175 research outputs found

    Understanding fans' responses to the sponsor of a rival team

    Get PDF
    Research Question What factors determine fans’ responses to the sponsor of a rival team? To what extent does higher in-group fan identification, more positive prior attitudes to the sponsor, and a more congruent fit between the sponsor and club, cause denigration or mitigate negative outcomes for the sponsor? Research Methods 300 questionnaires were collected from fans of English Premier League (EPL) football teams Newcastle United and Sunderland allowed us to test our model of sponsorship responses. Structural equation modelling (SEM) was used to evaluate each hypothesis. Results and Findings Brands will gain greater benefits from sponsorships deemed to be congruent with the rival team and where a higher pre-sponsorship attitude exists. More highly identified fans tend to pay greater attention to the sponsor of their rival team. We find that schadenfreude is a better predictor of affective and behavioural responses than fan identification, despite its popularity in recent research involving rival fans. Implications Brand managers concerned about the size and scope of out-groups can employ our findings to more effectively configure sponsorship activities

    Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity

    Get PDF
    Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations

    Shortened Modified Look-Locker Inversion recovery (ShMOLLI) for clinical myocardial T1-mapping at 1.5 and 3 T within a 9 heartbeat breathhold

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>T1 mapping allows direct <it>in-vivo </it>quantitation of microscopic changes in the myocardium, providing new diagnostic insights into cardiac disease. Existing methods require long breath holds that are demanding for many cardiac patients. In this work we propose and validate a novel, clinically applicable, pulse sequence for myocardial T1-mapping that is compatible with typical limits for end-expiration breath-holding in patients.</p> <p>Materials and methods</p> <p>The Shortened MOdified Look-Locker Inversion recovery (ShMOLLI) method uses sequential inversion recovery measurements within a single short breath-hold. Full recovery of the longitudinal magnetisation between sequential inversion pulses is not achieved, but conditional interpretation of samples for reconstruction of T1-maps is used to yield accurate measurements, and this algorithm is implemented directly on the scanner. We performed computer simulations for 100 ms<T1 < 2.7 s and heart rates 40-100 bpm followed by phantom validation at 1.5T and 3T. <it>In-vivo </it>myocardial T1-mapping using this method and the previous gold-standard (MOLLI) was performed in 10 healthy volunteers at 1.5T and 3T, 4 volunteers with contrast injection at 1.5T, and 4 patients with recent myocardial infarction (MI) at 3T.</p> <p>Results</p> <p>We found good agreement between the average ShMOLLI and MOLLI estimates for T1 < 1200 ms. In contrast to the original method, ShMOLLI showed no dependence on heart rates for long T1 values, with estimates characterized by a constant 4% underestimation for T1 = 800-2700 ms. <it>In-vivo</it>, ShMOLLI measurements required 9.0 ± 1.1 s (MOLLI = 17.6 ± 2.9 s). Average healthy myocardial T1 s by ShMOLLI at 1.5T were 966 ± 48 ms (mean ± SD) and 1166 ± 60 ms at 3T. In MI patients, the T1 in unaffected myocardium (1216 ± 42 ms) was similar to controls at 3T. Ischemically injured myocardium showed increased T1 = 1432 ± 33 ms (p < 0.001). The difference between MI and remote myocardium was estimated 15% larger by ShMOLLI than MOLLI (p < 0.04) which suffers from heart rate dependencies for long T1. The <it>in-vivo </it>variability within ShMOLLI T1-maps was only 14% (1.5T) or 18% (3T) higher than the MOLLI maps, but the MOLLI acquisitions were twice longer than ShMOLLI acquisitions.</p> <p>Conclusion</p> <p>ShMOLLI is an efficient method that generates immediate, high-resolution myocardial T1-maps in a short breath-hold with high precision. This technique provides a valuable clinically applicable tool for myocardial tissue characterisation.</p

    Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain

    Get PDF
    The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn^(2+) into the prefrontal cortex indicated that DAT KO mice have a truncated Mn^(2+) distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn^(2+) transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here

    Cisplatin and vinorelbine first-line chemotherapy in non-resectable malignant pleural mesothelioma

    Get PDF
    The aim was to evaluate the activity of cisplatin and vinorelbine in previously untreated, inoperable patients having histologically verified malignant pleural mesothelioma (MPM), normal organ function, and performance status 0–2. Treatment was vinorelbine 25 mg m−2 i.v. weekly and cisplatin 100 mg m−2 i.v. every 4 weeks with hydration and standard prophylactic antiemetic treatment. Patients gave written informed consent. Characteristics of 54 consecutive patients were: males 85%, epithelial subtype 74%, IMIG stages III and IV 35 and 46%, performance status 0, 1, and 2, 26, 69, and 6%, and median age 63 years (31–78 years). CTC grade 3 or 4 toxicity occurred with respect to leukocytopenia (48% of patients, grade 4 in 13%), nausea (13%), neurotoxicity (11%), nephrotoxicity (4%), and other toxicities (9%). There were no toxic deaths. The median number of cycles was four. The fraction of patients alive at 1-, 2-, and 3-years were 61, 31, and 4%, respectively, and median survival and median time to progression were 16.8 months (0.5 to 46.4 +months) and 7.2 months (1.6 to 40.6 + months). There were two CRs and 14 PRs (response rate 29.6%). Cisplatin and intravenous vinorelbine is a highly active regimen in MPM with a response rate and survival comparable to the most active regimens so far reported

    Propagation of Respiratory Aerosols by the Vuvuzela

    Get PDF
    Vuvuzelas, the plastic blowing horns used by sports fans, recently achieved international recognition during the FIFA World Cup soccer tournament in South Africa. We hypothesised that vuvuzelas might facilitate the generation and dissemination of respiratory aerosols. To investigate the quantity and size of aerosols emitted when the instrument is played, eight healthy volunteers were asked to blow a vuvuzela. For each individual the concentration of particles in expelled air was measured using a six channel laser particle counter and the duration of blowing and velocity of air leaving the vuvuzela were recorded. To allow comparison with other activities undertaken at sports events each individual was also asked to shout and the measurements were repeated while using a paper cone to confine the exhaled air. Triplicate measurements were taken for each individual. The mean peak particle counts were 658×103 per litre for the vuvuzela and 3.7×103 per litre for shouting, representing a mean log10 difference of 2.20 (95% CI: 2.03,2.36; p<0.001). The majority (>97%) of particles captured from either the vuvuzela or shouting were between 0.5 and 5 microns in diameter. Mean peak airflows recorded for the vuvuzela and shouting were 6.1 and 1.8 litres per second respectively. We conclude that plastic blowing horns (vuvuzelas) have the capacity to propel extremely large numbers of aerosols into the atmosphere of a size able to penetrate the lower lung. Some respiratory pathogens are spread via contaminated aerosols emitted by infected persons. Further investigation is required to assess the potential of the vuvuzela to contribute to the transmission of aerosol borne diseases. We recommend, as a precautionary measure, that people with respiratory infections should be advised not to blow their vuvuzela in enclosed spaces and where there is a risk of infecting others

    In vivo magnetic resonance spectroscopy: basic methodology and clinical applications

    Get PDF
    The clinical use of in vivo magnetic resonance spectroscopy (MRS) has been limited for a long time, mainly due to its low sensitivity. However, with the advent of clinical MR systems with higher magnetic field strengths such as 3 Tesla, the development of better coils, and the design of optimized radio-frequency pulses, sensitivity has been considerably improved. Therefore, in vivo MRS has become a technique that is routinely used more and more in the clinic. In this review, the basic methodology of in vivo MRS is described—mainly focused on 1H MRS of the brain—with attention to hardware requirements, patient safety, acquisition methods, data post-processing, and quantification. Furthermore, examples of clinical applications of in vivo brain MRS in two interesting fields are described. First, together with a description of the major resonances present in brain MR spectra, several examples are presented of deviations from the normal spectral pattern associated with inborn errors of metabolism. Second, through examples of MR spectra of brain tumors, it is shown that MRS can play an important role in oncology

    Contribution of DEAF1 Structural Domains to the Interaction with the Breast Cancer Oncogene LMO4

    Get PDF
    The proteins LMO4 and DEAF1 contribute to the proliferation of mammary epithelial cells. During breast cancer LMO4 is upregulated, affecting its interaction with other protein partners. This may set cells on a path to tumour formation. LMO4 and DEAF1 interact, but it is unknown how they cooperate to regulate cell proliferation. In this study, we identify a specific LMO4-binding domain in DEAF1. This domain contains an unstructured region that directly contacts LMO4, and a coiled coil that contains the DEAF1 nuclear export signal (NES). The coiled coil region can form tetramers and has the typical properties of a coiled coil domain. Using a simple cell-based assay, we show that LMO4 modulates the activity of the DEAF NES, causing nuclear accumulation of a construct containing the LMO4-interaction region of DEAF1

    Mixed Infection with cagA Positive and cagA Negative Strains of Helicobacter pylori Lowers Disease Burden in The Gambia

    Get PDF
    BACKGROUND: The prevalence of Helicobacter pylori including strains with putatively virulent genotypes is high, whereas the H. pylori-associated disease burden is low, in Africa compared to developed countries. In this study, we investigated the prevalence of virulence-related H. pylori genotypes and their association with gastroduodenal diseases in The Gambia. METHODS AND FINDINGS: DNA extracted from biopsies and H. pylori cultures from 169 subjects with abdominal pain, dyspepsia or other gastroduodenal diseases were tested by PCR for H. pylori. The H. pylori positive samples were further tested for the cagA oncogene and vacA toxin gene. One hundred and twenty one subjects (71.6%) were H. pylori positive. The cagA gene and more toxigenic s1 and m1 alleles of the vacA gene were found in 61.2%, 76.9% and 45.5% respectively of Gambian patients harbouring H. pylori. There was a high prevalence of cagA positive strains in patients with overt gastric diseases than those with non-ulcerative dyspepsia (NUD) (p = 0.05); however, mixed infection by cagA positive and cagA negative strains was more common in patients with NUD compared to patients with gastric disease (24.5% versus 0%; p = 0.002). CONCLUSION: This study shows that the prevalence of H. pylori is high in dyspeptic patients in The Gambia and that many strains are of the putatively more virulent cagA+, vacAs1 and vacAm1 genotypes. This study has also shown significantly lower disease burden in Gambians infected with a mixture of cag-positive and cag-negative strains, relative to those containing only cag-positive or only cag-negative strains, which suggests that harbouring both cag-positive and cag-negative strains is protective
    corecore