IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord. It is considered a severe variant of multiple sclerosis (MS), and frequently is misdiagnosed as MS, but prognosis and optimal treatments differ. A serum immunoglobulin G autoantibody (NMO-IgG) serves as a specific marker for NMO. Here we show that NMO-IgG binds selectively to the aquaporin-4 water channel, a component of the dystroglycan protein complex located in astrocytic foot processes at the blood-brain barrier. NMO may represent the first example of a novel class of autoimmune channelopathy

Concordance between a neuroradiologist, a consultant radiologist and trained reporting radiographers interpreting MRI head examinations: An empirical study

Introduction: This study assessed agreement between MRI reporting radiographers and a consultant radiologist compared with an index neuroradiologist when reporting MRI head (brain/internal auditory meati [IAMs]) examinations. The effect on patient management of any discordant reports was also examined. Methods: Two trained MRI reporting radiographers (RRs), a consultant radiologist (CR) and an index neuroradiologist (INR) reported on a random sample of 210 MRI examinations. The radiographers reported during clinical practice and the radiologists in clinical practice conditions. Two independent consultant physicians (neuro-rehabilitation and neuropsychiatry) compared these reports with the index neuroradiologist report for agreement and the clinical importance of discrepant reports. Results: Overall observer agreement between the RRs and CR was comparable in relation to agreement with the INR: RR; 93/210 (44.3%); and the CR; 83/210 (39.4%) for all head MRI examinations (p = 0.32). For brain examinations the difference was similar: RR; 64/180 (35.6%); and CR; 54/190 (30.0%), p = 0.26. Agreement rates for the IAMs examinations were identical, 29/30 (97.7%). For all head MRI examinations (n = 210) there was a very small observed difference of <0.5% in mean agreement between the reporting radiographers and the consultant radiologist (p = 0.92) for examinations where a major disagreement would have been likely to have led to a change in patient management. Conclusion: MRI reporting radiographers reported during clinical practice on MRI head examinations to a level of agreement comparable with a consultant radiologist. Implications for practice: This is an area in which radiographers could provide additional reporting roles to the reporting service to increase capacity. Wider potential benefits include cost-effectiveness and role development/retention of radiographers

Communal irrigation systems in South-Eastern Africa: findings on productivity and profitability

Significant expansion of irrigated agriculture is planned in Africa, though existing smallholder schemes perform poorly. Research at six schemes in Mozambique, Tanzania and Zimbabwe shows that a range of problems are exacerbated by poor management, with limited market linkages leading to underutilization and a lack of profit. Improving sustainability of these complex systems will require: multiple interventions at different scales; investing in people and institutions as much as hardware; clarity in governments’ objectives for their smallholder irrigation schemes; appropriate business models to enable farmers; and better market linkages

Disruption of the leptomeningeal blood barrier in neuromyelitis optica spectrum disorder

OBJECTIVE: To describe leptomeningeal blood-barrier impairment reflected by MRI gadolinium-enhanced lesions in patients with aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD). METHODS: A retrospective case series of 11 AQP4-IgG-positive NMOSD patients with leptomeningeal enhancement (LME) were collected from 5 centers. External neuroradiologists, blinded to the clinical details, evaluated MRIs. RESULTS: LME was demonstrated on postcontrast T1-weighted and fluid-attenuated inversion recovery images as a sign of leptomeningeal blood-barrier disruption and transient leakage of contrast agent into the subarachnoid space in 11 patients, 6 in the brain and 6 in the spinal cord. The patterns of LME were linear or extensive and were accompanied by periependymal enhancement in 5 cases and intraparenchymal enhancement in all cases. The location of LME in the spinal cord was adjacent to intraparenchymal contrast enhancement with involvement of a median number of 12 (range 5-17) vertebral segments. At the time of LME on MRI, all patients had a clinical attack such as encephalopathy (36%) and/or myelopathy (70%) with median interval between symptom onset and LME of 12 days (range 2-30). LME occurred in association with an initial area postrema attack (44%), signs of systemic infection (33%), or AQP4-IgG in CSF (22%) followed by clinical progression. LME was found at initial clinical presentation in 5 cases and at clinical relapses leading to a diagnosis of NMOSD in 6 cases. CONCLUSION: This study suggests that altered leptomeningeal blood barrier may be accompanied by intraparenchymal blood-brain barrier breakdown in patients with AQP4-IgG-positive NMOSD during relapses

Dreaming of drams: Authenticity in Scottish whisky tourism as an expression of unresolved Habermasian rationalities

In this paper, the production of whisky tourism at both independently owned and corporately owned distilleries in Scotland is explored by focusing on four examples (Arran, Glengoyne, Glenturret and Bruichladdich). In particular, claims of authenticity and Scottishness of Scottish whiskies through commercial materials, case studies, website-forum discussions and 'independent' writing about such whisky are analysed. It is argued that the globalisation and commodification of whisky and whisky tourism, and the communicative backlash to these trends typified by the search for authenticity, is representative of a Habermasian struggle between two irreconcilable rationalities. This paper will demonstrate that the meaning and purpose of leisure can be understood through such explorations of the tension between the instrumentality of commodification and the freedom of individuals to locate their own leisure lives in the lifeworld that remains. © 2011 Taylor & Francis

Prognosis of the individual course of disease - steps in developing a decision support tool for Multiple Sclerosis

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis is a chronic disease of uncertain aetiology. Variations in its disease course make it difficult to impossible to accurately determine the prognosis of individual patients. The Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR) developed an "online analytical processing (OLAP)" tool that takes advantage of extant clinical trials data and allows one to model the near term future course of this chronic disease for an individual patient.</p> <p>Results</p> <p>For a given patient the most similar patients of the SLCMSR database are intelligently selected by a model-based matching algorithm integrated into an OLAP-tool to enable real time, web-based statistical analyses. The underlying database (last update April 2005) contains 1,059 patients derived from 30 placebo arms of controlled clinical trials. Demographic information on the entire database and the portion selected for comparison are displayed. The result of the statistical comparison is provided as a display of the course of Expanded Disability Status Scale (EDSS) for individuals in the database with regions of probable progression over time, along with their mean relapse rate. Kaplan-Meier curves for time to sustained progression in the EDSS and time to requirement of constant assistance to walk (EDSS 6) are also displayed. The software-application OLAP anticipates the input MS patient's course on the basis of baseline values and the known course of disease for similar patients who have been followed in clinical trials.</p> <p>Conclusion</p> <p>This simulation could be useful for physicians, researchers and other professionals who counsel patients on therapeutic options. The application can be modified for studying the natural history of other chronic diseases, if and when similar datasets on which the OLAP operates exist.</p

The Code large-scale meteorological, sea surface temperature, and coastal sea level data set, 1980-84

Meteorological, sea surface temperature, and coastal sea level data were collected along the west coast of North America from northern Baja California to the Alaska/British Columbia border from 1980 to mid-1984 for the large-scale component of the Coastal Ocean Dynamics Experiment (CODE). This report presents statistical summaries and plots of selected meteorological variables, sea surface temperature, and coastal sea level from this data set

Aquaporin-4–binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2

Neuromyelitis optica (NMO)-immunoglobulin G (IgG) is a clinically validated serum biomarker that distinguishes relapsing central nervous system (CNS) inflammatory demyelinating disorders related to NMO from multiple sclerosis. This autoantibody targets astrocytic aquaporin-4 (AQP4) water channels. Clinical, radiological, and immunopathological data suggest that NMO-IgG might be pathogenic. Characteristic CNS lesions exhibit selective depletion of AQP4, with and without associated myelin loss; focal vasculocentric deposits of IgG, IgM, and complement; prominent edema; and inflammation. The effect of NMO-IgG on astrocytes has not been studied. In this study, we demonstrate that exposure to NMO patient serum and active complement compromises the membrane integrity of CNS-derived astrocytes. Without complement, astrocytic membranes remain intact, but AQP4 is endocytosed with concomitant loss of Na+-dependent glutamate transport and loss of the excitatory amino acid transporter 2 (EAAT2) . Our data suggest that EAAT2 and AQP4 exist in astrocytic membranes as a macromolecular complex. Transport-competent EAAT2 protein is up-regulated in differentiating astrocyte progenitors and in nonneural cells expressing AQP4 transgenically. Marked reduction of EAAT2 in AQP4-deficient regions of NMO patient spinal cord lesions supports our immunocytochemical and immunoprecipitation data. Thus, binding of NMO-IgG to astrocytic AQP4 initiates several potentially neuropathogenic mechanisms: complement activation, AQP4 and EAAT2 down-regulation, and disruption of glutamate homeostasis

CDR2 and CDR2L line blot performance in PCA-1/anti-Yo paraneoplastic autoimmunity

BackgroundPurkinje cytoplasmic autoantibody type 1 (PCA-1)/anti-Yo autoimmunity is a common high-risk paraneoplastic neurological disorder, traditionally attributed antigenically to cerebellar degeneration–related protein 2 (CDR2), predominantly affecting women with gynecologic or breast adenocarcinoma. Single-modality CDR2 testing may produce false-positive results. We assessed the performance characteristics of the more recently purported major PCA-1/Yo antigen, CDR2-like (CDR2L), side by side with CDR2, in a line blot format.MethodsCDR2 and CDR2L were tested in six specimen groups (serum and cerebrospinal fluid (CSF)). Group 1, PCA-1/Yo mouse brain indirect immunofluorescence assay (IFA) positives; Group 2, PCA-1/Yo IFA mimics; Group 3, suspected CDR2 line blot false positives; Group 4, consecutive patient samples tested for neural antibodies over 1 year; Group 5, healthy subject serums; and Group 6, polyclonal (non-specific) immunoglobulin G (IgG)-positive serums.ResultsGroup 1: Of 64 samples tested, all but two were CDR2 positive (both CSF samples) and all were CDR2L positive. In individual patients, CDR2L values were always higher than CDR2. The two “CDR2L-only” positives were CSF samples with low titer PCA-1/Yo by IFA with serum negativity but with typical clinical phenotype. Group 2: All 51 PCA-1/Yo mimics were CDR2/CDR2L negative. Group 3: Nine samples [six of 1289 (0.47%) serums and three of 700 CSF samples (0.43%) were PCA-1/Yo IFA negative/CDR2 positive; two of the six available (serums from the same patient) were also CDR2L positive; the other four CDR2L negative had low CDR2 values (17–22). Group 4: Twenty-two patients had unexpected CDR2 or CDR2L positivity; none had tissue IFA positivity. Eleven of the 2,132 serum (0.5%) and three of the 677 CSF (0.4%) samples were CDR2 positive; median value was 19 (range, 11–48). Seven of the 2,132 serum (0.3%) and three of the 677 CSF (0.4%) samples were CDR2L positive; median value was 18 (range, 11–96). Group 5: All 151 healthy serum samples were negative. Group 6: One of the 46 polyclonal serum samples was CDR2L positive. Optimum overall performance was accomplished by requiring both CDR2 and CDR2L positivity in serum (sensitivity, 100%; and specificity, 99.9%) and positivity for CDR2L in CSF (sensitivity, 100%; and specificity, 99.6%).ConclusionCDR2L provides additional PCA-1/anti-Yo sensitivity in CSF, and dual positivity with CDR2 provides additional specificity assurance in serum. Combining antigen-specific and tissue-based assays optimizes PCA-1/anti-Yo testing

A valoração da pesca em águas continentais

A pesca tem sido, e provavelmente continuará sendo, uma importante fonte de alimento e renda para sociedade. Nesse trabalho os autores mostram que o valor econômico total da pesca nem sempre é reconhecido. O valor econômico total (VET) em rios pode ser dividido em valor de uso direto e valor de não-uso/valor de preservação. VET é a soma de todos os valores de uso e não uso, não importando como são derivados. Os autores mostram que há extrema dificuldade de valorar o valor econômico total o que resultado na baixa valoração da pesca para o setor como um todo. A falta de progresso neste campo é resultado do fraco diálogo entre cientistas e os gestores com os especialistas em economia ambiental e ecológica. A importância integral da pesca pode ser abordada a partir do ponto de vista das populações tradicionais e seu modo de vida que depende de vários recursos naturais. A integração de estudos sobre a pesca precisam ser promovida para incentivar o uso sustentável dos recursos aquáticos em geral e da pesca fluvial, em particular e para trazer à luz a real importância do setor pesqueiro para a sociedade