47011 research outputs found
Sort by
Precision-Cut Lung Slices: Emerging Tools for Preclinical and Translational Lung Research: An Official American Thoracic Society Workshop Report
Get PDFThe urgent need for effective treatments for acute and chronic lung diseases underscores the significance of developing innovative preclinical human research tools. The 2023 American Thoracic Society Workshop on Precision-Cut Lung Slices (PCLSs) brought together 35 experts to discuss and address the role of human tissue–derived PCLSs as a unique tool for target and drug discovery and validation in pulmonary medicine. With increasing interest and usage, together with advancements in methods and technology, there is a growing need for consensus on PCLS methodology and readouts. The current document recommends standard reporting criteria and emphasizes the requirement for careful collection and integration of clinical metadata. We further discuss current clinically relevant readouts that can be applied to PCLSs and highlight recent developments and future steps for implementing novel technologies for PCLS modeling and analysis. The collection and correlation of clinical metadata and multiomic analysis will further advance the integration of this preclinical platform into patient endotyping and the development of tailored therapies for patients with lung disease
Insulin-like Growth Factor 1 (IGF1) and Its Isoforms: Insights into the Mechanisms of Endometrial Cancer
Get PDFEndometrial cancer (EC) is a common gynaecological malignancy associated with metabolic dysfunctions such as obesity, diabetes and insulin resistance, as well as hormonal imbalances, particularly involving oestrogen and progesterone. These factors disrupt normal cellular metabolism, heightening the risk of developing endometrioid EC (EEC), the most prevalent subtype of EC. The insulin-like growth factor-1 (IGF1) pathway, a key regulator of growth, metabolism, and organ function, is implicated in EC progression. Recent research highlights the distinct roles of IGF1 isoforms, including IGF1-Ea, IGF1-Eb, and IGF1-Ec, in promoting tumour growth, metastasis, and hormone signalling interactions, particularly with oestrogen. This review examines the function and clinical significance of IGF-1 isoforms, emphasising their mechanisms in gynaecological physiology and their contributions to EC pathogenesis. Evidence from other cancers further underscores the relevance of IGF1 isoforms in driving tumour behaviours, offering valuable insights into their potential as biomarkers and therapeutic targets. Understanding these mechanisms provides opportunities for novel approaches to the prevention, diagnosis, and treatment of EC, improving patient outcomes and advancing the broader field of hormone-driven cancers
Decision-Making-Based Multiobjective Direct Speed Predictive Control Without Weighting Factors
Get PDFA novel decision-making (DM) based direct speed predictive control (DSPC) strategy for an induction machine (IM) is presented in this article, eliminating the requirement for weighting factors (WFs). The proposed technique applies the Euclidean norm-based DM approach to DSPC, tackling the challenges observed in conventional WF-based model predictive control strategies. In addition, an extended Kalman filter (EKF) is considered to estimate the rotor flux and load torque, improving the robustness of the system and decreasing complexity by avoiding multiple estimators. The DM-based DSPC technique is validated by simulation and experimental results under different operating conditions. This article also demonstrates the effectiveness of the proposed technique by establishing a comparison with a conventional DSPC technique that uses WFs and the same EKF observer. Our results confirm that the DM-based DSPC scheme improves the control performance and robustness of the system, being a promising alternative for high-performance drive applications
Antimicrobial efficacy of chlorhexidine-treated surfaces against clinical isolates implicated in nosocomial infections
Get PDFIntroduction. Bacterial infections and antimicrobial resistance are significant threats to global public health, both of which spread through contamination of solid surfaces. We have previously developed an antimicrobial surface technology that directly bonds the broad-spectrum biocide chlorhexidine to steel surfaces. These surfaces were shown to kill bacteria within minutes of contact and to be effective against bacteria evolved in the laboratory for resistance to chlorhexidine in solution. Hypothesis/Gap Statement. We hypothesized that resistance to these surfaces could exist outside of the naive and chlorhexidine-resistant laboratory strains tested previously. We also sought to test whether strains that were resistant to chlorhexidine in solution were also resistant to chlorhexidine-based antimicrobial surfaces. Aim. To test the efficacy of these surfaces against a range of bacteria isolated from the hospital environment and to compare this to the resistance of these bacteria to chlorhexidine in solution or when dissolved in solid media. Methodology. Ninety-one isolates of mixed bacterial species were obtained from Queen Elizabeth Hospital Birmingham. The isolates, along with laboratory strains of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus, were tested for sensitivity to chlorhexidine-coated steel surfaces in a 30-min exposure simulated splash assay. Resistance to chlorhexidine in solution was also assayed by solid and broth media MIC assays. Results. We demonstrate that within 30 min of incubation, the surfaces reduced the survival of all 91 isolates. Over 85% of these isolates were killed (exhibiting a 7–8 log reduction compared with control surfaces), whilst 12% experienced a 3–4 log reduction. We also show that resistance to the surfaces did not correlate with resistance to freely diffusible chlorhexidine in liquid or solid media. Conclusion. The results demonstrate the efficacy of chlorhexidine-coated surfaces against a broad range of bacterial isolates from the hospital environment and imply the potential for a mode of exposure to dictate the effectiveness of different antimicrobial resistance mechanisms. Future studies should investigate the genetic mechanisms providing resistance to chlorhexidine-coated surfaces and whether these differ in the capacity to provide resistance to chlorhexidine in different modes of exposure
Hamilton, History and Hip-Hop: Essays on an American Musical ed. by Kevin J. Wetmore (review)
No full textGeometric characteristics of stromal collagen fibres in breast cancer using differential interference contrast microscopy
Get PDFBreast cancer (BC) is characterised by a high level of heterogeneity, which is influenced by the interaction of neoplastic cells with the tumour microenvironment. The diagnostic and prognostic role of the tumour stroma in BC remains to be defined. Differential interference contrast (DIC) microscopy is a label-free imaging technique well suited to visualise weak optical phase objects such as cells and tissue. This study aims to compare stromal collagen fibre characteristics between in situ and invasive breast tumours using DIC microscopy and investigate the prognostic value of collagen parameters in BC. A tissue microarray was generated from 200 cases, comprising ductal carcinoma in situ (DCIS; n=100) and invasive tumours (n=100) with an extra 50 (25 invasive BC and 25 DCIS) cases for validation was utilised. Two sections per case were used: one stained with haematoxylin and eosin (H&E) stain for histological review and one unstained for examination using DIC microscopy. Collagen fibre parameters including orientation angle, fibre alignment, fibre density, fibre width, fibre length and fibre straightness were measured. Collagen fibre density was higher in the stroma of invasive BC (161.68±11.2fibre/µm2) compared to DCIS (p<0.0001). The collagen fibres were thinner (13.78±1.08µm), straighter (0.96±0.006, on a scale of 0–1), more disorganised (95.07°±11.39°) and less aligned (0.20±0.09, on a 0–1 scale) in the invasive BC compared to DCIS (all p<0.0001). A model considering these features was developed that could distinguish between DCIS and invasive tumours with 94% accuracy. There were strong correlations between fibre characteristics and clinicopathological parameters in both groups. A statistically significant association between fibre characteristics and patients’ outcomes (breast cancer specific survival, and recurrence free survival) was observed in the invasive group but not in DCIS. Although invasive BC and DCIS were both associated with stromal reaction, the structural features of collagen fibres were significantly different in the two disease stages. Analysis of the stroma fibre characteristics in the preoperative core biopsy specimen may help to differentiate pure DCIS from those associated with invasion
A new heteroskedasticity-robust test for explosive bubbles
Get PDFWe propose a new class of modified regression-based tests for detecting asset price bubbles designed to be robust to the presence of general forms of both conditional and unconditional heteroskedasticity in the price series. This modification, based on the approach developed in Beare (2018) in the context of conventional unit root testing, is achieved by purging the impact of unconditional heteroskedasticity from the data using a kernel estimate of volatility before the application of the bubble detection methods proposed in Phillips, Shi and Yu (2015) (PSY). The modified statistic is shown to achieve the same limiting null distribution as the corresponding (heteroskedasticity-uncorrected) statistic from PSY would obtain under homoskedasticity, such that the usual critical values provided in PSY may still be used. Versions of the test based on regressions including either no intercept or a (redundant) intercept are considered. Representations for asymptotic local power against a single bubble model are also derived. Monte Carlo simulation results highlight that neither one of these tests dominates the other across different bubble locations and magnitudes, and across different models of time-varying volatility. Accordingly, we also propose a test based on a union of rejections between the with- and without-intercept variants of the modified PSY test. The union procedure is shown to perform almost as well as the better of the constituent tests for a given DGP, and also performs very well compared to existing heteroskedasticity-robust tests across a large range of simulation DGPs
The number of individuals alive in a branching process given only times of deaths
Get PDFThe study of many population growth models is complicated by only partial observation of the underlying stochastic process driving the model. For example, in an epidemic outbreak we might know when individuals show symptoms to a disease and are removed, but not when individuals are infected. Motivated by the above example and the long-established approximation of epidemic processes by branching processes, we explore the number of individuals alive in a time-inhomogeneous branching process with a general phase-type lifetime distribution given only (partial) information on the times of deaths of individuals. Deaths are detected independently with a detection probability that can vary with time and type. We show that the number of individuals alive immediately after the kth detected death can be expressed as the mixture of random variables each of which consists of the sum of k independent zero-modified geometric distributions. Furthermore, in the case of an Erlang lifetime distribution, we derive an easy-to-compute mixture of negative binomial distributions as an approximation of the number of individuals alive immediately after the kth detected death
Taking what you get or Getting what you Need: A Qualitative Study on Experiences with Mental Health and Welfare Services in Long-Term Recovery in First-Episode Psychosis
Get PDFHow people in long-term recovery (clinical and personal) in first-episode psychosis (schizophrenia and bipolar spectrum disorders) experience the mental health and welfare services they interact with is not frequently studied but has significant implications. We therefore aimed to explore which aspects of these services people with FEP evaluate as important for their long-term recovery. Twenty participants in clinical and/or personal recovery from two Norwegian long-term follow-up studies after FEP (TOP 10-year and TIPS 20-year) were sampled for this interview-based qualitative study. The research-team included service user experience. A deductive analysis based on personal accounts of recovery generated five service aspects. Few specific types of interventions were reported to promote recovery although medications, psychotherapy and employment support were mentioned. Participants valued services based in collaboration and that focused on their resources rather than limitations. The importance of long-term follow-up with a consistent aim was highlighted, as was the inclusion of caregivers and peers. Welfare services contributed to recovery by supporting basic needs and safety, but some experienced social exclusion when not participating in the labor market. This study is unique in exploring the role of services, including welfare, in long-term FEP recovery from service user perspectives. Participants evaluated that services played a more indirect role in long-term recovery by supporting their personal resources, although what they needed from services had frequently not been offered. Their expertise by experience contributes valuable knowledge. Better service coordination and consistent implementation of this knowledge are crucial to support recovery in FEP
Towards trustworthy medical AI ecosystems – a proposal for supporting responsible innovation practices in AI-based medical innovation
Get PDFIn this article, we explore questions about the culture of trustworthy artificial intelligence (AI) through the lens of ecosystems. We draw on the European Commission’s Guidelines for Trustworthy AI and its philosophical underpinnings. Based on the latter, the trustworthiness of an AI ecosystem can be conceived of as being grounded by both the so-called rational-choice and motivation-attributing accounts—i.e., trusting is rational because solution providers deliver expected services reliably, while trust also involves resigning control by attributing one’s motivation, and hence, goals, onto another entity. Our research question is: What aspects contribute to a responsible AI ecosystem that can promote justifiable trustworthiness in a healthcare environment? We argue that especially within devising governance and support aspects of a medical AI ecosystem, considering the so-called motivation-attributing account of trust provides fruitful pointers. There can and should be specific ways and governance structures supporting and nurturing trustworthiness beyond mere reliability. After compiling a list of preliminary requirements for this, we describe the emergence of one particular medical AI ecosystem and assess its compliance with and future ways of improving its functioning as a responsible AI ecosystem that promotes trustworthiness
Access Repository Dashboard
Do you manage Open Research Online? Become a CORE Member to access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard! 👇