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A wooden house frame consists of many different lumber pieces, but because of the regularity of these building blocks, the structure can be designed using straightforward geometrical principles. The design of multicomponent protein assemblies, in comparison, has been much more complex, largely owing to the irregular shapes of protein structures1. Here we describe extendable linear, curved and angled protein building blocks, as well as inter-block interactions, that conform to specified geometric standards; assemblies designed using these blocks inherit their extendability and regular interaction surfaces, enabling them to be expanded or contracted by varying the number of modules, and reinforced with secondary struts. Using X-ray crystallography and electron microscopy, we validate nanomaterial designs ranging from simple polygonal and circular oligomers that can be concentrically nested, up to large polyhedral nanocages and unbounded straight 'train track' assemblies with reconfigurable sizes and geometries that can be readily blueprinted. Because of the complexity of protein structures and sequence-structure relationships, it has not previously been possible to build up large protein assemblies by deliberate placement of protein backbones onto a blank three-dimensional canvas; the simplicity and geometric regularity of our design platform now enables construction of protein nanomaterials according to 'back of an envelope' architectural blueprints.

Spatial demonstratives exist in all languages, but currently there is much debate regarding the parameters that affect their use both between and within languages. In this work, we explore ‘perspective taking' as a means of accounting for variation in demonstrative use both between and within languages. Analysing primary and secondary data, we test the effects of egocentric distance and addressee position on demonstrative production in speakers of two languages with two purportedly different demonstrative systems: English and Japanese. Based on individual differences between speakers, we propose a framework unifying different theoretical accounts of demonstrative systems in which demonstratives require a spatial reference frame to be chosen prior to the application of a range of routines to select the appropriate term in a given context.

Abstract Cytokine release syndrome (CRS), commonly known as cytokine storm, is an acute systemic inflammatory response that is a significant global health threat. Interleukin-6 (IL-6) and interleukin-1 (IL-1) are key pro-inflammatory cytokines involved in CRS and are hence critical therapeutic targets. Current antagonists, such as tocilizumab and anakinra, target IL-6R/IL-1R but have limitations due to their long half-life and systemic anti-inflammatory effects, making them less suitable for acute or localized treatments. Here we present the de novo design of small protein antagonists that prevent IL-1 and IL-6 from interacting with their receptors to activate signaling. The designed proteins bind to the IL-6R, GP130 (an IL-6 co-receptor), and IL-1R1 receptor subunits with binding affinities in the picomolar to low-nanomolar range. X-ray crystallography studies reveal that the structures of these antagonists closely match their computational design models. In a human cardiac organoid disease model, the IL-1R antagonists demonstrated protective effects against inflammation and cardiac damage induced by IL-1β. These minibinders show promise for administration via subcutaneous injection or intranasal/inhaled routes to mitigate acute cytokine storm effects.

Abstract Solar energy harvesting and storage are essential in the future mix of renewable energy technologies. Hierarchical coral‐structured coatings have been shown to yield high solar absorptance in concentrating solar thermal (CST) systems. However, interfacial delamination and scalability challenges owing to material complexity pose significant hurdles for the widespread industrial adoption of these hierarchical CST coatings. Here, a coral‐structured coating is proposed whose black pigments are strongly bonded by titania, which is a material that mitigates interfacial delamination. Importantly, this coating follows a facile deposition procedure suitable for large‐scale solar receivers. The drone‐deposited coating inhibits cation diffusion and maintains a stable solar absorptance of 97.39±0.20% even after long‐term (3000 h) high‐temperature (800∘C) aging. The scalability of developed coating represents a substantial advancement in the implementation of light‐trapping enhancement and maintenance approaches across a wide range of CST applications.

Background Relapse of depression is common and contributes to the overall associated morbidity and burden. We lack evidence-based tools to estimate an individual’s risk of relapse after treatment in primary care, which may help us more effectively target relapse prevention.Objective The objective was to develop and validate a prognostic model to predict risk of relapse of depression in primary care.Methods Multilevel logistic regression models were developed, using individual participant data from seven primary care-based studies (n=1244), to predict relapse of depression. The model was internally validated using bootstrapping, and generalisability was explored using internal–external cross-validation.Findings Residual depressive symptoms (OR: 1.13 (95% CI: 1.07 to 1.20), p

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

Abstract Transdisciplinary co-produced health research and co-designed interventions have the capacity to improve research quality and the relevance, acceptability, and accessibility of healthcare. This approach also helps researchers to address power imbalances to share decision-making with service-users and the public. However, this growing methodology is currently difficult to appraise and develop as detailed sharing of practice is limited. The ‘CO-production of a Nature-based Intervention For children with ADHD study’ (CONIFAS) aimed to create a novel intervention with and for children with attention deficit hyperactivity disorder (ADHD) using co-production and co-design methodologies. This knowledge exchange paper will be of benefit to researchers with aspirations to undertake co-production, especially in the context of working with under-represented groups. Critical reflection on the use of co-production identified that every attempt was made to adequately resource the co-production, share power, value diversity, and develop trust. The team reflected that the re-conceptualisation of the role of the researcher in co-production can be challenging. Whilst the use of models of co-production provides a framework for study development, designing and running the specifics of the workshops, as well as how to effectively engage co-researchers in an equitable way, came from utilising clinical skills, networking, and creativity. These methods are particularly pertinent to involving neurodiverse children and their families who are under-represented in participatory research and in need of bespoke health interventions.

Practitioners routinely use the single leg heel raise (SLHR) to quantify calf function in healthy and injured populations. Despite this, approaches vary and the impact of cueing on SLHR performance and results interpretation in athletesis unknown. The primary aim of this study was to quantify the level of agreement of the cued versus non-cued SLHR tests. The secondary aim was to explore test outcomes and the potential impact of intrinsic factors. Cued and non-cued SLHR tests were conducted in fifty-one Australian football players (23 women, 28 men). Metronome pacing (60 bpm) and five key cues were included in the cued condition. The level of agreement (Bland–Altman) between tests was measured for capacity (repetitions to failure) and asymmetry. Data from 100 legs were included. The non-cued and cued SLHR tests demonstrated poor agreement in both capacity and asymmetry. More repetitions to failure were performed in the non-cued SLHR [Mean (SD) = 33.9 (10.3) vs. 21.9 (5.3), p < 0.001)], and men had greater capacity (36.8 (10.4) vs. 30.3 (9.2), p < 0.001). During the cued SLHR, older players (age ≥ 30 years: −5.1 repetitions, p = 0.01) and Indigenous players (−3.4 repetitions, p = 0.002) and had reduced calf muscle function. Cueing the SLHR test significantly changes the result—outcomes are not comparable or interchangeable with the commonly used non-cued SLHR. These findings can guide practitioners quantifying calf capacity.

De novo enzyme design has sought to introduce active sites and substrate-binding pockets that are predicted to catalyse a reaction of interest into geometrically compatible native scaffolds1,2, but has been limited by a lack of suitable protein structures and the complexity of native protein sequence-structure relationships. Here we describe a deep-learning-based 'family-wide hallucination' approach that generates large numbers of idealized protein structures containing diverse pocket shapes and designed sequences that encode them. We use these scaffolds to design artificial luciferases that selectively catalyse the oxidative chemiluminescence of the synthetic luciferin substrates diphenylterazine3 and 2-deoxycoelenterazine. The designed active sites position an arginine guanidinium group adjacent to an anion that develops during the reaction in a binding pocket with high shape complementarity. For both luciferin substrates, we obtain designed luciferases with high selectivity; the most active of these is a small (13.9 kDa) and thermostable (with a melting temperature higher than 95 °C) enzyme that has a catalytic efficiency on diphenylterazine (kcat/Km = 106 M-1 s-1) comparable to that of native luciferases, but a much higher substrate specificity. The creation of highly active and specific biocatalysts from scratch with broad applications in biomedicine is a key milestone for computational enzyme design, and our approach should enable generation of a wide range of luciferases and other enzymes.

Decades of research have revealed that spatial language is the result of a complex interplay between language-independent, conceptual factors and language-specific forces (e.g., Bowerman, 1996; Johnston & Slobin, 1979; Landau & Jackendoff, 1993; Levinson & Meira 2003; Levinson & Wilkins, 2006). However, currently, a growing body of research acknowledges the importance of a further, much less explored but highly important factor having to do with pragmatic pressures – the general communicative need to convey informative meanings with appropriate levels of required effort (Grice, 1975; Zipf, 1949). This symposium aims to present research documenting the effect of communicative/pragmatic pressures on how spatial language systems are organized, used by speakers of different languages and acquired during development. The contributed papers explore a variety of spatial language phenomena, across many different languages, using a variety of empirical methods and diverse populations of participants.

A higher proportion of students are privately educated in Australia, compared with many other nations. In this paper, we tested the assumption that private schools offer better quality education than public schools. We examined differences in student achievement on the National Assessment Programme: Literacy and Numeracy (NAPLAN) between public, independent, and catholic schools. Cross-sectional regressions using large samples of students (n = 1583-1810) at Years 3, 5, 7 and 9 showed few sector differences in NAPLAN scores in any domain. No differences were evident after controlling for socioeconomic status and prior NAPLAN achievement. Using longitudinal modelling, we also found no sector differences in the rate of growth for reading and numeracy between Year 3 and Year 9. Results indicate that already higher achieving students are more likely to attend private schools, but private school attendance does not alter academic trajectories, thus undermining conceptions of private schools adding value to student outcomes.

Abstract Background Motor coordination concerns are estimated to affect 5%–6% of school‐aged children. Motor coordination concerns have variable impact on children's lives, with gait and balance often affected. Textured insoles have demonstrated positive impact on balance and gait in adults with motor coordination disorders related to disease or the ageing process. The efficacy of textured insoles in children is unknown. Our primary aim was to identify the feasibility of conducting a randomised controlled trial involving children with motor control issues. The secondary aim was to identify the limited efficacy of textured insoles on gross motor assessment balance domains and endurance in children with movement difficulties. Methods An assessor‐blinded, randomised feasibility study. We advertised for children between the ages of 5–12 years, with an existing diagnosis or developmental coordination disorder or gross motor skill levels assessed as 15th percentile or below on a norm‐referenced, reliable and validated scale across two cities within Australia. We randomly allocated children to shoes only or shoes and textured insoles. We collected data across six feasibility domains; demand (recruitment), acceptability (via interview) implementation (adherence), practicality (via interview and adverse events), adaptation (via interview) and limited efficacy testing (6‐min walk test and balance domain of Movement ABC‐2 at baseline and 4 weeks). Results There were 15 children randomised into two groups (eight received shoes alone, seven received shoes and textured insoles). We experienced moderate demand, with 46 potential participants. The insoles were acceptable, however, some parents reported footwear fixture issues requiring modification. The 6‐min walk test was described as problematic for children, despite all but one child completing. Social factors impacted adherence and footwear wear time in both groups. Families reported appointment locations and parking impacting practicality. Underpowered, non‐significant small to moderate effect sizes were observed for different outcome measures. Improvement in balance measures favoured the shoe and insole group, while gait velocity increase favoured the shoe only group. Conclusion Our research indicates that this trial design is feasible with modifications such as recruiting with a larger multi‐disciplinary organisation, providing velcro shoe fixtures and using a shorter timed walk test. Furthermore, progressing to a larger well‐powered randomised control trial is justified considering our preliminary, albeit underpowered, efficacy findings. Trial Registration This trial was retrospectively registered with the Australian and New Zealand Clinical Trial Registration: ACTRN12624000160538.

The health inequities experienced by Aboriginal and Torres Strait Islander peoples, rooted in the historical and ongoing negative impacts of colonisation and disrupted traditional lifestyles, sees higher rates of illness and hospitalisations, increased morbidity and higher premature death rates than other Australians. Nurses represent the majority of Australia’s health workforce and nursing students must have knowledge to provide culturally safe care to Australia’s Aboriginal and Torres Strait Islander peoples. An Aboriginal and Torres Strait Islander Peoples’ Health and Wellbeing unit was developed and introduced into an undergraduate nursing curriculum. This project aimed to determine the effectiveness of the unit content in changing the attitude of nursing students towards care of First Nations peoples. A quasi-experimental design was used and included all undergraduate nursing students commencing this unit in 2020 at one university in Western Australia. Students completed a validated questionnaire prior to engaging with unit learning materials and again at completion of the unit. Complete paired data was available for 339 participants. Results demonstrated statistically significant change in attitude following completion of the unit. Embedding targeted education concerning Aboriginal and Torres Strait Islander peoples’ health and wellbeing positively influences attitudes in caring for this population of patients.

Abstract Pick’s disease (PiD) is a subtype of the tauopathy form of frontotemporal lobar degeneration (FTLD-tau) characterized by intraneuronal 3R-tau inclusions. PiD can underly various dementia syndromes, including primary progressive aphasia (PPA), characterized by an isolated and progressive impairment of language and left-predominant atrophy, and behavioral variant frontotemporal dementia (bvFTD), characterized by progressive dysfunction in personality and bilateral frontotemporal atrophy. In this study, we investigated the neocortical and hippocampal distributions of Pick bodies in bvFTD and PPA to establish clinicopathologic concordance between PiD and the salience of the aphasic versus behavioral phenotype. Eighteen right-handed cases with PiD as the primary pathologic diagnosis were identified from the Northwestern University Alzheimer’s Disease Research Center brain bank (bvFTD, N = 9; PPA, N = 9). Paraffin-embedded sections were stained immunohistochemically with AT8 to visualize Pick bodies, and unbiased stereological analysis was performed in up to six regions bilaterally [middle frontal gyrus (MFG), superior temporal gyrus (STG), inferior parietal lobule (IPL), anterior temporal lobe (ATL), dentate gyrus (DG) and CA1 of the hippocampus], and unilateral occipital cortex (OCC). In bvFTD, peak neocortical densities of Pick bodies were in the MFG, while the ATL was the most affected in PPA. Both the IPL and STG had greater leftward pathology in PPA, with the latter reaching significance (p

Abstract Light trapping enhancement by nanostructures is ubiquitous in engineering applications, for example, in improving highly-efficient concentrating solar thermal (CST) technologies. However, most nano-engineered coatings and metasurfaces are not scalable to large surfaces ( > 100 m2) and are unstable at elevated temperatures ( > 850 °C), hindering their wide-spread adoption in CST. Here, we propose a scalable layer nano-architecture that can significantly enhance the solar absorption of an arbitrary material. Our electromagnetics modelling predicts that the absorptance of cutting-edge light-absorbers can be further enhanced by more than 70%, i.e. relative improvement towards blackbody absorption from a baseline value without the nano-architecture. Experimentally, the nano-architecture yields a solar absorber that is 35% optically closer to a blackbody, even after long-term (1000 h) high-temperature (900 °C) ageing in air. A stable solar absorptance of more than 97.88 ± 0.14% is achieved, to the best of our knowledge, the highest so far reported for these extreme ageing conditions. The scalability of the layer nano-architecture is further demonstrated with a drone-assisted deposition, paving the way towards a simple yet significant solar absorptance boosting and maintenance method for existing and newly developed CST absorbing materials.

Function follows form in biology, and the binding of small molecules requires proteins with pockets that match the shape of the ligand. For design of binding to symmetric ligands, protein homo-oligomers with matching symmetry are advantageous as each protein subunit can make identical interactions with the ligand. Here, we describe a general approach to designing hyperstable C2 symmetric proteins with pockets of diverse size and shape. We first designed repeat proteins that sample a continuum of curvatures but have low helical rise, then docked these into C2 symmetric homodimers to generate an extensive range of C2 symmetric cavities. We used this approach to design thousands of C2 symmetric homodimers, and characterized 101 of them experimentally. Of these, the geometry of 31 were confirmed by small angle X-ray scattering and 2 were shown by crystallographic analyses to be in close agreement with the computational design models. These scaffolds provide a rich set of starting points for binding a wide range of C2 symmetric compounds.

Purpose: The Finke Desert Race is an offroad motorbike and buggy race held annually in central Australia. Owing to the treacherous conditions, this race sees a significant influx of trauma presentations to Alice Springs Hospital, the closest rural hospital. Completion of a tertiary trauma survey (TTS) within 24 hours of a patient's admission is part of standard trauma management. Method: A retrospective analysis was undertaken of trauma presentations managed by general surgery over a 5-day period of the Finke Desert Race weekend, compared to a 3-month control period from February to April of the same year. To be included, patients met the criteria for completion of a TTS. Results: The total number of trauma presentations over the 5-day period of the race weekend was 18 (an incidence rate of 3.6 cases/day), compared to a total of 31 in the 3-month control period (an incidence rate of 0.36 cases/day). The daily rate of major trauma presentations during the Finke race weekend was 9.9 times greater than during the control period. Completion of TTS was missed in only 5.6 % of patients over the Finke weekend, compared to 14.3 % of patients in the control period. The median time from presentation to the emergency department to completion of TTS during the Finke weekend was 20 h 19 min, compared to 20 h 36 min during the control period. Conclusion: Despite the substantial influx of trauma during the race weekend, fewer patients missed having a TTS completed compared to the control period. The median time taken to completion of TTS was similar between the two time periods. These findings suggest that the general surgery department was able to maintain standard trauma management principles.

Introduction People with severe mental illness (SMI), including schizophrenia and bipolar disorder, experience significant health inequalities and are more likely to develop long-term physical health conditions (LTCs), such as type 2 diabetes and cardiovascular disease. Many people with SMI rely on informal caregivers, typically friends and family, to support their health and enable them to live in the community. Informal caregivers of people with SMI experience high levels of caregiver burden, social isolation, and poor health outcomes. However, it is unclear how co-existing LTCs contribute to the caregiving experience. Objectives The aim of this study was to explore the lived experience of informal caregivers of people with co-existing SMI and LTCs. Methods We conducted a qualitative study with informal caregivers of people with co-existing SMI and LTCs in England. We recruited 12 informal caregivers and conducted five semi-structured interviews and two focus groups between December 2018 and April 2019. The interviews and focus groups were audio recorded, transcribed verbatim and thematically analysed. Results SMI impacts profoundly on the health and well-being of both service users and their informal caregivers. Service users were described as too unwell with their SMI to engage in self-management of their mental and physical health, with the primary responsibility for these tasks falling to informal caregivers. There were significant barriers to adequate physical healthcare for service users, therefore informal caregivers needed to advocate extensively for their loved ones to ensure access to services. Informal caregivers felt significantly under-supported and struggled with the caregiver burden associated with SMI and LTCs. This burden included the constant monitoring of risk, anxiety around the vulnerability of their loved one, repeated hospitalisations, physical health concerns, lack of respite services, lack of recognition of their role, the guilt associated with paternalistic care, shame and stigma, and the difficulties managing the changeable nature of SMI. Conclusions Informal caregivers of people with SMI face an additional caregiver burden resulting from co-existing LTCS. This adds substantially to their caring role, yet they do not receive the necessary support, and therefore their own health and wellbeing are negatively impacted. Improved recognition of the role of informal caregivers and additional support, including improved provision of respite services, are needed to improve the well-being of informal caregivers. Disclosure of Interest C. Carswell: None Declared, J. Brown: None Declared, D. Shiers Consultant of: DS is an expert adviser to the National Institute for Health and Care Excellence Centre for Guidelines; the views expressed are those of the authors and not those of National Institute for Health and Care Excellence., P. Coventry: None Declared, N. Siddiqi: None Declared

Second language vocabulary learning research has so far been predominantly focused on concrete nouns. However, recent work suggests that different word classes lead to differences in grounding, processing and learning of words (Markostamou, 2017; Martin & Tokowicz, 2019). To contribute to the basic understanding of the learning mechanisms, this study investigates how different learning methods influence learning of different types of words (nouns, verbs and prepositions) through either text-based or picture-based learning methods in adult population (N=160). Selected words vary in their translational ambiguity to additionally explore the modality effects in words with different levels of cross-linguistic (dis)similarity (Jarvis & Pavlenko, 2010). Production and recognition tasks are introduced after both learning sessions and again after a one-week delay to obtain comprehensive data about the learning curve across conditions. The results will contribute to understanding how words are represented and conceptualised and how they interact with different modalities during the initial learning phases.

The approximate number system (ANS) underlies our rapid and intuitive sense for quantities (Feigenson et al., 2004). The ANS, tapped into when performing rapid number judgement (DeWind et al., 2015), is affected by the properties of visual stimuli (e.g., object density and grouping). In these studies, we test whether the ANS is also affected by semantic information, an effect previously found in the processing of other types of spatial information (e.g., language presented at encoding affects spatial memory, see Gudde et al., 2016; Loewenstein & Gentner, 2005). We present the results of four experiments manipulating vague quantifiers (few, several, many, lots, 'no quantifier') prior to flashing a visual scene containing a number of objects. If higher-level cognition can penetrate the ANS, we expected that quantifiers presented at encoding would bias approximate number judgments towards the previously presented quantifier. Such results would provide compelling evidence that expectation mediates low-level visual processes.

Introduction Ethnic minorities (also called racialised groups) are more likely to experience severe mental illness (SMI). People with SMI are more likely to experience multimorbidity (MM), making psychosis among racialised groups more likely to lead to MM, poor outcomes, disability and premature mortality.Methods and analysis This National Institute for Health and Care Research-funded study (151887) seeks to use innovative participatory methods including photovoice and biographical narrative interviews in urban and rural areas of England to assemble experience data. These data will be subjected to polytextual thematic analysis, and alongside pictures and captions, will inform an experienced-based co-design of interventions, the implementation of which will be evaluated. There will be an economic analysis and a process evaluation of the implementation.Ethics and dissemination This programme of work has received ethical (IRAS 322421; Newcastle North Tyneside Research Ethics Committee 23/NE/0143) and sponsor approval. The findings will be disseminated in galleries showing the creative work, as lay and academic summaries and infographics; as practice briefings for practitioners, commissioners and policy makers; peer-reviewed publications.Trial registration number https://www.researchregistry.com/browse-the-registry%23home/registrationdetails/649c08111c037d0027b17d17/

The Australian Solar Thermal Research Institute (ASTRI) has been developing technologies designed to collect and store solar energy at high-temperature to drive a new high-efficiency power block based on the supercritical CO2 Brayton cycle. ASTRI is pursuing two alternative pathways: one based on the use of liquid sodium as a heat transfer fluid, and the other based on the use of solid particles. The current work describes ASTRI’s progress towards design and construction of a 700kWth prototype sodium receiver suited to this type of system, which will be installed and tested on Solar Field 2 at the CSIRO Energy Centre in Newcastle, Australia. The receiver is a cavity receiver with a circular aperture oriented at a tilt down towards the centre of the heliostat field. Inside the cavity are ten vertical tube banks in a semi-circular arrangement, with sodium flowing from the centre to the outside in a serpentine manner. Optical and thermal modelling at design point predicts aperture interception efficiency of 95.3%, receiver efficiency of 90.9% and thus a combined interception and receiver efficiency of 86.6%. Conservative flux limits are set based on the tube material’s (Alloy 625) time independent tensile strength, which is dominated by creep for the sodium temperatures considered. In the event of incident, the receiver is designed to drain and a door closes over the aperture to limit smoke egress. Insulation is SiO2-CaO-MgO blanket, and all pipes are heat traced. Fabrication of the receiver was completed in July 2022 and first on-sun testing is expected in September 2023.

Attention skills are strong cross-sectional predictors of reading comprehension from childhood through to adolescence. However, less is known about the developmental relations between these two domains across this period. This study examined the codevelopment of reading and attention in a community sample of 614 Australian school students (50% female). Reading and attention were assessed at ages 8, 10, 12, and 14. Results of univariate latent growth models demonstrated, on average, curvilinear trajectories for reading in which rapid growth across younger age spans decelerates as children reach adolescence. By contrast, attention skills remained relatively stable on average. Significant negative correlations were observed between the intercept and slope factors in separate reading (r = -0.62) and attention models (r = -0.39) suggesting compensatory growth patterns in which poorer performing students in both domains at age 8 have steeper trajectories than their higher performing peers. A comparison of a multivariate latent growth model and an autoregressive latent trajectory model with structured residuals (ALT-SR) examined the interrelatedness of development in reading and attention. Both between-individual and within-individual cross-domain parameters showed reading and attention to be positively related at Grade 3, indicating an association between better attention and higher reading achievement at age 8. However, there was little evidence for interrelated growth across domains in this sample. The results contribute to theories which explain whether and how multiple cognitive domains codevelop over a substantial period of childhood and early adolescence.

Abstract Background Point-of-care ultrasound (POCUS) is increasingly used as a non-invasive vascular access assessment method by clinicians from multiple disciplines worldwide, prior and during vascular access cannulations. While POCUS is a relatively new method to establish a vascular access in patients with complex vascular conditions, it is also essential to train and educate individuals who are novices in the techniques of cannulation so that they become proficient in performing this task subsequently on patients safely and successfully. A simulated environment may be a helpful tool to help healthcare providers establish skills in using POCUS safely and may also help them to successfully establish vascular access in patients. With this project, we sought to determine if participants of a simulated POCUS workshop for vascular access can use this technique successfully in their individual clinical environment after their attendance of a half-day workshop. Methods A mixed-methods longitudinal study design was chosen to evaluate a point-of-care ultrasound workshop for peripheral intravenous cannula insertion. The workshops used simulation models for cannulation in combination with multiple ultrasound devices from various manufacturers to expose participants to a broader variety of POCUS devices as they may also vary in different clinical areas. Participants self-assessed their cannulation skills using questionnaires on a 10-point rating scale prior to and directly after the workshop. Results A total of 85 Individuals participated in eleven half-day workshops through 2021 and 2022. Workshop participants claimed that attending the workshop had significantly enhanced their clinical skill of using ultrasound for the purpose of cannulating a venous vessel. The level of confidence in using this technique had increased in all participants directly after conclusion of the workshop. Conclusions Globally, clinicians are increasingly using POCUS to establish vascular access in patients, and it is necessary that they receive sufficient and adequately structured and formal training to successfully apply this technique in their clinical practice. Offering a workshop which uses simulation models in combination with various POCUS devices to demonstrate this technique in a hands-on approach has proven to be useful to establish this newly learned skill in clinicians.

Abstract Recently it has become possible to de novo design high affinity protein binding proteins from target structural information alone. There is, however, considerable room for improvement as the overall design success rate is low. Here, we explore the augmentation of energy-based protein binder design using deep learning. We find that using AlphaFold2 or RoseTTAFold to assess the probability that a designed sequence adopts the designed monomer structure, and the probability that this structure binds the target as designed, increases design success rates nearly 10-fold. We find further that sequence design using ProteinMPNN rather than Rosetta considerably increases computational efficiency.

Deictic communication is fundamentally multimodal. Spatial demonstratives frequently co-occur with eye gaze and physical pointing to draw the attention of an addressee to an object location (e.g. this cup; that chair). Yet the relative importance of language, gesture and eye gaze in deictic reference has not this far been elucidated. In three online experiments, we manipulated the congruency of pointing, gazing and verbal cues to establish their relative importance for demonstrative choice (Experiment 1) and choice of referent (Experiments 2 and 3). Participants saw an image with a person sitting behind a table, interacting with items placed proximally or distally relative to the pictured person, with manipulation of pointing, eye gaze and language (and congruence/incongruence of these modalities). While all three modalities affected demonstrative choice (Experiment 1) and referent choice (Experiments 2 and 3), results show that pointing is the dominant deictic cue to demonstrative/referent choice.

BackgroundHealth-related stigma can act as a barrier to seeking treatment and can negatively impact wellbeing. Comparing stigma communication across different conditions may generate insights previously lacking from condition-specific approaches and help to broaden our understanding of health stigma as a whole.MethodA sequential explanatory mixed-methods approach was used to investigate the prevalence and type of health-related stigma on Twitter by extracting 1.8 million tweets referring to five potentially stigmatized health conditions and disorders (PSHCDs): Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS), Diabetes, Eating Disorders, Alcoholism, and Substance Use Disorders (SUD). Firstly, 1,500 tweets were manually coded by stigma communication type, followed by a larger sentiment analysis (n = 250,000). Finally, the most prevalent category of tweets, “Anti-Stigma and Advice” (n = 273), was thematically analyzed to contextualize and explain its prevalence.ResultsWe found differences in stigma communication between PSHCDs. Tweets referring to substance use disorders were frequently accompanied by messages of societal peril. Whereas, HIV/AIDS related tweets were most associated with potential labels of stigma communication. We found consistencies between automatic tools for sentiment analysis and manual coding of stigma communication. Finally, the themes identified by our thematic analysis of anti-stigma and advice were Social Understanding, Need for Change, Encouragement and Support, and Information and Advice.ConclusionsDespite one third of health-related tweets being manually coded as potentially stigmatizing, the notable presence of anti-stigma suggests that efforts are being made by users to counter online health stigma. The negative sentiment and societal peril associated with substance use disorders reflects recent suggestions that, though attitudes have improved toward physical diseases in recent years, stigma around addiction has seen little decline. Finally, consistencies between our manual coding and automatic tools for identifying language features of harmful content, suggest that machine learning approaches may be a reasonable next step for identifying general health-related stigma online.

The Rosetta software for macromolecular modeling, docking and design is extensively used in laboratories worldwide. During two decades of development by a community of laboratories at more than 60 institutions, Rosetta has been continuously refactored and extended. Its advantages are its performance and interoperability between broad modeling capabilities. Here we review tools developed in the last 5 years, including over 80 methods. We discuss improvements to the score function, user interfaces and usability. Rosetta is available at http://www.rosettacommons.org.

Abstract The dentate gyrus (DG), a key hippocampal subregion in memory processing, generally resists phosphorylated tau accumulation in the amnestic dementia of the Alzheimer’s type due to Alzheimer’s disease (DAT-AD), but less is known about the susceptibility of the DG to other tauopathies. Here, we report stereologic densities of total DG neurons and tau inclusions in thirty-two brains of human participants with autopsy-confirmed tauopathies with distinct isoform profiles—3R Pick’s disease (PiD, N = 8), 4R corticobasal degeneration (CBD, N = 8), 4R progressive supranuclear palsy (PSP, N = 8), and 3/4R AD (N = 8). All participants were diagnosed during life with primary progressive aphasia (PPA), an aphasic clinical dementia syndrome characterized by progressive deterioration of language abilities with spared non-language cognitive abilities in early stages, except for five patients with DAT-AD as a comparison group. 51% of total participants were female. All specimens were stained immunohistochemically with AT8 to visualize tau pathology, and PPA cases were stained for Nissl substance to visualize neurons. Unbiased stereological analysis was performed in granule and hilar DG cells, and inclusion-to-neuron ratios were calculated. In the PPA group, PiD had highest mean total (granule + hilar) densities of DG tau pathology (p