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In synthetic biology, microbial chassis including yeast Saccharomyces cerevisiae are iteratively engineered with increasing complexity and scale. Wet-lab genetic engineering tools are developed and optimised to facilitate strain construction but are often incompatible with each other due to shared regulatory elements, such as the galactose-inducible (GAL) promoter in S. cerevisiae. Here, we prototyped the cyanamide-induced I−SceI expression, which triggered double-strand DNA breaks (DSBs) for selectable marker removal. We further combined cyanamide-induced I−SceI-mediated DSB and maltose-induced MazF-mediated negative selection for plasmid-free in situ promoter substitution, which simplified the molecular cloning procedure for promoter characterisation. We then characterised three tetracycline-inducible promoters showing differential strength, a non-leaky β-estradiol-inducible promoter, cyanamide-inducible DDI2 promoter, bidirectional MAL32/MAL31 promoters, and five pairs of bidirectional GAL1/GAL10 promoters. Overall, alternative regulatory controls for genome engineering tools can be developed to facilitate genomic engineering for synthetic biology and metabolic engineering applications.

Abstract Background The needs of the population and changes to the configuration of the NHS affect the role of the Trauma & Orthopaedic (T&O) surgeon. This impacts training and the number of consultant posts available at Certificate of Completion of Training. Aim of this study was to review advertised T&O Consultant posts and determine the trends in frequency and sub-specialisation requirements between 2011 and 2020 to assess the perceived reduction in advertised posts and increasing subspecialisation, also looking at the impact to the NHS. Methods 451 volumes of the BMJ were reviewed over Jan 2011 – April 2020. The total number of jobs advertised were recorded. Additionally, for each post, sub-specialisation, region and substantive or locum tenure were recorded. Statistical analysis was conducted with both negative binomial repeated measure and binomial repeated measure with multi-level structures along with GARCH model. Results 1141 jobs were advertised. There has been a decreasing trend in the total number of advertised posts of 13% per annum. Proportion of specialty jobs remain constant yearly. Posts listing Trauma as a subspeciality clearly decreased after 2012. Decreases were present in Northwest region and Scotland in number of posts. There has also been an increasing trend of advertisement of substantive posts, with locum posts forming less than 13% of total advertisements. Conclusions We found no significant increase in job specialisation contrary to previous literature. Overall, total number of Consultant posts in T&O decreased over this time period, especially in the North West region and Scotland. The needs of the population and NHS services need to be considered.

Abstract Objectives The objectives of this study are as follows: to assess the uropathogen antibiogram at two tertiary hospitals in Victoria to look at the difference in susceptibility patterns, to assess whether national guideline recommendations were applicable and to assess the feasibility of local antibiogram analysis to guide development of hospital‐specific guidelines for empirical treatment of urosepsis and for pre‐operative prophylaxis for urological procedures. Patients and methods All positive urine cultures analysed at Barwon Health and Monash Health, two tertiary hospitals in regional and metropolitan Victoria, Australia, respectively, between January 2019 and December 2020 were retrospectively identified. Data obtained included the organism cultured and their susceptibility profiles. Results Three thousand seven hundred and seventy‐seven positive urine cultures from Barwon Health and 6821 from Monash Health were identified. The most common uropathogen was Escherichia coli, which was cultured in 53.4% and 59.1% of urine cultures at Barwon Health and Monash Health, respectively. The main differences observed were in Enterococcus spp., which were cultured in 8.8% and 4.9% of cultures at Barwon Health and Monash Health, respectively, and Candida spp. in 4.2% and 1.5% of cultures at Barwon Health and Monash Health, respectively. The largest differences were found in fluoroquinolone resistance with 12.1% of organisms resistant to ciprofloxacin at Barwon Health compared to 6.4% at Monash Health and 7.1% of organisms resistant to vancomycin compared to 20.1% at Barwon Health and Monash Health, respectively. Conclusion This study demonstrates that there is considerable variability in the uropathogens and their antimicrobial susceptibility profile in two large health services in the same state. We recommend that each centre performs regular analysis of their uropathogen antibiogram to develop local guidelines for treatment and pre‐operative prophylaxis for uropathogens.

ABSTRACT Pleural infections are common and associated with substantial healthcare costs, morbidity, and mortality. Accurate diagnosis remains challenging due to low culture positivity rates, frequent polymicrobial involvement, and non-specific diagnostic biomarkers. Here, we undertook a prospective study examining the feasibility and performance of molecular methods for diagnosing suspected pleural infection. We prospectively characterized 26 consecutive clinically suspected pleural infections, and 10 consecutive patients with suspected non-infective pleural effusions, using shotgun metagenomics, bacterial metataxonomics, quantitative PCR, and conventional culture. Molecular methods exhibited excellent diagnostic performance, with each method identifying 54% (14 out of 26) positive cases among the pleural infection cohort, versus 38% (10 out of 26) with culture. Metagenomics and bacterial metataxonomics unveiled complex polymicrobial infections that were not captured by culture. Dominant microbes included streptococci (Streptococcus intermedius, Streptococcus pyogenes, and Streptococcus mitis), Prevotella spp. (Prevotella oris and Prevotella pleuritidis), staphylococci (S. aureus and S. saprophyticus), and Klebsiella pneumoniae. However, we encountered challenges that complicated pleural infection interpretation, including: (i) uncertainties regarding microbial pathogenicity and the impact of prior antibiotic therapy on diagnostic performance; (ii) lack of a clinical diagnostic gold-standard for molecular performance comparisons; (iii) potential microbial contamination during specimen collection or processing; and (iv) difficulties distinguishing background microbial noise from true microbial signal in low-biomass specimens. This pilot study demonstrates the potential utility and value of molecular methods in diagnosing pleural infection and highlights key concepts and challenges that should be addressed when designing larger prospective trials.IMPORTANCEConfident pleural infection diagnosis is often challenging due to low culture positivity rates, frequent polymicrobial involvement, and non-specific diagnostic biomarkers. Limitations of conventional diagnostic tests result in prolonged and inappropriately broad-spectrum antimicrobial use, encouraging antimicrobial resistance and leading to avoidable adverse effects. Here, we demonstrate the feasibility, utility, and challenges associated with the use of culture-independent molecular techniques for accurate pleural infection diagnosis in a real-world clinical setting. These data will help to inform the design of larger prospective clinical trials and identify potential obstacles to be overcome before next-generation sequencing technologies can be integrated into routine clinical practice.

IntroductionArtificial intelligence (AI) models trained on audio data may have the potential to rapidly perform clinical tasks, enhancing medical decision-making and potentially improving outcomes through early detection. Existing technologies depend on limited datasets collected with expensive recording equipment in high-income countries, which challenges deployment in resource-constrained, high-volume settings where audio data may have a profound impact on health equity.MethodsThis report introduces a novel protocol for audio data collection and a corresponding application that captures health information through guided questions.ResultsTo demonstrate the potential of Voice EHR as a biomarker of health, initial experiments on data quality and multiple case studies are presented in this report. Large language models (LLMs) were used to compare transcribed Voice EHR data with data (from the same patients) collected through conventional techniques like multiple choice questions. Information contained in the Voice EHR samples was consistently rated as equally or more relevant to a health evaluation.DiscussionThe HEAR application facilitates the collection of an audio electronic health record (“Voice EHR”) that may contain complex biomarkers of health from conventional voice/respiratory features, speech patterns, and spoken language with semantic meaning and longitudinal context–potentially compensating for the typical limitations of unimodal clinical datasets.

Bespoke therapies represent a promising tool to address a diverse range of genetic and acquired conditions, offering new hope where conventional treatments have fallen short. With the rapid rise of bespoke therapies, profound ethical and regulatory challenges emerge, making it crucial to establish a comprehensive framework that ensures these treatments reach clinical settings and meet patients’ needs as quickly as possible while protecting all parties involved. Although current guidelines are continually evolving to address the range of ethical tensions raised by these therapies, several gaps remain. A significant unresolved question is determining where personalized interventions fall on the research-care continuum and understanding the institutional, regulatory, and ethical implications when custom therapies are classified as research, care, or a mix of both. To address these questions, we introduce a conceptual model alongside practical guidance for the development, administration, and evaluation of individualized therapies, using CRISPR/Cas9-based interventions for Duchenne Muscular Dystrophy as a case study. We argue that the goals of an intervention should be as individualized as the bespoke product itself, tailored to the specifics of each case. Rather than attempting to pinpoint the exact location of an intervention on the continuum, which may be hard to operationalize and have limited utility, our approach focuses on the practical details of how such interventions are administered and the individual component parts of an intervention. It advocates for transparent discussions among all partners to anticipate and adjust various components/parameters along the process of administering individualized interventions. Our paper highlights the most critical of these parameters in (1) the planning and development of individualized therapies in laboratory settings, (2) their regulatory oversight, and (3) evaluation. By discussing these stages and parameters in detail, we aim to provide guidance on how to navigate the ethical complexities inherent to individualized interventions and offer a preliminary framework for balancing the interplay between research objectives and patient care needs. Acknowledging that the scientific rigor and adequacy of any new model must be evaluated, we also identify the types of evidence that are required to validate that our model effectively meets individual and societal needs.

Summary: Interleukin-10 (IL-10)-producing group 2 innate lymphoid cells (ILC210) regulate inflammatory immune responses, yet their therapeutic potential remains largely unexplored. Here, we demonstrate that cell therapy with human ILC210 inhibits pathogenic T cell responses in humanized mouse models of graft-versus-host disease (GVHD), resulting in reduced GVHD severity and improved overall survival without limiting the graft-versus-leukemia effect. ILC210 conferred superior protection from GVHD than IL-10−/low ILC2s, and blocking IL-10 and IL-4 abrogated ILC210 protective effects, indicating that these cytokines are important for the protective effects of ILC210. Notably, ILC210 provided comparable protection from GVHD to regulatory T cells without impairing T cell engraftment, instead decreasing intestinal T cell infiltration and suppressing CD4+ Th1 and CD8+ Tc1 cells. CITE-seq of expanded ILC2s revealed CD49d and CD86 are markers that allow for enrichment of ILC210 from conventional ILC2s and tracking of ILC210 in patient studies. Altogether, these findings demonstrate the potential of ILC210 in cell therapies for GVHD and other immune-mediated diseases.

Background Awake prone positioning (APP) may be beneficial in patients with respiratory failure who are not receiving mechanical ventilation. Randomized controlled trials of APP have been performed during peak COVID-19 periods in unvaccinated populations, with limited data on compliance or patient acceptability. We aimed to evaluate the efficacy and acceptability of APP in a lower-middle income country in an open-label randomized controlled trial using a dedicated APP implementation team and wearable continuous-monitoring devices. Methods The trial was performed at a tertiary level hospital in Ho Chi Minh City, Vietnam, recruiting adults (≥18 years) hospitalized with moderate or severe COVID-19 and receiving supplemental oxygen therapy via nasal/facemask systems or high-flow nasal cannula (HFNC). Patients were allocated by a computer-generated random number sequence in a 1:1 ratio to standard care or APP, where a dedicated team provided bedside support. Wearable devices continuously recorded pulse oximetry and body position continuously. Our primary outcome was escalation of respiratory support within 28 days of randomization. Results Ninety-three patients were enrolled in this study between March 2022 and March 2023. Eighty (86%) patients had received ≥2 doses of SARS-CoV2 vaccine. The study was terminated early because of a reduction in the number of eligible patients. Data from 46 patients allocated to APP and 47 to standard care were available for analysis. At baseline, 19/47 (40%) patients allocated to the standard care group and 14/46 (30%) patients allocated to the APP group received HFNC. Continuous monitoring data were available for all patients monitored with wearable devices. Significantly greater mean daily APP times were achieved in those allocated to APP, however, most achieved less than the target 8 h/day. We did not detect clear differences in the primary outcome (relative risk,RR, 0.85, 95% CI 0.40-1.78, p=0.67) or secondary outcomes, including intubation rate and 28-day mortality. Patients reported prone positioning was comfortable, although almost all patients preferred supine positioning. No adverse events associated with the intervention were observed. Conclusions APP was not associated with benefit, but there was no sign of harm. Continuous monitoring with wearable devices is both feasible and acceptable for patients. In our population, achieving prolonged APP time was challenging despite a dedicated support team, and patients preferred supine positioning. Clinical Trials Registration NCT05083130.

IntroductionThe 2024 Voice AI Symposium, hosted by the Bridge2AI-Voice Consortium in Tampa, FL, featured two keynote speeches that addressed the intersection of voice AI, healthcare, ethics, and law. Dr. Rupal Patel and Dr. Nicholson Price provided insights into the advancements, applications, and challenges of AI-driven voice tools in healthcare. The symposium aimed to advance cross-disciplinary collaboration and establish frameworks for the ethical use of AI technologies in healthcare.MethodsThe keynote speeches, delivered on May 1st and 2nd, were 30 minutes each, followed by 10-minutes Q&A sessions. The audio was recorded and transcribed using Whisper (v7.13.1). Content summaries were generated with the aid of ChatGPT (v4.0), and the authors reviewed and edited the final transcripts to ensure accuracy and clarity.ResultsDr. Rupal Patel’s keynote, “Reflections and New Frontiers in Voice AI”, explored the potential of voice AI for early detection of health conditions, monitoring disease progression, and promoting non-invasive global health management. She highlighted innovative uses beyond traditional applications, such as examining menopause-related symptoms. Dr. Nicholson Price’s keynote, “Governance for Clinical Voice AI”, addressed the regulatory and ethical challenges posed by AI in healthcare. He stressed the need for context-aware systems and dynamic legal frameworks to address liability and accountability.ConclusionsThe 2024 Voice AI Symposium highlighted the transformative potential of voice AI for early detection, health monitoring, and reducing healthcare disparities. It also underscored the importance of dynamic governance to address the ethical and regulatory challenges of deploying AI in clinical settings.

AbstractAgricultural extension services are supposed to provide farmers with the know-how and abilities they need to boost productivity, and create premium cocoa beans. In this study, a sample of 384 farmers participated and data collected was analysed using descriptive statistics. The findings reveal that demonstration farms (72.92%) are very effective for disseminating innovations to cocoa farmers. Farmers believe that agricultural extension services play a favourable role in improving the quality of cocoa (Mean = 3.93). Household size, years of farming, off-farm activities, access to credit and access to technical assistance statistically influence cocoa farmers’ choice of extension delivery methods (p

Adipose tissue plays a crucial role in metabolic syndrome, autoimmune diseases, and many cancers. Because of adipose’s role in so many aspects of human health, there is a critical need for in vitro models that replicate adipose architecture and function. Traditional monolayer models, despite their convenience, are limited, showing heterogeneity and functional differences compared to 3D models. While monolayer cultures struggle with detachment and inefficient differentiation, healthy adipocytes in 3D culture accumulate large lipid droplets, secrete adiponectin, and produce low levels of inflammatory cytokines. The shift from monolayer models to more complex 3D models aims to better replicate the physiology of healthy adipose tissue in culture. This study introduces a simple and accessible protocol for generating adipose organoids using a scaffold-free spheroid model. The method, utilizing either 96-well spheroid plates or agarose micromolds, demonstrates increased throughput, uniformity, and ease of handling compared to previous techniques. This protocol allows for diverse applications, including drug testing, toxin screening, tissue engineering, and co-culturing. The choice between the two methods depends on the experimental goals, with the 96-well plate providing individualized control and the micromold offering scale advantages. The outlined protocol covers isolation, expansion, and characterization of stromal vascular fraction cells, followed by detailed steps for spheroid formation and optional downstream analyses.

Quality assurance remains a significant challenge for laser powder bed fusion and metal additive manufacturing. Despite system manufacturers offering process monitoring as a possible solution, datasets are large and cumbersome with practical use limited without direct comparative data. Model datasets would enable individual build validation, highlight deviations, and facilitate intelligent build planning whereby challenging features or build strategies could be pre-emptively assessed.Herein a pragmatic approach has been developed to model process monitoring data from a commercial system using a relatively simple algorithm. Using a heuristic method, the algorithm response has been fitted to an experimental dataset to derive governing constants and their relationship to key process parameters. Predictability of constants and model fit has been shown to improve with increasing line energy up to a maximum R2=0.8. Algorithm variable trends, supported by corresponding sensitivity analysis, identified two different behavioural regimes. Under low linear energy density (

Abstract Background In Australia, university clinical programs rely heavily on external healthcare professionals to provide a range of authentic clinical training and professional development opportunities for students. There is, however, a limited understanding of the factors that motivate these professionals to be educators and whether this varies across different healthcare disciplines within Australia. As the demand for clinical placements continues to increase, it is critical for the ongoing success of these programs that universities identify both the barriers associated with teaching and the benefits that enhance job satisfaction. Methods A two-part questionnaire was emailed to 849 external healthcare educators teaching predominantly in Medicine, Medical Imaging, and Optometry programs at Deakin University. Part-one surveyed the socio-demographics, perceived benefits, and barriers to teaching, plus the utilisation of entitlements offered by the university. Part-two was modelled on Dybowski and Harendza’s validated Physician Teaching Motivation Questionnaire (PTMQ) and adapted to an Australian audience. Results Overall, 776 out of the 849 questionnaires were considered in the final participant pool. The response rate for part-one was 19.7% (n = 153/776) and 18.3% (n = 142/776) for part-two. Across all professions, altruism was the primary source of motivation for teaching in Deakin University’s healthcare programs. Medical Imaging educators placed a higher value on career-related teaching aspects compared to those in Medicine and Optometry (p

Abstract Background Mosquitoes are carriers of tropical diseases, thus demanding a comprehensive understanding of their behaviour to devise effective disease control strategies. In this article we show that machine learning can provide a performance assessment of 2D and 3D machine vision techniques and thereby guide entomologists towards appropriate experimental approaches for behaviour assessment. Behaviours are best characterised via tracking—giving a full time series of information. However, tracking systems vary in complexity. Single-camera imaging yields two-component position data which generally are a function of all three orthogonal components due to perspective; however, a telecentric imaging setup gives constant magnification with respect to depth and thereby measures two orthogonal position components. Multi-camera or holographic techniques quantify all three components. Methods In this study a 3D mosquito mating swarm dataset was used to generate equivalent 2D data via telecentric imaging and a single camera at various imaging distances. The performance of the tracking systems was assessed through an established machine learning classifier that differentiates male and non-male mosquito tracks. SHAPs analysis has been used to explore the trajectory feature values for each model. Results The results reveal that both telecentric and single-camera models, when placed at large distances from the flying mosquitoes, can produce equivalent accuracy from a classifier as well as preserve characteristic features without resorting to more complex 3D tracking techniques. Conclusions Caution should be exercised when employing a single camera at short distances as classifier balanced accuracy is reduced compared to that from 3D or telecentric imaging; the trajectory features also deviate compared to those from the other datasets. It is postulated that measurement of two orthogonal motion components is necessary to optimise the accuracy of machine learning classifiers based on trajectory data. The study increases the evidence base for using machine learning to determine behaviours from insect trajectory data. Graphical Abstract

The web-based office supplies requisition application is a significant step in modernizing office equipment procurement in various organizations, including universities. However, this website encounters problems due to immature planning and less effective implementation. The current website faces some problems with requesting office supplies on campus, where the current process lacks efficiency and transparency in the status of user requests. It often results in discrepancies between the registered stock of office supplies and the actual stock in the warehouse. Our research aims to improve this website using the Rapid Application Development methodology. We also include user feedback when designing this website. The result is a new web-based application that provides a much better user experience when requesting office supplies. This update is expected to increase the efficiency of office equipment request services, provide users with more transparent request status information, and ensure accurate stock availability.

IntroductionThe 2024 Voice AI Symposium, presented by the Bridge2AI-Voice Consortium, featured deep-dive educational workshops conducted by experts from diverse fields to explore the latest advancements in voice biomarkers and artificial intelligence (AI) applications in healthcare. Through five workshops, attendees learned about topics including international standardization of vocal biomarker data, real-world deployment of AI solutions, assistive technologies for voice disorders, best practices for voice data collection, and deep learning applications in voice analysis. These workshops aimed to foster collaboration between academia, industry, and healthcare to advance the development and implementation of voice-based AI tools.MethodsEach workshop featured a combination of lectures, case studies, and interactive discussions. Transcripts of audio recordings were generated using Whisper (Version 7.13.1) and summarized by ChatGPT (Version 4.0), then reviewed by the authors. The workshops covered various methodologies, from signal processing and machine learning operations (MLOps) to ethical concerns surrounding AI-powered voice data collection. Practical demonstrations of AI-driven tools for voice disorder management and technical discussions on implementing voice AI models in clinical and non-clinical settings provided attendees with hands-on experience.ResultsKey outcomes included the discussion of international standards to unify stakeholders in vocal biomarker research, practical challenges in deploying AI solutions outside the laboratory, review of Bridge2AI-Voice data collection processes, and the potential of AI to empower individuals with voice disorders. Additionally, presenters shared innovations in ethical AI practices, scalable machine learning frameworks, and advanced data collection techniques using diverse voice datasets. The symposium highlighted the successful integration of AI in detecting and analyzing voice signals for various health applications, with significant advancements in standardization, privacy, and clinical validation processes.DiscussionThe symposium underscored the importance of interdisciplinary collaboration to address the technical, ethical, and clinical challenges in the field of voice biomarkers. While AI models have shown promise in analyzing voice data, challenges such as data variability, security, and scalability remain. Future efforts must focus on refining data collection standards, advancing ethical AI practices, and ensuring diverse dataset inclusion to improve model robustness. By fostering collaboration among researchers, clinicians, and technologists, the symposium laid a foundation for future innovations in AI-driven voice analysis for healthcare diagnostics and treatment.

Background Awake prone positioning (APP) may be beneficial in patients with respiratory failure who are not receiving mechanical ventilation. Randomized controlled trials of APP have been performed during peak COVID-19 periods in unvaccinated populations, with limited data on compliance or patient acceptability. We aimed to evaluate the efficacy and acceptability of APP in a lower-middle income country in an open-label randomized controlled trial using a dedicated APP implementation team and wearable continuous-monitoring devices. Methods The trial was performed at a tertiary level hospital in Ho Chi Minh City, Vietnam, recruiting adults (≥18 years) hospitalized with moderate or severe COVID-19 and receiving supplemental oxygen therapy via nasal/facemask systems or high-flow nasal cannula (HFNC). Patients were allocated by a computer-generated random number sequence in a 1:1 ratio to standard care or APP, where a dedicated team provided bedside support. Wearable devices continuously recorded pulse oximetry and body position continuously. Our primary outcome was escalation of respiratory support within 28 days of randomization. Results Ninety-three patients were enrolled in this study between March 2022 and March 2023. Eighty (86%) patients had received ≥2 doses of SARS-CoV2 vaccine. The study was terminated early because of a reduction in the number of eligible patients. Data from 46 patients allocated to APP and 47 to standard care were available for analysis. At baseline, 19/47 (40%) patients allocated to the standard care group and 14/46 (30%) patients allocated to the APP group received HFNC. Continuous monitoring data were available for all patients monitored with wearable devices. Significantly greater mean daily APP times were achieved in those allocated to APP, however, most achieved less than the target 8 h/day. We did not detect clear differences in the primary outcome (relative risk,RR, 0.85, 95% CI 0.40-1.78, p=0.67) or secondary outcomes, including intubation rate and 28-day mortality. Patients reported prone positioning was comfortable, although almost all patients preferred supine positioning. No adverse events associated with the intervention were observed. Conclusions APP was not associated with benefit, but there was no sign of harm. Continuous monitoring with wearable devices is both feasible and acceptable for patients. In our population, achieving prolonged APP time was challenging despite a dedicated support team, and patients preferred supine positioning. Clinical Trials Registration NCT05083130.

This study describes Chrysobrycon calamar, a new stevardiine fish from the upper Río Vaupés basin in Colombia. The new species differs from its congeners by the following combined characters: adult males have a dark vertical blotch on the abdominal flanks that is confined to a small area immediately dorsal to the urogenital region and anterior to the third anal-fin ray; adult males with a well-developed vertically humeral blotch, numerous tiny bony hooks on nearly all the upper lobe caudal-fin rays (except C. guahibo, C. hesperus, and C. mojicai), and bony hooks on nearly all branched anal-fin rays (except C. hesperus); the number of vertebrae (43 vs. 38–42); an elongated maxillary anterior process, representing 40% or more of the total length of the bone (vs. with a shorter maxillary anterior process, representing less than 40% of that length); and the posterior portion of the maxilla not reaching the vertical through the anterior border of the eye when the mouth is closed (except from C. yoliae). Additionally, C. calamar differs from C. mojicai by the number of maxillary teeth (2–4 vs. 9–17) and shape of the distal tips of most maxillary teeth (straight along their lengths vs. lateroventrally curved). Remarks on the interspecific color variation associated with sexual dimorphism and other characteristics of the genus are provided. A key to the species of Chrysobrycon is presented. The discovery of C. calamar is a key advance in the understanding of fish biodiversity associated with endemism-rich regions that could be explored after the guerrilla demobilized in Colombia.

Abstract Background Subglottic stenosis is the narrowing of the airway below the vocal folds. It can present as a congenital or acquired condition. The primary clinical presentation is often noted as noisy breathing, also known as stridor. Diagnosis in the infant pediatric population poses challenges due to age-related factors and symptom variability. This case report highlights a pediatric patient whose predominant symptom was congestion during oral feeds. Case presentation A 3-month-old pre-term male, intubated following an episode of ventricular fibrillation with underlying viral infection, presented with prolonged, persistent congestion with oral feeds. Given persistent congestion, the differential diagnosis included aspiration, recovery from a viral illness, reflux, and an anatomical stricture. A videofluoroscopic swallow study was completed and ruled out oropharyngeal dysphagia from the differential. Despite this exclusion and the patient’s eventual recovery from his viral illness, congestion with oral feeds continued to worsen. A fiberoptic endoscopic evaluation was completed and revealed Grade 2 subglottic stenosis. The patient required immediate intervention via balloon dilation in the operating room. Conclusions Acquired subglottic stenosis is often a consequence of intubation. Symptoms are variable and can be difficult to diagnose in pediatric patients. Timely intervention is essential to prevent life-threatening conditions.

Abstract Introduction A standardised testing protocol for evaluation of a wide range of dental cone beam computed tomography (CBCT) performance and image quality (IQ) parameters is still limited and commercially available testing tool is unaffordable by some centres. This study aims to assess the performance of a low‐cost fabricated phantom for image quality assessment (IQA) of digital CBCT unit. Methods A customised polymethyl methacrylate (PMMA) cylindrical phantom was developed for performance evaluation of Planmeca ProMax 3D Mid digital dental CBCT unit. The fabricated phantom consists of four different layers for testing specific IQ parameters such as CT number accuracy and uniformity, noise and CT number linearity. The phantom was scanned using common scanning protocols in clinical routine (90.0 kV, 8.0 mA and 13.6 s). In region‐of‐interest (ROI) analysis, the mean CT numbers (in Hounsfield unit, HU) and noise for water and air were determined and compared with the reference values (0 HU for water and −1000 HU for air). For linearity test, the correlation between the measured HU of different inserts with their density was studied. Results The average CT number were −994.1 HU and −2.4 HU, for air and water, respectively and the differences were within the recommended acceptable limit. The linearity test showed a strong positive correlation (R2 = 0.9693) between the measured HU and their densities. Conclusion The fabricated IQ phantom serves as a simple and affordable testing tool for digital dental CBCT imaging.

This article examines the eschatology in Eph 4:17–32 and argues that the section represents an understanding of “inaugurated eschatology” that is consistent with the undisputed letters of Paul. In the letter, believers are called to a metaphorical resurrection from the corruption and ignorance of the old self (2:1–3; 4:17–22) to a renewed life in the present modeled after the image of God (4:24) and guided by the truth in Jesus (4:21). With minds renewed as such, readers of Ephesians may “discern what is pleasing to the Lord” (5:10) as they “understand what the will of the Lord is” (5:17) in everyday decisions of character and conduct (e.g., 4:25–6:9). The “already” resurrection and renewed mind yet await the “not yet” resurrection of the final day. Indeed, the renewal of the mind anticipates further and final renewal of the whole person (i.e., mind and body) on the future “day of redemption” (4:30)—the day in which the present rising will be made complete as the physical body rises to die no more (cf. 1 Thess 5:2; 4:2; 2 Thess 1:10; 2:2–3; 2 Tim 1:12, 18; 4:8).

ABSTRACT Background This study examines the perceptions of the Australian public canvassed in 2021 during the COVID‐19 pandemic about their health system compared to four previous surveys (2008, 2010, 2012 and 2018). Methods In 2021, a nationwide online survey was conducted with a representative sample of Australians (N = 5100) recruited via market research panels. The results were compared to previous nationwide Australian survey samples from 2018 (N = 1024), 2012 (N = 1200), 2010 (N = 1201) and 2008 (N = 1146). The survey included questions consistent with previous polls regarding self‐reported health status and overall opinions of, and confidence in, the Australian health system. Results There was an increase in the proportion of respondents reporting positive perceptions at each survey between 2008 and 2021, with a significantly higher proportion of respondents expressing a more positive view of the Australian healthcare system in 2021 compared to previous years (χ2(8, N = 9645) = 487.63, p

Objective To identify the availability of results for trials registered on the European Union Clinical Trials Register (EUCTR) compared with other dissemination routes to understand its value as a results repository.Design Cross sectional audit study.Setting EUCTR protocols and results sections, data extracted 1-3 December 2020.Population Random sample of 500 trials registered on EUCTR with a completion date of more than two years from the beginning of searches (ie, 1 December 2018).Main outcome measures Proportion of trials with results across the examined dissemination routes (EUCTR, ClinicalTrials.gov, ISRCTN registry, and journal publications), and for each dissemination route individually. Prespecified secondary outcomes were number and proportion of unique results, and the timing of results, for each dissemination route.Results In the sample of 500 trials, availability of results on EUCTR (53.2%, 95% confidence interval 48.8% to 57.6%) was similar to the peer reviewed literature (58.6%, 54.3% to 62.9%) and exceeded the proportion of results available on other registries with matched records. Among the 383 trials with any results, 55 (14.4%, 10.9% to 17.9%) were only available on EUCTR. Also, after the launch of the EUCTR results database, median time to results was fastest on EUCTR (1142 days, 95% confidence interval 812 to 1492), comparable with journal publications (1226 days, 1074 to 1551), and exceeding ClinicalTrials.gov (3321 days, 1653 to undefined). For 117 trials (23.4%, 19.7% to 27.1%), however, results were published elsewhere but not submitted to the EUCTR registry, and no results were located in any dissemination route for 117 trials (23.4%, 19.7% to 27.1).Conclusions EUCTR should be considered in results searches for systematic reviews and can help researchers and the public to access the results of clinical trials, unavailable elsewhere, in a timely way. Reporting requirements, such as the EU's, can help in avoiding research waste by ensuring results are reported. The registry's true value, however, is unrealised because of inadequate compliance with EU guidelines, and problems with data quality that complicate the routine use of the registry. As the EU transitions to a new registry, continuing to emphasise the importance of EUCTR and the provision of timely and complete data is critical. For the future, EUCTR will still hold important information from the past two decades of clinical research in Europe. With increased efforts from sponsors and regulators, the registry can continue to grow as a source of results of clinical trials, many of which might be unavailable from other dissemination routes.

Prior to the COVID-19 pandemic (hereafter, ‘the pandemic’), there was already widespread concern about the adequacy of health care resources across Canada. The COVID-19 pandemic exacerbated these concerns exponentially, widening already significant cracks in provincial health care systems. Currently the system is struggling with the exacerbation of wait times for surgeries previously delayed by mandated closures during the pandemic. In Ontario, the backlog of surgeries, and associated backlogs in radiology and other services critical to paediatric care, led to the creation of a consortium of paediatric hospitals committed to advocacy for more funding for paediatrics. Thus far, the provincial and federal governments have agreed to a one-time cash infusion, but the consortium is calling for a permanent increase in funding for paediatrics. A challenge is that the adult sector has also suffered from delays and backlogs. Furthermore, as already noted, older adults have borne the brunt of morbidity and mortality associated with COVID-19. The challenge for the paediatric sector is whether and how to defend the prioritization of children and youth. In this paper, we review four approaches to just allocation – utilitarian ageism, fair innings, the prudential lifespan approach, and prioritarian ageism – and examine their strengths and weaknesses. We conclude by endorsing prioritarian ageism (prioritarianism). Prioritarianism retains the strengths of utilitarian ageism and fair innings while avoiding their weaknesses. Furthermore, because prioritarianism does not treat age as an independent moral criterion, allocation schemes based on this foundation are less susceptible to legal challenge and may be more palatable to the general public.

Aims Doctors completing on-call shifts at sites across a mental health trust identified a need to improve aspects of on-call work. This quality improvement project (QIP) aimed to improve response to trainee concerns arising from on-call work and support to junior doctors on-call. Methods A previous QIP cycle identified trainee concerns regarding on-call processes. In our first QIP cycle, surveys were sent to all consultants and SpRs working on non-residential on-call rotas, and Foundation, GP and Core Psychiatry trainees (on residential on-call rotas) in the Trust, regarding perceptions of on-call processes, senior support and on-call issues. A monthly, online forum was introduced in August 2023 to improve on-call feedback and communication. Trainees, consultants and SpRs from 2 localities were invited, along with representatives from the medical staffing team, medical education team and medical management. After 4 forums, participants who had attended an on-call forum were sent a further feedback survey collecting quantitative and qualitative data. Subsequently, forum frequency and scheduling were amended, advertisement improved, and the forum was expanded to include on-call doctors across the whole Trust. Results First cycle data revealed consultant support for a regular meeting with trainees and senior colleagues to bring issues from on-calls for discussion (56% felt that an on-call forum would be helpful, 33% felt it might be helpful). Mean forum attendance was 14, with attendance from all grades. Feedback data from trainees (5 responses) was that most found the forum useful (80%); 80% felt listened to; all felt able to raise concerns, and all wanted the forums to continue. Qualitative feedback included: ‘we started a new QI project from the forum and many on-call guidelines became more defined.’ Consultant feedback (4 responses) was that most found the forums useful (75%); 100% gained a better understanding of trainee concerns; 100% thought forums should continue, although 50% thought the frequency should be reduced. Most consultants and trainees did not feel it would be useful to discuss clinical cases in the forums. Consultant qualitative feedback reported that the forum was helpful to understand trainee concerns, but there should be wider attendance. Conclusion Establishing an on-call forum was a valuable intervention for both consultants and trainees working on an on-call rota and has led to a further quality improvement project. Respondents felt that clinical supervision offered sufficient space to discuss clinical cases. Increasing trainee and consultant engagement with the forum is the next phase of this project.

Diapoma pampeana was recently described to occur in the upper Negro basin in Uruguay and Brazil. An isolated population tentatively identified as D. pampeana from the Pando stream, a perturbed coastal drainage in Uruguay, is studied and compared under the light of morphological and molecular data to test if there is evidence to consider it as a separate species. New geographical records for the species are presented and included in the comparisons. The specimens analyzed were pooled into four groups: Pando, Santa Lucía, Middle Negro and Upper Negro. We analyzed 32 morphological characters using statistical procedures and recovered a COI-based phylogeny of different populations of D. pampeana to test if they may represent different species. Size-corrected PCA revealed that the Pando and Upper Negro groups are greatly diverging in both morphometric and meristic data along PC1 (mainly by the snout to dorsal-fin origin, dorsal to adipose-fin origins, number of longitudinal scales and predorsal scales). This deviating pattern was also obtained in a cluster analysis. The Santa Lucía and Middle Negro groups were found to be intermediate morphotypes. In contrast, molecular analyses revealed that the Pando and Upper Negro specimens resemble genetically and, thus, are placed together in the Neighbor-joining and Bayesian topologies, as part of a monophyletic Diapoma. We proposed that the Pando population, despite its deviating morphology observed, can be classified as D. pampeana. Therefore, this population constitutes a remarkable example of an isolated population that is morphologically divergent but genetically similar to the geographically most distant conspecific population.

Rates of food insecurity in Ghana have been rising before the onset of COVID-19 and have remained unchanged since then despite the economy's expansion in the 1990s to date. Dryseason commercial vegetable production is one of the people's key activities for survival in the Upper East Region. This study sought to examine the extent and determinants of food insecurity through an econometric estimation with household data from 322 dry-season vegetable farmers in the region. The study revealed that close to half (45.7%) of the sampled farm households are food insecure (FI) while food secure (FS) is 54.3%. FI households have a head count index of 33.33%, a food insecurity gap of 31.20 and a severity of food insecurity of 12.97%. Vegetable income, non-farm employment and own food production have positive marginal effects on households’ calorie availability in the region. The Ministry of Food and Agriculture (MOFA) should provide logistics and capacity-building workshops for the Agricultural Extension Officers (AEOs) to improve their knowledge and skills and ensure their accessibility to dry season vegetable farmers to improve the productivity, increase output and income of farmers to enhance food security in the region.

The electricity grid has been transforming since its inception. The increase in carbon emissions and scarcity of fossil fuels has led to using renewable energy sources for power generation. In recent times, microgrids have been gaining popularity, as they can connect to the grid or disconnect from the grid to supply power to the local loads during grid failure and calamities. The presence or absence of the utility grid is crucial to the overall operation of the microgrid. This paper focuses on early islanding detection by considering the instantaneous values of phase voltage and line currents. In the proposed method, the relative position of voltage and current signals are monitored, and a coincidence index keeps track of any change in their relative positions. During the grid-connected operation, the coincidence index remains low. However, when the grid is disconnected, the coincidence index rises. Islanding is detected when the coincidence index crosses a fixed threshold. MATLAB/Simulink-based simulation studies were carried out on the IEEE 13 bus system to check the effectiveness of the proposed Instantaneous Islanding Detection technique during normal operation, faults, switching of loads, and switching of Distributed Generators. It was found that the proposed scheme could detect islanding in less than one-fourth of the cycle and has a low non-detection zone. Also, during the evaluation, the proposed instantaneous islanding detection technique identified islanding much earlier than existing methods.

Abstract Global climate models account for sea ice thickness by summing thermodynamic processes that affect thickness through phase change and dynamic processes that affect thicknesses through relative motion. Comparison of these individual processes with observations is essential for model interpretation and development. We utilized observational estimates of basal thermodynamic growth, overall thickness changes and their residual difference (including dynamics) to evaluate these processes in the National Center for Atmospheric Research (NCAR) Community Earth System Model 2 (CESM2) submission to the World Climate Research Program (WCRP) Ocean Model Comparison Project Phase 2 (OMIP2) and Pan‐Arctic Ice–Ocean Modeling and Assimilation System (PIOMAS). Both models exhibit a similar pattern of higher basal thermodynamic growth and lower residual effects and wintertime thickness in the central Arctic than observational estimates for 2010–2018, and vice versa in the peripheral seas. Correcting residual effect biases would ameliorate the biases in both mean thickness and basal thermodynamic growth.

Introduction Traumatic brain injury (TBI) is a heterogeneous condition in terms of pathophysiology and clinical course. Outcomes from moderate to severe TBI (msTBI) remain poor despite concerted research efforts. The heterogeneity of clinical management represents a barrier to progress in this area. PRECISION-TBI is a prospective, observational, cohort study that will establish a clinical research network across major neurotrauma centres in Australia. This network will enable the ongoing collection of injury and clinical management data from patients with msTBI, to quantify variations in processes of care between sites. It will also pilot high-frequency data collection and analysis techniques, novel clinical interventions, and comparative effectiveness methodology.Methods and analysis PRECISION-TBI will initially enrol 300 patients with msTBI with Glasgow Coma Scale (GCS)

Abstract The Laser Interferometer Space Antenna (LISA) has two scientific objectives of cosmological focus: to probe the expansion rate of the universe, and to understand stochastic gravitational-wave backgrounds and their implications for early universe and particle physics, from the MeV to the Planck scale. However, the range of potential cosmological applications of gravitational-wave observations extends well beyond these two objectives. This publication presents a summary of the state of the art in LISA cosmology, theory and methods, and identifies new opportunities to use gravitational-wave observations by LISA to probe the universe.

Abstract Background Preventative healthcare is crucial for improving individual patient outcomes and is integral to sustainable health systems. The effectiveness of prevention programs is enhanced by activated populations who are capable of managing their own health and are proactive to keep themselves well. However, little is known about the level of activation among people drawn from general populations. We used the Patient Activation Measure (PAM) to address this knowledge gap. Methods A representative, population‐based survey of Australian adults was conducted in October 2021 during the Delta strain outbreak of the COVID‐19 pandemic. Comprehensive demographic information was collected, and the participants completed the Kessler‐6 psychological distress scale (K6) and PAM. Multinomial and binomial logistic regression analyses were performed to determine the effect of demographic factors on PAM scores, which are categorised into four levels: 1—participants disengaged with their health; 2—becoming aware of how to manage their health; 3—acting on their health; and 4—engaging with preventative healthcare and advocating for themselves. Results Of 5100 participants, 7.8% scored at PAM level 1; 13.7% level 2, 45.3% level 3, and 33.2% level 4. The mean score was 66.1, corresponding to PAM level 3. More than half of the participants (59.2%) reported having one or more chronic conditions. Respondents aged 18 to 24 years old were twice as likely to score PAM level 1 compared with people aged 25–44 (p

IntroductionThe food-energy-water (FEW) nexus highlights the interdependencies between the systems that people rely on for these essential resources. For example, globally, over two thirds of freshwater withdrawals are used to produce food, and another 10% is used during energy generation. In addition, the food system uses one eighth of global net energy. Seafood is a nutritionally important food, and it is critical to use freshwater and energy resources efficiently throughout seafood supply chains to safeguard future supplies and to reduce environmental impacts. Diverse seafood production methods result in highly variable resource use across supply chains, which may contribute to siloed efforts within supply chains to improve efficiency, instead of larger efforts that involve multiple seafood supply chains. Additionally, efforts to develop and implement efficiency strategies must be informed by fishers, aquaculturists, processors, and other seafood supply chain actors to avoid investing time and resources into strategies that will have low uptake. A significant proportion of seafood is imported into the U.S., so engaging with industry and stakeholders in the U.S. and abroad is critical for understanding and improving the FEW nexus associated with seafood consumed by Americans.MethodsTo understand how resources are being used, current and potential strategies to improve resource use, and relevant motivations and barriers, we conducted 47 semi-structured interviews from 2019 to 2021 with seafood supply chain actors, including producers and processors. Seafood supply chains included were farmed catfish produced in the U.S., farmed pangasius and shrimp produced in Vietnam, farmed Atlantic salmon produced in Norway, and wild-caught sockeye and pink salmon caught in the U.S.ResultsWe provide detailed descriptions of stages within each supply chain regarding resource use and efficiency strategies, and report higher-level findings that apply across supply chains. There was variation across settings regarding how resources are used and opportunities and barriers for improving efficiencies, but we also found commonalities in settings, indicating that resource-saving strategies or innovations could lead to increased efficiency across multiple supply chains. Interviewees shared that cost savings drove past adoption of, and high interest in, energy conservation practices. Generally, direct costs did not motivate reduced use of freshwater, but associated costs like energy to run pumps and supplies to treat contaminated surface water drove interest in reducing water use.DiscussionEfforts to improve resource use in the U.S. seafood supply should focus on identifying and scaling-up strategies that (i) involve improved efficiency of more than one resource and/or (ii) apply across multiple settings. This work should involve partnerships between industry, government agencies, and academic researchers, and should be informed by supply chain actors’ experiences and insights. The qualitative insights from this study encompass rich descriptions of FEW-relevant factors at the level of specific supply chain stages as well as findings across six major seafood supply chains in three countries. The study provides an essential complement to existing quantitative characterizations of resource use, and enables nuanced and informed responses to challenges.

Abstract Brain‐derived extracellular vesicles (EVs) play an active role in Alzheimer's disease (AD), relaying important physiological information about their host tissues. The internal cargo of EVs is protected from degradation, making EVs attractive AD biomarkers. However, it is unclear how circulating EVs relate to EVs isolated from disease‐vulnerable brain regions. We developed a novel method for collecting EVs from the hippocampal interstitial fluid (ISF) of live mice. EVs (EVISF) were isolated via ultracentrifugation and characterized by nanoparticle tracking analysis, immunogold labelling, and flow cytometry. Mass spectrometry and proteomic analyses were performed on EVISF cargo. EVISF were 40–150 nm in size and expressed CD63, CD9, and CD81. Using a model of cerebral amyloidosis (e.g., APPswe, PSEN1dE9 mice), we found protein concentration increased but protein diversity decreased with Aβ deposition. Genotype, age, and Aβ deposition modulated proteostasis‐ and immunometabolic‐related pathways. Changes in the microglial EVISF proteome were sexually dimorphic and associated with a differential response of plaque associated microglia. We found that female APP/PS1 mice have more amyloid plaques, less plaque associated microglia, and a less robust‐ and diverse‐ EVISF microglial proteome. Thus, in vivo microdialysis is a novel technique for collecting EVISF and offers a unique opportunity to explore the role of EVs in AD.

Despite the high mortality rate involved with invasive cerebral mycoses, there is a relative lack of research available around antifungals capable of crossing the blood brain barrier. In this study the metabolites of four plants (Crocus vernus, Miniature Narcissus (daffodil), Osmanthus delavayi and Taraxacum officinale (common dandelion)) and two bacteria (Lacticaseibacillus paracasei and Staphylococcus epidermidis) were extracted and assayed for antifungal activity against Candida albicans and Saccharomyces cerevisiae. Thin layer chromatography and bioautography were then employed to assess the activity of the constituent components of sources showing antifungal activity. Metabolites of S.epidermidis, and extracts of miniature Narcissus and Taraxacum officinal demonstrated no antifungal activity, metabolites of Lacticaseibacillus paracasei demonstrated variable antifungal activity and extracts of Osmanthus delavayi demonstrated previously unreported antifungal activity, although there were issues with repeatability. Osmanthus delavayi warrants further study, with an aim to separate out each component, test it for bioactivity and/or asses for the presence of synergism between two or more components, determine their interactions with the blood brain barrier and any potential toxicities and therefore assess the therapeutic potential.

Background Data on right ventricular (RV) exercise adaptation following acute intermediate and high-risk pulmonary embolism (PE) remain limited. This study aimed to evaluate the symptom burden, RV functional recovery during exercise and cardiopulmonary exercise parameters in survivors of intermediate and high-risk acute PE.Methods We prospectively recruited patients following acute intermediate and high-risk PE at four sites in Australia and UK. Study assessments included stress echocardiography, cardiopulmonary exercise testing (CPET) and ventilation–perfusion (VQ) scan at 3 months follow-up.Results Thirty patients were recruited and 24 (median age: 55 years, IQR: 22) completed follow-up. Reduced peak oxygen consumption (VO2) and workload was seen in 75.0% (n=18), with a persistent high symptom burden (mean PEmb-QoL Questionnaire 48.4±21.5 and emPHasis-10 score 22.4±8.8) reported at follow-up. All had improvement in RV-focused resting echocardiographic parameters. RV systolic dysfunction and RV to pulmonary artery (PA) uncoupling assessed by stress echocardiography was seen in 29.2% (n=7) patients and associated with increased ventilatory inefficiency (V̇E/V̇CO2 slope 47.6 vs 32.4, p=0.03), peak exercise oxygen desaturation (93.2% vs 98.4%, p=0.01) and reduced peak oxygen pulse (p=0.036) compared with controls. Five out of seven patients with RV–PA uncoupling demonstrated persistent bilateral perfusion defects on VQ scintigraphy consistent with chronic thromboembolic pulmonary vascular disease.Conclusion In our cohort, impaired RV adaptation on exercise was seen in almost one-third of patients. Combined stress echocardiography and CPET may enable more accurate phenotyping of patients with persistent symptoms following acute PE to allow timely detection of long-term complications.

Rapid technological improvements in biomaterials, computer-aided design (CAD) and manufacturing (CAM) have endorsed clear aligner therapy (CAT) as a mainstay of orthodontic treatment, and the materials employed for aligner fabrication play an all-important role in determining the clinical performance of clear aligners. This narrative review has attempted to comprehensively encompass the entire gamut of materials currently used for the fabrication of clear aligners and elucidate their characteristics that are crucial in determining their performance in an oral environment. Historical developments and current protocols in aligner fabrication, features of contemporary bioactive materials, and emerging trends related to CAT are discussed. Advances in aligner material chemistry and engineering possess the potential to bring about radical transformations in the therapeutic applications of CAT; in the absence of which, clear aligners would continue to underperform clinically, due to their inherent biomechanical constraints. Finally, while innovations in aligner materials such as shape memory polymers, direct three-dimensional (3D) printed clear aligners and bioactive materials combined with clear aligner materials are essential to further advance the applications of CAT; increased awareness of environmental responsibilities among aligner manufacturers, aligner prescribing clinicians and aligner users is essential for better alignment of our climate change goals towards a sustainable planet.