Cold thermal processing in the spinal cord

Two recently identified transient receptor potential (TRP) channels, TRPM8 and TRPA1, have been proposed to play an important role in mammalian cool and cold peripheral sensory transduction. When expressed in cell-lines the cloned TRPM8 and TRPA1 receptors have distinct pharmacological and temperature response characteristics. Although these receptors are also transported to the central terminals of primary afferents, little is known about their centrally mediated actions. In this thesis, I use an in vitro electrophysiological approach to investigate the dorsal horn processing of cool afferent modalities and the role of TRP ion channels. The results of this thesis provide further information on thermal processing, indicate direction for further research and suggest possible therapeutic targets for the management of abnormal cold sensory processing. Initial experiments demonstrate that the cooling agents and known TRPM8 and TRPA1 agonists, menthol and icilin, inhibit primary afferent evoked excitatory postsynaptic currents (EPSCs) in rat spinal cord dorsal horn neurons. In addition, temperature reduction, menthol and icilin increase the frequency of miniature EPSCs without affecting amplitude distribution or kinetics. Little or no direct postsynaptic effect on dorsal horn neurons, GABAergic or glycinergic transmission was found. In combination, these observations demonstrate that temperature reduction, menthol and icilin act presynaptically to increase the probability of glutamate release from primary afferent fibres. Further examination of the changes in glutamatergic synaptic transmission induced by temperature reduction, menthol and icilin reveals a subset of neurons sensitive to innocuous cool (< 29 oC) and low concentrations of icilin (3-10 µM) which closely match the temperature activation and pharmacological profile of TRPM8. In addition, the majority of lamina I and II neurons displayed characteristics partly consistent with TRPA1-activation, including a concentration-dependent response to icilin and blockade by ruthenium red. The present experiments did not allow thermal characterisation of these TRPA1-like responses. Together these observations indicate that the effects of menthol and icilin on glutamatergic synaptic transmission in the superficial dorsal horn are mediated by TRPM8 and possibly by TRPA1. Examination of the anatomical location of neurons activated by temperature reduction, menthol, icilin and capsaicin allowed the central termination pattern of thermoreceptive primary afferent fibres with specific TRP-like response characteristics to be determined. TRPM8-like presynaptic activation was confined to a subpopulation of neurons located in lamina I and outer lamina II, while the majority of neurons throughout laminae I and II received inputs sensitive to menthol, high concentrations of icilin and capsaicin. These findings suggest that innocuous cool sensation projects to a specific subpopulation of superficial dorsal horn neurons unlike other modalities (mediated by TRPV1, possibly TRPA1 and other receptors), which non-selectively engage circuits within the entire superficial dorsal horn. No morphological specificity was identified for recovered neurons after electrophysiological characterisation. Finally, mu-opioids were shown to inhibit basal glutamatergic synaptic transmission as well as menthol- and icilin-induced transmission in the superficial dorsal horn. Of particular interest, delta-opioids selectively inhibited icilin-induced synaptic transmission within the same location. The selective effect of delta-opioids suggests a possible role in modulating receptors activated by icilin (TRPM8 and TRPA1). Overall, this thesis provides further evidence that TRPM8 is responsible for the transduction of innocuous cold sensation in mammals and is a potential therapeutic target in humans with cold hyperaesthesia secondary to abnormal thermal processing. The use of delta-opioid agonists warrants further investigation in cold hypersensitivity states and potentially other forms of pain

Towards a UK co-operative for the advancement of quantum technology

The meeting was the fourth in DSTL's series of community meetings and had a Systems Engineering theme – recognising the increasing importance of this topic for many in the Quantum Technology (QT) community. There is a growing recognition that, although there are significant research challenges associated with realising the commercial and societal benefits anticipated from quantum technologies, there are also other challenges which concern the physical, commercial, societal and regulatory environments into which these new technologies will be integrated. Similar difficulties have been faced and overcome by the information and communications industry. One of the striking characteristics of this sector over the past 20 years has been the speed at which advances in semiconductor technology have been exploited by industry. Each new generation of semiconductor devices has led to new system designs and to new user capabilities which represented a major advance upon the systems and capabilities that came before them. However, to achieve this required a large number of different components and tools to become available at the right time, and at an affordable price. The routine achievement of this is evidence of how companies and institutions within the sector have been able to communicate effectively and establish a high level of collaboration, whilst still maintaining intense competition at the product level. QT is very different to the semiconductor industry. While a number of target applications exist the discipline is very much in its infancy. At one end of the spectrum, there are some applications in communications and sensors that are relatively close to market, and, at the other end, there are some applications in computing and simulation that are still far from market. Many choices of enabling technologies and materials have yet to be fixed, and there is, as yet, very little first-hand experience of the problems that will arise when companies seek to establish repeatable manufacture of quantum components and systems. What can we learn from the International Technology Roadmap for Semiconductors (ITRS) that might benefit the Quantum Technology community? Generating an additional quantum roadmap would merely duplicate previous work – but establishing a small number of cross-community working groups might be a way to assist UK industry to gain a competitive edge in the application of quantum technologies, without duplicating the existing activities by other bodies such as InnovateUK, British Standards Institution (BSI), European Telecommunications Standards Institute (ETSI), Defence Science and Technology Laboratory (Dstl) etc. This document reports on discussions held at the meeting around this question and, leveraging this input, seeks to provide clear and appropriate recommendations to the UK QT community

Consensus for experimental design in electromyography (CEDE) project:Checklist for reporting and critically appraising studies using EMG (CEDE-Check)

The diversity in electromyography (EMG) techniques and their reporting present significant challenges across multiple disciplines in research and clinical practice, where EMG is commonly used. To address these challenges and augment the reproducibility and interpretation of studies using EMG, the Consensus for Experimental Design in Electromyography (CEDE) project has developed a checklist (CEDE-Check) to assist researchers to thoroughly report their EMG methodologies. Development involved a multi-stage Delphi process with seventeen EMG experts from various disciplines. After two rounds, consensus was achieved. The final CEDE-Check consists of forty items that address four critical areas that demand precise reporting when EMG is employed: the task investigated, electrode placement, recording electrode characteristics, and acquisition and pre-processing of EMG signals. This checklist aims to guide researchers to accurately report and critically appraise EMG studies, thereby promoting a standardised critical evaluation, and greater scientific rigor in research that uses EMG signals. This approach not only aims to facilitate interpretation of study results and comparisons between studies, but it is also expected to contribute to advancing research quality and facilitate clinical and other practical applications of knowledge generated through the use of EMG.</p

Patents and Industrialisation. An Historical Overview of the British Case, 1624-1907

A Report to the Strategic Advisory Board on Intellectual Property Policy (SABIP), U

Hip joint biomechanics during gait in people with and without symptomatic femoroacetabular impingement

Femoroacetabular impingement (FAI) is a morphological hip condition that can cause hip/groin pain and impaired function in younger active adults, and may lead to stiffness, muscle weakness, structural damage, and hip osteoarthritis. Understanding the impairments associated with FAI is crucial to guide treatment and rehabilitation strategies. Evidence is limited and conflicting about whether hip biomechanics are impaired during walking in people with symptomatic FAI. The objective of this study was to determine whether kinematics and kinetics during gait differ between people with symptomatic FAI and control participants. Fifteen participants diagnosed with symptomatic cam-type or combined (cam plus pincer) FAI who were scheduled for arthroscopic surgery and 14 age-, and sex-matched disease-free controls underwent three-dimensional gait analysis. Tri-planar hip kinematics and kinetics were compared between the two groups. There were limited significant between-group differences with respect to spatiotemporal variables. Participants with FAI walked with less range of motion in the sagittal plane during a gait cycle, but did not exhibit any significant kinematic differences in the frontal or transverse planes. There were no systematic differences in kinetics between the groups in any plane. Findings suggest that individuals with symptomatic FAI have minimal impairments in gait biomechanics. Although these individuals demonstrate reduced hip joint motion in the sagittal plane, the size of the difference is small and its significance for symptoms and function is unclear. More pronounced deficits in hip kinetics and kinematics may be evident during functional tasks that challenge the hip towards the position of impingement

Squatting biomechanics in individuals with symptomatic femoroacetabular impingement

Purpose Identification of the biomechanical alterations in individuals with symptomatic femoroacetabular impingement (FAI) is critical to understand the pathology and inform treatments. Yet hip function in this condition is poorly defined. Squatting requires large hip flexion range and involves motion toward the position of hip impingement; thus, it is likely to expose modified biomechanics in these individuals. This study aimed to determine whether hip and pelvis biomechanics differ between individuals with and without symptomatic FAI during an unconstrained deep squat and a constrained squat designed to limit compensation by the pelvis and trunk. Methods Fifteen participants with symptomatic cam-type or combined (cam plus pincer) FAI who were scheduled for arthroscopic surgery and 14 age- and sex-matched controls without FAI underwent three-dimensional motion analysis during the two squatting tasks. Trunk, pelvis, and hip kinematics and hip kinetics were compared between groups. Results There were no between-group differences in normalized squat depth for either task. Descent speed was slower for the FAI group during the unconstrained squat (P < 0.05). During the constrained squat, individuals with FAI demonstrated greater pelvic rise (P = 0.01) and hip adduction (P = 0.04) on the symptomatic side than controls. The hip external rotation moment was less in FAI patients during descent (P = 0.04), as was transverse plane hip angle variability (P = 0.04). Conclusions Individuals with symptomatic FAI can squat to a depth comparable with controls, regardless of task design. When the task is constrained, FAI patients demonstrate greater ipsilateral pelvic rise and maintain a more adducted hip position, which may coincide with a compensatory strategy to avoid end range flexion as the hip approaches impingement. These biomechanical alterations may put additional stress on adjacent regions and have relevance for rehabilitation

Isometric and isokinetic hip strength and agonist/antagonist ratios in symptomatic femoroacetabular impingement

Objectives This study investigated isometric and isokinetic hip strength in individuals with and without symptomatic femoroacetabular impingement (FAI). The specific aims were to: (i) determine whether differences exist in isometric and isokinetic hip strength measures between groups; (ii) compare hip strength agonist/antagonist ratios between groups; and (iii) examine relationships between hip strength and self-reported measures of either hip pain or function in those with FAI. Design Cross-sectional. Methods Fifteen individuals (11 males; 25\ua0±\ua05 years) with symptomatic FAI (clinical examination and imaging (alpha angle >55° (cam FAI), and lateral centre edge angle >39° and/or positive crossover sign (combined FAI))) and 14 age- and sex-matched disease-free controls (no morphological FAI on magnetic resonance imaging) underwent strength testing. Maximal voluntary isometric contraction strength of hip muscle groups and isokinetic hip internal (IR) and external rotation (ER) strength (20°/s) were measured. Groups were compared with independent t-tests and Mann–Whitney U tests. Results Participants with FAI had 20% lower isometric abduction strength than controls (p\ua0=\ua00.04). There were no significant differences in isometric strength for other muscle groups or peak isokinetic ER or IR strength. The ratio of isometric, but not isokinetic, ER/IR strength was significantly higher in the FAI group (p\ua0=\ua00.01). There were no differences in ratios for other muscle groups. Angle of peak IR torque was the only feature correlated with symptoms. Conclusions Individuals with symptomatic FAI demonstrate isometric hip abductor muscle weakness and strength imbalance in the hip rotators. Strength measurement, including agonist/antagonist ratios, may be relevant for clinical management of FAI