943 research outputs found
Sharing is caring vs. stealing is wrong: a moral argument for limiting copyright protection
Copyright is at the centre of both popular and academic debate. That emotions are running high is hardly surprising â copyright influences who contributes what to culture, how culture is used, and even the kind of persons we are and come to be. Consequentialist, Lockean, and personality interest accounts are generally advanced in the literature to morally justify copyright law. I argue that these approaches fail to ground extensive authorial rights in intellectual creations and that only a small subset of the rights accorded by copyright law is justified. The pared-down version of copyright that I defend consists of the right to attribution, the right to have oneâs non-endorsement of modifications or uses of oneâs work explicitly noted, and the right to a share of the profit resulting from the commercial uses of oneâs work. I also cursorily explore whether contribution to another personâs work gives rise to moral interests
Chronic white matter lesion activity predicts clinical progression in primary progressive multiple sclerosis.
Chronic active and slowly expanding lesions with smouldering inflammation are neuropathological correlates of progressive multiple sclerosis pathology. T1 hypointense volume and signal intensity on T1-weighted MRI reflect brain tissue damage that may develop within newly formed acute focal inflammatory lesions or in chronic pre-existing lesions without signs of acute inflammation. Using a recently developed method to identify slowly expanding/evolving lesions in vivo from longitudinal conventional T2- and T1-weighted brain MRI scans, we measured the relative amount of chronic lesion activity as measured by change in T1 volume and intensity within slowly expanding/evolving lesions and non-slowly expanding/evolving lesion areas of baseline pre-existing T2 lesions, and assessed the effect of ocrelizumab on this outcome in patients with primary progressive multiple sclerosis participating in the phase III, randomized, placebo-controlled, double-blind ORATORIO study (n = 732, NCT01194570). We also assessed the predictive value of T1-weighted measures of chronic lesion activity for clinical multiple sclerosis progression as reflected by a composite disability measure including the Expanded Disability Status Scale, Timed 25-Foot Walk and 9-Hole Peg Test. We observed in this clinical trial population that most of total brain non-enhancing T1 hypointense lesion volume accumulation was derived from chronic lesion activity within pre-existing T2 lesions rather than new T2 lesion formation. There was a larger decrease in mean normalized T1 signal intensity and greater relative accumulation of T1 hypointense volume in slowly expanding/evolving lesions compared with non-slowly expanding/evolving lesions. Chronic white matter lesion activity measured by longitudinal T1 hypointense lesion volume accumulation in slowly expanding/evolving lesions and in non-slowly expanding/evolving lesion areas of pre-existing lesions predicted subsequent composite disability progression with consistent trends on all components of the composite. In contrast, whole brain volume loss and acute lesion activity measured by longitudinal T1 hypointense lesion volume accumulation in new focal T2 lesions did not predict subsequent composite disability progression in this trial at the population level. Ocrelizumab reduced longitudinal measures of chronic lesion activity such as T1 hypointense lesion volume accumulation and mean normalized T1 signal intensity decrease both within regions of pre-existing T2 lesions identified as slowly expanding/evolving and in non-slowly expanding/evolving lesions. Using conventional brain MRI, T1-weighted intensity-based measures of chronic white matter lesion activity predict clinical progression in primary progressive multiple sclerosis and may qualify as a longitudinal in vivo neuroimaging correlate of smouldering demyelination and axonal loss in chronic active lesions due to CNS-resident inflammation and/or secondary neurodegeneration across the multiple sclerosis disease continuum
Analyzing nicotinamide adenine dinucleotide phosphate oxidase activation in aging and vascular amyloid pathology
In aging individuals, both protective as well as regulatory immune functions
are declining, resulting in an increased susceptibility to infections as well
as to autoimmunity. Nicotinamide adenine dinucleotide phosphate (NADPH)
oxidase 2-deficiency in immune cell subsets has been shown to be associated
with aging. Using intravital marker-free NAD(P)H-fluorescence lifetime
imaging, we have previously identified microglia/myeloid cells and astrocytes
as main cellular sources of NADPH oxidase (NOX) activity in the CNS during
neuroinflammation, due to an overactivation of NOX. The overactivated NOX
enzymes catalyze the massive production of the highly reactive Oâ2, which
initiates in a chain reaction the overproduction of diverse reactive oxygen
species (ROS). Age-dependent oxidative distress levels in the brain and their
cellular sources are not known. Furthermore, it is unclear whether in age-
dependent diseases oxidative distress is initiated by overproduction of ROS or
by a decrease in antioxidant capacity, subsequently leading to
neurodegeneration in the CNS. Here, we compare the activation level of NOX
enzymes in the cerebral cortex of young and aged mice as well as in a model of
vascular amyloid pathology. Despite the fact that a striking change in the
morphology of microglia can be detected between young and aged individuals, we
find comparable low-level NOX activation both in young and old mice. In
contrast, aged mice with the human APPE693Q mutation, a model for cerebral
amyloid angiopathy (CAA), displayed increased focal NOX overactivation in the
brain cortex, especially in tissue areas around the vessels. Despite activated
morphology in microglia, NOX overactivation was detected only in a small
fraction of these cells, in contrast to other pathologies with overt
inflammation as experimental autoimmune encephalomyelitis (EAE) or
glioblastoma. Similar to these pathologies, the astrocytes majorly contribute
to the NOX overactivation in the brain cortex during CAA. Together, these
findings emphasize the role of other cellular sources of activated NOX than
phagocytes not only during EAE but also in models of amyloid pathology.
Moreover, they may strengthen the hypothesis that microglia/monocytes show a
diminished potential for clearance of amyloid beta protein
Adherence and satisfaction of smartphone- and smartwatch-based remote active testing and passive monitoring in people with multiple sclerosis: nonrandomized interventional feasibility study
Smartphone; Multiple sclerosis; Patient adherenceTelĂ©fono inteligente; Esclerosis mĂșltiple; Adherencia del pacienteTelĂšfon intel·ligent; Esclerosi mĂșltiple; AdherĂšncia del pacientBackground: Current clinical assessments of people with multiple sclerosis are episodic and may miss critical features of functional fluctuations between visits.
Objective: The goal of the research was to assess the feasibility of remote active testing and passive monitoring using smartphones and smartwatch technology in people with multiple sclerosis with respect to adherence and satisfaction with the FLOODLIGHT test battery.
Methods: People with multiple sclerosis (aged 20 to 57 years; Expanded Disability Status Scale 0-5.5; n=76) and healthy controls (n=25) performed the FLOODLIGHT test battery, comprising active tests (daily, weekly, every two weeks, or on demand) and passive monitoring (sensor-based gait and mobility) for 24 weeks using a smartphone and smartwatch. The primary analysis assessed adherence (proportion of weeks with at least 3 days of completed testing and 4 hours per day passive monitoring) and questionnaire-based satisfaction. In-clinic assessments (clinical and magnetic resonance imaging) were performed.
Results: People with multiple sclerosis showed 70% (16.68/24 weeks) adherence to active tests and 79% (18.89/24 weeks) to passive monitoring; satisfaction score was on average 73.7 out of 100. Neither adherence nor satisfaction was associated with specific population characteristics. Test-battery assessments had an at least acceptable impact on daily activities in over 80% (61/72) of people with multiple sclerosis
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No evidence of disease activity (NEDA) analysis by epochs in patients with relapsing multiple sclerosis treated with ocrelizumab vs interferon beta-1a.
BackgroundNo evidence of disease activity (NEDA; defined as no 12-week confirmed disability progression, no protocol-defined relapses, no new/enlarging T2 lesions and no T1 gadolinium-enhancing lesions) using a fixed-study entry baseline is commonly used as a treatment outcome in multiple sclerosis (MS).ObjectiveThe objective of this paper is to assess the effect of ocrelizumab on NEDA using re-baselining analysis, and the predictive value of NEDA status.MethodsNEDA was assessed in a modified intent-to-treat population (nâ=â1520) from the pooled OPERA I and OPERA II studies over various epochs in patients with relapsing MS receiving ocrelizumab (600 mg) or interferon beta-1a (IFN ÎČ-1a; 44 ÎŒg).ResultsNEDA was increased with ocrelizumab vs IFN ÎČ-1a over 96 weeks by 75% (pâ<â0.001), from Week 0â24 by 33% (pâ<â0.001) and from Week 24â96 by 72% (pâ<â0.001). Among patients with disease activity during Weeks 0â24, 66.4% vs 24.3% achieved NEDA during Weeks 24â96 in the ocrelizumab and IFN ÎČ-1a groups (relative increase: 177%; pâ<â0.001).ConclusionSuperior efficacy with ocrelizumab compared with IFN ÎČ-1a was consistently seen in maintaining NEDA status in all epochs evaluated. By contrast with IFN ÎČ-1a, the majority of patients with disease activity early in the study subsequently attained NEDA status with ocrelizumab
Unconventional resistivity at the border of metallic antiferromagnetism in NiS2
We report low-temperature and high-pressure measurements of the electrical
resistivity \rho(T) of the antiferromagnetic compound NiS_2 in its
high-pressure metallic state. The form of \rho(T) suggests that metallic
antiferromagnetism in NiS_2 is quenched at a critical pressure p_c=76+-5 kbar.
Near p_c the temperature variation of \rho(T) is similar to that observed in
NiS_{2-x}Se_x near the critical composition x=1 where the Neel temperature
vanishes at ambient pressure. In both cases \rho(T) varies approximately as
T^{1.5} over a wide range below 100 K. However, on closer analysis the
resistivity exponent in NiS_2 exhibits an undulating variation with temperature
not seen in NiSSe (x=1). This difference in behaviour may be due to the effects
of spin-fluctuation scattering of charge carriers on cold and hot spots of the
Fermi surface in the presence of quenched disorder, which is higher in NiSSe
than in stoichiometric NiS_2.Comment: 7 page
InkjetâPrinted pâNiO/nâZnO Heterojunction Diodes for Photodetection Applications
Transparent Conducting Oxides (TCOs) are an enticing family of optoelectronic materials which have been proven to increase efficiency when incorporated into perovskite light emitting diode (PE-LED) and organic OLED architectures as transport layers. Solution-processed metal oxide inks have already been demonstrated, although there is still a need for high-quality inkjet-printable metal oxide inks with a thermal post-process below 200 °C. The set of inks in this work are adapted from low-boiling point colloidal suspensions of metal oxide nanoparticles synthesized via flame spray pyrolysis. High quality, pinhole- and wrinkle-free inkjet-printed layers are obtained at low temperatures through vacuum oven post process, as proven by scanning electron microscopy. The crystallinity of the layers is confirmed by X-ray diffraction, showing the expected hexagonal and cubic structures respectively for ZnO and NiO. The thin film layers reach over 70% (ZnO) and 90% (NiO) transparency in the visible spectrum. Their implementation in the inkjet-printed p-n diode shows excellent I-V rectifying behavior with an ON/OFF ratio of two orders of magnitude at ±3 V and a forward threshold voltage of 2 V. Furthermore, the device exhibits an increase in photocurrent around four orders of magnitude when illuminated under a 1-sun solar simulator
Microevolution during the emergence of a monophasic Salmonella Typhimurium epidemic in the United Kingdom
Microevolutionary events associated with the emergence and clonal expansion of new 27 epidemic clones of bacterial pathogens hold the key to understanding the drivers of 28 epidemiological success. We describe a comparative whole genome sequence and 29 phylogenomic analysis of monophasic Salmonella Typhimurium isolates from the UK 30 and Italy from 2005-2012. Monophasic isolates from this time formed a single clade 31 distinct from recent monophasic epidemic clones described previously from North 32 America and Spain. The current UK monophasic epidemic clones encode a novel 33 genomic island encoding resistance to heavy metals (SGI-3), and composite transposon 34 encoding antibiotic resistance genes not present in other Typhimurium isolates, that 35 may have contributed to the epidemiological success. We also report a remarkable 36 degree of genotypic variation that accumulated during clonal expansion of a UK 37 epidemic including multiple independent acquisitions of a novel prophage carrying the 38 sopE gene and multiple deletion events affecting the phase II flagellin locus
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