3,852 research outputs found

    Investigating Human Embryo Implantation – Developing Clinical Applications from in vitro Models

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    Introduction: While assisted conception success rates have increased, factors limiting IVF success include inadequacies in identifying viable embryos, and transfer of embryos into uteri with an unknown state of receptivity. Aims and experimental approaches: The aims of this project are to determine the possibility of using non-invasive techniques to reveal differences between preimplantation human embryos which successfully form a pregnancy and those that fail to implant. The experimental approaches are: 1 Sampling of conditioned media and co-culture with a 3D in vitro model of mid-secretory phase normal human endometrium, followed by transcriptomic analysis of these endometrial cells; 2 Development of a time lapse annotation system to improve selection of PN stage frozen embryos cultured to blastocyst and replaced in FET cycles. Methods: Endometrial epithelial and stromal cells in an in vitro model of mid-secretory phase human endometrium were exposed to conditioned media samples from 10 human embryos cultured singly to the blastocyst stage, with known pregnancy outcomes. These cells were subjected to RNA sequencing and transcriptomic analysis. Time lapse recordings of these embryos were taken through an experimental AI model (eM-Life). Retrospective analysis and annotation of time lapse videos of embryo development of 193 PN stage frozen embryos thawed and cultured to the blastocyst stage for replacement in an FET cycle was performed. Results: Endometrial epithelial cells showed changes in gene expression in response to media from successful embryos, while stromal cells responded to a lesser extent to media from unsuccessful embryos. The deep learning model ranked embryos on morphology but did not correlate with endometrial response in this project. From the analysis of 193 PN stage frozen embryos, statistically significant differences in several morphokinetic parameters between implanting and non-implanting embryos were found and morphological differences not previously studied in frozen thawed embryos relating to embryo viability were identified. Conclusions: Both experimental approaches revealed differences between embryos which implant successfully and those which fail, not detected by standard morphological grading. Further work is needed to identify upstream factors in conditioned media which cause gene expression changes in the in vitro endometrial model, and to test the morphokinetic model developed for frozen embryos in culture

    A clinical decision support system for detecting and mitigating potentially inappropriate medications

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    Background: Medication errors are a leading cause of preventable harm to patients. In older adults, the impact of ageing on the therapeutic effectiveness and safety of drugs is a significant concern, especially for those over 65. Consequently, certain medications called Potentially Inappropriate Medications (PIMs) can be dangerous in the elderly and should be avoided. Tackling PIMs by health professionals and patients can be time-consuming and error-prone, as the criteria underlying the definition of PIMs are complex and subject to frequent updates. Moreover, the criteria are not available in a representation that health systems can interpret and reason with directly. Objectives: This thesis aims to demonstrate the feasibility of using an ontology/rule-based approach in a clinical knowledge base to identify potentially inappropriate medication(PIM). In addition, how constraint solvers can be used effectively to suggest alternative medications and administration schedules to solve or minimise PIM undesirable side effects. Methodology: To address these objectives, we propose a novel integrated approach using formal rules to represent the PIMs criteria and inference engines to perform the reasoning presented in the context of a Clinical Decision Support System (CDSS). The approach aims to detect, solve, or minimise undesirable side-effects of PIMs through an ontology (knowledge base) and inference engines incorporating multiple reasoning approaches. Contributions: The main contribution lies in the framework to formalise PIMs, including the steps required to define guideline requisites to create inference rules to detect and propose alternative drugs to inappropriate medications. No formalisation of the selected guideline (Beers Criteria) can be found in the literature, and hence, this thesis provides a novel ontology for it. Moreover, our process of minimising undesirable side effects offers a novel approach that enhances and optimises the drug rescheduling process, providing a more accurate way to minimise the effect of drug interactions in clinical practice

    Current and Future Challenges in Knowledge Representation and Reasoning

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    Knowledge Representation and Reasoning is a central, longstanding, and active area of Artificial Intelligence. Over the years it has evolved significantly; more recently it has been challenged and complemented by research in areas such as machine learning and reasoning under uncertainty. In July 2022 a Dagstuhl Perspectives workshop was held on Knowledge Representation and Reasoning. The goal of the workshop was to describe the state of the art in the field, including its relation with other areas, its shortcomings and strengths, together with recommendations for future progress. We developed this manifesto based on the presentations, panels, working groups, and discussions that took place at the Dagstuhl Workshop. It is a declaration of our views on Knowledge Representation: its origins, goals, milestones, and current foci; its relation to other disciplines, especially to Artificial Intelligence; and on its challenges, along with key priorities for the next decade

    Archaeological palaeoenvironmental archives: challenges and potential

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    This Arts and Humanities Research Council (AHRC) sponsored collaborative doctoral project represents one of the most significant efforts to collate quantitative and qualitative data that can elucidate practices related to archaeological palaeoenvironmental archiving in England. The research has revealed that archived palaeoenvironmental remains are valuable resources for archaeological research and can clarify subjects that include the adoption and importation of exotic species, plant and insect invasion, human health and diet, and plant and animal husbandry practices. In addition to scientific research, archived palaeoenvironmental remains can provide evidence-based narratives of human resilience and climate change and offer evidence of the scientific process, making them ideal resources for public science engagement. These areas of potential have been realised at an imperative time; given that waterlogged palaeoenvironmental remains at significant sites such as Star Carr, Must Farm, and Flag Fen, archaeological deposits in towns and cities are at risk of decay due to climate change-related factors, and unsustainable agricultural practices. Innovative approaches to collecting and archiving palaeoenvironmental remains and maintaining existing archives will permit the creation of an accessible and thorough national resource that can service archaeologists and researchers in the related fields of biology and natural history. Furthermore, a concerted effort to recognise absences in archaeological archives, matched by an effort to supply these deficiencies, can produce a resource that can contribute to an enduring geographical and temporal record of England's biodiversity, which can be used in perpetuity in the face of diminishing archaeological and contemporary natural resources. To realise these opportunities, particular challenges must be overcome. The most prominent of these include inconsistent collection policies resulting from pressures associated with shortages in storage capacity and declining specialist knowledge in museums and repositories combined with variable curation practices. Many of these challenges can be resolved by developing a dedicated storage facility that can focus on the ongoing conservation and curation of palaeoenvironmental remains. Combined with an OASIS + module designed to handle and disseminate data pertaining to palaeoenvironmental archives, remains would be findable, accessible, and interoperable with biological archives and collections worldwide. Providing a national centre for curating palaeoenvironmental remains and a dedicated digital repository will require significant funding. Funding sources could be identified through collaboration with other disciplines. If sufficient funding cannot be identified, options that would require less financial investment, such as high-level archive audits and the production of guidance documents, will be able to assist all stakeholders with the improved curation, management, and promotion of the archived resource

    Investigating the learning potential of the Second Quantum Revolution: development of an approach for secondary school students

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    In recent years we have witnessed important changes: the Second Quantum Revolution is in the spotlight of many countries, and it is creating a new generation of technologies. To unlock the potential of the Second Quantum Revolution, several countries have launched strategic plans and research programs that finance and set the pace of research and development of these new technologies (like the Quantum Flagship, the National Quantum Initiative Act and so on). The increasing pace of technological changes is also challenging science education and institutional systems, requiring them to help to prepare new generations of experts. This work is placed within physics education research and contributes to the challenge by developing an approach and a course about the Second Quantum Revolution. The aims are to promote quantum literacy and, in particular, to value from a cultural and educational perspective the Second Revolution. The dissertation is articulated in two parts. In the first, we unpack the Second Quantum Revolution from a cultural perspective and shed light on the main revolutionary aspects that are elevated to the rank of principles implemented in the design of a course for secondary school students, prospective and in-service teachers. The design process and the educational reconstruction of the activities are presented as well as the results of a pilot study conducted to investigate the impact of the approach on students' understanding and to gather feedback to refine and improve the instructional materials. The second part consists of the exploration of the Second Quantum Revolution as a context to introduce some basic concepts of quantum physics. We present the results of an implementation with secondary school students to investigate if and to what extent external representations could play any role to promote students’ understanding and acceptance of quantum physics as a personal reliable description of the world

    A Theistic Critique of Secular Moral Nonnaturalism

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    This dissertation is an exercise in Theistic moral apologetics. It will be developing both a critique of secular nonnaturalist moral theory (moral Platonism) at the level of metaethics, as well as a positive form of the moral argument for the existence of God that follows from this critique. The critique will focus on the work of five prominent metaethical theorists of secular moral non-naturalism: David Enoch, Eric Wielenberg, Russ Shafer-Landau, Michael Huemer, and Christopher Kulp. Each of these thinkers will be critically examined. Following this critique, the positive moral argument for the existence of God will be developed, combining a cumulative, abductive argument that follows from filling in the content of a succinct apagogic argument. The cumulative abductive argument and the apagogic argument together, with a transcendental and modal component, will be presented to make the case that Theism is the best explanation for the kind of moral, rational beings we are and the kind of universe in which we live, a rational intelligible universe

    Semantic inconsistency measures using 3-valued logics

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    AI systems often need to deal with inconsistencies. One way of getting information about inconsistencies is by measuring the amount of information in the knowledgebase. In the past 20 years numerous inconsistency measures have been proposed. Many of these measures are syntactic measures, that is, they are based in some way on the minimal inconsistent subsets of the knowledgebase. Very little attention has been given to semantic inconsistency measures, that is, ones that are based on the models of the knowledgebase where the notion of a model is generalized to allow an atom to be assigned a truth value that denotes contradiction. In fact, only one nontrivial semantic inconsistency measure, the contension measure, has been in wide use. The purpose of this paper is to define a class of semantic inconsistency measures based on 3-valued logics. First, we show which 3-valued logics are useful for this purpose. Then we show that the class of semantic inconsistency measures can be developed using a graphical framework similar to the way that syntactic inconsistency measures have been studied. We give several examples of semantic inconsistency measures and show how they apply to three useful 3-valued logics. We also investigate the properties of these inconsistency measures and show their computation for several knowledgebases

    DEVELOPMENT AND VALIDITY INQUIRY OF A RUBRIC FOR INTERDISCIPLINARY COMPETENCIES IN OCCUPATIONAL SAFETY AND HEALTH IN CAPSTONE PROJECTS OF CARERC PROGRAM GRADUATES

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    Emerging demands in the field of interdisciplinary studies reveal a need for competent professionals who can apply their skills and experience to solving complex tasks of the workplace. This has placed inevitable demands on training institutions to adequately equip graduates to deliver on their mandate. Competency appraisal is an effective way to ensure proficiency in graduates. Meanwhile, transparent and valid rubrics provide opportunities for both students and trainers to continuously assess and evaluate the transfer of necessary skills. This study focused on evaluating interdisciplinary competencies in Occupational Safety and Health (OSH) in the capstone projects of the CARERC program, a graduate and continuing education package that combines the academic resources of seven colleges of two major universities in Kentucky for research and training in the region. An Interdisciplinary Competency Evaluation Rubric in OSH (iCER-OSH) confirming the “presence” or “not” of the relevant competencies in the final projects was developed from literature and program core-syllabi and was tested and calibrated using Rasch model. The psychometric evaluation of the rubric also supports the use of this tool for research and formative assessment in this population and related programs
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