBV patients from eight countries was 12.21 % (95 % CI: 9.69%–14.95%). China had an incidence of 13.38 % (95 % CI: 10.90%–16.07%) and seven other countries had an incidence of 9.90 % (95 % CI: 3.28%–19.55%), respectively. Lamivudine therapy would increase the risk of mutations 5.23 times higher than the untreated patients. A higher HBV DNA copy number was associated with increased incidence of natural YMDD mutation. No significant difference was found in YMDD mutation incidence between groups of different gender, age, HBeAg status, patients ’ ALT (alanine aminotransferase) level, and between the groups of HBV genotype B and C. Conclusions: The YMDD-motif mutations can occur spontaneously with a relatively high incidence in CHB patient

Pathogenic variants in SMARCA1 cause an X-linked neurodevelopmental disorder modulated by NURF complex composition

Pathogenic variants in ATP-dependent chromatin remodeling proteins are a recurrent cause of neurodevelopmental disorders (NDDs). The NURF complex consists of BPTF and either the SNF2H ( SMARCA5) or SNF2L ( SMARCA1) ISWI-chromatin remodeling enzyme. Pathogenic variants in BPTF and SMARCA5 were previously implicated in NDDs. Here, we describe 40 individuals from 30 families with de novo or maternally inherited pathogenic variants in SMARCA1. This novel NDD was associated with mild to severe ID/DD, delayed or regressive speech development, and some recurrent facial dysmorphisms. Individuals carrying SMARCA1 loss-of-function variants exhibited a mild genome-wide DNA methylation profile and a high penetrance of macrocephaly. Genetic dissection of the NURF complex using Smarca1, Smarca5, and Bptfsingle and double mouse knockouts revealed the importance of NURF composition and dosage for proper forebrain development. Finally, we propose that genetic alterations affecting different NURF components result in a NDD with a broad clinical spectrum

A New Erosion Model for Wind-Induced Structural Vibrations

In recent years, computational fluid dynamics (CFD) method has been widely utilized in simulating wind-induced snow drifting. In the simulating process, the erosion flux is the main controlling factor which can be calculated by the product of erosion coefficient and the differences between the flow stress and threshold stress. The erosion coefficient is often adopted as an empirical constant which is believed not to change with time and space. However, in reality, we do need to consider the influences of snow diameter, density, and wind speed on the erosion coefficient. In this technical note, a function of air density, sow particle density, snow particle radius, and snow particle strength bond is proposed for the erosion coefficient. Based on an experiment study, the effects of these parameters in erosion coefficient is analyzed and discussed. The probability distribution and value range of erosion coefficient are also presented in this technical note. The applicability of this approach is also demonstrated in a numerical study for predicting the snow distributions around a cube structure. The randomness of the structural vibrations is studied with details