Project PRIME: road markings for motorcycle casualty reduction (an overview of findings from 2020 to 2022).

Pioneering road markings for motorcyclists, designed as Perceptual Rider Information for Maximising Expertise and Enjoyment (PRIMEs) were installed on approach to demanding bends at 22 trial sites and two comparison sites across the West Highlands of Scotland. The markings provided a series of 'gateways' to encourage safer riding. With 32,213 motorcyclists observed, the following statistically significant results were observed: speed reductions at 10 trial sites; positive changes in lateral position at the final PRIME gateway marking at 15 trial sites and positive changes in lateral position at the apex of the bend at 13 trial sites; reductions in braking at nine trial sites; increases use of PRIME road markings across 18 of the 22 trial sites. No statistically significant effects were observed at the comparison sites. These findings are discussed in relation to the 'Road Safety Framework to 2030' and the 'Safe System' approach to reducing motorcycle casualties.

This world-first research presents the largest investigation of rider behaviour involving 32,213 motorcyclists. Pioneering road markings for motorcyclists produced statistically significant positive behavioural changes in speed, lateral lane position and braking. This work identifies important behavioural factors that support the 'Safe System' approach to motorcycle casualty reduction.

N6-methyladenosine modification is not a general trait of viral RNA genomes.

Despite the nuclear localization of the m6A machinery, the genomes of multiple exclusively-cytoplasmic RNA viruses, such as chikungunya (CHIKV) and dengue (DENV), are reported to be extensively m6A-modified. However, these findings are mostly based on m6A-Seq, an antibody-dependent technique with a high rate of false positives. Here, we address the presence of m6A in CHIKV and DENV RNAs. For this, we combine m6A-Seq and the antibody-independent SELECT and nanopore direct RNA sequencing techniques with functional, molecular, and mutagenesis studies. Following this comprehensive analysis, we find no evidence of m6A modification in CHIKV or DENV transcripts. Furthermore, depletion of key components of the host m6A machinery does not affect CHIKV or DENV infection. Moreover, CHIKV or DENV infection has no effect on the m6A machinery's localization. Our results challenge the prevailing notion that m6A modification is a general feature of cytoplasmic RNA viruses and underscore the importance of validating RNA modifications with orthogonal approaches.

The Connell Stitch: A Two-Generation Contribution to Gastrointestinal Surgery.

The history of the Connell Stitch begins at the Milwaukee County Hospital in 1887 and continues across two generations of surgeons, Dr. M.E. Connell and Dr. F Gregory Connell. With this historical article, we review the evolution of the Connell stitch in context of the surgeons responsible for the stitch's development and evolution. Understanding the history of the Connell stitch facilitates a better appreciation for the Connell Stitch that we know and use today.

m6A Regulates the Stability of Cellular Transcripts Required for Efficient KSHV Lytic Replication.

The epitranscriptomic modification N6-methyladenosine (m6A) is a ubiquitous feature of the mammalian transcriptome. It modulates mRNA fate and dynamics to exert regulatory control over numerous cellular processes and disease pathways, including viral infection. Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation from the latent phase leads to the redistribution of m6A topology upon both viral and cellular mRNAs within infected cells. Here we investigate the role of m6A in cellular transcripts upregulated during KSHV lytic replication. Our results show that m6A is crucial for the stability of the GPRC5A mRNA, whose expression is induced by the KSHV latent-lytic switch master regulator, the replication and transcription activator (RTA) protein. Moreover, we demonstrate that GPRC5A is essential for efficient KSHV lytic replication by directly regulating NFκB signalling. Overall, this work highlights the central importance of m6A in modulating cellular gene expression to influence viral infection.

Understanding brain functional architecture through robotics.

Robotics is increasingly seen as a useful test bed for computational models of the brain functional architecture underlying animal behavior. We provide an overview of past and current work, focusing on probabilistic and dynamical models, including approaches premised on the free energy principle, situating this endeavor in relation to evidence that the brain constitutes a layered control system. We argue that future neurorobotic models should integrate multiple neurobiological constraints and be hybrid in nature.

On the self-regulation of sport practice: Moving the narrative from theory and assessment toward practice.

This paper reviews theoretical developments specific to applied research around the "psychology of practice" in skill acquisition settings, which we argue is under-considered in applied sport psychology. Centered upon the Self-Regulation of Sport Practice Survey (SRSP), we explain how self-regulated learning conceptually underpins this survey and review recent data supporting its empirical validation for gauging athletes' psychological processes in relation to sport practice. This paper alternates between a review of applied research on self-regulated sport practice and new data analyses to: (a) show how scores on the SRSP combine to determine an expert practice advantage and (b) illustrate the large scope of self-organized or athlete-led time to which SRSP processes may apply. At this stage, the SRSP has been established as a reliable and valid tool in the empirical, theoretical domain. In order to move the narrative from theory and assessment toward applied practice, we present evidence to propose that it has relevance as a dialogue tool for fostering meaningful discussions between athletes and sport psychology consultants. We review initial case study insights on how the SRSP could be located in consultation in professional practice, propose initial considerations for its practical use and invite practitioners to examine its utility in applied settings.

Examining the validity of the polish short form version of the self-regulated learning-sport practice survey among competitive athletes.

Introduction: Self-regulated learning entails psychological processes that elite athletes employ to optimize their practice. Although self-regulated learning provides insights into athlete-led practice, research has been limited to few cultures, and the particularities of how SRL surveys perform in new cultural contexts require attention. Moreover, there exists no measure to assess SRL and its relationship to quality sport practice in Polish. Thus, we examined the Short Form of the Self-Regulated Learning-Sport Practice survey in Polish. Analyses addressed the factorial validity and reliability, the criterion validity (by assessing differences in scores between competition levels), and the concurrent validity (by correlating scores with conceptually related constructs) of a Polish Short Form survey. Methods: Athletes (N = 324, M age = 21.4, n females = 144, n males = 180) from amateur, regional, national, and international-elite levels completed the survey, along with concurrent subscales (General Self-Efficacy Scale; GSES; Metacognitive-Self Scale; MS-24; Action Control Scale; ACS-90). Results: Confirmatory factor analysis indicated a two-factor (metacognitive; motivational) model (RMSEA = 0.082, SRMR = 0.057, CFI = 0.89). Between-group tests showed international-elite scoring higher than all other groups on metacognitive and motivational subscales. On both subscales, significant trends indicated that more skilled levels consistently reported higher scores than lesser-skilled levels. The short form scores were associated with certain concurrent variables, including GSES (rmeta = 0.41, rmotiv = 0.48), MS-24 (rmeta = 0.39, rmotiv = 0 .24), and ACS-90 (AOF subscale: rmotiv = 0 .26). Discussion: On the basis of strong criterion validity, and moderate evidence for concurrent validity, we conclude that the Polish Short Form of the Self-Regulated Learning-Sport Practice survey is a promising tool for use in Polish sport and we discuss future avenues of work to enhance its validation. Limitations that inform future research include our reliance on a mixed-sport sample, the lack of priming of obstacles/challenge ahead of self-report, and a lack of consideration of sport-specific practice variables in analyses.

Wrist Arthrodesis Using the Medartis Carpometacarpal Joint Sparing Plate.

BACKGROUND: Total wrist arthrodesis is a well-established surgical technique that provides reliable pain relief in patients with advanced wrist disease. Key limitations of existing plating systems include hardware pull-out, hardware failure, and nonunion. There is limited literature on the newer style carpometacarpal joint (CMCJ) sparing plating system, produced by Medartis. The objective of this study was to determine the long-term clinical and radiological outcomes of wrist arthrodesis with a CMCJ sparing wrist plate. METHODS: This study retrospectively identified 23 wrist arthrodeses using the Medartis CMCJ sparing plate for review. This study assessed the outcomes of 18 unilateral wrist fusions and 1 bilateral wrist fusion. The study group consisted of 12 men and 5 women with an average age of 56 years (range: 29-82 years) with a mean follow-up period of 17 months. RESULTS: At the time of follow-up, all patients' wrists had fused without postsurgical complication. The final grip strength in the operative hand was 28.2 kg/cm2, which was 87% of the contralateral side. The mean Quick Disabilities of the Arm, Shoulder, and Hand score at follow-up was 23.9, with all patients returning to daily living activities and work. Patients reported minimal pain (1.3/10), with almost all (17/18) satisfied with the outcome of the surgery and describing that they would recommend this procedure. CONCLUSION: Our case series highlights that the Medartis wrist arthrodesis plate is a newer design that is a well-tolerated option for wrist arthrodesis based on clinical assessment, functional hand assessment, and patient satisfaction, when compared with the existing literature on traditional plating systems.

Comparing the development of cortex-wide gene expression patterns between two species in a common reference frame.

Advances in sequencing techniques have made comparative studies of gene expression a current focus for understanding evolutionary and developmental processes. However, insights into the spatial expression of genes have been limited by a lack of robust methodology. To overcome this obstacle, we developed methods and software tools for quantifying and comparing tissue-wide spatial patterns of gene expression within and between species. Here, we compare cortex-wide expression of RZRß and Id2 mRNA across early postnatal development in mice and voles. We show that patterns of RZRß expression in neocortical layer 4 are highly conserved between species but develop rapidly in voles and much more gradually in mice, who show a marked expansion in the relative size of the putative primary visual area across the first postnatal week. Patterns of Id2 expression, by contrast, emerge in a dynamic and layer-specific sequence that is consistent between the two species. We suggest that these differences in the development of neocortical patterning reflect the independent evolution of brains, bodies, and sensory systems in the 35 million years since their last common ancestor.

Biological action at a distance: Correlated pattern formation in adjacent tessellation domains without communication.

Tessellations emerge in many natural systems, and the constituent domains often contain regular patterns, raising the intriguing possibility that pattern formation within adjacent domains might be correlated by the geometry, without the direct exchange of information between parts comprising either domain. We confirm this paradoxical effect, by simulating pattern formation via reaction-diffusion in domains whose boundary shapes tessellate, and showing that correlations between adjacent patterns are strong compared to controls that self-organize in domains with equivalent sizes but unrelated shapes. The effect holds in systems with linear and non-linear diffusive terms, and for boundary shapes derived from regular and irregular tessellations. Based on the prediction that correlations between adjacent patterns should be bimodally distributed, we develop methods for testing whether a given set of domain boundaries constrained pattern formation within those domains. We then confirm such a prediction by analysing the development of 'subbarrel' patterns, which are thought to emerge via reaction-diffusion, and whose enclosing borders form a Voronoi tessellation on the surface of the rodent somatosensory cortex. In more general terms, this result demonstrates how causal links can be established between the dynamical processes through which biological patterns emerge and the constraints that shape them.

Scaffolding layered control architectures through constraint closure: insights into brain evolution and development.

The functional organization of the mammalian brain can be considered to form a layered control architecture, but how this complex system has emerged through evolution and is constructed during development remains a puzzle. Here we consider brain organization through the framework of constraint closure, viewed as a general characteristic of living systems, that they are composed of multiple sub-systems that constrain each other at different timescales. We do so by developing a new formalism for constraint closure, inspired by a previous model showing how within-lifetime dynamics can constrain between-lifetime dynamics, and we demonstrate how this interaction can be generalized to multi-layered systems. Through this model, we consider brain organization in the context of two major examples of constraint closure-physiological regulation and visual orienting. Our analysis draws attention to the capacity of layered brain architectures to scaffold themselves across multiple timescales, including the ability of cortical processes to constrain the evolution of sub-cortical processes, and of the latter to constrain the space in which cortical systems self-organize and refine themselves. This article is part of the theme issue 'Systems neuroscience through the lens of evolutionary theory'.

Pilot Examination of the Efficacy of the Internet-Delivered, Preoperative, Preparation Program (I-PPP).

Limited evidence-based, interactive, Internet-delivered preoperative preparation programs for children and their parents exist. The purpose of this investigation was to compare the Internet-delivered, preoperative program (I-PPP) in alleviating anxiety in children undergoing outpatient surgery delivered alone (I-PPP) and in conjunction with parental presence (I-PPP + parent) to treatment as usual (TAU). 104 children undergoing day surgery procedures at a local hospital and their parents/guardians participated. Primary outcome measures: (a) observer-rated child anxiety and (b) induction compliance. Results demonstrated an interaction between the I-PPP and TAU groups over time, F(1, 64) = 5.11, p = .027, partial η p2 = .07. At anesthetic induction, the I-PPP group demonstrated lower observer-rated anxiety than TAU, F(1, 64) = 4.72, p = .034, η p2 = .07. I-PPP group demonstrated the best anesthesia induction compliance, F(1, 64) = 4.84, p = .031, η p2 = .07. Our findings demonstrate that the I-PPP is an efficacious preoperative preparation intervention for children. The 'real-world' uptake and integration of the I-PPP into pediatric preoperative settings require exploration going forward. Trial retrospectively registered March 2019 (Open Science Registration https://doi.org/10.17605/osf.io/2x8rg ).

Talent Research in Sport 1990-2018: A Scoping Review.

Several recent systematic and targeted reviews have highlighted limitations in our understanding of talent in sport. However, a comprehensive profile of where the scientific research has focused would help identify gaps in current knowledge. Our goal in this scoping review was (a) to better understand what others have done in the field of research (e.g., what groups have been examined using what research designs and in what areas), (b) to summarize the constituent areas of research in a meaningful way, (c) to help identify gaps in the research, and (d) to encourage future research to address these gaps. Peer-reviewed articles written in English that met several inclusion criteria were analyzed. A total of 1,899 articles were identified, and the descriptive findings revealed a relatively narrow focus of research on talent in sport. Specifically, the majority of examined articles focused on (a) males only, (b) the sport of soccer, (c) perceptual cognitive variables, (d) developing athletes, (e) adult samples, and (f) cross-sectional designs. For better or worse, the concept of talent remains a central element of how coaches, practitioners, and scientists think about athlete development. Findings from this scoping review highlight the continued need to explore issues related to talent identification, selection, and development in more diverse samples (e.g., female athletes and younger ages) and contexts (e.g., from Africa, Asia, and South America). There is also a clear necessity to focus on under-researched areas using alternative methodologies.

Detecting SARS-CoV-2 at point of care: preliminary data comparing loop-mediated isothermal amplification (LAMP) to polymerase chain reaction (PCR).

BACKGROUND: A cost effective and efficient diagnostic tool for COVID-19 as near to the point of care (PoC) as possible would be a game changer in the current pandemic. We tested reverse transcription loop mediated isothermal amplification (RT-LAMP), a method which can produce results in under 30 min, alongside standard methods in a real-life clinical setting. METHODS: This prospective service improvement project piloted an RT-LAMP method on nasal and pharyngeal swabs on 21 residents of a high dependency care home, with two index COVID-19 cases, and compared it to multiplex tandem reverse transcription polymerase chain reaction (RT-PCR). We recorded vital signs of patients to correlate clinical and laboratory information and calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of a single swab using RT-LAMP compared with the current standard, RT-PCR, as per Standards for Reporting Diagnostic Accuracy Studies (STARD) guidelines. RESULTS: The novel method accurately detected 8/10 RT-PCR positive cases and identified a further 3 positive cases. Eight further cases were negative using both methods. Using repeated RT-PCR as a "gold standard", the sensitivity and specificity of a single novel test were 80 and 73% respectively. PPV was 73% and NPV was 83%. Incorporating retesting of low signal RT-LAMP positives improved the specificity to 100%. We also speculate that hypothermia may be a significant early clinical sign of COVID-19. CONCLUSIONS: RT-LAMP testing for SARS-CoV-2 was found to be promising, fast and to work equivalently to RT-PCR methods. RT-LAMP has the potential to transform COVID-19 detection, bringing rapid and accurate testing to the PoC. RT-LAMP could be deployed in mobile community testing units, care homes and hospitals to detect disease early and prevent spread.

Modelling the emergence of whisker barrels.

Brain development relies on an interplay between genetic specification and self-organization. Striking examples of this relationship can be found in the somatosensory brainstem, thalamus, and cortex of rats and mice, where the arrangement of the facial whiskers is preserved in the arrangement of cell aggregates to form precise somatotopic maps. We show in simulation how realistic whisker maps can self-organize, by assuming that information is exchanged between adjacent cells only, under the guidance of gene expression gradients. The resulting model provides a simple account of how patterns of gene expression can constrain spontaneous pattern formation to faithfully reproduce functional maps in subsequent brain structures.

How does the brain wire itself up? One possibility is that a precise genetic blueprint tells every brain cell explicitly how it should be connected to other cells. Another option is that complex patterns emerge from relatively simple interactions between growing cells, which are more loosely controlled by genetic instruction. The barrel cortex in the brains of rats and mice features one of the most distinctive wiring patterns. There, cylindrical clusters of cells ­ or barrels ­ are arranged in a pattern that closely matches the arrangement of the whiskers on the face. Neurons in a barrel become active when the corresponding whisker is stimulated. This precise mapping between individual whiskers and their brain counterparts makes the whisker-barrel system ideal for studying brain wiring. Guidance fields are a way the brain can create cell networks with wiring patterns like the barrels. In this case, genetic instructions help to create gradients of proteins across the brain. These help the axons that connect neurons together to grow in the right direction, by navigating towards regions of higher or lower concentrations. A large number of guidance fields could map out a set of centre-point locations for axons to grow towards, ensuring the correct barrel arrangement. However, there are too few known guidance fields to explain how the barrel cortex could form by this kind of genetic instruction alone. Here, James et al. tried to find a mechanism that could create the structure of the barrel cortex, relying only on two simple guidance fields. Indeed, two guidance fields should be enough to form a coordinate system on the surface of the cortex. In particular, it was examined whether the cortical barrel map could reliably self-organize without a full genetic blueprint pre-specifying the barrel centre-points in the cortex. To do so, James et al. leveraged a mathematical model to create computer simulations; these showed that only two guidance fields are required to reproduce the map. However, this was only the case if axons related to different whiskers competed strongly for space while making connections, causing them to concentrate into whisker-specific clusters. The simulations also revealed that the target tissue does not need to specify centre-points if, instead, the origin tissue directs how strongly the axons should respond to the guidance fields. So this model describes a simple way that specific structures can be copied across the central nervous system. Understanding the way the barrel cortex is set up could help to grasp how healthy brains develop, how brain development differs in certain neurodevelopmental disorders, and how brain wiring reorganizes itself in different contexts, for example after a stroke. Computational models also have the potential to reduce the amount of animal experimentation required to understand how brains are wired, and to cast light on how brain wiring is shaped by evolution.

Collective directional movement and the perception of social cohesion.

We argue that perceivers associate collective directional movement - groups moving from one place to the next - with higher levels of social cohesion. Study 1 shows that pairs are rated as being more cohesive when described as engaging in directional movement compared to non-directional activities. Study 2 replicates this finding using film clips. Study 3 reveals that the proximity of directionally moving dyads is a better predictor of perceived cohesion than behavioural synchrony. Study 4 replicates the original finding and reveals that perceptions of common fate and shared goals both contribute to the effect, with the former having more predictive power than the latter. We suggest that collective directional movement is an invariant part of social environments and is utilized by perceivers to make inferences about social dynamics.

Limit cycle dynamics can guide the evolution of gene regulatory networks towards point attractors.

Developmental dynamics in Boolean models of gene networks self-organize, either into point attractors (stable repeating patterns of gene expression) or limit cycles (stable repeating sequences of patterns), depending on the network interactions specified by a genome of evolvable bits. Genome specifications for dynamics that can map specific gene expression patterns in early development onto specific point attractor patterns in later development are essentially impossible to discover by chance mutation alone, even for small networks. We show that selection for approximate mappings, dynamically maintained in the states comprising limit cycles, can accelerate evolution by at least an order of magnitude. These results suggest that self-organizing dynamics that occur within lifetimes can, in principle, guide natural selection across lifetimes.

The Tudor SND1 protein is an m6A RNA reader essential for replication of Kaposi's sarcoma-associated herpesvirus.

N6-methyladenosine (m6A) is the most abundant internal RNA modification of cellular mRNAs. m6A is recognised by YTH domain-containing proteins, which selectively bind to m6A-decorated RNAs regulating their turnover and translation. Using an m6A-modified hairpin present in the Kaposi's sarcoma associated herpesvirus (KSHV) ORF50 RNA, we identified seven members from the 'Royal family' as putative m6A readers, including SND1. RIP-seq and eCLIP analysis characterised the SND1 binding profile transcriptome-wide, revealing SND1 as an m6A reader. We further demonstrate that the m6A modification of the ORF50 RNA is critical for SND1 binding, which in turn stabilises the ORF50 transcript. Importantly, SND1 depletion leads to inhibition of KSHV early gene expression showing that SND1 is essential for KSHV lytic replication. This work demonstrates that members of the 'Royal family' have m6A-reading ability, greatly increasing their epigenetic functions beyond protein methylation.