Automatic electrical stimulation of abdominal wall muscles increases tidal volume and cough peak flow in tetraplegia

<p>Paralysis of the respiratory muscles in people with tetraplegia affects their ability to breathe and contributes to respiratory complications. Surface functional electrical stimulation (FES) of abdominal wall muscles can be used to increase tidal volume (V_{T}) and improve cough peak flow (CPF) in tetraplegic subjects who are able to breathe spontaneously.</p> <p>This study aims to evaluate the feasibility and effectiveness of a novel abdominal FES system which generates stimulation automatically, synchronised with the subjects' voluntary breathing activity. Four subjects with complete tetraplegia (C4-C6), breathing spontaneously, were recruited.</p> <p>The automatic stimulation system ensured that consistent stimulation was achieved. We compared spirometry during unassisted and FES-assisted quiet breathing and coughing, and measured the effect of stimulation on end-tidal CO_2 (EtCO_2) during quiet breathing.</p> <p>The system dependably recognised spontaneous respiratory effort, stimulating appropriately, and was well tolerated by patients. Significant increases in V_T during quiet breathing (range 0.05–0.23 L) and in CPF (range 0.04–0.49 L/s) were observed. Respiratory rate during quiet breathing decreased in all subjects when stimulated, whereas minute ventilation increased by 1.05–2.07 L/min. The changes in EtCO_2 were inconclusive.</p> <p>The automatic stimulation system augmented spontaneous breathing and coughing in tetraplegic patients and may provide a potential means of respiratory support for tetraplegic patients with reduced respiratory capacity.</p&gt

Arm-cranking exercise assisted by Functional Electrical Stimulation in C6 tetraplegia: a pilot study

Tetraplegic volunteers undertook progressive exercise training, using novel systems for arm-cranking exercise assisted by Functional Electrical Stimulation (FES). The main aim was to determine potential training effects of FES-assisted arm-crank ergometry (FES-ACE) on upper limb strength and cardiopulmonary {fitness} in tetraplegia. Surface FES was applied to the biceps and triceps during exercise on an instrumented ergometer. Two tetraplegic volunteers with C6 Spinal Cord Injury (SCI) went through muscle strengthening, baseline exercise testing and three months of progressive FES-ACE training. Repeat exercise tests were carried out every four weeks during training, and post-training, to monitor upper-limb strength and cardiopulmonary fitness. At each test point, an incremental test was carried out to determine peak work rate, peak oxygen uptake, gas exchange threshold and oxygen uptake-work rate relationship during FES-ACE. Peak oxygen uptake for Subject A increased from 0.7 l/min to 1.1 l/min, and peak power output increased from 7 W to 38 W after FES-ACE training. For Subject B, peak oxygen uptake was unchanged, but peak power output increased from 3 W to 8 W. These case studies illustrate potential benefits of FES-ACE in tetraplegia, but also the differences in exercise responses between individuals. Keywords: electrical stimulation; spinal cord injury; cardiopulmonary fitness; rehabilitation; tetraplegi

Methods and protocols for incremental exercise testing in tetraplegia, using arm-crank ergometry assisted by Functional Electrical Stimulation

Cervical spinal cord injury (SCI) leads to tetraplegia, with paralysis and loss of sensation in the upper and lower limbs. The associated sedentary lifestyle results in an increased risk of cardiovascular disease. To address this, we require the design of exercise modalities aimed specifically at tetraplegia and methods to assess their efficacy. This paper describes methods for arm-crank ergometry (ACE) assisted by Functional Electrical Stimulation (FES) applied to the biceps and triceps. The instrumented ergometer enables work-rate control during exercise, implemented here for incremental exercise testing during FES-ACE. Detailed protocols for the tests are given. Experimental data collected during exercise tests with tetraplegic volunteers are provided to illustrate the feasibility of the proposed approach to testing and data analysis. Incremental tests enabled calculation of peak power output and peak oxygen uptake. We propose that the high-precision exercise testing protocols described here are appropriate to assess the efficacy of the novel exercise modality, FES-ACE, in tetraplegia

Comparison of stimulation patterns for FES-cycling using measures of oxygen cost and stimulation cost

<b>Aim</b><p></p> The energy efficiency of FES-cycling in spinal cord injured subjects is very much lower than that of normal cycling, and efficiency is dependent upon the parameters of muscle stimulation. We investigated measures which can be used to evaluate the effect on cycling performance of changes in stimulation parameters, and which might therefore be used to optimise them. We aimed to determine whether oxygen cost and stimulation cost measurements are sensitive enough to allow discrimination between the efficacy of different activation ranges for stimulation of each muscle group during constant-power cycling. <p></p> <b>Methods</b><p></p> We employed a custom FES-cycling ergometer system, with accurate control of cadence and stimulated exercise workrate. Two sets of muscle activation angles (“stimulation patterns”), denoted “P1” and “P2”, were applied repeatedly (eight times each) during constant-power cycling, in a repeated measures design with a single paraplegic subject. Pulmonary oxygen uptake was measured in real time and used to determine the oxygen cost of the exercise. A new measure of stimulation cost of the exercise is proposed, which represents the total rate of stimulation charge applied to the stimulated muscle groups during cycling. A number of energy-efficiency measures were also estimated. <p></p> <b>Results</b><p></p> Average oxygen cost and stimulation cost of P1 were found to be significantly lower than those for P2 (paired <i>t</i>-test, <i>p</i> < 0.05): oxygen costs were 0.56 ± 0.03 l min<sup>−1</sup> and 0.61 ± 0.04 l min<sup>−1</sup>(mean ± S.D.), respectively; stimulation costs were 74.91 ± 12.15 mC min<sup>−1</sup> and 100.30 ± 14.78 mC min<sup>−1</sup> (mean ± S.D.), respectively. Correspondingly, all efficiency estimates for P1 were greater than those for P2. <p></p> <b>Conclusion</b><p></p> Oxygen cost and stimulation cost measures both allow discrimination between the efficacy of different muscle activation patterns during constant-power FES-cycling. However, stimulation cost is more easily determined in real time, and responds more rapidly and with greatly improved signal-to-noise properties than the ventilatory oxygen uptake measurements required for estimation of oxygen cost. These measures may find utility in the adjustment of stimulation patterns for achievement of optimal cycling performance. <p></p&gt

An investigation of the clinical impact and therapeutic relevance of a DNA damage immune response (DDIR) signature in patients with advanced gastroesophageal adenocarcinoma

Background: An improved understanding of which gastroesophageal adenocarcinoma (GOA) patients respond to both chemotherapy and immune checkpoint inhibitors (ICI) is needed. We investigated the predictive role and underlying biology of a 44-gene DNA damage immune response (DDIR) signature in patients with advanced GOA. Materials and methods: Transcriptional profiling was carried out on pretreatment tissue from 252 GOA patients treated with platinum-based chemotherapy (three dose levels) within the randomized phase III GO2 trial. Cross-validation was carried out in two independent GOA cohorts with transcriptional profiling, immune cell immunohistochemistry and epidermal growth factor receptor (EGFR) fluorescent in situ hybridization (FISH) (n = 430). Results: In the GO2 trial, DDIR-positive tumours had a greater radiological response (51.7% versus 28.5%, P = 0.022) and improved overall survival in a dose-dependent manner (P = 0.028). DDIR positivity was associated with a pretreatment inflamed tumour microenvironment (TME) and increased expression of biomarkers associated with ICI response such as CD274 (programmed death-ligand 1, PD-L1) and a microsatellite instability RNA signature. Consensus pathway analysis identified EGFR as a potential key determinant of the DDIR signature. EGFR amplification was associated with DDIR negativity and an immune cold TME. Conclusions: Our results indicate the importance of the GOA TME in chemotherapy response, its relationship to DNA damage repair and EGFR as a targetable driver of an immune cold TME. Chemotherapy-sensitive inflamed GOAs could benefit from ICI delivered in combination with standard chemotherapy. Combining EGFR inhibitors and ICIs warrants further investigation in patients with EGFR-amplified tumours

An investigation of the clinical impact and therapeutic relevance of a DNA damage immune response (DDIR) signature in patients with advanced gastroesophageal adenocarcinoma

BackgroundAn improved understanding of which gastroesophageal adenocarcinoma (GOA) patients respond to both chemotherapy and immune checkpoint inhibitors (ICI) is needed. We investigated the predictive role and underlying biology of a 44-gene DNA damage immune response (DDIR) signature in patients with advanced GOA.Materials and methodsTranscriptional profiling was carried out on pretreatment tissue from 252 GOA patients treated with platinum-based chemotherapy (three dose levels) within the randomized phase III GO2 trial. Cross-validation was carried out in two independent GOA cohorts with transcriptional profiling, immune cell immunohistochemistry and epidermal growth factor receptor (EGFR) fluorescent in situ hybridization (FISH) (n = 430).ResultsIn the GO2 trial, DDIR-positive tumours had a greater radiological response (51.7% versus 28.5%, P = 0.022) and improved overall survival in a dose-dependent manner (P = 0.028). DDIR positivity was associated with a pretreatment inflamed tumour microenvironment (TME) and increased expression of biomarkers associated with ICI response such as CD274 (programmed death-ligand 1, PD-L1) and a microsatellite instability RNA signature. Consensus pathway analysis identified EGFR as a potential key determinant of the DDIR signature. EGFR amplification was associated with DDIR negativity and an immune cold TME.ConclusionsOur results indicate the importance of the GOA TME in chemotherapy response, its relationship to DNA damage repair and EGFR as a targetable driver of an immune cold TME. Chemotherapy-sensitive inflamed GOAs could benefit from ICI delivered in combination with standard chemotherapy. Combining EGFR inhibitors and ICIs warrants further investigation in patients with EGFR-amplified tumours

A novel keratin 13 variant in a four-generation family with white sponge nevus

Dermatology-oncolog

Observation of hard scattering in photoproduction events with a large rapidity gap at HERA

Events with a large rapidity gap and total transverse energy greater than 5 GeV have been observed in quasi-real photoproduction at HERA with the ZEUS detector. The distribution of these events as a function of the $\gamma p$ centre of mass energy is consistent with diffractive scattering. For total transverse energies above 12 GeV, the hadronic final states show predominantly a two-jet structure with each jet having a transverse energy greater than 4 GeV. For the two-jet events, little energy flow is found outside the jets. This observation is consistent with the hard scattering of a quasi-real photon with a colourless object in the proton.Comment: 19 pages, latex, 4 figures appended as uuencoded fil

Ergonomics and sustainability: Towards and embrace of complexity and emergence

Technology offers a promising route to a sustainable future, and ergonomics can serve a vital role. The argument of this article is that the lasting success of sustainability initiatives in ergonomics hinges on an examination of ergonomics' own epistemology and ethics. The epistemology of ergonomics is fundamentally empiricist and positivist. This places practical constraints on its ability to address important issues such as sustainability, emergence and complexity. The implicit ethical position of ergonomics is one of neutrality, and its positivist epistemology generally puts value-laden questions outside the parameters of what it sees as scientific practice. We argue, by contrast, that a discipline that deals with both technology and human beings cannot avoid engaging with questions of complexity and emergence and seeking innovative ways of addressing these issues.No Full Tex