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Abstract Free-swimming polychaetes are common in marine habitats and exhibit a unique form of swimming whereby a metachronal wave occurs simultaneously with a bending body wave. This body wave is unusual among swimming animals because it travels in the same direction as the animal’s swimming direction. However, we currently lack a mechanistic understanding of this unusual form of locomotion. In this study we use a combination of high-speed, high-resolution video and particle image velocimetry (PIV) to quantify kinematics and fluid dynamics for three species of swimming polychaetes, spanning two orders of magnitude in size. We find that in all species, flows generated by metachronal waves of parapodia dominate while typical flows associated with body bending is absent. However, the parapodia are less flexible than propulsive structures in other metachronal swimmers. This creates a localized, but substantial upstream flow during the recovery stroke. Using body bending, the recovery stroke can occur mostly beneath the bulk flow from the power strokes, resulting in minimal inference while the subsequent power stroke can benefit from the pressure field generated during recovery. These results may have implications for future vehicle designs that incorporate metachronal locomotion.

Background Tuberculosis (TB) has a significant treatment burden for patients, requiring at least six months of anti-TB treatment (ATT) with multiple medicines. Ensuring good adherence to ATT is central to global TB strategies, including those in high-income, low-TB incidence (HILI) settings. For adherence interventions to be successful and deliverable, they need to address the personal and environmental factors influencing patient and provider behaviour.Purpose This paper describes the application of theory and research evidence to inform the design process of the IMPACT manualised intervention to support ATT adherence for adults with TB disease in the United Kingdom (UK). It also provides a full description of the resulting intervention.Methods We synthesised findings from our formative research (qualitative and quantitative scoping reviews and patient and carer interviews) and supplemented these with clinic observations, a literature review, and healthcare provider interviews. Findings were mapped to the guiding theoretical framework (Perceptions and Practicalities Approach) which was operationalised to design the intervention components and content. An Intervention Development Group (IDG) of relevant stakeholders were consulted to adapt the intervention to local clinical settings.Results The pragmatic, deliverable components and content for the IMPACT intervention included: (1) an enhanced, structured, risk assessment to systematically identify risk factors for non-adherence plus locally-adapted guidance to mitigate these; and (2) patient educational materials (an animated video and interactive patient booklet) about TB and its treatment, to communicate the need for treatment and address common concerns.Conclusions Using a theory– and evidence– based approach incorporating stakeholder input, we have developed a multi-component, pragmatic, manualised intervention, which addresses patients’ personal barriers to adherence within local service resources to improve adherence to ATT within UK TB services.

Objectives To examine the impact of the COVID-19 pandemic on deprivation-related inequalities in hospitalisations for cardiovascular disease (CVD) conditions in Denmark and England between March 2018 and December 2021.Design Time-series studies in England and Denmark.Setting With the approval of National Health Service England, we used English primary care electronic health records, linked to secondary care and death registry data through the OpenSAFELY platform and nationwide Danish health registry data.Participants We included adults aged 18 and over without missing age, sex or deprivation information. On 1 March 2020, 16 234 700 people in England and 4 491 336 people in Denmark met the inclusion criteria.Primary outcome measures Hospital admissions with the primary reason for myocardial infarction (MI), ischaemic or haemorrhagic stroke, heart failure and venous thromboembolism (VTE).Results We saw deprivation gradients in monthly CVD hospitalisations in both countries, with differences more pronounced in Denmark. Based on pre-pandemic trends, in England, there were an estimated 2608 fewer admissions than expected for heart failure in the most deprived quintile during the pandemic compared with an estimated 979 fewer admissions in the least deprived quintile. For all other outcomes, there was little variation by deprivation quintile. In Denmark, there were an estimated 1013 fewer admissions than expected over the pandemic for MI in the most deprived quintile compared with 619 in the least deprived quintile. Similar trends were seen for stroke and VTE, though absolute numbers were smaller. Heart failure admissions were similar to pre-pandemic levels with little variation by deprivation quintile.Conclusions Overall, we did not find that the pandemic substantially worsened pre-existing deprivation-related differences in CVD hospitalisations, though there were exceptions in both countries.

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.

Diffusible iodine-based contrast-enhanced computed tomography (diceCT) is an increasingly used digital complement, supplement, or alternative to traditional dissection-based anatomical research. The diceCT protocol, which has evolved and expanded over the past decade, employs passive diffusion of Lugol’s iodine (KI3) to increase soft tissue radiodensity and improve structure contrast in the CT or microCT imaging of specimens. The development and application of diceCT has focused largely on specimens under 1 kg, and the varying reporting of methods on studies of both small and large specimens has initiated, but not yet established, an effective diceCT protocol for larger specimens based on monitored experiments of several fundamental variables (e.g., Lugol’s iodine concentration, duration, and impacts of Lugol’s iodine on tissues). In this study, we have experimentally assessed the efficacy of diceCT protocols for imaging whole-body specimens of the 1–4.5 kg Australian brushtail possum (Trichosurus vulpecula) using sequential CT imaging assessment across experimental conditions. We assessed the impact of varying Lugol’s iodine concentration, the presence/absence of skin, solution volume and agitation on tissue radiodensity changes through weekly CT-based monitoring of tissue radiodensities over an 8-week experimental period. We have also quantified tissue volumetric changes across our experiment to assess the impact of diceCT applications on subsequent analyses of imaging datasets. Our results indicate that substantial changes in both soft-tissue radiodensity and soft-tissue volume occur within the first 28 days of Lugol’s iodine treatment, followed by a slower rate of progressive soft-tissue radiodensity and volume changes across the experiment duration. Our results demonstrate the negligible benefit of skinning larger specimens to improve solution diffusion, and document significant soft-tissue volumetric changes with high concentration solutions (e.g., 10%) and long-duration exposure (e.g., beyond 5 weeks) that should guide individual diceCT protocol design and/or quantification and analysis for mammal specimens above 1 kg.

Background Codelists are required to extract meaningful information on characteristics and events from routinely collected health data such as electronic health records. Research using routinely collected health data relies on codelists to define study populations and variables, thus, trustworthy codelists are important. Here, we provide a checklist, in the style of commonly used reporting guidelines, to help researchers adhere to best practice in codelist development and sharing. Methods Based on a literature search and a workshop with researchers experienced in the use of routinely collected health data, we created a set of recommendations that are 1. broadly applicable to different datasets, research questions, and methods of codelist creation; 2. easy to follow, implement and document by an individual researcher, and 3. fit within a step-by-step process. We then formatted these recommendations into a checklist. Results We have created a 10-step checklist, comprising 28 items, with accompanying guidance on each step. The checklist advises on which metadata to provide, how to define a clinical concept, how to identify and evaluate existing codelists, how to create new codelists, and how to review, check, finalise, and publish a created codelist. Conclusions Use of the checklist can reassure researchers that best practice was followed during the development of their codelists, increasing trust in research that relies on these codelists and facilitating wider re-use and adaptation by other researchers.

Abstract Pre-clinical and clinical studies have shown that PEGPH20 depletes intratumoral hyaluronic acid (HA), which is linked to high interstitial fluid pressures and poor distribution of chemotherapies. 29 patients with metastatic advanced solid tumors received quantitative magnetic resonance imaging (qMRI) in 3 prospective clinical trials of PEGPH20: HALO-109-101 (NCT00834704), HALO-109-102 (NCT01170897), and HALO-109-201 (NCT01453153). Apparent Diffusion Coefficient of water (ADC), T1, k trans , v p , v e , and iAUC maps were computed from qMRI acquired at baseline and ≥ 1 time point post-PEGPH20. Tumor ADC and T1 decreased, while iAUC, k trans , v p , and v e increased, on day 1 post-PEGPH20 relative to baseline values. This is consistent with HA depletion leading to a decrease in tumor extracellular water content and an increase in perfusion, permeability, extracellular matrix space, and vascularity. Baseline parameter values predictive of pharmacodynamic responses were: ADC > 1.46 × 10−3 mm2/s (Balanced Accuracy (BA) = 72%, p 0.54 s (BA = 82%, p

Abstract Background With conference attendees having expressed preference for hybrid meeting formats (containing both in-person and virtual components), organisers are challenged to find the best combination of events for academic meetings. Better understanding what attendees prioritise in a hybrid conference should allow better planning and need fulfilment. Methods An online survey with closed and open-ended questions was distributed to registrants of an international virtual conference. Responses were then submitted to descriptive statistical analysis and directed content analysis. Results 823 surveys (Response Rate = 4.9%) were received. Of the 813 who expressed a preference, 56.9% (N = 463) desired hybrid conference formats in the future, 32.0% (N = 260) preferred in-person conferences and 11.1% (N = 90) preferred virtual conferences. Presuming a hybrid meeting could be adopted, 67.4% (461/684) preferred that virtual sessions take place both during the in-person conference and be spread throughout the year. To optimise in-person components of hybrid conferences, recommendations received from 503 respondents included: prioritising clinical skills sessions (26.2%, N = 132), live international expert presentations and discussions (15.7%, N = 79) and interaction between delegates (13.5%, N = 68). To optimise virtual components, recommendations received from 486 respondents included: prioritising a live streaming platform with international experts’ presentations and discussions (24.3%, N = 118), clinical case discussions (19.8%, N = 96) and clinical update sessions (10.1%, N = 49). Conclusions Attendees envision hybrid conferences in which organisers can enable the vital interaction between individuals during an in-person component (e.g., networking, viewing and improving clinical skills) while accessing virtual content at their convenience (e.g., online expert presentations with latest advancements, clinical case discussions and debates). Having accessible virtual sessions throughout the year, as well as live streaming during the in-person component of hybrid conferences, allows for opportunity to prolong learning beyond the conference days.

Abstract Despite advancements in cancer immunotherapy, solid tumors remain formidable challenges. In glioma, profound inter- and intra-tumoral heterogeneity of antigen landscape hampers therapeutic development. Therefore, it is critical to consider alternative sources to expand the repertoire of targetable (neo-)antigens and improve therapeutic outcomes. Accumulating evidence suggests that tumor-specific alternative splicing (AS) could be an untapped reservoir of antigens. In this study, we investigated tumor-specific AS events in glioma, focusing on those predicted to generate major histocompatibility complex (MHC)-presentation-independent, cell-surface antigens that could be targeted by antibodies and chimeric antigen receptor-T cells. We systematically analyzed bulk RNA-sequencing datasets comparing 429 tumor samples (from The Cancer Genome Atlas) and 9166 normal tissue samples (from the Genotype-Tissue Expression project), and identified 13 AS events in 7 genes predicted to be expressed in more than 10% of the patients, including PTPRZ1 and BCAN, which were corroborated by an external RNA-sequencing dataset. Subsequently, we validated our predictions and elucidated the complexity of the isoforms using full-length transcript amplicon sequencing on patient-derived glioblastoma cells. However, analyses of the RNA-sequencing datasets of spatially mapped and longitudinally collected clinical tumor samples unveiled remarkable spatiotemporal heterogeneity of the candidate AS events. Furthermore, proteomics analysis did not reveal any peptide spectra matching the putative antigens. Our investigation illustrated the diverse characteristics of the tumor-specific AS events and the challenges of antigen exploration due to their notable spatiotemporal heterogeneity and elusive nature at the protein levels. Redirecting future efforts toward intracellular, MHC-presented antigens could offer a more viable avenue.

Abstract To assess cardiometabolic profiles and proteomics to identify biomarkers associated with the metabolically healthy and unhealthy obesity. Young adults (N = 156) enrolled were classified as not having obesity, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO) based on NCEP ATP-III criteria. Plasma proteomics at study entry were measured using Olink Cardiometabolic Explore panel. Linear regression was used to assess associations between proteomics and obesity groups as well as cardiometabolic traits of glucose, insulin, and lipid profiles at baseline and follow-up visits. Enriched biological pathways were further identified based on the significant proteomic features. Among the baseline 95 (61%) and 61 (39%) participants classified as not having obesity and having obesity (8 MHO and 53 MUHO), respectively. Eighty of the participants were followed-up with an average 4.6 years. Forty-one proteins were associated with obesity (FDR

Objectives Long-term sickness absence from employment has negative consequences for the economy and can lead to widened health inequalities. Sick notes (also called ‘fit notes’) are issued by general practitioners when a person cannot work for health reasons for more than 7 days. We quantified the sick note rate in people with evidence of COVID-19 in 2020, 2021 and 2022, as an indication of the burden for people recovering from COVID-19.Design Cohort study.Setting With National Health Service (NHS) England approval, we used routine clinical data (primary care, hospital and COVID-19 testing records) within the OpenSAFELY-TPP database.Participants People 18–64 years with a recorded positive test or diagnosis of COVID-19 in 2020 (n=365 421), 2021 (n=1 206 555) or 2022 (n=1 321 313); general population matched in age, sex and region in 2019 (n=3 140 326), 2020 (n=3 439 534), 2021 (n=4 571 469) and 2022 (n=4 818 870); people hospitalised with pneumonia in 2019 (n=29 673).Primary outcome measure Receipt of a sick note in primary care.Results Among people with a positive SARS-CoV-2 test or COVID-19 diagnosis, the sick note rate was 4.88 per 100 person-months (95% CI 4.83 to 4.93) in 2020, 2.66 (95% CI 2.64 to 2.67) in 2021 and 1.73 (95% CI 1.72 to 1.73) in 2022. Compared with the age, sex and region-matched general population, the adjusted HR for receipt of a sick note over the entire follow-up period (up to 10 months) was 4.07 (95% CI 4.02 to 4.12) in 2020 decreasing to 1.57 (95% CI 1.56 to 1.58) in 2022. The HR was highest in the first 30 days postdiagnosis in all years. Among people hospitalised with COVID-19, after adjustment, the sick note rate was lower than in people hospitalised with pneumonia.Conclusions Given the under-recording of postacute COVID-19-related symptoms, these findings contribute a valuable perspective on the long-term effects of COVID-19. Despite likely underestimation of the sick note rate, sick notes were issued more frequently to people with COVID-19 compared with those without, even in an era when most people are vaccinated. Most sick notes occurred in the first 30 days postdiagnosis, but the increased risk several months postdiagnosis may provide further evidence of the long-term impact.

Introduction Obstructive sleep apnoea (OSA) is a common, but underdiagnosed, sleep disorder. If untreated, it leads to poor health outcomes, including Alzheimer’s disease, cancer, cardiovascular disease and all-cause mortality. Our aim is to determine the feasibility and cost-effectiveness of moving the testing for OSA into general practice and how general practitioner (GP)-based screening affects overall detection rates.Methods and analysis Randomised controlled trial of case finding of OSA in general practice using a novel Medicines and Healthcare products Regulatory Agency-registered device (AcuPebble SA100) compared with usual care with internal feasibility phase. A diverse sample of general practices (approximately 40) from across the West Midlands Clinical Research Network will identify participants from their records. Eligible participants will be aged 50–70 years with body mass index >30 kg/m2 and diabetes (type 1 or 2) and/or hypertension (office blood pressure >145/90 mm Hg or on treatment). They will exclude individuals with known OSA or chronic obstructive pulmonary disease, or those they deem unable to take part. After eligibility screening, consent and baseline assessment, participants will be randomised to either the intervention or control group. Participants in the intervention arm will receive by post the AcuPebble sleep test kit. Those in the control arm will continue with usual care. Follow-up questionnaires will be completed at 6 months. The study is powered (90%) to detect a 5% difference and will require 606 patients in each arm (713 will be recruited to each arm to allow for attrition). Due to the nature of the intervention, participants and GPs will not be blinded to the allocation.Outcomes Primary: Detection rate of moderate-to-severe OSA in the intervention group versus control group. Secondary: Time to diagnosis and time to treatment for intervention versus control group for mild, moderate and severe OSA; cost-effectiveness analysis comparing the different testing pathways.Ethics and dissemination The trial started on 1 November 2022. Ethical approval was granted from the South Central Oxford A Research Ethics Committee on 9 June 2023 (23/SC/0188) (protocol amendment version 1.3; update with amendment and approval to renumber to V2.0 on 29 August 2023). Patient recruitment began on 7 January 2024; initial planned end date will be on 31 April 2025.Results will be uploaded to the ISRCTN register within 12 months of the end of the trial date, presented at conferences, submitted to peer-reviewed journals and distributed via our patient and public involvement networks.The University of Warwick will act as the trial sponsor. The trial will be conducted in accordance with the Sponsor and Primary Care Clinical Trials Unit standard operating procedures.Trial registration number ISRCTN 16982033.

Abstract Flat hydrodynamic shells likely represent an evolutionary trade-off between adaptation to an aquatic lifestyle and the instability of more rounded shells, thought beneficial for self-righting. Trade-offs often result in compromises, this is particularly true when freshwater turtles, with flatter shells, must self-right to avoid the negative effects of inverting. These turtles, theoretically, invest more biomechanical effort to achieve successful and timely self-righting when compared to turtles with rounded carapaces. This increase in effort places these hatchlings in a precarious position; prone to inversion and predation and with shells seemingly maladapted to the act of self-righting. Here, we examine hatchling self-righting performance in three morphologically distinct freshwater turtle species (Apalone spinifera, Chelydra serpentina and Trachemys scripta scripta) that inhabit similar environmental niches. We demonstrate that these hatchlings were capable of rapid self-righting and used considerably less biomechanical effort relative to adult turtles. Despite differences in shell morphology the energetic efficiency of self-righting remained remarkably low and uniform between the three species. Our results confound theoretical predictions of self-righting ability based on shell shape metrics and indicate that other morphological characteristics like neck or tail morphology and shell material properties must be considered to better understand the biomechanical nuances of Testudine self-righting.

Abstract The aim of the current study is to develop and characterise novel complex multi-phase in vitro 3D models, for advanced microbiological studies. More specifically, we enriched our previously developed bi-phasic polysaccharide (Xanthan Gum)/protein (Whey Protein) 3D model with a fat phase (Sunflower Oil) at various concentrations, i.e., 10%, 20%, 40% and 60% (v/v), for better mimicry of the structural and biochemical composition of real food products. Rheological, textural, and physicochemical analysis as well as advanced microscopy imaging (including spatial mapping of the fat droplet distribution) of the new tri-phasic 3D models revealed their similarity to industrial food products (especially cheese products). Furthermore, microbial growth experiments of foodborne bacteria, i.e., Listeria monocytogenes, Escherichia coli, Pseudomonas aeruginosa and Lactococcus lactis on the surface of the 3D models revealed very interesting results, regarding the growth dynamics and distribution of cells at colony level. More specifically, the size of the colonies formed on the surface of the 3D models, increased substantially for increasing fat concentrations, especially in mid- and late-exponential growth phases. Furthermore, colonies formed in proximity to fat were substantially larger as compared to the ones that were located far from the fat phase of the models. In terms of growth location, the majority of colonies were located on the protein/polysaccharide phase of the 3D models. All those differences at microscopic level, that can directly affect the bacterial response to decontamination treatments, were not captured by the macroscopic kinetics (growth dynamics), which were unaffected from changes in fat concentration. Our findings demonstrate the importance of developing structurally and biochemically complex 3D in vitro models (for closer proximity to industrial products), as well as the necessity of conducting multi-level microbial analyses, to better understand and predict the bacterial behaviour in relation to their biochemical and structural environment. Such studies in advanced 3D environments can assist a better/more accurate design of industrial antimicrobial processes, ultimately, improving food safety.

Abstract Familial dysautonomia (FD) is a rare neurodevelopmental and neurodegenerative disease caused by a splicing mutation in the Elongator Acetyltransferase Complex Subunit 1 (ELP1) gene. The reduction in ELP1 mRNA and protein leads to the death of retinal ganglion cells (RGCs) and visual impairment in all FD patients. Currently patient symptoms are managed, but there is no treatment for the disease. We sought to test the hypothesis that restoring levels of Elp1 would thwart the death of RGCs in FD. To this end, we tested the effectiveness of two therapeutic strategies for rescuing RGCs. Here we provide proof-of-concept data that gene replacement therapy and small molecule splicing modifiers effectively reduce the death of RGCs in mouse models for FD and provide pre-clinical foundational data for translation to FD patients.

Abstract Background The CHILD-BRIGHT Network created a parent peer mentor (PPM) role to support other parents who were engaging as partners in the different research projects and activities of the network. We aim to describe how a PPM functioned to support parent-partners of children with disabilities in research projects within the Network. Methods In this case study, the PPM approached 50 parent-partners and scheduled a 1-on-1 initial telephone call to offer support for any issues arising. When consent was provided, the PPM recorded interactions with network parent-partners in a communication report in an Excel form. Also, verbatim transcription from one in-depth interview with the PPM was included for data analysis using qualitative description. The Guidance for Reporting Involvement of Patients and the Public (GRIPP2-SF) was used to report on involvement of patient-partners. Results A total of 55 interactions between 25 parent-partners and the PPM were documented between May 2018 and June 2021. The PPM’s support and liaison role contributed to adaptation of meeting schedules for parent-partners, amendment of the compensation guidelines, and ensuring that internal surveys and the newsletter were more accessible and engaging. The PPM also facilitated community-building by keeping parent-partners connected with researchers in the Network. Families and caregivers in the Network were comfortable sharing their experiences and emotions with the PPM who was also a parent herself, allowing researchers and the Network to learn more about parents’ experiences in partnering with them and how to improve engagement. Conclusions We highlight the important complementary role that a PPM can play in enhancing patient engagement in research by better understanding the experiences and needs of parent-partners.

Abstract Over the two last decades, whole-body cryotherapy/cryostimulation (WBC) has emerged as an exciting non-pharmacological treatment influencing inflammatory events at a cellular and physiological level, which can result in improved sleep quality, faster neuromuscular recovery after high-intensity exercise, and chronic pain relief for patients suffering different types of diseases (fibromyalgia, rheumatism, arthritis). Some evidence even suggests that WBC has benefits on mental health (depression, anxiety disorders) and cognitive functions in both adults and older adults, due to increased circulating BDNF levels. Recently, some safety concerns have been expressed by influential public health authorities (e.g., FDA, INSERM) based on reports from patients who developed adverse events upon or following WBC treatment. However, part of the data used to support these claims involved individuals whose entire body (except head) was exposed to extreme cold vaporized liquid nitrogen while standing in a narrow bathtub. Such a procedure is known as partial-body cryotherapy (PBC), and is often erroneously mistaken to be whole-body cryotherapy. Although having similarities in terms of naming and pursued aims, these two approaches are fundamentally different. The present article reviews the available literature on the main safety concerns associated with the use of true whole-body cryotherapy. English- and French-language reports of empirical studies including case reports, case series, and randomized controlled trials (RCTs) were identified through searches of PubMed, Scopus, Cochrane, and Web of Science electronic databases. Five case reports and two RCTs were included for a total of 16 documented adverse events (AEs). A critical in-depth evaluation of these AEs (type, severity, context of onset, participant’s medical background, follow-up) is proposed and used to illustrate that WBC-related safety risks are within acceptable limits and can be proactively prevented by adhering to existing recommendations, contraindications, and commonsense guidelines.

The purpose of this work was to provide a simple method to determine reactive strength during the 6-meter timed hop test (6mTH) and evaluate its association with isokinetic peak torque in patients following anterior cruciate ligament reconstruction (ACLR). Twenty-nine ACLR patients who were at least four months from surgery were included in this analysis. Participants were brought into the laboratory on one occasion to complete functional testing. Quadriceps and hamstring isokinetic testing was completed bilaterally at 60, 180, and 300 deg∙s-1, using extension peak torque from each speed as the outcome measure. The 6mTH was completed bilaterally using a marker-based motion capture system, and reactive strength ratio (RSR) was calculated from the vertical velocity of the pelvis during the test. An adjustment in RSR was made using the velocity of the 6mTH test to account for different strategies employed across participants. Repeated measures correlations were used to determine associations among isokinetic and hop testing variables. A two-way mixed analysis of variance was used to determine differences in isokinetic and hop testing variables between operated and non-operated legs and across male and female participants. Moderate positive associations were found between RSR (and adjusted RSR) and isokinetic peak torque at all speeds (r = .527 to .577). Mean comparisons showed significant main effects for leg and sex. Patients showed significant deficits in their operated versus non-operated legs in all isokinetic and hop testing variables, yet only isokinetic peak torque and timed hop time showed significant differences across male and female groups. Preliminary results are promising but further development is needed to validate other accessible technologies available to calculate reactive strength during functional testing after ACLR. Pending these developments, the effects of movement strategies, demographics, and levels of participation on RSR can then be explored to translate this simple method to clinical environments.

Many conservation actions must be implemented with limited data. This is especially true when planning recovery efforts for extirpated populations, such as grizzly bears (Ursus arctos) within the Bitterroot Ecosystem (BE), where strategies for reestablishing a resident population are being evaluated. Here, we applied individual-based movement models developed for a nearby grizzly bear population to predict habitat use in and near the BE, under scenarios of natural recolonization, reintroduction, and a combination. All simulations predicted that habitat use by grizzly bears would be higher in the northern half of the study area. Under the natural recolonization scenario, use was concentrated in Montana, but became more uniform across the northern BE in Idaho over time. Use was more concentrated in east-central Idaho under the reintroduction scenario. Assuming that natural recolonization continues even if bears are reintroduced, use remained widespread across the northern half of the BE and surrounding areas. Predicted habitat maps for the natural recolonization scenario aligned well with outlier and GPS collar data available for grizzly bears in the study area, with Spearman rank correlations of ≥0.93 and mean class values of ≥9.1 (where class 10 was the highest relative predicted use; each class 1-10 represented 10% of the landscape). In total, 52.4% of outlier locations and 79% of GPS collar locations were in class 10 in our predicted habitat maps for natural recolonization. Simulated grizzly bears selected habitats over a much larger landscape than the BE itself under all scenarios, including multiple-use and private lands, similar to existing populations that have expanded beyond recovery zones. This highlights the importance of recognizing and planning for the role of private lands in recovery efforts, including understanding resources needed to prevent and respond to human-grizzly bear conflict and maintain public acceptance of grizzly bears over a large landscape.

AbstractBackground Bright light therapy (BLT) is widely used for treating Seasonal Affective Disorder (SAD). However, the neural mechanisms underlying the therapeutic effects of BLT remain largely unexplored. The present study used a diurnal rodent (Nile grass rats; Arvicanthis niloticus) to test the hypothesis that the therapeutic effects of BLT could be, in part, due to reduced neuroinflammation and/or enhanced neuroplasticity. Our previous research has demonstrated that compared to grass rats housed in a summer-like daytime bright light condition (1000 lux), those housed in a winter-like daytime dim light condition (50 lux) showed increased depression- and anxiety-like behaviours, as well as impaired sociosexual behaviours and spatial memory, similar to what is observed in patients suffering from SAD.Materials and Methods In the present study, male and female grass rats were housed under the winter-like dim daytime light condition (lights on 600–1800 hr, 50 lux). The experimental groups received daily 1-h early morning BLT from 0600-0700 using full-spectrum light (10,000 lux), while the control groups received narrowband red light (λmax, 780 nm). Following 4 weeks of treatment, the expression of several neuroinflammatory or plasticity markers was examined in the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and the CA1 of the dorsal hippocampus.Results For the neuroinflammatory markers, BLT reduced TNF-α in the BLA of females, and upregulated CD11b in the mPFC and IL6 in the BLA in males. For the neuroplasticity markers, BLT downregulated BDNF in the CA1 and TrkB in all three brain regions in females but upregulated BDNF in the BLA and CA1 in males.Conclusions These results indicate that the therapeutic effects of BLT on sleep, mood, and cognition may be attributed in part to mechanisms involving neuroinflammation and neuroplasticity in corticolimbic brain regions. Moreover, these effects appear to vary between sexes.

Background Young people will suffer most from climate change yet are rarely engaged in dialogue about it. Citizen science offers a method for collecting policy-relevant data, whilst promoting awareness and capacity building. We tested the feasibility and acceptability of engaging Nepalese adolescents in climate change and health-related citizen science. Methods We purposively selected 33 adolescents from two secondary schools in one remote and one relatively accessible district of Nepal. We contextualised existing apps and developed bespoke apps to survey climate hazards, waste and water management, local biodiversity, nutrition and sociodemographic information. We analysed and presented quantitative data using a descriptive analysis. We captured perceptions and learnings via focus group discussions and analysed qualitative data using thematic analysis. We shared findings with data collectors using tables, graphs, data dashboards and maps. Results Adolescents collected 1667 biodiversity observations, identified 72 climate-change related hazards, and mapped 644 geolocations. They recorded 286 weights, 248 heights and 340 dietary recalls. Adolescents enjoyed learning how to collect the data and interpret the findings and gained an appreciation of local biodiversity which engendered ‘environmental stewardship’. Data highlighted the prevalence of failing crops and landslides, revealed both under- and over-nutrition and demonstrated that children consume more junk foods than adults. Adolescents learnt about the impacts of climate change and the importance of eating a diverse diet of locally grown foods. A lack of a pre-established sampling frame, multiple records of the same observation and spurious nutrition data entries by unsupervised adolescents limited data quality and utility. Lack of internet access severely impacted feasibility, especially of apps which provide online feedback. Conclusions Citizen science was largely acceptable, educational and empowering for adolescents, although not always feasible without internet access. Future projects could improve data quality and integrate youth leadership training to enable climate-change advocacy with local leaders.

Children with postpericardiotomy syndrome may develop hemodynamically significant pericardial effusions warranting drainage by surgical pericardial window or pericardiocentesis. The optimal approach is unknown. We performed a retrospective observational study at two pediatric cardiac centers. We included 42 children aged

Introduction In an age of increasingly face-to-face, blended, and online Health Professions Education, students have more choices of institutions at which to study their degree. For an applicant, oftentimes, the first step is to learn more about a program through its website. Websites allow programs to convey their unique voice and to share their mission and values with others such as applicants, researchers, and academics. Additionally, as the number of master in health professions education (MHPE), or equivalent, programs rapidly grows, websites can share the priorities of these programs. Methods In this study, we conducted a website review of 158 MHPE websites to explore their geographical distributions, missions, educational concentrations, and various programmatic components. Results We compiled this information and synthesized pertinent aspects, such as program similarities and differences, or highlighted the omission of critical data. Conclusions Given that websites are often the first point of contact for prospective applicants, curious collaborators, and potential faculty, the digital image of MHPE programs matters. We believe our findings demonstrate opportunities for growth within institutions and assist the field in identifying the priorities of MHPE programs. As programs begin to shape their websites with more intentionality, they can reflect their relative divergence/convergence compared to other programs as they see fit and, therefore, attract individuals to best match this identity. Periodic reviews of the breadth of programs, such as those undergone here, are necessary to capture diversifying goals, and serves to help advance the field of MHPE as a whole.

Species richness has been found to increase from the poles to the tropics but with a small dip near the equator over all marine fishes. Phylogenetic diversity measures offer an alternative perspective on biodiversity linked to evolutionary history. If phylogenetic diversity is standardized for species richness, then it may indicate places with relatively high genetic diversity. Latitudes and depths with both high species and phylogenetic diversity would be a priority for conservation. We compared latitudinal and depth gradients of species richness, and three measures of phylogenetic diversity, namely average phylogenetic diversity (AvPD), the sum of the higher taxonomic levels (STL) and the sum of the higher taxonomic levels divided by the number of species (STL/spp) for modelled ranges of 5,619 marine fish species. We distinguished all, bony and cartilaginous fish groups and four depth zones namely: whole water column; 0 –200 m; 201–1,000 m; and 1,001–6,000 m; at 5° latitudinal intervals from 75°S to 75°N, and at 100 m depth intervals from 0 m to 3,500 m. Species richness and higher taxonomic richness (STL) were higher in the tropics and subtropics with a small dip at the equator, and were significantly correlated among fish groups and depth zones. Species assemblages had closer phylogenetic relationships (lower AvPD and STL/spp) in warmer (low latitudes and shallow water) than colder environments (high latitudes and deep sea). This supports the hypothesis that warmer shallow latitudes and depths have had higher rates of evolution across a range of higher taxa. We also found distinct assemblages of species in different depth zones such that deeper sea species are not simply a subset of shallow assemblages. Thus, conservation needs to be representative of all latitudes and depth zones to encompass global biodiversity.

Taxonomic species are the best standardised metric of biodiversity. Therefore, there is broad scientific and public interest in how many species have already been named and how many more may exist. Crustaceans comprise about 6% of all named animal species and isopods about 15% of all crustaceans. Here, we review progress in the naming of isopods in relation to the number of people describing new species and estimate how many more species may yet be named by 2050 and 2100, respectively. In over two and a half centuries of discovery, 10,687 isopod species in 1,557 genera and 141 families have been described by 755 first authors. The number of authors has increased over time, especially since the 1950s, indicating increasing effort in the description of new species. Despite that the average number of species described per first author has declined since the 1910s, and the description rate has slowed down over the recent decades. Authors’ publication lifetimes did not change considerably over time, and there was a distinct shift towards multi-authored publications in recent decades. Estimates from a non-homogeneous renewal process model predict that an additional 660 isopod species will be described by 2100, assuming that the rate of description continues at its current pace.

Historical fishing effort has resulted, in many parts of the ocean, in increasing catches of smaller, lower trophic level species once larger higher trophic level species have been depleted. Concurrently, changes in the geographic distribution of marine species have been observed as species track their thermal affinity in line with ocean warming. However, geographic shifts in fisheries, including to deeper waters, may conceal the phenomenon of fishing down the food web and effects of climate warming on fish stocks. Fisheries-catch weighted metrics such as the Mean Trophic Level (MTL) and Mean Temperature of the Catch (MTC) are used to investigate these phenomena, although apparent trends of these metrics can be masked by the aforementioned geographic expansion and deepening of fisheries catch across large areas and time periods. We investigated instances of both fishing down trophic levels and climate-driven changes in the geographic distribution of fished species in New Zealand waters from 1950–2019, using the MTL and MTC. Thereafter, we corrected for the masking effect of the geographic expansion of fisheries within these indices by using the Fishing-in-Balance (FiB) index and the adapted Mean Trophic Level (aMTL) index. Our results document the offshore expansion of fisheries across the New Zealand Exclusive Economic Zone (EEZ) from 1950–2019, as well as the pervasiveness of fishing down within nearshore fishing stock assemblages. We also revealed the warming of the MTC for pelagic-associated fisheries, trends that were otherwise masked by the depth- and geographic expansion of New Zealand fisheries across the study period.

The functional traits of species depend both on species’ evolutionary characteristics and their local environmental conditions and opportunities. The temperature-size rule (TSR), gill-oxygen limitation theory (GOLT), and temperature constraint hypothesis (TCH) have been proposed to explain the gradients of body size and trophic level of marine species. However, how functional traits vary both with latitude and depth have not been quantified at a global scale for any marine taxon. We compared the latitudinal gradients of trophic level and maximum body size of 5,619 marine fish from modelled species ranges, based on (1) three body size ranges, 100 cm, and (2) four trophic levels, 3.70. These were parsed into 5° latitudinal intervals in four depth zones: whole water column, 0–200, 201–1,000, and 1,001–6,000 m. We described the relationship between latitudinal gradients of functional traits and salinity, sea surface and near seabed temperatures, and dissolved oxygen. We found mean body sizes and mean trophic levels of marine fish were smaller and lower in the warmer latitudes, and larger and higher respectively in the high latitudes except for the Southern Ocean (Antarctica). Fish species with trophic levels ≤2.80 were dominant in warmer and absent in colder environments. We attribute these differences in body size and trophic level between polar regions to the greater environmental heterogeneity of the Arctic compared to Antarctica. We suggest that fish species’ mean maximum body size declined with depth because of decreased dissolved oxygen. These results support the TSR, GOLT and TCH hypotheses respectively. Thus, at the global scale, temperature and oxygen are primary factors affecting marine fishes’ biogeography and biological traits.

Climate warming generally induces poleward range expansions and equatorward range contractions of species’ environmental niches on a global scale. Here, we examined the direction and magnitude of species biomass centroid geographic shifts in relation to temperature and depth for 83 fish species in 9,522 standardised research trawls from the North Sea (1998–2020) to the Norwegian (2000–2020) and Barents Sea (2004–2020). We detected an overall significant northward shift of the marine fish community biomass in the North Sea, and individual species northward shifts in the Barents and North Seas, in 20% and 25% of the species’ biomass centroids in each respective region. We did not detect overall community shifts in the Norwegian Sea, where two species (8%) shifted in each direction (northwards and southwards). Among 9 biological traits, species biogeographic assignation, preferred temperature, age at maturity and maximum depth were significant explanatory variables for species latitudinal shifts in some of the study areas, and Arctic species shifted significantly faster than boreal species in the Barents Sea. Overall, our results suggest a strong influence of other factors, such as biological interactions, in determining several species’ recent geographic shifts.

Introduction: The application of single-cell RNA sequencing has greatly improved our understanding of various cellular and molecular mechanisms involved in physiological and pathophysiological processes. However, obtaining living cells for this technique can be difficult under certain conditions. To solve this problem, the methanol fixation method appeared as a promising alternative for routine clinical use. Materials and Methods: In this study, we selected two AML samples that had been fixed in methanol for 12–18 months. Once the cells were rehydrated, these samples were subjected to single-cell RNA sequencing. We then compared the results obtained from these samples with those obtained from the same samples cryopreserved in DMSO. Results: We used a previously validated methanol fixation protocol to perform scRNA-seq on DMSO cryopreserved cells and cells fixed in methanol for more than one year. Preliminary results show that methanol fixation induces some genetic and transcriptional modification compared with DMSO cryopreservation but remains a valuable method for single-cell analysis of primary human leukemia cells. Conclusions: The initial findings from this study highlight certain resemblances in methanol fixation over a 12-month period and cryopreservation with DMSO, along with associated transcriptional level modifications. However, we observed genetic degradation in the fixation condition when extending beyond one year. Despite certain study limitations, it is evident that short-term methanol fixation can be effectively used for leukemia blast samples. Its ease of implementation holds the potential to simplify the integration of this technique into routine clinical practice.

Decades ago, the treatment for acute myeloid leukemia relied on cytarabine and anthracycline. However, advancements in medical research have introduced targeted therapies, initially employing monoclonal antibodies such as ant-CD52 and anti-CD123, and subsequently utilizing specific inhibitors that target molecular mutations like anti-IDH1, IDH2, or FLT3. The challenge lies in determining the role of these therapeutic options, considering the inherent tumor heterogeneity associated with leukemia diagnosis and the clonal drift that this type of tumor can undergo. Targeted drugs necessitate an examination of various therapeutic targets at the individual cell level rather than assessing the entire population. It is crucial to differentiate between the prognostic value and therapeutic potential of a specific molecular target, depending on whether it is found in a terminally differentiated cell with limited proliferative potential or a stem cell with robust capabilities for both proliferation and self-renewal. However, this cell-by-cell analysis is accompanied by several challenges. Firstly, the scientific aspect poses difficulties in comparing different single cell analysis experiments despite efforts to standardize the results through various techniques. Secondly, there are practical obstacles as each individual cell experiment incurs significant financial costs and consumes a substantial amount of time. A viable solution lies in the ability to process multiple samples simultaneously, which is a distinctive feature of the cell hashing technique. In this study, we demonstrate the applicability of the cell hashing technique for analyzing acute myeloid leukemia cells. By comparing it to standard single cell analysis, we establish a strong correlation in various parameters such as quality control, gene expression, and the analysis of leukemic blast markers in patients. Consequently, this technique holds the potential to become an integral part of the biological assessment of acute myeloid leukemia, contributing to the personalized and optimized management of the disease, particularly in the context of employing targeted therapies.

Amphipod crustaceans are an essential component of tropical marine biodiversity. However, their distribution and biogeography have not been analysed in one of the world’s largest tropical countries nested in the Coral Triangle, Indonesia. We collected and identified amphipod crustaceans from eight sites in Indonesian waters and combined the results with data from 32 additional sites in the literature. We analysed the geographic distribution of 147 benthic amphipod crustaceans using cluster analysis and the ‘Bioregions Infomaps’ neural network method of biogeographic discrimination. We found five groups of benthic amphipod crustaceans which show relationships with sampling methods, depth, and substrata. Neural network biogeographic analysis indicated there was only one biogeographic region that matched with the global amphipod regions and marine biogeographic realms defined for all marine taxa. There was no support for Wallaces or other lines being marine biogeographic boundaries in the region. Species richness was lower than expected considering the region is within the Coral Triangle. We hypothesise that this low richness might be due to the intense fish predation which may have limited amphipod diversification. The results indicated that habitat rather than biogeography determines amphipod distribution in Indonesia. Therefore, future research needs to sample more habitats, and consider habitat in conservation planning.

Novel tools and methods for monitoring marine environments can improve efficiency but must not compromise long-term data records. Quantitative comparisons between new and existing methods are therefore required to assess their compatibility for monitoring. Monitoring of shallow water coral reefs is typically conducted using diver-based collection of benthic images along transects. Diverless systems for obtaining underwater images (e.g. towed-cameras, remotely operated vehicles, autonomous underwater vehicles) are increasingly used for mapping coral reefs. Of these imaging platforms, towed-cameras offer a practical, low cost and efficient method for surveys but their utility for repeated measures in monitoring studies has not been tested. We quantitatively compare a towed-camera approach to repeated surveys of shallow water coral reef benthic assemblages on fixed transects, relative to benchmark data from diver photo-transects. Differences in the percent cover detected by the two methods was partly explained by differences in the morphology of benthic groups. The reef habitat and physical descriptors of the site—slope, depth and structural complexity—also influenced the comparability of data, with differences between the tow-camera and the diver data increasing with structural complexity and slope. Differences between the methods decreased when a greater number of images were collected per tow-camera transect. We attribute lower image quality (variable perspective, exposure and focal distance) and lower spatial accuracy and precision of the towed-camera transects as the key reasons for differences in the data from the two methods and suggest changes to the sampling design to improve the application of tow-cameras to monitoring.

In 2010, the Conference of the Parties of the Convention on Biological Diversity agreed on the Strategic Plan for Biodiversity 2011–2020 in Aichi Prefecture, Japan. As this plan approaches its end, we discussed whether marine biodiversity and prediction studies were nearing the Aichi Targets during the 4th World Conference on Marine Biodiversity held in Montreal, Canada in June 2018. This article summarises the outcome of a five-day group discussion on how global marine biodiversity studies should be focused further to better understand the patterns of biodiversity. We discussed and reviewed seven fundamental biodiversity priorities related to nine Aichi Targets focusing on global biodiversity discovery and predictions to improve and enhance biodiversity data standards (quantity and quality), tools and techniques, spatial and temporal scale framing, and stewardship and dissemination. We discuss how identifying biodiversity knowledge gaps and promoting efforts have and will reduce such gaps, including via the use of new databases, tools and technology, and how these resources could be improved in the future. The group recognised significant progress toward Target 19 in relation to scientific knowledge, but negligible progress with regard to Targets 6 to 13 which aimed to safeguard and reduce human impacts on biodiversity.

At present, amphipod crustaceans comprise 9,980 species, 1,664 genera, 444 subfamilies, and 221 families. Of these, 1,940 species (almost 20%) have been discovered within the last decade, including 18 fossil records for amphipods, which mostly occurred in Miocene amber and are probably all freshwater species. There have been more authors describing species since the 1950s and fewer species described per author since the 1860s, implying greater taxonomic effort and that it might be harder to find new amphipod species, respectively. There was no evidence of any change in papers per author or publication life-times of taxonomists over time that might have biased apparent effort. Using a nonhomogeneous renewal process model, we predicted that by the year 2100, 5,600 to 6,600 new amphipod species will be discovered. This indicates that about two-thirds of amphipods remain to be discovered which is twice the proportion than for species overall. Amphipods thus rank amongst the least well described taxa. To increase the prospect of discovering new amphipod species, studying undersampled areas and benthic microhabitats are recommended.

Urban estuarine sediments are sinks to a range of contaminants of anthropogenic origin, and a key challenge is to characterize the risk of these compounds to receiving environments. In this study, the toxicity of urban estuarine sediments was tested using acute and chronic bioassays in the benthic harpacticoid Quinquelaophonte sp., and in the planktonic calanoid Gladioferens pectinatus, two New Zealand copepod species. The sediment samples from the estuary tributary sites significantly impacted reproduction in Quinquelaophonte sp. However, results from one of the estuary sites were not significantly different to those from the tributaries sites, suggesting that chemicals other than trace metals, polycyclic aromatic hydrocarbons and ammonia may be the causative stressors. Sediment elutriate samples had significant effects on reproductive endpoints in G. pectinatus, and on the induction of DNA damage in cells, as shown by the comet assay. The results indicate that sediment contamination at the Ahuriri Estuary has the potential to impact biological processes of benthic and pelagic organisms. The approach used provides a standardized methodology to assess the toxicity of estuarine sediments.

Citizen science approaches are of great interest for their potential to efficiently and sustainably monitor wildlife populations on both public and private lands. Here we present two studies that worked with volunteers to set camera traps for ecological surveys. The photographs recorded by these citizen scientists were archived and verified using the eMammal software platform, providing a professional grade, vouchered database of biodiversity records. Motivated by managers’ concern with perceived high bear activity, our first example enlisted the help of homeowners in a short-term study to compare black bear activity inside a National Historic Site with surrounding private land. We found similar levels of bear activity inside and outside the NHS, and regional comparisons suggest the bear population is typical. Participants benefited from knowing their local bear population was normal and managers refocused bear management given this new information. Our second example is a continuous survey of wildlife using the grounds of a nature education center that actively manages habitat to maintain a grassland prairie. Center staff incorporated the camera traps into educational programs, involving visitors with camera setup and picture review. Over two years and 5,968 camera-nights this survey has collected 41,393 detections of 14 wildlife species. Detection rates and occupancy were higher in open habitats compared to forest, suggesting that the maintenance of prairie habitat is beneficial to some species. Over 500 volunteers of all ages participated in this project over two years. Some of the greatest benefits have been to high school students, exemplified by a student with autism who increased his communication and comfort level with others through field work with the cameras. These examples show how, with the right tools, training and survey design protocols, citizen science can be used to answer a variety of applied management questions while connecting participants with their secretive mammal neighbors.