Discovering Differences in Acoustic Emission Between Healthy and Osteoarthritic Knees Using a Four-Phase Model of Sit-Stand-Sit Movements

By performing repeated sit-stand-sit movements to create stress on knee joints, short transient bursts of high frequency acoustic emission (AE) released by the knee joints were acquired from two age matched groups consisting of healthy and osteoarthritic (OA) knees, and significant differences between these two groups were discovered from the signal analysis performed. The analysis is based on a four-phase model of sit-stand-sit movements and a two-feature descriptor of AE bursts. The four phases are derived from joint angle measurement during movement, and they consist of the ascending-acceleration and ascending-deceleration phases in the sit-to-stand movement, followed by the descending-acceleration and descending-deceleration phases in the stand-to-sit movement. The two features are extracted from AE measurement during movement, and they consist of the peak magnitude value and average signal level of each AE burst. The proposed analysis method is shown to provide a high sensitivity for differentiation of the two age matched healthy and OA groups, with the most significant difference found to come from the peak magnitude value in the ascending-deceleration phase, clear quantity and strength differences in the image based visual display of their AE feature profiles due to substantially more AE bursts from OA knee joints with higher peak magnitude values and higher average signal levels, and two well separated clusters in the space formed by the principal components. These results provide ample support for further development of AE as a novel tool to facilitate dynamic integrity assessment of knee joints in clinic and home settings

Can long-range PCR be used to amplify genetically divergent mitochondrial genomes for comparative phylogenetics?: a case study within spiders (Arthropoda: Araneae)

The development of second generation sequencing technology has resulted in the rapid production of large volumes of sequence data for relatively little cost, thereby substantially increasing the quantity of data available for phylogenetic studies. Despite these technological advances, assembling longer sequences, such as that of entire mitochondrial genomes, has not been straightforward. Existing studies have been limited to using only incomplete or nominally intra-specific datasets resulting in a bottleneck between mitogenome amplification and downstream high-throughput sequencing. Here we assess the effectiveness of a wide range of targeted long-range PCR strategies, encapsulating single and dual fragment primer design approaches to provide full mitogenomic coverage within the Araneae (Spiders). Despite extensive rounds of optimisation, full mitochondrial genome PCR amplifications were stochastic in most taxa, although 454 Roche sequencing confirmed the successful amplification of 10 mitochondrial genomes out of the 33 trialled species. The low success rates of amplification using long-Range PCR highlights the difficulties in consistently obtaining genomic amplifications using currently available DNA polymerases optimised for large genomic amplifications and suggests that there may be opportunities for the use of alternative amplification methods

The 3Mg trial: A randomised controlled trial of intravenous or nebulised magnesium sulphate versus placebo in adults with acute severe asthma

Background: Magnesium sulphate, administered by the intravenous (i.v.) or inhaled (nebulised) route, has been proposed as a treatment for adults with acute severe asthma. Existing trials show mixed results and uncertain evidence of benefit. Objectives: We aimed to determine whether i.v. or nebulised magnesium sulphate improves symptoms of breathlessness and reduces the need for hospital admission in adults with acute severe asthma. Design: Multicentre, double-blind, placebo-controlled, three-arm, randomised trial. Setting: The emergency departments of 34 acute hospitals in the UK. Participants: We recruited 1109 adults (age > 16 years) with acute severe asthma [peak expiratory flow rate (PEFR) 25 breaths per minute, heart rate > 110 beats per minute or inability to complete sentences in one breath]. Patients with life-threatening features or a contraindication to either nebulised or intravenous magnesium sulphate were excluded. Interventions: Participants were randomly allocated to i.v. magnesium sulphate (2 g over 20 minutes) or nebulised magnesium sulphate (3 × 500 mg over 1 hour) or standard therapy alone. Main outcome measures: The primary outcome was the proportion of patients admitted to hospital (either after emergency department treatment or at any time over the subsequent 7 days) and breathlessness measured on a 100-mm visual analogue scale (VAS) over 2 hours after initiation of treatment. Results: We randomised 406 patients to i.v. magnesium sulphate, 339 to nebulised magnesium sulphate and 364 to placebo. Hospital admission was recorded for 394, 332 and 358 patients, respectively, and VAS breathlessness for 357, 296 and 323 patients respectively. Mean age was 36.1 years and 763 out of 1084 (70%) patients were female. Intravenous magnesium sulphate was associated with an odds ratio (OR) of 0.73 [95% confidence interval (CI) 0.51 to 1.04; p = 0.083] for hospital admission, an improvement in VAS breathlessness that was 2.6mm (95% CI -1.6 to 6.8 mm; p = 0.231) greater than that associated with placebo and an improvement in PEFR that was 2.4 l/minute (95% CI -8.8 to 13.6 l/minute; p = 0.680) greater than that associated with placebo. Nebulised magnesium sulphate was associated with an OR of 0.96 (95% CI 0.65 to 1.40; p = 0.819) for hospital admission, an improvement in VAS breathlessness that was 2.6mm (95% CI -1.8mm to 7.0 mm; p = 0.253) less than that associated with placebo and an improvement in PEFR that was 2.6 l/minute (95% CI -9.2 to 14.5 l/minute; p = 0.644) less than that associated with placebo. There were no significant differences between i.v. or nebulised magnesium sulphate and placebo for any other outcomes. The number (%) of patients reporting any side effect was 61 (15.5%) in the i.v. group, 52 (15.7%) in the nebuliser group and 36 (10.1%) in the placebo group. The ORs for suffering any side effect were 1.68 (95% CI 1.07 to 2.63; p = 0.025) for i.v. compared with placebo and 1.67 (95% CI 1.05 to 2.66; p = 0.031) for nebuliser compared with placebo. Conclusions: We were unable to demonstrate a clinically worthwhile benefit from magnesium sulphate in acute severe asthma. There was some weak evidence of an effect of i.v. magnesium sulphate on hospital admission, but no evidence of an effect on VAS breathlessness or PEFR compared with placebo. We found no evidence that nebulised magnesium sulphate was more effective than placebo. Trial registration: Current Controlled Trials ISRCTN04417063. Source of funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 22. See the NIHR Journals Library programme website for further project information. © Queen's Printer and Controller of HMSO 2014

Designing an Exascale Interconnect using Multi-objective Optimization

Exascale performance will be delivered by systems composed of millions of interconnected computing cores. The way these computing elements are connected with each other (network topology) has a strong impact on many performance characteristics. In this work we propose a multi-objective optimizationbased framework to explore possible network topologies to be implemented in the EU-funded ExaNeSt project. The modular design of this system’s interconnect provides great flexibility to design topologies optimized for specific performance targets such as communications locality, fault tolerance or energyconsumption. The generation procedure of the topologies is formulated as a three-objective optimization problem (minimizing some topological characteristics) where solutions are searched using evolutionary techniques. The analysis of the results, carried out using simulation, shows that the topologies meet the required performance objectives. In addition, a comparison with a well-known topology reveals that the generated solutions can provide better topological characteristics and also higher performance for parallel applications

Discovering Associations between Acoustic Emission and Magnetic Resonance Imaging Biomarkers from 10 Osteoarthritic Knees

Objective: Acoustic emission (AE) sensed from knee joints during weight-bearing movements greatly increases with joint deterioration, but the relationship between AE patterns and specific anatomical damage, as seen for example in magnetic resonance imaging (MRI), is unknown. This knowledge is essential to validate AE biomarkers for the evaluation of knee joints, and forms the objective of this exploratory work to associate knee AE and MRI. Methods: A novel processing framework is proposed to enable direct correlation between static 3D MRI of knees and their dynamic 1D AE during sit-stand-sit movements. It comprises a method to estimate articular cartilage thickness according to joint angle from knee MRI, and a method to derive statistically representative waveform features according to joint angle from movement and load-dependent knee AE. Results: In 10 subjects diagnosed with knee osteoarthritis, age 55~79 years and body mass index 25~35 kg/m2, a strong inverse relationship between knee AE and cartilage thickness in the medial tibiofemoral compartment around the fully standing position was observed. Knees with thinner articular cartilage generated more AE with higher amplitude, greater energy, longer duration, and higher frequencies, in agreement with the assumption of more intense articulation friction under full body weight. Conclusion: AE provides promising quantitative biomarkers in knee joint disease. Significance: These findings provide impetus for the further development of AE as a low-cost non-invasive biomarker modality to improve the management of knee joint disease

Single Event Effects Assessment of UltraScale+ MPSoC Systems under Atmospheric Radiation

The AMD UltraScale+ XCZU9EG device is a Multi-Processor System-on-Chip (MPSoC) with embedded Programmable Logic (PL) that excels in many Edge (e.g., automotive or avionics) and Cloud (e.g., data centres) terrestrial applications. However, it incorporates a large amount of SRAM cells, making the device vulnerable to Neutron-induced Single Event Upsets (NSEUs) or otherwise soft errors. Semiconductor vendors incorporate soft error mitigation mechanisms to recover memory upsets (i.e., faults) before they propagate to the application output and become an error. But how effective are the MPSoC's mitigation schemes? Can they effectively recover upsets in high altitude or large scale applications under different workloads? This article answers the above research questions through a solid study that entails accelerated neutron radiation testing and dependability analysis. We test the device on a broad range of workloads, like multi-threaded software used for pose estimation and weather prediction or a software/hardware (SW/HW) co-design image classification application running on the AMD Deep Learning Processing Unit (DPU). Assuming a one-node MPSoC system in New York City (NYC) at 40k feet, all tested software applications achieve a Mean Time To Failure (MTTF) greater than 148 months, which shows that upsets are effectively recovered in the processing system of the MPSoC. However, the SW/HW co-design (i.e., DPU) in the same one-node system at 40k feet has an MTTF = 4 months due to the high failure rate of its PL accelerator, which emphasises that some MPSoC workloads may require additional NSEU mitigation schemes. Nevertheless, we show that the MTTF of the DPU can increase to 87 months without any overhead if one disregards the failure rate of tolerable errors since they do not affect the correctness of the classification output.Comment: This manuscript is under review at IEEE Transactions on Reliabilit

Troponin in Acute chest pain to Risk stratify and Guide EffecTive use of Computed Tomography Coronary Angiography (TARGET-CTCA):A randomised controlled trial

Background: The majority of patients with suspected acute coronary syndrome presenting to the emergency department will be discharged once myocardial infarction has been ruled out, although a proportion will have unrecognised coronary artery disease. In this setting, high-sensitivity cardiac troponin identifies those at increased risk of future cardiac events. In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been ruled out, this trial aims to investigate whether outpatient computed tomography coronary angiography (CTCA) reduces subsequent myocardial infarction or cardiac death. Methods: TARGET-CTCA is a multicentre prospective randomised open label with blinded endpoint parallel group event driven trial. After myocardial infarction and clear alternative diagnoses have been ruled out, participants with intermediate cardiac troponin concentrations (5 ng/L to 99th centile upper reference limit) will be randomised 1:1 to outpatient CTCA plus standard of care or standard of care alone. The primary endpoint is myocardial infarction or cardiac death. Secondary endpoints include clinical, patient-centred, process and cost-effectiveness. Recruitment of 2270 patients will give 90% power with a two-sided P value of 0.05 to detect a 40% relative risk reduction in the primary endpoint. Follow-up will continue until 97 primary outcome events have been accrued in the standard care arm with an estimated median follow-up of 36 months. Discussion: This randomised controlled trial will determine whether high-sensitivity cardiac troponin-guided CTCA can improve outcomes and reduce subsequent major adverse cardiac events in patients presenting to the emergency department who do not have myocardial infarction. Trial registration: ClinicalTrials.gov Identifier: NCT03952351. Registered on May 16, 2019

Use of acoustic emission to identify novel candidate biomarkers for knee osteoarthritis (OA)

Our objective was to determine the efficacy and feasibility of a new approach for identifying candidate biomarkers for knee osteoarthritis (OA), based on selecting promising candidates from a range of high-frequency acoustic emission (AE) measurements generated during weight-bearing knee movement. Candidate AE biomarkers identified by this approach could then be validated in larger studies for use in future clinical trials and stratified medicine applications for this common health condition. A population cohort of participants with knee pain and a Kellgren-Lawrence (KL) score between 1-4 were recruited from local NHS primary and secondary care sites. Focusing on participants’ self-identified worse knee, and using our established movement protocol, sources of variation in AE measurement and associations of AE markers with other markers were explored. Using this approach we identified 4 initial candidate AE biomarkers, of which “number of hits” showed the best reproducibility, in terms of within-session, day to day, week to week, between-practitioner, and between-machine variation, at 2 different machine upper frequency settings. “Number of hits” was higher in knees with KL scores of 2 than in KL1, and also showed significant associations with pain in the contralateral knee, and with body weight. “Hits” occurred predominantly in 2 of 4 defined movement quadrants. The protocol was feasible and acceptable to all participants and professionals involved. This study demonstrates how AE measurement during simple sit-stand-sit movements can be used to generate novel candidate knee OA biomarkers. AE measurements probably reflect a composite of structural changes and joint loading factors. Refinement of the method and increasing understanding of factors contributing to AE will enable this approach to be used to generate further candidate biomarkers for validation and potential use in clinical trials