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Motion Compensation in Pulmonary Fluorescence Lifetime Imaging: An Image Processing Pipeline for Artefact Reduction and Clinical Precision
No full textGoal: This study introduces Temporal Reliability and Accuracy via Correlation Enhanced Registration (TRACER), a novel image processing pipeline that addresses motion artefacts in real-time Fluorescence Lifetime Imaging (FLIm) data for in-vivo pulmonary Optical Endomicroscopy (OEM). Its primary objective is to improve the accuracy and reliability of FLIm image sequences. Methods: The proposed TRACER pipeline comprises a comprehensive sequence of pre-processing steps and a novel registration approach. This includes the removal of uninformative frames and motion characterisation through dense optical flow, followed by a tracking-based Normalised Cross Correlation image registration method leveraging Channel and Spatial Reliability Tracker for precise alignment. Results: The complete TRACER pipeline delivers significant performance improvements, with 20% to 30% enhancement across different metrics for all tested registration methods. In particular, the unique TRACER registration approach outperforms state-of-theart methods in image registration performance and achieves an order-of-magnitude faster runtime than the next best-performing approach. Conclusion: By addressing motion artefacts through its integrated pre-processing and novel registration strategy, TRACER offers a robust solution that ensures improved image quality and real-time feasibility for FLIm data processing in in-vivo pulmonary OEM
Descriptions of advanced multimorbidity:A scoping review with content analysis
No full textINTRODUCTION: Multimorbidity is associated with adverse clinical outcomes, including increased symptom burden and healthcare utilisation, particularly towards the end of life. Despite this, there is no accepted method to identify the point at which individuals with deteriorating health due to long-term conditions are nearing the end of life or might benefit from a palliative care approach - conceptualised as 'Advanced Multimorbidity'. This scoping review explored how Advanced Multimorbidity is described and operationalised within the literature.METHODS: Multiple electronic databases and Grey Literature sources were searched following scoping review frameworks. Two reviewers independently performed screening and data extraction. Content analysis was used to examine the different descriptions of Advanced Multimorbidity. Stakeholder consultations were undertaken with clinicians, academics and public participants. Patient and public involvement was separately integrated throughout this review from conceptualisation, design and reporting.RESULTS: Forty-four different descriptions of Advanced Multimorbidity were identified from 38 publications. These varied in terms of the clinical conditions and descriptors used. Eighteen descriptions relied on a single indicator to identify Advanced Multimorbidity; 24 used a multidimensional approach. Stakeholder consultations highlighted the need for descriptions that are user-friendly and actionable.CONCLUSION: The lack of a standardised definition of Advanced Multimorbidity risks variance in clinical and research practice, potentially affecting patient care. A consensus on defining Advanced Multimorbidity would enable better identification of patients who could benefit from a palliative care approach, ensuring more consistent and person-centred care, as well as supporting research and policy development.</p
Drosophila complement-like Mcr acts as a wound-induced inflammatory chemoattractant
No full textSterile tissue injury is accompanied by an acute inflammatory response whereby innate immune cells rapidly migrate to the site of injury guided by pro-inflammatory chemotactic damage signals released at the wound. Understanding this immune response is key to improving human health, and recent advances in imaging technology have allowed researchers using different model organisms to observe this inflammatory response in vivo. Over recent decades, offering a unique combination of live time-lapse microscopy and genetics, the fruit fly Drosophila has emerged as a powerful model system to study inflammatory cell migration within a living animal. 1 , 2 , 3 , 4 However, we still know relatively little regarding the identity of the earliest signals that drive this immune cell recruitment and the mechanisms by which they act within the complex, in vivo setting of a multicellular organism. Here, we couple the powerful genetics and live imaging of Drosophila with mathematical modeling to identify the fly complement ortholog—macroglobulin complement-related (Mcr)—as an early, wound-induced chemotactic signal responsible for the inflammatory recruitment of immune cells to injury sites in vivo. We show that epithelial-specific knockdown of Mcr suppresses the recruitment of macrophages to wounds and combine predictive mathematical modeling with in vivo genetics to understand macrophage migration dynamics following manipulation of this chemoattractant. We propose a model whereby Mcr operates alongside hydrogen peroxide to ensure a rapid and efficient immune response to damage, uncovering a novel function for this protein that parallels the chemotactic role of the complement component C5a in mammals.</p
Leases of shooting rights over land
Get PDFLeases of rights to shoot over land are commercially important in Scotland. The question of whether these remain effective if the land is sold, in other words whether these rights are real and bind successor landlords has proved an elusive one. There is a considerable amount of conflicting case law and commentary on the subject. This article is the first to analyse the subject comprehensively. It reaches the conclusion that the tenants’ rights under such leases are not real and recommends statutory intervention to address this
Notes from the archives:Re-analysis of skeletal assemblages from three later fourth millennium BC Irish passage tombs
Get PDFPassage tombs are one of the best-known aspects of the Irish Neolithic, with over 200 surviving examples recorded. A small fraction of these monuments have been excavated with any associated human remains rarely recorded to modern osteoarchaeological standards. This makes it challenging to make robust inferences on the nature of mortuary practice and social structure in the Irish Neolithic, but overcoming these challenges is not an impossible task. In this paper we outline recent and ongoing re-analysis of skeletal assemblages from three late fourth-millennium BC passage tombs — Knockroe, Co. Kilkenny, and Fourknocks and Newgrange, Co. Meath — all excavated between 1950 and 2010. The burial deposits from Knockroe and Fourknocks were fully sampled during excavation and represent a rare opportunity to fully analyse and assess what may come close to a complete sequence of prehistoric burial activity. The surviving archive from Newgrange, while incomplete, is nevertheless providing new insight on the nature of activity within the tomb. We highlight the value of approaching older excavation archives with new methods and fresh eyes, and underscore the importance of constructing robust, standardised baselines of archaeologically analysable populations
Fast, Accurate, and Versatile Data Analysis Platform for the Quantification of Molecular Spatiotemporal Signals
Get PDFOptical recording of intricate molecular dynamics is becoming an indispensable technique for biological studies, accelerated by the development of new or improved biosensors and microscopy technology. This creates major computational challenges to extract and quantify biologically meaningful spatiotemporal patterns embedded within complex and rich data sources, many of which cannot be captured with existing methods. Here, we introduce activity quantification and analysis (AQuA2), a fast, accurate, and versatile data analysis platform built upon advanced machine-learning techniques. It decomposes complex live-imaging-based datasets into elementary signaling events, allowing accurate and unbiased quantification of molecular activities and identification of consensus functional units. We demonstrate applications across a wide range of biosensors, cell types, organs, animal models, microscopy techniques, and imaging approaches. As exemplar findings, we show how AQuA2 identified drug-dependent interactions between neurons and astroglia, as well as distinct sensorimotor signal propagation patterns in the mouse spinal cord
The Estonian Biobank’s journey from biobanking to personalized medicine
Get PDFLarge biobanks have set a new standard for research and innovation in human genomics and implementation of personalized medicine. The Estonian Biobank was founded a quarter of a century ago, and its biological specimens, clinical, health, omics, and lifestyle data have been included in over 800 publications to date. What makes the biobank unique internationally is its translational focus, with active efforts to conduct clinical studies based on genetic findings, and to explore the effects of return of results on participants. In this review, we provide an overview of the Estonian Biobank, highlight its strengths for studying the effects of genetic variation and quantitative phenotypes on health-related traits, development of methods and frameworks for bringing genomics into the clinic, and its role as a driving force for implementing personalized medicine on a national level and beyond
A Cost-Effectiveness Analysis of Abemaciclib in Combination with Adjuvant Endocrine Therapy for HR+, HER2–, Node-Positive, High-Risk Early Breast Cancer
Get PDFIntroductionThe monarchE trial demonstrated that the addition of 2 years of abemaciclib to adjuvant endocrine therapy (ET) significantly reduced the risk of disease recurrence in patients with hormone receptor positive (HR+), and human epidermal growth factor receptor 2–negative (HER2–), node-positive early breast cancer (EBC) at high risk of disease recurrence. Abemaciclib meets a critical unmet need for more effective adjuvant therapy for this patient population. This study evaluates the cost-effectiveness (CE) of abemaciclib plus ET compared to ET alone.MethodsA five-state cohort transition model, which presents a United Kingdom (UK) perspective, is parameterized using data from the monarchE trial and literature. Cost-effectiveness results are presented in terms of cost/quality-adjusted life year (QALY) over a lifetime time horizon. Various assumptions were tested through sensitivity and scenario analyses and uncertainty was assessed through probabilistic analysis.ResultsPatients receiving abemaciclib plus ET were predicted to experience higher QALYs (11.16 compared to 10.42) at an increased cost (£87,541 compared to £48,625), leading to an incremental cost-effectiveness ratio (ICER) of £52,317 per QALY gain compared to ET alone. The increased costs associated with the addition of abemaciclib were partially offset by a reduction in distant disease recurrence and associated costs. The scenario and sensitivity analyses supported robust base case results.ConclusionDespite the ICER exceeding usual willingness-to-pay (WTP) levels in the UK, a consequence of using list prices, the CE model utilizing the latest data cut from the monarchE trial, demonstrated that the upfront cost of abemaciclib reduces the risk of a terminal breast cancer prognosis and its associated cost and quality of life impact. The addition of 2 years of abemaciclib provides an option for the treatment of HR+, HER2–, node-positive, high-risk EBC
When those fleeing the war are blue-eyed and blond:The effects of message content and social identity on blatant dehumanization in four nations
Get PDFVarying behaviours and attitudes towards those who experience the same devastating event are increasingly becoming the focus of criticism. Open expressions of these distinctions based on group membership, such as Kelly Cobiella's statement on NBC about refugees who fled Russia's invasion of Ukraine, "These are not refugees from Syria; these are refugees from neighbouring Ukraine", have raised the question of the social psychological antecedents of these varying attitudes. This research examines how refugees' social identity (ingroup vs. outgroup) and the given reason for their fleeing from a regional war (fear vs. human rights violations) affect the blatant dehumanization of refugees by receiving country communities in four different countries (Ntotal = 1274). In Study 1, we found that Turks in Türkiye showed higher dehumanization toward Syrian refugees (outgroup members compared to Turkmen refugees) and toward those portrayed as fleeing the war due to fear (vs. human rights violations). Study 2, which focused on Germans' attitudes toward Ukrainian and Afghan refugees, showed that dehumanization was negatively associated with the perception of ingroup similarity. In Study 3, with a Spanish sample, we found that ethnic outgroup refugees (Syrians) were more dehumanized than ethnic ingroup refugees (Ukrainians). Similarly, Study 4, which sampled British participants and focused on the same ingroup and outgroup, found that ethnic outgroup refugees were more dehumanized than ethnic ingroup refugees. We discuss the consisted findings in four countries that there is more dehumanization towards members of groups that are less similar to participants from the perspective of the social identity approach
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