Objectives:
The aim of this study was to assess the Dutch nationwide incidence of myelin oligodendrocyte glycoprotein (MOG)-IgG-associated acquired demyelinating syndromes (ADS) and to describe the ...clinical and serological characteristics of these patients.
Methods:
All serum samples for routine diagnostics from February 2014 to December 2017 were sent to the single central reference laboratory for the full-length MOG-IgG cell-based assay (CBA) in the Netherlands. Clinical data from patients known in our National ADS centre were available.
Results:
A total of 1414 samples of 1277 patients were received; of these, 92 patients (7%) were MOG-IgG-seropositive. The mean incidence was 0.16/100,000 people, with higher seropositivity in children (0.31/100,000) than in adults (0.13/100,000). In MOG-IgG-positive patients at the National ADS centre (61/92, 66%), the most common presenting phenotype is acute disseminated encephalomyelitis (ADEM, 56%) in children and optic neuritis (ON, 44%) in adults. Relapsing disease occurred in 9/34 (26%) children and 11/27 (41%) adults during median follow-up of 27.5 months. Patients were tested MOG-IgG-positive >200 months after the initial attack, suggesting an extended time to first relapse (TTFR). Longitudinal analysis of MOG-IgG (25/61, 41%) showed that 67% of the monophasic patients remain seropositive and 60% in relapsing patients. Majority of seronegative patients had no relapses (89%).
Conclusion:
This nationwide study shows that the overall incidence of MOG-IgG-seropositive disorders is 0.16 per 100,000 people. The distribution over the clinical phenotypes differs between adults and children. Seropositivity can be maintained over years even without clinical activity, while seronegative patients generally had no relapses.
Background and purpose
Neuromyelitis optica spectrum disorders (NMOSDs) are a group of rare inflammatory demyelinating disorders of the central nervous system. The identification of specific ...antibodies directed to aquaporin 4 (AQP4‐IgG) led to the distinction from multiple sclerosis. However, up to 25% of the clinically diagnosed NMO patients are seronegative for AQP4‐IgG. A subgroup of these patients might be identified by antibodies directed to myelin oligodendrocyte glycoprotein (MOG‐IgG). Our objective was to investigate whether the clinical characteristics of these patients differ.
Methods
Using a cell‐based assay, samples of 61 AQP4‐IgG seronegative patients and 41 AQP4‐IgG seropositive patients with clinically NMOSD were analysed for the presence of MOG‐IgG. Clinical characteristics of the AQP4‐IgG, MOG‐IgG seropositive and double seronegative NMOSD patients were compared.
Results
Twenty of the 61 AQP4‐IgG seronegative patients tested MOG‐IgG seropositive (33%). MOG‐IgG seropositive patients were more frequently males in contrast to AQP4‐IgG seropositive patients (55% vs. 15%, P < 0.01) and Caucasians (90% vs. 63%, P = 0.03). They more frequently presented with coincident optic neuritis and transverse myelitis (40% vs. 12%, P = 0.02) and had a monophasic disease course (70% vs. 29%, P < 0.01). AQP4‐IgG seropositive patients were 2.4 times more likely to suffer from relapses compared with MOG‐IgG seropositive patients (relative risk 2.4, 95% confidence interval 1.2–4.7). AQP4‐IgG seropositive patients had higher Expanded Disability Status Scale levels at last follow‐up (P < 0.01).
Conclusion
Antibodies directed to MOG identify a subgroup of AQP4‐IgG seronegative NMO patients with generally a favourable monophasic disease course.
Background and purpose
Clinically isolated syndrome (CIS) is a first demyelinating event of the central nervous system and can be a single event. After CIS, a chronic disease course with ongoing ...inflammation and relapses might occur, resulting in a diagnosis of multiple sclerosis (MS). As yet, there has been no prospective exploration of whether children and adults with CIS have the same disease course.
Methods
Patients with CIS, whose age ranged from 1 to 50 years, were prospectively followed. We divided the patients into three different age groups, i.e. 1–10, 11–17 and 18–50 years old. Demographic data, disease course, time to MS diagnosis and annualized relapse rates (ARRs) were compared among these groups.
Results
We included 383 patients with CIS, of whom 218 (56.9%) were diagnosed with MS. Children of between 11 and 17 years old had the highest rate of MS conversion (83.5% vs. 50.0% in the other age groups together, P < 0.01) and the shortest time to MS diagnosis median time 2.6 months (interquartile range, 0.6–6.0) vs. 8.2 months (interquartile range, 1.9–28.2) in the other age groups together, P < 0.01). ARRs corrected for follow‐up were higher in children of <18 years old than in adults of ≥18 years old with MS (mean ARR, 0.65 vs. 0.43, P < 0.01).
Conclusion
Children with CIS tend to have a more inflammatory disease course appearing from higher ARRs in all children and the highest rate of MS conversion in 11–17‐year‐old children. This supports early initiation of disease‐modifying therapy in children, perhaps even at the first event in children at high risk for MS in line with clinical practice in adults.
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We describe and test a two-horizontal-dimension subglacial hydrology model which combines till with a distributed system of water-filled, linked cavities which open through sliding and close through ...ice creep. The addition of this sub-model to the Parallel Ice Sheet Model (PISM) accomplishes three specific goals: (a) conservation of the mass of water, (b) simulation of spatially and temporally variable basal shear stress from physical mechanisms based on a minimal number of free parameters, and (c) convergence under grid refinement. The model is a common generalization of four others: (i) the undrained plastic bed model of Tulaczyk et al. (2000b), (ii) a standard "routing" model used for identifying locations of subglacial lakes, (iii) the lumped englacial-subglacial model of Bartholomaus et al. (2011), and (iv) the elliptic-pressure-equation model of Schoof et al. (2012). We preserve physical bounds on the pressure. In steady state a functional relationship between water amount and pressure emerges. We construct an exact solution of the coupled, steady equations and use it for verification of our explicit time stepping, parallel numerical implementation. We demonstrate the model at scale by 5 year simulations of the entire Greenland ice sheet at 2 km horizontal resolution, with one million nodes in the hydrology grid.
Routine microbiological and chemical analysis of cerebrospinal fluid (CSF) is often performed to diagnose external drainage-related bacterial meningitis (ED-BM) at an early stage. A cohort study was ...performed to investigate the value of several commonly used CSF parameters for the prediction and diagnosis of ED-BM.
In a cohort of 230 consecutive patients in whom external drains had been placed, CSF samples were collected daily, prospectively evaluated for the presence of bacteria using Gram stain and microbiological culture, and analyzed for leukocyte count, protein concentration, glucose concentration, and ratio of CSF glucose to blood glucose. In addition, the CSF concentration of interleukin-6 (IL-6) was determined. The definition of ED-BM was based on positive culture results in combination with clinical symptoms. A matched case-control study was performed to evaluate the cohort longitudinally and to control for biasing factors such as duration of external drainage. External drainage-related bacterial meningitis developed in 22 patients (9.6%). Results from analyses of 1516 CSF samples showed no significant differences between the patients in whom ED-BM developed and a control group without ED-BM during the first 3 days of infection or during the 3 days preceding the infection with regard to leukocyte count, protein concentration, glucose concentration, and CSF/blood glucose ratio. No significant difference between groups was found for the CSF IL-6 concentration during the 3 days preceding the infection. In the matched case-control study, none of the parameters had significant predictive or diagnostic value for ED-BM in analyses using absolute values, ratios, and differences between the current and previous day's values. A comparison of the results from Gram stains and CSF cultures showed that the Gram staining had a very high specificity (99.9%) but a low sensitivity (18% four of 22 patients on the 1st day of infection and 60% nine of 15 patients on the 2nd day).
Severe disturbances in the CSF of patients with external drains limit the value of routine CSF analysis for prediction or diagnosis of ED-BM. Routine Gram stain of CSF has also limited predictive or diagnostic value due to its low sensitivity in screening for ED-BM.
Dry playa lake beds can be significant sources of fine dust emission. This study used a portable field wind tunnel to quantify the PM10 emissions from a bare, fine-textured playa surface located in ...the far northern Chihuahua Desert. The natural, undisturbed crust and its subjection to two levels of animal disturbance (one and ten cow passes) were tested. The wind tunnel generated dust emissions under controlled conditions for firstly an initial blow-off of the surface, followed by two longer runs with sand added to the flow as an abrader material. Dust was measured using a GRIMM particle monitor. For the study playa, no significant differences in PM10 concentration and emission flux were found between the untrampled surface and following a single animal pass. This was the case for both the initial blow-offs and tests on plots under a steady abrader rate. Significantly higher dust loading was only associated with the effect of 10 animal passes. In the blow-offs, the higer PM10 yield after 10 passes reflected the greater availability of easily entrainable fine particles. Under abrasion, the effect of the heaviest trampling increased the emission flux by a third and abrasion efficiency by around 50% more than values on the untrampled surface. This enhanced abrasion efficiency peristed for a 30 minute period under abrasion before the positive effect of the disturbance was no longer evident. The findings highlight the role of a threshold of disturbance that determines if supply-limited surfaces will exhibit enhanced wind erosion or not after undergoing perturbation.
Two enzymatically modified derivatives of tobramycin have been prepared by gentamicin nucleotidyl transferase-catalyzed adenylylation of tobramycin, using ATP and (Sp)-ATP alpha S as adenylylation ...substrates. (EC 2.7.7.46). The 1H, 13C, and 31P NMR spectra have been assigned for tobramycin, 2''-(adenosine-5'-phosphoryl)-tobramycin (TbAMP) and 2''-(adenosine-5'-thiophosphoryl)-tobramycin (TbAMPS). Several one- and two-dimensional NMR techniques have been utilized, notably, 1H-1H homonuclear correlation spectroscopy at 470 or 500 MHz and 13C-1H heteronuclear correlation spectroscopy at 50.3 MHz. The 1H assignments for tobramycin are similar to those previously reported for rings I and III of kanamycin A. The 13C assignments for tobramycin were similar to those previously reported, except for reversal of the assignments for anomeric carbons in the glycosyl rings. The 1H and 13C assignments for tobramycin were used to guide the assignments of the spectra for TbAMP and TbAMPS. Nearly complete assignments were obtained for these two derivatives of tobramycin. From the measured proton coupling constants, only small conformational changes were observed upon modification of tobramycin by adenylylation. From the proton and carbon spectra of the adenylylated derivatives the 2'' position is shown to be the site of adenylation. Large downfield shifts of the 2''proton and carbon resonances are easily observed and are more pronounced for TbAMPS than for TbAMP.
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