GNAO1 encephalopathy: broadening the phenotype and evaluating treatment and outcome

OBJECTIVE: To describe better the motor phenotype, molecular genetic features, and clinical course of GNAO1-related disease. METHODS: We reviewed clinical information, video recordings, and neuroimaging of a newly identified cohort of 7 patients with de novo missense and splice site GNAO1 mutations, detected by next-generation sequencing techniques. RESULTS: Patients first presented in early childhood (median age of presentation 10 months, range 0-48 months), with a wide range of clinical symptoms ranging from severe motor and cognitive impairment with marked choreoathetosis, self-injurious behavior, and epileptic encephalopathy to a milder phenotype, featuring moderate developmental delay associated with complex stereotypies, mainly facial dyskinesia and mild epilepsy. Hyperkinetic movements were often exacerbated by specific triggers, such as voluntary movement, intercurrent illnesses, emotion, and high ambient temperature, leading to hospital admissions. Most patients were resistant to drug intervention, although tetrabenazine was effective in partially controlling dyskinesia for 2/7 patients. Emergency deep brain stimulation (DBS) was life saving in 1 patient, resulting in immediate clinical benefit with complete cessation of violent hyperkinetic movements. Five patients had well-controlled epilepsy and 1 had drug-resistant seizures. Structural brain abnormalities, including mild cerebral atrophy and corpus callosum dysgenesis, were evident in 5 patients. One patient had a diffuse astrocytoma (WHO grade II), surgically removed at age 16. CONCLUSIONS: Our findings support the causative role of GNAO1 mutations in an expanded spectrum of early-onset epilepsy and movement disorders, frequently exacerbated by specific triggers and at times associated with self-injurious behavior. Tetrabenazine and DBS were the most useful treatments for dyskinesia

Elevated temperature material properties of stainless steel reinforcing bar

Corrosion of carbon steel reinforcing bar can lead to deterioration of concrete structures, especially in regions where road salt is heavily used or in areas close to sea water. Although stainless steel reinforcing bar costs more than carbon steel, its selective use for high risk elements is cost-effective when the whole life costs of the structure are taken into account. Considerations for specifying stainless steel reinforcing bars and a review of applications are presented herein. Attention is then given to the elevated temperature properties of stainless steel reinforcing bars, which are needed for structural fire design, but have been unexplored to date. A programme of isothermal and anisothermal tensile tests on four types of stainless steel reinforcing bar is described: 1.4307 (304L), 1.4311 (304LN), 1.4162 (LDX 2101®) and 1.4362 (2304). Bars of diameter 12 mm and 16 mm were studied, plain round and ribbed. Reduction factors were calculated for the key strength, stiffness and ductility properties and compared to equivalent factors for stainless steel plate and strip, as well as those for carbon steel reinforcement. The test results demonstrate that the reduction factors for 0.2% proof strength, strength at 2% strain and ultimate strength derived for stainless steel plate and strip can also be applied to stainless steel reinforcing bar. Revised reduction factors for ultimate strain and fracture strain at elevated temperatures have been proposed. The ability of two-stage Ramberg-Osgood expressions to capture accurately the stress-strain response of stainless steel reinforcement at both room temperature and elevated temperatures is also demonstrated

Crossbow Volume 1

Student Integrated ProjectIncludes supplementary materialDistributing naval combat power into many small ships and unmanned air vehicles that capitalize on emerging technology offers a transformational way to think about naval combat in the littorals in the 2020 time frame. Project CROSSBOW is an engineered systems of systems that proposes to use such distributed forces to provide forward presence to gain and maiantain access, to provide sea control, and to project combat power in the littoral regions of the world. Project CROSSBOW is the result of a yearlong, campus-wide, integrated research systems engineering effort involving 40 student researchers and 15 supervising faculty members. This report (Volume I) summarizes the CROSSBOW project. It catalogs the major features of each of the components, and includes by reference a separate volume for each of the major systems (ships, aircraft, and logistics). It also prresents the results of the mission and campaign analysis that informed the trade-offs between these components. It describes certain functions of CROSSBOW in detail through specialized supporting studies. The student work presented here is technologically feasible, integrated and imaginative. The student project cannot by itself provide definitive designs or analyses covering such a broad topic. It does strongly suggest that the underlying concepts have merit and deserve further serious study by the Navy as it transforms itself

Eye movements and brain oscillations to symbolic safety signs with different comprehensibility

Background: The aim of this study was to investigate eye movements and brain oscillations to symbolic safety signs with different comprehensibility. Methods: Forty-two young adults participated in this study, and ten traffic symbols consisting of easy-to-comprehend and hard-to-comprehend signs were used as stimuli. During the sign comprehension test, real-time eye movements and spontaneous brain activity [electroencephalogram (EEG) data] were simultaneously recorded. Results: The comprehensibility level of symbolic traffic signs significantly affects eye movements and EEG spectral power. The harder to comprehend the sign is, the slower the blink rate, the larger the pupil diameter, and the longer the time to first fixation. Noticeable differences on EEG spectral power between easy-to-comprehend and hard-to-comprehend signs are observed in the prefrontal and visual cortex of the human brain. Conclusions: Sign comprehensibility has significant effects on real-time nonintrusive eye movements and brain oscillations. These findings demonstrate the potential to integrate physiological measures from eye movements and brain oscillations with existing evaluation methods in assessing the comprehensibility of symbolic safety signs.open

Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab

Pharmacological inhibition of VEGF-A has proven to be effective in inhibiting angiogenesis and vascular leak associated with cancers and various eye diseases. However, little information is currently available on the binding kinetics and relative biological activity of various VEGF inhibitors. Therefore, we have evaluated the binding kinetics of two anti-VEGF antibodies, ranibizumab and bevacizumab, and VEGF Trap (also known as aflibercept), a novel type of soluble decoy receptor, with substantially higher affinity than conventional soluble VEGF receptors. VEGF Trap bound to all isoforms of human VEGF-A tested with subpicomolar affinity. Ranibizumab and bevacizumab also bound human VEGF-A, but with markedly lower affinity. The association rate for VEGF Trap binding to VEGF-A was orders of magnitude faster than that measured for bevacizumab and ranibizumab. Similarly, in cell-based bioassays, VEGF Trap inhibited the activation of VEGFR1 and VEGFR2, as well as VEGF-A induced calcium mobilization and migration in human endothelial cells more potently than ranibizumab or bevacizumab. Only VEGF Trap bound human PlGF and VEGF-B, and inhibited VEGFR1 activation and HUVEC migration induced by PlGF. These data differentiate VEGF Trap from ranibizumab and bevacizumab in terms of its markedly higher affinity for VEGF-A, as well as its ability to bind VEGF-B and PlGF

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

The Impact of Emotional Intelligence Element on Academic Achievement

The purpose of this study is to examine the impact of the five emotional intellingence elements identified as self-awareness, emotional management, self motivation, empathy, interpersonal skills towards secondary school students’ academic achievement. This study also aims to identify whether the five elements of emotional intelligence have been able to contribute to academic achievement. Statistical inference of the Pearson-r and multiple regression is used to analyze the data. The results showed that the significant relationship between self awareness (r = 0.21), emotional management (r = 0.21) and empathy (r = 0.21) at the level of p <0.05 with academic achievement. Multiple regression analysis (stepwise) result showed that only three elements of emotional intelligence which is self-awareness (ß = 0261), self motivation (ß =- 0182) and empathy (ß = 0167) accounted for 8.7% of variation in criterion (academic achievement). Research also presented a model designed to reflect the relationship between the elements of emotional intelligence and academic achievement. These studies imply that the level of emotional intelligence contributes to and enhances the cognitive abilities in student. Thus, to produce a competent generation and successful country in line with the philosophy of education, persistence of the emotional intelligence in student is essential. Key words: emotional intelligence, academic achievement, self-awareness, emotional management, self motivation, empathy, interpersonal skill