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NMR standardization approach that uses the 2H integral of deuterated solvent for quantitative multinuclear analysis of pharmaceuticals is described. As a proof of principle, the existing NMR procedure for the analysis of heparin products according to US Pharmacopeia monograph is extended to the determination of Na+ and Cl- content in this matrix. Quantification is performed based on the ratio of a 23Na (35Cl) NMR integral and 2H NMR signal of deuterated solvent, D2O, acquired using the specific spectrometer hardware. As an alternative, the possibility of 133Cs standardization using the addition of Cs2CO3 stock solution is shown. Validation characteristics (linearity, repeatability, sensitivity) are evaluated. A holistic NMR profiling of heparin products can now also be used for the quantitative determination of inorganic compounds in a single analytical run using a single sample. In general, the new standardization methodology provides an appealing alternative for the NMR screening of inorganic and organic components in pharmaceutical products.
Although several successful applications of benchtop nuclear magnetic resonance (NMR) spectroscopy in quantitative mixture analysis exist, the possibility of calibration transfer remains mostly unexplored, especially between high- and low-field NMR. This study investigates for the first time the calibration transfer of partial least squares regressions [weight average molecular weight (Mw) of lignin] between high-field (600 MHz) NMR and benchtop NMR devices (43 and 60 MHz). For the transfer, piecewise direct standardization, calibration transfer based on canonical correlation analysis, and transfer via the extreme learning machine auto-encoder method are employed. Despite the immense resolution difference between high-field and low-field NMR instruments, the results demonstrate that the calibration transfer from high- to low-field is feasible in the case of a physical property, namely, the molecular weight, achieving validation errors close to the original calibration (down to only 1.2 times higher root mean square errors). These results introduce new perspectives for applications of benchtop NMR, in which existing calibrations from expensive high-field instruments can be transferred to cheaper benchtop instruments to economize.
Das Gesundheitswesen ist konfrontiert mit steigenden Kosten und einer immer schwieriger werdenden Personalsituation. Zeitgleich versprechen moderne Sprachsteuerungssysteme Prozesse in Arztpraxen und Krankenhäusern zu verschlanken und Vorgänge zu beschleunigen. Dennoch wird derzeit der Einsatz von Sprachsteuerungssystemen in Arztpraxen oder Krankenhäusern nur selten beobachtet, was auch an den besonders strengen Datenschutzauflagen der Datenschutzgrundverordnung (DSGVO) liegt. Darüber hinaus wirft die niedrige Nutzungsrate die Frage nach den konkreten Anforderungen und ihrer Umsetzbarkeit auf, was durch den vorliegenden Beitrag adressiert wird, indem die Ergebnisse von Interviews mit acht medizinischen Fachexperten ausgewertet werden. Ergänzend wird die technische Umsetzbarkeit einzelner Anforderungen mit unterschiedlichen Cloud-Anbietern erprobt.
We study the possibility to fabricate an arbitrary phase mask in a one-step laser-writing process inside the volume of an optical glass substrate. We derive the phase mask from a Gerchberg–Saxton-type algorithm as an array and create each individual phase shift using a refractive index modification of variable axial length. We realize the variable axial length by superimposing refractive index modifications induced by an ultra-short pulsed laser at different focusing depth. Each single modification is created by applying 1000 pulses with 15 μJ pulse energy at 100 kHz to a fixed spot of 25 μm diameter and the focus is then shifted axially in steps of 10 μm. With several proof-of-principle examples, we show the feasibility of our method. In particular, we identify the induced refractive index change to about a value of Δn=1.5⋅10−3. We also determine our current limitations by calculating the overlap in the form of a scalar product and we discuss possible future improvements.
This study addresses a proof-of-concept experiment with a biocompatible screen-printed carbon electrode deposited onto a biocompatible and biodegradable substrate, which is made of fibroin, a protein derived from silk of the Bombyx mori silkworm. To demonstrate the sensor performance, the carbon electrode is functionalized as a glucose biosensor with the enzyme glucose oxidase and encapsulated with a silicone rubber to ensure biocompatibility of the contact wires. The carbon electrode is fabricated by means of thick-film technology including a curing step to solidify the carbon paste. The influence of the curing temperature and curing time on the electrode morphology is analyzed via scanning electron microscopy. The electrochemical characterization of the glucose biosensor is performed by amperometric/voltammetric measurements of different glucose concentrations in phosphate buffer. Herein, systematic studies at applied potentials from 500 to 1200 mV to the carbon working electrode (vs the Ag/AgCl reference electrode) allow to determine the optimal working potential. Additionally, the influence of the curing parameters on the glucose sensitivity is examined over a time period of up to 361 days. The sensor shows a negligible cross-sensitivity toward ascorbic acid, noradrenaline, and adrenaline. The developed biocompatible biosensor is highly promising for future in vivo and epidermal applications.
Retinal vessels are similar to cerebral vessels in their structure and function. Moderately low oscillation frequencies of around 0.1 Hz have been reported as the driving force for paravascular drainage in gray matter in mice and are known as the frequencies of lymphatic vessels in humans. We aimed to elucidate whether retinal vessel oscillations are altered in Alzheimer's disease (AD) at the stage of dementia or mild cognitive impairment (MCI). Seventeen patients with mild-to-moderate dementia due to AD (ADD); 23 patients with MCI due to AD, and 18 cognitively healthy controls (HC) were examined using Dynamic Retinal Vessel Analyzer. Oscillatory temporal changes of retinal vessel diameters were evaluated using mathematical signal analysis. Especially at moderately low frequencies around 0.1 Hz, arterial oscillations in ADD and MCI significantly prevailed over HC oscillations and correlated with disease severity. The pronounced retinal arterial vasomotion at moderately low frequencies in the ADD and MCI groups would be compatible with the view of a compensatory upregulation of paravascular drainage in AD and strengthen the amyloid clearance hypothesis.
Edge-based and face-based smoothed finite element methods (ES-FEM and FS-FEM, respectively) are modified versions of the finite element method allowing to achieve more accurate results and to reduce sensitivity to mesh distortion, at least for linear elements. These properties make the two methods very attractive. However, their implementation in a standard finite element code is nontrivial because it requires heavy and extensive modifications to the code architecture. In this article, we present an element-based formulation of ES-FEM and FS-FEM methods allowing to implement the two methods in a standard finite element code with no modifications to its architecture. Moreover, the element-based formulation permits to easily manage any type of element, especially in 3D models where, to the best of the authors' knowledge, only tetrahedral elements are used in FS-FEM applications found in the literature. Shape functions for non-simplex 3D elements are proposed in order to apply FS-FEM to any standard finite element.
The mechanical behavior of the large intestine beyond the ultimate stress has never been investigated. Stretching beyond the ultimate stress may drastically impair the tissue microstructure, which consequently weakens its healthy state functions of absorption, temporary storage, and transportation for defecation. Due to closely similar microstructure and function with humans, biaxial tensile experiments on the porcine large intestine have been performed in this study. In this paper, we report hyperelastic characterization of the large intestine based on experiments in 102 specimens. We also report the theoretical analysis of the experimental results, including an exponential damage evolution function. The fracture energies and the threshold stresses are set as damage material parameters for the longitudinal muscular, the circumferential muscular and the submucosal collagenous layers. A biaxial tensile simulation of a linear brick element has been performed to validate the applicability of the estimated material parameters. The model successfully simulates the biomechanical response of the large intestine under physiological and non-physiological loads.
Image reconstruction analysis for positron emission tomography with heterostructured scintillators
(2022)
The concept of structure engineering has been proposed for exploring the next generation of radiation detectors with improved performance. A TOF-PET geometry with heterostructured scintillators with a pixel size of 3.0×3.1×15 mm3 was simulated using Monte Carlo. The heterostructures consisted of alternating layers of BGO as a dense material with high stopping power and plastic (EJ232) as a fast light emitter. The detector time resolution was calculated as a function of the deposited and shared energy in both materials on an event-by-event basis. While sensitivity was reduced to 32% for 100 μm thick plastic layers and 52% for 50 μm, the CTR distribution improved to 204±49 ps and 220±41 ps respectively, compared to 276 ps that we considered for bulk BGO. The complex distribution of timing resolutions was accounted for in the reconstruction. We divided the events into three groups based on their CTR and modeled them with different Gaussian TOF kernels. On a NEMA IQ phantom, the heterostructures had better contrast recovery in early iterations. On the other hand, BGO achieved a better contrast to noise ratio (CNR) after the 15th iteration due to the higher sensitivity. The developed simulation and reconstruction methods constitute new tools for evaluating different detector designs with complex time responses.