Increasing the efficacy of automated instruction set extension

The use of Instruction Set Extension (ISE) in customising embedded processors for a specific application has been studied extensively in recent years. The addition of a set of complex arithmetic instructions to a baseline core has proven to be a cost-effective means of meeting design performance requirements. This thesis proposes and evaluates a reconfigurable ISE implementation called “Configurable Flow Accelerators” (CFAs), a number of refinements to an existing Automated ISE (AISE) algorithm called “ISEGEN”, and the effects of source form on AISE. The CFA is demonstrated repeatedly to be a cost-effective design for ISE implementation. A temporal partitioning algorithm called “staggering” is proposed and demonstrated on average to reduce the area of CFA implementation by 37% for only an 8% reduction in acceleration. This thesis then turns to concerns within the ISEGEN AISE algorithm. A methodology for finding a good static heuristic weighting vector for ISEGEN is proposed and demonstrated. Up to 100% of merit is shown to be lost or gained through the choice of vector. ISEGEN early-termination is introduced and shown to improve the runtime of the algorithm by up to 7.26x, and 5.82x on average. An extension to the ISEGEN heuristic to account for pipelining is proposed and evaluated, increasing acceleration by up to an additional 1.5x. An energyaware heuristic is added to ISEGEN, which reduces the energy used by a CFA implementation of a set of ISEs by an average of 1.6x, up to 3.6x. This result directly contradicts the frequently espoused notion that “bigger is better” in ISE. The last stretch of work in this thesis is concerned with source-level transformation: the effect of changing the representation of the application on the quality of the combined hardwaresoftware solution. A methodology for combined exploration of source transformation and ISE is presented, and demonstrated to improve the acceleration of the result by an average of 35% versus ISE alone. Floating point is demonstrated to perform worse than fixed point, for all design concerns and applications studied here, regardless of ISEs employed

Club, country and clinicians united : ensuring collaborative care in elite sport medical handovers

Medical handovers are fundamental to optimal patient care but can be a source of errors in clinical care with important implications on patient welfare and safety. Care of international athletes presents unique challenges to open and effective communication between medical teams. Handover of complete medical records should occur with athlete consent between medical teams on the transfer of an athlete between clubs. There are currently no specific guidelines or published recommendations advising sports and exercise medicine clinicians about medical handovers. The aim of this editorial is to provide a checklist of recommendations for the handover of elite athlete care between clubs and national medical and sports science teams, with lessons shared from professional football (soccer).http://bjsm.bmj.compm2021Sports Medicin

Enhancing medical students` confidence and performance in integrated structured clinical examinations (ISCE) through a novel near-peer, mixed model approach during the COVID-19 pandemic

Background: Near-peer medical education serves as an important method of delivering education to junior students by senior students. Due to the reduced clinical exposure because of the COVID-19 pandemic, we developed a mentorship scheme to help medical students with their Integrated Structured Clinical Examinations (ISCEs) by providing a combination of near-peer mentorship together with lecture-based teaching on a weekly basis for a 12-week period. Students attended a specialty-focused lecture every Tuesday followed by a small group teaching session organised by their tutor. Methods: A longitudinal evaluative interventional study was undertaken by the international student led medical education organisation, OSCEazy. The teaching programme was organised and conducted by third year medical students to a recruited cohort of second year medical students. Students’ perceptions of ISCEs (confidence, anxiety, and overall performance) were evaluated using 5-point Likert scales while their knowledge of the specialty was assessed using 10 single best answer questions which were distributed via Google® forms at the start and end of each week. In addition, we assessed tutor perceptions of their teaching and learning experience. Results: Seventy-two tutees were enrolled in the programme (mean age: 24.4, female: 77.8%). 88.9% of the participants had not attended any online ISCE teaching prior to this. They preferred in-person ISCE teaching as compared to virtual sessions [median 4.5 (IQR 4–5) vs 3 (IQR 3–4), p < 0.0001), respectively]. There was a significant overall increase in knowledge when comparing pre-session and post-session performance [mean 53.7% vs 70.7%, p < 0.0001)]. There was a significant increase in student confidence [Confidence: median 3 (IQR:3–4) vs 4 (IQR 3–4), p < 0.0001] while no change was seen in the anxiety and perception of their overall performance in an ISCE. [Anxiety: median 3 (IQR 2–4) vs 3 (IQR 3–4), p = 0.37, Performance: median 3 (IQR 3–4) vs median 3 (IQR 3–4), p < 0.0001]. The tutors reported an increase in their confidence in teaching ISCEs online [median 3 (IQR 2–3.25) vs median 4 (IQR 4–5), p < 0.0001)]. Conclusion: Online near-peer teaching increases the confidence of both tutees and tutors involved while enhancing the tutees’ knowledge of the specialty. Thus, medical schools should incorporate near-peer teaching in their curriculum to enhance the student learning experience

Cosmic structure formation in Hybrid Inflation models

A wide class of inflationary models, known as Hybrid Inflation models, may produce topological defects during a phase transition at the end of the inflationary epoch. We point out that, if the energy scale of these defects is close to that of Grand Unification, then their effect on cosmic structure formation and the generation of microwave background anisotropies cannot be ignored. Therefore, it is possible for structure to be seeded by a combination of the adiabatic perturbations produced during inflation and active isocurvature perturbations produced by defects. Since the two mechanisms are uncorrelated the power spectra can be computed by a weighted average of the individual contributions. We investigate the possible observational consequences of this with reference to general Hybrid Inflation models and also a specific model based on Supergravity. These mixed perturbation scenarios have some novel observational consequences and these are discussed qualitatively.Comment: 22 Page

Individual common variants exert weak effects on the risk for autism spectrum disorders.

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm&lt; 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest

Delay discounting and under-valuing of recent information predict poorer adherence to social distancing measures during the COVID-19 pandemic

The COVID-19 pandemic has brought about unprecedented global changes in individual and collective behaviour. To reduce the spread of the virus, public health bodies have promoted social distancing measures while attempting to mitigate their mental health consequences. The current study aimed to identify cognitive predictors of social distancing adherence and mental health symptoms, using computational models derived from delay discounting (the preference for smaller, immediate rewards over larger, delayed rewards) and patch foraging (the ability to trade-off between exploiting a known resource and exploring an unknown one). In a representative sample of the UK population (N=442), we find that steeper delay discounting predicted poorer adherence to social distancing measures and greater sensitivity to reward magnitude during delay discounting predicted higher levels of anxiety symptoms. Furthermore, under-valuing recently sampled information during foraging independently predicted greater violation of lockdown guidance. Our results suggest that those who show greater discounting of delayed rewards struggle to maintain social distancing. Further, those who adapt faster to new information are better equipped to change their behaviour in response to public health measures. These findings can inform interventions that seek to increase compliance with social distancing measures whilst minimising negative repercussions for mental health

Key steps in the structure-based optimization of the hepatitis C virus NS3/4A protease inhibitor SCH503034

Crystal structures of protease/inhibitor complexes guided optimization of the buried nonpolar surface area thereby maximizing hydrophobic binding. The resulting potent tripeptide inhibitor is in clinical trials

METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration: an initiative of the Joint Programme for Neurodegenerative Disease Research

Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically “silent” cerebrovascular disease, long-term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow-up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular-related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention

The stranding anomaly as population indicator: the case of Harbour Porpoise <i>Phocoena phocoena</i> in North-Western Europe

Ecological indicators for monitoring strategies are expected to combine three major characteristics: ecological significance, statistical credibility, and cost-effectiveness. Strategies based on stranding networks rank highly in cost-effectiveness, but their ecological significance and statistical credibility are disputed. Our present goal is to improve the value of stranding data as population indicator as part of monitoring strategies by constructing the spatial and temporal null hypothesis for strandings. The null hypothesis is defined as: small cetacean distribution and mortality are uniform in space and constant in time. We used a drift model to map stranding probabilities and predict stranding patterns of cetacean carcasses under H-0 across the North Sea, the Channel and the Bay of Biscay, for the period 1990-2009. As the most common cetacean occurring in this area, we chose the harbour porpoise <i>Phocoena phocoena</i> for our modelling. The difference between these strandings expected under H-0 and observed strandings is defined as the stranding anomaly. It constituted the stranding data series corrected for drift conditions. Seasonal decomposition of stranding anomaly suggested that drift conditions did not explain observed seasonal variations of porpoise strandings. Long-term stranding anomalies increased first in the southern North Sea, the Channel and Bay of Biscay coasts, and finally the eastern North Sea. The hypothesis of changes in porpoise distribution was consistent with local visual surveys, mostly SCANS surveys (1994 and 2005). This new indicator could be applied to cetacean populations across the world and more widely to marine megafauna