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We present an overview of the UK's Global Sea Ice model configuration version 9 (GSI9), the sea ice component of the latest Met Office Global Coupled model, GC5. The GC5 configuration will, amongst other uses, form the physical basis for the HadGEM3 (Hadley Centre Global Environment Model version 3) climate model and UKESM2 (UK Earth System Model version 2) Earth system model that will provide the Met Office Hadley Centre/UK model contributions to CMIP7 (Coupled Model Intercomparison Project Phase 7). Although UK ocean model configurations have been developed for many years around the NEMO (Nucleus for European Modelling of the Ocean) ocean modelling framework, the GSI9 configuration is the first UK sea ice model configuration to use the new native NEMO sea ice model, SI3 (Sea Ice modelling Integrated Initiative). This replaces the CICE (Community Ice CodE) model used in previous configuration versions. In this paper we document the physical and technical options used within the GSI9 sea ice configuration. We provide details of the implementation of SI3 into the Met Office coupled model and the adaptations required to work with our “conductivity coupling” approach and provide a thorough description of the GC5 coupling methodology. A brief evaluation of sea ice simulated by the GC5 model is included, with results compared to observational references and a previous Global Coupled model version (GC3.1) used for CMIP6, to demonstrate the scientific credibility of the results.

Abstract Future projections of Arctic and Antarctic sea ice suffer from uncertainties largely associated with inter-model spread. Ocean heat transport has been hypothesised as a source of this uncertainty, based on correlations with sea ice extent across climate models. However, a physical explanation of what sets the sea ice sensitivity to ocean heat transport remains to be uncovered. Here, we derive a simple equation using an idealised energy-balance model that captures the emergent relationship between ocean heat transport and sea ice in climate models. Inter-model spread of Arctic sea ice loss depends strongly on the spread in ocean heat transport, with a sensitivity set by compensation of atmospheric heat transport and radiative feedbacks. Southern Ocean heat transport exhibits a comparatively weak relationship with Antarctic sea ice and plays a passive role secondary to atmospheric heat transport. Our results suggest that addressing ocean model biases will substantially reduce uncertainty in projections of Arctic sea ice.

Dissemination of food-borne L. monocytogenes in the host relies on internalin-mediated invasion, but the underlying invasion strategies remain elusive. Here we use live-cell microscopy to follow single cell interactions between individual human cells and L. monocytogenes and elucidate mechanisms associated with internalin B (InlB)-mediated invasion. We demonstrate that whilst a replicative invasion of nonphagocytic cells is a rare event even at high multiplicities of invasion, L. monocytogenes overcomes this by utilising a strategy relaying on PrfA-mediated ActA-based aggregation. We show that L. monocytogenes forms aggregates in extracellular host cell environment, which promote approximately 5-fold more host cell adhesions than the non-aggregating actA-ΔC mutant (which lacks the C-terminus coding region), with the adhering bacteria inducing 3-fold more intracellular invasions. Aggregation is associated with robust MET tyrosine kinase receptor clustering in the host cells, a hallmark of InlB-mediated invasion, something not observed with the actA-ΔC mutant. Finally, we show via RNA-seq analyses that aggregation involves a global adaptive response to host cell environment (including iron depletion), resulting in metabolic changes in L. monocytogenes and upregulation of the PrfA virulence regulon. Overall, our analyses provide new mechanistic insights into internalin-mediated host-pathogen interactions of L. monocytogenes.

Objective: The assessment of primary aldosteronism incorporates adrenal vein sampling (AVS) to lateralize aldosterone excess. Current adrenal vein sampling protocols rely on concurrent cortisol measurements to assess successful cannulation and lateralization and may be inaccurate in the setting of autonomous cortisol secretion. We aimed to compare the measurement of plasma cortisol and metanephrine concentrations to assess cannulation and lateralization during AVS. Design: This is a diagnostic accuracy study in a tertiary referral endocrinology department. Methods: Forty-one consecutive patients with confirmed primary aldosteronism undergoing AVS (49 procedures) were included. None had cortisol autonomy. The use of plasma metanephrine-based ratios were compared with standard cortisol-based ratios to assess cannulation and lateralization during ACTH-stimulated AVS. Results: There was strong agreement between a cortisol selectivity index (SI) ≥5.0 and an adrenal vein (AV) to peripheral vein (PV) plasma metanephrine ratio (AVmet–PVmet) of ≥12.0 to indicate successful cannulation of the AV (n = 117, sensitivity 98%, specificity 89%, positive predictive value (PPV) 95%, negative predictive value (NPV) 94%). There was strong agreement between the standard cortisol-based SI and an AV plasma metanephrine-to-normetanephrine ratio (AVmet–AVnormet) of ≥2.0 to indicate successful cannulation (n = 117, sensitivity 93%, specificity 86%, PPV 94%, NPV 84%). There was strong agreement between the cortisol- or metanephrine-derived lateralization index (LI) > 4.0 for determining lateralization (n = 26, sensitivity 100%, specificity 94.1%, PPV 91.6%, NPV 100%). Conclusions: Ratios incorporating plasma metanephrines provide comparable outcomes to standard cortisol-based measurements for interpretation of AVS. Further studies are required to assess the use of metanephrine-derived ratios in the context of confirmed cortisol autonomy.

Movement sonification has emerged as a promising approach for rehabilitation and motion control. Despite significant advancements in sensor technologies, challenges remain in developing cost-effective, user-friendly, and reliable systems for gait detection and sonification. This study introduces a novel wearable personalised sonification and biofeedback device to enhance movement awareness for individuals with irregular gait and posture. Through the integration of inertial measurement units (IMUs), MATLAB, and sophisticated audio feedback mechanisms, the device offers real-time, intuitive cues to facilitate gait correction and improve functional mobility. Utilising a single wearable sensor attached to the L4 vertebrae, the system captures kinematic parameters to generate auditory feedback through discrete and continuous tones corresponding to heel strike events and sagittal plane rotations. A preliminary test that involved 20 participants under various audio feedback conditions was conducted to assess the system’s accuracy, reliability, and user synchronisation. The results indicate a promising improvement in movement awareness facilitated by auditory cues. This suggests a potential for enhancing gait and balance, particularly beneficial for individuals with compromised gait or those undergoing a rehabilitation process. This paper details the development process, experimental setup, and initial findings, discussing the integration challenges and future research directions. It also presents a novel approach to providing real-time feedback to participants about their balance, potentially enabling them to make immediate adjustments to their posture and movement. Future research should evaluate this method in varied real-world settings and populations, including the elderly and individuals with Parkinson’s disease.

In the past decade groundbreaking new satellite observations of the Arctic sea ice cover have been made, allowing researchers to understand the state of the Arctic sea ice system in greater detail than before. The derived estimates of sea ice thickness are useful but limited in time and space. In this study the first results of a new sea ice data assimilation system are presented. Observations assimilated (in various combinations) are monthly mean sea ice thickness and monthly mean sea ice thickness distribution from CryoSat-2 and NASA daily Bootstrap sea ice concentration. This system couples the Centre for Polar Observation and Modelling's (CPOM) version of the Los Alamos Sea Ice Model (CICE) to the localised ensemble transform Kalman filter (LETKF) from the Parallel Data Assimilation Framework (PDAF) library. The impact of assimilating a sub-grid-scale sea ice thickness distribution is of particular novelty. The sub-grid-scale sea ice thickness distribution is a fundamental component of sea ice models, playing a vital role in the dynamical and thermodynamical processes, yet very little is known of its true state in the Arctic. This study finds that assimilating CryoSat-2 products for the mean thickness and the sub-grid-scale thickness distribution can have significant consequences for the modelled distribution of the ice thickness across the Arctic and particularly in regions of thick multi-year ice. The assimilation of sea ice concentration, mean sea ice thickness and sub-grid-scale sea ice thickness distribution together performed best when compared to a subset of CryoSat-2 observations held back for validation. Regional model biases are reduced: the thickness of the thickest ice in the Canadian Arctic Archipelago (CAA) is decreased, but the thickness of the ice in the central Arctic is increased. When comparing the assimilation of mean thickness with the assimilation of sub-grid-scale thickness distribution, it is found that the latter leads to a significant change in the volume of ice in each category. Estimates of the thickest ice improve significantly with the assimilation of sub-grid-scale thickness distribution alongside mean thickness.

IntroductionMultipurpose prevention technologies (MPTs) combining contraception with HIV prevention offer a promising solution to uptake and adherence challenges faced with oral pre-exposure prophylaxis (PrEP). The Dual Prevention Pill (DPP), which combines oral PrEP with an oral contraceptive pill (OCP), could address unmet need for family planning (FP) and HIV prevention. This study aimed to identify barriers and motivators for DPP uptake to inform the development of a DPP demand generation strategy and broader introduction efforts for MPTs.Materials and methodsQualitative, ethnographic research employing human-centered design techniques was conducted in Kenya, South Africa, and Zimbabwe. A research consortium conducted 45 immersions, 34 key informant interviews, and 12 friendship circles with potential end users, male romantic partners, healthcare providers (HCPs), and cultural commentators. Creative concepts were subsequently co-created and validated in workshops with end users, male partners, and HCPs.ResultsFour major themes emerged. Women struggled to balance personal motivations with societal expectations. Relationship goals strongly influenced sexual and reproductive health decisions, particularly related to financial security and social status. Negative experiences, such as untrustworthy partners, were significant triggers for OCP and PrEP use. Lastly, male partners were concerned about the DPP upending gender norms but held more positive individual attitudes. Five initial audience segments for the DPP were identified: women seeking enjoyment outside of their primary relationship; new mothers adhering to social norms; women wanting to maintain romantic relationships; women at risk of unintended pregnancy; and women with unfaithful partners. Segments informed the development of three communication themes, with the preferred route highlighting the DPP as a tool to prepare for life's unpredictability.DiscussionTo effectively generate demand for the DPP, several strategies should be considered. Connecting with women's diverse identities and goals and celebrating their individuality is crucial. Linking the DPP to relationship goals reframes it as a means to protect relationships rather than a risk. Leveraging negative triggers through targeted media campaigns empowers women to take control of their sexual health during challenging moments. A balance in channel placement is necessary to raise public awareness while using more discrete channels for potentially controversial messages with male partners and wider communities.

The study explores the pedagogical practices employed by ballet instructors for engaging boys in ballet. Inclusive practices for gender non-conforming children in ballet are also considered. Four ballet instructors shared their experiences in semi-structured interviews. Findings indicate that male-focused strategies in both recruitment and pedagogy are prevalent in the field. Participants noted the need for parents to be open to ballet for all genders of children, to value their child's gender expression, and to support the implementation of inclusive studio practices. Recommendations are made for teachers and studios regarding the implementation of gender-inclusive practices and the establishment of welcoming environments for all students.

Sensory-neural studies indicate that children with developmental dyslexia show impairments in processing acoustic speech envelope information. Prior studies suggest that this arises in part from reduced sensory sensitivity to amplitude rise times (ARTs or speech “edges”) in the envelope, accompanied by less accurate neural encoding of low-frequency envelope information. Accordingly, enhancing these characteristics of the speech envelope may enhance neural speech processing in children with dyslexia. Here we applied an envelope modulation enhancement (EME) algorithm to a 10-min story read in child-directed speech (CDS), enhancing ARTs and also enhancing low-frequency envelope information. We compared neural speech processing (as measured using MEG) for the EME story with the same story read in natural CDS for 9-year-old children with and without dyslexia. The EME story affected neural processing in the power domain for children with dyslexia, particularly in the delta band (0.5–4 Hz) in the superior temporal gyrus. This may suggest that prolonged experience with EME speech could ameliorate some of the impairments shown in natural speech processing by children with dyslexia.

Pathogens have developed intricate strategies to overcome the host’s innate immune responses. In this paper we use live-cell microscopy with a single bacterium resolution to follow in real time interactions between the food-borne pathogen L. monocytogenes and host macrophages, a key event controlling the infection in vivo. We demonstrate that infection results in heterogeneous outcomes, with only a subset of bacteria able to establish a replicative invasion of macrophages. The fate of individual bacteria in the same host cell was independent from the host cell and non-cooperative, being independent from co-infecting bacteria. A higher multiplicity of infection resulted in a reduced probability of replication of the overall bacterial population. By use of internalisation assays and conditional probabilities to mathematically describe the two-stage invasion process, we demonstrate that the higher MOI compromises the ability of macrophages to phagocytose bacteria. We found that the rate of phagocytosis is mediated via the secreted Listeriolysin toxin (LLO), while the probability of replication of intracellular bacteria remained constant. Using strains expressing fluorescent reporters to follow transcription of either the LLO-encoding hly or actA genes, we show that replicative bacteria exhibited higher PrfA regulon expression in comparison to those bacteria that did not replicate, however elevated PrfA expression per se was not sufficient to increase the probability of replication. Overall, this demonstrates a new role for the population-level, but not single cell, PrfA-mediated activity to regulate outcomes of host pathogen interactions.

The purpose of this article is to contribute new insights to critical disability and disabled children’s childhood studies that center on the valuing of disabled children’s lives—a guiding purpose in the disability justice movement. We use published findings from the Inclusive Early Childhood Service System project, a longitudinal, institutional ethnography of the ways that families and children are organized around categories of disability, which show social inclusions and exclusions before and during the pandemic. These findings illuminate: (a) institutional flexibility for the purpose of social inclusion and isolation during the pandemic as a result of institutional organization; (b) the impact of institutional decisions around closures, remote programs, and support on families’ choices and self‐determination; and (3) the ways safety is differently applied and rationalized for disabled children allowing institutions to exclude disabled children and families. We use critical disability studies and disabled children’s childhood studies to interpret these findings and position the valuing of disabled children’s lives with a call for disability justice actions.

This essay describes an undergraduate research project involving collaboration among two professors and a student. The result, a business case about the student's workplace, was ultimately presented at an academic conference and is now under consideration for publication. We describe the circumstances that led to the project, its outcomes, and our experiences. In addition, we provide guidance to other professors who wish to promote research collaborations with undergraduate students, referring to principles of assignment design as articulated by John Bean (2011) and the National Council of Teachers of English (2016), among others.

This paper presents the design, development, and feasibility testing of a wearable sonification system for real-time posture monitoring and feedback. The system utilizes inexpensive motion sensors integrated into a compact, wearable package to measure body movements and standing balance continuously. The sensor data is processed through sonification algorithms to generate real-time auditory feedback cues indicating the user’s balance and posture. The system aims to improve movement awareness and physical conditioning, with potential applications in balance rehabilitation and physical therapy. Initial feasibility testing was conducted with a small group of healthy participants performing standing balance tasks with eyes open and closed. Results indicate that the real-time audio feedback improved participants’ ability to maintain balance, especially in the case of closed eyes. This preliminary study demonstrates the potential for wearable sonification systems to provide intuitive real-time feedback on posture and movement to improve motor skills and balance.

Sea ice is composed of discrete units called floes. Observations show that these floes can adopt a range of sizes spanning orders of magnitude, from metres to tens of kilometres. Floe size impacts the nature and magnitude of interactions between the sea ice, ocean, and atmosphere including lateral melt rate and momentum and heat exchange. However, large-scale geophysical sea ice models employ a continuum approach and traditionally either assume floes adopt a constant size or do not include an explicit treatment of floe size. In this study we apply novel observations to analyse two alternative approaches to modelling a floe size distribution (FSD) within the state-of-the-art CICE sea ice model. The first model considered is a prognostic floe size–thickness distribution where the shape of the distribution is an emergent feature of the model and is not assumed a priori. The second model considered, the WIPoFSD (Waves-in-Ice module and Power law Floe Size Distribution) model, assumes floe size follows a power law with a constant exponent. We introduce a parameterisation motivated by idealised models of in-plane brittle fracture to the prognostic model and demonstrate that the inclusion of this scheme enables the prognostic model to achieve a reasonable match against the novel observations for mid-sized floes (100 m–2 km). While neither FSD model results in a significant improvement in the ability of CICE to simulate pan-Arctic metrics in a stand-alone sea ice configuration, larger impacts can be seen over regional scales in sea ice concentration and thickness. We find that the prognostic model particularly enhances sea ice melt in the early melt season, whereas for the WIPoFSD model this melt increase occurs primarily during the late melt season. We then show that these differences between the two FSD models can be explained by considering the effective floe size, a metric used to characterise a given FSD. Finally, we discuss the advantages and disadvantages to these different approaches to modelling the FSD. We note that although the WIPoFSD model is unable to represent potentially important features of annual FSD evolution seen with the prognostic model, it is less computationally expensive and produces a better fit to novel FSD observations derived from 2 m resolution MEDEA imagery, possibly making this a stronger candidate for inclusion in climate models.

The Kelch-like ECH-associated protein 1 (KEAP1) - nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway senses reactive oxygen species and regulates cellular oxidative stress. Inhibiting KEAP1 to activate the NRF2 antioxidant response has been proposed as a promising strategy to treat chronic diseases caused by oxidative stress. Here, we developed a proteolysis targeting chimera (PROTAC) that depletes KEAP1 from cells through the ubiquitin-proteasome pathway. A previously developed KEAP1 inhibitor and thalidomide were incorporated in the heterobifunctional design of the PROTAC as ligands for KEAP1 and CRBN recruitment, respectively. Optimization of the chemical composition and linker length resulted in PROTAC 14 which exhibited potent KEAP1 degradation with low nanomolar DC50 in HEK293T (11 nM) and BEAS-2B (

tag-Targeted Protein Degrader (tTPD) systems are powerful tools for preclinical target validation. Here the authors extend the tTPD platform by developing NanoTACs that degrade NanoLuc tagged substrates and benchmark each tTPD system using an interchangeable tag reporter system.

We present an overview of the UK's Global Sea Ice model configuration version 9 (GSI9), the sea ice component of the latest Met Office Global Coupled model, GC5. The GC5 configuration will, amongst other uses, form the physical basis for the HadGEM3 (Hadley Centre Global Environment Model version 3) climate model and UKESM2 (UK Earth System Model version 2) Earth system model that will provide the Met Office Hadley Centre/UK model contributions to CMIP7 (Coupled Model Intercomparison Project Phase 7). Although UK ocean model configurations have been developed for many years around the NEMO (Nucleus for European Modelling of the Ocean) ocean modelling framework, the GSI9 configuration is the first UK sea ice model configuration to use the new native NEMO sea ice model, SI3 (Sea Ice modelling Integrated Initiative). This replaces the CICE (Community Ice CodE) model used in previous configuration versions. In this paper we document the physical and technical options used within the GSI9 sea ice configuration. We provide details of the implementation of SI3 into the Met Office coupled model and the adaptations required to work with our "conductivity coupling" approach and provide a thorough description of the GC5 coupling methodology. A brief evaluation of sea ice simulated by the GC5 model is included, with results compared to observational references and a previous Global Coupled model version (GC3.1) used for CMIP6, to demonstrate the scientific credibility of the results. [ABSTRACT FROM AUTHOR]

Movement sonification has emerged as a promising approach for rehabilitation and motion control. Despite significant advancements in sensor technologies, challenges remain in developing cost-effective, user-friendly, and reliable systems for gait detection and sonification. This study introduces a novel wearable personalised sonification and biofeedback device to enhance movement awareness for individuals with irregular gait and posture. Through the integration of inertial measurement units (IMUs), MATLAB, and sophisticated audio feedback mechanisms, the device offers real-time, intuitive cues to facilitate gait correction and improve functional mobility. Utilising a single wearable sensor attached to the L4 vertebrae, the system captures kinematic parameters to generate auditory feedback through discrete and continuous tones corresponding to heel strike events and sagittal plane rotations. A preliminary test that involved 20 participants under various audio feedback conditions was conducted to assess the system's accuracy, reliability, and user synchronisation. The results indicate a promising improvement in movement awareness facilitated by auditory cues. This suggests a potential for enhancing gait and balance, particularly beneficial for individuals with compromised gait or those undergoing a rehabilitation process. This paper details the development process, experimental setup, and initial findings, discussing the integration challenges and future research directions. It also presents a novel approach to providing real-time feedback to participants about their balance, potentially enabling them to make immediate adjustments to their posture and movement. Future research should evaluate this method in varied real-world settings and populations, including the elderly and individuals with Parkinson's disease. [ABSTRACT FROM AUTHOR]

In this essay, we tell the story of how a team of English and nursing professors came together to develop curriculum for a mandatory first-semester writing course in the collaborative Bachelor of Science, Nursing (BScN) at Fanshawe College and Western University, both in London, Ontario. The discussion focuses on the implementation of the course at the Fanshawe site. Following a review of literature that has informed our thinking about writing in nursing, we discuss how the team, consisting of both English/writing and nursing faculty, solved curriculum problems to develop an effective course. We also look forward to areas for future development.

Abstract Suppressor of cytokine signaling (SOCS)2 protein is a key negative regulator of the growth hormone (GH) and Janus kinase (JAK)-Signal Transducers and Activators of Transcription (STAT) signaling cascade. The central SOCS2-Src homology 2 (SH2) domain is characteristic of the SOCS family proteins and is an important module that facilitates recognition of targets bearing phosphorylated tyrosine (pTyr) residues. Here we identify an exosite on the SOCS2-SH2 domain which, when bound to a non-phosphorylated peptide (F3), enhances SH2 affinity for canonical phosphorylated ligands. Solution of the SOCS2/F3 crystal structure reveals F3 as an α-helix which binds on the opposite side of the SH2 domain to the phosphopeptide binding site. F3:exosite binding appears to stabilise the SOCS2-SH2 domain, resulting in slower dissociation of phosphorylated ligands and consequently, enhances binding affinity. This biophysical enhancement of SH2:pTyr binding affinity translates to increase SOCS2 inhibition of GH signaling.