The design and testing of a novel mechanomyogram-driven switch controlled by small eyebrow movements

<p>Abstract</p> <p>Background</p> <p>Individuals with severe physical disabilities and minimal motor behaviour may be unable to use conventional mechanical switches for access. These persons may benefit from access technologies that harness the volitional activity of muscles. In this study, we describe the design and demonstrate the performance of a binary switch controlled by mechanomyogram (MMG) signals recorded from the frontalis muscle during eyebrow movements.</p> <p>Methods</p> <p>Muscle contractions, detected in real-time with a continuous wavelet transform algorithm, were used to control a binary switch for computer access. The automatic selection of scale-specific thresholds reduced the effect of artefact, such as eye blinks and head movement, on the performance of the switch. Switch performance was estimated by cued response-tests performed by eleven participants (one with severe physical disabilities).</p> <p>Results</p> <p>The average sensitivity and specificity of the switch was 99.7 ± 0.4% and 99.9 ± 0.1%, respectively. The algorithm performance was robust against typical participant movement.</p> <p>Conclusions</p> <p>The results suggest that the frontalis muscle is a suitable site for controlling the MMG-driven switch. The high accuracies combined with the minimal requisite effort and training show that MMG is a promising binary control signal. Further investigation of the potential benefits of MMG-control for the target population is warranted.</p

Pneumonic Tularemia in Rabbits Resembles the Human Disease as Illustrated by Radiographic and Hematological Changes after Infection

Background: Pneumonic tularemia is caused by inhalation of the gram negative bacterium, Francisella tularensis. Because of concerns that tularemia could be used as a bioterrorism agent, vaccines and therapeutics are urgently needed. Animal models of pneumonic tularemia with a pathophysiology similar to the human disease are needed to evaluate the efficacy of these potential medical countermeasures. Principal Findings: Rabbits exposed to aerosols containing Francisella tularensis strain SCHU S4 developed a rapidly progressive fatal pneumonic disease. Clinical signs became evident on the third day after exposure with development of a fever (>40.5°C) and a sharp decline in both food and water intake. Blood samples collected on day 4 found lymphopenia and a decrease in platelet counts coupled with elevations in erythrocyte sedimentation rate, alanine aminotransferase, cholesterol, granulocytes and monocytes. Radiographs demonstrated the development of pneumonia and abnormalities of intestinal gas consistent with ileus. On average, rabbits were moribund 5.1 days after exposure; no rabbits survived exposure at any dose (190-54,000 cfu). Gross evaluation of tissues taken at necropsy showed evidence of pathology in the lungs, spleen, liver, kidney and intestines. Bacterial counts confirmed bacterial dissemination from the lungs to the liver and spleen. Conclusions/Significance: The pathophysiology of pneumonic tularemia in rabbits resembles what has been reported for humans. Rabbits therefore are a relevant model of the human disease caused by type A strains of F. tularensis. © 2011 Reed et al

Consequences of converting graded to action potentials upon neural information coding and energy efficiency

Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a ‘footprint’ in the generator potential that obscures incoming signals. These three processes reduce information rates by ~50% in generator potentials, to ~3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation

Mechanomyography versus Electromyography, in monitoring the muscular fatigue

BACKGROUND: The use of the mechanomyogram (MMG) which detects muscular vibrations generated by fused individual fiber twitches has been refined. The study addresses a comparison of the MMG and surface electromyogram (SEMG) in monitoring muscle fatigue. METHODS: The SEMG and MMG were recorded simultaneously from the same territory of motor units in two muscles (Biceps, Brachioradialis) of the human (n = 18), during sustained contraction at 25 % MVC (maximal voluntary contraction). RESULTS: The RMS (root mean square) of the SEMG and MMG increased with advancing fatigue; MF (median frequency) of the PSD (power density spectra) progressively decreased from the onset of the contraction. These findings (both muscles, all subjects), demonstrate both through the SEMG and MMG a central component of the fatigue. The MF regression slopes of MMG were closer to each other between men and women (Biceps 1.55%; Brachialis 13.2%) than were the SEMG MF slopes (Biceps 25.32%; Brachialis 17.72%), which shows a smaller inter-sex variability for the MMG vs. SEMG. CONCLUSION: The study presents another quantitative comparison (MF, RMS) of MMG and SEMG, showing that MMG signal can be used for indication of the degree of muscle activation and for monitoring the muscle fatigue when the application of SEMG is not feasible (chronical implants, adverse environments contaminated by electrical noise)

Uncovering treatment burden as a key concept for stroke care: a systematic review of qualitative research

&lt;b&gt;Background&lt;/b&gt; Patients with chronic disease may experience complicated management plans requiring significant personal investment. This has been termed ‘treatment burden’ and has been associated with unfavourable outcomes. The aim of this systematic review is to examine the qualitative literature on treatment burden in stroke from the patient perspective.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods and findings&lt;/b&gt; The search strategy centred on: stroke, treatment burden, patient experience, and qualitative methods. We searched: Scopus, CINAHL, Embase, Medline, and PsycINFO. We tracked references, footnotes, and citations. Restrictions included: English language, date of publication January 2000 until February 2013. Two reviewers independently carried out the following: paper screening, data extraction, and data analysis. Data were analysed using framework synthesis, as informed by Normalization Process Theory. Sixty-nine papers were included. Treatment burden includes: (1) making sense of stroke management and planning care, (2) interacting with others, (3) enacting management strategies, and (4) reflecting on management. Health care is fragmented, with poor communication between patient and health care providers. Patients report inadequate information provision. Inpatient care is unsatisfactory, with a perceived lack of empathy from professionals and a shortage of stimulating activities on the ward. Discharge services are poorly coordinated, and accessing health and social care in the community is difficult. The study has potential limitations because it was restricted to studies published in English only and data from low-income countries were scarce.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Stroke management is extremely demanding for patients, and treatment burden is influenced by micro and macro organisation of health services. Knowledge deficits mean patients are ill equipped to organise their care and develop coping strategies, making adherence less likely. There is a need to transform the approach to care provision so that services are configured to prioritise patient needs rather than those of health care systems

Stochastic Drift in Mitochondrial DNA Point Mutations: A Novel Perspective Ex Silico

The mitochondrial free radical theory of aging (mFRTA) implicates Reactive Oxygen Species (ROS)-induced mutations of mitochondrial DNA (mtDNA) as a major cause of aging. However, fifty years after its inception, several of its premises are intensely debated. Much of this uncertainty is due to the large range of values in the reported experimental data, for example on oxidative damage and mutational burden in mtDNA. This is in part due to limitations with available measurement technologies. Here we show that sample preparations in some assays necessitating high dilution of DNA (single molecule level) may introduce significant statistical variability. Adding to this complexity is the intrinsically stochastic nature of cellular processes, which manifests in cells from the same tissue harboring varying mutation load. In conjunction, these random elements make the determination of the underlying mutation dynamics extremely challenging. Our in silico stochastic study reveals the effect of coupling the experimental variability and the intrinsic stochasticity of aging process in some of the reported experimental data. We also show that the stochastic nature of a de novo point mutation generated during embryonic development is a major contributor of different mutation burdens in the individuals of mouse population. Analysis of simulation results leads to several new insights on the relevance of mutation stochasticity in the context of dividing tissues and the plausibility of ROS ”vicious cycle” hypothesis

The Global Health System: Actors, Norms, and Expectations in Transition

In the first in a series of four articles highlighting the changing nature of global health institutions, Nicole Szlezák and colleagues outline the origin and aim of the series

Inappropriate prescribing and adverse drug events in older people

Inappropriate prescribing (IP) in older patients is highly prevalent and is associated with an increased risk of adverse drug events (ADEs), morbidity, mortality and healthcare utilisation. Consequently, IP is a major safety concern and with changing population demographics, it is likely to become even more prevalent in the future. IP can be detected using explicit or implicit prescribing indicators. Theoretically, the routine clinical application of these IP criteria could represent an inexpensive and time efficient method to optimise prescribing practice. However, IP criteria must be sensitive, specific, have good inter-rater reliability and incorporate those medications most commonly associated with ADEs in older people. To be clinically relevant, use of prescribing appropriateness tools must translate into positive patient outcomes, such as reduced rates of ADEs. To accurately measure these outcomes, a reliable method of assessing the relationship between the administration of a drug and an adverse clinical event is required. The Naranjo criteria are the most widely used tool for assessing ADE causality, however, they are often difficult to interpret in the context of older patients. ADE causality criteria that allow for the multiple co-morbidities and prescribed medications in older people are required. Ultimately, the current high prevalence of IP and ADEs is unacceptable. IP screening criteria need to be tested as an intervention to assess their impact on the incidence of ADEs in vulnerable older patients. There is a role for IP screening tools in everyday clinical practice. These should enhance, not replace good clinical judgement, which in turn should be based on sound pharmacogeriatric training

Permutation criteria to evaluate multiple clinical endpoints in a proof-of-concept study: lessons from Pre-RELAX-AHF

Clinically relevant endpoints cannot be routinely targeted with reasonable power in a small study. Hence, proof-of-concept studies are often powered to a primary surrogate endpoint. However, in acute heart failure (AHF) effects on surrogates have not translated into clinical benefit in confirmatory studies. Although observing an effect on one of many endpoints due to chance is likely, observing concurrent positive trends across several outcomes by chance is usually unlikely. Pre-RELAX-AHF, which compared 4 relaxin doses with placebo in AHF, has shown favourable trends versus placebo (one-sided P <0.10) on six of nine clinical endpoints in the 30 mu g/kg/day group. To illustrate evaluation of multiple, correlated clinical endpoints for evidence of efficacy and for dose selection, a permutation method was applied retrospectively. By randomly re-assigning the treatment group to the actual data for each of the 229 subjects, 20,000 permutation samples were constructed. The permutation P value for at least six favourable trends among nine endpoints in any dose groups was 0.0073 (99.9% CI 0.0053-0.0093). This is higher than would be expected if the endpoints were uncorrelated (0.00026), but much lower than the probability of observing one of nine comparisons significant at the traditional two-sided P <0.05 (0.74). Thus, the result was unlikely due to correlated endpoints or to chance. Examining consistency of effect across multiple clinical endpoints in a proof-of-concept study may identify efficacious therapies and enable dose selection for confirmatory trials. The merit of the approach described requires confirmation through prospective application in designing future studies