Specialist intellectual disability liaison nurses in general hospitals in England: cohort study using a large mortality dataset.

OBJECTIVE: Intellectual disability liaison nurses in general hospitals could enhance access to high-quality, adapted healthcare and improve outcomes. We aimed to explore associations between the input of intellectual disability liaison nurses and the quality of care in people with intellectual disability who are admitted to hospital. DESIGN: Retrospective analysis of a national dataset of mortality reviews. SETTING: General hospitals in England. PARTICIPANTS: 4742 adults with intellectual disability who died in hospital between 2016 and 2021 and whose deaths were reviewed as part of the Learning from Lives and Deaths mortality review programme. OUTCOME MEASURES: We used logistic regression to compare the sociodemographic and clinical characteristics of those who did, and did not, receive input from an intellectual disability liaison nurse. We explored associations between liaison nurse input, care processes and overall quality of care. RESULTS: One-third of people with intellectual disability who died in hospital in England between 2016 and 2021 had input from an intellectual disability liaison nurse. Intellectual disability liaison nurse input was not evenly distributed across England and was more common in those who died of cancer. Having an intellectual disability liaison nurse involved in an individual's care was associated with increased likelihood of reasonable adjustments being made to care (adjusted OR (aOR) 1.95, 95% CI 1.63 to 2.32) and of best practice being identified (aOR 1.37, 95% CI 1.17 to 1.60) but was not associated with a rating of overall quality of care received (aOR 0.94, 95% CI 0.78 to 1.12). CONCLUSIONS: Intellectual disability liaison nurses see only a minority of people with intellectual disability who are admitted to hospital in England. Increasing the availability of intellectual disability liaison nurses could improve care for this disadvantaged group.

Dynamical decoding of the competition between charge density waves in a kagome superconductor.

The kagome superconductor CsV3Sb5 hosts a variety of charge density wave (CDW) phases, which play a fundamental role in the formation of other exotic electronic instabilities. However, identifying the precise structure of these CDW phases and their intricate relationships remain the subject of intense debate, due to the lack of static probes that can distinguish the CDW phases with identical spatial periodicity. Here, we unveil the out-of-equilibrium competition between two coexisting 2 × 2 × 2 CDWs in CsV3Sb5 harnessing time-resolved X-ray diffraction. By analyzing the light-induced changes in the intensity of CDW superlattice peaks, we demonstrate the presence of both phases, each displaying a significantly different amount of melting upon excitation. The anomalous light-induced sharpening of peak width further shows that the phase that is more resistant to photo-excitation exhibits an increase in domain size at the expense of the other, thereby showcasing a hallmark of phase competition. Our results not only shed light on the interplay between the multiple CDW phases in CsV3Sb5, but also establish a non-equilibrium framework for comprehending complex phase relationships that are challenging to disentangle using static techniques.

Constipation prevalence and risk from prescribed medications in people with intellectual disability: Findings from an English mortality programme.

Constipation is common in people with intellectual disability, with case reports of associated deaths. Risk factors include lifestyle factors, health conditions, and certain medications. We aimed to explore constipation in a sample of people with intellectual disability who died in 2021. We described prevalence of constipation, causes of death and the risk of secondary constipation from prescribed medications. Medications were scored based on the risk of constipation indicated in the drug profile. Forty-eight percent of the sample had constipation. Half of the sample were prescribed at least two medications that are commonly associated with side effects of constipation. There were high rates of antipsychotic (30%) and laxative (40%) drug prescription. Five people with a history of constipation died of causes of death associated with constipation. Our findings highlight the risk of secondary constipation due to prescribed medication and the seriousness of the condition in people with intellectual disability.

Predicting recovery following stroke: Deep learning, multimodal data and feature selection using explainable AI.

Machine learning offers great potential for automated prediction of post-stroke symptoms and their response to rehabilitation. Major challenges for this endeavour include the very high dimensionality of neuroimaging data, the relatively small size of the datasets available for learning and interpreting the predictive features, as well as, how to effectively combine neuroimaging and tabular data (e.g. demographic information and clinical characteristics). This paper evaluates several solutions based on two strategies. The first is to use 2D images that summarise MRI scans. The second is to select key features that improve classification accuracy. Additionally, we introduce the novel approach of training a convolutional neural network (CNN) on images that combine regions-of-interests (ROIs) extracted from MRIs, with symbolic representations of tabular data. We evaluate a series of CNN architectures (both 2D and a 3D) that are trained on different representations of MRI and tabular data, to predict whether a composite measure of post-stroke spoken picture description ability is in the aphasic or non-aphasic range. MRI and tabular data were acquired from 758 English speaking stroke survivors who participated in the PLORAS study. Each participant was assigned to one of five different groups that were matched for initial severity of symptoms, recovery time, left lesion size and the months or years post-stroke that spoken description scores were collected. Training and validation were carried out on the first four groups. The fifth (lock-box/test set) group was used to test how well model accuracy generalises to new (unseen) data. The classification accuracy for a baseline logistic regression was 0.678 based on lesion size alone, rising to 0.757 and 0.813 when initial symptom severity and recovery time were successively added. The highest classification accuracy (0.854), area under the curve (0.899) and F1 score (0.901) were observed when 8 regions of interest were extracted from each MRI scan and combined with lesion size, initial severity and recovery time in a 2D Residual Neural Network (ResNet). This was also the best model when data were limited to the 286 participants with moderate or severe initial aphasia (with area under curve = 0.865), a group that would be considered more difficult to classify. Our findings demonstrate how imaging and tabular data can be combined to achieve high post-stroke classification accuracy, even when the dataset is small in machine learning terms. We conclude by proposing how the current models could be improved to achieve even higher levels of accuracy using images from hospital scanners.

Sequencing-guided design of genetically encoded small RNAs targeting CAG repeats for selective inhibition of mutant huntingtin.

Huntington's disease (HD) is an incurable neurodegenerative disorder caused by genetic expansion of a CAG repeat sequence in one allele of the huntingtin (HTT) gene. Reducing expression of the mutant HTT (mutHTT) protein has remained a clear therapeutic goal, but reduction of wild-type HTT (wtHTT) is undesirable, as it compromises gene function and potential therapeutic efficacy. One promising allele-selective approach involves targeting the CAG repeat expansion with steric binding small RNAs bearing central mismatches. However, successful genetic encoding requires consistent placement of mismatches to the target within the small RNA guide sequence, which involves 5' processing precision by cellular enzymes. Here, we used small RNA sequencing (RNA-seq) to monitor the processing precision of a limited set of CAG repeat-targeted small RNAs expressed from multiple scaffold contexts. Small RNA-seq identified expression constructs with high-guide strand 5' processing precision and promising allele-selective inhibition of mutHTT. Transcriptome-wide mRNA-seq also identified an allele-selective small RNA with a favorable off-target profile. These results support continued investigation and optimization of genetically encoded repeat-targeted small RNAs for allele-selective HD gene therapy and underscore the value of sequencing methods to balance specificity with allele selectivity during the design and selection process.

Global mpox lineage discovery and rapid outbreak tracking with nanopore sequencing.

Insufficient tracking of virus introduction, spread, and new lineage emergence for the human monkeypox (mpox) virus 1 (hMPXV1) outbreak of 2022 hindered epidemiological studies and public health response. hMPXV1 mutations accumulated unexpectedly faster than predicted. Thus, new variants with altered pathogenicity could emerge and spread without early detection. Whole genome sequencing addresses this gap when implemented but requires widely accessible and standardized methodologies to be effective both regionally and globally. Here we developed a rapid nanopore whole genome sequencing method complete with working protocols, from DNA extraction to phylogenetic analysis tools. Using this method, we sequenced 84 complete hMPXV1 genomes from Illinois, a Midwestern region of the United States, spanning the first few months of the outbreak. The resulting five-fold increase in hMPXV1 genomes from this region established two previously unnamed global lineages, several mutational profiles not seen elsewhere, multiple separate introductions of the virus into the region, and the likely emergence and spread of new lineages from within this region. These results demonstrate that a dearth of genomic sequencing of hMPXV1 slowed our understanding and response to the mpox outbreak. This accessible nanopore sequencing approach makes near real-time mpox tracking and rapid lineage discovery straightforward and creates a blueprint for how to deploy nanopore sequencing for genomic surveillance of diverse viruses and future outbreaks.

An exploratory study into the relationship between playing at home or away and concussion.

PRIMARY OBJECTIVE: To investigate the effect of home and away game travel on risk of concussion across different levels of rugby union. RESEARCH DESIGN: Exploration study across school, university, and professional rugby teams. METHODS AND PROCEDURES: Retrospective analysis of concussion incidence and symptomology of surveillance data and prospective data collection for potential concussions via surveys. Data was collected from school rugby teams (n = 344 matches, over 2 years), a university rugby (n = 6 matches), and a professional rugby team (n = 64 matches, over two seasons). MAIN OUTCOMES AND RESULTS: School level rugby had an increased prevalence of concussions in away matches (p = 0.02). Likewise, there was a significant increase (p < 0.05) in concussions at away matches in university rugby. In addition, the professional rug by team had significant differences in recovery times and symptoms with away fixtures, including longer recovery times (p < 0.01), more initial symptoms (p < 0.01), as well as greater and more severe symptoms at 48 hours (p < 0.05). CONCLUSIONS: This research highlights an increased prevalence of concussion in school and university-aged rugby players away from home, as well as increased symptoms, symptom severity, and recovery times in professional rugby players.

From eye-blinks to state construction: Diagnostic benchmarks for online representation learning.

We present three new diagnostic prediction problems inspired by classical-conditioning experiments to facilitate research in online prediction learning. Experiments in classical conditioning show that animals such as rabbits, pigeons, and dogs can make long temporal associations that enable multi-step prediction. To replicate this remarkable ability, an agent must construct an internal state representation that summarizes its interaction history. Recurrent neural networks can automatically construct state and learn temporal associations. However, the current training methods are prohibitively expensive for online prediction-continual learning on every time step-which is the focus of this paper. Our proposed problems test the learning capabilities that animals readily exhibit and highlight the limitations of the current recurrent learning methods. While the proposed problems are nontrivial, they are still amenable to extensive testing and analysis in the small-compute regime, thereby enabling researchers to study issues in isolation, ultimately accelerating progress towards scalable online representation learning methods.

Compulsory collisions and corporate interests in school rugby: challenging distortions in the framing of childhood injury.

This article examines how 'framing' is used to resist a proposal to remove rugby tackling from UK schools. It focuses on rugby tackling for UK school children, which is often a compulsory part of many schools' curricula. Specifically, we explore the importance of framing in how the problem is described in various academic publications, how ideas about risk are articulated and how advocates themselves are represented. We show how the corporate interests of rugby governing bodies can become entangled with distortions about injury prevention. These distortions (or framing practices) include omitting arguments, conflating arguments, changing the argument, misrepresenting advocacy positions and skewing advocate identities. Next, the article demonstrates how a combination of recent advocacy, political interventions, research and cultural shifts appears to be changing perceptions about the risks associated with rugby tackling for children in school settings. In conclusion, we argue that while framing can be a useful strategy for policy advocates, there is value in paying attention to how framing is used by different stakeholder groups.

A Qualitative Exploration of Parents' Perceptions of Risk in Youth Contact Rugby.

The purpose of this study was to explore the understandings and perceptions of risk related to brain trauma amongst parents of children that play contact rugby. A qualitative approach was taken, using semi-structured interviews with 7 mothers and 27 fathers of children that participate in contact rugby. A thematic analysis of data suggests that parents used two primary cognitive strategies to process the risk they consented to with their children's participation in rugby; (1) minimalizing rugby risk to be equivalent to less injurious sports; and (2) elevating physical and social advantages above what they think other sports are capable of providing. From the findings it is suggested that parents who permit their children to play contact rugby are both aware of the high risks of injury in the sport, but simultaneously utilize two cognitive distortion techniques to rectify the dissonance caused between their choice to have their children play, and the salient number of concussions they observe. These results suggest that it will take properly informed consent, inclusive of concussion rates compared to other sports, in order to reduce cognitive distortion and effectively communicate risks associated with participation in contact rugby.

Selecting the best candidates for resurrecting extinct-in-the-wild plants from herbaria.

Resurrecting extinct species is a fascinating and challenging idea for scientists and the general public. Whereas some theoretical progress has been made for animals, the resurrection of extinct plants (de-extinction sensu lato) is a relatively recently discussed topic. In this context, the term 'de-extinction' is used sensu lato to refer to the resurrection of 'extinct in the wild' species from seeds or tissues preserved in herbaria, as we acknowledge the current impossibility of knowing a priori whether a herbarium seed is alive and can germinate. In plants, this could be achieved by germinating or in vitro tissue-culturing old diaspores such as seeds or spores available in herbarium specimens. This paper reports the first list of plant de-extinction candidates based on the actual availability of seeds in herbarium specimens of globally extinct plants. We reviewed globally extinct seed plants using online resources and additional literature on national red lists, resulting in a list of 361 extinct taxa. We then proposed a method of prioritizing candidates for seed-plant de-extinction from diaspores found in herbarium specimens and complemented this with a phylogenetic approach to identify species that may maximize evolutionarily distinct features. Finally, combining data on seed storage behaviour and longevity, as well as specimen age in the novel 'best de-extinction candidate' score (DEXSCO), we identified 556 herbarium specimens belonging to 161 extinct species with available seeds. We expect that this list of de-extinction candidates and the novel approach to rank them will boost research efforts towards the first-ever plant de-extinction.

A bead-based method for high-throughput mapping of the sequence- and force-dependence of T cell activation.

Adaptive immunity relies on T lymphocytes that use αß T cell receptors (TCRs) to discriminate among peptides presented by major histocompatibility complex molecules (pMHCs). Identifying pMHCs capable of inducing robust T cell responses will not only enable a deeper understanding of the mechanisms governing immune responses but could also have broad applications in diagnosis and treatment. T cell recognition of sparse antigenic pMHCs in vivo relies on biomechanical forces. However, in vitro screening methods test potential pMHCs without force and often at high (nonphysiological) pMHC densities and thus fail to predict potent agonists in vivo. Here, we present a technology termed BATTLES (biomechanically assisted T cell triggering for large-scale exogenous-pMHC screening) that uses biomechanical force to initiate T cell triggering for peptides and cells in parallel. BATTLES displays candidate pMHCs on spectrally encoded beads composed of a thermo-responsive polymer capable of applying shear loads to T cells, facilitating exploration of the force- and sequence-dependent landscape of T cell responses. BATTLES can be used to explore basic T cell mechanobiology and T cell-based immunotherapies.

Metasurface optofluidics for dynamic control of light fields.

The ability to manipulate light and liquids on integrated optofluidics chips has spurred a myriad of important developments in biology, medicine, chemistry and display technologies. Here we show how the convergence of optofluidics and metasurface optics can lead to conceptually new platforms for the dynamic control of light fields. We first demonstrate metasurface building blocks that display an extreme sensitivity in their scattering properties to their dielectric environment. These blocks are then used to create metasurface-based flat optics inside microfluidic channels where liquids with different refractive indices can be directed to manipulate their optical behaviour. We demonstrate the intensity and spectral tuning of metasurface colour pixels as well as on-demand optical elements. We finally demonstrate automated control in an integrated meta-optofluidic platform to open up new display functions. Combined with large-scale microfluidic integration, our dynamic-metasurface flat-optics platform could open up the possibility of dynamic display, imaging, holography and sensing applications.

Applying the Bradford Hill Criteria for Causation to Repetitive Head Impacts and Chronic Traumatic Encephalopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with a history of repetitive head impacts (RHI). CTE was described in boxers as early as the 1920s and by the 1950s it was widely accepted that hits to the head caused some boxers to become "punch drunk." However, the recent discovery of CTE in American and Australian-rules football, soccer, rugby, ice hockey, and other sports has resulted in renewed debate on whether the relationship between RHI and CTE is causal. Identifying the strength of the evidential relationship between CTE and RHI has implications for public health and medico-legal issues. From a public health perspective, environmentally caused diseases can be mitigated or prevented. Medico-legally, millions of children are exposed to RHI through sports participation; this demographic is too young to legally consent to any potential long-term risks associated with this exposure. To better understand the strength of evidence underlying the possible causal relationship between RHI and CTE, we examined the medical literature through the Bradford Hill criteria for causation. The Bradford Hill criteria, first proposed in 1965 by Sir Austin Bradford Hill, provide a framework to determine if one can justifiably move from an observed association to a verdict of causation. The Bradford Hill criteria include nine viewpoints by which to evaluate human epidemiologic evidence to determine if causation can be deduced: strength, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy. We explored the question of causation by evaluating studies on CTE as it relates to RHI exposure. Through this lens, we found convincing evidence of a causal relationship between RHI and CTE, as well as an absence of evidence-based alternative explanations. By organizing the CTE literature through this framework, we hope to advance the global conversation on CTE mitigation efforts.

An assessment of current concussion identification and diagnosis methods in sports settings: a systematic review.

BACKGROUND: Concussion in sport is an ongoing global concern. The head injury assessment (HIA) by the field of play is acknowledged as the first step in recognising and identifying concussion. While previous systematic literature reviews have evaluated the sensitivity of side-line screening tools and assessment protocols, no systematic review has evaluated the research designs and assessments used in a field setting. This systematic review investigated existing screening and diagnostic tools used in research as part of the HIA protocol to identify concussion that are currently used in professional, semi-professional and amateur (club) sports settings. METHODS: A systematic searching of relevant databases was undertaken for peer-reviewed literature between 2015 and 2020. RESULTS: Twenty-six studies met the inclusion criteria. Studies were of moderate to good quality, reporting a variety of designs. The majority of studies were undertaken in professional/elite environments with medical doctors and allied health practitioners (e.g., physical therapists) involved in 88% of concussion assessments. While gender was reported in 24 of the 26 studies, the majority of participants were male (77%). There was also a variety of concussion assessments (n = 20) with the sports concussion assessment tool (SCAT) used in less than half of the included studies. CONCLUSION: The majority of studies investigating concussion HIAs are focused on professional/elite sport. With concussion an issue at all levels of sport, future research should be directed at non-elite sport. Further, for research purposes, the SCAT assessment should also be used more widely to allow for consistency across studies.

Imposing Compulsory Rugby Union on Schoolchildren: An Analysis of English State-Funded Secondary Schools.

Objective: To establish the extent to which Rugby Union was a compulsory physical education activity in state-funded secondary schools in England and to understand the views of Subject Leaders for Physical Education with respect to injury risk. Method: A cross-sectional research study using data obtained under the Freedom of Information Act (2000) from 288 state-funded secondary schools. Results: Rugby Union was delivered in 81% (n = 234 of 288) of state-funded secondary school physical education curricula, including 83% (n = 229 of 275) of state-funded secondary school boys' and 54% (n = 151 of 282) of girls' physical education curricular. Rugby Union was compulsory in 91% (n = 208 of 229) of state-funded secondary schools that delivered it as part of the boys' physical education curriculum and 54% (n = 82 of 151) of state-funded secondary schools that delivered contact Rugby Union as part of the girls' physical education curriculum. Subject Leaders for Physical Education also perceived Rugby Union to have the highest risk of harm of the activities they delivered in their school physical education curriculum. Conclusion: Notwithstanding discussions of appropriate measures (i.e., mandatory concussion training, Rugby Union specific qualifications and CPD) to reduce injury risk, it is recommended that Rugby Union should not be a compulsory activity given that it has a perceived high risk of injury and is an unnecessary risk for children in physical education.

Efficient Cloning and Sequence Validation of Repetitive and High GC-Content Short Hairpin RNAs.

Short hairpin RNAs, or short hairpin RNAs (shRNAs), are a proven tool for gene knockdown and a promising therapeutic approach for suppression of disease-associated genes. The efficient preparation of shRNA-expressing vectors can sometimes become a bottleneck due to the complexity of shRNA hairpin sequence and structure, especially for repetitive or high GC-content targets. Here, we present improved shRNA cloning and validation methods that enabled efficient and rapid cloning of several shRNAs targeting disease-associated repeat expansions, including GGGGCC, CAG, CTG, CCTG, and CGG into modified pLKO.1 vectors. Improvements included shRNA insert design and preparation, recombination-based cloning, and sequencing-based validation that included Sanger and nanopore long-read sequencing. This improved method should enable practical, efficient cloning of nearly any shRNA sequence.

High throughput nanopore sequencing of SARS-CoV-2 viral genomes from patient samples.

In late 2019, a novel coronavirus began spreading in Wuhan, China, causing a potentially lethal respiratory viral infection. By early 2020, the novel coronavirus, called SARS-CoV-2, had spread globally, causing the COVID-19 pandemic. The infection and mutation rates of SARS-CoV-2 make it amenable to tracking introduction, spread and evolution by viral genome sequencing. Efforts to develop effective public health policies, therapeutics, or vaccines to treat or prevent COVID-19 are also expected to benefit from tracking mutations of the SARS-CoV-2 virus. Here we describe a set of comprehensive working protocols, from viral RNA extraction to analysis using established visualization tools, for high throughput sequencing of SARS-CoV-2 viral genomes using a MinION instrument. This set of protocols should serve as a reliable "how-to" reference for generating quality SARS-CoV-2 genome sequences with ARTIC primer sets and long-read nanopore sequencing technology. In addition, many of the preparation, quality control, and analysis steps will be generally applicable to other sequencing platforms.

Pressure. A Qualitative Analysis of the Perception of Concussion and Injury Risk in Retired Professional Rugby Players.

This study interviewed retired professional rugby union players (≤10 years since retirement) to discuss their careers in the game of rugby union. The primary aim of the study was to document their understanding of concussion knowledge and the analogies they use to describe concussion. In addition, these interviews were used to determine any explicit and implicit pressures of playing professional rugby as described by ex-professional rugby players. Overall, 23 retired professional rugby players were interviewed. The participants had played the game of rugby union (n = 23) at elite professional standard. A semi-structured individual interview design was conducted with participants between June to August 2020. The research team reviewed the transcripts to identify the major themes from the interviews using a reflexive thematic analysis approach. Four major themes were identified: (1) medical and theoretical understanding of concussion, (2) descriptions of concussion and disassociated language, (3) personal concussion experience, and (4) peer influences on concussion within the sport. These were further divided into categories and subcategories. The interviews highlighted that players did not fully understand the ramifications of concussive injury and other injury risk, as it became normalised as part of their sport. This normalisation was supported by trivialising the seriousness of concussions and using dismissive language amongst themselves as players, or with coaching staff. As many of these ex-professional players are currently coaching rugby (48%), these interviews could assist coaches in treating concussion as a significant injury and not downplaying the seriousness of concussion in contact sports.