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Heterozygous defects in runt-related transcription factor 1 (RUNX1) are causative of a familial platelet disorder with associated myeloid malignancy (FPDMM). Because RUNX1-deficient animal models do not mimic bleeding disorder or leukemic risk associated with FPDMM, development of a proper model system is critical to understanding the underlying mechanisms of the observed phenotype and to identifying therapeutic interventions. We previously reported an in vitro megakaryopoiesis system comprising human CD34+ hematopoietic stem and progenitor cells that recapitulated the FPDMM quantitative megakaryocyte defect through a decrease in RUNX1 expression via a lentiviral short hairpin RNA strategy. We now show that shRX-megakaryocytes have a marked reduction in agonist responsiveness. We then infused shRX-megakaryocytes into immunocompromised NOD scid gamma (NSG) mice and demonstrated that these megakaryocytes released fewer platelets than megakaryocytes transfected with a nontargeting shRNA, and these platelets had a diminished half-life. The platelets were also poorly responsive to agonists, unable to correct thrombus formation in NSG mice homozygous for a R1326H mutation in von Willebrand Factor (VWFR1326H), which switches the species-binding specificity of the VWF from mouse to human glycoprotein Ibα. A small-molecule inhibitor RepSox, which blocks the transforming growth factor β1 (TGFβ1) pathway and rescued defective megakaryopoiesis in vitro, corrected the thrombopoietic defect, defects in thrombus formation and platelet half-life, and agonist response in NSG/VWFR1326H mice. Thus, this model recapitulates the defects in FPDMM megakaryocytes and platelets, identifies previously unrecognized defects in thrombopoiesis and platelet half-life, and demonstrates for the first time, reversal of RUNX1 deficiency–induced hemostatic defects by a drug.

Recently, the R&D of weapon systems has been strengthened in terms of economic cost management throughout the entire life cycle from performance. This study proposes the method for setting the optimal maintenance concept based on RAM-C in weapon system acquisition stage by calculating the operation & maintenance cost as well as reliability, availability, and maintainability. First, we design a simulation model for analysis of weapon system logistic supportability. In addition, information such as weapon system Part Breakdown Structure, operation & maintenance system, cost, and etc for simulation analysis, is applied. Based on the obtained simulation results, the optimal plan is selected among alternatives designed with various maintenance concepts through normalization and weight setting. It is expected to be of technical help in the application of RAM-C in the weapon system acquisition stage.

Purpose Fast food consumption is examined through the theoretical lens of the food consumption value model. Specifically, this study aims to examine whether process value moderates the impact of fast-food consumption value on consumer decision-making. Design/methodology/approach Data is collected from 380 US consumers via a self-administered online questionnaire. Structural equation modeling and moderated mediation analysis are used to test the relationships between fast-food consumption values (product value, location value, emotional value, social value and process value), attitude and behavioral intention. Findings Location value (physical and experiential environment of fast-food consumption) and emotional value (positive affect from fast-food consumption) of fast food positively influence behavioral intention through positive attitude toward fast food. Positive impact of product value (physical attributes of fast food) on behavioral intention through attitude is attenuated by process value (consumers’ level of concern on sustainability of fast-food production). Practical implications Fast-food restaurants should prioritize their investments in providing location value (e.g. pleasant restaurant atmosphere) and emotional value. It is also important to take caution in focusing too much on product value and consider investing more resources into implementing sustainable practices. Originality/value The consumption value-based approach not only updates previous understanding of fast-food consumption behavior but also offers insights on how consumers’ decision-making process is influenced by their perception toward sustainability issues of fast-food production.

In an electric railway, an overhead contact system (OCS) is assembled with many components, and it maintains a voltage of 25 kV to supply electricity to the electric trains. As electric trains grow faster, the overhead line comes to employ a diverse range of materials to deliver electricity and maintain high tension. Overhead lines supply electricity to electric trains through mechanical contact with a pantograph, and since they are not fault-tolerant, they require high reliability. That makes it take a long time to develop and supply components and also makes it difficult and time consuming to apply new materials or new designs to components. This study proposes a manufacturing process for overhead line components using 3D printing technology. For this, a clevis terminal clamp for high-speed railway was chosen and a design drawing was created with 3D scanning. For molding, additive manufacturing technology was used. The study castings were obtained by applying precision casting and sand mold casting methods, respectively, and their elongation and tensile strength were compared with products made with a traditional method.

In this paper, we implement a digital multi-beamformer using FPGA(Field Programmable Gate Array) which has advantages in parallel and real-time data processing. This is accomplished through the use of not only high-speed data communication but also multiple beam forming, which is currently required by MFR(Multi Function Radar). As a result, the beamformer can process 24 Gbps throughput in real-time and form 5 digital beams at the same time. It is also compared to the results of Matlab simulations. We demonstrate how an implemented beamformer can be used in an MFR system by using a digital array antenna.

Introduction Aneurysmal subarachnoid hemorrhage (aSAH) commonly presents with hydrocephalus due to obstruction of cerebrospinal fluid (CSF) passage across the ventricular system in the brain. Placement of an external ventricular device (EVD) and in some cases ventriculoperitoneal shunt (VPS) are often necessary for patients requiring prolonged CSF diversion. The study aimed at evaluating critical factors that play a role in determining the need for extended extraventricular drainage. Methods We performed a retrospective observational cohort study of two groups of patients with radiological imaging confirmed high grade aSAH (Hunt & Hess grades 3-5) who required VPS placement, shunt-dependent group, and who did not require long term CSF diversion, non-shunt-dependent group. We collected and analyzed data regarding the daily CSF output for 10 days following EVD placement, daily EVD height, intracranial pressure (ICP) and cerebral perfusion pressure (CPP), indicators of hydrocephalus, and CSF characteristics. Results The cohort, comprising of 8 patients in the shunt-dependent group and 32 patients in the non-shunt-dependent group, displayed median daily CSF output of 275.1 mL/day and 193.4 mL/day, respectively ( P = .0005). ROC curve for CSF drainage for the two groups showed an area under the curve (AUC) of 0.71 with a 95% confidence interval (CI) 0.65 to 0.77. Qualitative analysis of CSF characteristics revealed that the shunt-dependent group had more proteinaceous, darker red color, and greater proportion of red blood cells (RBCs) although not statistically significant. Conclusions Determinants of prolonged CSF drainage requirements in patients with high grade aSAH are not fully elucidated to this date and there is no standardized protocol for CSF diversion. Our study revealed potential markers that can be used in the assessment for the need for long term CSF diversion. Our limited sample size necessitates further research to establish clear correlations and cutoffs of these parameters in predicting long term CSF diversion requirements.

A well-known functional gastrointestinal disorder called functional dyspepsia (FD) is defined by dyspeptic symptoms without any structural abnormalities. In alternative intervention, electrolyzed alkaline-reduced water (EARW) consumption is regarded as a treatment modality for gastrointestinal symptoms despite its mechanism not yet fully understood. The present clinical study aimed to investigate the effects of EARW on gastrointestinal symptoms of patients with FD. Forty-eight participants with FD were screened, and 42 were enrolled. Participants were randomly allocated to the EARW (n = 21) and purified water (PW) (n = 21) groups. The EARW group ingested EARW (10 mL/kg body weight/day) for 6 weeks. The gastrointestinal symptom rating scale (GSRS), functional dyspepsia-related quality of life (FD-QoL), the Korean version of the Nepean Dyspepsia Index (NDI-K) were used as primary outcome measures at baseline and at 6 weeks, and inflammatory markers were measured as the secondary outcome. Two participants dropped out, and 40 participants (EARW = 20 and PW = 20) completed the trial. Total GSRS score was significantly lower in the EARW group (34.27%, p < 0.01) than in the PW (18.16%) group. In the five subcategories of GSRS, the decreased score between baseline and post-intervention for the EARW and PW groups were 43.59% and 21.33% in abdominal pain score, respectively; 38.98% and 18.92% in reflux syndrome, respectively; 25.42% and 20.90% in diarrhea, respectively; 35.87% and 21.48% in indigestion, respectively; and 32.81% and 10.71% in constipation, respectively, and all the parameters were significantly different in the EARW group compared with those in the PW group. The NDI-K score was also lower in the EARW group (p < 0.01) than in the PW group. FD-QoL score decreased significantly more in the EARW group after intervention than in the PW group (p < 0.05). Additionally, inflammatory cytokines (TNF-α and IFN-γ) levels significantly suppressed in the EARW group after 6 weeks of drinking compared with the levels at the baseline. Our clinical study suggests that long-term drinking of EARW (pH 9.5) may improve FD-related symptoms and the quality of life of FD patients through home-based administration.

In the failure analysis (FA) of an organic light emitting diode (OLED) display device, fault isolation and physical failure analysis (PFA) were used to identify the root cause of display failure. It is challenging to conduct the FA of a display device, as it consists of display panel, a circuit board and components like semiconductor chips and this integration makes the failure complicated and difficult to analyze and understand. In the case of the display failure studied in this paper, the first work of fault isolation did not clearly identify the origin of the malfunction and its PFA didn’t show any specific defects. To precisely identify the defect location before destructive analysis, the fault isolation technique of OBIRCH was applied to the display device and subsequent PFA successfully identified a crack defect causing the display failure. This finding was given as feedback to the wafer fab and processing parameters were adjusted to prevent generation of the defect in the OLED display device.

Background and setting Electronic data capture facilitates timely use of data. Population-based HIV impact assessments (PHIAs) were led by host governments, with funding from the President's Emergency Plan for AIDS Relief, technical assistance from the Centers for Disease Control, and implementation support from ICAP at Columbia University. We described data architectures, code-based processes, and resulting data volume and quality for 14 national PHIA surveys with concurrent timelines and varied country-level data governance (2015-2020). Methods PHIA project data were collected through tablets, point-of-care and laboratory testing instruments, and inventory management systems, using open-source software, vendor solutions, and custom-built software. Data were securely uploaded to the PHIA data warehouse daily or weekly and then used to populate survey-monitoring dashboards and return timely laboratory-based test results on an ongoing basis. Automated data processing allowed timely reporting of survey results. Results Fourteen data architectures were successfully established, and data from more than 450,000 participants in 30,000 files across 13 countries with completed PHIAs, and blood draws producing approximately 6000 aliquots each week per country, were securely collected, transmitted, and processed by 17 full-time equivalent staff. More than 25,600 viral load results were returned to clinics of participants' choice. Data cleaning was not needed for 98.5% of household and 99.2% of individual questionnaires. Conclusion The PHIA data architecture permitted secure, simultaneous collection and transmission of high-quality interview and biomarker data across multiple countries, quick turnaround time of laboratory-based biomarker results, and rapid dissemination of survey outcomes to guide President's Emergency Plan for AIDS Relief epidemic control.

Heterozygous defects in runt-related transcription factor-1 (RUNX1) are causative of a familial platelet disorder with associated myeloid malignancy (FPDMM). Since RUNX1-deficient animal models do not mimic FPDMM’s bleeding disorder or leukemic risk, establishment of a proper model system is critical to understand the underlying mechanisms of the observed phenotype and to identify therapeutic interventions. We previously reported an in vitro-megakaryopoiesis system using human CD34+-hematopoietic stem and progenitor cells that recapitulated the FPDMM quantitative megakaryocyte defect by decreasing RUNX1 expression using a lentiviral short-hairpin RNA (shRNA for RUNX1 or shRX) strategy. We now show that shRX-megakaryocytes have a marked reduction in agonist responsiveness. We then infused shRX-megakaryocytes into immunocompromised NOD-SCID gamma (NSG) mice and demonstrated that these megakaryocytes released fewer platelets than megakaryocytes transfected with a non-targeting shRNA, and these platelets had a diminished half-life. The platelets were also poorly responsive to agonists, unable to correct thrombus formation in NSG mice homozygous for a R1326H mutation in von Willebrand Factor (VWFR1326H), which switches species-binding specificity of the VWF from mouse to human glycoprotein Ibα. A small-molecule inhibitor RepSox, which blocks the transforming-growth factor beta pathway, and which rescued defective megakaryopoiesis in vitro, corrected the thrombopoietic defect, platelet half-life and agonist response, and thrombus formation in NSG/VWFR1326H mice. Thus, this model recapitulates the defect in FPDMM megakaryocytes and platelets, identifies previously unrecognized defects in thrombopoiesis and platelet half-life, and demonstrates, for the first time, reversal of RUNX1 deficiency’s hemostatic defects by a drug.Key PointsRUNX1-deficient megakaryocytes exhibit thrombopoietic and platelet defects in NSG/VWFR1326H mice.Pre-exposure of RUNX1-deficient megakaryocytes to a TGFβ1-pathway inhibitor ameliorated both defects, correcting hemostasis.

Spinal traction is a physical intervention that provides constant or intermittent stretching axial force to the lumbar vertebrae to gradually distract spinal tissues into better alignment, reduce intervertebral disc (IVD) pressure, and manage lower back pain (LBP). However, such axial traction may change the normal lordotic curvature, and result in unwanted side effects and/or inefficient reduction of the IVD pressure. An alternative to axial traction has been recently tested, consisting of posteroanterior (PA) traction in supine posture, which was recently shown effective to increase the intervertebral space and lordotic angle using MRI. PA traction aims to maintain the lumbar lordosis curvature throughout the spinal traction therapy while reducing the intradiscal pressure. In this study, we developed finite element simulations of mechanical therapy produced by a commercial thermo-mechanical massage bed capable of spinal PA traction. The stress relief produced on the lumbar discs by the posteroanterior traction system was investigated on human subject models with different BMI (normal, overweight, moderate obese and extreme obese BMI cases). We predict typical traction levels lead to significant distraction stresses in the lumbar discs, thus producing a stress relief by reducing the compression stresses normally experienced by these tissues. Also, the stress relief experienced by the lumbar discs was effective in all BMI models, and it was found maximal in the normal BMI model. These results are consistent with prior observations of therapeutic benefits derived from spinal AP traction.

PurposeCrises influence individuals’ career development. The COVID-19 crisis has global impacts in financial, health and social aspects and service industries are at the forefront of the pervasive impacts. This study investigated how college students’ perceptions of COVID-19 interplayed with self-efficacy on their academic plans and further identified major differences between students in service-oriented and nonservice-oriented majors.Design/methodology/approachA self-administered online survey was conducted with 299 undergraduates at a large Midwestern university during COVID-19. Regression analyses, including conditional analyses, examined the study hypotheses using SPSS.FindingsThe results showed that, in general, students’ self-efficacy reduced their intentions to change their academic majors. The joint effects of self-efficacy and perception of COVID-19 diverged among students in nonservice-oriented majors but converged among students in service-oriented majors (e.g. hospitality and tourism). These students in the service fields showed more commitment to their current majors even as their concerns about the social implications of COVID-19 increased.Practical implicationsThis study suggests that academic institutions should try to improve students’ self-efficacy to maintain their career commitments during crisis times. Furthermore, service organizations should highlight the importance of social aspects as recovery from COVID-19 begins as a tool to recruit college graduates.Originality/valueThe literature on career decisions of students in service industries is quite limited. This study enriches the body of career decisions research in the context of service management by highlighting how service sectors are influenced by COVID-19.

As hospitals rapidly implement mechanical thrombectomy (MT) into stroke protocols following the pivotal trials in 2015, access to and outcomes from MT may be poorer for weekend-admitted patients. We sought to investigate whether a "weekend effect" influences MT outcomes nationally.We identified stroke patients from 2010-2014 (pre-trials) to 2015-2017 (posttrials) using the Nationwide Readmissions Database. On multivariate analyses, we determined factors independently associated with receiving MT. Among MT patients, we then determined whether weekend admission was independently associated with inpatient mortality and unfavorable discharge.We identified 2,121,462 patients from 2010 to 2014, of whom 1.11% of weekday-admitted and 1.08% of weekend-admitted patients underwent MT. Of the 1,286,501 patients identified from 2015 to 2017, MT was performed in 2.82% and 2.91%, respectively. In the earlier cohort, weekend admission was independently associated with reduced odds of MT (odds ratio [OR] = 0.92, 95% confidence interval [CI]: 0.89-0.95,While nationwide access to MT has improved for weekend-admitted patients, the elderly and those at smaller, nonteaching hospitals remain underserved. Although we found no effect of weekend admission on inpatient mortality, since the major shift in practice, an emerging "weekend effect" may influence discharge outcomes. Data suggest that some hospitals are being challenged to provide this new standard of care efficiently and equitably.

BackgroundEarly identification of people at risk for cognitive decline is an important step in delaying the occurrence of cognitive impairment. This study investigated whether multimodal signals assessed using electroencephalogram (EEG) and gait kinematic parameters could be used to identify individuals at risk of cognitive impairment.MethodsThe survey was conducted at the Veterans Medical Research Institute in the Veterans Health Service Medical Center. A total of 220 individuals volunteered for this study and provided informed consent at enrollment. A cap-type wireless EEG device was used for EEG recording, with a linked-ear references based on a standard international 10/20 system. Three-dimensional motion capture equipment was used to collect kinematic gait parameters. Mild cognitive impairment (MCI) was evaluated by Seoul Neuropsychological Screening Battery-Core (SNSB-C).ResultsThe mean age of the study participants was 73.5 years, and 54.7% were male. We found that specific EEG and gait parameters were significantly associated with cognitive status. Individuals with decreases in high-frequency EEG activity in high beta (25–30 Hz) and gamma (30–40 Hz) bands increased the odds ratio of MCI. There was an association between the pelvic obliquity angle and cognitive status, assessed by MCI or SNSB-C scores. Results from the ROC analysis revealed that multimodal signals combining high beta or gamma and pelvic obliquity improved the ability to discriminate MCI individuals from normal controls.ConclusionThese findings support prior work on the association between cognitive status and EEG or gait, and offer new insights into the applicability of multimodal signals to distinguish cognitive impairment.

Objective: Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. The study aims are to discuss the implementation of tES digital trials by performing a systematic scoping review and strategic process mapping, evaluate methodological aspects of tES digital trial designs, and provide Delphi-based recommendations for implementing digital trials using tES.Methods: We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided.Results: The main strengths/opportunities of tES were: (i) non-pharmacological nature (92% of agreement), safety of these techniques (80%), affordability (88%), and potential scalability (78%). As for weaknesses/threats, we listed insufficient supervision (76%) and unclear regulatory status (69%). Many issues related to methodological biases did not reach consensus. Device appraisal showed moderate digitalization readiness, with high safety and potential for trial implementation, but low connectivity.Conclusions: Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; with no consensus about aspects regarding methodological biases. Significance: We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials. (C) 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Background Sentinel headache (SH) is often assumed to portend an increased risk of delayed cerebral ischemia (DCI) and aneurysm rebleeding. This study aimed to re-evaluate the associations between SH and aneurysm rebleeding, DCI, and outcome after SAH. Methods We retrospectively analyzed 1102 patients with spontaneous SAH and available data regarding history of SH who were enrolled in the Columbia University SAH Outcomes Project between 1996 and 2009. Patients were asked whether they had experienced any episodes of acute, sudden-onset severe headache in the 2 weeks preceding the most recent bleeding event. DCI was defined as neurologic deterioration, infarction, or both due to vasospasm. Rebleeding was defined as the appearance of new hemorrhage on computed tomography. Outcome was assessed at 3 months by telephone interview using the modified Rankin Scale. Results SH was reported in 152 (14%) of 1102 patients. There were no significant differences between patients with and without SH with regard to admission Hunt–Hess grade or modified Fisher Scale. There was also no difference with regard to the frequency of aneurysm rebleeding (10% vs. 8%, P = 0.42), DCI (18% vs, 20%, P = 0.64), moderate-or-severe angiographic vasospasm on follow-up angiography (51% vs. 56%, P = 0.43), highest recorded mean middle cerebral artery flow velocity on transcranial Doppler (134 versus 128 cm/s, P = 0.30), or the distribution of modified Rankin Scale scores at 3 months. Conclusions A history of sentinel headache before the clinical diagnosis of SAH does not imply an increased risk of DCI or further rebleeding, and carries no prognostic significance.

Background Higher tDCS current may putatively enhance efficacy, with tolerability the perceived limiting factor. Objective We designed and validated electrodes and an adaptive controller to provide tDCS up to 4 mA, while managing tolerability. The adaptive 4 mA controller included incremental ramp up, impedance-based current limits, and a Relax-mode where current is transiently decreased. Relax-mode was automatically activated by self-report VAS-pain score >5 and in some conditions by a Relax-button available to participants. Methods In a parallel-group participant-blind design with 50 healthy subjects, we used specialized electrodes to administer 3 daily session of tDCS for 11 min, with a lexical decision task as a distractor, in 5 study conditions: adaptive 4 mA, adaptive 4 mA with Relax-button, adaptive 4 mA with historical-Relax-button, 2 mA, and sham. A tablet-based stimulator with a participant interface regularly queried VAS pain score and also limited current based on impedance and tolerability. An Abort-button provided in all conditions stopped stimulation. In the adaptive 4 mA with Relax-button and adaptive 4 mA with historical-Relax-button conditions, participants could trigger a Relax-mode ad libitum, in the latter case with incrementally longer current reductions. Primary outcome was the average current delivered during each session, VAS pain score, and adverse event questionnaires. Current delivered was analyzed either excluding or including dropouts who activated Abort (scored as 0 current). Results There were two dropouts each in the adaptive 4 mA and sham conditions. Resistance based current attenuation was rarely activated, with few automatic VAS pain score triggered relax-modes. In conditions with Relax-button option, there were significant activations often irrespective of VAS pain score. Including dropouts, current across conditions were significantly different from each other with maximum current delivered during adaptive 4 mA with Relax-button. Excluding dropouts, maximum current was delivered with adaptive 4 mA. VAS pain score and adverse events for the sham was only significantly lower than the adaptive 4 mA with Relax-button and adaptive 4 mA with historical-Relax-button. There was no difference in VAS pain score or adverse events between 2 mA and adaptive 4 mA. Conclusions Provided specific electrodes and controllers, adaptive 4 mA tDCS is tolerated and effectively blinded, with acceptability likely higher in a clinical population and absence of regular querying. Indeed, presenting participants with overt controls increases rumination on sensation.

Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided. Device appraisal showed moderate digitalization readiness, with high safety and the possibility of trial implementation, but low connectivity. Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; although they reached no consensus about aspects regarding methodological biases. We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials.Graphical Abstract. Consensus Roadmap(A) Recruitment process. The study procedure started with defining the components of the research problem by the core research team. After defining the problems, two different sets of participants (the steering committee (SC) including key leaders of the field identified by the core team and the expert panel (EP) as a more diverse group of experts identified based on the number of publications based on a systematic review) were identified and were invited to participate in a Delphi study. The study facilitators (first and last authors) led the communications with the SC to design the initial questionnaire through an iterative approach. (B) Evidence synthesis: To collect the available evidence, companies producing portable tES (ptES) devices were contacted, based on the companies suggested by the SC and EP to provide details about the available devices. For mapping methodological processes of digitizing tES trials, two distinct strategies were performed and embedded into the questionnaire, namely SIPOC (Suppliers, Inputs, Process, Outputs, and Customer) and SWOT (Strengths, Weaknesses, Opportunities, and Threats) assessment were performed and embedded into the questionnaire. (C) Consensus development: In the next phase, the questionnaire was validated and finalized via collecting and summarizing opinions. Afterward, the SC and EP responded to the final questionnaire, and results were analyzed providing a list of recommendations for running tES digital trials based on a pre-registered consensus threshold.

Two mRNA COVID-19 vaccines (mRNA-1273, Moderna; and BNT162b2, Pfizer-BioNTech) and one viral vector vaccine (JNJ-78436735, Janssen/Johnson and Johnson) are authorized in the US to hinder COVID-19 infections. We analyzed severe and common adverse events in response to COVID-19 vaccines using real-world, Vaccine Adverse Effect Reporting System (VAERS) data. From 14 December 2020 to 30 September 2021, 481,172 (50.7 ± 17.5 years, males 27.89%, 12.35 per 100,000 people) individuals reported adverse events (AEs). The median time to severe AEs was 2 days after injection. The risk of severe AEs following the one viral vector vaccine (OR = 1.044, 95% CI = 1.005–1.086) was significantly higher than that after the two mRNA vaccines, and the risk among males (OR = 1.374, 95% CI = 1.342–1.406) was higher than among females, except for anaphylaxis. For common AEs, however, the risk to males (OR = 0.621, 95% CI = 0.612–0.63) was lower than to females. In conclusion, we provided medical insight and clinical guidance about vaccine types by characterizing AEs using real-world data. In particular, COVID-19 mRNA vaccines are safer than viral vector vaccines with regard to coagulation disorders, whereas inflammation-related AEs are lower in the viral vaccine. The risk–benefit ratio of vaccines should be carefully considered, and close monitoring and management of severe AEs is needed.

Background Clinical considerations for drug treatment of acute seizures involve variables such as safety, tolerability, drug-drug interactions, dosage, route of administration, and alterations in pharmacokinetics because of critical illness. Therapy options that are easily and quickly administered without dilution, well tolerated, and effective are needed for the treatment of acute seizures. The objective of this review is to focus on the clinical considerations relating to the use of intravenous brivaracetam (IV BRV) for the treatment of acute seizures in the hospital, focusing on critically ill patients. Methods This was a scoping literature review of PubMed from inception to April 13, 2021, and search of the American Academy of Neurology (AAN) 2021 Annual Meeting website for English language publications/conference abstracts reporting the results of IV BRV use in hospitalized patients, particularly in the critical care setting. Outcomes of interest relating to the clinical pharmacology, safety, tolerability, efficacy, and effectiveness of IV BRV were reviewed and are discussed. Results Twelve studies were included for analysis. One study showed that plasma concentrations of IV BRV 15 min after the first dose were similar between patients receiving IV BRV as bolus or infusion. IV BRV was generally well tolerated in patients with acute seizures in the hospital setting, with a low incidence of individual TEAEs classified as behavioral disorders. IV BRV demonstrated efficacy and effectiveness and had a rapid onset, with clinical and electrophysiological improvement in seizures observed within minutes. Although outside of the approved label, findings from several studies suggest that IV BRV reduces seizures and is generally well tolerated in patients with status epilepticus. Conclusions IV BRV shows effectiveness, and is generally well tolerated in the management of acute seizures in hospitalized patients where rapid administration is needed, representing a clinically relevant antiseizure medication for potential use in the critical care setting.

Introduction: Transcutaneous electrical nerve stimulation (TENS) for migraine involves the application of pulsatile stimulation through electrodes placed on the forehead to target the underlying trigeminal nerves. It is a simple, safe modality and has secured clinical approval in several markets including the European Union and the United States. Despite nearing almost 7 years of use (postclinical approval), the exact mechanism of action is not fully known. Guided by the need to stimulate the trigeminal nerves bilaterally, electrode dimensions are simply required to extend enough to cover the underlying nerves. The goal of this study is to examine induced current flow [magnitude and spatial distribution of electric field (EF)] and another driver of stimulation [activating function (AF)] due to TENS therapy for migraine for the first time. We further consider the effect of changing the electrode dimension and shape and propose a design modification to deliver optimal flow.Methods: We developed the first ultra-high-resolution finite element (FE) model of TENS for migraine incorporating the target supratrochlear (ST) and the supraorbital (SO) nerves. We first simulated the clinically approved V-shaped geometry. We then considered three additional designs: extended V-shaped, idealized pill-shaped, and finally an extended V-shaped but with greater contact spacing (extended V-shaped +CS).Results: Our findings revealed that the clinically approved electrode design delivered substantially higher mean current flow to the ST nerve in comparison with the SO nerves (Medial: 53% and Lateral: 194%). Consideration of an extended design (~10 mm longer and ~ 4 mm shorter) and a pill-like design had negligible impact on the induced current flow pattern. The extended V-shaped +CS montage delivered relatively comparable current flow to each of the three target nerves. The EF induced in the ST nerve was 49 and 141% higher in the Medial and Lateral SO nerve, respectively. When considering maximum induced values, the delivery of comparable stimulation was further apparent. Given the existing electrode design's established efficacy, our results imply that preferential targeting of the ST nerve is related to the mechanism of action. Additionally, if comparable targeting of all three nerves continues to hold promise, the extended V-shaped +CS montage presents an optimized configuration to explore in clinical studies.

Spontaneous intracerebral hemorrhage (ICH) is the second most prevalent subtype of stroke and has high mortality and morbidity. The utility of radiographic features to predict secondary brain injury related to hematoma expansion (HE) or increased intracranial pressure has been highlighted in patients with ICH, including the computed tomographic angiography (CTA) spot sign and intraventricular hemorrhage (IVH). Understanding the pathophysiology of spot sign and IVH may help identify optimal therapeutic strategies. We examined factors related to the spot sign and IVH, including coagulation status, hematoma size, and location, and evaluated their prognostic value in patients with ICH.Prospectively collected data from a single center between 2012 and 2015 were analyzed. Patients who underwent thromboelastography within 24 h of symptom onset and completed follow-up brain imaging and CTA within 48 h after onset were included for analysis. Multivariate logistic regression analyses were performed to identify determinants of the spot sign and IVH and their predictive value for HE, early neurological deterioration (END), in-hospital mortality, and functional outcome at discharge.Of 161 patients, 50 (31.1%) had a spot sign and 93 (57.8%) had IVH. In multivariable analysis, the spot sign was associated with greater hematoma volume (odds ratio [OR] 1.02; 95% confidence interval [CI] 1.00-1.03), decreased white blood cell count (OR 0.88; 95% CI 0.79-0.98), and prolonged activated partial thromboplastin time (OR 1.14; 95% CI 1.06-1.23). IVH was associated with greater hematoma volume (OR 1.02; 95% CI 1.01-1.04) and nonlobar location of hematoma (OR 0.23; 95% CI 0.09-0.61). The spot sign was associated with greater risk of all adverse outcomes. IVH was associated with an increased risk of END and reduced HE, without significant impact on mortality or functional outcome.The spot sign and IVH are associated with specific hematoma characteristics, such as size and location, but are related differently to coagulation status and clinical course. A combined analysis of the spot sign and IVH can improve the understanding of pathophysiology and risk stratification after ICH.

The majority of cloud applications are created or delivered to provide users with access to system resources or prebuilt processing algorithms for efficient data storage, management, and production. The number of cases linking cloud computing to the use of global observation satellite data continues to rise, owing to the benefits of cloud computing. This study aims to develop a cloud software as a service (SaaS) that yields reflectance products in high-resolution Korea Multi-Purpose Satellite (KOMPSAT)-3/3A satellite images. The SaaS model was designed as three subsystems: a Calibration Processing System (CPS), a Request System for CPS supporting RESTful application programming interface (API), and a Web Interface Application System. Open-source components, libraries, and frameworks were used in this study’s SaaS, including an OpenStack for infrastructure as a service. An absolute atmospheric correction scheme based on a Second Simulation of a Satellite Signal in the Solar Spectrum (6S) radiative transfer code with atmospheric variable inputs was used to generate the top-of-atmosphere (TOA) and top-of-canopy (TOC) reflectance products. The SaaS implemented in this study provides users with the absolute atmospheric calibration functionality to apply their KOMPSAT-3/3A satellite image set through a web browser and obtain output directly from this service. According to experiments to check the total performance time for images, bundled with four bands of red, green, blue, and near-infrared, it took approximately 4.88 min on average for the execution time to obtain all reflectance results since satellite images were registered into the SaaS. The SaaS model proposed and implemented in this study can be used as a reference model for the production system to generate reflectance products from other optical sensor images. In the future, SaaS, which offers professional analysis functions based on open source, is expected to grow and expand into new application fields for public users and communities.

As high-performance computing (HPC) plays a key role in the Fourth Industrial Revolution, the application of HPC in various industries is becoming increasingly important. Several studies have reviewed the research trends of HPC but considered only the functional aspects, causing limitations when discussing the application. Thus, this study aims to identify the knowledge structure of the application of HPC, enabling practical and policy support in various industrial fields. Co-word analysis is mainly used to establish the knowledge structure. We first collected 28,941 published papers related to HPC applications and built a co-word network that used author keywords. We performed centrality analysis and cluster analysis of the co-word network, as a result, we derived the major keywords and 18 areas of HPC applications. To validate the knowledge structure, we conducted a case study to find opportunities for HPC research plans in the research community. As a result, we discovered 17 new research topics and presented their research priorities by conducting expert interviews and Analytic Hierarchy Process. The findings of this study contribute to an understanding of the application of HPC, to exploring promising research fields for technological and social development, and to supporting research plans for successful technology commercialization.

Objectives To evaluate the effectiveness of a new mandibular advancement device (MAD) (Prosomnus® [IA] Sleep Device, Prosomnus Sleep Technologies, Pleasanton CA) fitted with a compliance tracker as a first-line treatment in a population of patients with mild to severe obstructive sleep apnea (OSA). Methods Treatment effectiveness was measured using pre and post-treatment home sleep testing (HST) and validated sleep and quality of life questionnaires. Mean disease alleviation (MDA) was calculated to compare the treatment effectiveness of MAD to historical continuous positive airway pressure (CPAP) effectiveness data. Results MAD was found to be an effective first-line treatment for patients with mild, moderate, and severe sleep apnea with excellent compliance rates, similar to or better than CPAP, and an equal or better MDA of 56.7% compared to literature values of 50% for CPAP. Conclusions MAD should be considered an effective first-line treatment for patients with mild and moderate sleep apnea and for severe sleep apnea for patients who prefer, refuse, or are not candidates for CPAP.

Background Preliminary data suggest that Coronavirus Disease-2019 (COVID-19) is associated with hypercoagulability and neurovascular events, but data on outcomes is limited. Objective To report the clinical course and outcomes of a case series of COVID-19 patients with a variety of cerebrovascular events. Methods We performed a multicentric, retrospective chart review at our three academic tertiary care hospitals, and identified all COVID-19 patients with cerebrovascular events requiring neuro-intensive care and/or neurosurgical consultation. Results We identified 26 patients between March 1 and May 24, 2020, of whom 12 (46%) died. The most common event was a large-vessel occlusion (LVO) in 15 patients (58%), among whom 8 died (8/15, 53%). A total of 9 LVO patients underwent mechanical thrombectomy, of whom 5 died (5/9, 56%). A total of 7 patients (27%) presented with intracranial hemorrhage. Of the remaining patients, 2 had small-vessel occlusions, 1 had cerebral venous sinus thrombosis, and another had a vertebral artery dissection. Acute Respiratory Distress Syndrome occurred in 8 patients, of whom 7 died. Mortalities had a higher D-dimer on admission (mean 20 963 ng/mL) than survivors (mean 3172 ng/mL). Admission Glasgow Coma Scale (GCS) score was poor among mortalities (median 7), whereas survivors had a favorable GCS at presentation (median 14) and at discharge (median 14). Conclusion COVID-19 may be associated with hemorrhage as well as ischemia, and prognosis appears poorer than expected-particularly among LVO cases, where outcome remained poor despite mechanical thrombectomy. However, a favorable neurological condition on admission and lower D-dimer may indicate a better outcome.

Background: Coronavirus disease 2019 (COVID-19) has placed a tremendous strain on healthcare services. This study, prepared by a large international panel of stroke experts, assesses the rapidly growing research and personal experience with COVID-19 stroke and offers recommendations for stroke management in this challenging new setting: modifications needed for prehospital emergency rescue and hyperacute care; inpatient intensive or stroke units; posthospitalization rehabilitation; follow-up including at-risk family and community; and multispecialty departmental developments in the allied professions. Summary: The severe acute respiratory syndrome coronavirus 2 uses spike proteins binding to tissue angiotensin-converting enzyme (ACE)-2 receptors, most often through the respiratory system by virus inhalation and thence to other susceptible organ systems, leading to COVID-19. Clinicians facing the many etiologies for stroke have been sobered by the unusual incidence of combined etiologies and presentations, prominent among them are vasculitis, cardiomyopathy, hypercoagulable state, and endothelial dysfunction. International standards of acute stroke management remain in force, but COVID-19 adds the burdens of personal protections for the patient, rescue, and hospital staff and for some even into the postdischarge phase. For pending COVID-19 determination and also for those shown to be COVID-19 affected, strict infection control is needed at all times to reduce spread of infection and to protect healthcare staff, using the wealth of well-described methods. For COVID-19 patients with stroke, thrombolysis and thrombectomy should be continued, and the usual early management of hypertension applies, save that recent work suggests continuing ACE inhibitors and ARBs. Prothrombotic states, some acute and severe, encourage prophylactic LMWH unless bleeding risk is high. COVID-19-related cardiomyopathy adds risk of cardioembolic stroke, where heparin or warfarin may be preferable, with experience accumulating with DOACs. As ever, arteritis can prove a difficult diagnosis, especially if not obvious on the acute angiogram done for clot extraction. This field is under rapid development and may generate management recommendations which are as yet unsettled, even undiscovered. Beyond the acute management phase, COVID-19-related stroke also forces rehabilitation services to use protective precautions. As with all stroke patients, health workers should be aware of symptoms of depression, anxiety, insomnia, and/or distress developing in their patients and caregivers. Postdischarge outpatient care currently includes continued secondary prevention measures. Although hoping a COVID-19 stroke patient can be considered cured of the virus, those concerned for contact safety can take comfort in the increasing use of telemedicine, which is itself a growing source of patient-physician contacts. Many online resources are available to patients and physicians. Like prior challenges, stroke care teams will also overcome this one. Key Messages: Evidence-based stroke management should continue to be provided throughout the patient care journey, while strict infection control measures are enforced.

Surface reflectance products obtained through the absolute atmospheric correction of multispectral satellite images are useful for precise scientific applications. For broader applications, the reflectance products computed using high-resolution images need to be validated with field measurement data. This study dealt with 2.2-m resolution Korea Multi-Purpose Satellite (KOMPSAT)-3A images with four multispectral bands, which were used to obtain top-of-atmosphere (TOA) and top-of-canopy (TOC) reflectance products. The open-source Orfeo Toolbox (OTB) extension was used to generate these products. Next, these were subsequently validated by considering three sites (i.e., Railroad Valley Playa, NV, USA (RVUS), Baotou, China (BTCN), and La Crau, France (LCFR)) in RadCalNet, as well as a calibration and validation portal for remote sensing. We conducted the validations comparing satellite image-based reflectance products and field measurement reflectance based on data sets acquired at different times. The experimental results showed that the overall trend of validation accuracy of KOPSAT-3A was well fitted in all the RadCalNet sites and that the accuracy remained quite constant. Reflectance bands showing the minimum and maximum differences between the sets of experimental data are presented in this paper. The vegetation indices (i.e., the atmospherically resistant vegetation index (ARVI) and the structure insensitive pigment index (SIPI)) and three TOC reflectance bands obtained from KOMPSAT-3A were computed as a case study and used to achieve a detailed vegetation interpretation; finally, the correspondent results were compared with those obtained from Landsat-8 images (downloaded from the Google Earth Engine (GEE)). The validation and the application scheme presented in this study can be potentially applied to the generation of analysis ready data from high-resolution satellite sensor images.

Historically, AAV defective interfering particles (DI) were known as abnormal virions arising from natural replication and encapsidation errors. Through single virion genome analysis, we revealed that a major category of DI particles contains a double stranded DNA genome in a “snapback” configuration (SBG). The 5’-SBGs include the P5 promoters and partial rep gene sequences. The 3’-SBGs contains the capsid region. The molecular configuration of 5’-SBGs allowed double stranded RNA transcription in their dimer configuration, which in turn regulate AAV rep expression and may improve AAV packaging. In contrast, 3’-SBGs at its dimer configuration increased levels of cap protein. The generation and accumulation of 5’-SBGs and 3’-SBGs appears to be coordinated to balance the viral gene expression level. Therefore, the functions of 5’-SBGs and 3’-SBGs may help maximize the yield of AAV progenies. We postulate that AAV virus population behaved as a colony and utilizes its subgenomic particles to overcome the size limit of viral genome and encodes additional essential functions.

Neurorehabilitation for stroke is important for upper limb motor recovery. Conventional rehabilitation such as occupational therapy has been used, but novel technologies are expected to open new opportunities for better recovery. Virtual reality (VR) is a technology with a set of informatics that provides interactive environments to patients. VR can enhance neuroplasticity and recovery after a stroke by providing more intensive, repetitive, and engaging training due to several advantages, including: (1) tasks with various difficulty levels for rehabilitation, (2) augmented real-time feedback, (3) more immersive and engaging experiences, (4) more standardized rehabilitation, and (5) safe simulation of real-world activities of daily living. In this comprehensive narrative review of the application of VR in motor rehabilitation after stroke, mainly for the upper limbs, we cover: (1) the technologies used in VR rehabilitation, including sensors; (2) the clinical application of and evidence for VR in stroke rehabilitation; and (3) considerations for VR application in stroke rehabilitation. Meta-analyses for upper limb VR rehabilitation after stroke were identified by an online search of Ovid-MEDLINE, Ovid-EMBASE, the Cochrane Library, and KoreaMed. We expect that this review will provide insights into successful clinical applications or trials of VR for motor rehabilitation after stroke.

Surface reflectance data obtained by the absolute atmospheric correction of satellite images are useful for land use applications. For Landsat and Sentinel-2 images, many radiometric processing methods exist, and the images are supported by most types of commercial and open-source software. However, multispectral KOMPSAT-3A images with a resolution of 2.2 m are currently lacking tools or open-source resources for obtaining top-of-canopy (TOC) reflectance data. In this study, an atmospheric correction module for KOMPSAT-3A images was newly implemented into the optical calibration algorithm in the Orfeo Toolbox (OTB), with a sensor model and spectral response data for KOMPSAT-3A. Using this module, named OTB extension for KOMPSAT-3A, experiments on the normalized difference vegetation index (NDVI) were conducted based on TOC reflectance data with or without aerosol properties from AERONET. The NDVI results for these atmospherically corrected data were compared with those from the dark object subtraction (DOS) scheme, a relative atmospheric correction method. The NDVI results obtained using TOC reflectance with or without the AERONET data were considerably different from the results obtained from the DOS scheme and the Landsat-8 surface reflectance of the Google Earth Engine (GEE). It was found that the utilization of the aerosol parameter of the AERONET data affects the NDVI results for KOMPSAT-3A images. The TOC reflectance of high-resolution satellite imagery ensures further precise analysis and the detailed interpretation of urban forestry or complex vegetation features.

We had previously demonstrated that phlorotannins, which are marine polyphenols, enhance sleep in mice via the GABAA-benzodiazepine (BZD) receptor. Among the constituents of phlorotannin, dieckol is a major marine polyphenol from the brown alga Ecklonia cava. Although phlorotannins are known to exert hypnotic effects, the sleep-enhancing effect of dieckol has not yet been determined. We evaluated the effect of dieckol on sleep-wake state of mice by analyzing electroencephalograms (EEGs) and electromyograms. Flumazenil, a GABAA-BZD antagonist, was used to investigate the molecular mechanism underlying the effects of dieckol on sleep. The polygraphic recordings and corresponding hypnograms revealed that dieckol accelerated the initiation of non-rapid eye movement sleep (NREMS); it shortened sleep latency and increased NREMS duration. According to the change in time-course, dieckol showed sleep-enhancing effects by increasing the amount of NREMS and decreasing wakefulness during the same hours. Additionally, sleep quality was evaluated by analyzing the EEG power density, and dieckol was found to not affect sleep intensity while zolpidem was found to reduce it. Finally, we treated mice with zolpidem or dieckol in combination with flumazenil and found the latter to inhibit the sleep-enhancing effect of dieckol and zolpidem, thereby indicating that dieckol exerts sleep-enhancing effects by activating the GABAA-BZD receptor, similar to zolpidem. These results implied that dieckol can be used as a promising herbal sleep aid with minimal side effects, unlike the existing hypnotics.