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Perelman M.,Nottingham Technology | Knight A.,Evicom Ltd.
International Journal of Clinical Pharmacology and Therapeutics | Year: 2013

Objective: Fentanyl pectin nasal spray (FPNS) is approved for management of breakthrough pain in cancer. It is available in 100 and 400 μg strength products which allow for doses of 100-800 μg (1 or 2 sprays). Existing titration strategies require a transition from the 100 μg product to the 400 μg product when increasing the dose from 200 to 400 μg. This study assessed the pharmacokinetic (PK) profile of FPNS administered as 4 sprays of 100 μg as an alternate titration strategy. Methods: In this 3-way, crossover study, healthy subjects aged 18-65 years were randomized to receive each of 3 dosages of FPNS (4 x 100 μg, 2 x 100 μg, and 1 x 400 μg). PK samples were collected over 24 hours. Results: Of 22 subjects randomized, 20 were included in the PK analysis. Administration of both 400 μg regimens (4 x 100 μg and 1 x 400 μg) provided greater systemic fentanyl exposure compared with the 200 μg dose (Cmax: 1,748 and 1,485 pg/ml vs. 1,051 pg/ml; AUC0-1h: 1,012 and 944 pgxh/ml vs. 665 pgxh/ml; and tmax: 0.25 hours and 0.50 hours vs. 0.25 hours); fentanyl exposure after 4 x 100 μg and 1 x 400 μg regimens was similar. Adverse events (AEs) were all mild or moderate in intensity; most common AEs were nausea (50%) and headache (23%). AE frequency was similar across treatments without reports of nasal effects. Conclusions: Given that systemic fentanyl exposure from FPNS administered as 4 x 100 μg is similar to that from FPNS as 1 x 400 μg, the 4 x 100 μg regimen provides an alternate titration strategy for patients needing more than 200 μg. This alternate strategy will facilitate a patient's ability to achieve an optimized FPNS regimen and reduce opioid wastage. ©2013 Dustri-Verlag Dr. K. Feistle.


Fisher A.,Nottingham Technology | Watling M.,Nottingham Technology | Smith A.,Nottingham Technology | Knight A.,Somerset House
International Journal of Clinical Pharmacology and Therapeutics | Year: 2010

Objectives: Fentanyl pectin nasal spray (FPNS) is formulated as a solution utilizing PecSys®; pectin based enabling technology (Archimedes). On contact with the nasal mucosa the formulation will gel and modulate fentanyl absorption while limiting nasal drip or runoff. This single-dose volunteer study compared the pharmacokinetics of FPNS 100, 200, 400, and 800 μg doses and assessed bioavailability relative to oral transmucosal fentanyl (OTFC) 200 μg. Safety and dose proportionality were also examined. Subjects and methods: 16, opioid-naïve subjects were dosed on five separate visits under naltrexone block. FPNS doses were administered using a Pfeiffer device delivering 100 μl. Devices were filled with either 1.57 mg/ml (100 and 200 μg dosing) or 6.28 mg/ml fentanyl citrate (400 and 800 μg). Venous blood samples were collected up to 48 h after dosing and plasma fentanyl concentrations measured. Results: Median tmax values for FPNS ranged from 15 to 21 min post-dose and were dose-independent. At 200 μg Cmaxvalues were 2.3-fold higher for FPNS compared with OTFC. Mean relative bioavailability of FPNS to OTFC ranged from 103% to 163%. Dose proportionality for Cmax and AUC0-1 across the FPNS range was statistically confirmed. Drug absorption also increased in a close to dose-proportional manner for AUC 0-∞. Conclusions: FPNS has a shorter tmax, higher Cmax and greater bioavailability than OTFC and is well tolerated. The dose proportionality of Cmax and AUC0-1 was demonstrated. It is concluded that the pharmacokinetic profile of FPNS suggests this product is suitable for clinical investigation in breakthrough pain in cancer patients. ©2010 Dustri-Verlag Dr. K. Feistle.


Federici S.,University of Perugia | Meloni F.,University of Perugia | Bracalenti M.,University of Perugia | De Filippis M.L.,Nottingham Technology
NeuroRehabilitation | Year: 2015

OBJECTIVE: This review examines the utility of current active, powered, wearable lower limb exoskeletons as aids to rehabilitation in paraplegic patients with gait disorders resulting from central nervous system lesions. METHOD: The PRISMA guidelines were used to review literature on the use of powered and active lower limb exoskeletons for neurorehabilitative training in paraplegic subjects retrieved in a search of the electronic databases PubMed, EBSCO, Web of Science, Scopus, ProQuest, and Google Scholar. RESULTS:We reviewed 27 studies published between 2001 and 2014, involving a total of 144 participants from the USA, Japan, Germany, Sweden, Israel, Italy, and Spain. Seventy percent of the studies were experimental tests of safety or efficacy and 29% evaluated rehabilitative effectiveness through uncontrolled (22%) or controlled (7%) clinical trials. CONCLUSIONS: Exoskeletons provide a safe and practical method of neurorehabilitation which is not physically exhausting and makes minimal demands on working memory. It is easy to learn to use an exoskeleton and they increase mobility, improve functioning and reduce the risk of secondary injury by reinstating a more normal gait pattern. A limitation of the field is the lack of experimental methods for demonstrating the relative effectiveness of the exoskeleton in comparison with other rehabilitative techniques and technologies. © 2015 - IOS Press and the authors. All rights reserved.


Popov A.A.,University of Nottingham | Rowell S.,Nottingham Technology | Meijaard J.P.,University of Twente
Vehicle System Dynamics | Year: 2010

The paper is a review of the state of knowledge and understanding of steering control in motorcycles and of the existing rider models. Motorcycles are well known to have specific instability characteristics, which can detrimentally affect the rider's control, and as such a suitable review of these characteristics is covered in the first instance. Next, early models which mostly treat riding as a regulatory task are considered. A rider applies control based on sensory information available to him/her, predominantly from visual perception of a target path. The review therefore extends to cover also the knowledge and research findings into aspects of road preview control. Here, some more emphasis is placed on recent applications of optimal control and model predictive control to the riding task and the motorcycle-rider interaction. The review concludes with some open questions which naturally present a scope for further study. © 2010 Taylor & Francis.


Shahaj A.,Nottingham Technology | Garvey S.D.,University of Nottingham
IEEE Transactions on Magnetics | Year: 2011

This paper introduces a magnetic bimorph concept as a means of manipulating magnetostriction in the stator teeth so that components of magnetostrictive force act to cancel out selected components of Maxwell force. This leads to zero net electromagnetic excitation of targeted vibration modes and reduces the vibration and resultant noise emission from the machine. The proposed noise reduction technique is suitable for large electrical machines with vibration modes that experience tooth rocking at natural frequencies within the range of acoustic interest. Experimental and finite-element investigations illustrate that this concept is a practical and low-cost method to implement without degrading the performance of the machine. A finite-element investigation has shown that the contributions to vibration of a large electrical machine from Maxwell forces in the air gap and the magnetostriction effect in the stator iron are comparable. Magnetostriction can act either to reduce or increase the overall modal excitation compared to the excitation of Maxwell forces. © 2006 IEEE.


Crowther A.,Nottingham Technology | Ramakrishnan V.,Michigan State University | Zaidi N.A.,Nottingham Technology | Halse C.,Nottingham Technology
Wind Energy | Year: 2011

Recent data shows that 90% of large wind turbines include a gearbox, and industry forecasts expect this figure to remain relatively stable. With global annual volumes (2009) of around 18,600 units, the quality, cost and performance of gearboxes is of paramount importance to the wind sector. The industry has been focusing some attention on gearbox reliability, as demonstrated by a growth in the number of specific seminars and collaborative programs on this topic. One aspect that needs to be brought to an industry-wide forum is the understanding of the complexity of bearing design in the gearbox and the careful attention that needs to be paid to ensure a reliable gearbox design. This paper seeks to address this issue by clear demonstration of design issues using a model of the gearbox from the National Renewable Energy Lab's Gearbox Reliability Collaborative. Detailed models are presented with focus on determining the quality of the function of the planetary gear stages. Key design drivers are discussed such as the quality of alignment at the gears and bearings and the loads and stresses seen on these components. Under a design load case with a significant rotor off-axis moment the stresses in the planet gears and bearings are investigated. It is shown how the misalignment of the planet pins varies with the rotation of the planetary set and how subsequently time-varying contact stresses and load distributions occur in the planet gears and bearings. These factors strongly influence the fatigue life of the gearbox components as well as the level of vibration. Design tools are then used to demonstrate how small variations in the clearances of the planet carrier bearings can have a big effect on the quality of the design. Numerical studies show where optimal clearance settings lie and how the misalignment of the planetary set can be improved. Furthermore, a demonstration is made of how redesign of the bearing arrangement and subsequent optimization of the planet tooth geometry further improves the misalignment and results in significantly reduced time-varying contact stresses, better load distribution and reduced vibration. It is illustrated that small clearances, such as in the carrier bearings, can have a large effect on the performance of the design and a study shows how to identify and reduce time-varying misalignment and contact stresses resulting in lower vibration, lower fatigue and a more reliable product. © 2011 John Wiley & Sons, Ltd.


Li S.,Nottingham Technology
International Journal of Mechanical Sciences | Year: 2014

This paper results from a reflection on the problem of finite rotations in plates and shells and its presentation in finite element formulation, a well-attended subject with a wide diversity of treatments, often extremely complicated. For instance, the very topic attracted 3 out of total 15 chapters over 120 out of total 494 pages in a monograph on nonlinear FEA [5]. In another instance, a 71 page journal paper was published [2] specifically on this topic alone. Review papers on this matter can be found in various sources including Appl Mech Rev, (e.g. Ibrahimbegovic, 1997 [8]). No attempt is to be made on reviewing these sophisticated approaches but the present paper will bring answers to questions, if they have ever been asked, such as whether the sophistication in existing approaches is really necessary and whether there is a much simpler and conceptually more direct and accurate approach. A proper re-examination of the existing approaches would reveal a fundamental inconsistency: rigid body rotations have been assumed without reservation to describe the deformations of deformable plates and shells. After re-establishing the consistency based on the very basics of conventional plate and shell theories as a simple reflection, one can conclude surprisingly that the whole issue on 'finite rotations' results from a logic fallacy of faulty generalisation. The so-called 'rotations' should be displacement gradients instead. They can be considered as 'rotations' as conventionally perceived hitherto under the condition of small deformation. Somehow, the concept of 'rotations' got generalised regardless the magnitude of the deformation. Instead of calling the problem as 'finite displacement gradients' as it should be called, a falsely generalised term of 'finite rotations' have been used. Since they were called 'rotations', the definition of those of rigid body kinematics has been taken for granted. Finite displacement gradients should not present any additional problem apart from introducing nonlinear nature into the problem, which can be addressed as a geometrically nonlinear problem in a conventional manner. However, along the line of a falsely generalised concept of finite rigid body rotations, complications have been the norm. The complicated accounts on the 'finite rotation' problem in the literature, which might have enhanced the understanding of rigid body kinematics, are entirely unnecessary as far as the deformable plates and shells are concerned, involving infinitesimal or finite deformations. © 2014 Elsevier Ltd. All rights reserved.


Naden B.J.,Nottingham Technology
Materials and Structures/Materiaux et Constructions | Year: 2015

The adsorption affinity of a surfactant foaming agent (SFA), α-olefin sulphonate (AOS)—used for generation of foam for low density concrete—to organically-modified montmorillonite (OMMT) has been investigated. OMMT has been proposed as an additive to cement and concrete for improved strength and durability. Similar thermodynamic processes are involved in the generation and stabilisation of foam and in the compatibilisation and stabilisation of organic particles in aqueous environments, so interaction between SFA and OMMT particles is likely. Association of foaming agent molecules with organoclay may lead to poor foaming performance and potential instability of the nanoparticles due to displacement of dispersants from the particle surface by foaming agent. Adsorption isotherms determined using a combination of ion-pair reverse phase high performance liquid chromatography (RP-HPLC) and gravimetric methods revealed that there is a relatively high affinity of AOS for the organoclay particles. This is a dynamic process, with smaller molecules adsorbing quickly but being displaced by larger molecules at higher surfactant loading. From the adsorption isotherm it was possible to calculate the minimum AOS addition that will ensure the full foaming performance in the cement formulation. Relative adsorption affinity and competitive adsorption at the particle surface of AOS with non-ionic and anionic surfactants commonly used as wetting and dispersing agents, was studied. The dispersants displayed considerably higher relative adsorption onto the organoclay than AOS, particularly in the case of the anionic species. There is evidence that some AOS adsorption takes place in particle systems stabilised by non-ionic dispersants; displacement of high adsorption affinity dispersants by the lower affinity AOS from the OMMT particle surface was not observed. © 2015 RILEM


Lopez-Anton M.A.,Nottingham Technology | Yuan Y.,Nottingham Technology | Perry R.,Nottingham Technology | Maroto-Valer M.M.,Nottingham Technology
Fuel | Year: 2010

Mercury in coal and its emissions from coal-fired boilers is a topic of primary environmental concern in the United States and Europe. The predominant forms of mercury in coal-fired flue gas are elemental (Hg0) and oxidized (Hg2+, primarily as HgCl2). Because Hg2+ is more condensable and far more water soluble than Hg0, the wide variability in mercury speciation in coal-fired flue gases undermines the total mercury removal efficiency of most mercury emission control technologies. It is important therefore to have an understanding of the behaviour of mercury during coal combustion and the mechanisms of mercury oxidation along the flue gas path. In this study, a temperature programmed decomposition technique was applied in order to acquire an understanding of the mode of decomposition of mercury species during coal combustion. A series of mercury model compounds were used for qualitative calibration. The temperature appearance range of the main mercury species can be arranged in increasing order as HgCl2 < HgS < HgO < HgSO4. Different fly ashes with certified and reference values for mercury concentration were used to evaluate the method. This study has shown that the thermal decomposition test is a newly developed efficient method for identifying and quantifying mercury species from coal combustion products. © 2009 Elsevier Ltd. All rights reserved.


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