The Spin--Symmetry of the Quark Model

Corrections to the exact heavy--quark symmetry results are expected to follow the $1/m_{Q}$ mass effect of the heavy--quark. We show, by an explicit calculation, that there is something other than the mass effect that suppresses the breaking of the spin symmetry

The extent and specificity of relative age effects on mental health and functioning in early adolescence

BACKGROUND: Although extensive evidence indicates that being younger within a school cohort is associated with poorer academic functioning, much less is known about such relative-age effects (RAEs) for mental health. METHODS: Data from 23,378 11-13 year olds attending state-maintained secondary schools in England were analysed to investigate RAEs on mental health measured using the Strengths and Difficulties Questionnaire. Participants were grouped into oldest, middle and youngest thirds of their academic year based on their month of birth relative to their cohort. Hierarchical linear regression analysis evaluated RAEs and gender- or deprivation-related moderation of such effects. RESULTS: Relatively younger adolescents had significantly more emotional symptoms and peer problems compared to relatively older individuals in a year group, though effect sizes were small. These effects were not moderated by gender or deprivation. Impact of mental health difficulties on other aspects of functioning were also greater among relatively younger children. Larger RAEs are observed in the younger cohort (11-12 years) compared to in the 12-13 year olds, thereby indicating that RAEs might attenuate with age. CONCLUSION: Being relatively younger than classmates is associated with increased internalising symptoms, poorer peer relationships, and higher impact of mental health difficulties on functioning at school and home. The findings support wider inclusion of relative age in understanding mental health difficulties and its inclusion as a potential risk factor in studies investigating the development of psychopathology, especially for internalising symptoms. Possible mechanisms of the effects detected are discussed

Online, interactive user guidance for high-dimensional, constrained motion planning

We consider the problem of planning a collision-free path for a high-dimensional robot. Specifically, we suggest a planning framework where a motion-planning algorithm can obtain guidance from a user. In contrast to existing approaches that try to speed up planning by incorporating experiences or demonstrations ahead of planning, we suggest to seek user guidance only when the planner identifies that it ceases to make significant progress towards the goal. Guidance is provided in the form of an intermediate configuration $\hat{q}$, which is used to bias the planner to go through $\hat{q}$. We demonstrate our approach for the case where the planning algorithm is Multi-Heuristic A* (MHA*) and the robot is a 34-DOF humanoid. We show that our approach allows to compute highly-constrained paths with little domain knowledge. Without our approach, solving such problems requires carefully-crafting domain-dependent heuristics

Quantitative analysis of cryptic splicing associated with TDP-43 depletion

BACKGROUND: Reliable exon recognition is key to the splicing of pre-mRNAs into mature mRNAs. TDP-43 is an RNA-binding protein whose nuclear loss and cytoplasmic aggregation are a hallmark pathology in amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). TDP-43 depletion causes the aberrant inclusion of cryptic exons into a range of transcripts, but their extent, relevance to disease pathogenesis and whether they are caused by other RNA-binding proteins implicated in ALS/FTD are unknown. METHODS: We developed an analysis pipeline to discover and quantify cryptic exon inclusion and applied it to publicly available human and murine RNA-sequencing data. RESULTS: We detected widespread cryptic splicing in TDP-43 depletion datasets but almost none in another ALS/FTD-linked protein FUS. Sequence motif and iCLIP analysis of cryptic exons demonstrated that they are bound by TDP-43. Unlike the cryptic exons seen in hnRNP C depletion, those repressed by TDP-43 cannot be linked to transposable elements. Cryptic exons are poorly conserved and inclusion overwhelmingly leads to nonsense-mediated decay of the host transcript, with reduced transcript levels observed in differential expression analysis. RNA-protein interaction data on 73 different RNA-binding proteins showed that, in addition to TDP-43, 7 specifically bind TDP-43 linked cryptic exons. This suggests that TDP-43 competes with other splicing factors for binding to cryptic exons and can repress cryptic exon inclusion. CONCLUSIONS: Our quantitative analysis pipeline confirms the presence of cryptic exons during the depletion of TDP-43 but not FUS providing new insight into to RNA-processing dysfunction as a cause or consequence in ALS/FTD

Advancing methodology for scoping reviews: recommendations arising from a scoping literature review (SLR) to inform transformation of Children and Adolescent Mental Health Services

Background There is consensus that health services commissioning and clinical practice should be driven by scientific evidence. However, workload pressures, accessibility of peer reviewed publications and skills to find, appraise, and synthesise relevant evidence are often cited as barriers to uptake of research evidence by practitioners and commissioners alike. In recent years a growing requirement for rapid evidence synthesis to inform commissioning decisions about healthcare service delivery and provision of care contributed to an increasing popularity of scoping literature reviews (SLRs). Yet, comprehensive guidelines for conducting and reporting SLRs are still relatively scarce. Methods The exemplar review used as a worked example aimed to provide a readily available, comprehensive, and user-friendly repository of research evidence for local commissioners to help them make evidence-informed decisions about redesigning East of England Children and Adolescent Mental Health Services. In conducting the review, we were broadly guided by Arksey and O’Malley’s framework, however some modifications were made at different stages to better reflect the largely pragmatic objective of this review. This paper compares the methodology used with existing methodological frameworks for scoping studies, to add to the existing knowledge base. Results We proposed the following advancements to the existing SLR frameworks: (i) Assemble a research team with complementary skills and expertise; (ii); Draw on expertise of external partners, particularly practitioners, decision-makers and commissioners who will be translating findings into practice; (iii) Pre-register the review protocol. Keep a detailed record of all steps and decisions and consider how they would impact on generalisability and utility of review findings; (iv) Use systematic procedures for literature searchers, selection of studies, data extraction and analysis; (v) If feasible, appraise the quality of included evidence; (vi) Be transparent about limitations of findings. Conclusions Despite some methodological limitations, scoping literature reviews are a useful method of rapidly synthesising a large body of evidence to inform commissioning and transformation of CAMHS. SLRs allow researchers to start with a broader questions, to explore the issue from different perspectives and perhaps find more comprehensive solutions that are not only effective, but also accounted for their feasibility and acceptability to key stakeholders

Analytical and numerical analyses of the micromechanics of soft fibrous connective tissues

State of the art research and treatment of biological tissues require accurate and efficient methods for describing their mechanical properties. Indeed, micromechanics motivated approaches provide a systematic method for elevating relevant data from the microscopic level to the macroscopic one. In this work the mechanical responses of hyperelastic tissues with one and two families of collagen fibers are analyzed by application of a new variational estimate accounting for their histology and the behaviors of their constituents. The resulting, close form expressions, are used to determine the overall response of the wall of a healthy human coronary artery. To demonstrate the accuracy of the proposed method these predictions are compared with corresponding 3-D finite element simulations of a periodic unit cell of the tissue with two families of fibers. Throughout, the analytical predictions for the highly nonlinear and anisotropic tissue are in agreement with the numerical simulations