Identification of pattern mining algorithm for rugby league players positional groups separation based on movement patterns.

The application of pattern mining algorithms to extract movement patterns from sports big data can improve training specificity by facilitating a more granular evaluation of movement. Since movement patterns can only occur as consecutive, non-consecutive, or non-sequential, this study aimed to identify the best set of movement patterns for player movement profiling in professional rugby league and quantify the similarity among distinct movement patterns. Three pattern mining algorithms (l-length Closed Contiguous [LCCspm], Longest Common Subsequence [LCS] and AprioriClose) were used to extract patterns to profile elite rugby football league hookers (n = 22 players) and wingers (n = 28 players) match-games movements across 319 matches. Jaccard similarity score was used to quantify the similarity between algorithms' movement patterns and machine learning classification modelling identified the best algorithm's movement patterns to separate playing positions. LCCspm and LCS movement patterns shared a 0.19 Jaccard similarity score. AprioriClose movement patterns shared no significant Jaccard similarity with LCCspm (0.008) and LCS (0.009) patterns. The closed contiguous movement patterns profiled by LCCspm best-separated players into playing positions. Multi-layered Perceptron classification algorithm achieved the highest accuracy of 91.02% and precision, recall and F1 scores of 0.91 respectively. Therefore, we recommend the extraction of closed contiguous (consecutive) over non-consecutive and non-sequential movement patterns for separating groups of players.

Worldwide absence of canonical benzimidazole resistance-associated mutations within ß-tubulin genes from Ascaris.

BACKGROUND: The giant roundworm Ascaris is an intestinal nematode, causing ascariasis by infecting humans and pigs worldwide. Recent estimates suggest that Ascaris infects over half a billion people, with chronic infections leading to reduced growth and cognitive ability. Ascariasis affects innumerable pigs worldwide and is known to reduce production yields via decreased growth and condemnation of livers. The predominant anthelminthic drugs used to treat ascariasis are the benzimidazoles. Benzimidazoles interact with ß-tubulins and block their function, and several benzimidazole resistance-associated mutations have been described in the ß-tubulins of ruminant nematodes. Recent research on ascarids has shown that these canonical benzimidazole resistance-associated mutations are likely not present in the ß-tubulins of Ascaris, Ascaridia or Parascaris, even in phenotypically resistant populations. METHODS: To further determine the putative absence of key ß-tubulin polymorphisms, we screened two ß-tubulin isotypes of Ascaris, highly expressed in adult worms. Using adult and egg samples of Ascaris obtained from pigs and humans worldwide, we performed deep amplicon sequencing to look for canonical resistance-associated mutations in Ascaris ß-tubulins. Subsequently, we examined these data in closer detail to study the population dynamics of Ascaris and genetic diversity within the two isotypes and tested whether genotypes appeared to partition across human and pig hosts. RESULTS: In the 187 isolates, 69 genotypes were found, made up of eight haplotypes of ß-tubulin isotype A and 20 haplotypes of isotype B. Single nucleotide polymorphisms were seen at 14 and 37 positions for ß-tubulin isotype A and isotype B, respectively. No evidence of any canonical benzimidazole resistance-associated mutations was found in either human- or pig-derived Ascaris isolates. There was, however, a difference in the genetic diversity of each isotype and distribution of ß-tubulin genotypes between human- and pig-derived Ascaris. Statistical tests of population differentiation show significant differences (p < 0.001) between pig- and human-derived worms; however, more diversity was seen between worms from different populations than worms from different hosts. CONCLUSIONS: Our work suggests an absence of canonical ß-tubulin mutations within Ascaris, but alternative modes of anthelminthic resistance may emerge necessitating continued genetic scrutiny alongside monitoring of drug efficacy.

Longitudinal changes in anthropometric, physiological, and physical qualities of international women's rugby league players.

This is the first study to assess longitudinal changes in anthropometric, physiological, and physical qualities of international women's rugby league players. Thirteen forwards and 11 backs were tested three times over a 10-month period. Assessments included: standing height and body mass, body composition measured by dual x-ray absorptiometry (DXA), a blood panel, resting metabolic rate (RMR) assessed by indirect calorimetry, aerobic capacity (i.e.,[Formula: see text]) evaluated by an incremental treadmill test, and isometric force production measured by a force plate. During the pre-season phase, lean mass increased significantly by ~2% for backs (testing point 1: 47 kg; testing point 2: 48 kg) and forwards (testing point 1: 50 kg; testing point 2: 51 kg) (p = ≤ 0.05). Backs significantly increased their [Formula: see text] by 22% from testing point 1 (40 ml kg-1 min-1) to testing point 3 (49 ml kg-1 min-1) (p = ≤ 0.04). The [Formula: see text] of forwards increased by 10% from testing point 1 (41 ml kg-1 min-1) to testing point 3 (45 ml kg-1 min-1), however this change was not significant (p = ≥ 0.05). Body mass (values represent the range of means across the three testing points) (backs: 68 kg; forwards: 77-78 kg), fat mass percentage (backs: 25-26%; forwards: 30-31%), resting metabolic rate (backs: 7 MJ day-1; forwards: 7 MJ day-1), isometric mid-thigh pull (backs: 2106-2180 N; forwards: 2155-2241 N), isometric bench press (backs: 799-822 N; forwards: 999-1024 N), isometric prone row (backs: 625-628 N; forwards: 667-678 N) and bloods (backs: ferritin 21-29 ug/L, haemoglobin 137-140 g/L, iron 17-21 umol/L, transferrin 3 g/L, transferring saturation 23-28%; forwards: ferritin 31-33 ug/L, haemoglobin 141-145 g/L, iron 20-23 umol/L, transferrin 3 g/L, transferrin saturation 26-31%) did not change (p = ≥ 0.05). This study provides novel longitudinal data which can be used to better prepare women rugby league players for the unique demands of their sport, underpinning female athlete health.

Collaborative care approaches for people with severe mental illness.

BACKGROUND: Collaborative care for severe mental illness (SMI) is a community-based intervention that promotes interdisciplinary working across primary and secondary care. Collaborative care interventions aim to improve the physical and/or mental health care of individuals with SMI. This is an update of a 2013 Cochrane review, based on new searches of the literature, which includes an additional seven studies. OBJECTIVES: To assess the effectiveness of collaborative care approaches in comparison with standard care (or other non-collaborative care interventions) for people with diagnoses of SMI who are living in the community. SEARCH METHODS: We searched the Cochrane Schizophrenia Study-Based Register of Trials (10 February 2021). We searched the Cochrane Common Mental Disorders (CCMD) controlled trials register (all available years to 6 June 2016). Subsequent searches on Ovid MEDLINE, Embase and PsycINFO together with the Cochrane Central Register of Controlled Trials (with an overlap) were run on 17 December 2021. SELECTION CRITERIA: Randomised controlled trials (RCTs) where interventions described as 'collaborative care' were compared with 'standard care' for adults (18+ years) living in the community with a diagnosis of SMI. SMI was defined as schizophrenia, other types of schizophrenia-like psychosis or bipolar affective disorder. The primary outcomes of interest were: quality of life, mental state and psychiatric admissions at 12 months follow-up. DATA COLLECTION AND ANALYSIS: Pairs of authors independently extracted data. We assessed the quality and certainty of the evidence using RoB 2 (for the primary outcomes) and GRADE. We compared treatment effects between collaborative care and standard care. We divided outcomes into short-term (up to six months), medium-term (seven to 12 months) and long-term (over 12 months). For dichotomous data we calculated the risk ratio (RR) and for continuous data we calculated the standardised mean difference (SMD), with 95% confidence intervals (CIs). We used random-effects meta-analyses due to substantial levels of heterogeneity across trials. We created a summary of findings table using GRADEpro. MAIN RESULTS: Eight RCTs (1165 participants) are included in this review. Two met the criteria for type A collaborative care (intervention comprised of the four core components). The remaining six met the criteria for type B (described as collaborative care by the trialists, but not comprised of the four core components). The composition and purpose of the interventions varied across studies. For most outcomes there was low- or very low-certainty evidence. We found three studies that assessed the quality of life of participants at 12 months. Quality of life was measured using the SF-12 and the WHOQOL-BREF and the mean endpoint mental health component scores were reported at 12 months. Very low-certainty evidence did not show a difference in quality of life (mental health domain) between collaborative care and standard care in the medium term (at 12 months) (SMD 0.03, 95% CI -0.26 to 0.32; 3 RCTs, 227 participants). Very low-certainty evidence did not show a difference in quality of life (physical health domain) between collaborative care and standard care in the medium term (at 12 months) (SMD 0.08, 95% CI -0.18 to 0.33; 3 RCTs, 237 participants). Furthermore, in the medium term (at 12 months) low-certainty evidence did not show a difference between collaborative care and standard care in mental state (binary) (RR 0.99, 95% CI 0.77 to 1.28; 1 RCT, 253 participants) or in the risk of being admitted to a psychiatric hospital at 12 months (RR 5.15, 95% CI 0.67 to 39.57; 1 RCT, 253 participants). One study indicated an improvement in disability (proxy for social functioning) at 12 months in the collaborative care arm compared to usual care (RR 1.38, 95% CI 0.97 to 1.95; 1 RCT, 253 participants); we deemed this low-certainty evidence. Personal recovery and satisfaction/experience of care outcomes were not reported in any of the included studies. The data from one study indicated that the collaborative care treatment was more expensive than standard care (mean difference (MD) international dollars (Int$) 493.00, 95% CI 345.41 to 640.59) in the short term. Another study found the collaborative care intervention to be slightly less expensive at three years. AUTHORS' CONCLUSIONS: This review does not provide evidence to indicate that collaborative care is more effective than standard care in the medium term (at 12 months) in relation to our primary outcomes (quality of life, mental state and psychiatric admissions). The evidence would be improved by better reporting, higher-quality RCTs and the assessment of underlying mechanisms of collaborative care. We advise caution in utilising the information in this review to assess the effectiveness of collaborative care.

Lipid regulation of the glucagon receptor family.

The glucagon receptor family are typical class B1 G protein-coupled receptors (GPCRs) with important roles in metabolism, including the control of pancreas, brain, and liver function. As proteins with seven transmembrane domains, GPCRs are intimately in contact with lipid bilayers and therefore can be putatively regulated by interactions with their lipidic components, including cholesterol, sphingolipids, and other lipid species. Additionally, these receptors, as well as the agonists they bind to, can undergo lipid modifications, which can influence their binding capacity and/or elicit modified or biased signalling profiles. While the effect of lipids, and in particular cholesterol, has been widely studied for other GPCR classes, information about their role in regulating the glucagon receptor family is only beginning to emerge. Here we summarise our current knowledge on the effects of cholesterol modulation of glucagon receptor family signalling and trafficking profiles, as well as existing evidence for specific lipid-receptor binding and indirect effects of lipids via lipid modification of cognate agonists. Finally, we discuss the different methodologies that can be employed to study lipid-receptor interactions and summarise the importance of this area of investigation to increase our understanding of the biology of this family of metabolically relevant receptors.

Sequences Related to Chimay Rhabdovirus Are Widely Distributed in Ixodes ricinus Ticks across England and Wales.

Ticks are the main arthropod vector of pathogens to humans and livestock in the British Isles. Despite their role as a vector of disease, many aspects of tick biology, ecology, and microbial association are poorly understood. To address this, we investigated the composition of the microbiome of adult and nymphal Ixodes ricinus ticks. The ticks were collected on a dairy farm in Southwest England and RNA extracted for whole genome sequencing. Sequences were detected from a range of microorganisms, particularly tick-associated viruses, bacteria, and nematodes. A majority of the viruses were attributed to phlebo-like and nairo-like virus groups, demonstrating a high degree of homology with the sequences present in I. ricinus from mainland Europe. A virus sharing a high sequence identity with Chimay rhabdovirus, previously identified in ticks from Belgium, was detected. Further investigations of I. ricinus ticks collected from additional sites in England and Wales also identified Chimay rhabdovirus viral RNA with varying prevalence in all tick populations. This suggests that Chimay rhabdovirus has a wide distribution and highlights the need for an extended exploration of the tick microbiome in the United Kingdom (UK).

The bioequivalence study design recommendations for immediate-release solid oral dosage forms in the international pharmaceutical regulators programme participating regulators and organisations: differences and commonalities.

Bioequivalence (BE) studies are considered the standard for demonstrating that the performance of a generic drug product in the human body is sufficiently similar to that of its comparator product. The objective of this article is to describe the recommendations from participating Bioequivalence Working Group for Generics (BEWGG) members of the International Pharmaceutical Regulators Programme (IPRP) regarding the conduct and acceptance criteria for BE studies of immediate release solid oral dosage forms. A survey was conducted among BEWGG members regarding their BE recommendations and requirements related to study subjects, study design, sample size, single or multiple dose administration, study conditions (fasting or fed), analyte to be measured, selection of product strength, drug content, handling of endogenous substances, BE acceptance criteria, and additional design aspects. All members prefer conducting single dose cross-over designed studies in healthy subjects with a minimum of 12 subjects and utilizing the parent drug data to assess BE. However, differences emerged among the members when the drug's pharmacokinetics and pharmacodynamics become more complex, such that the study design (e.g., fasting versus fed conditions) and BE acceptance criteria (e.g., highly variable drugs, narrow therapeutic index drugs) may be affected. The survey results and discussions were shared with the ICH M13 Expert Working Group (EWG) and played an important role in identifying and analyzing gaps during the harmonization process. The draft ICH M13A guideline developed by the M13 EWG was endorsed by ICH on 20 December 2022, under Step 2.

When to Pull the Trigger: Conceptual Considerations for Approximating Head Acceleration Events Using Instrumented Mouthguards.

Head acceleration events (HAEs) are acceleration responses of the head following external short-duration collisions. The potential risk of brain injury from a single high-magnitude HAE or repeated occurrences makes them a significant concern in sport. Instrumented mouthguards (iMGs) can approximate HAEs. The distinction between sensor acceleration events, the iMG datum for approximating HAEs and HAEs themselves, which have been defined as the in vivo event, is made to highlight limitations of approximating HAEs using iMGs. This article explores the technical limitations of iMGs that constrain the approximation of HAEs and discusses important conceptual considerations for stakeholders interpreting iMG data. The approximation of HAEs by sensor acceleration events is constrained by false positives and false negatives. False positives occur when a sensor acceleration event is recorded despite no (in vivo) HAE occurring, while false negatives occur when a sensor acceleration event is not recorded after an (in vivo) HAE has occurred. Various mechanisms contribute to false positives and false negatives. Video verification and post-processing algorithms offer effective means for eradicating most false positives, but mitigation for false negatives is less comprehensive. Consequently, current iMG research is likely to underestimate HAE exposures, especially at lower magnitudes. Future research should aim to mitigate false negatives, while current iMG datasets should be interpreted with consideration for false negatives when inferring athlete HAE exposure.

Innovation in sport medicine and science: a global social network analysis of stakeholder collaboration in rugby union.

Objectives: To investigate the network of stakeholders involved in rugby union research across the globe. Methods: Using author affiliations listed on scientific publications, we identified the organisations that contributed to rugby union research from 1977 to 2022 and examine collaboration through coauthorship indicators. We determined the locations and sectors of identified organisations and constructed a collaboration network. Network metrics, including degree centrality and betweenness centrality, are computed to identify influential organisations and measure intersector collaboration. Results: There is an increase in scientific knowledge creation and collaboration between organisations for rugby union research over time. Among the sectors, the university, professional sports team and sports governing body sectors exhibit the highest intersectoral and intrasectoral density. Predominantly, influential actors are located in England, Australia, France, New Zealand, Ireland and South Africa. Australian Catholic University, Leeds Beckett University, Stellenbosch University, Swansea University, University College London and the University of Cape Town emerge as influential actors between 2016 and 2022. Conclusions: Our study underscores the ongoing growth of scientific knowledge generation in rugby union, primarily led by organisations in tier 1 rugby-playing nations within the university sector. Intersectoral collaboration with sports governing bodies plays a crucial role, acting as a broker between sectors. However, the overall collaboration landscape between and within sectors is low. These results highlight an opportunity for improved collaboration opportunities, as the organisations driving knowledge creation have been identified.

Computational modelling of dynamic cAMP responses to GPCR agonists for exploration of GLP-1R ligand effects in pancreatic ß-cells and neurons.

The glucagon-like peptide-1 receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) which plays important physiological roles in insulin release and promoting fullness. GLP-1R agonists initiate cellular responses by cyclic AMP (cAMP) pathway signal transduction. Understanding of the potential of GLP-1R agonists in the treatment of type 2 diabetes may be advanced by considering the cAMP dynamics for agonists at GLP-1R in both pancreatic ß-cells (important in insulin release) and neurons (important in appetite regulation). Receptor desensitisation in the cAMP pathway is known to be an important regulatory mechanism, with different ligands differentially promoting G protein activation and desensitisation. Here, we use mathematical modelling to quantify and understand experimentally obtained cAMP timecourses for two GLP-1R agonists, exendin-F1 (ExF1) and exendin-D3 (ExD3), which give markedly different signals in ß-cells and neurons. We formulate an ordinary differential equation (ODE) model for the dynamics of cAMP signalling in response to G protein-coupled receptor (GPCR) ligands, encompassing ligand binding, receptor activation, G protein activation, desensitisation and second messenger generation. We validate our model initially by fitting to timecourse data for HEK293 cells, then proceed to parameterise the model for ß-cells and neurons. Through numerical simulation and sensitivity studies, our analysis adds support to the hypothesis that ExF1 offers more potential glucose regulation benefit than ExD3 over long timescales via signalling in pancreatic ß-cells, but that there is little difference between the two ligands in the potential appetite suppression effects offered via long-time signalling in neurons on the same timescales.

Injury Profile in Youth Female Athletes: A Systematic Review and Meta-Analysis.

BACKGROUND: An increasing number of epidemiological studies assessing the incidence, prevalence and severity of injury in youth female sport are available. However, no study has sought to synthesise the current evidence base across all youth female sport. As such, a systematic review and meta-analysis of injury in this cohort is necessary to understand the diversity of injury and its associated burden between sports in addition to identifying the density of research available. OBJECTIVE: To conduct a systematic review and meta-analysis of epidemiological data of injuries in youth female athletes with particular attention to injury incidence, mean days lost and injury burden. METHODS: Searches were performed in PubMed, EBSCO (SPORTDiscus with Full Text MEDLINE, APA PsycINFO, CINAHL, Academic Search Complete) and Cochrane databases. Studies were considered if they reported time-loss injury incidence or prevalence in youth female (≤ 19 years old) athletes. Study quality and risk of bias were assessed using STROBE-SIIS extension, Newcastle-Ottawa Scale, and funnel plots, respectively. Injury incidence and burden rate data were modelled using a mixed-effect Poisson regression model. Days lost data were modelled using a generalised linear mixed model. RESULTS: Thirty-two studies were included. The overall incidence rate, mean days lost per injury, and burden rate were 4.4 injuries per 1000 h (95% CI 3.3-5.9), 10 days (95% CI 6-15), and 46 days per 1000 h (95% CI 23-92), respectively. Forty percent of athletes sustained at least one time-loss injury. Competitive level was a significant moderator of match and training injury incidence, with elite youth athletes presenting greater pooled injury incidence estimates than non-elite athletes (p = 0.0315 and p = 0.0047, respectively). The influence of moderators on days lost and injury burden could not be determined due to an insufficient number of studies for analysis. CONCLUSION: Despite a broad inclusion criterion, there is limited injury surveillance research available across youth female sport. Outside of soccer, little research density is evidenced with single studies available in popular team sports such as Australian football and rugby union. Insufficient study numbers reporting mean days lost and injury burden data were available for analysis, and pooled days lost data could only be estimated for soccer. This highlights a need for future research to report days lost data alongside injury number and exposure so burden can be calculated and the full risk of injury to youth female athletes can be identified.

Review article: Emergency medical services transfer of severe traumatic brain injured patients to a neuroscience centre: A systematic review.

Patients with severe traumatic brain injuries require urgent medical attention at a hospital. We evaluated whether transporting adult patients with a severe traumatic brain injury (TBI) to a Neuroscience Centre is associated with reduced mortality. We reviewed studies published between 2010 and 2023 on severe TBI in adults (>18 years) using Medline, CINAHL, Google Scholar and Cochrane databases. We focused on mortality rates and the impact of transferring patients to a Neuroscience Centre, delays to neurosurgery and EMS triage accuracy. This review analysed seven studies consisting of 53 365 patients. When patients were directly transported to a Neuroscience Centre, no improvement in survivability was demonstrated. Subsequently, transferring patients from a local hospital to a Neuroscience Centre was significantly associated with reduced mortality in one study (adjusted odds ratio: 0.79, 95% confidence interval: 0.64-0.96), and 24-h (relative risk [RR]: 0.31, 0.11-0.83) and 30-day (RR: 0.66, 0.46-0.96) mortality in another. Patients directly transported to a Neuroscience Centre were more unwell than those taken to a local hospital. Subsequent transfers increased time to CT scanning and neurosurgery in several studies, although these were not statistically significant. Additionally, EMS could accurately triage. None of the included studies demonstrated statistically significant findings indicating that direct transportation to a Neuroscience Centre increased survivability for patients with severe traumatic brain injuries. Subsequent transfers from a non-Neuroscience Centre to a Neuroscience Centre reduced mortality rates at 24 h and 30 days. Further research is required to understand the differences between direct transport and subsequent transfers to Neuroscience Centres.

The Frequency and Severity of Gastrointestinal Symptoms in Rugby Players.

This study aimed to assess the self-reported frequency and severity of gastrointestinal symptoms (GIS) at rest and around rugby training and match play in male and female rugby union players. An online questionnaire was sent to registered rugby union players (sevens or fifteens). Thirteen GIS were assessed alongside perceptions of appetite around rugby and rest using Likert and visual analog scales. Questions investigating a range of medical and dietary factors were included. Three hundred and twenty-five players (male n=271, female n=54) participated in the study. More frequent GIS (at least one GIS experienced weekly/more often) was reported by players at rest (n=203; 62%) compared to around rugby (n=154; 47%). The overall severity of GIS was low (mild discomfort), but a portion of players (33%) did report symptoms of moderate severity around rugby. Female players reported more frequent and severe symptoms compared to male counterparts (p<0.001). Self-reported appetite was significantly lower after matches compared to training. There were no dietary or medical factors associated with GIS severity scores. This study describes GIS characteristics in male and female rugby union players. Half of the players assessed experienced some form of GIS that may affect nutrition, training, or performance, and should thus be a consideration for practitioners supporting this cohort.

Cold-Water Immersion and Lower Limb Muscle Oxygen Consumption as Measured by Near-Infrared Spectroscopy in Trained Endurance Athletes.

CONTEXT: Cold-water immersion (CWI) has been reported to reduce tissue metabolism postimmersion, but physiological data are lacking regarding the muscle metabolic response to its application. Near-infrared spectroscopy (NIRS) is a noninvasive optical technique that can inform muscle hemodynamics and tissue metabolism. OBJECTIVE: To investigate the effects of CWI at 2 water temperatures (10°C and 15°C) on NIRS-calculated measurements of muscle oxygen consumption (mVO2). DESIGN: Crossover study. SETTING: University sports rehabilitation center. PATIENTS OR OTHER PARTICIPANTS: A total of 11 male National Collegiate Athletic Association Division II long-distance runners (age = 23.4 ± 3.4 years, height = 1.8 ± 0.1 m, mass = 68.8 ± 10.7 kg, mean adipose tissue thickness = 6.7 ± 2.7 mm). INTERVENTION(S): Cold-water immersion at 10°C and 15°C for 20 minutes. MAIN OUTCOME MEASURE(S): We calculated mVO2 preimmersion and postimmersion at water temperatures of 10°C and 15°C. Changes in tissue oxyhemoglobin (O2Hb), deoxyhemoglobin (HHb), total hemoglobin (tHb), hemoglobin difference (Hbdiff), and tissue saturation index (TSI %) were measured during the 20-minute immersion at both temperatures. RESULTS: We observed a decrease in mVO2 after immersion at both 10°C and 15°C (F1,9 = 27.7801, P = .001). During the 20-minute immersion at both temperatures, we noted a main effect of time for O2Hb (F3,27 = 14.227, P = .001), HHb (F3,27 = 5.749, P = .009), tHb (F3,27 = 24.786, P = .001), and Hbdiff (F3,27 = 3.894, P = .020), in which values decreased over the course of immersion. Post hoc pairwise comparisons showed that these changes occurred within the final 5 minutes of immersion for tHb and O2Hb. CONCLUSIONS: A 20-minute CWI at 10°C and 15°C led to a reduction in mVO2. This was greater after immersion at 10°C. The reduction in mVO2 suggests a decrease in muscle metabolic activity (ie, O2 use after CWI). Calculating mVO2 via the NIRS-occlusion technique may offer further insight into muscle metabolic responses beyond what is attainable from observing the NIRS primary signals.

Bridging Eulerian and Lagrangian Poisson-Boltzmann solvers by ESES.

The Poisson-Boltzmann (PB) model is a widely used electrostatic model for biomolecular solvation analysis. Formulated as an elliptic interface problem, the PB model can be numerically solved on either Eulerian meshes using finite difference/finite element methods or Lagrangian meshes using boundary element methods. Molecular surface generators, which produce the discretized dielectric interfaces between solutes and solvents, are critical factors in determining the accuracy and efficiency of the PB solvers. In this work, we investigate the utility of the Eulerian Solvent Excluded Surface (ESES) software for rendering conjugated Eulerian and Lagrangian surface representations, which enables us to numerically validate and compare the quality of Eulerian PB solvers, such as the MIBPB solver, and the Lagrangian PB solvers, such as the TABI-PB solver. Furthermore, with the ESES software and its associated PB solvers, we are able to numerically validate an interesting and useful but often neglected source-target symmetric property associated with the linearized PB model.

Evaluation of a COVID-19 fundamental nursing care guideline versus usual care: The COVID-NURSE cluster randomized controlled trial.

AIM: To evaluate the impact of usual care plus a fundamental nursing care guideline compared to usual care only for patients in hospital with COVID-19 on patient experience, care quality, functional ability, treatment outcomes, nurses' moral distress, patient health-related quality of life and cost-effectiveness. DESIGN: Parallel two-arm, cluster-level randomized controlled trial. METHODS: Between 18th January and 20th December 2021, we recruited (i) adults aged 18 years and over with COVID-19, excluding those invasively ventilated, admitted for at least three days or nights in UK Hospital Trusts; (ii) nurses caring for them. We randomly assigned hospitals to use a fundamental nursing care guideline and usual care or usual care only. Our patient-reported co-primary outcomes were the Relational Aspects of Care Questionnaire and four scales from the Quality from the Patient Perspective Questionnaire. We undertook intention-to-treat analyses. RESULTS: We randomized 15 clusters and recruited 581 patient and 418 nurse participants. Primary outcome data were available for 570-572 (98.1%-98.5%) patient participants in 14 clusters. We found no evidence of between-group differences on any patient, nurse or economic outcomes. We found between-group differences over time, in favour of the intervention, for three of our five co-primary outcomes, and a significant interaction on one primary patient outcome for ethnicity (white British vs. other) and allocated group in favour of the intervention for the 'other' ethnicity subgroup. CONCLUSION: We did not detect an overall difference in patient experience for a fundamental nursing care guideline compared to usual care. We have indications the guideline may have aided sustaining good practice over time and had a more positive impact on non-white British patients' experience of care. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: We cannot recommend the wholescale implementation of our guideline into routine nursing practice. Further intervention development, feasibility, pilot and evaluation studies are required. IMPACT: Fundamental nursing care drives patient experience but is severely impacted in pandemics. Our guideline was not superior to usual care, albeit it may sustain good practice and have a positive impact on non-white British patients' experience of care. REPORTING METHOD: CONSORT and CONSERVE. PATIENT OR PUBLIC CONTRIBUTION: Patients with experience of hospitalization with COVID-19 were involved in guideline development and writing, trial management and interpretation of findings.

Abolishing ß-arrestin recruitment is necessary for the full metabolic benefits of G protein-biased glucagon-like peptide-1 receptor agonists.

AIM: Earlier studies have shown that peptide glucagon-like peptide-1 receptor (GLP-1R) agonists with reduced ß-arrestin recruitment show enhanced anti-hyperglycaemic efficacy through avoidance of GLP-1R desensitization. However, the ligand modifications needed to decrease ß-arrestin recruitment usually also reduces GLP-1R affinity, therefore higher doses are needed. Here we aimed to develop new, long-acting, G protein-biased GLP-1R agonists with acute signalling potency comparable with semaglutide, to provide insights into specific experimental and therapeutic scenarios. MATERIALS AND METHODS: New GLP-1R agonist peptides were assessed using a variety of in vitro and in vivo assays. RESULTS: First, we show that very substantial reductions in ß-arrestin recruitment efficacy are required to realize fully the benefits of GLP-1R agonism on blood glucose lowering in mice, with more moderate reductions being less effective. Secondly, our lead compound (SRB107) performs substantially better than semaglutide for effects on blood glucose and weight loss, which may be jointly attributable to its biased agonist action and protracted pharmacokinetics. Thirdly, we show that biased agonist-specific GLP-1R internalization profiles occur at clinically relevant pharmacological concentrations. Finally, we show that SRB107 cAMP signalling is differentially modulated by single and double GLP1R coding variants seen in human populations, with implications for GLP-1R agonist pharmacogenomics. CONCLUSIONS: Completely abolishing ß-arrestin recruitment improves the anti-hyperglycaemic effects of GLP-1R agonists in mice.

Specialist healthcare services for concussion/mild traumatic brain injury in England: a consensus statement using modified Delphi methodology.

OBJECTIVE: To establish a consensus on the structure and process of healthcare services for patients with concussion in England to facilitate better healthcare quality and patient outcome. DESIGN: This consensus study followed the modified Delphi methodology with five phases: participant identification, item development, two rounds of voting and a meeting to finalise the consensus statements. The predefined threshold for agreement was set at ≥70%. SETTING: Specialist outpatient services. PARTICIPANTS: Members of the UK Head Injury Network were invited to participate. The network consists of clinical specialists in head injury practising in emergency medicine, neurology, neuropsychology, neurosurgery, paediatric medicine, rehabilitation medicine and sports and exercise medicine in England. PRIMARY OUTCOME MEASURE: A consensus statement on the structure and process of specialist outpatient care for patients with concussion in England. RESULTS: 55 items were voted on in the first round. 29 items were removed following the first voting round and 3 items were removed following the second voting round. Items were modified where appropriate. A final 18 statements reached consensus covering 3 main topics in specialist healthcare services for concussion; care pathway to structured follow-up, prognosis and measures of recovery, and provision of outpatient clinics. CONCLUSIONS: This work presents statements on how the healthcare services for patients with concussion in England could be redesigned to meet their health needs. Future work will seek to implement these into the clinical pathway.