206 research outputs found
CNS inflammation other than multiple sclerosis: how likely is diagnosis?
The incidence, diagnostic landscape, and workload impact of CNS inflammatory diseases other than multiple sclerosis (MS) (CIDOMS) in a tertiary setting is unknown. We describe a retrospective case series of 64 patients identified over a 2-year period (2009–2010) at the Wessex Neurological Centre in the United Kingdom, accounting for 4% of all patients seen at the center. As expected, neurosarcoidosis and neuromyelitis optica (NMO) were the most common diagnoses reached (14% each); other diagnoses singly accounted for <10%. However, the likeliest diagnostic outcome (strikingly, in 25%) was nondiagnosis, despite intensive investigation and a mean follow-up period of 3 years. Undiagnosed patients with CIDOMS represented the largest workload of the neurology center
Interacting Frobenius Algebras are Hopf
Theories featuring the interaction between a Frobenius algebra and a Hopf
algebra have recently appeared in several areas in computer science: concurrent
programming, control theory, and quantum computing, among others. Bonchi,
Sobocinski, and Zanasi (2014) have shown that, given a suitable distributive
law, a pair of Hopf algebras forms two Frobenius algebras. Here we take the
opposite approach, and show that interacting Frobenius algebras form Hopf
algebras. We generalise (BSZ 2014) by including non-trivial dynamics of the
underlying object---the so-called phase group---and investigate the effects of
finite dimensionality of the underlying model. We recover the system of Bonchi
et al as a subtheory in the prime power dimensional case, but the more general
theory does not arise from a distributive law.Comment: 32 pages; submitte
Suppression of Lymphoma and Epithelial Malignancies Effected by Interferon γ
The immunosurveillance of transformed cells by the immune system remains one of the most controversial and poorly understood areas of immunity. Gene-targeted mice have greatly aided our understanding of the key effector molecules in tumor immunity. Herein, we describe spontaneous tumor development in gene-targeted mice lacking interferon (IFN)-γ and/or perforin (pfp), or the immunoregulatory cytokines, interleukin (IL)-12, IL-18, and tumor necrosis factor (TNF). Both IFN-γ and pfp were critical for suppression of lymphomagenesis, however the level of protection afforded by IFN-γ was strain specific. Lymphomas arising in IFN-γ-deficient mice were very nonimmunogenic compared with those derived from pfp-deficient mice, suggesting a comparatively weaker immunoselection pressure by IFN-γ. Single loss of IL-12, IL-18, or TNF was not sufficient for spontaneous tumor development. A significant incidence of late onset adenocarcinoma observed in both IFN-γ– and pfp-deficient mice indicated that some epithelial tissues were also subject to immunosurveillance
A High Power Hydrogen Target for Parity Violation Experiments
Parity-violating electron scattering measurements on hydrogen and deuterium,
such as those underway at the Bates and CEBAF laboratories, require
luminosities exceeding cms, resulting in large beam
power deposition into cryogenic liquid. Such targets must be able to absorb 500
watts or more with minimal change in target density. A 40~cm long liquid
hydrogen target, designed to absorb 500~watts of beam power without boiling,
has been developed for the SAMPLE experiment at Bates. In recent tests with
40~A of incident beam, no evidence was seen for density fluctuations in
the target, at a sensitivity level of better than 1\%. A summary of the target
design and operational experience will be presented.Comment: 13 pages, 9 postscript figure
Recommended from our members
Clinical progression of progressive supranuclear palsy: impact of trials bias and phenotype variants.
Funder: Cambridge Brain BankProgressive supranuclear palsy causes diverse clinical presentations, including classical Richardson's syndrome and several variant phenotypes. Clinical trials of disease-modifying therapies have recently been completed, with more planned for the next 2 years. However, many people with progressive supranuclear palsy do not meet eligibility criteria for these clinical trials. Understanding clinical progression with different phenotypes would improve trial design and enhance the accuracy of risk-benefit and cost-benefit assessments of new treatments for progressive supranuclear palsy. We set out to determine rates of motor and cognitive progression of possible, probable and definite progressive supranuclear palsy, with different phenotypes, from a representative cohort in a regional UK healthcare service. Longitudinal clinical data from people with Richardson's syndrome and variant phenotypes were analysed using linear mixed-modelling, using both the full and modified versions of the Progressive Supranuclear Palsy Rating Scale, Mini-Mental State Examination and the revised Addenbrooke's Cognitive Examination. Subgroup analyses considered patients meeting recent Phase II trial entry criteria and patients with neuropathological confirmation. Two hundred and twenty-seven patients [male = 59%, mean age (±standard deviation), 71.8 (±7.0) years] were followed for a mean 21.6 (±15.6) months. One hundred and seventy-four (77%) had Richardson's syndrome at the outset, 25 had cortical variant presentations (13%, frontal, corticobasal, speech and language variants) and 28 had subcortical variant presentations (14%, parkinsonism, postural instability and gait freezing variants). Across all participants, annual progression in Richardson's syndrome was faster than variant phenotypes on the Mini-Mental State Examination (-1.8 versus -0.9/year, P = 0.005) and revised Addenbrooke's Cognitive Examination (-5.3 versus -3.0/year, P = 0.01) but not the Progressive Supranuclear Palsy Rating Scale (9.0 versus 7.1/year, P = 0.2) nor the modified Progressive Supranuclear Palsy Rating Scale (2.7 versus 2.3/year, P = 0.4). However, for those with more than 1 years' follow-up, a significant difference was observed between Richardson's syndrome and variant phenotypes in Progressive Supranuclear Palsy Rating Scale (8.7 versus 6.3/year, P = 0.04). Survival was longer in variant phenotypes than Richardson's syndrome [7.3 (±3.9) versus 5.6 (±2.0) years, P = 0.02]. Pathologically confirmed cases (n = 49) supported these findings. Patients meeting basic trial-eligibility criteria (n = 129) progressed faster on the Progressive Supranuclear Palsy Rating Scale than trial-not-eligible patients (10.1 versus 6.1/year, P = 0.001). In conclusion, phenotypes other than Richardson's syndrome show slower progression and longer survival. Trial criteria do not select representative progressive supranuclear palsy cases. This has implications for trial design, and application of trial results to clinically more diverse patient populations
'It's a film' : medium specificity as textual gesture in Red road and The unloved
British cinema has long been intertwined with television. The
buzzwords of the transition to digital media, 'convergence' and
'multi-platform delivery', have particular histories in the British
context which can be grasped only through an understanding of the
cultural, historical and institutional peculiarities of the British film
and television industries. Central to this understanding must be two
comparisons: first, the relative stability of television in the duopoly
period (at its core, the licence-funded BBC) in contrast to the repeated
boom and bust of the many different financial/industrial combinations
which have comprised the film industry; and second, the cultural and
historical connotations of 'film' and 'television'. All readers of this
journal will be familiar – possibly over-familiar – with the notion that
'British cinema is alive and well and living on television'. At the end of
the first decade of the twenty-first century, when 'the end of medium
specificity' is much trumpeted, it might be useful to return to the
historical imbrication of British film and television, to explore both
the possibility that medium specificity may be more nationally specific
than much contemporary theorisation suggests, and to consider some
of the relationships between film and television manifest at a textual
level in two recent films, Red Road (2006) and The Unloved (2009)
Recommended from our members
GABAergic cortical network physiology in frontotemporal lobar degeneration.
The clinical syndromes caused by frontotemporal lobar degeneration are heterogeneous, including the behavioural variant frontotemporal dementia (bvFTD) and progressive supranuclear palsy. Although pathologically distinct, they share many behavioural, cognitive and physiological features, which may in part arise from common deficits of major neurotransmitters such as γ-aminobutyric acid (GABA). Here, we quantify the GABAergic impairment and its restoration with dynamic causal modelling of a double-blind placebo-controlled crossover pharmaco-magnetoencephalography study. We analysed 17 patients with bvFTD, 15 patients with progressive supranuclear palsy, and 20 healthy age- and gender-matched controls. In addition to neuropsychological assessment and structural MRI, participants undertook two magnetoencephalography sessions using a roving auditory oddball paradigm: once on placebo and once on 10 mg of the oral GABA reuptake inhibitor tiagabine. A subgroup underwent ultrahigh-field magnetic resonance spectroscopy measurement of GABA concentration, which was reduced among patients. We identified deficits in frontotemporal processing using conductance-based biophysical models of local and global neuronal networks. The clinical relevance of this physiological deficit is indicated by the correlation between top-down connectivity from frontal to temporal cortex and clinical measures of cognitive and behavioural change. A critical validation of the biophysical modelling approach was evidence from parametric empirical Bayes analysis that GABA levels in patients, measured by spectroscopy, were related to posterior estimates of patients' GABAergic synaptic connectivity. Further evidence for the role of GABA in frontotemporal lobar degeneration came from confirmation that the effects of tiagabine on local circuits depended not only on participant group, but also on individual baseline GABA levels. Specifically, the phasic inhibition of deep cortico-cortical pyramidal neurons following tiagabine, but not placebo, was a function of GABA concentration. The study provides proof-of-concept for the potential of dynamic causal modelling to elucidate mechanisms of human neurodegenerative disease, and explains the variation in response to candidate therapies among patients. The laminar- and neurotransmitter-specific features of the modelling framework, can be used to study other treatment approaches and disorders. In the context of frontotemporal lobar degeneration, we suggest that neurophysiological restoration in selected patients, by targeting neurotransmitter deficits, could be used to bridge between clinical and preclinical models of disease, and inform the personalized selection of drugs and stratification of patients for future clinical trials
GABAergic cortical network physiology in frontotemporal lobar degeneration.
The clinical syndromes caused by frontotemporal lobar degeneration are heterogeneous, including the behavioural variant frontotemporal dementia (bvFTD) and progressive supranuclear palsy. Although pathologically distinct, they share many behavioural, cognitive and physiological features, which may in part arise from common deficits of major neurotransmitters such as γ-aminobutyric acid (GABA). Here, we quantify the GABAergic impairment and its restoration with dynamic causal modelling of a double-blind placebo-controlled crossover pharmaco-magnetoencephalography study. We analysed 17 patients with bvFTD, 15 patients with progressive supranuclear palsy, and 20 healthy age- and gender-matched controls. In addition to neuropsychological assessment and structural MRI, participants undertook two magnetoencephalography sessions using a roving auditory oddball paradigm: once on placebo and once on 10 mg of the oral GABA reuptake inhibitor tiagabine. A subgroup underwent ultrahigh-field magnetic resonance spectroscopy measurement of GABA concentration, which was reduced among patients. We identified deficits in frontotemporal processing using conductance-based biophysical models of local and global neuronal networks. The clinical relevance of this physiological deficit is indicated by the correlation between top-down connectivity from frontal to temporal cortex and clinical measures of cognitive and behavioural change. A critical validation of the biophysical modelling approach was evidence from parametric empirical Bayes analysis that GABA levels in patients, measured by spectroscopy, were related to posterior estimates of patients' GABAergic synaptic connectivity. Further evidence for the role of GABA in frontotemporal lobar degeneration came from confirmation that the effects of tiagabine on local circuits depended not only on participant group, but also on individual baseline GABA levels. Specifically, the phasic inhibition of deep cortico-cortical pyramidal neurons following tiagabine, but not placebo, was a function of GABA concentration. The study provides proof-of-concept for the potential of dynamic causal modelling to elucidate mechanisms of human neurodegenerative disease, and explains the variation in response to candidate therapies among patients. The laminar- and neurotransmitter-specific features of the modelling framework, can be used to study other treatment approaches and disorders. In the context of frontotemporal lobar degeneration, we suggest that neurophysiological restoration in selected patients, by targeting neurotransmitter deficits, could be used to bridge between clinical and preclinical models of disease, and inform the personalized selection of drugs and stratification of patients for future clinical trials
- …