4,591 research outputs found

    Disruption of smooth pursuit eye movements in cirrhosis: relationship to hepatic encephalopathy and its treatment.

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    Smooth pursuit eye movements (SPEM) are the conjugate movements used to track the smooth trajectory of small dots. Jerky or 'saccadic' ocular pursuit has been reported in patients with cirrhosis, but no formal assessment of SPEM has ever been undertaken. The aim of this study was to evaluate SPEM in patients with cirrhosis and varying degrees of hepatic encephalopathy. The patient population comprised 56 individuals (31 men, 25 women) of mean age 51.1 (range, 25-70) years, with biopsy-proven cirrhosis, classified, using clinical, electroencephalographic, and psychometric variables, as either neuropsychiatrically unimpaired or as having minimal or overt hepatic encephalopathy; patients were further categorized in relation to their treatment status. The reference population comprised 28 healthy volunteers (12 men, 16 women) of mean age 47.3 (range, 26-65) years. SPEM was assessed using an electro-oculographic technique. Visual inspection of the SPEM recordings showed clear disruption of smooth pursuit in the patients with minimal hepatic encephalopathy, and more pronounced disruption, if not complete loss, of smooth pursuit in patients with overt hepatic encephalopathy. The differences observed in quantifiable SPEM indices between the healthy volunteers/unimpaired patients and those with overt hepatic encephalopathy were significant (P < .05). In conclusion, SPEM performance is impaired in patients with hepatic encephalopathy in parallel with the degree of neuropsychiatric disturbance: the pathophysiology of these changes is unknown, but retinal, extrapyramidal, and attentional abnormalities are likely to play a role. Treatment status confounds the classification of neuropsychiatric status and should be taken into account when categorizing these patients

    Controlling light-with-light without nonlinearity

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    According to Huygens' superposition principle, light beams traveling in a linear medium will pass though one another without mutual disturbance. Indeed, it is widely held that controlling light signals with light requires intense laser fields to facilitate beam interactions in nonlinear media, where the superposition principle can be broken. We demonstrate here that two coherent beams of light of arbitrarily low intensity can interact on a metamaterial layer of nanoscale thickness in such a way that one beam modulates the intensity of the other. We show that the interference of beams can eliminate the plasmonic Joule losses of light energy in the metamaterial or, in contrast, can lead to almost total absorbtion of light. Applications of this phenomenon may lie in ultrafast all-optical pulse-recovery devices, coherence filters and THz-bandwidth light-by-light modulators

    Unleashing the potential of the TQM and Industry 4.0 to achieve sustainability performance in the context of a developing country

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    Business organizations may be able to improve their sustainability performance (SP) by adopting Total Quality Management (TQM) concepts combined with Industry 4.0 (I4.0) technologies. This research has developed a model to investigate the influence of TQM and I4.0 on SP. It also analyzes the mediating role of TQM in the relationship between I4.0 and SP. A survey was conducted among 240 respondents employed in ready-made garment (RMG) industries in Bangladesh. A Structural Equation Modelling (SEM) technique was used to analyze the collected data. Research findings show that both TQM and I4.0 technologies have a significant impact on the sustainable growth of the Bangladeshi RMG sector. Moreover, it is observed that TQM mediates the relationship between I4.0 and SP. The findings show that TQM helps to explain the relationship between I4.0 and sustainable performance. This study will provide a guideline for industrial executives on securing sustainability through the adoption of TQM concepts and I4.0 technologies. We are not aware of any additional studies that look at the possible link between TQM, I4.0, and SP, as well as the mediating role of TQM between I4.0 and SP

    Osteoblastoma of the rib with CT and MR imaging: a case report and literature review

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    Osteoblastoma is a rare bone tumor which is mostly found in the vertebral column and long bone. We describe a 59-year-old woman with osteoblastoma in the right fifth posterior segment of the rib, whose presenting symptoms were right back pain for two years and awakened at night. Chest computer tomography (CT) and thoracic spine magnetic resonance (MR) imaging findings included an expansile lesion of the right fifth rib and an ossified matrix. Surgical resection of the lesion confirmed a benign osteoblastoma. 12 months follow-up revealed disappearance of right back pain. Rib osteoblastoma in plain film has been described previously; however, to our knowledge this is the only case report emphasized in CT and MR imaging

    Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma.

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    BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse

    HPV16 and 18 genome amplification show different E4-dependence, with 16E4 enhancing E1 nuclear accumulation and replicative efficiency via its cell cycle arrest and kinase activation functions

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    To clarify E1^E4's role during high-risk HPV infection, the E4 proteins of HPV16 and 18 were compared side by side using an isogenic keratinocyte differentiation model. While no effect on cell proliferation or viral genome copy number was observed during the early phase of either virus life cycle, time-course experiments showed that viral genome amplification and L1 expression were differently affected upon differentiation, with HPV16 showing a much clearer E4 dependency. Although E4 loss never completely abolished genome amplification, its more obvious contribution in HPV16 focused our efforts on 16E4. As previously suggested, in the context of the virus life cycle, 16E4s G2-arrest capability was found to contribute to both genome amplification success and L1 accumulation. Loss of 16E4 also lead to a reduced maintenance of ERK, JNK and p38MAPK activity throughout the genome amplifying cell layers, with 16E4 (but not 18E4) co-localizing precisely with activated cytoplasmic JNK in both wild type raft tissue, and HPV16-induced patient biopsy tissue. When 16E1 was co-expressed with E4, as occurs during genome amplification in vivo\textit{in vivo}, the E1 replication helicase accumulated preferentially in the nucleus, and in transient replication assays, E4 stimulated viral genome amplification. Interestingly, a 16E1 mutant deficient in its regulatory phosphorylation sites no longer accumulated in the nucleus following E4 co-expression. E4-mediated stabilisation of 16E2 was also apparent, with E2 levels declining in organotypic raft culture when 16E4 was absent. These results suggest that 16E4-mediated enhancement of genome amplification involves its cell cycle inhibition and cellular kinase activation functions, with E4 modifying the activity and function of viral replication proteins including E1. These activities of 16E4, and the different kinase patterns seen here with HPV18, 31 and 45, may reflect natural differences in the biology and tropisms of these viruses, as well as differences in E4 function.The work was supported by the UK Medical Research Council (grant ref. MC_PC_13050 / Molecular biology of human papilloma virus infection to JD, http://gtr.rcuk.ac.uk/ project/A691 306C-DAA9- 4078-B5D E- 2096CF3C8A18)

    Interplay between Fermi gamma-ray lines and collider searches

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    We explore the interplay between lines in the gamma-ray spectrum and LHC searches involving missing energy and photons. As an example, we consider a singlet Dirac fermion dark matter with the mediator for Fermi gamma-ray line at 130 GeV. A new chiral or local U(1) symmetry makes weak-scale dark matter natural and provides the axion or Z 0 gauge boson as the mediator connecting between dark matter and electroweak gauge bosons. In these models, the mediator particle can be produced in association with a monophoton at colliders and it produces large missing energy through the decays into a DM pair or ZZ; Z with at least one Z decaying into a neutrino pair. We adopt the monophoton searches with large missing energy at the LHC and impose the bounds on the coupling and mass of the mediator field in the models. We show that the parameter space of the Z 0 mediation model is already strongly constrained by the LHC 8TeV data, whereas a certain region of the parameter space away from the resonance in axion-like mediator models are bounded. We foresee the monophoton bounds on the Z 0 and axion mediation models at the LHC 14 TeV

    Identification of Class I HLA T Cell Control Epitopes for West Nile Virus

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    The recent West Nile virus (WNV) outbreak in the United States underscores the importance of understanding human immune responses to this pathogen. Via the presentation of viral peptide ligands at the cell surface, class I HLA mediate the T cell recognition and killing of WNV infected cells. At this time, there are two key unknowns in regards to understanding protective T cell immunity: 1) the number of viral ligands presented by the HLA of infected cells, and 2) the distribution of T cell responses to these available HLA/viral complexes. Here, comparative mass spectroscopy was applied to determine the number of WNV peptides presented by the HLA-A*11:01 of infected cells after which T cell responses to these HLA/WNV complexes were assessed. Six viral peptides derived from capsid, NS3, NS4b, and NS5 were presented. When T cells from infected individuals were tested for reactivity to these six viral ligands, polyfunctional T cells were focused on the GTL9 WNV capsid peptide, ligands from NS3, NS4b, and NS5 were less immunogenic, and two ligands were largely inert, demonstrating that class I HLA reduce the WNV polyprotein to a handful of immune targets and that polyfunctional T cells recognize infections by zeroing in on particular HLA/WNV epitopes. Such dominant HLA/peptide epitopes are poised to drive the development of WNV vaccines that elicit protective T cells as well as providing key antigens for immunoassays that establish correlates of viral immunity. © 2013 Kaabinejadian et al
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