• Back to the beginning: identifying lesions of diffuse idiopathic skeletal hyperostosis before vertebral ankylosis

      Castells Navarro, Laura; Buckberry, Jo (2020-03)
      Objective: To better understand the pathogenesis of DISH, identifying early or pre-DISH lesions in the spine and investigating the relationship between spinal and extra-spinal manifestations of DISH. Material: 44 skeletonized individuals with DISH from the WM Bass Donated Skeletal Collection. Methods: For each vertebra, location, extension, point of origin and appearance of vertebral outgrowths were recorded. The size of the enthesophytes at the olecranon process, patella and calcaneal tuberosity was measured with digital callipers. Results: At either end of the DISH-ankylosed segment, isolated vertical outgrowths arising from the central third of the anterior aspect of the vertebral body can usually be observed. These bone outgrowths show a well-organized external cortical layer, an internal structure of trabecular bone and usually are unaccompanied by or show minimal associated endplate degeneration. Analysis of the relationship between spinal and extra-spinal manifestations (ESM) suggests great inter-individual variability. No correlation between any ESM and the stage of spinal DISH was found. Conclusions: Small isolated outgrowths represent the earliest stages of the spinal manifestations of DISH. The use of ESM as an indicator of DISH should be undertaken with great caution until the relationship between these two features is understood. Significance: Improved accuracy of paleopathological diagnostic criteria of DISH. Limitations: Small sample comprised of only individuals with DISH. Future research: micro-CT analysis to investigate the internal structure of the spinal lesions. Analysis of extra-spinal enthesophytes in individuals with and without DISH to understand their pathogenesis and association with the spinal lesions in individuals with DISH.
    • Bacterial attachment to polymeric materials correlates with molecular flexibility and hydrophilicity

      Sanni, O.; Chang, Chien-Yi; Anderson, D.G.; Langer, R.; Davies, M.C.; Williams, P.M.; Williams, P.; Alexander, M.R.; Hook, A.L. (2015-04-02)
      A new class of material resistant to bacterial attachment has been discovered that is formed from polyacrylates with hydrocarbon pendant groups. In this study, the relationship between the nature of the hydrocarbon moiety and resistance to bacteria is explored, comparing cyclic, aromatic, and linear chemical groups. A correlation is shown between bacterial attachment and a parameter derived from the partition coefficient and the number of rotatable bonds of the materials' pendant groups. This correlation is applicable to 86% of the hydrocarbon pendant moieties surveyed, quantitatively supporting the previous qualitative observation that bacteria are repelled from poly(meth)acrylates containing a hydrophilic ester group when the pendant group is both rigid and hydrophobic. This insight will help inform and predict the further development of polymers resistant to bacterial attachment.
    • Bacterial diversity in Buruli ulcer skin lesions: Challenges in the clinical microbiome analysis of a skin disease

      Van Leuvenhaege, C.; Vandelannoote, K.; Affolabi, D.; Portaels, F.; Sopoh, G.; de Jong, B.C.; Eddyani, M.; Meehan, Conor J. (2017-07-27)
      Background Buruli ulcer (BU) is an infectious disease caused by Mycobacterium ulcerans and considered the third most prevalent mycobacterial disease in humans. Secondary bacterial infections in open BU lesions are the main cause of pain, delayed healing and systemic illness, resulting in prolonged hospital stay. Thus, understanding the diversity of bacteria, termed the microbiome, in these open lesions is important for proper treatment. However, adequately studying the human microbiome in a clinical setting can prove difficult when investigating a neglected tropical skin disease due to its rarity and the setting. Methodology/Principal findings Using 16S rRNA sequencing, we determined the microbial composition of 5 BU lesions, 3 non-BU lesions and 3 healthy skin samples. Although no significant differences in diversity were found between BU and non-BU lesions, the former were characterized by an increase of Bacteroidetes compared to the non-BU wounds and the BU lesions also contained significantly more obligate anaerobes. With this molecular-based study, we were also able to detect bacteria that were missed by culture-based methods in previous BU studies. Conclusions/Significance Our study suggests that BU may lead to changes in the skin bacterial community within the lesions. However, in order to determine if such changes hold true across all BU cases and are either a cause or consequence of a specific wound environment, further microbiome studies are necessary. Such skin microbiome analysis requires large sample sizes and lesions from the same body site in many patients, both of which can be difficult for a rare disease. Our study proposes a pipeline for such studies and highlights several drawbacks that must be considered if microbiome analysis is to be utilized for neglected tropical diseases.
    • Barriers and facilitators to the uptake of new medicines into clinical practice: a systematic review

      Medlinskiene, Kristina; Tomlinson, Justine; Marques, Iuri; Richardson, S.; Stirling, K.; Petty, Duncan R. (2021-11)
      Implementation and uptake of novel and cost-effective medicines can improve patient health outcomes and healthcare efficiency. However, the uptake of new medicines into practice faces a wide range of obstacles. Earlier reviews provided insights into determinants for new medicine uptake (such as medicine, prescriber, patient, organization, and external environment factors). However, the methodological approaches used had limitations (e.g., single author, narrative review, narrow search, no quality assessment of reviewed evidence). This systematic review aims to identify barriers and facilitators affecting the uptake of new medicines into clinical practice and identify areas for future research. A systematic search of literature was undertaken within seven databases: Medline, EMBASE, Web of Science, CINAHL, Cochrane Library, SCOPUS, and PsychINFO. Included in the review were qualitative, quantitative, and mixed-methods studies focused on adult participants (18 years and older) requiring or taking new medicine(s) for any condition, in the context of healthcare organizations and which identified factors affecting the uptake of new medicines. The methodological quality was assessed using QATSDD tool. A narrative synthesis of reported factors was conducted using framework analysis and a conceptual framework was utilised to group them. A total of 66 studies were included. Most studies (n = 62) were quantitative and used secondary data (n = 46) from various databases, e.g., insurance databases. The identified factors had a varied impact on the uptake of the different studied new medicines. Differently from earlier reviews, patient factors (patient education, engagement with treatment, therapy preferences), cost of new medicine, reimbursement and formulary conditions, and guidelines were suggested to influence the uptake. Also, the review highlighted that health economics, wider organizational factors, and underlying behaviours of adopters were not or under explored. This systematic review has identified a broad range of factors affecting the uptake of new medicines within healthcare organizations, which were grouped into patient, prescriber, medicine, organizational, and external environment factors. This systematic review also identifies additional factors affecting new medicine use not reported in earlier reviews, which included patient influence and education level, cost of new medicines, formulary and reimbursement restrictions, and guidelines. PROSPERO database (CRD42018108536).
    • Basal fatty acid oxidation increases after recurrent low glucose in human primary astrocytes

      Weightman Potter, P.G.; Vlachaki Walker, J.M.; Robb, J.L.; Chilton, J.K.; Williamson, Ritchie; Randall, A.D.; Ellacott, K.L.J.; Beall, C. (2019-01)
      Aims/hypothesis Hypoglycaemia is a major barrier to good glucose control in type 1 diabetes. Frequent hypoglycaemic episodes impair awareness of subsequent hypoglycaemic bouts. Neural changes underpinning awareness of hypoglycaemia are poorly defined and molecular mechanisms by which glial cells contribute to hypoglycaemia sensing and glucose counterregulation require further investigation. The aim of the current study was to examine whether, and by what mechanism, human primary astrocyte (HPA) function was altered by acute and recurrent low glucose (RLG). Methods To test whether glia, specifically astrocytes, could detect changes in glucose, we utilised HPA and U373 astrocytoma cells and exposed them to RLG in vitro. This allowed measurement, with high specificity and sensitivity, of RLG-associated changes in cellular metabolism. We examined changes in protein phosphorylation/expression using western blotting. Metabolic function was assessed using a Seahorse extracellular flux analyser. Immunofluorescent imaging was used to examine cell morphology and enzymatic assays were used to measure lactate release, glycogen content, intracellular ATP and nucleotide ratios. Results AMP-activated protein kinase (AMPK) was activated over a pathophysiologically relevant glucose concentration range. RLG produced an increased dependency on fatty acid oxidation for basal mitochondrial metabolism and exhibited hallmarks of mitochondrial stress, including increased proton leak and reduced coupling efficiency. Relative to glucose availability, lactate release increased during low glucose but this was not modified by RLG. Basal glucose uptake was not modified by RLG and glycogen levels were similar in control and RLG-treated cells. Mitochondrial adaptations to RLG were partially recovered by maintaining euglycaemic levels of glucose following RLG exposure. Conclusions/interpretation Taken together, these data indicate that HPA mitochondria are altered following RLG, with a metabolic switch towards increased fatty acid oxidation, suggesting glial adaptations to RLG involve altered mitochondrial metabolism that could contribute to defective glucose counterregulation to hypoglycaemia in diabetes.
    • Basic colour names for 2D samples: Effects of presentation media and illuminants.

      Hedrich, Monika; Bloj, Marina (2010)
      We have previously shown (Bloj et al., 2008; Abstracts Materials & Sensations 2008) that under particular conditions colour memory is independent of presentation media, and of the illuminants under which colours are viewed. In the present study we investigate whether colour naming is also unaffected by these two factors. Forty-eight colour samples from the Natural Colour System (NCS) collection were presented as real paper samples or as accurate computer simulations displayed on a calibrated monitor. The colour swatches could be presented under a daylight illuminant ¿ two intensities, 85 ( D1 ) or 60 cd m)2 ( D2 ) ¿ or a purple illuminant, 45 cd m)2 ( Lily ). The colour samples were shown in arrays of 16 (4 · 4 layout) and the observer s task was to assign one of the eleven basic colour terms to each of the samples. Six observers repeated this colour naming task five times for each presentation medium and illuminant. On average, in 73% of the cases the same colour term was assigned to surface and display colours. This level of agreement was highest for colour samples under daylight (D1-82%, D2-73%) and poor for Lily (65%). Although colour memory is unaffected by the nature of the colour stimulus, here we show that there are limitations to cross-media agreement in colour naming.
    • Basic evidence for epidermal H2O2/ONOO--mediated oxidation/nitration in segmental vitiligo is supported by repigmentation of skin and eyelashes after reduction of epidermal H2O2 with topical NB-UVB-activated pseudocatalase PC-KUS

      Schallreuter, Karin U.; Salem, Mohamed M.A.; Holtz, Sarah; Panske, Angela (2013-08)
      Nonsegmental vitiligo (NSV) is characterized by loss of inherited skin color. The cause of the disease is still unknown despite accumulating in vivo and in vitro evidence of massive epidermal oxidative stress via H2O2 and peroxynitrite (ONOO−) in affected individuals. The most favored hypothesis is based on autoimmune mechanisms. Strictly segmental vitiligo (SSV) with dermatomal distribution is a rare entity, often associated with stable outcome. Recently, it was documented that this form can be associated with NSV (mixed vitiligo). We here asked the question whether ROS and possibly ONOO− could be players in the pathogenesis of SSV. Our in situ results demonstrate for the first time epidermal biopterin accumulation together with significantly decreased epidermal catalase, thioredoxin/thioreoxin reductase, and MSRA/MSRB expression. Moreover, we show epidermal ONOO− accumulation. In vivo FT-Raman spectroscopy reveals the presence of H2O2, methionine sulfoxide, and tryptophan metabolites; i.e., N-formylkynurenine and kynurenine, implying Fenton chemistry in the cascade (n=10). Validation of the basic data stems from successful repigmentation of skin and eyelashes in affected individuals, regardless of SSV or segmental vitiligo in association with NSV after reduction of epidermal H2O2 (n=5). Taken together, our contribution strongly supports H2O2/ONOO-mediated stress in the pathogenesis of SSV. Our findings offer new treatment intervention for lost skin and hair color.—Schallreuter, K. U., Salem, M. A. E. L., Holtz, S., Panske, A. Basic evidence for epidermal H2O2/ONOO−-mediated oxidation/nitration in segmental vitiligo is supported by repigmentation of skin and eyelashes after reduction of epidermal H2O2 with topical NB-UVB-activated pseudocatalase PC-KUS.
    • Basics in paleodemography: A comparison of age indicators applied to the early medieval skeletal sample of Lauchheim.

      Wittwer-Backofen, U.; Buckberry, Jo; Czarnetzki, A.; Doppler, S.; Grupe, G.; Hotz, G.; Kemkes, A.; Spencer Larsen, C.; Prince, D.; Wahl, J.; et al. (2007)
      Recent advances in the methods of skeletal age estimation have rekindled interest in their applicability to paleodemography. The current study contributes to the discussion by applying several long established as well as recently developed or refined aging methods to a subsample of 121 adult skeletons from the early medieval cemetery of Lauchheim. The skeletal remains were analyzed by 13 independent observers using a variety of aging techniques (complex method and other multimethod approaches, Transition Analysis, cranial suture closure, auricular surface method, osteon density method, tooth root translucency measurement, and tooth cementum annulation counting). The age ranges and mean age estimations were compared and results indicate that all methods showed smaller age ranges for the younger individuals, but broader age ranges for the older age groups.
    • Basilar portion porosity: A pathological lesion possibly associated with infantile scurvy

      Moore, Joanna; Koon, Hannah E.C. (2017-09)
      Recent analysis of the juvenile (≤12 years) human remains from a 19th century site in Wolverhampton, England revealed a relatively high level of nutritional deficiency diseases within the population. Indeed, 41.7% of the 48 juvenile skeletons analysed exhibited a combination of porous and proliferative bone lesions consistent with the pathological alterations associated with nutritional stress. This paper describes a pathological lesion on the inferior surface of the basilar portion of the occipital bone, not previously reported in association with infantile scurvy, but which was exhibited by 90% (N=9) of the 10 scorbutic individuals identified during this study.
    • Basis of intentions as a moderator of the intention health behavior relationship

      Conner, M.; McEachan, Rosemary; Lawton, R.; Gardner, Peter H. (2016-03)
      Objective: Previous research has shown that the degree to which individuals base their intentions on particular underlying cognitions (i.e., motives) significantly moderates the intention-behavior relationship. Studies have individually examined the moderating effect of intentions based on overall attitude, affective attitudes, injunctive norms, and moral norms. The present research used a within-persons approach to simultaneously test the moderating effects of intentions based on instrumental attitude, affective attitude, anticipated affective reactions, injunctive norms, descriptive norms, and moral norms on the intention-behavior relationship and the impact of controlling for intention stability, self-efficacy and past behavior. Main Outcome Measures: Self-reported performance of 20 health behaviors. Design: Adults (N = 366) completed questionnaires assessing instrumental attitude, affective attitude, anticipated affective reactions, injunctive norms, descriptive norms, moral norms, self-efficacy and past behavior at baseline; intentions at baseline and one month follow-up; and behavior at two month follow-up for 20 health behaviors. Results: When tested simultaneously using multi-level modelling the only significant moderator of the intention-behavior relationship was the extent to which intentions were based on anticipated affective reactions (intentions more strongly based on anticipated affective reactions were significantly stronger predictors of behavior). This effect remained when we also controlled for intention stability (which also moderated the intention-behavior relationship), self-efficacy and past behavior. Conclusions: Intentions based on anticipated affective reactions may be particularly important predictors of health behaviors. Studies manipulating such intentions to test their effects on behavior change are required.
    • The battle of the bulge: re-evaluating hair follicle stem cells in wound repair

      Garcin, C.L.; Ansell, David M. (2017-02)
      The hair follicle has an established role in wound re-epithelialisation, a phenomenon that has been appreciated since at least the first half of the last century. The bulge niche, one location of hair follicle epithelial stem cells has been of particular interest to researchers over recent years, with numerous studies showing its ability to directly contribute to epidermal repair. However, recent work has highlighted other progenitor regions of the hair follicle that appear to act as stem cells during epidermal repair. In addition, several studies within the last 12 months have questioned the importance of the bulge during re-epithelialisation, producing conflicting literature. Here we provide a new model to demonstrate how several important differences in experimental design between studies could account for these seemingly opposing findings, which may have implications for how future studies are conducted.
    • A Bayesian approach to linking archaeological, paleoenvironmental and documentary datasets relating to the settlement of Iceland (Landnám)

      Schmid, M.M.E.; Zori, D.; Erlendsson, E.; Batt, Catherine M.; Damiata, B.N.; Byock, J. (2017)
      Icelandic settlement (Landnám) period farmsteads offer opportunities to explore the nature and timing of anthropogenic activities and environmental impacts of the first Holocene farming communities. We employ Bayesian statistical modelling of archaeological, paleoenvironmental and documentary datasets to present a framework for improving chronological robustness of archaeological events. Specifically, we discuss events relevant to the farm Hrísbrú, an initial and complex settlement site in southwest Iceland. We demonstrate that tephra layers are key in constraining reliable chronologies, especially when combined with related datasets and treated in a Bayesian framework. The work presented here confirms earlier interpretations of the chronology of the site while providing increased confidence in the robustness of the chronology. Most importantly, integrated modelling of AMS radiocarbon dates on Hordeum vulgare grains, palynological data, documented evidence from textual records and typologically diagnostic artefacts yield increased dating reliability. The analysis has also shown that AMS radiocarbon dates on bone collagen need further scrutiny. Specifically for the Hrísbrú farm, first anthropogenic footprint palynomorph taxa are estimated to around AD 830–881 (at 95.4% confidence level), most likely before the tephra fall out of AD 877 ± 1 (the Landnám tephra layer), demonstrating the use of arable fields before the first known structures were built at Hrísbrú (AD 874–951) and prior to the conventionally accepted date of the settlement of Iceland. Finally, we highlight the importance of considering multidisciplinary factors for other archaeological and paleoecological studies of early farming communities of previously uninhabited island areas.
    • Bayesian methods applied to the interpretation of multiple OSL dates: high precision sediment ages from Old Scatness Broch excavations, Shetland Isles.

      Rhodes, E.J.; Bronk Ramsey, C.; Outram, Zoe; Batt, Catherine M.; Willis, Laura H.; Dockrill, Stephen J.; Bond, Julie M. (2009-10-12)
      In this paper, we illustrate the ways in which Bayesian statistical techniques may be used to enhance chronological resolution when applied to a series of OSL sediment dates. Such application can achieve an optimal chronological model by incorporating stratigraphic and age information. The application to luminescence data is not straightforward owing to the sources of uncertainty in each date, and here we present one solution to overcoming these difficulties, and introduce the concept of "unshared systematic" errors. Using OSL sediment dates from the site of Old Scatness Broch, Shetland Isles, UK, many measured with a high degree of precision, we illustrate some of the ways in which Bayesian techniques may be applied, as a tool for assessing systematic errors when combined with independent chronological information, and to determine the optimum chronological information for specific events and contexts. We provide a detailed procedure for the application of Bayesian methods to OSL dates using the widely available radiocarbon calibration programme OxCal.
    • The Beaker Phenomenon And The Genomic Transformation Of Northwest Europe

      Olalde, I.; Brace, S.; Allentoft, M.E.; Armit, Ian; Kristiansen, K.; Rohland, N.; Mallick, S.; Booth, T.; Szecsenyi-Nagyi, A.; Mittnik, A.; et al. (2018-02-21)
      Bell Beaker pottery spread across western and central Europe beginning around 2750 BCE before disappearing between 2200-1800 BCE. The mechanism of its expansion is a topic of long-standing debate, with support for both cultural diffusion and human migration. We present new genome-wide ancient DNA data from 170 Neolithic, Copper Age and Bronze Age Europeans, including 100 Beaker-associated individuals. In contrast to the Corded Ware Complex, which has previously been identified as arriving in central Europe following migration from the east, we observe limited genetic affinity between Iberian and central European Beaker Complex-associated individuals, and thus exclude migration as a significant mechanism of spread between these two regions. However, human migration did have an important role in the further dissemination of the Beaker Complex, which we document most clearly in Britain using data from 80 newly reported individuals dating to 3900-1200 BCE. British Neolithic farmers were genetically similar to contemporary populations in continental Europe and in particular to Neolithic Iberians, suggesting that a portion of the farmer ancestry in Britain came from the Mediterranean rather than the Danubian route of farming expansion. Beginning with the Beaker period, and continuing through the Bronze Age, all British individuals harboured high proportions of Steppe ancestry and were genetically closely related to Beaker-associated individuals from the Lower Rhine area. We use these observations to show that the spread of the Beaker Complex to Britain was mediated by migration from the continent that replaced >90% of Britain's Neolithic gene pool within a few hundred years, continuing the process that brought Steppe ancestry into central and northern Europe 400 years earlier.
    • Beeswax preserved in a Late Chalcolithic Bevelled Rim bowl from the Tehran Plain, Iran

      Mayyas, A.; Stern, Ben; Gillmore, Gavin; Coningham, Robin A.E.; Fazeli Nashli, H. (2012)
      References Citations Metrics Reprints & Permissions Get access Abstract This paper presents the observation of lipid residue, identified as beeswax, preserved in the ceramic matrix of a Late Chalcolithic (c. 3700–3000 BC) bevelled-rim bowl (BRB) from the site of Tepe Sofalin on the Tehran Plain. Gas chromatography-mass spectrometry (GC-MS) was used to separate and identify the lipid constituents preserved in the matrix of a BRB sherd. Lipid biomarkers were recovered including long-chain n-alkanes, n-alkenes, palmitic wax monoesters, fatty acids and n-alcohols characteristic of beeswax. In addition to two disaccharides, cholesterol and β-sitosterol as contaminants were retrieved by solvent soluble extraction from a number of different locations from the ceramic matrix of the analysed sherd.
    • Below the salt: a preliminary study of the dating and biology of five salt-preserved bodies from Zanjan Province, Iran

      Pollard, A. Mark; Brothwell, D.R.; Aali, A.; Buckley, S.; Fazeli, H.; Hadian Dehkordi, M.; Holden, T.; Jones, A.K.G.; Shokouhi, J.J.; Vatandoust, R.; et al. (2008)
    • Benzodiazepines for psychosis-induced aggression or agitation

      Zaman, Hadar; Sampson, S.J.; Beck, A.L.S.; Sharma, T.; Clay, F.J.; Spyridi, S.; Zhao, S.; Gillies, D. (2017)
    • Benzodiazepines for psychosis-induced aggression or agitation

      Zaman, Hadar; Sampson, S.; Beck, A.; Sharma, T.; Clay, F.; Spyridi, S.; Zhao, S.; Gillies, D. (2018-08)