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Abstract The South Atlantic Ocean hosts several well‐studied volcanic ridges and seamount chains, but the origin of their associated mantle plumes is debated. Reduced seismicity on the southern Mid‐Atlantic Ridge (MAR) suggests anomalously ductile thermomechanical conditions at 52°S and 47.5°S. These low seismicity patches extend 120–560 km along‐axis, and correspond with axial high spreading ridge morphology, geochemical anomalies, and mantle wave speed patterns likely associated with the Shona and Discovery plumes. Bathymetric data show that the northern extent of the Shona swell is associated with increased volcanism, elevated axial bathymetry, and a series of northward‐propagating rifts, with the overall swell geometry suggesting a buoyancy flux of 0.4–0.5 Mg s−1. The nearby Bouvet Island may be a product of a branch of the larger Shona plume swell, which has influenced crustal accretion on the southern MAR for the past 24 million years.

In 1983, Andrea Dworkin gave a speech entitled “I Want a Twenty-Four-Hour Truce during Which There Is No Rape,” in which she argued that the only way to put an end to the culture of rape in society is for men to take responsibility for it. The view that it is up to men to dismantle the culture of rape—including “friendly” men, who do not actively endorse and perpetuate this culture—might have been considered radical at the time, but the same is no longer true today. Dworkin’s view, or something very close to it, is now garnering widespread attention and credibility. The purpose of this article is to find a philosophical theory of responsibility that can vindicate and elucidate Dworkin’s claims. In order to do so, I develop a view that combines Zheng’s role-ideal model of responsibility with Witt’s conception of gender as a mega social role. I argue that by combining these accounts we find a philosophically satisfying theory of what it means to say, with Dworkin, that men are responsible for the culture of rape.

Abstract Characterizing human movement is essential for understanding movement disorders, evaluating progress in rehabilitation, or even analyzing how a person adapts to the use of assistive devices. Thanks to the improvement of motion capture technology, recording human movement has become increasingly accessible and easier to conduct. Over the last few years, multiple methods have been proposed for characterizing inter-joint coordination. Despite this, there is no real consensus regarding how these different inter-joint coordination metrics should be applied when analyzing the coordination of discrete movement from kinematic data. In this work, we consider 12 coordination metrics identified from the literature and apply them to a simulated dataset based on reaching movements using two degrees of freedom. Each metric is evaluated according to eight criteria based on current understanding of human motor control physiology, i.e, each metric is graded on how well it fulfills each of these criteria. This comparative analysis highlights that no single inter-joint coordination metric can be considered as ideal. Depending on the movement characteristics that one seeks to understand, one or several metrics among those reviewed here may be pertinent in data analysis. We propose four main factors when choosing a metric (or a group of metrics): the importance of temporal vs. spatial coordination, the need for result explainability, the size of the dataset, and the computational resources. As a result, this study shows that extracting the relevant characteristics of inter-joint coordination is a scientific challenge and requires a methodical choice. As this preliminary study is conducted on a limited dataset, a more comprehensive analysis, introducing more variability, could be complementary to these results.

Introduction: Successfully completing the Institute of Biomedical Science (IBMS) registration portfolio is essential to becoming a Health and Care Professions Council (HCPC) registered Biomedical Scientist. In the West Midlands, a unique collaboration between four universities (Aston, Wolverhampton, Coventry, and Keele) and local NHS Trusts supports student placements and portfolio development. The universities support Training Officers in delivering components of the registration portfolio through the delivery of eight combined placement workshops. These have been designed to align to the IBMS registration portfolio and help students meet the HCPC Standards of Proficiency. This study aimed to evaluate the effectiveness of a redesigned workshop where students generated and presented medical case studies to peers, academics, and training leads.Materials and Methods: The three phases of the case study intervention included a pre-intervention survey, academic-led sessions focussing on medical case presentations and delivery of the presentation followed by a post-intervention survey.Results: Analysing survey responses pre- and post-intervention, students demonstrated enhanced confidence in their understanding of clinical conditions (p

Undergraduate Biomedical Science dissertations are the culmination of a student’s academic journey and allow students to refine technical proficiencies, experimental design and data analysis. However, traditional dissertation projects may not fully meet the requirements of diverse student populations and employer’s needs. This research project aims to assess the effectiveness of modifying the assessment format for final-year projects, incorporating elements such as lay summaries, project proposals, scientific research papers, and oral poster defences. The objective was to cultivate higher-order critical thinking skills and enhance written and verbal communication competencies, in addition to developing a suite of transferable skills which are highly sought by employers. Quantitative data were primarily generated via end-of-module feedback reports and the module satisfaction survey. Students rated their confidence in a suite of transferable skills pre and post-completion of the project module using a four-point Likert scale. Staff perceptions (n = 30) and module board reports were also evaluated. For all data, a paired t-test for related groups was conducted. Thematic analysis was used to analyse qualitative data using the Braun and Clark Framework. The end-of-module feedback was overwhelmingly positive with all students agreeing that they were satisfied with the module. Students reported a statistically significant increase in confidence within 11 transferable skills which are considered core within the industry, for example, critical thinking, problem-solving and time management. Furthermore, the mean module mark increased following the module redesign from 66.3% ± 0.2% in 2019 to 70.9% ± 0.6% in 2020 (p ≤ 0.05). Staff provided free text comments, reporting an overall improvement in the module, a reduction in workload and a better teaching experience. Students exhibited appreciation of the new module structure, assessment suit and creative liberty within the projects. The redesigned project module enhanced the teaching experience for staff, whilst students appreciated the diverse range of projects and assessments that featured shorter word limits and a creative flair. Universities must reinvent undergraduate dissertations to equip students with essential employability skills.

Theorists of human evolution are interested in understanding major shifts in human behavioural capacities (e.g. the creation of a novel technological industry, such as the Acheulean). This task faces empirical challenges arising both from the complexity of these events and the time-depths involved. However, we also confront issues of a more philosophical nature, such as how to best think about causation and explanation. This article considers such fundamental questions from the perspective of a prominent theory of causation in the philosophy of science literature, namely, the interventionist theory of causation. A signature feature of this framework is its recognition of a family of distinct types of causes. We set out several of these causal notions and show how they can contribute to explaining transitions in human behavioural complexity. We do so, first, in a preliminary way, and then in a more detailed way, taking the origins of behavioural modernity as our extended case study. We conclude by suggesting some ways in which the approach developed here might be elaborated and extended.

Modern and effective patient care requires specialist healthcare professionals working together. Interprofessional learning (IPL) seeks to provide opportunities for different healthcare disciplines to learn with, from and about each other. This study focused on the delivery and evaluation of a cytomegalovirus (CMV) case study workshop to facilitate IPL between two Health and Care Professions Council (HCPC) regulated courses: Biomedical Science and Audiology. The 2 h online workshop consisted of 1) defining the roles, responsibilities and skills of the two healthcare professions, 2) the structure of the Biomedical Science and Audiology departments, 3) routes to HCPC registration, 4) core curriculum of both degree programmes and 5) interpreting interdisciplinary data related to a CMV patient case. The workshop was interactive, with the virtual learning environment promoting peer discussions and the use of online polling. Student responses were collected through an online questionnaire. A total of 108 respondents completed a post-event survey and Mann-Whitney U tests revealed there were no significant differences in the responses between the two student cohorts in response to each of the survey statements (p > 0.05). A total of 82.4% of students agreed that they need to know the role of other healthcare professionals for their future practice, whilst 84.2% agreed that the CMV case study was a good format to facilitate effective IPL. A total of 93.5% of respondents recognised the importance of both professions in diagnosing a patient with CMV. Thematic analysis identified four common themes, including appreciation of shared roles, recognition of similarities in registration pathways, working together to provide holistic patient care and the role of clinicians in the patient journey. This novel collaboration between Biomedical Science and Audiology facilitated effective IPL whilst meeting the interprofessional education HCPC requirements. Collaborative working is an essential component of delivering effective patient care and allied healthcare degrees need to provide opportunities within their curriculum to foster this. We hope this study encourages other higher education institutes to expand and develop their current IPL activities to include a broader spectrum of healthcare courses.

Abstract Oceanic transform faults connect spreading centers and are imprinted with previous tectonic events. However, their tectonic interactions are not well understood due to limited observations. The Discovery transform fault system at 4°S, East Pacific Rise (EPR), represents a young transform system, offering a unique opportunity to study the interplay between faulting and other tectonic events at an early phases of an oceanic transform system. Discovery regularly hosts M5–6 characteristic earthquakes, and the seafloor north of Discovery includes a 35 km‐long rift zone that records a complex history of rifting, faulting and volcanism, suggesting that the transform faults likely interact with regional tectonic activity. We apply a machine‐learning enabled workflow to locate 21,391 earthquakes recorded during a 1‐year ocean bottom seismometer experiment in 2008. Our results indicate that seismicity on the western Discovery fault is separated into seven patches with distinct aseismic and seismic slip modes. Additionally, we observe a patch of off‐fault seismicity near where seafloor abyssal hills intersect the rift zone. This seismicity may have been caused by varying opening rates as spreading rate decreases from north to south in the rift zone. Our findings suggest that the Discovery system is still evolving, and that system equilibrium has not been reached between rifting and faulting. These results reflect the complex yet rarely observed interactions between fault slip, plate rotation, and rifting which are likely ubiquitous at oceanic transform systems.

Abstract Fissures and faults provide insight into how plate separation is accommodated by magmatism and brittle deformation during crustal accretion. Although fissure and fault geometry can be used to quantify the spreading process at mid‐ocean ridges, accurate measurements are rare due to insufficiently detailed mapping data. Here, fissures and faults at the fast‐spreading 9°50′N segment of the East Pacific Rise were mapped using bathymetric data collected at 1‐m horizontal resolution by autonomous underwater vehicle Sentry. Fault dip estimates from the bathymetric data were calibrated using co‐registered near‐bottom imagery and depth transects acquired by remotely operated vehicle Jason. Fissures are classified as either eruptive or non‐eruptive (i.e., cracks). Tectonic strain estimated from corrected fault heaves suggests that faulting plays a negligible role in the plate separation on crust younger than 72 kyr (2 km from the ridge are spatially associated with off‐axis lower‐crustal magma lenses identified in multichannel seismic data. Deep, closely spaced fissures overlie a relatively shallow portion of the axial magma lens. The width of on‐axis fissures and inferred subsurface dike geometry imply a ∼9‐year long diking recurrence interval to fully accommodate plate spreading, which is broadly consistent with cycle intervals obtained from estimates of melt extraction rates, eruption volumes, and spreading rate.

Abstract This study analyzes up‐to‐date gravity data in the Galapagos triple junction region to understand crustal structure and melt distribution beneath the propagating Cocos‐Nazca spreading center (CNSC). Application of a standard thermal model to the mantle Bouguer gravity anomaly (MBA) does not appear to result in a realistic crustal thickness in this region. The cross‐CNSC MBA profiles flatten and axial values increase from east toward the western end of the CNSC. A simple smoothing filter applied to the standard thermal model with different filter widths can explain the progressive flattening of the MBA and is interpreted as different distribution widths (concentrations) of partial melt in the mantle. The east‐west residual MBA gradient along the CNSC is similar to the east flank of the East Pacific Rise (EPR), suggesting that the along‐CNSC gradient could partly reflect the shallow mantle properties associated with the EPR.

Estimation of chlorophyll (CHL) using ocean colour remote sensing (OCRS) signals in coastal waters is difficult due to the presence of two other constituents altering the light signal: coloured dissolved organic material (CDOM) and mineral suspended sediments (MSS). Artificial neural networks (NNs) have the capacity to deal with signal complexity and are a potential solution to the problem. Here NNs are developed to operate on two datasets replicating MODIS Aqua bands simulated using Hydrolight 5.2. Artificial noise is added to the simulated signal to improve realism. Both datasets use the same ranges of in water constituent concentrations, and differ by the type of logarithmic concentration distributions. The first uses a Gaussian distribution to simulate samples from natural water conditions. The second uses a flat distribution and is intended to allow exploration of the impact of undersampling extremes at both high and low concentrations in the Gaussian distribution. The impact of the concentration distribution structure is assessed and no benefits were found by switching to a flat distribution. The normal distribution performs better because it reduces the number of low concentration samples that are relatively difficult to resolve against varying concentrations of other constituents. In this simulated environment NNs have the capacity to estimate CHL with outstanding performance compared to real in situ algorithms, except for low values when other constituents dominate the light signal in coastal waters. CDOM and MSS can also be predicted with very high accuracies using NNs. It is found that simultaneous retrieval of all three constituents using multitask learning (MTL) does not provide any advantage over single parameter retrievals. Finally it is found that increasing the number of wavebands generally improves NN performance, though there appear to be diminishing returns beyond ∼8 bands. It is also shown that a smaller number of carefully selected bands performs better than a uniformly distributed band set of the same size. These results provide useful insight into future performance for NNs using hyperspectral satellite sensors and highlight specific wavebands benefits.

Abstract Volcanic seamount chains on the flanks of mid‐ocean ridges record variability in magmatic processes associated with mantle melting over several millions of years. However, the relative timing of magmatism on individual seamounts along a chain can be difficult to estimate without in situ sampling and is further hampered by Ar40/Ar39 dating limitations. The 8°20’N seamount chain extends ∼170 km west from the fast‐spreading East Pacific Rise (EPR), north of and parallel to the western Siqueiros fracture zone. Here, we use multibeam bathymetric data to investigate relationships between abyssal hill formation and seamount volcanism, transform fault slip, and tectonic rotation. Near‐bottom compressed high‐intensity radiated pulse, bathymetric, and sidescan sonar data collected with the autonomous underwater vehicle Sentry are used to test the hypothesis that seamount volcanism is age‐progressive along the seamount chain. Although sediment on seamount flanks is likely to be reworked by gravitational mass‐wasting and current activity, bathymetric relief and Sentry vehicle heading analysis suggest that sedimentary accumulations on seamount summits are likely to be relatively pristine. Sediment thickness on the seamounts' summits does not increase linearly with nominal crustal age, as would be predicted if seamounts were constructed proximal to the EPR axis and then aged as the lithosphere cooled and subsided away from the ridge. The thickest sediments are found at the center of the chain, implying the most ancient volcanism there, rather than on seamounts furthest from the EPR. The nonlinear sediment thickness along the 8°20’N seamounts suggests that volcanism can persist off‐axis for several million years.

Upper limb exoskeletons may confer significant mechanical advantages across a range of tasks. The potential consequences of the exoskeleton upon the user’s sensorimotor capacities however, remain poorly understood. The purpose of this study was to examine how the physical coupling of the user’s arm to an upper limb exoskeleton influenced the perception of handheld objects. In the experimental protocol, participants were required to estimate the length of a series of bars held in their dominant right hand, in the absence of visual feedback. Their performance in conditions with an exoskeleton fixed to the forearm and upper arm was compared to conditions without the upper limb exoskeleton. Experiment 1 was designed to verify the effects of attaching an exoskeleton to the upper limb, with object handling limited to rotations of the wrist only. Experiment 2 was designed to verify the effects of the structure, and its mass, with combined movements of the wrist, elbow, and shoulder. Statistical analysis indicated that movements performed with the exoskeleton did not significantly affect perception of the handheld object in experiment 1 (BF01 = 2.3) or experiment 2 (BF01 = 4.3). These findings suggest that while the integration of an exoskeleton complexifies the architecture of the upper limb effector, this does not necessarily impede transmission of the mechanical information required for human exteroception.

Abstract Seafloor volcanic eruptions are difficult to directly observe due to lengthy eruption cycles and the remote location of mid‐ocean ridges. Volcanic eruptions in 2005–2006 at 9°50′N on the East Pacific Rise have been well documented, but the lava volume and flow extent remain uncertain because of the limited near‐bottom bathymetric data. We present near‐bottom data collected during 19 autonomous underwater vehicle (AUV) Sentry dives at 9°50′N in 2018, 2019, and 2021. The resulting 1 m‐resolution bathymetric grid and 20 cm‐resolution sidescan sonar images cover 115 km2, and span the entire area of the 2005–2006 eruptions, including an 8 km2 pre‐eruption survey collected with AUV ABE in 2001. Pre‐ and post‐eruption surveys, combined with sidescan sonar images and seismo‐acoustic impulsive events recorded during the eruptions, are used to quantify the lava flow extent and to estimate changes in seafloor depth caused by lava emplacement. During the 2005–2006 eruptions, lava flowed up to ∼3 km away from the axial summit trough, covering an area of ∼20.8 km2; ∼50% larger than previously thought. Where pre‐ and post‐eruption surveys overlap, individual flow lobes can be resolved, confirming that lava thickness varies from ∼1 to 10 m, and increases with distance from eruptive fissures. The resulting lava volume estimate indicates that ∼57% of the melt extracted from the axial melt lens probably remained in the subsurface as dikes. These observations provide insights into recharge cycles in the subsurface magma system, and are a baseline for studying future eruptions at the 9°50′N area.

Background Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. Methods We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. Results We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67–82]), than encephalopathy (54% [42–65]). Intensive care use was high (38% [35–41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27–32]. The hazard of death was comparatively lower for patients in the WHO European region. Interpretation Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission.

Understanding and quantifying inter-joint coordination is valuable in several domains such as neurorehabilitation, robot-assisted therapy, robotic prosthetic arms, and control of supernumerary arms. Inter-joint coordination is often understood as a consistent spatiotemporal relation among kinematically redundant joints performing functional and goal-oriented movements. However, most approaches in the literature to investigate inter-joint coordination are limited to analysis of the end-point trajectory or correlation analysis of the joint rotations without considering the underlying task; e.g., creating a desirable hand movement toward a goal as in reaching motions. This work goes beyond this limitation by taking a model-based approach to quantifying inter-joint coordination. More specifically, we use the weighted pseudo-inverse of the Jacobian matrix and its associated null-space to explain the human kinematics in reaching tasks. We propose a novel algorithm to estimate such Inverse Kinematics weights from observed kinematic data. These estimated weights serve as a quantification for spatial inter-joint coordination; i.e., how costly a redundant joint is in its contribution to creating an end-effector velocity. We apply our estimation algorithm to datasets obtained from two different experiments. In the first experiment, the estimated Inverse Kinematics weights pinpoint how individuals change their Inverse Kinematics strategy when exposed to the viscous field wearing an exoskeleton. The second experiment shows how the resulting Inverse Kinematics weights can quantify a robotic prosthetic arm's contribution (or the level of assistance).

Solar flare electron acceleration is an efficient process, but its properties (mechanism, location) are not well constrained. Via hard X-ray (HXR) emission, we routinely observe energetic electrons at the Sun, and sometimes we detect energetic electrons in interplanetary space. We examine if the plasma properties of an acceleration region (size, temperature, density) can be constrained from in situ observations, helping to locate the acceleration region in the corona, and infer the relationship between electrons observed in situ and at the Sun. We model the transport of energetic electrons, accounting for collisional and non-collisional effects, from the corona into the heliosphere (to 1.0 au). In the corona, electrons are transported through a hot, over-dense region. We test if the properties of this region can be extracted from electron spectra (fluence and peak flux) at different heliospheric locations. We find that cold, dense coronal regions significantly reduce the energy at which we see the peak flux and fluence for distributions measured out to 1.0 au, the degree of which correlates with the temperature and density of plasma in the region. Where instrument energy resolution is insufficient to differentiate the corresponding peak values, the spectral ratio of [7–10) to [4–7) keV can be more readily identified and demonstrates the same relationship. If flare electrons detected in situ are produced in, and/or transported through, hot, over-dense regions close to HXR-emitting electrons, then this plasma signature should be present in their lower-energy spectra (1–20 keV), observable at varying heliospheric distances with missions such as Solar Orbiter.

Aedes aegypti mosquitoes are the principal vectors of dengue and continue to pose a threat to human health, with ongoing urbanization, climate change, and trade all impacting the distribution and abundance of this species. Hot periods are becoming increasingly common and their impacts on insect mortality have been well established, but they may have even greater impacts on insect fertility. In this study, we investigated the impacts of high temperatures on Ae. aegypti fertility both within and across generations. Mosquitoes developing under elevated temperatures exhibited higher critical thermal maxima (CTmax) reflecting developmental acclimation, but their fertility declined with increasing developmental temperature. In females, elevated developmental temperatures decreased fecundity while in males it tended to decrease egg hatch proportions and the proportion of individuals producing viable offspring. Rearing both sexes at 35°C increased fecundity in the subsequent generation but effects of elevated temperatures persisted across gonotrophic cycles within the same generation. Moreover, exposure of adults to 35°C further decreased fertility beyond the effects of developmental temperature alone. These findings highlight sub-lethal impacts of elevated temperatures on Ae. aegypti fertility and plastic responses to thermal stress within and across generations. This has significant implications for predicting the distribution and abundance of mosquito populations thriving in increasingly warmer environments., (© 2025. Published by The Company of Biologists.)

Aedes aegypti mosquitoes are well adapted to dry climates and can retain their eggs for extended periods in the absence of suitable habitat. Wolbachia strains transferred from other insects to mosquitoes can be released to combat dengue transmission by blocking virus replication and spreading through populations, but host fitness costs imposed by Wolbachia , particularly under some environments, can impede spread. We, therefore, assessed the impact of two Wolbachia strains being released for dengue control ( w AlbB and w MelM) on fecundity and egg viability following extended egg retention (up to 24 days) under laboratory conditions. Egg viability following retention decreased to a greater extent in females carrying w MelM compared to uninfected or w AlbB females. Fertility fully recovered in uninfected females following a second blood meal after laying retained eggs, while w MelM females experienced only partial recovery. Effects of w MelM on egg retention were similar regardless of whether females were crossed to uninfected or w MelM males, suggesting that fitness costs were triggered by Wolbachia presence in females. The fecundity and hatch proportions of eggs of w MelM females declined with age, regardless of whether females used stored sperm or were recently inseminated. Costs of some Wolbachia strains during egg retention may affect the invasion and persistence of Wolbachia in release sites where larval habitats are scarce and/or intermittent.IMPORTANCE Wolbachia mosquito releases are expanding around the world with substantial impacts on dengue transmission. Releases have succeeded in many locations, but the establishment of Wolbachia has been challenging in some environments, and the factors contributing to this outcome remain unresolved. Here, we explore the effects of Wolbachia on a novel trait, egg retention, which is likely to be important for the persistence of mosquito populations in locations with intermittent rainfall. We find substantial impacts of the Wolbachia strain w MelM on the quality of retained eggs but not the w AlbB strain. This cost is driven by the Wolbachia infection status of the female and can partially recover following a second blood meal. The results of our study may help to explain the difficulty in establishing Wolbachia strains at some field release sites and emphasize the need to characterize Wolbachia phenotypes across a variety of traits and strains.

Previous studies suggest that patients with diabetic peripheral neuropathy (DPN) frequently do not receive the minimum effective doses of a gabapentinoid according to guidance from national organizations. There is opportunity to assess the implementation of pharmacist intervention for patients not meeting minimum effective gabapentinoid dosing for DPN. This prospective, single site quality improvement project was conducted at a primary care clinic and included patients with DPN prescribed a gabapentinoid by their primary care provider (PCP) at a dose lower than minimum effective dosing. Pharmacists assessed patient-reported pain ratings, adverse effects, and renal function for appropriate dosing and titrated to minimum effective dosing based on clinical judgment. All patients that were followed through week 13 had a clinically significant improvement in pain. No patients met a 50% reduction in patient-reported pain rating scales on guidance-directed minimum effective dosing. No patients were able to meet the minimum effective dose. The majority of patients declined pharmacist services due to neuropathy being controlled on the current gabapentinoid dose. This study supports the ability for pharmacists to assess patient specific factors for adequate dosing, titration, and deprescribing recommendations for analgesic medications in diabetic peripheral neuropathy.

There is increasing interest in exploring how endosymbionts could be useful in pest control, including in aphids, which can carry a diversity of endosymbionts. Endosymbionts often have a large impact on host traits, and their presence can be self-sustaining. Identifying useful host-endosymbiont combinations for pest control is facilitated by the transfer of specific endosymbionts into target species, particularly if the species lacks the endosymbiont. Here, we complete a comprehensive literature review, which included 56 relevant papers on endosymbiont transfer experiments in aphids, to uncover factors that might influence transfer success. We then report on our own microinjection attempts of diverse facultative endosymbionts from a range of donor species into three agriculturally important aphid species as recipients: the green peach aphid (Myzus persicae), bird cherry-oat aphid (Rhopalosiphum padi), and Russian wheat aphid (Diuraphis noxia). Combining this information, we consider reasons that impact the successful establishment of lines carrying transferred endosymbionts. These include a lack of stability in donors, deleterious effects on host fitness, the absence of plant-based (versus vertical) transmission, high genetic variation in the endosymbiont, and susceptibility of an infection to environmental factors. Taking these factors into account should help in increasing success rates in future introductions., (© 2024 The Author(s). Environmental Microbiology published by John Wiley & Sons Ltd.)

Wolbachia, an endosymbiotic bacterium, relies on nutrients from its host to complete its life cycle. The presence of Wolbachia strain wAlbB in the mosquito Aedes aegypti during egg or larval stages affects the host's development, leading to the absence of developed and visible ovaries in adult mosquito females. In this study, we investigated the impacts of egg quiescence and Wolbachia infection on lipid profiles of adult Ae. aegypti females, and discerned the role of ovaries in lipid synthesis in the reproductive process. The lipidomes of Wolbachia infected and uninfected female individuals at various developmental stages were quantitatively analyzed by LC-MS/MS. Lipidomic change patterns were systematically further investigated in wAlbB-infected fertile females and infertile females following blood feeding. Prolonged egg quiescence induced a shortage of acyl-carnitine (CAR) and potentially impacted some molecules of diacyl-phospholipid (diacyl-PL) and sphingolipid (SL) in young adult mosquitoes. After the first gonotrophic cycle, infertile females accumulated more CAR and lyso-phospholipid (lyso-PL) than fertile females. Then in the second gonotrophic cycle, the patterns of different lipid groups remained similar between fertile and infertile females. Only a small proportion of molecules of triglyceride (TG), phospholipid (lyso-PL and diacyl-PL) and ceramide (Cer) increased exclusively in fertile females from 0 h to 16 h post blood meal, suggesting that the generation or prescence of these lipids rely on ovaries. In addition, we found cardiolipins (CL) might be impacted by Wolbachia infection at the egg stage, and infected mosquitoes also showed distinct patterns between fertile and infertile females at their second gonotrophic cycle. Our study provides new insights into the long-term influence of Wolbachia on lipid profiles throughout various life stages of mosquitoes. Additionally, it suggests a role played by ovaries in lipid synthesis during mosquito reproduction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aim: This study aims to identify demographic factors, area-based social determinants of health (SDOH), and clinical features associated with medical decision-making after pediatric out-of-hospital cardiac arrest (OHCA)., Methods: This is a retrospective, exploratory, descriptive analysis of patients < 18 years old admitted to the pediatric intensive care unit (ICU) after OHCA from 2011 to 2022 (n = 217) at an urban tertiary care, free-standing children's hospital. Outcomes of interest included: (1) whether a new advance care plan (ACP) (defined as a written advance directive including do not resuscitate and/or do not intubate) was ordered during hospitalization, and (2) whether the patient was discharged with new medical technology (defined as tracheostomy and/or feeding tube). Logistic regression models identified features associated with these outcomes., Results: Of the 217 patients, 78 patients (36%) had a new ACP placed during their admission. Of the survivors, 26% (27/102) were discharged home with new medical technology. Factors associated with ACP were greater change in Pediatric Cerebral Performance Category (PCPC) score (aOR = 1.49, 95% CI [1.28-1.73], p-value < 0.001) and palliative care consultation (aOR = 2.39, 95% CI [1.16-4.89], p-value 0.018). Factors associated with new medical technology were lower change in PCPC score (aOR = 0.76, 95% C.I. [0.61-0.95], p-value = 0.015) and palliative care consultation (aOR = 7.07, 95% CI [3.01-16.60], p-value < 0.001). There were no associations between area-based SDOH and outcomes., Conclusions: Understanding factors associated with decision-making related to ACP after OHCA is critical to optimize counseling for families. Multi-institutional studies are warranted to identify whether these findings are generalizable., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Myzus persicae, a serious sap-sucking pest of a large variety of host plants in agriculture, is traditionally controlled using chemical insecticides but there is interest in using biopesticides as restrictions are increasingly placed on the use of broad-spectrum pesticides., Results: Here, we show that in Petri dish experiments, high concentrations of the fungal entomopathogen Beauveria bassiana led to rapid mortality of M. persicae, although at a low concentration (1 × 10 4 conidia mL -1 ) there is a hormetic effect in which survival and fecundity are enhanced. Hormetic effects persisted across a generation with reduced development time and increased fecundity in the offspring of M. persicae exposed to B. bassiana. The whole-plant experiment points to a hormetic effect being detected in two out of three tested lines. The impact of these effects might also depend on whether M. persicae was transinfected with the endosymbiont Rickettsiella viridis, which decreases fecundity and survival compared with aphids lacking this endosymbiont. This fecundity cost was ameliorated in the generation following exposure to the entomopathogen., Conclusion: Although B. bassiana is effective in controlling M. persicae especially at higher spore concentrations, utilization of this entomopathogen requires careful consideration of hormetic effects at lower spore concentrations, and further research to optimize its application for sustainable agriculture is recommended. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Objective: Our aim was to confirm whether extreme hyperoxemic events had been associated with excess mortality in our diverse critical care population., Methods: Retrospective analysis of 9 years of data collected in the pediatric and cardiothoracic ICUs in Children's Hospital Los Angeles was performed. The analysis was limited to those mechanically ventilated for at least 24 h, with at least 1 arterial blood gas measurement. An extreme hyperoxemic event was defined as a PaO 2 of ≥300 torr. Multivariable logistic regression was used to assess the association of extreme hyperoxemia events and mortality, adjusting for confounding variables. Selected a-priori, these were Pediatric Risk of Mortality III predicted mortality, general or cardiothoracic ICU, number of blood gas measurements, as well as an abnormal blood gas measurements (pH < 7.25, pH > 7.45, and PaO 2  < 50 torr)., Results: There were 4,003 admissions included with a predicted mortality of 7.1% and an actual mortality of 9.7%. Their care was associated with 75,129 blood gas measurements, in which abnormal measurements were common. With adjustments for these covariates, any hyperoxemic event was associated with excess mortality ( p  < 0.001). Excess mortality increased with multiple hyperoxemic events ( p  < 0.046). Additionally, treatment resulting in SpO 2  > 98% markedly increased the risk of a hyperoxemic event., Conclusion: Retrospective analysis of critical care admissions showed that extreme hyperoxemic events were associated with higher mortality. Supplemental oxygen levels resulting in SpO 2  > 98% should be avoided., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Bachman, Newth, Ross, Patel and Bhalla.)

Wolbachia continue to be reported in species previously thought to lack them, particularly Aedes aegypti mosquitoes. The presence of Wolbachia in this arbovirus vector is considered important because releases of mosquitoes with transinfected Wolbachia are being used around the world to suppress pathogen transmission and these efforts depend on a lack of Wolbachia in natural populations of this species. We previously assessed papers reporting Wolbachia in natural populations of Ae . aegypti and found little evidence that seemed convincing. However, since our review, more and more papers are emerging on Wolbachia detections in this species. Our purpose here is to evaluate these papers within the context of criteria we previously established but also new criteria that include the absence of releases of transinfections within the local areas being sampled which has contaminated natural populations in at least one case where novel detections have been reported. We also address the broader issue of Wolbachia detection in other insects where similar issues may arise which can affect overall estimates of this endosymbiont more generally. We note continuing shortcomings in papers purporting to find natural Wolbachia in Ae . aegypti which are applicable to other insects as well., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Bacteria sense changes in their environment and transduce signals to adjust their cellular functions accordingly. For this purpose, bacteria employ various sensors feeding into multiple signal transduction pathways. Signal recognition by bacterial sensors is studied mainly in a few model organisms, but advances in genome sequencing and analysis offer new ways of exploring the sensory repertoire of many understudied organisms. The human gut is a natural target of this line of study: it is a nutrient-rich and dynamic environment and is home to thousands of bacterial species whose activities impact human health. Many gut commensals are also poorly studied compared to model organisms and are mainly known through their genome sequences. To begin exploring the signals human gut commensals sense and respond to, we have designed a framework that enables the identification of sensory domains, prediction of signals that they recognize, and experimental verification of these predictions. We validate this framework's functionality by systematically identifying amino acid sensors in selected bacterial genomes and metagenomes, characterizing their amino acid binding properties, and demonstrating their signal transduction potential.IMPORTANCESignal transduction is a central process governing how bacteria sense and respond to their environment. The human gut is a complex environment with many living organisms and fluctuating streams of nutrients. One gut inhabitant, Escherichia coli , is a model organism for studying signal transduction. However, E. coli is not representative of most gut microbes, and signaling pathways in the thousands of other organisms comprising the human gut microbiota remain poorly understood. This work provides a foundation for how to explore signals recognized by these organisms., Competing Interests: The authors declare no conflict of interest.

The susceptibility of insects to rising temperatures has largely been measured by their ability to survive thermal extremes. However, the capacity for maternally inherited endosymbionts to influence insect heat tolerance has been overlooked. Further, while some studies have addressed the impact of heat on traits like fertility, which can decline at temperatures below lethal thermal limits, none have considered the impact of endosymbionts. Here, we assess the impact of three Wolbachia strains (wRi, wAu and wNo) on the survival and fertility of Drosophila simulans exposed to heat stress during development or as adults. The effect of Wolbachia infection on heat tolerance was generally small and trait/strain specific. Only the wNo infection significantly reduced the survival of adult males after a heat shock. When exposed to fluctuating heat stress during development, the wRi and wAu strains reduced egg-to-adult survival but only the wNo infection reduced male fertility. Wolbachia densities of all three strains decreased under developmental heat stress, but reductions occurred at temperatures above those that reduced host fertility. These findings emphasize the necessity to account for endosymbionts and their effect on both survival and fertility when investigating insect responses to heat stress., (© 2024 The Authors. Environmental Microbiology published by John Wiley & Sons Ltd.)

Objective: Terminal extubation (TE) and terminal weaning (TW) during withdrawal of life-sustaining therapies (WLSTs) have been described and defined in adults. The recent Death One Hour After Terminal Extubation study aimed to validate a model developed to predict whether a child would die within 1 hour after discontinuation of mechanical ventilation for WLST. Although TW has not been described in children, pre-extubation weaning has been known to occur before WLST, though to what extent is unknown. In this preplanned secondary analysis, we aim to describe/define TE and pre-extubation weaning (PW) in children and compare characteristics of patients who had ventilatory support decreased before WLST with those who did not., Design: Secondary analysis of multicenter retrospective cohort study., Setting: Ten PICUs in the United States between 2009 and 2021., Patients: Nine hundred thirteen patients 0-21 years old who died after WLST., Interventions: None., Measurements and Main Results: 71.4% ( n = 652) had TE without decrease in ventilatory support in the 6 hours prior. TE without decrease in ventilatory support in the 6 hours prior = 71.4% ( n = 652) of our sample. Clinically relevant decrease in ventilatory support before WLST = 11% ( n = 100), and 17.6% ( n = 161) had likely incidental decrease in ventilatory support before WLST. Relevant ventilator parameters decreased were F io2 and/or ventilator set rates. There were no significant differences in any of the other evaluated patient characteristics between groups (weight, body mass index, unit type, primary diagnostic category, presence of coma, time to death after WLST, analgosedative requirements, postextubation respiratory support modality)., Conclusions: Decreasing ventilatory support before WLST with extubation in children does occur. This practice was not associated with significant differences in palliative analgosedation doses or time to death after extubation., Competing Interests: Dr. Pringle’s institution received funding from the National Institutes of Health (NIH) (Ul1TR001427); she received support for article research from the NIH. Dr. Winter received support for article research from the LK Whittier Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Lines of Aedes aegypti mosquitoes infected with heritable Wolbachia bacteria are being developed and released for arbovirus control. Coordinated releases of lab-reared Wolbachia mosquitoes have reduced local disease incidence by spreading virus-blocking Wolbachia strains and by crashing mosquito populations through incompatible male releases. The phenotypic effects of Wolbachia are diverse and depend on both genetics and the environment. Accurate assessments of Wolbachia effects in mosquitoes are essential, as such effects can make the difference between success and failure of a Wolbachia release program. This chapter provides guidelines for testing key Wolbachia host effects and transmission in Aedes aegypti: the most important arbovirus vector and the most common target of Wolbachia release programs. The protocols should be useful for evaluating mosquito strains prior to field release., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The barley yellow dwarf virus (BYDV) of cereals is thought to substantially increase the high-temperature tolerance of its aphid vector, Rhopalosiphum padi , which may enhance its transmission efficiency. This is based on experiments with North American strains of BYDV and R. padi . Here, we independently test these by measuring the temperature tolerance, via Critical Thermal Maximum (CTmax) and knockdown time, of Australian R. padi infected with a local BYDV isolate. We further consider the interaction between BYDV transmission, the primary endosymbiont of R. padi ( Buchnera aphidicola ), and a transinfected secondary endosymbiont ( Rickettsiella viridis) which reduces the thermotolerance of other aphid species. We failed to find an increase in tolerance to high temperatures in BYDV-infected aphids or an impact of Rickettsiella on thermotolerance. However, BYDV interacted with R. padi endosymbionts in unexpected ways, suppressing the density of Buchnera and Rickettsiella . BYDV density was also fourfold higher in Rickettsiella -infected aphids. Our findings indicate that BYDV does not necessarily increase the temperature tolerance of the aphid transmission vector to increase its transmission potential, at least for the genotype combinations tested here. The interactions between BYDV and Rickettsiella suggest new ways in which aphid endosymbionts may influence how BYDV spreads, which needs further testing in a field context.

Many mosquito species live close to humans where females feed on human blood. While male mosquitoes do not feed on blood, it has long been recognized that males of some species can be attracted to human hosts. To investigate the frequency of male mosquito attraction to humans, we conducted a literature review and human-baited field trials, as well as laboratory experiments involving males and females of three common Aedes species. Our literature review indicated that male attraction to humans is limited to a small number of species, including Ae. aegypti and Ae. albopictus . In our human-baited field collections, only 4 out of 13 species captured included males. In laboratory experiments, we found that male Ae. notoscriptus and Ae. vigilax showed no attraction to humans, while male Ae. aegypti exhibited persistent attraction for up to 30 min. Both male and female Ae. aegypti displayed similar preferences for different human subjects, suggesting that male Ae. aegypti respond to similar cues as females. Additionally, we found that mosquito repellents applied to human skin effectively repelled male mosquitoes. These findings shed light on mosquito behaviour and have implications for mosquito control programmes, particularly those involving the release or monitoring of the male mosquito population., Competing Interests: We declare we have no competing interests., (© 2023 The Authors.)

There is increasing interest in the use of endosymbionts in pest control, which will benefit from the identification of endosymbionts from potential donor species for transfer to pest species. Here, we screened for endosymbionts in 123 Australian aphid samples across 32 species using 16S DNA metabarcoding. We then developed a qPCR method to validate the metabarcoding data set and to monitor endosymbiont persistence in aphid cultures. Pea aphids (Acyrthosiphon pisum) were frequently coinfected with Rickettsiella and Serratia, and glasshouse potato aphids (Aulacorthum solani) were coinfected with Regiella and Spiroplasma; other secondary endosymbionts detected in samples occurred by themselves. Hamiltonella, Rickettsia and Wolbachia were restricted to a single aphid species, whereas Regiella was found in multiple species. Rickettsiella, Hamiltonella and Serratia were stably maintained in laboratory cultures, although others were lost rapidly. The overall incidence of secondary endosymbionts in Australian samples tended to be lower than recorded from aphids overseas. These results indicate that aphid endosymbionts probably exhibit different levels of infectivity and vertical transmission efficiency across hosts, which may contribute to natural infection patterns. The rapid loss of some endosymbionts in cultures raises questions about factors that maintain them under field conditions, while endosymbionts that persisted in laboratory culture provide candidates for interspecific transfers., (© 2023 The Authors. Environmental Microbiology published by Applied Microbiology International and John Wiley & Sons Ltd.)

Background: Effort of Breathing (EOB) calculations may be a reliable alternative to Work of Breathing (WOB) calculations in which Respiratory Inductance Plethysmography (RIP) replaces spirometry. We sought to compare EOB and WOB measurements in a nonhuman primate model of increasing extrathoracic inspiratory resistance simulating upper airway obstruction (UAO)., Methods: RIP, spirometry, and esophageal manometry were measured in spontaneously breathing, intubated Rhesus monkeys utilizing 11 calibrated resistors randomly applied for 2-min. EOB was calculated breath-by-breath as Pressure Rate Product (PRP) and Pressure Time Product (PTP). WOB was calculated from the Pressure-Volume curve based on spirometry (WOB SPIR ) or RIP flow (WOB RIP )., Results: WOB, PRP and PTP showed similar linear increases when exposed to higher levels of resistive loads. When comparing WOB SPIR to WOB RIP , a similar strong correlation was seen for both signals as resistance increased and there were no statistically significant differences., Conclusion: EOB and WOB parameters utilizing esophageal manometry and RIP, independent of spirometry, showed a strong correlation as a function of increasing inspiratory resistance in nonhuman primates. This allows several potential monitoring possibilities for non-invasively ventilated patients or situations where spirometry is not available., Impact: EOB and WOB parameters showed a strong correlation as a function of increasing inspiratory resistance in nonhuman primates. There was a strong correlation between spirometry-based WOB versus RIP-based WOB. To date, it has remained untested as to whether EOB is a reliable alternative for WOB and if RIP can replace spirometry in these measurements. Our results enable additional potential monitoring possibilities for non-invasively ventilated patients or situations where spirometry is not available. Where spirometry is not available, there is no need to apply a facemask post extubation to a spontaneously breathing, non-intubated infant to make objective EOB measurements., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)