• When is visual information used to control locomotion when descending a kerb?

      Buckley, John G.; Timmis, Matthew A.; Scally, Andy J.; Elliott, David B. (2011)
      Background: Descending kerbs during locomotion involves the regulation of appropriate foot placement before the kerb-edge and foot clearance over it. It also involves the modulation of gait output to ensure the body-mass is safely and smoothly lowered to the new level. Previous research has shown that vision is used in such adaptive gait tasks for feedforward planning, with vision from the lower visual field (lvf) used for online updating. The present study determined when lvf information is used to control/update locomotion when stepping from a kerb. Methodology/Principal Findings: 12 young adults stepped down a kerb during ongoing gait. Force sensitive resistors (attached to participants' feet) interfaced with an high-speed PDLC 'smart glass' sheet, allowed the lvf to be unpredictably occluded at either heel-contact of the penultimate or final step before the kerb-edge up to contact with the lower level. Analysis focussed on determining changes in foot placement distance before the kerb-edge, clearance over it, and in kinematic measures of the step down. Lvf occlusion from the instant of final step contact had no significant effect on any dependant variable (p>0.09). Occlusion of the lvf from the instant of penultimate step contact had a significant effect on foot clearance and on several kinematic measures, with findings consistent with participants becoming uncertain regarding relative horizontal location of the kerb-edge. Conclusion/Significance: These findings suggest concurrent feedback of the lower limb, kerb-edge, and/or floor area immediately in front/below the kerb is not used when stepping from a kerb during ongoing gait. Instead heel-clearance and pre-landing-kinematic parameters are determined/planned using lvf information acquired in the penultimate step during the approach to the kerb-edge, with information related to foot placement before the kerb-edge being the most salient.
    • The White Stuff: Milking in the Outer Scottish Isles

      Bond, Julie M.; Mulville, J.; Craig, O.E. (2005)
    • Who were these people? A sideways view and a non-answer of political proportions

      Gibson, Alex M. (2016-05)
      This chapter looks at the variability of burial practices inthe Neolithic and Bronze Age and questions accepted orthodoxies.
    • Whole genome sequence of Mycobacterium kansasii isolates of the genotype 1 from Brazilian patients with pulmonary disease demonstrates considerable heterogeneity

      Machado, E.; Vasconcellos, S.E.G.; Cerdeira, C.; Gomes, L.L.; Junqueira, R.; de Carvalho, L.D.; Ramos, J.P.; Redner, P.; Campos, C.E.D.; de Souza Caldas, P.C.; et al. (2018-06)
      Mycobacterium kansasii is an opportunistic pathogen and one of the most commonly encountered species in individuals with lung disease. We here report the complete genome sequence of 12 clinical isolates of M. kansasii from patients with pulmonary disease in Brazil.
    • Whole genome sequencing of Mycobacterium tuberculosis: current standards and open issues

      Meehan, Conor J.; Goig, G.A.; Kohl, T.A.; Verboven, L.; Dippenaar, A.; Ezewudo, M.; Farhat, M.R.; Guthrie, J.L.; Laukens, K.; Miotto, P.; et al. (2019-09)
      Whole genome sequencing (WGS) of Mycobacterium tuberculosis has rapidly progressed from a research tool to a clinical application for the diagnosis and management of tuberculosis and in public health surveillance. This development has been facilitated by drastic drops in cost, advances in technology and concerted efforts to translate sequencing data into actionable information. There is, however, a risk that, in the absence of a consensus and international standards, the widespread use of WGS technology may result in data and processes that lack harmonization, comparability and validation. In this Review, we outline the current landscape of WGS pipelines and applications, and set out best practices for M. tuberculosis WGS, including standards for bioinformatics pipelines, curated repositories of resistance-causing variants, phylogenetic analyses, quality control and standardized reporting.
    • Whole genome sequencing reveals mycobacterial microevolution among concurrent isolates from sputum and blood in HIV infected TB patients

      Ssengooba, W.; de Jong, B.C.; Joloba, M.L.; Cobelens, F.G.; Meehan, Conor J. (2016-08-05)
      Background In the context of advanced immunosuppression, M. tuberculosis is known to cause detectable mycobacteremia. However, little is known about the intra-patient mycobacterial microevolution and the direction of seeding between the sputum and blood compartments. Methods From a diagnostic study of HIV-infected TB patients, 51 pairs of concurrent blood and sputum M. tuberculosis isolates from the same patient were available. In a previous analysis, we identified a subset with genotypic concordance, based on spoligotyping and 24 locus MIRU-VNTR. These paired isolates with identical genotypes were analyzed by whole genome sequencing and phylogenetic analysis. Results Of the 25 concordant pairs (49 % of the 51 paired isolates), 15 (60 %) remained viable for extraction of high quality DNA for whole genome sequencing. Two patient pairs were excluded due to poor quality sequence reads. The median CD4 cell count was 32 (IQR; 16–101)/mm3 and ten (77 %) patients were on ART. No drug resistance mutations were identified in any of the sequences analyzed. Three (23.1 %) of 13 patients had SNPs separating paired isolates from blood and sputum compartments, indicating evidence of microevolution. Using a phylogenetic approach to identify the ancestral compartment, in two (15 %) patients the blood isolate was ancestral to the sputum isolate, in one (8 %) it was the opposite, and ten (77 %) of the pairs were identical. Conclusions Among HIV-infected patients with poor cellular immunity, infection with multiple strains of M. tuberculosis was found in half of the patients. In those patients with identical strains, whole genome sequencing indicated that M. tuberculosis intra-patient microevolution does occur in a few patients, yet did not reveal a consistent direction of spread between sputum and blood. This suggests that these compartments are highly connected and potentially seed each other repeatedly.
    • Whole genome sequencing to complement tuberculosis drug resistance surveys in Uganda

      Ssengooba, W.; Meehan, Conor J.; Lukoye, D.; Kasule, G.W.; Musisi, K.; Joloba, M.L.; Cobelens, F.G.; de Jong, B.C. (2016-06)
      Understanding the circulating Mycobacterium tuberculosis resistance mutations is vital for better TB control strategies, especially to inform a new MDR-TB treatment programme. We complemented the phenotypic drug susceptibility testing (DST) based drug resistance surveys (DRSs) conducted in Uganda between 2008 and 2011 with Whole Genome Sequencing (WGS) of 90 Mycobacterium tuberculosis isolates phenotypically resistant to rifampicin and/or isoniazid to better understand the extent of drug resistance. A total of 31 (34.4 %) patients had MDR-TB, 5 (5.6 %) mono-rifampicin resistance and 54 (60.0 %) mono-isoniazid resistance by phenotypic DST. Pyrazinamide resistance mutations were identified in 32.3% of the MDR-TB patients. Resistance to injectable agents was detected in 4/90 (4.4%), and none to fluoroquinolones or novel drugs. Compensatory mutations in rpoC were identified in two patients. The sensitivity and specificity of drug resistance mutations compared to phenotypic DST were for rpoB 88.6% and 98.1%, katG 60.0% and 100%, fabG1 16.5% and 100%, katG and/or fabG1 71.8% and 100%, embCAB 63.0% and 82.5%, rrs 11.4% and 100%, rpsL 20.5% and 95.7% and rrs and/or rpsL 31.8% and 95.7%. Phylogenetic analysis showed dispersed MDR-TB isolate, with only one cluster of three Beijing family from South West Uganda. Among tuberculosis patients in Uganda, resistance beyond first-line drugs as well as compensatory mutations remain low, and MDR-TB isolates did not arise from a dominant clone. Our findings show the potential use of sequencing for complementing DRSs or surveillance in this setting, with good specificity compared to phenotypic DST. The reported high confidence mutations can be included in molecular assays, and population-based studies can track transmission of MDR-TB including the Beijing family strains in the South West of the country.
    • Whole plant extracts versus single compounds for the treatment of malaria: synergy and positive interactions.

      Rasoanaivo, P.; Wright, Colin W.; Willcox, M.L.; Gilbert, B. (2011)
      Background In traditional medicine whole plants or mixtures of plants are used rather than isolated compounds. There is evidence that crude plant extracts often have greater in vitro or/and in vivo antiplasmodial activity than isolated constituents at an equivalent dose. The aim of this paper is to review positive interactions between components of whole plant extracts, which may explain this. Methods Narrative review. Results There is evidence for several different types of positive interactions between different components of medicinal plants used in the treatment of malaria. Pharmacodynamic synergy has been demonstrated between the Cinchona alkaloids and between various plant extracts traditionally combined. Pharmacokinetic interactions occur, for example between constituents of Artemisia annua tea so that its artemisinin is more rapidly absorbed than the pure drug. Some plant extracts may have an immunomodulatory effect as well as a direct antiplasmodial effect. Several extracts contain multidrug resistance inhibitors, although none of these has been tested clinically in malaria. Some plant constituents are added mainly to attenuate the side-effects of others, for example ginger to prevent nausea. Conclusions More clinical research is needed on all types of interaction between plant constituents. This could include clinical trials of combinations of pure compounds (such as artemisinin + curcumin + piperine) and of combinations of herbal remedies (such as Artemisia annua leaves + Curcuma longa root + Piper nigum seeds). The former may enhance the activity of existing pharmaceutical preparations, and the latter may improve the effectiveness of existing herbal remedies for use in remote areas where modern drugs are unavailable.
    • The whole tooth and nothing but the tooth: or why temporal resolution of bone collagen may be unreliable

      Beaumont, Julia (Wiley, 2020-06)
      The carbon (δ13C) and nitrogen (δ15N) isotope ratios of human bone collagen have been used extensively over the last 40 years to investigate the diet of past populations. It has become apparent that bone collagen can give an unreliable temporal dietary signature especially in juveniles. With higher temporal resolution sampling of collagen from tooth dentine, it is possible to identify short‐term changes in diet previously invisible in bone. This paper discusses the inherent problems of using bone collagen for dietary studies and suggests better sample choices which can make our interpretations more robust, using breastfeeding and weaning as an example.
    • Whole-cell Currents Recording from Ion Channels in Human Lymphocytes Treated with Anti-inflammatory Drugs in Nanoparticles Forms

      Shang, Lijun; Najafzadeh, Mojgan; Anderson, Diana (2014)
      channels that are critical for their development and function. Many ion channels contribute to T cell-mediated autoimmune and/or inflammatory responses, so they are attractive targets for pharmacological immune modulations. In this study, we conduct patch clamp experiments to exam the whole cell currents from lymphocytes after nanoparticles exposure with the aim to test if nanoparticles exposure brings any electrophysiological changes for lymphocytes, and to compare the electrophysiological responses of lymphocytes to drugs in nanoparticles forms. Our result suggests a potential inhibition of effects of IBU N on lymphocytes. Such cytotoxicity of nanoparticles in Lymphocytes may be mainly associated with the early membrane damage. These results are also mirrored by the DNA damages occurred on lymphocytes after exposure of nanoparticles. Further detailed investigation is needed to explain the changes of Lymphocytes in response to NPs in real time and dose differences. This would provide useful information in the evaluation of toxicology of nanoparticles and in understanding the underlying mechanism of their effects on ion channels in health and diseases.
    • Whole-genome analysis of quorum-sensing Burkholderia sp. strain A9

      Chan, K.; Chen, J.W.; Tee, K.K.; Chang, Chien-Yi; Yin, W.; Chan, X. (2015-03)
      Burkholderia spp. rely on N-acyl homoserine lactone as quorum-sensing signal molecules which coordinate their phenotype at the population level. In this work, we present the whole genome of Burkholderia sp. strain A9, which enables the discovery of its N-acyl homoserine lactone synthase gene.
    • Whole-genome sequence and fosfomycin resistance of Bacillus sp. strain G3(2015) isolated from seawater off the coast of Malaysia

      Chan, X.; Chen, J.; Adrian, T.; Hong, K.; Chang, Chien-Yi; Yin, W.; Chan, K. (2017-03)
      Bacillus sp. is a Gram-positive bacterium that is commonly found in seawater. In this study, the genome of marine Bacillus sp. strain G3(2015) was sequenced using MiSeq. The fosfomycin resistant gene fosB was identified upon bacterial genome annotation.
    • Whole-genome sequencing analysis of quorumsensing Aeromonas hydrophila strain M023 from freshwater

      Tan, W.; Yin, W.; Chang, Chien-Yi; Chan, K. (2015-02)
      Aeromonas hydrophila is a well-known waterborne pathogen that recently was found to infect humans. Here, we report the draft genome of a freshwater isolate from a Malaysian waterfall, A. hydrophila strain M023, which portrays N-acylhomoserine lactone-dependent quorum sensing.
    • Whole-genome shotgun sequencing of mitochondria from ancient hair shafts

      Gilbert, M.T.P.; Tomsho, L.P.; Rendulic, S.; Packard, M.; Drautz, D.I.; Sher, A.; Tikhonov, A.; Dalen, L.; Kuznetsova, T.; Kosintsev, P.; et al. (2007-09-28)
      Although the application of sequencing-by-synthesis techniques to DNA extracted from bones has revolutionized the study of ancient DNA, it has been plagued by large fractions of contaminating environmental DNA. The genetic analyses of hair shafts could be a solution: We present 10 previously unexamined Siberian mammoth (Mammuthus primigenius) mitochondrial genomes, sequenced with up to 48-fold coverage. The observed levels of damage-derived sequencing errors were lower than those observed in previously published frozen bone samples, even though one of the specimens was >50,000 14C years old and another had been stored for 200 years at room temperature. The method therefore sets the stage for molecular-genetic analysis of museum collections.
    • Why do people drive when they can’t see clearly?

      Fylan, F.; Hughes, A.; Wood, J.M.; Elliott, David B. (2018-07)
      Purpose Refractive blur is associated with decreased hazard perception and impairments in driving performance, but little is known about why people who have spectacles to correct their distance vision drive with uncorrected vision. Methods We conducted six focus groups. Participants were 30 drivers (mean age 45) who reported having driven uncorrected at least twice in the past six months despite having spectacles to correct their distance vision. Focus groups were audio recorded, transcribed verbatim and analysed thematically. Results We identified three themes. 1. Responsibility: participants did not feel obliged to drive with optimal vision and believed that others have a responsibility to ensure drivers maintain clear vision. 2. Safe Enough: participants felt safe to drive uncorrected, did not believe they need to wear spectacles to see sufficiently clearly and that they would know if their uncorrected eyesight fails to meet minimum standards. 3. Situations: participants discussed how they would drive uncorrected for short and familiar journeys, when they feel alert, in daylight and in good weather. Conclusions Beliefs about the importance of driving with clear vision compete with the benefits of not wearing spectacles. Eyecare professionals should provide more direct advice to patients regarding the need to wear their visual correction for driving.
    • Why is the General Ophthalmic Services (GOS) Contract that underpins primary eye care in the UK contrary to the public health interest?

      Shickle, D.; Davey, Christopher J.; Slade, S.V. (2015)
      The model for delivery of primary eye care in Europe varies from country to country with differing reliance on ophthalmologists, optometrists and dispensing opticians. Comparative analysis of models has tended to focus on interprofessional working arrangements, training and regulatory issues, rather than on whether a particular model is effective for delivering public health goals for that country. National Health Service (NHS) primary eye care services in the UK are predominantly provided under a General Ophthalmic Services (GOS) Contract between the NHS and practice owners (Contractors). Over two-thirds of sight tests conducted in England, Wales and Northern Ireland and all in Scotland are performed under a GOS Contract, however many people entitled to a GOS sight test do not take up their entitlement. The fee paid for sight tests conducted under a GOS Contract in England, Wales and Northern Ireland does not cover the full cost of conducting the examination. The shortfall must be made up through profits of sale of optical appliances but this business model can be a deterrent to establishing practices within socioeconomically deprived communities, and can also be a barrier to uptake of sight tests, even though many people are entitled to a NHS optical voucher towards the cost of spectacles or contact lenses. This paper critiques the GOS Contracts within the UK. We argue that aspects of the way the GOS Contract is implemented are contrary to the public health interest and that different approaches are needed to address eye health inequalities and to reduce preventable sight loss.
    • Will-o'-the-Wisp: an ancient mystery with extremophile origins?

      Edwards, Howell G.M. (2014)
      This paper draws a comparison between the 700-year-old historically reported will-o'-the-wisp phenomenon and the more recent discovery of extremophilic colonization of hostile environments; both have been observed as present in isolated, stressed environmental regions and originating from biological phenomena. However, whereas extremophilic activity can be understood in terms of a survival strategy based upon the synthesis of specific suites of protective biochemicals which are designed to control biogeologically the stressed habitats and to provide protection against the extreme environments, the analytical techniques that have proved so successful for the illumination of these survival strategies of extremophiles and which are now being miniaturized for in-field studies and for extraterrestrial exploration have not been applied to a clarification or evaluation of the phenomenon of will-o'-the-wisp. The reason is simply that the will-o'-the-wispsightings have now disappeared completely. Tantalizingly, all of the most reasonable physico-chemical and biological explanations for the will-o'-the-wisp phenomenon proved to be unsatisfactory in some respect and it is clear that, just as in the case of extremophilic colonization, will-o'-the-wisp would benefit from a modern rigorous analytical study which would produce the data from which the potentially novel biological behaviour could be characterized and which would help a better understanding to be made of our natural world.
    • Wise Up to Cancer Bradford: Improving cancer prevention and earlier diagnosis for South Asian women in Bradford

      Almas, N.; Haith-Cooper, Melanie; Nejadhamzeegilani, Z.; Payne, D.; Rattray, Marcus (University of Bradford, 2019-09)