Shuffling and Unshuffling

We consider various shuffling and unshuffling operations on languages and words, and examine their closure properties. Although the main goal is to provide some good and novel exercises and examples for undergraduate formal language theory classes, we also provide some new results and some open problems

Delays in Multiple Sclerosis diagnosis (DIMES): protocol for a multicentre, observational study of multiple sclerosis diagnostic pathways in the United Kingdom and Republic of Ireland.

BACKGROUND: Multiple sclerosis (MS) is a leading cause of non-traumatic disability in young adults. Accumulating evidence indicates early diagnosis and early treatment improves long-term outcomes. However, the MS diagnostic pathway is increasingly complex, and delays may occur at several stages. Factors causing delays remain understudied. We aim to quantify the time taken for MS to be diagnosed, and characterise the diagnostic pathway and initial care provided, in the United Kingdom (UK) and Republic of Ireland (ROI). METHODS: Delays In MultiplE Sclerosis diagnosis (DIMES) in the UK and ROI is a multicentre, observational, retrospective study that will be conducted via the Neurology and Neurosurgery Interest Group (NANSIG) collaborative network. Any hospital in the UK and ROI providing an MS diagnostic service is eligible to participate. Data on consecutive individuals newly diagnosed with MS between 1st July 2022 and 31st December 2022 will be collected. The primary outcomes are 1) time from symptoms/signs prompting referral to neurology, to MS diagnosis; and 2) time from referral to neurology for suspected MS, to MS diagnosis. Secondary outcomes include: MS symptoms, referring specialties, investigations performed, neurology appointments, functional status, use of disease modifying treatments, and support at diagnosis including physical activity, and follow up. Demographic characteristics of people newly diagnosed with MS will be summarised, adherence to quality standards summarised as percentages, and time-to-event variables presented with survival curves. Multivariable models will be used to investigate the association of demographic and clinical factors with time to MS diagnosis, as defined in our primary outcomes. DISCUSSION: DIMES aims to be the largest multicentre study of the MS diagnostic pathway in the UK and ROI. The proposed data collection provides insights that cannot be provided from contemporary registries, and the findings will inform approaches to MS services nationally in the future

Cellular dissection of malaria parasite invasion of human erythrocytes using viable Plasmodium knowlesi merozoites

Plasmodium knowlesi, a zoonotic parasite causing severe-to-lethal malaria disease in humans, has only recently been adapted to continuous culture with human red blood cells (RBCs). In comparison with the most virulent human malaria, Plasmodium falciparum, there are, however, few cellular tools available to study its biology, in particular direct investigation of RBC invasion by blood-stage P. knowlesi merozoites. This leaves our current understanding of biological differences across pathogenic Plasmodium spp. incomplete. Here, we report a robust method for isolating viable and invasive P. knowlesi merozoites to high purity and yield. Using this approach, we present detailed comparative dissection of merozoite invasion (using a variety of microscopy platforms) and direct assessment of kinetic differences between knowlesi and falciparum merozoites. We go on to assess the inhibitory potential of molecules targeting discrete steps of invasion in either species via a quantitative invasion inhibition assay, identifying a class of polysulfonate polymer able to efficiently inhibit invasion in both, providing a foundation for pan-Plasmodium merozoite inhibitor development. Given the close evolutionary relationship between P. knowlesi and P. vivax, the second leading cause of malaria-related morbidity, this study paves the way for inter-specific dissection of invasion by all three major pathogenic malaria species

Enhanced tensile ductility in Al-Mg alloys by solid-solution interactions

The development of methods for obtaining high tensile elongation in aluminum alloys is of great importance for the practical forming of near-net-shape parts. Current superplastic alloys are limited in use by high material costs. The utilization of solute-drag creep processes, the approach used in this study, to obtain enhanced tensile ductility in aluminum alloys has lead to tensile elongations of up to 325% in simple, binary Al-Mg alloys with coarse grain sizes. This method has the advantage of lowering processing costs in comparison with superplastic alloys because a fine grain size is not necessary. Whereas superplastic alloys typically have a strain-rate sensitivity of m = 0.5, the enhanced ductility Al-Mg alloys typically exhibit m = 0.3 where maximum ductility is observed. Although a strain-rate sensitivity of rn = 0.5 can lead to elongations of over 1000% (superplastic materials) a value of m = 0.3 is shown experimentally to be sufficient for obtaining elongations of 150% to a maximum observed of 325%. Enhanced ductility is also affected strongly by ternary alloying additions, such as Mn, for which a preliminary understanding is pursued

Expression of LMO4 and outcome in pancreatic ductal adenocarcinoma

Identification of a biomarker of prognosis and response to therapy that can be assessed preoperatively would significantly improve overall outcomes for patients with pancreatic cancer. In this study, patients whose tumours exhibited high LMO4 expression had a significant survival advantage following operative resection, whereas the survival of those patients whose tumours had low or no LMO4 expression was not significantly different when resection was compared with operative biopsy alone

Environmentally vulnerable noble chafers exhibit unusual pheromone-mediated behaviour

Conserving populations of environmentally vulnerable insect species requires a greater understanding of the factors that determine their abundance and distribution, which requires detailed knowledge of their population and community ecology. Chemical ecological tools such as pheromones can be used for non-destructive monitoring of scarab beetle populations, enabling European countries to detect and, in some cases, map the range of some of these species, proving a valuable technique for monitoring elusive saproxylic beetles. In this paper, we investigated the behavioural and chemical ecology of the noble chafer, Gnorimus nobilis L., a model insect species of conservation concern across a Europe-wide distribution, and a red-listed UK Biodiversity Action Plan priority species. We identified a potential pheromone of adult beetles using electrophysiological recordings, behavioural measurements and field trials in the UK. Gnorimus nobilis is highly unusual in that although both sexes produce, at high metabolic cost, the natural product 2-propyl (E)-3-hexenoate, it only attracts males. This pattern of chemical signalling makes the classification of the compound, based on current semiochemical terminology, somewhat problematic, but in our view, it should be termed an aggregation pheromone as a consequence of the production pattern. Since both sexes emit it, but apparently only males respond positively to it, 2-propyl (E)-3-hexenoate may reflect an intermediate evolutionary stage towards developing into a sex-specific signal. From an applied perspective, our study provides a model for the non-invasive surveillance of cryptic vulnerable insect species, without the need for habitat searching or disturbance, and continuous human monitoring

Functional modelling of complex multi‑disciplinary systems using the enhanced sequence diagram

YesThis paper introduces an Enhanced Sequence Diagram (ESD) as the basis for a structured framework for the functional analysis of complex multidisciplinary systems. The ESD extends the conventional sequence diagrams (SD) by introducing a rigorous functional flow-based modelling schemata to provide an enhanced basis for model-based functional requirements and architecture analysis in the early systems design stages. The proposed ESD heuristics include the representation of transactional and transformative functions required to deliver the use case sequence, and fork and join nodes to facilitate analysis of combining and bifurcating operations on flows. A case study of a personal mobility device is used to illustrate the deployment of the ESD methodology in relation to three common product development scenarios: (i) reverse engineering, (ii) the introduction of a specific technology to an existent system; and (iii) the introduction of a new feature as user-centric innovation for an existing system, at a logical design level, without reference to any solution. The case study analysis provides further insights into the effectiveness of the ESD to support function modelling and functional requirements capture, and architecture development. The significance of this paper is that it establishes a rigorous ESD-based functional analysis methodology to guide the practitioner with its deployment, facilitating its impact to both the engineering design and systems engineering communities, as well as the design practice in the industry

Functional modelling of complex multi‑disciplinary systems using the enhanced sequence diagram

YesThis paper introduces an Enhanced Sequence Diagram (ESD) as the basis for a structured framework for the functional analysis of complex multidisciplinary systems. The ESD extends the conventional sequence diagrams (SD) by introducing a rigorous functional flow-based modelling schemata to provide an enhanced basis for model-based functional requirements and architecture analysis in the early systems design stages. The proposed ESD heuristics include the representation of transactional and transformative functions required to deliver the use case sequence, and fork and join nodes to facilitate analysis of combining and bifurcating operations on flows. A case study of a personal mobility device is used to illustrate the deployment of the ESD methodology in relation to three common product development scenarios: (i) reverse engineering, (ii) the introduction of a specific technology to an existent system; and (iii) the introduction of a new feature as user-centric innovation for an existing system, at a logical design level, without reference to any solution. The case study analysis provides further insights into the effectiveness of the ESD to support function modelling and functional requirements capture, and architecture development. The significance of this paper is that it establishes a rigorous ESD-based functional analysis methodology to guide the practitioner with its deployment, facilitating its impact to both the engineering design and systems engineering communities, as well as the design practice in the industry

The utilisation of health research in policy-making: Concepts, examples and methods of assessment

The importance of health research utilisation in policy-making, and of understanding the mechanisms involved, is increasingly recognised. Recent reports calling for more resources to improve health in developing countries, and global pressures for accountability, draw greater attention to research-informed policy-making. Key utilisation issues have been described for at least twenty years, but the growing focus on health research systems creates additional dimensions. The utilisation of health research in policy-making should contribute to policies that may eventually lead to desired outcomes, including health gains. In this article, exploration of these issues is combined with a review of various forms of policy-making. When this is linked to analysis of different types of health research, it assists in building a comprehensive account of the diverse meanings of research utilisation. Previous studies report methods and conceptual frameworks that have been applied, if with varying degrees of success, to record utilisation in policy-making. These studies reveal various examples of research impact within a general picture of underutilisation. Factors potentially enhancing utilisation can be identified by exploration of: priority setting; activities of the health research system at the interface between research and policy-making; and the role of the recipients, or 'receptors', of health research. An interfaces and receptors model provides a framework for analysis. Recommendations about possible methods for assessing health research utilisation follow identification of the purposes of such assessments. Our conclusion is that research utilisation can be better understood, and enhanced, by developing assessment methods informed by conceptual analysis and review of previous studies