Background
Aquaporin-4 immunoglobulin G (AQP4-IgG) antibody-positive neuromyelitis optica spectrum disorders (NMOSD) are frequently associated with other autoimmune disorders, including systemic ...lupus erythematosus (SLE). Eculizumab (ECU) is a highly effective long-term treatment for NMOSD. However, ECU is known to increase significantly the risk of infection with encapsulated bacteria and sepsis. Recently, increased insulin resistance (IR) in patients with NMOSD has been suggested. Type B IR (TBIR) is a rare autoimmune condition often accompanying or preceding SLE. TBIR has not yet been reported in NMOSD. Objective: To report an ECU-treated patient with AQP4-IgG-positive NMOSD who developed fatal septic complications after the emergence of TBIR. Methods: Description of the clinical course over a period of 8 years. Results: A female patient was diagnosed with NMOSD at the age of 16 years. A variety of disease-modifying drugs failed to achieve sufficient disease control, resulting in severe tetraparesis. Treatment with ECU was started 6 years after NMOSD diagnosis and stabilized the disease. The patient developed TBIR 8 months after initiation of ECU therapy. Following high-dose intravenous methylprednisolone therapy for a clinical relapse and three further courses of ECU, the patient was admitted with severe pneumonia caused by the encapsulated bacterium
Klebsiella pneumoniae
and hypoglycemia. Despite multimodal therapy, the patient died from sepsis-related multiorgan failure 18 months after initiation of ECU. Conclusions: TBIR should be considered as differential diagnosis in patients with NMOSD presenting with disturbed glucose metabolism, irrespective of the presence of SLE. More real-world data are needed on the risk/benefit ratio of ECU treatment in patients who have co-existing autoimmune comorbidities that may compromise immune function. Strategies to mitigate the risk of serious infection in patients treated with ECU are discussed.
In the field of bioprocess development miniaturization, parallelization and flexibility play a key role reducing costs and time. To precisely meet these requirements, additive manufacturing ...(3D‐printing) is an ideal technology. 3D‐printing enables rapid prototyping and cost‐effective fabrication of individually designed devices with complex geometries on demand. For successful bioprocess development, monitoring of process‐relevant parameters, such as pH, dissolved oxygen (DO), and biomass, is crucial. Online monitoring is preferred as offline sampling is time‐consuming and leads to loss of information. In this study, 3D‐printed cultivation vessels with optical prisms are evaluated for the use in upstream processes of different industrially relevant microorganisms and cell lines. It was shown, that the 3D‐printed optically modified well (OMW) is of benefit for a wide range of biotechnologically relevant microorganisms and even for mammalian suspension cells. Evaluation tests with Escherichia coli, Bacillus subtilis, Saccharomyces cerevisiae, and Chinese hamster ovary (CHO) cells were performed, providing highly reproducible results. Growth behavior of OMW cultures was comparable to behavior of shake flask (SF) cultivations and the signal to noise ratio in online biomass measurement was shown to be reduced up to 95.8% by using the OMW. Especially the cultivation phases with low turbidity respective optical densities below 1.0 rel.AU could be monitored accurately for the first time. Furthermore, it was demonstrated that the 3D‐printed optics are transferable to different well geometries and sizes, enabling efficient biomass monitoring for individual requirements with tailor‐made 3D‐printed cultivation vessels in small scale.
Background
Myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD) is the most important differential diagnosis of both ...multiple sclerosis and neuromyelitis optica spectrum disorders. A recent proposal for new diagnostic criteria for MOG-EM/MOGAD explicitly recommends the use of immunoglobulin G subclass 1 (IgG1)- or IgG crystallizable fragment (Fc) region-specific assays and allows the use of heavy-and-light-chain-(H+L) specific assays for detecting MOG-IgG. By contrast, the utility of MOG-IgG3-specific testing has not been systematically evaluated.
Objective
To assess whether the use of MOG-IgG3-specific testing can improve the sensitivity of MOG-IgG testing.
Methods
Re-testing of 22 patients with a definite diagnosis of MOG-EM/MOGAD and clearly positive MOG-IgG status initially but negative or equivocal results in H+L- or Fc-specific routine assays later in the disease course (i.e. patients with spontaneous or treatment-driven seroreversion).
Results
In accordance with previous studies that had used MOG-IgG1-specific assays, IgG subclass-specific testing yielded a higher sensitivity than testing by non-subclass-specific assays. Using subclass-specific secondary antibodies, 26/27 supposedly seroreverted samples were still clearly positive for MOG-IgG, with MOG-IgG1 being the most frequently detected subclass (25/27 93% samples). However, also MOG-IgG3 was detected in 14/27 (52%) samples (from 12/22 55% patients). Most strikingly, MOG-IgG3 was the predominant subclass in 8/27 (30%) samples (from 7/22 32% patients), with no unequivocal MOG-IgG1 signal in 2 and only a very weak concomitant MOG-IgG1 signal in the other six samples. By contrast, no significant MOG-IgG3 reactivity was seen in 60 control samples (from 42 healthy individuals and 18 patients with MS). Of note, MOG-IgG3 was also detected in the only patient in our cohort previously diagnosed with MOG-IgA
+
/IgG
–
MOG-EM/MOGAD, a recently described new disease subvariant. MOG-IgA and MOG-IgM were negative in all other patients tested.
Conclusions
In some patients with MOG-EM/MOGAD, MOG-IgG is either exclusively or predominantly MOG-IgG3. Thus, the use of IgG1-specific assays might only partly overcome the current limitations of MOG-IgG testing and—just like H+L- and Fcγ-specific testing—might overlook some genuinely seropositive patients. This would have potentially significant consequences for the management of patients with MOG-EM/MOGAD. Given that IgG3 chiefly detects proteins and is a strong activator of complement and other effector mechanisms, MOG-IgG3 may be involved in the immunopathogenesis of MOG-EM/MOGAD. Studies on the frequency and dynamics as well as the clinical and therapeutic significance of MOG-IgG3 seropositivity are warranted.
Silicon detectors produced from materials with different resistivities and oxygen concentrations have been irradiated with energetic neutrons, protons and pions. Isothermal annealing studies have ...shown correlation between microscopic defect evolution and the macroscopic detector performance. It was found that the annealing behavior of the electron traps attributed to the single and double charged divacancy is strongly related to the current related damage parameter
α. In both cases the isothermal evolution is independent of the oxygen and doping concentration in the material under investigation (
2×10
14<
O<10
18
cm
−3
and
10
12<
P<4×10
13
cm
−3
) and the absolute values do not depend on the particles used for the irradiation provided the fluence is properly normalized by the nonionizing energy loss (NIEL). In contrast to this result the introduction rates of the observed point defects VO
i and C
iC
s were however found to depend on the particle type. Thus clear indication is given that the generation of point defects does not scale with NIEL. Compared to neutron irradiated samples the introduction rate after irradiation with charged hadrons was found to be higher by a factor around 2.
Micro structuring of glassy carbon (GC) can be performed by various methods such as sawing, laser ablation, and reactive ion etching (RIE). Our combined laser and reactive ion etching process ...comprises a laser mask writing step in a sputter-deposited metal layer and a pattern transfer step performed by reactive ion etching. The laser mask writing is achieved by a XeCl laser (308 nm) and a computer controlled setup that allows flexible variation of the pattern. The layout input from plotter files (HPGL) and the writing speed of up to 1 mm/s make this method suitable for rapid prototyping. Subsequent reactive ion etching in oxygen plasma results in channels with trapezoid cross-section, a depth of ∼100 μm, and aspect ratios ∼1.5. A complete flow field with a size of 1 cm2, consisting of 5 meandering channels with a depth of 72 μm and a top width of 59 μm, was prepared for micro fuel cell operation.
Structuring of glassy carbon (GC) can be performed by various methods such as sawing, laser ablation, and reactive ion etching (RIE). Laser machining with a tripled Nd:YAG laser at an irradiation ...wavelength of 355 nm allows the fabrication of V-shaped channels with depths >600 μm and aspect ratios >5. This method is very flexible for rapid prototyping, but is comparatively slow due to the sequential machining. A complete flowfield consisting of 100 parallel channels with a depth of 250 μm and a top width of 50 μm was prepared by direct laser ablation and tested in a micro fuel cell. As an alternative, a novel process combining laser structuring of a metal mask with subsequent reactive ion etching was developed. The quality of the metal layer and the ablation behavior are strongly influenced by the metal adhesion, which depends on the GC pretreatment and the deposition technique. Reactive ion etching of glassy carbon can be performed with etch rates of ≈40 μm h−1, but the high pressure conditions of 100 mTorr (0.13 mbar) limit the aspect ratio to <1.5 due to pronounced underetching. The fabrication of structures with aspect ratios >4 and etch rates of ≈10 μm h−1 is possible with the use of alternative etching devices with different design or plasma sources.
Diffusion-weighted imaging (DWI) has become an important component in modern stroke imaging. This MR technique detects diffusion abnormalities, which can be quantified by computing apparent diffusion ...coefficient (ADC) maps. ADC values are typically calculated from a set of MR images obtained with varying degrees of diffusion weighting (b-values) using nonlinear regression. However, there is no agreement concerning the number of images needed for ADC calculation. The aim of our study was to determine how many b-values are necessary to reliably calculate ADC maps.
In 100 consecutive patients with clinical signs of acute ischemic stroke, 6 identically oriented and centered diffusion data sets with different b-values were acquired. ROI analysis was performed for DWI-positive lesions, normal-appearing gray and white matter, CSF, and background noise. ADC values for each ROI were calculated using a nonlinear regression model. Additionally, the CNR and SNR were calculated for each ROI.
Acquisition time was 0:39 min for 2 b-values and up to 2:49 min for a sequence with 7 b-values. The mean ADC (× 10(-3) mm2/s) for ischemic lesions was 58.29, 58.47, 57.83, 57.81, 57.58 and 54.51 using 2, 3, 4, 5, 6, and 7 b-values. Ischemic lesions had significantly different mean ADC values only for high b-values (b = 2000 s/mm2).
ADC values can be reliably calculated using 2 b-values. Radiologists may use the more time-efficient 2-point method for reliably estimating ADC values and detecting ischemic lesions in the daily clinical routine.
The active layer of gas diffusion electrodes, widely used in low temperature polymer electrolyte fuel cells, contains either metal-blacks (mostly Pt-black) or metallic nanoparticles (mostly Pt ...particles or Pt based alloy particles) supported on high surface area carbon. Depending on the nature of the catalyst in the active layer and the applied pretreatment of the gas diffusion electrodes, cyclic voltammetry reveals varying H-adsorption/desorption characteristics and catalyst surface utilization properties. Our aim was the development of model electrodes with defined surface geometry and platinum distribution pattern, which exhibit electrocatalytic effects equal to the ones observed on gas diffusion electrodes with different active layers like e.g., Pt on carbon or Pt-black. We describe the successful application of microstructured glassy carbon model electrodes. These models allow a correlation between the electrochemically determined platinum surface area and the different parts of the model electrode. Differences in catalyst surface utilization depending on the different distribution patterns can then be determined quantitatively and related directly to differences of the structured electrodes. Possible H-adsorption and diffusion mechanisms are discussed, which could serve as an explanation for the observed effects.
The annealing of the cluster damage after fast neutron and high energy /spl pi//sup +/-pion irradiations is studied employing the deep-level transient spectroscopy (DLTS) method. The clusters consist ...mainly of divacancies. However, other unidentified defects contribute to the signal of the single negative charge state of the divacancy. The unidentified defects are located in the cluster region. Strain and deformation fields are assumed to change the emission parameters of the defects in the cluster region resulting in a distribution of energy states. Simulations of the DLTS signals, which take into account an exponential density distribution of energy states, were carried out. During annealing a decay of divacancies and the other unidentified defects is observed.
The pyroelectric and piezoelectric properties of thick PZT films processed via a new sol–gel method are being investigated. The films were deposited on gold-coated alumina substrates. The ...pyroelectric properties are being evaluated using pyrodynamic measurements with either a laser or thermoelectric heat source. The pyroelectric coefficient is obtained from pyroelectric current measurements. The piezoelectric properties are being measured using a laser vibrometer-lock-in amplifier set-up. It is shown that the pyroelectric coefficient obtained with laser heating lies in the range of 108
μC/m
2
K, whereas heating from the rear of the specimen with the thermoelectric element lead to a value of in the range of 350
μC/m
2
K. These results are explained in terms through thickness temperature gradients. The piezoelectric displacement amplitude versus applied voltage shows a no-linear behaviour, which is explained in terms of materials chemistry. The maximum effective piezoelectric coefficient,
d
33, is obtained as 340
pm/V, and is superior to the values known for ferroelectric thin films.
