Metabolic adaptations to repeated periods of contraction with reduced blood flow in canine skeletal muscle

BACKGROUND: Patients suffering from Intermittent Claudication (IC) experience repeated periods of muscle contraction with low blood flow, throughout the day and this may contribute to the hypothesised skeletal muscle abnormalities. However, no study has evaluated the consequences of intermittent contraction with low blood flow on skeletal muscle tissue. Our aim was to generate this basic physiological data, determining the 'normal' response of healthy skeletal muscle tissue. We specifically proposed that the metabolic responses to contraction would be modified under such circumstances, revealing endogenous strategies engaged to protect the muscle adenine nucleotide pool. Utilizing a canine gracilis model (n = 9), the muscle was stimulated to contract (5 Hz) for three 10 min periods (separated by 10 min rest) under low blood flow conditions (80% reduced), followed by 1 hr recovery and then a fourth period of 10 min stimulation. Muscle biopsies were obtained prior to and following the first and fourth contraction periods. Direct arterio-venous sampling allowed for the calculation of muscle metabolite efflux and oxygen consumption. RESULTS: During the first period of contraction, [ATP] was reduced by ~30%. During this period there was also a 10 fold increase in muscle lactate concentration and a substantial increase in muscle lactate and ammonia efflux. Subsequently, lactate efflux was similar during the first three periods, while ammonia efflux was reduced by the third period. Following 1 hr recovery, muscle lactate and phosphocreatine concentrations had returned to resting values, while muscle [ATP] remained 20% lower. During the fourth contraction period no ammonia efflux or change in muscle ATP content occured. Despite such contrasting metabolic responses, muscle tension and oxygen consumption were identical during all contraction periods from 3 to 10 min. CONCLUSION: repeated periods of muscle contraction, with low blood flow, results in cessation of muscle ammonia production which is suggestive of a dramatic reduction in flux through AMP deaminase

A self-insulating, high-power, microwave source

We present first predictions for the performance of a novel, mildly relativistic (500keV, 2kA), X-band Cherenkov oscillator, nominally a variant of the backward-wave oscillator. The source operates with no externally-applied magnetic insulation, relying only on the self-fields of the electron beam for propagation. This significantly reduces the overall energy requirements for operation, along with the complexity; conventional (magnetically insulated) sources of this type typically require magnetic field strengths of 1 – 2T for efficient beam propagation, translating to a relatively large solenoid and associated power-supply. By eliminating this factor, the overall-efficiency of the source is tightly coupled to the conversion-efficiency between the beam and the wave. Conversion efficiencies in excess of 30% have been predicted for the source, when driven by a high-quality electron beam; the parameters of which were determined via numerical modelling of the electron gun. A tolerance study of variation in the beam parameters shows the efficiency remains better than ∼25% over the variation in critical control parameters expected in experiment, with clean excitation of the intended TM01 operating mode achieved at a stable output frequency of ~9.4GHz. The resonant frequency of the source was found to be insensitive to variation in the electron energy over an extended range (400-600keV)

Linear plasma experiment for non-linear microwave interaction experiments

As a non-linear medium, plasma can exhibit diverse dynamics when excited bymultiple EM waves. Electromagnetic waves are vital to the introduction of energyin laser plasma interactions and the heating of magnetically confined fusion reactors.In laser plasma applications Raman coupling via a Langmuir oscillation or Brillouinscattering mediated by ion-acoustic waves are of interest. Signals with normalisedintensities approaching those used in some recent laser plasma interactions can begenerated using powerful and flexible microwave amplifiers, interacting in relativelytenuous, cool and accessible plasma. Other multi-wave interactions are interesting formagnetic confinement fusion plasmas, for example beat-wave interactions betweentwo microwave signals coupling to cyclotron motion of the ions and electrons or thelower hybrid oscillations may be useful in heating the plasmas or for driving currents.A linear plasma experiment is being built to test such multifrequency microwaveinteraction in plasma, based on prior research on geophysical cyclotron wave emissionand propagation [1,2]. The main section of the plasma will be magnetised at up to0.05T, with the plasma created by an RF helicon source to generate a dense, large,cool plasma with a high ionisation fraction. A range of frequency-flexible sources willprovide microwave beams to enable multi-wave coupling experiments. The paper willpresent progress on this apparatus and experiments.The authors gratefully acknowledge support from the EPSRC, MBDA UK Ltd andTMD Technologies Ltd.[1] Ronald K., Speirs D.C., McConville S.L., Phelps A.D.R., Robertson C.W., WhyteC.G., He W., Gillespie K.M., Cross A.W., Bingham R., 2008, Phys. Plasmas, 15,art.056503[2] Speirs, D.C., Bingham, R., Cairns, R.A., Vorgul, I., Kellett, B.J., Phelps, A.D.R.,Ronald, K, 2014, Phys. Rev. Lett., 113, art 15500

A high-power Ka-band free electron maser, defined by a 2D – 1D Bragg lasing cavity

One of the on-going research programs, at the University of Strathclyde, involves the development of high-power, pulsed, Free-Electron Masers (FEMs) with the lasing cavity defined using periodic corrugations on the drift-tube walls 1-4 . These corrugations form 1D and 2D Bragg resonators, whose reflection bands determine the dominant resonance of the maser 5 . Proper selection of the FEM undulator magnetic field strength, allows for efficient extraction of energy from a mildly relativistic (400 - 500 keV) electron beam at the resonant frequency of the lasing cavity, leading to monochromatic output at power levels of several tens of megawatts and pulse durations of ~150ns (determined primarily by the pulse duration of the driving power supply of ~250ns)

Experiences, acceptability and feasibility of an isometric exercise intervention for stage 1 hypertension: embedded qualitative study in a randomised controlled feasibility trial.

Background Healthy lifestyle changes for patients with stage 1 hypertension are recommended before antihypertensive medication. Exercise has antihypertensive benefits; however, low adoption and high attrition are common. Patients need easily adoptable, effective and manageable exercise interventions that can be sustained for life. We present participant and stakeholder perceptions of an isometric exercise intervention for stage 1 hypertension delivered in the National Health Service (NHS, UK). Methods An embedded qualitative study within a randomised-controlled feasibility study included intervention arm participants (n = 10), healthcare professionals from participating NHS sites (n = 3) and non-participating NHS sites (n = 5) taking part in semi-structured interviews to explore feasibility of delivering an isometric exercise intervention within the study design and an NHS context. Data was analysed using reflective thematic analysis. Results Three themes were identified: study deliverability; motivators and barriers; support for study participation. Findings indicated that the study was well designed. Health benefits, unwillingness to take medication, altruism and interest in the study helped motivation and adherence. Study support received was good, but healthcare professionals were insecure in intervention delivery with regular training/supervision needed. Perception of health improvement was mixed, but, in some, uptake of wider lifestyle changes resulted from participation. Stakeholders felt that current service challenges/demand would make implementation challenging. Conclusions Despite participant positivity, delivery of an isometric intervention in an NHS setting was considered challenging given the current service demand, although possible with robust effectiveness evidence. Findings support further effectiveness data and implementation development of the isometric exercise intervention. Trial registration ISRCTN, ISRCTN13472393. Registered 18 September 2020

Delivering clinical studies of exercise in the COVID-19 pandemic: challenges and adaptations using a feasibility trial of isometric exercise to treat hypertension as an exemplar.

The COVID-19 pandemic has significantly impacted on the delivery of clinical trials in the UK, posing complicated organisational challenges and requiring adaptations, especially to exercise intervention studies based in the community. We aim to identify the challenges of public involvement, recruitment, consent, follow-up, intervention and the healthcare professional delivery aspects of a feasibility study of exercise in hypertensive primary care patients during the COVID-19 pandemic. While these challenges elicited many reactive changes which were specific to, and only relevant in the context of 'lockdown' requirements, some of the protocol developments that came about during this unprecedented period have great potential to inform more permanent practices for carrying out this type of research. To this end, we detail the necessary adaptations to many elements of the feasibility study and critically reflect on our approach to redesigning and amending this ongoing project in order to maintain its viability to date. Some of the more major protocol adaptations, such as moving the study to remote means wherever possible, had further unforeseen and undesirable outcomes (eg, additional appointments) with regards to extra resources required to deliver the study. However, other changes improved the efficiency of the study, such as the remote informed consent and the direct advertising with prescreening survey. The adaptations to the study have clear links to the UK Plan for the future of research delivery. It is intended that this specific documentation and critical evaluation will help those planning or delivering similar studies to do so in a more resource efficient and effective way. In conclusion, it is essential to reflect and respond with protocol changes in the current climate in order to deliver clinical research successfully, as in the case of this particular study. [Abstract copyright: © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.

Design and experiments of a five-fold helically corrugated waveguide for microwave pulse compression

Metal waveguide can be used as a dispersive medium to convert long duration, lower power pulses into short, higher peak power pulses. This provides an advanced method to generate radiation with gigawatts power in the millimeter and sub-millimeter wavelength range by compressing a megawatt level long duration pulse. In this paper, a five-fold helically corrugated waveguide operating in X-band was designed and constructed. The experiments conducted show that a 5.75 kW average power microwave pulse with a 6% bandwidth and duration of 80 ns can be compressed into a 144.8 kW, 1.6 ns pulse with a power compression factor of 25.2

Feasibility study to assess the delivery of a novel isometric exercise intervention for people with stage 1 hypertension in the NHS: protocol for the IsoFIT-BP study including amendments to mitigate the risk of COVID-19.

BackgroundHypertension  (HTN) affects approximately 25% of the UK population and is a leading cause of mortality. Associated annual health care costs run into billions. National treatment guidance includes initial lifestyle advice, followed by anti-hypertensive medication if blood pressure (BP) remains high. However, adoption and adherence to recommended exercise guidelines, dietary advice and anti-hypertensive medication is poor. Four short bouts of isometric exercise (IE) performed 3 days per week (d/wk) at home elicits clinically significant reductions in BP in those with normal to high-normal BP. This study will determine the feasibility of delivering personalised IE to patients with stage 1 hypertension for whom lifestyle changes would be recommended before medication within NHS primary care.MethodsThis is a randomised controlled feasibility study. Participants were 18+ years, with stage 1 hypertension, not on anti-hypertensive medication and without significant medical contraindications. Trial arms will be standard lifestyle advice (control) or isometric wall squat exercise and standard lifestyle advice. Primary outcomes include the feasibility of healthcare professionals to deliver isometric exercise prescriptions in a primary care NHS setting and estimation of the variance of change in systolic BP. Secondary outcomes include accuracy of protocol delivery, execution of and adherence to protocol, recruitment rate, attrition, perception of intervention viability, cost, participant experience and accuracy of home BP. The study will last 18 months. Sample size of 100 participants (50 per arm) allows for 20% attrition and 6.5% incomplete data, based upon 74 (37 each arm) participants (two-sided 95% confidence interval, width of 1.33 and standard deviation of 4) completing 4 weeks. Ethical approval IRAS ID is 274676.DiscussionBefore the efficacy of this novel intervention to treat stage 1 hypertension can be investigated in any large randomised controlled trial, it is necessary to ascertain if it can be delivered and carried out in a NHS primary care setting. Findings could support IE viability as a prophylactic/alternative treatment option.Trial registrationISRCTN13472393 , registered 18 August 2020

Numerical analysis of high-power X-band sources, at low magnetic confinement, for use in a multi-source array

High-power microwave sources are typically relativistic in nature, employing multi-kilo-ampere electron beams that require significant magnetic confinement for efficient operation. As the desired output power increases so does the complexity, and overall energy requirements, of the source. It can therefore be advantageous to consider the use of several, moderate-power, sources operating as a phased array; for an array of N sources the far-field peak intensity scales as N2, and the peak-of-field may be steered electronically by varying the relative phases of the different output signals. In this paper we present the numerical analysis of a short-pulse (∼1ns) X-band backward-wave oscillator, driven by a 210keV, 1.4kA electron beam, suitable for use as the radiative element in such an array. Investigation of the required magnetic confinement showed two peaks in performance, with the highest efficiency, of 43%, predicted at the low magnetic confinement peak at 0.3T, corresponding to 125MW peak output power. The magnitude, and timing, of the peak in the output pulse were functions of the rise-time of the electron beam energy, with longer rise-times resulting in delayed peak-of-field and lower peak output power. When operating in an array, to maintain effective output in the region of N2, it was determined that the beam rise-times, across all sources, should be ≤150ps with the adjustment of the relative timing between output’s being ±30ps

Sub-THz and THz Cherenkov radiation source with two-dimensional periodic surface lattice and multistage depressed collector

We present the theory, concept and design of an efficient, megawatt coherent Cherenkov radiation source based on a two-dimensional periodic surface lattice (2D-PSL) cavity combined with a novel energy recovery system for the generation of highly efficient (> 50%) single-frequency radiation. We demonstrate the scalability of the transverse dimension of the 2D-PSL cavity of the Cherenkov source and thus the potential for efficient, continuous-wave, high-power (> 1 MW) operation; fundamental to the eventual realization of clean, fusion energy. These new sources, with the capacity to operate in the 0.1-10THz range, hold strong promise to address the long-standing “Terahertz gap”. By combining a Cherenkov oscillator driven by a non-gyrating beam with an innovative four-stage depressed collector energy recovery system, the overall device efficiency can be increased to be competitive with gyrotrons in the requirements for heating and current drive in fusion plasma. In these Cherenkov devices, the frequency independence of the magnetic guide field enables advantageous frequency scaling without deployment constraints, making them especially attractive for high-impact applications in fusion science, turbulence diagnostics, non-destructive testing and biochemical spectroscopy. The novel energy recovery techniques presented in this paper have broad applicability to many electron-beam driven devices, bringing revolutionary potential to future THz source technologies