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Gaurav P Patel, Susan A Smith, Michelle Romej, Billynda McAdoo, Elizabeth A Wilson Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, 30322, USACorrespondence: Gaurav P Patel, Department of Anesthesiology, Emory University School of Medicine, 1364 Clifton Road, NE, Atlanta, GA, 30322, USA, Tel +1 404-778-3900, Email gppatel@emory.eduAbstract: Hypotension during kidney transplantation can be common. Vasopressor use during these procedures is often avoided, with a fear of decreasing renal perfusion in the transplanted kidney. However, adequate perfusion for the rest of the body is also necessary, and given that these patients often have underlying hypertension or other comorbid conditions, an appropriate mean arterial pressure (MAP) has to be maintained. Intramuscular injections of ephedrine have been studied in the anesthesiology literature in a variety of case types, and it is seen as a safe and effective method to boost MAP. We present a case series of three patients who underwent renal transplantation and who received an intramuscular injection of ephedrine for hypotension control. The medication worked well for increasing blood pressures without apparent side effects. All three patients were followed for more than one year, and all patients had good graft function at the end of that time period. This series shows that while further research is necessary in this arena, intramuscular ephedrine may have a place in the management of persistent hypotension in the operating room during kidney transplantation.Keywords: kidney transplant, hypotension, general anesthesia, intramuscular ephedrine, perfusion pressure

Richard G Abramson,1,2,9 Lori R Arlinghaus,1,2 Jared A Weis,1,2 Xia Li,1,2 Adrienne N Dula,1,2 Eduard Y Chekmenev,1–4,9 Seth A Smith,1–3,5 Michael I Miga,1–3,6 Vandana G Abramson,7,9 Thomas E Yankeelov1–3,5,8,91Institute of Imaging Science, 2Department of Radiology and Radiological Sciences, 3Department of Biomedical Engineering, 4Department of Biochemistry, 5Department of Physics, 6Department of Neurosurgery, 7Department of Medical Oncology, 8Department of Cancer Biology, 9Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville,TN, USAAbstract: Reliable early assessment of breast cancer response to neoadjuvant therapy (NAT) would provide considerable benefit to patient care and ongoing research efforts, and demand for accurate and noninvasive early-response biomarkers is likely to increase. Response assessment techniques derived from quantitative magnetic resonance imaging (MRI) hold great potential for integration into treatment algorithms and clinical trials. Quantitative MRI techniques already available for assessing breast cancer response to neoadjuvant therapy include lesion size measurement, dynamic contrast-enhanced MRI, diffusion-weighted MRI, and proton magnetic resonance spectroscopy. Emerging yet promising techniques include magnetization transfer MRI, chemical exchange saturation transfer MRI, magnetic resonance elastography, and hyperpolarized MR. Translating and incorporating these techniques into the clinical setting will require close attention to statistical validation methods, standardization and reproducibility of technique, and scanning protocol design.Keywords: treatment response, presurgical treatment, neoadjuvant chemotherapy

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. We present a silica nanoparticle (SNP) functionalized with polyphosphate (polyP) that accelerates the natural clotting process of the body. SNPs initiate the contact pathway of the blood-clotting system; short-chain polyP accelerates the common pathway by the rapid formation of thrombin, which enhances the overall blood-clotting system, both by accelerating fibrin generation and by facilitating the regulatory anticoagulation mechanisms essential for hemostasis. Analysis of the clotting properties of bare SNPs, bare polyP, and polyP-functionalized SNPs in plasma demonstrated that the attachment of polyP to SNPs to form polyP-SNPs creates a substantially enhanced synergistic effect that lowers clotting time and increases thrombin production at low concentrations. PolyP-SNP even retains its clotting function at ambient temperature. The polyP-SNP system has the potential to significantly improve trauma-treatment protocols and outcomes in hospital and prehospital settings.

The enormous composition possibilities and the potential of developing alloys with improved properties have resulted in a spike in research interest in the area of high entropy alloys (HEAs) since 2010. Being multicomponent alloys with five or more metallic elements mixed in equimolar or non-equimolar ratio, HEAs offer limitless possibilities in the development of new alloys with unique properties as compared to the conventional alloys development techniques that involve the addition of one or more alloying elements in minute quantity to the principal element. Despite the tremendous interest in the field of HEAs and the development of new HEAs with unique properties, a comprehensive review of the effects of fabrication techniques on the mechanical properties of the developed alloys is still limited in the open literature. Hence, an attempt was made in this review to show the different techniques used in the manufacturing and synthesizing of HEAs and the effects of the used techniques on the mechanical properties of the alloys. Finally, some of the major challenges associated with the manufacturing and synthesizing of HEAs are reported.

Storage tanks are essential components in various industries, particularly in power generation, where they are utilized for oil storage. The stress developed within these tanks due to internal pressure significantly influences their useful life and buckling behaviour during service. In this study, finite element analysis is employed to investigate the stress development and buckling behaviour of a fixed, closed-rooftop cylindrical oil storage tank used in a power generation company when filled and half-filled with diesel. The stress analysis results reveal that the stress developed in the tanks under both operating conditions considered is below the yield stress of the tank material. This suggests that, under these conditions, the tank is poised to have an infinite useful life, as long as it is not subjected to external pressure. The eigenvalue buckling analysis indicates that the during buckling of the storage tank the maximum displacement in the filled tank will occur in the middle if the bifurcation point is reached while the maximum displacement in the half-filled tank varies depending on the mode being considered. Based on the finite element analysis, it is concluded that the oil storage tank, under the specified conditions, experiences stresses below the yield point, thus, ensuring an extended useful life.

This review paper encompasses a comprehensive exploration of fatigue failure and fatigue life estimation techniques which spans from the classical methods to new and innovative approaches. The paper looks into the limitations and advancements of these techniques and highlights their respective strengths and areas for improvement. Some of the models such as artificial neural networks and genetic algorithms exhibit clear advantages in terms of processing speed, accuracy, and adaptability to diverse materials and loading scenarios. For instance, in estimating fatigue life under multiaxial loading, the stress scale factor model emerges as a viable alternative to the critical plane-based approach, as this technique offers superior efficiency under both constant and variable amplitude loadings. Additionally, optimization algorithms such as artificial neural networks and genetic algorithms show promising potential in efficiently estimating fatigue life due to their rapid computational capabilities. Despite the notable successes achieved by these techniques, none of them can be ascribed as a universal model capable of accurately estimating the fatigue life of all materials across diverse operating conditions as each of the techniques possesses its unique strengths and weaknesses, thus, necessitating the study for a better understanding of their applicability. Hence, this paper serves as a valuable compilation of various fatigue analysis techniques, targeted at paving the way towards the development of a universal model capable of handling different materials and loading conditions.

Investigating the structural behaviour and buckling susceptibility of cylindrical oil storage tanks is crucial for ensuring their safe and reliable operation. In this study, the structural behaviour and buckling susceptibility of closed roof-top cylindrical oil storage tanks under combined internal and external pressure scenarios were investigated using the finite element analysis (FEA) technique. By utilizing the FEA technique, the combined effect of wind-induced pressure of 250 Pa, applied on the outer surface of the tank and internal pressure of 0.5 MPa, applied on the outer surface of the storage was analysed. The result reveals significant stress concentrations and deformation patterns, particularly on the windward side of the tank, thus, emphasizing the susceptibility of the storage tank to buckling under the specified operating conditions for both the filled and half-filled tank; with internal pressure emerging as the primary contributor to mechanical strain and deformation experienced in the tank, while the wind load plays a secondary but significant role in the deformation of the tank. The fe-safe predicted useful life shows that under the specified operating conditions, the filled storage tank will survive 1 429 hours (2 months) while the half-filled tank will survive 3 551 hours (5 months) before failure due to buckling. Thus, the useful life estimation results show the importance of varying oil levels and operating conditions in the structural assessments of storage tanks.

Spark plasma sintering (SPS) technique was employed in the consolidation of Cr20Mn20Ni20Cu20Nb10Co10 high entropy alloy (HEA) reinforced aluminium matrix composites. Phase stability and prediction expressions were used in the determination of the powder combination for the HEA. The microstructural analysis showed that an interdiffusion layer was formed between the aluminium matrix and the HEA particles in the sintered composites. Further investigation of the composites by X-ray diffraction (XRD) showed that in addition to the Al matrix phase present, other new phases (BCC, FCC and other intermetallics) were formed as a result of the reaction between the Al matrix and the atoms precipitated from the added HEA during sintering. The density of the HEA-reinforced Al matrix composites decreases with an increase in the wt.% of HEA from 98.6 % for pure aluminium to 98.1 % for the reinforced alloy with 10 % HEA, while the microhardness increases with an increase in the wt.% of the HEA from 35 HV for pure aluminium to 96.0 HV for the alloy reinforced with 10 % HEA.

While IN738 Ni-based superalloy is a high strength alloy, it is feasible to improve its properties at the bulk level by reinforcing with graphene nanoplatelets (GNPs), taking advantage of the superior mechanical, tribological and thermal properties using the spark plasma sintering technique. In the present study, the influence of spark plasma sintering temperature range between 900 and 1100 °C on the microstructure, mechanical, tribological and thermophysical properties of GNPs/IN738 composite is assessed. The dispersion of GNPs reinforcement and alloying metals to form composite powder is conducted using a turbular mixer and low-frequency planetary ball milling, followed by spark plasma sintering. The relative density of the sintered samples assessed following Archimedes' method indicates increasing densification with the increasing sintering temperature from 94.7% (900 °C) to 98.5% (1100 °C). The microstructure assessed via SEM, XRD and Raman spectroscopy indicates the formation of precipitate gamma, intermetallic gamma prime, solid solution and GNPs strengthening phases. Thus, the mechanical (micro/nano hardness and Young's modulus), tribological (wear rate and coefficient of friction), and thermophysical (thermal diffusivity, thermal conductivity, and specific heat capacity) properties increased with the increasing sintering temperature. The microhardness increased from 354HV (900 °C) to 469HV (1100 °C), nanohardness from 8 GPa (900 °C) to 17 GPa (900 °C), and Young's modulus from 190 GPa (900 °C) to 291 GPa (1100 °C). The wear rate reduced with an increase in sintering temperature for the three loads of 5, 10 and 20N. The thermophysical properties assessed from 25 to 600 °C show the formation of few inflection points as the temperature increases, which is attributed to the dissolution and rearrangement of precipitate gamma prime and Cr in solid solution phases. Similarly, the small increment in the thermal diffusivity is equally associated with the smoother phonon transition at the GNPs/matrix interface.

Background Peripheral arterial disease is common and associated with increased cardiovascular morbidity and mortality. While patients with peripheral arterial disease are known to benefit from supervised exercise therapy, it is not always available. Neuromuscular electrical stimulation devices may offer a similar benefit. A randomised controlled trial was required to ascertain whether such devices can benefit patients who receive supervised exercise therapy and those who do not. Objective(s) The primary objective was to assess the mean difference in absolute walking distance at 3 months in intermittent claudication patients receiving either a neuromuscular electrical stimulation device and local standard care (intervention), or local standard care alone (control). Design A pragmatic, multicentre, randomised controlled trial stratified by centre. Setting Secondary-care National Health Service hospitals in the United Kingdom. Participants Patients aged ≥18 years, with a diagnosis of intermittent claudication according to the Edinburgh Claudication Questionnaire and ankle–brachial pressure index (or stress test), without contraindications to neuromuscular electrical stimulation were deemed eligible to partake. Interventions Participants were randomised 1 : 1 to either local standard care or local standard care and neuromuscular electrical stimulation. Due to the nature of the intervention, it was unfeasible to blind the research nurse or participant to the study allocation. Main outcome measures The primary outcome measure was absolute walking distance measured by treadmill testing at 3 months. Secondary outcomes included change in initial claudication distance, quality of life, compliance with interventions and haemodynamic assessments. Results Two hundred patients underwent randomisation, with 160 patients having analysable primary outcome data for the intention-to-treat analysis intervention (n = 80); control (n = 80). As the data were right-censored, a Tobit regression model was used to analyse the primary outcome, utilising the square root of the absolute walking distance to accommodate the skewed data. However, as this made the data difficult to interpret, a Tobit regression model using raw absolute walking distance data was used as well. Neuromuscular electrical stimulation improved the difference in absolute walking distance at 3 months but this was not statistically significant (square root of absolute walking distance: 0.835 units, 95% confidence interval −0.67 to 2.34 units; p = 0.28/absolute walking distance raw data: 27.18 m, 95% confidence interval −26.92 to 81.28 m; p = 0.323). Supervised exercise therapy participants showed a markedly improved absolute walking distance compared with patients receiving best medical therapy only at 3 months (square root of absolute walking distance: 3.295 units 95% confidence interval 1.77 to 4.82; p < 0.001/absolute walking distance raw data: 121.71 m, 95% confidence interval 67.32 to 176.10; p ≤ 0.001). Neuromuscular electrical stimulation significantly improved absolute walking distance at 3 months for mild claudicants (square root of absolute walking distance: 2.877 units, 95% confidence interval 0.51 to 5.25; p = 0.019/absolute walking distance raw data: 120.55 m, 95% confidence interval 16.03 to 225.06; p = 0.03) compared to the control arm. This was an unplanned (post hoc) analysis. There were no clear differences in mechanistic measurements between the two treatment groups over the follow-up period. Serious adverse events were evenly reported between the two groups; all being classified as either not related or unlikely to be related to the study device. Limitations Absolute walking distance was used as the primary outcome measure; there was a large range of baseline distances in both groups with right-skewed distribution. We did not stratify by baseline absolute walking distance for the primary outcome analysis. Additionally, only 160 patients had analysable primary outcome data due to missing treadmill data. Conclusions Supervised exercise therapy is an effective treatment for intermittent claudication. Neuromuscular electrical stimulation appears to be beneficial as an adjunct to supervised exercise therapy and on its own in mild claudicants. Future work Further studies are needed to confirm the effectiveness of neuromuscular electrical stimulation in combination with supervised exercise therapy, and in mild to moderate claudicants in a larger sample size. Study registration This trial is registered as ISRCTN18242823. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR) partnership (project number 15/180/68). This will be published in full in Efficacy and Mechanism Evaluation; Vol. 10, No. 2. See the NIHR Journals Library website for further project information. Infrastructure support for this research was provided by the NIHR Imperial Biomedical Research Centre (BRC) (with others, e.g. NIHR Imperial CRF, Imperial College ECMC, NIHR Imperial PSTRC, NIHR London MIC, etc.). Plain language summary Why did we conduct this research? Patients with intermittent claudication present with pain in the lower limbs on exercising, relieved by rest. This negatively impacts on exercise tolerance and quality of life. Initially, such patients should be offered best medical therapy, including exercise advice, and a supervised exercise therapy programme. Supervised exercise therapy involves leg and feet exercises supervised by health-care professionals and, despite evidence favouring supervised versus unsupervised exercise, are underutilised in the United Kingdom. Therefore, there remains a significant difference between recommended standard care (best medical therapy and supervised exercise therapy) and ‘real-world’ standard care (best medical therapy only). Neuromuscular electrical stimulation devices have emerged as safe, portable and readily accessible, with some evidence suggesting they can improve outcomes, including pain-free walking distance and quality of life. This study investigated whether a neuromuscular electrical stimulation device improved the walking distance of patients with intermittent claudication compared to local standard care available (which may include supervised exercise therapy). What did we do? Two hundred patients diagnosed with intermittent claudication at 11 hospitals in England took part. A computer program randomly assigned half the patients to local standard care only, while the other half were given a neuromuscular electrical stimulation device which delivers electrical stimulation to leg and feet muscles through foot-pads, plus local standard care. What did we find? There was no clear difference in maximal walking distances between those who received a device and those who didn’t. However, neuromuscular electrical stimulation improved walking distances in patients who attended a supervised exercise therapy programme (although not significant), and clearly improved walking distances in those patients with a good baseline upper walking limit. Supervised exercise therapy significantly improved walking distances. What could be done next? Future research studies should further evaluate the effectiveness of neuromuscular electrical stimulation in combination with supervised exercise therapy, and in patients who have a good baseline walking distance in a larger sample of patients with intermittent claudication. Scientific summary Background Peripheral arterial disease (PAD) is a common condition that is predominantly caused by atherosclerosis, resulting in a reduced blood flow to the affected limb. It presents a significant global health burden, affecting over 200 million people worldwide. These individuals are at higher risk of other cardiovascular events and PAD itself has its own associated sequelae – for example, ulcer development. Intermittent claudication (IC) is the commonest symptom of PAD, patients experiencing leg pain while walking which is relieved by rest. This has a significant impact on exercise tolerance and quality of life. According to National Institute for Health and Care Excellence guidelines, all patients suffering from IC should receive both first-line treatment of best medical therapy (BMT) (including exercise advice) and supervised exercise therapy (SET). SET is known to significantly improve absolute walking distance (AWD) in IC patients but despite these guidelines, recommended care for the first-line management of claudication is significantly below standard, largely due to lack of National Health Service capability. Without a demonstrable benefit of non-invasive strategies for the management of IC, there is an increased likelihood of invasive treatment options. Neuromuscular electrical stimulation (NMES) is an emerging technology and such devices are readily accessible and can be used in the patient’s own home. Although some evidence of the efficacy of NMES in the management of patients with IC exists, in improving both functional and quality-of-life measures, further high-quality research is required. The NESIC (A Multicenter Randomised Controlled Study: Does Neuromuscular Electrical Stimulation Improve the Absolute Walking Distance in Patients with Intermittent Claudication (NESIC) compared to best available treatment?) study provides an evidence base for the efficacy of the REVITIVE IXTM (Actegy Health Ltd, Bracknell, UK) device in the non-invasive management of claudicants and assesses the cost-effectiveness of the device compared to SET. Objectives (list of research questions) 1.Primary objective: To assess the clinical efficacy of a NMES device as an adjunct to the local standard care available at the study randomisation sites to improve AWD in patients with IC. 2.Secondary objectives: a.To understand the underlying mechanisms for change in clinical and subjective outcomes in the form of lower-limb gross (duplex ultrasound) and superficial haemodynamic assessment (laser doppler flowmetry) b.To determine compliance with NMES device and SET programme c.To compare quality of life between those receiving local standard care alone and those receiving both local standard care and NMES d.To assess the actual cost-effectiveness of the NMES device compared to SET. Methods Design A multicentre, pragmatic, randomised clinical trial to compare the mean difference in AWD in patients with IC who are given NMES in addition to local standard care and those receiving local standard care only. Setting Eleven secondary-care NHS hospitals across England; a combination of centres with and without established provision of SET. Participants Between March 2018 and 17 March 2020, 200 participants were randomised into the NESIC trial. Follow-up was completed on 31 March 2021. Written informed consent was obtained from all participants, who then underwent eligibility assessments. Participants, as defined by the inclusion and exclusion criteria, were randomised 1 : 1 to either local standard care alone (standard care), or NMES and local standard care (intervention). Inclusion criteria •positive Edinburgh Claudication Questionnaire •ankle–brachial pressure index 30 mmHg, 40 seconds post 1 minute treadmill at 10% gradient, 4 km/hour) •able to give informed consent to participate in the trial after reading the patient information documentation •age ≥18 years. Exclusion criteria •severe IC requiring invasive intervention as determined by the treating clinician •critical limb ischaemia as defined by the European Consensus Document •comorbid disease prohibiting walking on a treadmill or taking part in SET •able to walk for longer than 15 minutes on the study treadmill assessment •have attended SET classes in the previous 6 months •popliteal entrapment syndrome •commenced vascular-symptom-specific medication in previous 6 months – for example, naftidrofuryl oxalate, cilostazol •pregnancy •any implanted electronic, cardiac or defibrillator device •acute deep vein thrombosis •broken or bleeding skin, including leg ulceration •peripheral neuropathy •recent lower-limb injury or lower back pain •already using a NMES device. Randomisation Randomisation (1 : 1) was web-based and hosted by Oracle Health Sciences InForm™ (Oracle®; Health Sciences, Austin, TX, USA) electronic data capture on an Oracle platform. Randomisation used random block size and was stratified by centres. Interventions The NMES device (REVITIVE IX) can be used in the patient’s own home. It delivers a 30-minute pre-programmed session of electrical stimulation to the lower-limb muscles through foot pads while the patient is in a seated position. The user controls the intensity of the impulses, and therapeutic benefit is deemed to occur when impulses are sufficient to cause contraction of the calf muscles, increasing venous return to the heart. The IsoRocker feature allows the device to tilt back and forth as the muscles contract and relax. The device is to be used for at least one 30-minute session daily (up to a maximum of six sessions) for 3 months (treatment period). Diabetic patients are to use the device for a minimum of two 30-minute sessions daily for the duration of the treatment period to better reflect the evidence supporting the diabetic patient group and improvement of their symptoms. A SET programme is usually led by a physiotherapist or allied health-care provider supervising exercise, usually within the physiotherapy gymnasium with equipment including a treadmill, steps and walking cones. SET classes usually involve a circuit of lower-limb exercises, for a minimum of 30 minutes per week, and usually over a 3-month duration. Outcomes and follow-up The primary outcome was AWD at 3 months, measured by treadmill testing. Secondary outcomes included quality of life over 12 months as measured by generic health-related quality of life tools, European Quality of Life 5-Dimensions 5-Level (EQ-5D-5L®) (EuroQol Group, Rotterdam, The Netherlands), Short-Form Health Survey-36 (SF-36®) (RAND Health Care, Santa Monica, CA, USA) and the intermittent claudication questionnaire; compliance with NMES and SET as measured against self-report participant diaries and device data loggers; change in initial claudication distance measured by treadmill testing; and haemodynamic assessments measured by duplex ultrasound and laser doppler flowmetry. Participants in both groups were followed up for 12 months post randomisation. In-person visits were performed at screening/baseline (randomisation), 3 months, 6 months and 12 months. The treadmill assessment (Gardner-Skinner protocol) and laser doppler flowmetry of the foot were completed at each visit and the duplex ultrasound was performed by a vascular scientist at baseline and 3 months only. Self-report health resource-use participant diaries were completed throughout the 12-month duration of the study. Additionally, the self-report exercise diaries were completed by all participants for 3 months or for the duration of the SET programme, and the device compliance diaries were completed by participants randomised to NMES for the duration of the treatment period. A device experience questionnaire was completed at 3 months for participants in the NMES arm of the trial. The quality-of-life questionnaires were administered at baseline and each follow-up either in person, via the telephone or via post. Participant follow-up is summarised in Appendix 1. Due to the COVID-19 crisis, a substantial amendment was submitted to Ethics in April 2020 to allow all follow-up visits to take place remotely (i.e. over the telephone completely or in combination with postal questionnaires) in the event that the participant was unable to attend in clinic or the site was unable to accommodate the on-site visit. Missed (physical) assessments as a result of a remote visit were rescheduled at a later date as a separate on-site visit, where possible. If an on-site visit was rescheduled at a later date, all quality-of-life questionnaires that were completed remotely were repeated at the on-site visit. Results (research findings) Two hundred participants underwent randomisation and 160 were included in the intention-to-treat primary analysis [intervention (n = 80); control (n = 80)]. NMES improved AWD in patients with IC following the 3-month treatment period but this was not statistically significant [square root of AWD: 0.835 units, 95% confidence interval (CI) −0.67 to 2.34; p = 0.276/AWD raw data: 27.18 m, 95% CI −26.92 to 81.28; p = 0.323]. Participants who had access to a SET programme showed a clear improvement in AWD compared with patients who received BMT only at 3 months (square root of AWD: 3.295 units, 95% CI 1.77 to 4.82; p < 0.001/AWD raw data: 121.1 m, 95% CI 67.32 to 176.10; p < 0.001). Improvements in the AWD at 3 months were seen when NMES was used in combination with SET, but this was not significant (square root of AWD: 1.724 units, 95% CI −0.56 to 4.01; p = 0.137/AWD raw data: 64.26 units, 95% CI −20.03 to 148.54; p = 0.13). NMES significantly improved AWD at 3 months for patients who could walk for more than 340 m at baseline (square root of AWD: 2.877 units, 95% CI 0.51 to 5.25; p = 0.019/AWD raw data: 120.55 m, 95% CI 16.03 to 225.06; p = 0.03) compared to the control arm. Mechanistic findings of the laser doppler flowmetry found no clear differences in blood flux between the two treatment groups over the 12-month follow-up period, nor any significant differences in volume flow or time average mean velocity (duplex ultrasound) groups at 3 months. Serious adverse events (n = 29) were reported in 24 participants, with all events being classified as either not related or unlikely to be related to the study device. The number of SAEs in the treatment arm was 13 and 16 in the control arm. Most of the events required hospitalisation; there were four deaths. Conclusions The results of the NESIC trial indicate that SET is the most effective treatment option for patients with IC. Although not significant, NMES improves walking distances when used in combination with a SET programme, and significantly improves AWD in mild claudicants. Implications for health care Findings from this trial suggest that all IC patients should have access to a SET programme and changes to such programmes may need to be made to encourage and/or retain participants. NMES may be an effective adjunct to SET and in patients with a good baseline walking distance. Recommendations for research (numbered in priority order) 1.Randomised controlled trial of NMES as an adjunct to SET in IC patients stratified by baseline AWD, as the NESIC study showed promise of non-invasive effectiveness in mild and/or moderate claudicants at improving walking distances, but larger numbers are required to validate this finding. 2.Research to examine the poor patient motivation and adherence to SET, as SET is clearly an effective treatment option for claudicants as seen in this study and many other studies but uptake/compliance remains an issue. 3.Research to evaluate the long-term effectiveness of SET programmes on maximal walking distance (MWD) and secondary outcomes such as quality of life and long-term engagement in physical activity. The NESIC study showed the effectiveness of SET at 12 months at improving AWD but longer-term follow-up is required to evaluate whether this is sustained years later. Previous studies have shown mixed results on the impact of SET on other outcomes, such as quality of life, and therefore further research is required. Study registration This trial is registered as ISRCTN18242823. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR) partnership (project number 15/180/68). This will be published in full in Efficacy and Mechanism Evaluation; Vol. 10, No. 2. See the NIHR Journals Library website for further project information. Infrastructure support for this research was provided by the NIHR Imperial Biomedical Research Centre (BRC) (with others, e.g. NIHR Imperial CRF, Imperial College ECMC, NIHR Imperial PSTRC, NIHR London MIC, etc.).

The microstructure, mechanical and tribological properties of Ni–Cr–ZrO2 composites, manufactured by using the spark plasma sintering technique with different sintering temperatures, were investigated. The individual powder was measured and mixed thoroughly in a tubular mixer for 8 h before being transferred to the sintering machine. The sintering temperatures of: 800, 900, 950 and 1000 °C with a pressure of 50 MPa, a holding time of 5 min and heating rate of 100 °C/min were used as the process parameters in order to develop four compositional composite systems, used in this investigation. Wear tests were, performed on the sintered composites at 10 N, 15 N and 20 N loads. The microstructural analyses of the sintered sample revealed the associated compositional homogeneities, formation of phases and pores. The results showed that the sintering temperature influenced the mechanical and tribological properties of the sintered composites, such that the increasing sintering temperature led to an increase in the relative density. The microhardness and wear resistance increased with the increasing sintering temperature, which showed that the composites developed, possessed improved properties by using high sintering temperature. Thus, the sample sintered at 1000 °C maintained the least wear rate and consequently, the best hardness property.

The consolidation of polylactic acid/graphene nanocomposite via a novel SPS powder metallurgy route was elaborated in this study. The nanocomposite powders were prepared using the three-dimensional (3-D) tubular mixer and consolidated under different parameters of spark plasma sintering (SPS). The densification, porosity, hardness, and crystalline properties of the consolidated specimen were investigated as a measure of its mechanical strength. These properties were observed to have an obvious dependence on the sintering process parameters. The fracture morphology of the sample reveals the ductile fractured at elevated sintering temperature of 160 °C while a fragile intergranular fracture type was revealed at a lower sintering temperature of 135 °C. SEM images revealed a well-distributed and dispersed GNP in the PLA matrix across the varied process parameters of temperature and pressure. The crystallinity of the nanocomposite peak was enhanced via the process engineering of SPS. This was observed with increased crystalline peaks on the XRD and percentage crystallinity reported on the DSC. Changes in the range of transmittance with respect to sintering parameters were observed on the FTIR. The thermal stability improves with respect to the sintering temperature and pressure within the range of the parameters reported. This reveals a better mass barrier effect of the nanocomposite due to better intermolecular diffusion and reduced pore spaces in the sintered samples. The thermal stability was observed to appreciate due to the better polymer nanoparticle interaction. Hence, this study further attests that aside from the use of nucleation agents such as GNP and plasticisation, process engineering of SPS could help in modifying desired properties of nanocomposite.

Environmental conservation and waste control have informed and encouraged the use of biodegradable polymeric materials over synthetic non-biodegradable materials. It has been recognized that nano-sized biodegradable materials possess relatively good properties as compared to conventional micron-sized materials. However, the strength characteristics of these materials are inferior to fossil-based non-biodegradable materials. In this study, biodegradable polylactide (PLA), reinforced with treated coconut husk particulates (CCP) for improved mechanical properties, was fabricated using an electrospinning process and representative volume element (RVE) technique, and some of the obtained mechanical properties were compared. It was observed that the electrospun CCP-PLA nanofibre composites show improved mechanical properties, and some of these mechanical properties using both techniques compared favourably well. The electrospun fibres demonstrate superior properties, mostly at 4 wt.% reinforcement. Thus, achieving good mechanical properties utilising agro waste as reinforcement in PLA to manufacture nanocomposite materials by electrospinning method is feasible and provides insight into the development of biodegradable nanocomposite materials.