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Immune watchdogs: Tissue-resident lymphocytes as key players in cancer defense
Get PDFTissue-resident lymphocytes play a crucial role in immune surveillance against cancer, yet their complex interactions and regulatory pathways remain underexplored, highlighting the need for a deeper understanding to enhance cancer immunotherapy strategies. Lymphocytes across the range of innate-adaptive responses can establish long-lasting presence in tissues, exerting a vital function in the local immune response against diverse antigens. These tissue-resident lymphocytes identify antigens and alarmins secreted by microbial infections and non-infectious stresses at barrier locations by closely interacting with epithelial and endothelial cells. Then they initiate effector responses to restore tissue homeostasis. Significantly, this immune defense system has been demonstrated to monitor the processes of epithelial cell transformation, carcinoma advancement, and cancer metastasis at remote locations, so establishing it as an essential element of cancer immunological surveillance. This review aims to elucidate the roles of diverse tissue-resident lymphocyte populations in shaping cancer immune responses and to investigate their synergistic effector mechanisms for advancing cancer immunotherapy.</p
Delirium and Cognitive Screening in National Hip Fracture Registries: Scoping Review Protocol [version 2; peer review: 2 approved]
Get PDFBackgroundDelirium and cognitive impairment are common in hip fracture populations and are associated with significant adverse patient outcomes. National hip fracture registries facilitate improvements in patient outcomes and care quality, such as reduced mortality and the development of specialist multidisciplinary services. However, there is substantial variation in the data collected and reported in relation to delirium and cognition, which impedes international comparison and may reduce quality of care.ObjectiveThis scoping review aims to identify delirium and cognition data items currently collected by hip fracture registries internationally, to identify associated registry guidance that exists for the administration of delirium and cognitive screening tools, and report outcomes of these data items across the most recently published annual reports of identified hip fracture registries.MethodsThis scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews extension for Scoping Reviews (PRISMA-ScR). We will search the following databases: Medline Ovid; Embase; CINAHL EBSCOHost. Relevant websites such as the Fragility Fracture Network (FFN) will also be searched. Study selection and review will be carried out independently by two research team members, with discrepancies resolved by a third member of the research team. Data extraction and synthesis will be conducted by one reviewer and checked for accuracy and omissions by another. The scoping review findings will be informed and validated through engagement with the FFN Hip Fracture Audit Special Interest Group, who will share their knowledge, expertise, and research to achieve consensus over core aspects of the scoping review findings.ConclusionBy identifying existing heterogeneity in delirium and cognitive screening tool use and administration, it is hoped that administration and specific screening tool use will become standardised to optimise comparability across countries and ensure that high quality and reliable data are included across international registry reports
Consensus recommendations for measuring the impact of contraception on the menstrual cycle in contraceptive clinical trials
Get PDFObjective: We sought to develop consensus recommendations for measurement and analysis of data on contraceptive-induced menstrual changes (CIMCs) in contraceptive clinical trials. We built upon previous standardization efforts over the last 50 years and prioritized input from a variety of global experts and current regulatory authority guidance on patient-reported outcomes. Study design: We completed a formal consensus-building process with an interdisciplinary group of 57 experts from 30 organizations and 14 countries in five global regions who work across academia, nonprofit research organizations, the pharmaceutical industry, and funding agencies. Smaller topical working groups drafted and revised recommendations. Results: We developed 44 consensus recommendations, including research approaches to establish the evidence for future improvement in the measurement and analysis of CIMC data and guidance for investigators to implement presently. Priority recommendations call for simplification of terminology to make measurement accessible and patient-centered, accounting for intrinsic and extrinsic factors that may impact outcomes during study design and recruitment, standardized data collection of primary CIMC and acceptability outcomes, and harmonized approaches for analysis of these data, including addressing missing data. Conclusion: By virtually convening a large group of global experts working across disciplines and sectors via a formal methodology, we developed consensus recommendations that will improve the current and future measurement and analysis of CIMC data in contraceptive clinical trials. Using these standardized approaches will permit valid and reliable contraceptive product labeling on CIMC outcomes that matter to users and greater comparability across trials that can inform clinical guidance and contraceptive counseling. Implications: Consensus recommendations on measuring bleeding changes and related outcomes in contraceptive clinical trials can improve reporting of standardized, patient-centered outcomes in future product labeling. These improvements can enable healthcare providers to offer more relevant guidance on contraceptives and users to make more informed decisions about their choice of method.</p
Income, education, and the clustering of risk in cardiovascular disease in the US, 1999-2018:An observational study
Get PDFBACKGROUND: Health metrics in the United States (US) have lagged behind other high-income countries in recent decades, and show persistent gaps between socio-demographic groups. Top 20% income earners and college graduates have also increasingly diverged from the reminder of the population in various dimensions over the past few decades. This study described population patterns in cardiovascular diseases (CVD) by income and education over a twenty-year period.METHODS: This analysis used nationally representative data from 10 cycles (1999-2018) of the National Health and Nutrition Examination Survey (NHANES). Participants were stratified by income and education into four groups: top 20% income earners, college graduates; top 20% income earners, non-college graduates; bottom 80% income earners, college graduates; and bottom 80% income earners, non-college graduates. For income, we created a binary variable (ratio > 5 cutoff) using NHANES income-to-poverty ratio variable to create a standardized measure of income. We calculated the age-standardized prevalence and odds ratios of four conditions: congestive heart failure (CHF), angina, heart attack, and stroke, for each income-education group.FINDINGS: 49,704 participants reported data for both income and education. The age-standardized prevalence of CVD outcomes varied across the four groups. This was most significant when comparing the prevalence among the top 20% income, college graduate group to the bottom 80% income, non-college graduate group: CHF (0.5% vs. 3.0%), angina (1.4% vs. 2.8%), heart attack (1.7% vs. 3.9%), and stroke (1.1% vs. 3.4%). Compared to the top 20% income, college graduate group, the odds of all CVD conditions were significantly higher in the bottom 80% income groups (college graduates: odds ratios (ORs) 1.48-3.67; non-college graduates: ORs 2.36-6.52), as well as for CHF and heart attack in the top 20% income, non-college graduates (OR 3.11 [95% CI: 1.92, 5.06] and OR 1.92 [95% CI: 1.35, 2.73], respectively).INTERPRETATION: Health gaps extend beyond extremes, with risk clustering favoring top 20% income earners with college degrees while most Americans are left behind. Future research should include longitudinal studies that focus on the mechanisms through which both income and education intersect to shape CVD outcomes in the US.FUNDING: The Rockefeller Foundation.</p
Smoothing of the Higher-Order Stokes Phenomenon
Get PDFFor over a century, the Stokes phenomenon had been perceived as a discontinuous change in the asymptotic representation of a function. In 1989, Berry demonstrated it is possible to smooth this discontinuity in broad classes of problems with the prefactor for the exponentially small contribution switching on/off taking a universal error function form. Following pioneering work of Berk, Nevins, and Roberts and the Japanese school of formally exact asymptotics, the concept of the higher-order Stokes phenomenon was introduced, whereby the ability for the exponentially small terms to cause a Stokes phenomenon may change, depending on the values of parameters in the problem, corresponding to the associated Borel-plane singularities transitioning between Riemann sheets. Until now, the higher-order Stokes phenomenon has also been treated as a discontinuous event. In this paper, we show how the higher-order Stokes phenomenon is also smooth and occurs universally with a prefactor that takes the form of a new special function, based on a Gaussian convolution of an error function. We provide a rigorous derivation of the result, with examples spanning the gamma function, a second-order nonlinear ODE, and the telegraph equation, giving rise to a ghost-like smooth contribution present in the vicinity of a Stokes line, but which rapidly tends to zero on either side. We also include a rigorous derivation of the effect of the smoothed higher-order Stokes phenomenon on the individual terms in the asymptotic series, where the additional contributions appear prefactored by an error function
Satellite remote sensing can operationalise the IUCN Global Ecosystem Typology in the biome-diverse North-East of Brazil
Get PDFAccurate biome delineation is difficult where biomes occupy the same climatic space, as is the case for tropical dry forest and savanna. The resulting confusion limits our ability to understand and manage impacts of global change on these biomes. To address this, we developed an unsupervised, repeatable method to delineate biomes and their component functional ecosystems, based on landscape-level vegetation structure measured using remote sensing and an understanding of the ecology of the region. This approach contrasts with previous definitions, based on climate differences amongst savanna, dry forest and rain forest.Using the heterogeneous north-east Brazil, where several biomes interdigitate, as a case study, a hierarchical functional ecosystem classification is proposed that aligns with both the IUCN Global Ecosystem Typology (GET) and previous work. Based on fuzzy clustering of remotely sensed vegetation attributes, seven groups were found, identified as rain forest, cerrado (savanna) and five caatinga vegetation groups. These groups broadly align with the literature, for example, sedimentary and arboreal caatinga. These groups align with three ‘Ecosystem Functional Groups’ (EFGs) described by the IUCN GET and, additionally, suggest there is a new, fourth EFG in the region: non-pyric shrublands. Random Forest models showed soil pH was the most important environmental variable distinguishing these vegetation groups.These results suggest a remotely sensed structure-based approach is an effective method for operationalising the IUCN GET. North-East Brazil – where many EFGs are interdigitated – serves as a challenging case study and, therefore, we hope our approach will have generality for other regions globally
Privacy-preserving Facial Emotion Classification with Visual Micro-Doppler Signatures for Hearing Aid Applications
Get PDFFacial expressions are a crucial aspect of nonverbal communication and often reflect underlying emotional states. Researchers often use facial emotion detection as a tool to gain insights into cognitive processes, emotional states and cognitive load. The conventional camera-based methods to sense human emotions are privacy intrusive, lack adaptability, and are sensitive to variability. These technologies have limited generalization and may not adapt well to variations in ambient lighting, facial landmark localization, facial occlusions and emotion intensity. Radio Frequency (RF) sensing offers promising avenues for improvement with contactless, non-invasive, privacy-preserving and reliable radar-based measurements. The proposed framework utilizes deep-learning techniques to classify facial micro-doppler signatures, generated from an ultra-wideband (UWB) radar. The method relies on continuous multi-level feature learning from radar time-frequency Doppler measurements. The spatiotemporal facial features are extracted from the radar data to train deep learning models. The proposed system achieves a high multiclass classification accuracy of 77% on the continuous streamed data covering basic emotions of anger, disgust, fear, happy, neutral and sadness. The system can transform next-generation multi-modal hearing aids with emotion-aware listening effort and cognitive load detection. This can be particularly useful in translating the emotion-assisted cognitive effort for real-time speech enhancement and personalized auditory experience
Saying "I'm sorry" at the bedside:When and why should apologies following medical mishaps be protected from legal liability?
Get PDFPatients harmed by medical mishaps are often driven to litigation because of a lack of apologies and candour rather than a desire for monetary compensation. Despite attempts at clinical negligence reform, patients continue to receive unsatisfactory responses. Physicians have cited fears of legal liability as a key reason for withholding apologies. Apology legislation has been proposed as a possible solution to encourage apologies by rendering them inadmissible as evidence of liability, thereby reducing the legal risks of apologies. Critics, however, contend that apology legislation may encourage strategic formulaic responses instead of compassionate patient-centred support. This article delivers a comprehensive rejoinder to these concerns, and argues that bold legislative change similar to that of Hong Kong’s enactment of full apology protection aligns with English and Welsh clinical negligence reform goals. Through a robust comparative legal analysis of various jurisdictions in which apology laws have been enacted, this article explores the legal, ethical and practical factors that contribute to the proper functioning of such laws. It then recommends concrete ways to improve the effectiveness of such laws in the context of clinical negligence reform, thereby removing barriers to apologetic discourse and breathing ethical and professional life into the doctor’s apology
Forelimb reduction and digit loss were evolutionarily decoupled in oviraptorosaurian theropod dinosaurs
Get PDFTheropod forelimbs exhibit wide morphological disparity, from the elongated wings of birds to the diminutive arms of T. rex. A wealth of work has sought to understand the evolution of bird flight via arm elongation, but despite widespread occurrences of forelimb reduction and digit loss throughout theropod dinosaurs, the evolutionary drivers behind these patterns are poorly understood. Previous studies demonstrate broad allometric trends that can account for some instances of forelimb reduction, but the repeated loss of digits, and their hypothesized link to forelimb shortening, has received less attention. Here, we evaluate evolutionary associations between digit loss and forelimb reduction in an iconic and data-rich theropod clade, Oviraptorosauria. Unexpectedly, we find that the evolution of digit III and the rest of the forelimb are decoupled. Support for different evolutionary models and a lower phylogenetic signal in digit III than the rest of the forelimb suggests these segments were subject to different evolutionary processes leading to independent morphological change. Oviraptorosaurs exhibit four distinct forelimb morphotypes, but these do not exactly correspond to patterns of dietary niche partitioning. Overall, forelimb evolution in oviraptorosaurs is more complex than anticipated, potentially as a result of an evolutionary radiation they underwent in the Late Cretaceous
Recent amplification of the Siberian High decadal variability significantly influenced by anthropogenic aerosols in CanESM5
Get PDFThe Siberian High (SibH), a prominent feature of the Northern Hemisphere atmospheric circulation, exhibited enhanced interdecadal variability since 1970, characterized by a sharp decline from 1970 to 1990 followed by a steep recovery from 1990 to 2010. The factors underpinning these variations are unclear. Using the CanESM5 large ensemble, including the single forcing simulations, we find that anthropogenic aerosols played an important role in influencing the above SibH trends on top of pronounced internally-generated variations. Changes in the SibH during both periods are embedded in aerosol-induced upper-tropospheric mid-latitude wave trains propagating from upstream regions, with subsequent downward propagation of the signal to the surface via three-dimensional dynamical adjustments. Further insights into the physical mechanisms using regional aerosol perturbation experiments with CESM1 reveal a dominant role of decreased North American aerosol emissions in driving the atmospheric wave train through interaction with the North Atlantic jet during the first period. In the second period, European aerosol emissions, characterized by a large and extensive decrease, are crucial to explain the SibH recovery. A better understanding of the factors driving multidecadal variability of the SibH, and in particular of the interplay between internal variability and external forcing, is critical to reducing uncertainties in future projections of regional extremes, such as cold surges, which can cause large social and economic impacts on densely populated East Asia
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