The term “betel” most accurately refers to the betel pepper (Piper betle). Confusingly, this term is also frequently used to refer to a street drug that often—but not always—includes the betel leaf as a constituent. This linguistic misdirection only intensifies with terms such as “betel nut,” which, in common usage, may refer to this same composite street drug or to a single isolated constituent of that street drug: the nut of the areca palm (Areca catechu), which is otherwise wholly unrelated to the betel pepper. This composite street drug, colloquially referred to as “betel” or “betel nut” or “betel quid,” is one of the most frequently used psychoactive substances in the world. It carries a cultural legacy spanning over 10,000 years and a current user base numbering in the hundreds of millions. Its primary psychoactive constituent is arecoline, a well-established parasympathomimetic agent. Early studies exploring arecoline’s ability to modulate cholinergic signaling pathways and exert therapeutic psychiatric effects on conditions such as Alzheimer’s disease were initially mired by intolerable parasympathetic side effects. Indeed, over the course of its long history, various hints regarding the therapeutic utility of arecoline have been obfuscated by a variety of challenges which have only recently been overcome. Now, developments in psychopharmacology and our growing understanding of neurochemical brain circuitry have unlocked a new mechanism of action by which arecoline-derived medications interact with dopaminergic processes to improve outcomes for schizophrenia patients. One such medication, xanomeline-trospium (Cobenfy), has emerged as the first such agent to receive U.S. Food and Drug Administration (FDA) approval for the treatment of schizophrenia and represents an entirely new class of pro-cholinergic medication within the field of psychiatry. Many in the field believe that this heralds the beginning of a new era of psychopharmacology: the era of muscarinic agonism. This article briefly described the fascinating journey from ancient betel nuts to modern muscarinic therapeutics.

Current evidence underscores a need to transform how we do clinical research, shifting from academic-driven priorities to co-led community partnership focused programs, accessible and relevant career pathway programs that expand opportunities for career development, and design of trainings and practices to develop cultural competence among research teams. Failures of equitable research translation contribute to health disparities. Drivers of this failed translation include lack of diversity in both researchers and participants, lack of alignment between research institutions and the communities they serve, and lack of attention to structural sources of inequity and drivers of mistrust for science and research. The Duke University Research Equity and Diversity Initiative (READI) is a program designed to better align clinical research programs with community health priorities through community engagement. Organized around three specific aims, READI-supported programs targeting increased workforce diversity, workforce training in community engagement and cultural competence, inclusive research engagement principles, and development of trustworthy partnerships.

The performance and confidence in fault detection and diagnostic systems can be undermined by data pipelines that feature multiple compounding sources of uncertainty. These issues further inhibit the deployment of data-based analytics in industry, where variable data quality and lack of confidence in model outputs are already barriers to their adoption. The methodology proposed in this paper supports trustworthy data pipeline design and leverages knowledge gained from one fully-observed data pipeline to a similar, under-observed case. The transfer of uncertainties provides insight into uncertainty drivers without repeating the computational or cost overhead of fully redesigning the pipeline. A SHAP-based human-readable explainable AI (XAI) framework was used to rank and explain the impact of each choice in a data pipeline, allowing the decoupling of positive and negative performance drivers to facilitate the successful selection of highly-performing pipelines. This empirical approach is demonstrated in bearing fault classification case studies using well-understood open-source data.

Oat being a rabi/winter crop in Kashmir, experiences extremely low temperatures which has detrimental effects on its growth and development. Therefore, this study was designed to evaluate a set of 130 oat genotypes in multi-location trials across temperate conditions of Kashmir valley from 2018 to 2022. From the preliminary data of 56 genotypes, including five checks, were selected and evaluated for nutritional and yield attributing traits under cold stress conditions at two locations. The results demonstrated significant genetic variation and high heritability for majority of traits, except for days to 50% flowering, days to maturity and dry fodder. Positive correlations were observed between green fodder yield and other traits, indicating their potential for enhancing yield. Principal component analysis identified four principal components that accounted for 69.87% of the total variation. Cluster analysis categorized the genotypes into two main clusters and six sub-clusters. Frost damage assessment was conducted at tillering stage after the snow melted in late January 2021 and 2022 using cold tolerance rating scale and subsequently tested for chilling injury through an electrolyte leakage test. From field and lab data analysis, five most promising cold tolerant, nutritious and high-yielding genotypes were identified. These genotypes have significant potential for utilization in future breeding programmes to improve cold tolerance in cultivated oats within the Kashmir valley thus promoting agricultural productivity and sustainability. The outcomes also provide valuable insights into the genetic variation, heritability, genotype-by-environment interactions, correlations and cold tolerance of oat genotypes in Kashmir.

A classic lift decomposition (Von Kármán & Sears, J. Aeronaut. Sci., vol. 5, 1938, pp. 379–390) is conducted on potential flow simulations of a near-ground pitching hydrofoil. It is discovered that previously observed stable and unstable equilibrium altitudes are generated by a balance between positive wake-induced lift and negative quasi-steady lift while the added mass lift does not play a role. Using both simulations and experiments, detailed analyses of each lift component's near-ground behaviour provide further physical insights. When applied to three-dimensional pitching hydrofoils the lift decomposition reveals that the disappearance of equilibrium altitudes for ${A{\kern-4pt}R}\ {\rm (aspect\ ratio)} <1.5$ occurs due to the magnitude of the quasi-steady lift outweighing the magnitude of the wake-induced lift at all ground distances. Scaling laws for the quasi-steady lift, wake-induced lift and the stable equilibrium altitude are discovered. A simple scaling law for the lift of a steady foil in ground effect is derived. This scaling shows that both circulation enhancement and the velocity induced at a foil's leading edge by the bound vortex of its ground image foil are the essential physics to understand steady ground effect. The scaling laws for unsteady pitching foils can predict the equilibrium altitude to within $20\,\%$ of its value when $St\ {\rm (Strouhal\ number)} < 0.45$. For $St \ge 0.45$ there is a wake instability effect, not accounted for in the scaling relations, that significantly alters the wake-induced lift. These results not only provide key physical insights and scaling laws for steady and unsteady ground effects, but also for two schooling hydrofoils in a side-by-side formation with an out-of-phase synchronization.

Scaling laws for the thrust production and power consumption of a purely pitching hydrofoil in ground effect are presented. For the first time, ground-effect scaling laws based on physical insights capture the propulsive performance over a wide range of biologically relevant Strouhal numbers, dimensionless amplitudes and dimensionless ground distances. This is achieved by advancing previous scaling laws (Moored & Quinn (AIAA J., 2018, pp. 1–15)) with physics-driven modifications to the added mass and circulatory forces to account for ground distance variations. The key physics introduced are the increase in the added mass of a foil near the ground and the reduction in the influence of a wake-vortex system due to the influence of its image system. The scaling laws are found to be in good agreement with new inviscid simulations and viscous experiments, and can be used to accelerate the design of bio-inspired hydrofoils that oscillate near a ground plane or two out-of-phase foils in a side-by-side arrangement.

Since the beginning of 2020, the coronavirus disease (COVID-19) pandemic has dramatically influenced almost every aspect of human life. Activities requiring human gatherings have either been postponed, canceled, or held completely virtually. To supplement lack of in-person contact, people have increasingly turned to virtual settings online, advantages of which include increased inclusivity and accessibility and a reduced carbon footprint. However, emerging online technologies cannot fully replace in-person scientific events. In-person meetings are not susceptible to poor Internet connectivity problems, and they provide novel opportunities for socialization, creating new collaborations and sharing ideas. To continue such activities, a hybrid model for scientific events could be a solution offering both in-person and virtual components. While participants can freely choose the mode of their participation, virtual meetings would most benefit those who cannot attend in-person due to the limitations. In-person portions of meetings should be organized with full consideration of prevention and safety strategies, including risk assessment and mitigation, venue and environmental sanitation, participant protection and disease prevention, and promoting the hybrid model. This new way of interaction between scholars can be considered as a part of a resilience system, which was neglected previously and should become a part of routine practice in the scientific community.

Wake-up stroke (WUS) or ischemic stroke occurring during sleep accounts for 14%–29.6% of all ischemic strokes. Management of WUS is complicated by its narrow therapeutic time window and attributable risk factors, which can affect the safety and efficacy of administering intravenous (IV) tissue plasminogen activator (t-PA). This manuscript will review risk factors of WUS, with a focus on obstructive sleep apnea, potential mechanisms of WUS, and evaluate studies assessing safety and efficacy of IV t-PA treatment in WUS patients guided by neuroimaging to estimate time of symptom onset. The authors used PubMed (1966 to March 2018) to search for the term “Wake-Up Stroke” cross-referenced with “pathophysiology,” ‘‘pathogenesis,” “pathology,” “magnetic resonance imaging,” “obstructive sleep apnea,” or “treatment.” English language Papers were reviewed. Also reviewed were pertinent papers from the reference list of the above-matched manuscripts. Studies that focused only on acute Strokes with known-onset of symptoms were not reviewed. Literature showed several potential risk factors associated with increased risk of WUS. Although the onset of WUS is unknown, a few studies investigated the potential benefit of magnetic resonance imaging (MRI) in estimating the age of onset which encouraged conducting clinical trials assessing the efficacy of MRI-guided thrombolytic therapy in WUS.

Experiments and computations are presented for a foil pitching about its leading edge near a planar, solid boundary. The foil is examined when it is constrained in space and when it is unconstrained or freely swimming in the cross-stream direction. It was found that the foil has stable equilibrium altitudes: the time-averaged lift is zero at certain altitudes and acts to return the foil to these equilibria. These stable equilibrium altitudes exist for both constrained and freely swimming foils and are independent of the initial conditions of the foil. In all cases, the equilibrium altitudes move farther from the ground when the Strouhal number is increased or the reduced frequency is decreased. Potential flow simulations predict the equilibrium altitudes to within 3 %–11 %, indicating that the equilibrium altitudes are primarily due to inviscid mechanisms. In fact, it is determined that stable equilibrium altitudes arise from an interplay among three time-averaged forces: a negative jet deflection circulatory force, a positive quasistatic circulatory force and a negative added mass force. At equilibrium, the foil exhibits a deflected wake and experiences a thrust enhancement of 4 %–17 % with no penalty in efficiency as compared to a pitching foil far from the ground. These newfound lateral stability characteristics suggest that unsteady ground effect may play a role in the control strategies of near-boundary fish and fish-inspired robots.

OBJECTIVES/SPECIFIC AIMS: The aim of this study is to determine whether quantitative measures of knee structures including effusion, bone marrow lesions, cartilage, and meniscal damage can improve upon an existing model of demographic and clinical characteristics to classify accelerated knee osteoarthritis (AKOA). METHODS/STUDY POPULATION: We conducted a case-control study using data from baseline and four annual follow-up visits from the osteoarthritis initiative. Participants had no radiographic knee osteoarthritis (KOA) at baseline. AKOA is defined as progressing from no KOA to advance-stage KOA in at least 1 knee within 48 months. AKOA knees were matched 1:1 based on sex to (1) participants who did not develop KOA within 48 months and (2) participants who developed KOA but not AKOA. Analyses were person based. Classification and regression tree analysis was used to determine the important variables and percent of variance explained. RESULTS/ANTICIPATED RESULTS: A previous classification and regression tree analysis found that age, BMI, serum glucose, and femorotibial angle explained 31% of the variability between those who did and did not develop AKOA. Including structural measurements as candidate variables yielded a model that included effusion, BMI, serum glucose, cruciate ligament degeneration and coronal slope and explained 39% of the variability. DISCUSSION/SIGNIFICANCE OF IMPACT: Knee structural measurements improve classification of participants who developed AKOA Versus those who did not. Further research is needed to better classify patients at risk for AKOA.

Selective transsphenoidal adenomectomy is generally recommended for initial treatment of Cushing's disease (CD) because it achieves a high (70-85%) rate of remission. However, if initial surgery is not successful, the approach to persistent or recurrent CD is more complex. Because residual or recurrent adenoma is typically found at the site of the original adenoma, repeat transsphenoidal surgery is recommended including selective adenomectomy, hemihypophysectomy or total hypophysectomy. If repeat pituitary surgery does not achieve remission, then possible adjuvant therapies include radiosurgery or stereotactic radiotherapy, bilateral adrenalectomy, and/or medical therapy. In all cases of persistent or recurrent CD, successful treatment requires close collaboration of endocrinologists, radiation oncologists and neurosurgeons.

Mesoporous silicas were synthesized via a surfactant-templated sol-gel route using castor oil as the templating agent under acidic medium. The resulting silicas were subsequently amine functionalized with 3-aminopropyltriethoxysilane (NH2-MTS), [3-(2-aminoethylamino)-propyl]trimethoxysilane (NN-MTS), and [3-(diethylamino)propyl]trimethoxysilane(DN-MTS) to introduce surface basicity. Surface physicochemical properties were characterized by field emission gun scanning electron microscopy (FEGSEM), nitrogen porosimetry, X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and diffuse reflectance infrared fourier transform spectroscopy (DRIFTS). As-synthesised materials exhibit type IV adsorption-desorption isotherms characteristic of mesoporous structures. Clusters of spherical shaped materials were observed by FEGSEM, suggesting growth of silica occurs within colloidal dispersions. High-resolution N 1s XP spectra and DRIFT spectra confirmed the presence of amine groups in the organo-amine functionalised mesoporous silicas. The amine functionalised mesoporous silicas were active for the transesterification of tributyrin with methanol, with conversion found to increase from NH2-MTS< NN-MTS< DN-MTS.

Human resource management in agriculture and associated risks are under-researched topics. To identify the sources of human resource management risks confronting dairy farms, gain insights into how dairy farmers perceive the impacts of these risks, and identify control strategies, four focus group discussions were held with dairy farm managers. Managers' perceptions served to develop a framework for the analysis of human resource management risks in agriculture and derive recommendations for reducing these risks. Results of this study have been used to tailor educational programs for farmers and suggest strategies for future research.