Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacometric and Electrocardiographic Evaluation of Chloroquine and Azithromycin in Healthy Volunteers

Chloroquine and azithromycin were developed in combination for the preventive treatment of malaria in pregnancy, and more recently were proposed as coronavirus disease 2019 (COVID‐19) treatment options. Billions of doses of chloroquine have been administered worldwide over the past 70 years but concerns regarding cardiotoxicity, notably the risk of torsades de pointes (TdP), remain. This investigation aimed to characterize the pharmacokinetics and electrocardiographic effects of chloroquine and azithromycin observed in a large previously conducted healthy volunteer study. Healthy adult volunteers (n = 119) were randomized into 5 arms: placebo, chloroquine alone (600 mg base), or chloroquine with either 500 mg, 1,000 mg, or 1,500 mg of azithromycin all given daily for 3 days. Chloroquine and azithromycin levels, measured using liquid‐chromatography tandem mass spectrometry, and electrocardiograph intervals were recorded at frequent intervals. Time‐matched changes in the PR, QRS, and heart rate‐corrected JT, and QT intervals were calculated and the relationship with plasma concentrations was evaluated using linear and nonlinear mixed‐effects modeling. Chloroquine and azithromycin pharmacokinetics were described satisfactorily by two‐ and three‐compartment distribution models, respectively. No drug–drug interaction between chloroquine and azithromycin was observed. Chloroquine resulted in concentration‐dependent prolongation of the PR, QRS, JTc and QTc intervals with a minimal additional effect of azithromycin. QRS widening contributed ~ 28% of the observed QT prolongation. Chloroquine causes significant concentration‐dependent delays in both ventricular depolarization and repolarization. Co‐administration of azithromycin did not significantly increase these effects. The arrhythmogenic risk of TdP associated with chloroquine may have been substantially overestimated in studies which did not separate electrocardiograph QRS and JT prolongation.
The potential benefits of divergent thinking and metacognitive skills in STEAM learning: A discussion paper

In the wake of an almost decade long economic downturn and increasing competition from developing economies, a new agenda in the Australian Government for science, technology, engineering, and mathematics (STEM) education and research has emerged as a national priority. However, to art and design educators, the pervasiveness and apparent exclusivity of STEM can be viewed as another instance of art and design education being relegated to the margins of curriculum (Greene, 1995). In the spirit of interdisciplinarity, there have been some recent calls to expand STEM education to include the arts and design, transforming STEM into STEAM in education (Maeda, 2013). As with STEM, STEAM education emphasises the connections between previously disparate disciplines, meaning that education has been conceptualised in different ways, such as focusing on the creative design thinking process that is fundamental to engineering and art (Bequette & Bequette, 2012). In this article, we discuss divergent creative design thinking process and metacognitive skills, how, and why they may enhance learning in STEM and STEAM.
Physiological Basis of Water Stress Tolerance in Soybean

An experiment was conducted to study the effects of water stress on physiological parameters associated to drought tolerance in soybean at the Department of Agronomy, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur, Bangladesh during January to April, 2015. Four soybean genotypes namely i) BU Soybean 1 ii) Binasoybean 1 iii) Galarsum and iv) BARI Soybean 5 were grown in two watering regimes viz. control (80% of the field capacity) and water stress (50% of the field capacity). Genotypic variability was found in water stress tolerance in soybean. Highest accumulation of leaf proline, sugar and water content and lower accumulation of malondialdehyde were found in Binasoybean 1 compared to other genotypes. Lowest yield reduction was found in Binasoybean 1. Binasoybean 1 showed relatively higher drought tolerance whereas BARI Soybean 5 was found susceptible to yield. It was found that higher water stress tolerance in Binasoybean 1 was associated with better water relations and higher accumulation of sugar and proline and lower accumulation of malondialdehyde content in leaf. Bangladesh Agron. J. 2015, 18(2): 71-78
leads to well-deﬁned fragment size

Stefan Kooij, ∗ Gerard van Dalen, Jean-François Molinari, and Daniel Bonn 3 Van der Waals-Zeeman Institute, University of Amsterdam, Science Park 904, Amsterdam, Netherlands 4 Unilever Research and Development Vlaardingen, Olivier van Noortlaan, 5 P.O. Box 114, 3130 AC Vlaardingen, The Netherlands 6 Department of Materials Science and Engineering, 7 École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland 8
Towards Shared Control of Hydraulic Excavators

Presently, excavator operators manually control all functions of the machine. Decreases to a task's time or energy cost are historically achieved by designing better systems and components or through operator training. In contrast, the approach discussed here allows the human and machine to share control of the end effector to improve machine performance. The paper will introduce the idea of blended shared control in the context of excavation, and will show methods of describing the operator task. A filter that increases the robustness of the task identification is presented. Examples using experimental data are presented to illustrate the results. This approach can potentially decrease task completion time without requiring modification of the machine hardware.
Survey of the training needs in Oregon's lumber manufacturing industry

Oregon's lumber manufacturing industry, an important segment of the state's economy, provides jobs and an industrial base for many communities. Continuing education programs and training workshops for sawmill personnel contribute to improved productivity and resource utilization. To determine industry training needs, a questionnaire was developed and mailed to all sawmill owners and managers in Oregon. The questionnaire addressed general attitudes toward training and staff development, and interest in various subjects and training methods. About 60 percent of operating mills responded ; these mills accounted for approximately 90 percent of the state's estimated production. Almost all respondents agreed that training leads to increased productivity, is necessary to assure a skilled workforce, helps promote workers to management positions, and is a continuous process. However, at the time of the survey, 49 percent of the mills allocated 1/2 hour or less of training per employee per month. Of the subjects presented in the questionnaire, respondents felt that quality control, safety, manager training, and maintenance were the most needed. Wood technology, business economics, yard practices, and industrial-personal health were the least-needed subjects.
UvA-DARE (Digital Search for heavy ZZ resonances in the ℓ ⁺ℓ ⁻ℓ ⁺ℓ⁻ and ℓ ⁺ℓ ⁻νν̄ final states using proton–proton collisions at √s̅= 13 TeV with the ATLAS detector

A search for heavy resonances decaying into a pair of Z bosons leading to (cid:3) + (cid:3) − (cid:3) + (cid:3) − and (cid:3) + (cid:3) − ν ¯ ν ﬁnal states, where (cid:3) stands for either an electron or a muon, is presented. The search uses proton–proton collision data at a centre-of-mass energy of 13 TeV corresponding to an integrated luminosity of 36.1 fb − 1 collected with the ATLAS detector during 2015 and 2016 at the Large Hadron Collider. Different mass ranges for the hypothetical resonances are considered, depending on the ﬁnal state and model. The different ranges span between 200 and 2000 GeV. The results are interpreted as upper limits on the production cross section of a spin-0 or spin-2 resonance. The upper limits for the spin-0 resonance are translated to exclusion contours in the context of Type-I and Type-II two-Higgs-doublet models, while those for the spin-2 resonance are used to constrain the Randall–Sundrum model with an extra dimension giving rise to spin-2 graviton excitations.
2-D Numerical Simulation of Charge Handling Capacity in Buried-channel CCDs

In terms of two-dimensional device simulator PISCES-IIB,quantitative analysis is made on charge handling capacity of buried-channel charge coupled devices(CCDs) by means of injection of magnitude controllable electrons under the depletion region of a CCD electrode.Transient simulation is carried out for the charge handling capacity of a CCD with channel width of 7 μm,followed by discussion on the effect of different channel junction depth and impurity on charge handling capacity.An optimum is obtained i.e.the maximum charge handling capacity can be up to 6×10 4/μm at CCD channel impurity concentration of 3×10 16 cm -3 and junction depth of 1 μm.
Strengthened second law for multi-dimensional systems coupled to multiple thermodynamic reservoirs

The second law of thermodynamics can be formulated as a restriction on the evolution of the entropy of any system undergoing Markovian dynamics. Here I show that this form of the second law is strengthened for multi-dimensional, complex systems, coupled to multiple thermodynamic reservoirs, if we have a set of a priori constraints restricting how the dynamics of each coordinate can depend on the other coordinates. As an example, this strengthened second law (SSL) applies to complex systems composed of multiple physically separated, co-evolving subsystems, each identified as a coordinate of the overall system. In this example, the constraints concern how the dynamics of some subsystems are allowed to depend on the states of the other subsystems. Importantly, the SSL applies to such complex systems even if some of its subsystems can change state simultaneously, which is prohibited in a multipartite process. The SSL also strengthens previously derived bounds on how much work can be extracted from a system using feedback control, if the system is multi-dimensional. Importantly, the SSL does not require local detailed balance. So it potentially applies to complex systems ranging from interacting economic agents to co-evolving biological species. This article is part of the theme issue ‘Emergent phenomena in complex physical and socio-technical systems: from cells to societies’.
High-Dosage Fosfomycin Results in Adequate Plasma and Target-Site Exposure in Morbidly Obese and Nonobese Nonhyperfiltration Patients

The objectives of this study were the identification in (morbidly) obese and nonobese patients of (i) the most appropriate body size descriptor for fosfomycin dose adjustments and (ii) adequacy of the currently employed dosing regimens. Plasma and target site (interstitial fluid of subcutaneous adipose tissue) concentrations after fosfomycin administration (8 g) to 30 surgery patients (15 obese/15 nonobese) were obtained from a prospective clinical trial. ABSTRACT The objectives of this study were the identification in (morbidly) obese and nonobese patients of (i) the most appropriate body size descriptor for fosfomycin dose adjustments and (ii) adequacy of the currently employed dosing regimens. Plasma and target site (interstitial fluid of subcutaneous adipose tissue) concentrations after fosfomycin administration (8 g) to 30 surgery patients (15 obese/15 nonobese) were obtained from a prospective clinical trial. After characterization of plasma and microdialysis-derived target site pharmacokinetics via population analysis, short-term infusions of fosfomycin 3 to 4 times daily were simulated. The adequacy of therapy was assessed by probability of pharmacokinetic/pharmacodynamic target attainment (PTA) analysis based on the unbound drug-related targets of an %fT>MIC (the fraction of time that unbound fosfomycin concentrations exceed the MIC during 24 h) of 70 and an fAUC0-24h/MIC (the area under the concentration-time curve from 0 to 24 h for the unbound fraction of fosfomycin relative to the MIC) of 40.8 to 83.3. Lean body weight, fat mass, and creatinine clearance calculated via adjusted body weight (ABW) (CLCRCG_ABW) of all patients (body mass index [BMI] = 20.1 to 52.0 kg/m2) explained a considerable proportion of between-patient pharmacokinetic variability (up to 31.0% relative reduction). The steady-state unbound target site/plasma concentration ratio was 26.3% lower in (morbidly) obese than nonobese patients. For infections with fosfomycin-susceptible pathogens (MIC ≤ 16 mg/L), intermittent “high-dosage” intravenous (i.v.) fosfomycin (8 g, three times daily) was sufficient to treat patients with a CLCRCG_ABW of <130 mL/min, irrespective of the pharmacokinetic/pharmacodynamic indices considered. For infections by Pseudomonas aeruginosa with a MIC of 32 mg/L, when the index fAUC0-24h/MIC is applied, fosfomycin might represent a promising treatment option in obese and nonobese patients, especially in combination therapy to complement β-lactams, in which carbapenem-resistant P. aeruginosa is critical. In conclusion, fosfomycin showed excellent target site penetration in obese and nonobese patients. Dosing should be guided by renal function rather than obesity status. (This study has been registered in the EU Clinical Trials Register under EudraCT no. 2012-004383-22.)
Research on the Online Recognition of the Motion Image of the Adjacent Joints of the Lower Limbs

At present, offline analysis and research of lower limb motor imagery brain computer interface (MI-BCI) are relatively mature, but there are few researches on the online recognition of lower limb MI-BCI. The online recognition of the two MI tasks of the knee-ankle adjacent joints of the right lower extremity was carried out, and the EEG signals of the two MI tasks assisted by electrical stimulation are collected. The Filter Bank Common Spatial Pattern (FBCSP) is used for feature extraction, and BP neural network is used for online recognition. The average recognition accuracy rate of online motor imagery of 13 subjects reaches 79.62%, and the recognition accuracy rate of the highest person is 92.50%, which verified the feasibility and practicability of online MI-BCI in adjacent joints of lower limbs.
Disrupt the upper or the lower conduit? The dual role of gas exsolution in the conduits of persistently active volcanoes

Abstract Many volcanoes emit a significant portion of the gas they transport to the atmosphere during continual passive degassing rather than during eruptions. To maintain a high gas and thermal flux without erupting magma, the flow field in the volcanic conduit must be approximately balanced with gas-rich, buoyant magma ascending and degassed, heavy magma descending. In vertical conduits, this exchange flow takes the form of core–annular flow, where the gas-rich magma forms a core enclosed by an annulus of degassed magma. The flow dynamics of core–annular flow have been studied extensively in fluid dynamics, but mostly for constant material properties. Our study aims to advance our understanding of how core–annular flow responds to volatile exsolution – a simple, yet ubiquitous disruption in volcanic conduits, which alters both the density and the viscosity of the core fluid. By deriving an evolution equation for the core–annular interface based on a generalized exchange-flow condition using a lubrication approximation, we find that the response of the system to volatile exsolution depends on the conduit flow regime. The same nucleation event can lead to a flow adjustment only in the upper, only in the lower or in both portions of the volcanic conduit. Our results emphasize that the thermodynamic evolution of magma properties and volcanic conduit flow are intricately linked, which may help understand the observed variability of eruptive behaviour at persistently degassing volcanoes.
COVID-19 and Support for Executive Aggrandizement

Abstract The COVID-19 pandemic offers a critical opportunity to assess the extent to which Canadians can be considered reliable defenders of democratic norms and institutions. In the face of such a serious threat to their physical and economic well-being, how willing are Canadians to condone the loosening of restraints on the power of the executive? This article addresses this question by drawing on the terror management and threat literatures. Combining a cross-sectional regression analysis with a vignette experiment and a candidate-choice conjoint experiment, it tests two hypotheses: that people experiencing debilitating anxiety about COVID-19 are more likely to favour weakening checks on the executive and that people will be willing to trade off legislative checks for the sake of their preferred lockdown policy. Both hypotheses are confirmed. In the face of an unprecedented health crisis, COVID-related anxiety and a desire for protective policies may trump respect for democratic norms.
Case Report: Supernormal Vascular Aging in Leningrad Siege Survivors

Age-related changes in the vascular system play an important role in the biological age and lifespan of a person and maybe affected from an early age onward. One of the indicators of changes in the vascular system is arterial wall stiffness and its main measure, i.e., carotid-femoral pulse wave velocity (cfPWV). We examined arterial wall stiffness in a sample of 305 Leningrad Siege survivors to assess how hunger and stressful conditions during fetal development and early childhood affected the state of the cardiovascular system at a later age and what factors may neutralize the negative impact sustained in early childhood. Here, we presented an evaluation of two unique patients with supernormal vascular aging (SUPERNOVA) phenotype from this cohort and described the details of congruence between hereditary resistance and practiced lifestyle yielding slower biological aging rate.
Impact of APOE ε4 Carrier Status on Associations Between Subthreshold, Positive Amyloid-β Deposition, Brain Function, and Cognitive Performance in Cognitively Normal Older Adults: A Prospective Study

Background A growing body of evidence suggests a deteriorating effect of subthreshold amyloid-beta (Aβ) accumulation on cognition before the onset of clinical symptoms of Alzheimer's disease (AD). Despite the association between the Aβ-dependent pathway and the APOE ε4 allele, the impact of this allele on the progression from the subthreshold Aβ deposits to cognitive function impairment is unclear. Furthermore, the comparative analysis of positive Aβ accumulation in the preclinical phase is lacking. Objective This study aimed to explore the differential effect of the APOE ε4 carrier status on the association between Aβ deposition, resting-state brain function, and cognitive performance in cognitively normal (CN) older adults, depending on the Aβ burden status. Methods One hundred and eighty-two older CN adults underwent resting-state functional magnetic resonance imaging, [18F] flutemetamol (FMM) positron emission tomography, a neuropsychological battery, and APOE genotyping. We evaluated the resting-state brain function by measuring the local and remote functional connectivity (FC) and measured the remote FC in the default-mode network (DMN), central-executive network (CEN), and salience network (SN). In addition, the subjects were dichotomized into those with subthreshold and positive Aβ deposits using a neocortical standardized uptake value ratio with the cut-off value of 0.62, which was calculated with respect to the pons. Results The present result showed that APOE ε4 carrier status moderated the relationship between Aβ deposition, local and remote resting-state brain function, and cognitive performance in each CN subthreshold and positive Aβ group. We observed the following: (i) the APOE ε4 carrier status-Aβ deposition and APOE ε4 carrier status-local FC interaction for the executive and memory function; (ii) the APOE ε4 carrier status-regional Aβ accumulation interaction for the local FC; and (iv) the APOE ε4 carrier status-local FC interaction for the remote inter-network FC between the DMN and CEN, contributing higher cognitive performance in the APOE ε4 carrier with higher inter-network FC. Finally, these results were modulated according to Aβ positivity. Conclusion This study is the first attempt to thoroughly examine the influence of the APOE ε4 carrier status from the subthreshold to positive Aβ accumulation during the preclinical phase.
Bibliometric Analysis of Quantitative Electroencephalogram Research in Neuropsychiatric Disorders From 2000 to 2021

Background With the development of quantitative electroencephalography (QEEG), an increasing number of studies have been published on the clinical use of QEEG in the past two decades, particularly in the diagnosis, treatment, and prognosis of neuropsychiatric disorders. However, to date, the current status and developing trends of this research field have not been systematically analyzed from a macroscopic perspective. The present study aimed to identify the hot spots, knowledge base, and frontiers of QEEG research in neuropsychiatric disorders from 2000 to 2021 through bibliometric analysis. Methods QEEG-related publications in the neuropsychiatric field from 2000 to 2021 were retrieved from the Web of Science Core Collection (WOSCC). CiteSpace and VOSviewer software programs, and the online literature analysis platform (bibliometric.com) were employed to perform bibliographic and visualized analysis. Results A total of 1,904 publications between 2000 and 2021 were retrieved. The number of QEEG-related publications in neuropsychiatric disorders increased steadily from 2000 to 2021, and research in psychiatric disorders requires more attention in comparison to research in neurological disorders. During the last two decades, QEEG has been mainly applied in neurodegenerative diseases, cerebrovascular diseases, and mental disorders to reveal the pathological mechanisms, assist clinical diagnosis, and promote the selection of effective treatments. The recent hot topics focused on QEEG utilization in neurodegenerative disorders like Alzheimer's and Parkinson's disease, traumatic brain injury and related cerebrovascular diseases, epilepsy and seizure, attention-deficit hyperactivity disorder, and other mental disorders like major depressive disorder and schizophrenia. In addition, studies to cross-validate QEEG biomarkers, develop new biomarkers (e.g., functional connectivity and complexity), and extract compound biomarkers by machine learning were the emerging trends. Conclusion The present study integrated bibliometric information on the current status, the knowledge base, and future directions of QEEG studies in neuropsychiatric disorders from a macroscopic perspective. It may provide valuable insights for researchers focusing on the utilization of QEEG in this field.