6,255 research outputs found
Coordinated RhoA signaling at the leading edge and uropod is required for T cell transendothelial migration
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Alemtuzumab use in neuromyelitis optica spectrum disorders: a brief case series.
Alemtuzumab is an anti-CD52 monoclonal antibody recently licensed for use in relapsing-remitting multiple sclerosis. Here, we report our experience of its use in neuromyelitis optica (NMO) spectrum disorders. A retrospective case review of patients treated with alemtuzumab in Cambridge, UK, was conducted to identify those who fulfil the criteria for NMO spectrum disorder. Three cases were identified. Case 1, 9-year-old female, presented with transverse myelitis and bilateral optic neuritis,with one lower medullary and several longitudinally extensive cord lesions. Despite immunosuppression including two courses of alemtuzumab, she continued to relapse, was wheelchair bound and registered blind by age 12, and died at age 18. Case 2, 41-year-old female, presented with bilateral optic neuritis and transverse myelitis with longitudinally extensive cervical cord lesions. Despite three courses of alemtuzumab, she had five relapses with visual impairment and new cord lesions. She later developed tumefactive white matter lesions and died aged 51.Case 3, 31-year-old female, presented with transverse myelitis with longitudinally extensive cervical cord lesions and positive aquaporin-4 antibody. After one course of alemtuzumab, she relapsed with 4 episodes of myelitis with new enhancing lesions and accumulating disability. She became relapse free after rituximab and mycophenolate mofetil. From this case series, we conclude that alemtuzumab failed to prevent disabling relapses and poor outcome in NMO. We hypothesise that rituximab is more effective, as in case 3, because it causes much more prolonged B lymphocyte depletion than alemtuzumab. We therefore caution against the use of alemtuzumab in NMO.Clinical work is performed at the Wellcome Clinical Research Facility. JLJ and AJC are supported by the Cambridge Biomedical Research Centre of the National Institute for Health Research
Methods for estimating the case fatality ratio for a novel, emerging infectious disease.
During the course of an epidemic of a potentially fatal disease, it is important that the case fatality ratio be well estimated. The authors propose a novel method for doing so based on the Kaplan-Meier survival procedure, jointly considering two outcomes (death and recovery), and evaluate its performance by using data from the 2003 epidemic of severe acute respiratory syndrome in Hong Kong, People's Republic of China. They compare this estimate obtained at various points in the epidemic with the case fatality ratio eventually observed; with two commonly quoted, naïve estimates derived from cumulative incidence and mortality statistics at single time points; and with estimates in which a parametric mixture model is used. They demonstrate the importance of patient characteristics regarding outcome by analyzing subgroups defined by age at admission to the hospital
Anomalous Nernst effect in Co2MnSi thin films
Separation of the anomalous Nernst and spin Seebeck voltages in bilayer devices is often problematic when both layers are metallic, and the anomalous Nernst effect (ANE) becomes non-negligible. Co2MnSi, a strong candidate for the spin generator in spin Seebeck devices, is a predicted half-metal with 100% spin polarisation at the Fermi energy, however, typically B2 or L21 order is needed to achieve this. We demonstrate the optimisation of thin film growth of Co2MnSi on glass, where choice of deposition and annealing temperature can promote various ordered states. The contribution from the ANE is then investigated to inform futuremeasurements of the spin Seebeck. A maximum ANE coefficient of 0.662 µV K−1 is found for an A2 disordered polycrystalline Co2MnSi film. This value is comparable to ordered Heuslerthin films deposited onto single crystal substrates but obtained at a far lower fabrication temperature and material cost.</div
Distant X-ray Galaxies: Insights from the Local Population
A full understanding of the origin of the hard X-ray background requires a
complete and accurate census of the distant galaxies that produce it.
Unfortunately, distant X-ray galaxies tend to be very faint at all wavelengths,
which hinders efforts to perform this census. This chapter discusses the
insights that can be obtained through comparison of the distant population to
local X-ray galaxies, whose properties are well characterized. Such comparisons
will ultimately aid investigations into the cosmic evolution of supermassive
black holes and their environments.Comment: 19 pages, 10 figures, to appear as Chapter 7 in "Supermassive Black
Holes in the Distant Universe" (2004), ed. A. J. Barger, Kluwer Academic
Publishers, in pres
Survival Analysis to Estimate Association between Short-Term Mortality and Air Pollution
BACKGROUND: Ecologic studies are commonly used to report associations between short-term air pollution and mortality. In such studies, the unit of observation is the day rather than the individual. Moreover, individual data on the subjects are rarely available, which limits the assessment of individual risk factors. These associations can also be investigated using case–crossover studies. However, by definition, individual risk factors are not studied, and such studies analyze only dead subjects, which limits the statistical power. OBJECTIVE: We suggest that the survival analysis is more suitable when cohorts are examined with a time-dependent ecologic exposure. To our knowledge, to date this type of analysis has never been proposed. DESIGN, PARTICIPANTS, MEASUREMENTS: In the present study we used a Cox proportional hazards model to investigate the distribution over time of the short-term effect of black smoke and sulfur dioxide in 439 nonaccidental and 158 cardiorespiratory deaths among the 1,469 subjects of the Personnes Agées QUID (PAQUID) cohort in Bordeaux, France. The model has a delayed entry and a polynomial distributed lag from 0 to 5 days. Results are adjusted for individual risk factors, temperature, relative humidity, weekday, season, influenza epidemics, and a time function to control temporal trends. RESULTS: We identified a positive and significant association between cardiorespiratory mortality and black smoke, with a 24% increase in deaths 3 days after a 10-μg/m(3) increase in black smoke (95% confidence interval, 4–47%). CONCLUSIONS: We conclude that the Cox proportional hazards model with time-dependent covariates is very suitable to investigate simultaneously the short-term effect of air pollution on health and the effect of individual risk factors on a cohort study
Neuromorphic Dynamics at the Nanoscale in Silicon Suboxide RRAM
Resistive random-access memories, also known as memristors, whose resistance can be modulated by the electrically driven formation and disruption of conductive filaments within an insulator, are promising candidates for neuromorphic applications due to their scalability, low-power operation and diverse functional behaviors. However, understanding the dynamics of individual filaments, and the surrounding material, is challenging, owing to the typically very large cross-sectional areas of test devices relative to the nanometer scale of individual filaments. In the present work, conductive atomic force microscopy is used to study the evolution of conductivity at the nanoscale in a fully CMOS-compatible silicon suboxide thin film. Distinct filamentary plasticity and background conductivity enhancement are reported, suggesting that device behavior might be best described by composite core (filament) and shell (background conductivity) dynamics. Furthermore, constant current measurements demonstrate an interplay between filament formation and rupture, resulting in current-controlled voltage spiking in nanoscale regions, with an estimated optimal energy consumption of 25 attojoules per spike. This is very promising for extremely low-power neuromorphic computation and suggests that the dynamic behavior observed in larger devices should persist and improve as dimensions are scaled down
Enhancement of vaccinia virus based oncolysis with histone deacetylase inhibitors
Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interferon production and have been shown to increase the growth of vesicular stomatitis virus and HSV. As attenuated tumour-selective oncolytic vaccinia viruses (VV) are already undergoing clinical evaluation, the goal of this study is to determine whether HDI can also enhance the potency of these poxviruses in infection-resistant cancer cell lines. Multiple HDIs were tested and Trichostatin A (TSA) was found to potently enhance the spread and replication of a tumour selective vaccinia virus in several infection-resistant cancer cell lines. TSA significantly decreased the number of lung metastases in a syngeneic B16F10LacZ lung metastasis model yet did not increase the replication of vaccinia in normal tissues. The combination of TSA and VV increased survival of mice harbouring human HCT116 colon tumour xenografts as compared to mice treated with either agent alone. We conclude that TSA can selectively and effectively enhance the replication and spread of oncolytic vaccinia virus in cancer cells. © 2010 MacTavish et al
Survey of pickup ion signatures in the vicinity of Titan using CAPS/IMS
Pickup ion detection at Titan is challenging because ion cyclotron waves are rarely detected in the vicinity of the moon. In this work, signatures left by freshly produced pickup heavy ions (m/q ∼ 16 to m/q ∼ 28) as detected in the plasma data by the Cassini Plasma Spectrometer/Ion Mass Spectrometer (CAPS/IMS) instrument on board Cassini are analyzed. In order to discern whether these correspond to ions of exospheric origin, one of the flybys during which the reported signatures were observed is investigated in detail. For this purpose, ion composition data from time-of-flight measurements and test particle simulations to constrain the ions' origin are used. After being validated, the detection method is applied to all the flybys for which the CAPS/IMS instrument gathered valid data, constraining the region around the moon where the signatures are observed. The results reveal an escape region located in the anti-Saturn direction as expected from the nominal corotation electric field direction. These findings provide new constraints for the area of freshly produced pickup ion escape, giving an approximate escape rate of inline image ions· s−1
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