Foreground Detection Analysis of Ultrasound Image Sequences Identifies Markers of Motor Neurone Disease across Diagnostically Relevant Skeletal Muscles

© 2019 The Authors Diagnosis of motor neurone disease (MND) includes detection of small, involuntary muscle excitations, termed fasciculations. There is need to improve diagnosis and monitoring of MND through provision of objective markers of change. Fasciculations are visible in ultrasound image sequences. However, few approaches that objectively measure their occurrence have been proposed; their performance has been evaluated in only a few muscles; and their agreement with the clinical gold standard for fasciculation detection, intramuscular electromyography, has not been tested. We present a new application of adaptive foreground detection using a Gaussian mixture model (GMM), evaluating its accuracy across five skeletal muscles in healthy and MND-affected participants. The GMM provided good to excellent accuracy with the electromyography ground truth (80.17%–92.01%) and was robust to different ultrasound probe orientations. The GMM provides objective measurement of fasciculations in each of the body segments necessary for MND diagnosis and hence could provide a new, clinically relevant disease marker

A technical note on variable inter-frame interval as a cause of non-physiological experimental artefacts in ultrasound

Ultrasound (US) imaging is a well-recognized technique for the study of static tissues but its suitability for studying tissue dynamics depends upon accurate frame time information, which may not always be available to users. Here we present methods to quantify the inter-frame interval (IFI) variability, and evaluate different procedures for collecting temporal information from two US-imaging devices. The devices tested exhibited variable IFIs that could only be confirmed by direct measures of timing signals, available by means of electrical signals (triggers) and/or temporal information contained in the software used for the US data collection. Interpolating frame-by-frame measures of dynamic changes within image sequences using individual IFI values provided improved synchronization between measures of skeletal muscle movement and activation; validating US as a valuable technique for the study of musculoskeletal tissue dynamics, when correctly implemented

Ultrasound-Based Detection of Fasciculations in Healthy and Diseased Muscles

Involuntary muscle activations are diagnostic indicators of neurodegenerative pathologies. Currently detected by invasive intramuscular electromyography, these muscle twitches are found to be visible in ultrasound images. We present an automated computational approach for the detection of muscle twitches, and apply this to two muscles in healthy and motor neuron disease-affected populations. The technique relies on motion tracking within ultrasound sequences, extracting local movement information from muscle. A statistical analysis is applied to classify the movement, either as noise or as more coherent movement indicative of a muscle twitch. The technique is compared to operator identified twitches, which are also assessed to ensure operator agreement. We find that, when two independent operators manually identified twitches, higher interoperator agreement (Cohen's k) occurs when more twitches are present (k = 0.94), compared to a lower number (k = 0.49). Finally, we demonstrate, via analysis of receiver operating characteristics, that our computational technique detects muscle twitches across the entire dataset with a high degree of accuracy (0.83 <; accuracy <; 0.96)

Clades and clans: a comparison study of two evolutionary models

The Yule-Harding-Kingman (YHK) model and the proportional to distinguishable arrangements (PDA) model are two binary tree generating models that are widely used in evolutionary biology. Understanding the distributions of clade sizes under these two models provides valuable insights into macro-evolutionary processes, and is important in hypothesis testing and Bayesian analyses in phylogenetics. Here we show that these distributions are log-convex, which implies that very large clades or very small clades are more likely to occur under these two models. Moreover, we prove that there exists a critical value $\kappa(n)$ for each $n\geqslant 4$ such that for a given clade with size $k$, the probability that this clade is contained in a random tree with $n$ leaves generated under the YHK model is higher than that under the PDA model if $1<k<\kappa(n)$, and lower if $\kappa(n)<k<n$. Finally, we extend our results to binary unrooted trees, and obtain similar results for the distributions of clan sizes.Comment: 21page

An evaluation of a morphine public health programme for cancer and AIDS pain relief in Sub-Saharan Africa

BACKGROUND: Despite growing HIV and cancer prevalence in Sub-Saharan Africa, and WHO advocacy for a public health approach to palliative care provision, opioid availability is severely limited. Uganda has achieved a morphine roll-out programme in partnership with the Ministry of Health. This study aimed to evaluate that programme by identifying challenges to implementation that may inform replication. METHODS: A multi-methods protocol appraised morphine regulation, storage, prescribing, and consumption in three phases: key informant interviews throughout the opioid supply chain, and direct observation and audit of clinical practice. RESULTS: Regulation had achieved its goal of preventing misuse and leakage from the supply chain. However, the Government felt that relaxation of regulation was now appropriate. Confusion and complexity in storage and authorisation rules led to discontinuation of opioid pain management at the patient level and also wasted service time in trying to obtain supplies to which they were entitled. Continued neglect to prescribe among clinicians and public fear of opioids led to under prescribing, and clinical skills showed some evidence of need for improvement with respect to physical assessment and follow-up. CONCLUSION: The Ugandan programme offers a successful model for both advocacy and Governmental support in achieving opioid roll-out across health districts. Despite initial concerns, abuse of opioids has not been evident. Further work is required to ensure that available supplies of opioids are prescribed to those in need, and that clinical standards are met. However, the programme for roll-out has proved a useful model to expand opioid availability as the first step in improving patient care, and may prove a useful template for other Sub-Saharan African countries

Student midwives perspectives on the efficacy of feedback after objective structured clinical examination

Students’ experience of feedback is considered an indicator of the efficacy of the assessment process. Negative experiences of feedback are unproductive in terms of the likelihood that students will act upon and learn from assessment. To understand the impact of feedback on learning this study explored the experiences of student midwives after receiving feedback following Objective Structured Clinical Examination (OSCE). Data were collected from second year undergraduate student midwives who had recently completed OSCE, via a focus group. Students reported raised stress levels, concerns around legitimacy of feedback, and inconsistencies in the manner in which feedback was articulated. Assessment feedback in higher education should be used to empower students to become self-regulated learners. This is important for student midwives for whom a considerable amount of leaning is spent in practice. The study has implications for midwifery academics concerned with modes of assessment and quality of assessment feedback in midwifery education

Conduction in ulnar nerve bundles that innervate the proximal and distal muscles: a clinical trial

<p>Abstract</p> <p>Background</p> <p>This study aims to investigate and compare the conduction parameters of nerve bundles in the ulnar nerve that innervates the forearm muscles and hand muscles; routine electromyography study merely evaluates the nerve segment of distal (hand) muscles.</p> <p>Methods</p> <p>An electrophysiological evaluation, consisting of velocities, amplitudes, and durations of ulnar nerve bundles to 2 forearm muscles and the hypothenar muscles was performed on the same humeral segment.</p> <p>Results</p> <p>The velocities and durations of the compound muscle action potential (CMAP) of the ulnar nerve bundle to the proximal muscles were greater than to distal muscles, but the amplitudes were smaller.</p> <p>Conclusions</p> <p>Bundles in the ulnar nerve of proximal muscles have larger neuronal bodies and thicker nerve fibers than those in the same nerve in distal muscles, and their conduction velocities are higher. The CMAPs of proximal muscles also have smaller amplitudes and greater durations. These findings can be attributed to the desynchronization that is caused by a wider range of distribution in nerve fiber diameters.</p> <p>Conduction parameters of nerve fibers with different diameters in the same peripheral nerve can be estimated.</p

Scaling properties of protein family phylogenies

One of the classical questions in evolutionary biology is how evolutionary processes are coupled at the gene and species level. With this motivation, we compare the topological properties (mainly the depth scaling, as a characterization of balance) of a large set of protein phylogenies with a set of species phylogenies. The comparative analysis shows that both sets of phylogenies share remarkably similar scaling behavior, suggesting the universality of branching rules and of the evolutionary processes that drive biological diversification from gene to species level. In order to explain such generality, we propose a simple model which allows us to estimate the proportion of evolvability/robustness needed to approximate the scaling behavior observed in the phylogenies, highlighting the relevance of the robustness of a biological system (species or protein) in the scaling properties of the phylogenetic trees. Thus, the rules that govern the incapability of a biological system to diversify are equally relevant both at the gene and at the species level.Comment: Replaced with final published versio

Listening In on the Past: What Can Otolith δ18O Values Really Tell Us about the Environmental History of Fishes?

Oxygen isotope ratios from fish otoliths are used to discriminate marine stocks and reconstruct past climate, assuming that variations in otolith δ18O values closely reflect differences in temperature history of fish when accounting for salinity induced variability in water δ18O. To investigate this, we exploited the environmental and migratory data gathered from a decade using archival tags to study the behaviour of adult plaice (Pleuronectes platessa L.) in the North Sea. Based on the tag-derived monthly distributions of the fish and corresponding temperature and salinity estimates modelled across three consecutive years, we first predicted annual otolith δ18O values for three geographically discrete offshore sub-stocks, using three alternative plausible scenarios for otolith growth. Comparison of predicted vs. measured annual δ18O values demonstrated >96% correct prediction of sub-stock membership, irrespective of the otolith growth scenario. Pronounced inter-stock differences in δ18O values, notably in summer, provide a robust marker for reconstructing broad-scale plaice distribution in the North Sea. However, although largely congruent, measured and predicted annual δ18O values of did not fully match. Small, but consistent, offsets were also observed between individual high-resolution otolith δ18O values measured during tag recording time and corresponding δ18O predictions using concomitant tag-recorded temperatures and location-specific salinity estimates. The nature of the shifts differed among sub-stocks, suggesting specific vital effects linked to variation in physiological response to temperature. Therefore, although otolith δ18O in free-ranging fish largely reflects environmental temperature and salinity, we counsel prudence when interpreting otolith δ18O data for stock discrimination or temperature reconstruction until the mechanisms underpinning otolith δ18O signature acquisition, and associated variation, are clarified

Retarded PDI diffusion and a reductive shift in poise of the calcium depleted endoplasmic reticulum

Background: Endoplasmic reticulum (ER) lumenal protein thiol redox balance resists dramatic variation in unfolded protein load imposed by diverse physiological challenges including compromise in the key upstream oxidases. Lumenal calcium depletion, incurred during normal cell signaling, stands out as a notable exception to this resilience, promoting a rapid and reversible shift towards a more reducing poise. Calcium depletion induced ER redox alterations are relevant to physiological conditions associated with calcium signaling, such as the response of pancreatic cells to secretagogues and neuronal activity. The core components of the ER redox machinery are well characterized; however, the molecular basis for the calcium-depletion induced shift in redox balance is presently obscure. Results: In vitro, the core machinery for generating disulfides, consisting of ERO1 and the oxidizing protein disulfide isomerase, PDI1A, was indifferent to variation in calcium concentration within the physiological range. However, ER calcium depletion in vivo led to a selective 2.5-fold decline in PDI1A mobility, whereas the mobility of the reducing PDI family member, ERdj5 was unaffected. In vivo, fluorescence resonance energy transfer measurements revealed that declining PDI1A mobility correlated with formation of a complex with the abundant ER chaperone calreticulin, whose mobility was also inhibited by calcium depletion and the calcium depletion-mediated reductive shift was attenuated in cells lacking calreticulin. Measurements with purified proteins confirmed that the PDI1A-calreticulin complex dissociated as Ca2+ concentrations approached those normally found in the ER lumen ([Ca2+] K-0.5max = 190 mu M). Conclusions: Our findings suggest that selective sequestration of PDI1A in a calcium depletion-mediated complex with the abundant chaperone calreticulin attenuates the effective concentration of this major lumenal thiol oxidant, providing a plausible and simple mechanism for the observed shift in ER lumenal redox poise upon physiological calcium depletion.Wellcome Trust [Wellcome 084812/Z/08/Z]; European Commission (EU FP7 Beta-Bat) [277713]; Fundacao para a Ciencia e Tecnologia, Portugal [PTDC/QUI-BIQ/119677/2010]info:eu-repo/semantics/publishedVersio