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Abstract Objective This study aims to document and analyze the challenges and outcomes of performing complex airway surgery in a low‐resource, post‐war setting in Mekelle, Ethiopia. Methods This prospective case series examines clinical data from five patients who underwent airway reconstruction surgeries and one patient who underwent total laryngectomy at Ayder Comprehensive Specialized Hospital in Mekelle. Data included patient demographics, airway stenosis etiology and severity, operative details, postoperative outcomes, complications, and hospital length of stay. Ethical approval was obtained from institutional review boards at Mayo Clinic and Mekelle University. Results The study included six patients aged 9–62 years, with surgeries comprising three cricotracheal resections, two tracheal resections, and one laryngectomy. Three reconstructions were for war‐related injuries. Challenges included power outages during surgeries, limitations in medical supplies and equipment, and inadequate perioperative care. Despite these, three patients requiring tracheostomies were successfully decannulated within a year. However, complications such as restenosis, infections, and the need for reintubation were common. Conclusion Airway surgeries in a low‐resource, post‐war setting face significant hurdles, including perioperative care quality, resource limitations, and infrastructure issues. Successful outcomes require multidisciplinary training tailored to local contexts, investments in hospital infrastructure and reliable electricity, and proper perioperative nutrition. This study highlights the need for comprehensive interventions to improve surgical care in such settings. Level of evidence: IV.

Abstract Advances in instrumentation and tracer materials are still required to enable sensitive, accurate, and localized in situ 3D temperature monitoring by magnetic particle imaging (MPI). We have developed a high-resolution magnetic particle imaging instrument and implemented a low-noise multi-harmonic lock-in detection method to observe and quantify temperature variations in iron oxide nanoparticle tracers using the harmonic ratio method for determining temperature. Using isolated harmonics for MPI and temperature imaging revealed an apparent dependence of imaging resolution on harmonic number. Thus, we present experimental and simulation studies to quantify the imaging resolution dependence on temperature and harmonic number, and directly validate the fundamental origin of MPI imaging resolution on harmonic number based on the concept of a harmonic point-spread-function.

IntroductionTumor immunotherapy is designed to control malignancies through the host immune response but requires circumventing tumor-dysregulated immunomodulation through immunostimulation, relieving immunorepression, or a combination of both approaches. Here we designed and characterized cavrotolimod (formerly AST-008), an immunostimulatory spherical nucleic acid (SNA) compound targeting Toll-like receptor 9 (TLR9). We assessed the safety and pharmacodynamic (PD) properties of cavrotolimod in healthy participants in a first-in-human Phase 1 study under protocol AST-008-101 (NCT03086278; https://clinicaltrials.gov/ct2/show/NCT03086278).MethodsHealthy participants aged 18 to 40 years were enrolled to evaluate four dose levels of cavrotolimod across four cohorts. Each cohort included four participants, and all received a single subcutaneous dose of cavrotolimod. The dose levels were 5, 10, 12.5 and 18.8 µg/kg.Results and discussionCavrotolimod was well tolerated and elicited no serious adverse events or dose limiting toxicities at the doses tested. The results demonstrated that cavrotolimod is a potent innate immune activator, specifically stimulating Th1-type immune responses, and exhibits PD properties that may result in anti-tumor effects in patients with cancer. This study suggests that cavrotolimod is a promising clinical immunotherapy agent.

Objective: This study aims to document and analyze the challenges and outcomes of performing complex airway surgery in a low‐resource, post‐war setting in Mekelle, Ethiopia. Methods: This prospective case series examines clinical data from five patients who underwent airway reconstruction surgeries and one patient who underwent total laryngectomy at Ayder Comprehensive Specialized Hospital in Mekelle. Data included patient demographics, airway stenosis etiology and severity, operative details, postoperative outcomes, complications, and hospital length of stay. Ethical approval was obtained from institutional review boards at Mayo Clinic and Mekelle University. Results: The study included six patients aged 9–62 years, with surgeries comprising three cricotracheal resections, two tracheal resections, and one laryngectomy. Three reconstructions were for war‐related injuries. Challenges included power outages during surgeries, limitations in medical supplies and equipment, and inadequate perioperative care. Despite these, three patients requiring tracheostomies were successfully decannulated within a year. However, complications such as restenosis, infections, and the need for reintubation were common. Conclusion: Airway surgeries in a low‐resource, post‐war setting face significant hurdles, including perioperative care quality, resource limitations, and infrastructure issues. Successful outcomes require multidisciplinary training tailored to local contexts, investments in hospital infrastructure and reliable electricity, and proper perioperative nutrition. This study highlights the need for comprehensive interventions to improve surgical care in such settings. Level of evidence: IV. [ABSTRACT FROM AUTHOR]

Premise: Reticulate evolution, often accompanied by polyploidy, is prevalent in plants, and particularly in the ferns. Resolving the resulting non‐bifurcating histories remains a major challenge for plant phylogenetics. Here, we present a phylogenomic investigation into the complex evolutionary history of the vining ferns, Lygodium (Lygodiaceae, Schizaeales). Methods: Using a targeted enrichment approach with the GoFlag 408 flagellate land plant probe set, we generated large nuclear and plastid sequence datasets for nearly all taxa in the genus and constructed the most comprehensive phylogeny of the family to date using concatenated maximum likelihood and coalescence approaches. We integrated this phylogeny with cytological and spore data to explore karyotype evolution and generate hypotheses about the origins of putative polyploids and hybrids. Results: Our data and analyses support the origins of several putative allopolyploids (e.g., L. cubense, L. heterodoxum) and hybrids (e.g., L. ×fayae) and also highlight the potential prevalence of autopolyploidy in this clade (e.g., L. articulatum, L. flexuosum, and L. longifolium). Conclusions: Our robust phylogenetic framework provides valuable insights into dynamic reticulate evolution in this clade and demonstrates the utility of target‐capture data for resolving these complex relationships. [ABSTRACT FROM AUTHOR]

Summary: Lycopodiaceae are one of three surviving families of lycopsids, a lineage of vascular plants with a fossil history dating to at least the Early Devonian or perhaps the Late Silurian (c. 415 Ma). Many fossils have been linked to crown Lycopodiaceae, but the lack of well‐preserved material has hindered definitive recognition of this group in the paleobotanical record.New, exceptionally well‐preserved permineralized lycopsid fossils from the Early Cretaceous (125.6 ± 1.0 Ma) of Inner Mongolia, China, were examined in detail using acetate peel and micro‐computed tomography techniques. The anatomy of extant Lycopodiaceae was analyzed for comparison using fluorescence microscopy. Phylogenetic relationships of the new fossil to extant Lycopodiaceae were evaluated using parsimony and maximum likelihood analyses.Lycopodicaulis oellgaardii gen. et sp. nov. provides the earliest unequivocal and best‐documented evidence of crown Lycopodiaceae and Lycopodioideae, based on anatomically‐preserved fossil material.Recognition of Lycopodicaulis in Asia during the Early Cretaceous indicates the presence of crown Lycopodiaceae at this time, and striking similarities of stem anatomy with extant species provide a framework for the understanding of the interaction of branching and vascular anatomy in crown‐group lycopsids. [ABSTRACT FROM AUTHOR]

This article explores the construction of the self in romance fiction written today and argues for a reading of romance and selfhood through a negativist lens, suggesting that romance is best understood as participating in the relational selfhood as the means by which happily-ever-afters are achieved. To that end, this article first surveys broad approaches to reader-centric scholarship of the romance from Janice Radway to the present and concludes that such scholarship understands the romance as working to build or construct a sense of social self for its characters and readers. This article argues that this understanding, while foundational to the field and useful in its own moment, face problems as the genre evolves in the present. Sketching some queer theoretical approaches to problems of identity from which this article takes its cues, this article then offers a negativist alternative. To that end, this article explores the negativist, disruptive potential for selfhood through romance fiction either disseminated on or written about the internet, and explores how the negativist lens evades the theoretical problems discussed earlier. Finally, this article concludes by offering a close reading of the 2020 novel The Love Study by Kris Ripper as a case in which a romance novel featuring the internet deconstructs its hero's selfhood to enable his happily-ever-after.

Objectives: The determinants of rheumatoid arthritis (RA) severity and excess cardiovascular disease (CVD) are incompletely understood. Biomechanical factors are known to influence RA severity. Articular stiffness correlates with arterial and skin stiffness. This study explored the hypothesis that constitutional stiffness is a common determinant of RA severity and excess CVD., Methods: Fifty-eight patients with anti-CCP antibody (ACPA) positive RA and 57 controls were enrolled noting age, sex, body mass index, alcohol and tobacco exposure, Shared Epitope status and in RA disease duration, disease activity, ACPA titre and radiographic damage. Severe RA was defined as radiographic progression >1.3 mSharp points/year or requiring biological disease-modifying antirheumatic drugs (bDMARDs). Articular stiffness (Beighton Score and right 5th metacarpophalangeal (MCP) joint stress-strain responses), carotid-femoral pulse wave velocity and skin extensibility (percent increase distance two dots with manual traction dorsum right hand) were assessed., Results: Right 5th MCP stiffness correlated with Beighton Score and with arterial and skin stiffness. High radiographic rate was associated with greater MCP articular (t test p 0.014), arterial (p 0.044) and, in RA <5 years duration, greater skin stiffness (p 0.002) with similar trends in subjects requiring bDMARDs. In RA, arterial stiffness correlated with age (ß p<0.005), articular (ß p<0.001) and skin stiffness (ß p 0.037) and inversely with alcohol consumption (p 0.035)., Conclusions: Articular, arterial and skin stiffness correlated with each other and with RA severity. As skin is not affected by RA, this association suggests that constitutional stiffness might be a common determinant of RA and CVD. Prospective studies of at-risk preclinical and early RA are required to determine if this relationship is causal., Trials Registration Number: ACTRN12617000170325., Competing Interests: Competing interests: SPO has received speaker fees and honoraria (Abbvie, Pfizer, UCB, Janssen, Lilley, Novartis, Roche, Bristol Meyers Squibb) and an educational travel grant (Pfizer)., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective . Image reconstruction is a fundamental step in magnetic particle imaging (MPI). One of the main challenges is the fact that the reconstructions are computationally intensive and time-consuming, so choosing an algorithm presents a compromise between accuracy and execution time, which depends on the application. This work proposes a method that provides both fast and accurate image reconstructions. Approach . Image reconstruction algorithms were implemented to be executed in parallel in graphics processing units (GPUs) using the CUDA framework. The calculation of the model-based MPI calibration matrix was also implemented in GPU to allow both fast and flexible reconstructions. Main results . The parallel algorithms were able to accelerate the reconstructions by up to about6,100times in comparison to the serial Kaczmarz algorithm executed in the CPU, allowing for real-time applications. Reconstructions using the OpenMPIData dataset validated the proposed algorithms and demonstrated that they are able to provide both fast and accurate reconstructions. The calculation of the calibration matrix was accelerated by up to about 37 times. Significance . The parallel algorithms proposed in this work can provide single-frame MPI reconstructions in real time, with frame rates greater than 100 frames per second. The parallel calculation of the calibration matrix can be combined with the parallel reconstruction to deliver images in less time than the serial Kaczmarz reconstruction, potentially eliminating the need of storing the calibration matrix in the main memory, and providing the flexibility of redefining scanning and reconstruction parameters during execution., (Not subject to copyright in the USA. Contribution of National Institute of Standards and Technology.)

The technique of recording local field potentials (LFPs) is an electrophysiological method used to measure the electrical activity of localized neuronal populations. It serves as a crucial tool in cognitive research, particularly in brain regions like the hippocampus and prefrontal cortex. Dual LFP recordings between these areas are of particular interest as they allow the exploration of interregional signal communication. However, methods for performing these recordings are rarely described, and most commercial recording devices are either expensive or lack adaptability to accommodate specific experimental designs. This study presents a comprehensive protocol for performing dual-electrode LFP recordings in the mouse hippocampus and the prefrontal cortex to investigate the effects of antipsychotic drugs and potassium channel modulators on LFP properties in these areas. The technique enables the measurement of LFP properties, including power spectra within each brain region and coherence between the two. Additionally, a low-cost, custom-designed recording device has been developed for these experiments. In summary, this protocol provides a means to record signals with high signal-to-noise ratios in different brain regions, facilitating the investigation of interregional information communication within the brain.

Practitioner understanding of patients' preferences, wishes and needs is essential for personalised health care i.e., focusing on 'what matters' to people based on their individual life situation. To develop such an understanding, dementia practitioners need to use communication practices that help people share their experiences, preferences, and priorities. Following the COVID-19 pandemic, dementia support is likely to continue to be delivered both remotely and in-person. This study analysed multiple sources of qualitative data to examine the views of practitioners, people living with dementia and carers, and researchers on how an understanding of what matters to people living with dementia can be developed remotely via telephone and video call. Access to environmental stimuli, the remote use of visual tools, peoples' tendency to downplay or omit details about their troubles and carers' ability to disclose privately were interpreted, through thematic analysis, to be factors affecting how practitioners sought to develop understanding remotely. Cumulatively, findings show that while remote support created unique challenges to practitioners' ability to develop understanding for personalised care, practitioners developed adaptive strategies to overcome some of these challenges. Further research should examine how, when and for whom these adapted practices for remote personalised care work, informing the development of evidence-based guidance and training on how practitioners can remotely develop the understanding required for personalised care.

Background: Different dementia support roles exist but evidence is lacking on which aspects are best, for whom, and in what circumstances, and on their associated costs and benefits. Phase 1 of the Dementia PersonAlised Care Team programme (D-PACT) developed a post-diagnostic primary care-based intervention for people with dementia and their carers and assessed the feasibility of a trial., Aim: Phase 2 of the programme aims to 1) refine the programme theory on how, when, and for whom the intervention works; and 2) evaluate its value and impact., Design & Setting: A realist longitudinal mixed-methods evaluation will be conducted in urban, rural, and coastal areas across South West and North West England where low-income or ethnic minority populations (for example, South Asian) are represented. Design was informed by patient, public, and professional stakeholder input and phase 1 findings., Method: High-volume qualitative and quantitative data will be collected longitudinally from people with dementia, carers, and practitioners. Analyses will comprise the following: 1) realist longitudinal case studies; 2) conversation analysis of recorded interactions; 3) statistical analyses of outcome and experience questionnaires; 4a) health economic analysis examining costs of delivery; and 4b) realist economic analysis of high-cost events and 'near misses'. All findings will be synthesised using a joint display table, evidence appraisal tool, triangulation, and stakeholder co-analysis., Conclusion: The realist evaluation will describe how, why, and for whom the intervention does or does not lead to change over time. It will also demonstrate how a non-randomised design can be more appropriate for complex interventions with similar questions or populations., (Copyright © 2023, The Authors.)