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Characterizing Oxylipins in Human Milk Extracellular Vesicles
Get PDFExtracellular vesicles (EVs) are non-replicating lipid bilayer membrane-bound particle formed by a parent cell and secreted into the extracellular environment. EVs in human milk are bioavailable and influence physiologic pathways that may contribute to newborn growth and development. There is interest in the oxylipin content of EVs that may contribute to the bioavailability of EVs. This research aims to characterize the oxylipin content of human milk EVs. Centrifugation and precipitation were used to isolate EVs from human milk (n = 20). The Folch method was used to extract lipids, and liquid chromatography-mass spectrometry (LC– MS) was used to qualify and quantify the presence of oxylipins. The relative content of oxylipins in human milk EVs were analyzed in relation to the relative content of oxylipins in whole human milk, with values standardized to the total protein content. The research found a higher relative abundance of n-6 PUFA-derived oxylipins (93-97%) than n-3 PUFAs (2.9-6.3%) in both EVs and whole human milk. EVs revealed higher amounts of LA-derived oxylipins (88.37%) than whole human milk (81.69%) (p \u3c 0.0001). While whole human milk displayed higher amounts of AA-, DHA-, and EPA-derived oxylipins (12%, 5.43%, 0.89%, respectively) than EVs (8.74%, 2.71%, 0.18%, respectively) (p-values for AA, DHA, and EPA are 0.0003, \u3c 0.0001, \u3c 0.0001, respectively). Most oxylipins were derived from the LOX pathway in both EVs (93.9%) and whole human milk (90.7%). PGE2, 13-HODE, and 9-HODE were significantly more abundant in EVs (1.64, 1.14, 1.01-fold, respectively), while 17-HDHA, 14-HDHA, and RsVD1 Mix 5 were the three oxylipins most enriched in human milk (0.0485, 0.0425, 0.0371-fold, respectively). The other oxylipins considered significantly higher in human milk than EVs are 13-HDHA, 4-vii HDHA, 12,13-DiHOME, and 11,12-DiHET. This contribution is significant since selected oxylipins present in human milk EVs versus whole human milk may be critical to the bioavailability and passage of dietary EVs across physiologic barriers
Estimating Post-Fire Flood Infrastructure Clogging and Overtopping Hazards
Get PDFCycles of wildfire and rainfall produce sediment-laden floods that pose a hazard to development and may clog or overtop protective infrastructure, including debris basins and flood channels. The compound, post-fire flood hazards associated with infrastructure overtopping and clogging are challenging to estimate due to the need to account for interactions between sequences of wildfire and storm events and their impact on flood control infrastructure over time. Here we present data sources and calibration methods to estimate infrastructure clogging and channel overtopping hazards on a catchment-by-catchment basis using the Post-Fire Flood Hazard Model (PF2HazMo), a stochastic modeling approach that utilizes continuous simulation to resolve the effects of antecedent conditions and system memory. Publicly available data sources provide parameter ranges needed for stochastic modeling, and several performance measures are considered for model calibration. With application to three catchments in southern California, we show that PF2HazMo predicts the median of the simulated distribution of peak bulked flows within the 95% confidence interval of observed flows, with an order of magnitude range in bulked flow estimates depending on the performance measure used for calibration. Using infrastructure overtopping data from a post-fire wet season, we show that PF2HazMo accurately predicts the number of flood channel exceedances. Model applications to individual watersheds reveal where infrastructure is undersized to contain present-day and future overtopping hazards based on current design standards. Model limitations and sources of uncertainty are also discussed
Axiomatic Characterization of Generalized NEO-EU Preferences and the Falsifiability of Ambiguity Theories
Get PDFWe introduce a new weakening of the independence axiom, co-extreme independence, which we show characterizes a class that encompasses popular ambiguity models including Hurwicz preferences, ϵ-contamination preferences, and NEOEU preferences. Importantly, our representation unifies these as forms of simple ambiguity models as we show that the Vapnik-Chervonenkis (VC) dimension of these models is either unity or increases linearly with the number of states. In contrast, standard ambiguity models characterized in the Anscombe-Aumann framework are complex ambiguity models that have a VC dimension that is either infinite or increases exponentially in the number of states. We show that simple ambiguity preferences are efficient to compute by introducing a linear program for finding the parameters of a NEO-EU representation given an arbitrary dataset of binary choices between acts. In contrast to recent work showing that ambiguity theories have large VC dimension compared to expected utility theory (EU), simple ambiguity preferences provide a counter-example to the conjectures that axiomatic models of ambiguity attitudes are substantially more difficult to falsify or are substantially more complex than EU
Global Perspective of the Risks of Falsified and Counterfeit Medicines: A Critical Review of the Literature
Get PDFBackground The increasing prevalence of falsified and counterfeit medicines globally poses risks to international travellers. This narrative literature review examines the global challenge of falsified and counterfeit medicines, with a specific focus on risks for travellers. The aim is to provide a comprehensive understanding of this multidimensional issue, exploring potential solutions for effective intervention. Methods A comprehensive search of databases, including PubMed, MEDLINE, and Scopus, as well as relevant reports from international organisations, was undertaken. There was a focus on extracting information pertaining to the prevalence, types, and geographical patterns of falsified and counterfeit medicines encountered by international travellers. Synthesising this information helped to identify overarching trends and patterns. This narrative review utilised a thematic analysis approach to synthesise the findings. Results The findings revealed a diverse range of counterfeit drug categories, spanning from antibiotics to lifestyle medications, posing unique risks to travellers navigating the global pharmaceutical landscape. The review emphasises the geographical distribution of these drugs, with varying consequences for both high- and low-income nations. The inadequate formulations and inconsistent drug release arising from these practices pose severe threats to public health, especially for individuals travelling abroad. The review also highlights the significance of international collaboration in addressing this global challenge, as pharmaceutical supply chains seamlessly cross borders, necessitating a collaborative approach for effective regulation and enforcement. Conclusions This review underscores the need for targeted research, collaborative interventions, and technological innovations to address the complexities associated with falsified and counterfeit medicines, ensuring the safety and well-being of international travellers
AARS Online: A Collaborative Database on the Structure, Function, and Evolution of the Aminoacyl-tRNA Synthetases
Get PDFThe aminoacyl-tRNA synthetases (aaRS) are a large group of enzymes that implement the genetic code in all known biological systems. They attach amino acids to their cognate tRNAs, moonlight in various translational and non-translational activities beyond aminoacylation, and are linked to many genetic disorders. The aaRS have a subtle ontology characterized by structural and functional idiosyncrasies that vary from organism to organism, and protein to protein. Across the tree of life, the 22 coded amino acids are handled by 16 evolutionary families of Class I aaRS and 21 families of Class II aaRS. We introduce AARS Online, an interactive Wikipedia-like tool curated by an international consortium of field experts. This platform systematizes existing knowledge about the aaRS by showcasing a taxonomically diverse selection of aaRS sequences and structures. Through its graphical user interface, AARS Online facilitates a seamless exploration between protein sequence and structure, providing a friendly introduction to the material for non-experts and a useful resource for experts. Curated multiple sequence alignments can be extracted for downstream analyses. Accessible at www.aars.online, AARS Online is a free resource to delve into the world of the aaRS
Justice via Chat? How Litigants’ Preferences and Attorneys’ Recommendations Influence the Choice to Use Online Dispute Resolution
Get PDFThere is a significant need for empirical evidence concerning how litigants compare and choose between various modalities of online dispute resolution (ODR) and traditional in-person mediation for resolving legal disputes. To fill this need, we examined three potentially relevant psychological factors: (a) baseline attitudes toward in-person, video, and text-based mediation; (b) past communication style used by litigants; and (c) expert advice via attorney recommendations. We utilized a 2 × 3 × 3 design with communication style as a between-subjects variable, mediation modality as a within-subjects variable, and attorney recommendation randomized as either aligning with or differing from the participant’s baseline preference across 261 participants. We also identified the factors that litigants believe influence their decisions and examined how these factors shape their perceptions and ultimate choice. Participants read two cases and indicated their preferred mediation modality for each by ranking and rating the three modality options. They then learned which option their hypothetical attorney recommended and ranked and rated the options again. Using a mixed-model factorial analysis of variance, we found that (a) parties generally disfavored text-based mediation; (b) parties were swayed by their attorneys’ modality recommendation; and (c) the influence of attorney recommendation was tempered when the attorney suggested text-based mediation. The findings have implications for both legal psychology and policies surrounding ODR, including the current trend in state courts to offer text-based ODR
Local Hydroclimate Alters Interpretation of Speleothem δ18O Records
Get PDFOxygen isotopes (δ18O) are the most commonly utilized speleothem proxy and have provided many foundational records of paleoclimate. Thus, understanding processes affecting speleothem δ18O is crucial. Yet, prior calcite precipitation (PCP), a process driven by local hydrology, is a widely ignored control of speleothem δ18O. Here we investigate the effects of PCP on a stalagmite δ18O record from central Vietnam, spanning 45 – 4 ka. We employ a geochemical model that utilizes speleothem Mg/Ca and cave monitoring data to correct the δ18O record for PCP effects. The resulting record exhibits improved agreement with regional speleothem δ18O records and climate model simulations, suggesting that the corrected record more accurately reflects precipitation δ18O (δ18Op). Without considering PCP, our interpretations of the δ18O record would have been misleading. To avoid misinterpretations of speleothem δ18O, our results emphasize the necessity of considering PCP as a significant driver of speleothem δ18O
A Tale of Two Bills: Lessons Learned in Expanding Pharmacist-Led HIV Pre-Exposure and Post-Exposure Prophylaxis
No full textIn December 2023, JACCP published a content analysis of state legislative bills focused on expanding pharmacist scope of practice to provide human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP).1 All states permit pharmacists to prescribe under a collaborative practice agreement with approximately half of the states granting HIV PrEP and post-exposure prophylaxis (PEP) authority to prescribe either via legislation, standing orders, or statewide protocols.2-4 New York was the first state to expand pharmacists\u27 specific authority for HIV prevention in 2017; however, California was the first state to pass legislation with Senate Bill 159 (SB 159) in 2019 using the term “furnishing” instead of prescribing.5 Fast forward to 2024, and California passed a new Senate Bill (SB 339) expanding pharmacist-prescribed HIV PrEP and PEP. While California was one of the early pioneers in codifying the importance of the pharmacist\u27s role in HIV prevention, there are also many lessons to be learned from this tale of two bills that other states should consider as they attempt to expand the pharmacist\u27s HIV prevention efforts
Introducing the Transcendent Media Experience Model (TMEM)
Get PDFEudaimonic media experiences are vast. A comprehensive theoretical model of inward- and outward-focused eudaimonic media outcomes, that can explain how they come about and how they can be discriminated, is still missing. The current manuscript introduces the Transcendent Media Experiences Model (TMEM) to categorize eudaimonic content and experiences as they pertain to healthy self-focus or outward-focused (transcendent) responses and outcomes using self-construal theory as a backbone. This model allows for a more cohesive understanding of when, how, and for whom inward- or outward focused eudaimonic media experiences develop and the mechanisms for why they do so. As such, the model provides a framework for future research directions to systematically address the challenges of predicting, describing, and measuring eudaimonic media experiences and effects