• Using evidence from hair and other soft tissues to infer the need for and receipt of health-related care provision

      Brown, Emma L.; Wilson, Andrew S. (2019-06)
      The Bioarchaeology of Care approach developed by Tilley is usually applied to skeletalized human remains, given the usual constraints of preservation bias that are seen with archaeological assemblages. However, other tissues, such as hair are sometimes preserved and can provide a wealth of information that can supplement the skeletal data. Archaeological hair has been analysed for drug compounds for almost thirty years. This article integrates data from hair analyses for coca metabolites, stable light isotope analysis and aDNA to expand the potential of the Bioarchaeology of Care approach using the example of a spontaneously mummified adult female from northern Chile.
    • Using experimental archaeology to answer the unanswerable: a case study using Roman dyeing

      Hopkins, Heather J. (2008)
      This paper introduces a new approach to understanding the dying industry in Pompeii. This study began with the construction of a full-scale replica dyeing apparatus, copied from remains in Pompeii, to establish the operating parameters of an apparatus. A determination of cycle time, fuel type and requirement was made. The skeletal data of Herculaneum was matched to a modern population and an ergonomic assessment of each dyeing apparatus was made. The replica was amended to allow exploration of the eff ects of a change in design and ventilation. A computer simulation using Finite Element Analysis was undertaken. The design, cycle times and temperatures were taken from the excavated remains and experimental fi ndings. The FE Analysis allowed the determination of physical changes in materials during heating, the mode of failure of the apparatus and the time span within which this occurred. The approach and fi ndings of this study are both novel and new. The study took a theoretical problem through replicative experimental archaeology into Finite Element modelling. It allowed the problem to be understood and explored by those from diff ering disciplines. While this study answers specifi c questions about the size of the dyeing industry, it may be used to illustrate the application of a technique to answer `unanswerable¿ questions.
    • Using haloperidol as an anti-emetic in palliative care: informing practice through evidence from cancer treatment and post-operative contexts

      McLean, Samantha L.; Blenkinsopp, Alison; Bennett, M.I. (2013)
      Nausea and vomiting are common symptoms in palliative care. Haloperidol is often used as an antiemetic in this context, although direct evidence supporting this practice is limited. To evaluate the efficacy and clinical use of haloperidol as an antiemetic in nonpalliative care contexts to inform practice, the authors conducted a rapid review of (i) published evidence to supplement existing systematic reviews, and (ii) practical aspects affecting the use of haloperidol including formulations and doses that are commonly available internationally. In nausea and vomiting related to cancer treatment, haloperidol was superior to control in two small studies. In postoperative nausea and vomiting (PONV), two randomized controlledtrials found treatment with haloperidol comparable to ondansetron. In palliative care, an observational study found a complete response rate of 24% with haloperidol (one in four patients) which would be consistent with a number needed to treat (NNT) of 3 to 5 derived from PONV. There remains insufficient direct evidence to definitively support the use of haloperidol for the management of nausea and vomiting in palliative care. However, generalizing evidence from other clinical contexts may have some validity.
    • Using secondary data to analyse the impact of water management actions

      Westling, E.L.; Lerner, D.N.; Sharp, Liz (2009)
      This paper provides an analysis of the socio-economic impacts of river restoration schemes, and is novel in considering how a wide range of socio-economic variables can be used to understand impacts on the entire resident population within an area. A control-impacted approach was applied to explore differences in socio-economic characteristics of areas within which a restoration scheme had been carried out compared to areas without such a scheme. The results show that significant differences exist between control and impacted areas for a range of socio-economic variables. However, due to constraints in the methods and the data available, there are currently limitations in the extent to which socio-economic impacts of river restoration schemes can be fully explored. Additional datasets that become available in the future may increase the ability to detect associations between improvements in the water environment and socio-economic benefits. However, whilst the secondary data used in this paper are potentially powerful, they should be used alongside other techniques for assessing the impacts of decisions as part of future frameworks to deliver sustainable water management.
    • The utility of carpals for sex assessment: a preliminary study

      Sulzmann, C.E.; Buckberry, Jo; Pastor, R.F. (2008-03)
      Sex assessment is key when investigating human remains either from medicolegal contexts or archaeological sites. Sex is usually assessed by examination of the skull and pelvis, but this may not always be possible if skeletal material is fragmented or incomplete. The present study investigated the potential for using carpals to assess sex, utilizing one hundred individuals of known-sex from the Christ Church, Spitalfields Collection, curated at the Natural History Museum (London). A series of newly-defined measurements are applied to all eight carpals. Inter- and intra- observer error tests show that all measurements are satisfactorily reproduced by the first author and another observer. Paired t-tests to investigate side asymmetry of the carpals reveal that some, but not all, measurements are consistently larger on the right hand side than the left. Independent t-tests confirm that all carpals are sexually dimorphic. Univariate measurements produce accuracy levels that range from 64.6 to 84.7%. Stepwise discriminant function analysis, devised separately for left and right sides, provides reliable methods for assessing sex from single and multiple carpals, with an accuracy range of 71.7 to 88.6%. All functions derived are tested for accuracy on a sample of twenty additional individuals from the Christ Church, Spitalfields Collection.
    • Utility of Peripheral Visual Cues in Planning and Controlling Adaptive Gait

      Graci, Valentina; Elliott, David B.; Buckley, John G. (2010-01)
      The purpose of this article is to determine the relative importance to adaptive locomotion of peripheral visual cues provided by different parts of the visual field. Twelve subjects completed obstacle crossing trials while wearing goggles that provided four visual conditions: upper visual field occlusion, lower visual field occlusion (LO), circumferential peripheral visual field occlusion (CPO), and full vision. The obstacle was either positioned as a lone structure or within a doorframe. Given that subjects completed the task safely without cues from the lower or peripheral visual field, this suggests that subjects used exteroceptive information provided in a feed-forward manner under these conditions. LO and CPO led to increased foot placement distance from the obstacle and to increased toe clearance over the obstacle with a reduced crossing-walking velocity. The increased variability of dependent measures under LO and CPO suggests that exproprioceptive information from the peripheral visual field is generally used to provide online control of lower limbs. The presence of the doorframe facilitated lead-foot placement under LO by providing exproprioceptive cues in the upper visual field. However, under CPO conditions, the doorframe led to a further reduction in crossing velocity and increase in trail-foot horizontal distance and lead-toe clearance, which may have been because of concerns about hitting the doorframe with the head and/or upper body. Our findings suggest that exteroceptive cues are provided by the central visual field and are used in a feed-forward manner to plan the gait adaptations required to safely negotiate an obstacle, whereas exproprioceptive information is provided by the peripheral visual field and used online to “fine tune” adaptive gait. The loss of the upper and lower peripheral visual fields together had a greater effect on adaptive gait compared with the loss of the lower visual field alone, likely because of the absence of lamellar flow visual cues used to control egomotion.
    • Validation of a novel particle isolation procedure using particle doped tissue samples

      Patel, J.; Lal, S.; Wilshaw, Stacy-Paul; Hall, R.M.; Tipper, J.L. (2018-06)
      A novel particle isolation method for tissue samples was developed and tested using particle-doped peri-articular tissues from ovine cadavers. This enabled sensitivity of the isolation technique to be established by doping tissue samples of 0.25 g with very low particle volumes of 2.5 µm3 per sample. Image analysis was used to verify that the method caused no changes to particle size or morphologies.
    • Validation of a voltage-sensitive dye (di-4-ANEPPS)-based method for assessing drug-induced delayed repolarisation in Beagle dog left ventricular midmyocardial myocytes

      Hardy, Matthew E.; Pollard, C.E.; Small, B.G.; Bridgland-Taylor, M.; Woods, A.J.; Valentin, J.-P.; Abi-Gerges, N. (2009)
      Evaluation of drug candidates in in-vitro assays of action potential duration (APD) is one component of preclinical safety assessment. Current assays are limited by technically-demanding, time-consuming electrophysiological methods. This study aimed to assess whether a voltage-sensitive dye-based assay could be used instead. Methods Optical APs were recorded using di-4-ANEPPS in electrically field stimulated Beagle left ventricular midmyocardial myocytes (LVMMs). Pharmacological properties of di-4-ANEPPS on the main cardiac ion channels that shape the ventricular AP were investigated using IonWorks™ and conventional electrophysiology. Effects of 9 reference drugs (dofetilide, E4031, d-sotalol, ATXII, cisapride, terfenadine, alfuzosin, diltiazem and pinacidil) with known APD-modulating effects were assessed on optically measured APD at 1 Hz. Results Under optimum conditions, 0.1 μM di-4-ANEPPS could be used to monitor APs paced at 1 Hz during nine, 5 s exposures without altering APD. di-4-ANEPPS had no effect on either hIERG, hINa, hIKs and hIto currents in transfected CHO cells (up to 10 µM) or ICa,L current in LVMMs (at 16 µM). di-4-ANEPPS had no effect on APs recorded with microelectrodes at 1 or 0.5 Hz over a period of 30 min di-4-ANEPPS displayed the sensitivity to record changes in optically measured APD in response to altered pacing frequencies and sequential vehicle additions did not affect the optically measured APD. APD data obtained with 9 reference drugs were as expected except (i) d-sotalol-induced increases in duration were smaller than those caused by other IKr blockers and (ii) increases in APD were not detected using low concentrations of terfenadine. Discussion Early in drug discovery, the di-4-ANEPPS-based method can reliably be used to assess drug effects on APD as part of a cardiac risk assessment strategy.
    • Validation of high-performance liquid chromatography assay for quantification of formoterol in urine samples after inhalation using UV detection technique.

      Nadarassan, D.K.; Chrystyn, Henry; Clark, Brian J.; Assi, Khaled H. (2007)
      A novel high-performance liquid chromatography (HPLC) assay for the estimation of formoterol in urine samples was developed and validated. A solid phase extraction (SPE) using Oasis HLB was optimised to isolate formoterol from a urine matrix followed by HPLC with UV detection. This extraction procedure concentrated the final analyte forty times so that UV detection can be used to determine even a low concentration of formoterol in urine samples. The urinary assay was performed in accordance with FDA and ICH regulations for the validation of bioanalytical samples. The samples were injected onto a C18 Spherisorb® (250 mm x 4.6 mm x 5 ¿m) analytical column maintained at 30 °C. The mobile phase consisted of 5 mM of potassium dihydrogen orthophosphate buffer (adjusted to pH 3 with ortho phosphoric acid):acetonitrile (ACN) (70:30, v/v), and the formoterol peak was detected at wavelength 214 nm. The extraction recovery of formoterol from the urine sample was >95%. The calibration curve was linear (r2=0.99) over formoterol concentrations ranging from 1.5 to 25 ng/mL (n=6). The method had an accuracy of >92% and intra and inter-day precision CV% of <3.9% and <2.2%, respectively, at three different concentrations low, medium and high (10, 15, 20 ng/mL). The limit of quantification (LOQ) for formoterol was found to be 1.50 ng/mL. The accuracy and precision at the LOQ level were 95% and %CV <3.7% (n = 10), respectively. The method reported is simple, reliable, precise, and accurate and has the capacity to be used for determination of formoterol in urine samples.
    • Vascular smooth muscle as a target for novel therapeutics

      Porter, K.E.; Riches-Suman, Kirsten (2015-10)
      Cardiovascular disease is the principal cause of death in patients with type 2 diabetes (T2DM). Exposure of the vasculature to metabolic disturbances leaves a persistent imprint on vascular walls, and specifically on smooth muscle cells (SMC) that favours their dysfunction and potentially underlies macrovascular complications of T2DM. Current diabetes therapies and continued development of newer treatments has led to the ability to achieve more efficient glycaemic control. There is also some evidence to suggest that some of these treatments may exert favourable pleiotropic effects, some of which may be at the level of SMC. However, emerging interest in epigenetic markers as determinants of vascular disease, and a putative link with diabetes, opens the possibility for new avenues to develop robust and specific new therapies. These will likely need to target cell-specific epigenetic changes such as effectors of DNA histone modifications that promote or inhibit gene transcription, and/or microRNAs capable of regulating entire cellular pathways through target gene repression. The growing epidemic of T2DM worldwide, and its attendant cardiovascular mortality, dictates a need for novel therapies and personalised approaches to ameliorate vascular complications in this vulnerable population.
    • Vegetation Changes on Ilkley Moor 1964-1984

      Cotton, David E.; Hale, William H.G. (1989)
      In 1970 a set of maps was published which summarized the results of an extensive survey of the vegetation of Ilkley Moor. This paper presents new maps showing the distribution of selected vegetation communities based on a detailed survey undertaken in 1983-84, and examines the changes which have occurred in the period 1964--1984. Comparison of the maps reveals that Calluna vulgaris and Pteridium aquilinum have increased their occupancy of the moor, whilst there has been a marked reduction in the abundance of Empetrum nigrum and Eriophorum spp. These changes indicate that the degradation of the moor which was recorded during the 1960s was reversed, at least partially, between 1964 and 1984.
    • Vegetation Changes on Ilkley Moor between 1964 and 1984, and Possible Environmental Causes

      Hale, William H.G.; Cotton, David E. (1993)
      In recent years there has been concern about the decrease in the quality and quantity of Britain's heaths and moorlands. This concern has prompted attempts to monitor change in moorland vegetation, and programmes of action designed to halt the decline, both nationally and locally (Bunce, 1989; Hudson & Newborn, 1989a). In northern England the decline has been brought about partly by a reduction in the areal extent of the moors but mainly by changes in their species composition, with Calluna vulgaris (L.) Hull (heather) declining and grasses, Empetrum nigrum L. (crowberry) and other species increasing. These changes have been attributed to changed management practices, such as less effective burning regimes and increased sheep grazing (Bunce, 1989). However, there are few detailed quantitative studies of long-term vegetation change. This paper draws upon historical records to determine the nature and extent of change in the vegetation of Ilkley Moor over a twenty-year interval.
    • The vesicular acetylcholine transporter is present in melanocytes and keratinocytes in the human epidermis

      Schallreuter, Karin U.; Chavan, Bhavan; Elwary, Souna M.A. (2006)
      The human epidermis holds the full machinery for cholinergic signal transduction. However, the presence of the vesicular transporter (vesicular acetylcholine (ACh) transporter (VAChT)) for both choline and ACh has never been shown in this compartment. The results of this study confirm the presence of VAChT in cutaneous nerves and in both epidermal melanocytes and keratinocytes as well as in their nuclei using immunofluorescence labelling in situ and in vitro, Western blot analysis of cellular and nuclear extracts and reverse transcription-PCR. These results underline that ACh/choline transport in the non-neuronal epidermis is no different from the neuronal pathway. However, the function of VAChT in the nucleus remains to be shown.
    • Vibrational spectroscopic characterisation of salmeterol xinafoate polymorphs and a preliminary investigation of their transformation using simultaneous in situ portable Raman spectroscopy and differential scanning calorimetry

      Ali, H.R.H.; Edwards, Howell G.M.; Hargreaves, Michael D.; Munshi, Tasnim; Scowen, Ian J.; Telford, Richard (2008-07)
      Knowledge and control of the polymorphic phases of chemical compounds are important aspects of drug development in the pharmaceutical industry. Salmeterol xinafoate, a long acting β-adrenergic receptor agonist, exists in two polymorphic Forms, I and II. Raman and near infrared spectra were obtained of these polymorphs at selected wavelengths in the range of 488–1064 nm; significant differences in the Raman and near-infrared spectra were apparent and key spectral marker bands have been identified for the vibrational spectro-scopic characterisation of the individual polymorphs which were also characterised with X ray diffractometry. The solid-state transition of salmeterol xinafoate polymorphs was studied using simultaneous in situ portable Raman spectroscopy and differential scanning calorimetry isothermally between transitions. This method assisted in the unambiguous characterisation of the two polymorphic forms by providing a simultaneous probe of both the thermal and vibrational data. The study demonstrates the value of a rapid in situ analysis of a drug polymorph which can be of potential value for at-line in-process control.
    • Vibrational spectroscopic study of budesonide

      Edwards, Howell G.M.; Ali, H.R.H.; Kendrick, John; Munshi, Tasnim; Scowen, Ian J. (2007)
      The Raman spectrum of budesonide is reported for the first time, and molecular assignments are proposed on the basis of ab initio BLYP DFT calculations with a 6-31 G* basis set and vibrational wavenumbers predicted on a quasi-harmonic approximation. Comparison with previously published infrared data has explained several spectral features, and the relative band intensities in the CO and CC stretching regions are interpreted. The results from this study provide data that can be used for the preparative process monitoring of budesonide, an important steroidal pharmaceutical in various dosage forms, and its interaction with excipients and other components.
    • Vibrational spectroscopic study of fluticasone propionate

      Ali, H.R.H.; Edwards, Howell G.M.; Kendrick, John; Scowen, Ian J. (Elsevier, 2009)
      Luticasone propionate is a synthetic glucocorticoid with potent anti-inflammatory activity that has been used effectively in the treatment of chronic asthma. The present work reports a vibrational spectroscopic study of fluticasone propionate and gives proposed molecular assignments on the basis of ab initio calculations using BLYP density functional theory with a 6-31G* basis set and vibrational frequencies predicted within the quasi-harmonic approximation. Several spectral features and band intensities are explained. This study generated a library of information that can be employed to aid the process monitoring of fluticasone propionate.
    • Vibrational spectroscopic study of salbutamol hemisulphate

      Ali, H.R.H.; Edwards, Howell G.M.; Kendrick, John; Scowen, Ian J. (Elsevier, 01/01/2009)
      Salbutamol hemisulphate is a relatively selective ß2-adrenergic agonist and is used as a bronchodilator. In this work, we present a detailed vibrational spectroscopic investigation of salbutamol hemisulphate using mid-infrared and near-infrared Fourier-transform (NIR-FT) Raman spectroscopies. These data are supported by quantum chemical calculations, which allow us to characterise the vibrational spectra of this compound reasonably. As such, this study could be viable for examining the way in which this drug interacts with its target molecules.
    • Vibrational spectroscopic study of terbutaline hemisulphate

      Ali, H.R.H.; Edwards, Howell G.M.; Kendrick, John; Scowen, Ian J. (01/05/2009)
      The Raman spectrum of terbutaline hemisulphate is reported for the first time, and molecular assignments are proposed on the basis of ab initio BLYP DFT calculations with a 6-31G* basis set and vibrational frequencies predicted within the quasi-harmonic approximation; these predictions compare favourably with the observed vibrational spectra. Comparison with previously published infrared data explains several spectral features. The results from this study provide data that can be used for the preparative process monitoring of terbutaline hemisulphate, an important ß2 agonist drug in various dosage forms and its interaction with excipients and other components.