Inhibition of Intestinal Thiamin Transport in Rat Model of Sepsis.

ObjectivesThiamin deficiency is highly prevalent in patients with sepsis, but the mechanism by which sepsis induces thiamin deficiency is unknown. This study aimed to determine the influence of various severity of sepsis on carrier-mediated intestinal thiamin uptake, level of expressions of thiamin transporters (thiamin transporter-1 and thiamin transporter-2), and mitochondrial thiamin pyrophosphate transporter.DesignRandomized controlled study.SettingResearch laboratory at a Veterans Affairs Medical Center.SubjectsTwenty-four Sprague-Dawley rats were randomized into controls, mild, moderate, and severe sepsis with equal number of animals in each group.InterventionsSepsis was induced by cecal ligation and puncture with the cecum ligated below the cecal valve at 25%, 50%, and 75% of cecal length, defined as severe, moderate, and mild sepsis, respectively. Control animals underwent laparotomy only.Measurements and main resultsAfter 2 days of induced sepsis, carrier-mediated intestinal thiamin uptake was measured using [H]thiamin. Expressions of thiamin transporter-1, thiamin transporter-2, and mitochondrial thiamin pyrophosphate transporter proteins and messenger RNA were measured. Proinflammatory cytokines (interleukin-1β and interleukin-6) and adenosine triphosphate were also measured. Sepsis inhibited [H]thiamin uptake, and the inhibition was a function of sepsis severity. Both cell membrane thiamin transporters and mitochondrial thiamin pyrophosphate transporter expression levels were suppressed; also levels of adenosine triphosphate in the intestine of animals with moderate and severe sepsis were significantly lower than that of sham-operated controls.ConclusionsFor the first time, we demonstrated that sepsis inhibited carrier-mediated intestinal thiamin uptake as a function of sepsis severity, suppressed thiamin transporters and mitochondrial thiamin pyrophosphate transporter, leading to adenosine triphosphate depletion

Evolution and identity of synapsid carpal bones

To date there is little information on carpal bone homology in late Palaeozoic and Mesozoic Synapsida. Crucial to the understanding of homology in synapsid carpal elements is the fact that different nomenclatures are used for the carpals of non-mammaliamorph Synapsida (Gegenbauer?s canonical nomenclature) and Mammaliaformes (mammalian nomencla-ture). The homologies of the carpals of non-mammaliamorph synapsids and mammals were established early last century and have not been reviewed since then. Here we provide a detailed study of the carpal bones of synapsids ranging in age from the early Permian to Late Cretaceous. The mammaliamorph lunate, previously considered the homologue of the intermedium of non-mammaliamorph synapsids, is interpreted here as homologous to their lateral centrale. We interpret the single mammaliamorph centrale as a homologue of the medial centrale of non-mammaliamorph synapsids. In some synapsid specimens, we found that one or two centralia are fused to the radiale (e.g., the gorgonopsian Arctognathus and tritylodontid Bienotheroides), supporting a digging habit. A third centrale is present in the therocephalian Theriognathus, very likely an abnormal duplication. An additional medial bone in a biarmosuchian was interpreted as a prepollex/sesamoid. A cartilaginous prepollex/sesamoid may also have been present in several non-mammaliamorph synapsids, which have an open space proximal to distal carpal I. Distal carpal V is completely lost in dicynodonts and it is mainly fused to distal carpal IV in the adult stage of most other therapsid groups, but showed a delayed development in most non-mammaliamorph cynodonts. In mammaliamorphs, distal carpal V is not present. Our observations provide an up-dated revision of synapsid carpal homologies, mainly on the basis of position and anatomical contacts and also taking into account the results of embryological studiesFil: Kummell, S.. University Witten/herdecke; AlemaniaFil: Abdala, Nestor Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Sassoon, J.. University Of Bristol; Reino UnidoFil: Abdala, Virginia Sara Luz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Biodiversidad Neotropical. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto de Biodiversidad Neotropical. Instituto de Biodiversidad Neotropical; Argentin

EQRbot: A chatbot delivering EQR argument-based explanations

Data availability statement: The provided link: https://github.com/FCast07/EQRbot refers to the GitHub repository that stores the chatbot programming code.Recent years have witnessed the rise of several new argumentation-based support systems, especially in the healthcare industry. In the medical sector, it is imperative that the exchange of information occurs in a clear and accurate way, and this has to be reflected in any employed virtual systems. Argument Schemes and their critical questions represent well-suited formal tools for modeling such information and exchanges since they provide detailed templates for explanations to be delivered. This paper details the EQR argument scheme and deploys it to generate explanations for patients' treatment advice using a chatbot (EQRbot). The EQR scheme (devised as a pattern of Explanation-Question-Response interactions between agents) comprises multiple premises that can be interrogated to disclose additional data. The resulting explanations, obtained as instances of the employed argumentation reasoning engine and the EQR template, will then feed the conversational agent that will exhaustively convey the requested information and answers to follow-on users' queries as personalized Telegram messages. Comparisons with a previous baseline and existing argumentation-based chatbots illustrate the improvements yielded by EQRbot against similar conversational agents.This research was partially funded by the UK Engineering & Physical Sciences Research Council (EPSRC) under Grant #EP/P010105/1

A formalisation and prototype implementation of argumentation for statistical model selection

© 2019 – IOS Press and the authors. The task of data collection is becoming routine in many disciplines and this results in increased availability of data. This routinely collected data provides a valuable opportunity for analysis with a view to support evidence based decision making. In order to confidently leverage the data in support of decision making the most appropriate statistical method needs to be selected, and this can be difficult for an end user not trained in statistics. This paper outlines an application of argumentation to support the analysis of clinical data, that uses Extended Argumentation Frameworks in order to reason with the meta-level arguments derived from preference contexts relevant to the data and the analysis objective of the end user. We outline a formalisation of the argument scheme for statistical model selection, its critical questions and the structure of the knowledge base required to support the instantiation of the arguments and meta-level arguments through the use of Z notation. This paper also describes the prototype implementation of argumentation for statistical model selection based on the Z specification outlined herein.CONSULT EPSRC grant no. EP-P010105-1

On the Complexity of Determining Defeat Relations Consistent with Abstract Argumentation Semantics

Presented at Computational Models of Argument Proceedings of COMMA 2022 ((9th International Conference on Computational Models of Argument COMMA 2022, Cardiff, UK, 14-16 September, 2022) Available at https://ebooks.iospress.nl/ISBN/978-1-64368-306-5Copyright 2022 The authors and IOS Press. Typically in abstract argumentation, one starts with arguments and a defeat relation, and applies some semantics in order to determine the acceptability status of the arguments. We consider the converse case where we have knowledge of the acceptability status of arguments and want to identify a defeat relation that is consistent with the known acceptability data – the σ-consistency problem. Focusing on complete semantics as underpinning the majority of the major semantic types, we show that the complexity of determining a defeat relation that is consistent with some set of acceptability data is highly dependent on how the data is labelled. The extension-based 2-valued σ-consistency problem for complete semantics is revealed as NP-complete, whereas the labelling-based 3-valued σ-consistency problem is solvable within polynomial time. We then present an informal discussion on application to grounded, stable, and preferred semantics