Improving the sensitivity of myelin oligodendrocyte glycoprotein-antibody testing: exclusive or predominant MOG-IgG3 seropositivity-a potential diagnostic pitfall in patients with MOG-EM/MOGAD.

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.

Experimental Realization of Nonunitary Multiqubit Operations.

We demonstrate a novel experimental tool set that enables irreversible multiqubit operations on a quantum platform. To exemplify our approach, we realize two elementary nonunitary operations: the or and nor gates. The electronic states of two trapped ^{40}Ca^{+} ions encode the logical information, and a cotrapped ^{88}Sr^{+} ion provides the irreversibility of the gate by a dissipation channel through sideband cooling. We measure 87% and 81% success rates for the or and nor gates, respectively. The presented methods are a stepping stone toward other nonunitary operations such as in quantum error correction and quantum machine learning.

Local probe of single phonon dynamics in warm ion crystals.

The detailed characterization of non-trivial coherence properties of composite quantum systems of increasing size is an indispensable prerequisite for scalable quantum computation, as well as for understanding non-equilibrium many-body physics. Here, we show how autocorrelation functions in an interacting system of phonons as well as the quantum discord between distinct degrees of freedoms can be extracted from a small controllable part of the system. As a benchmark, we show this in chains of up to 42 trapped ions, by tracing a single phonon excitation through interferometric measurements of only a single ion in the chain. We observe the spreading and partial refocusing of the excitation in the chain, even on a background of thermal excitations. We further show how this local observable reflects the dynamical evolution of quantum discord between the electronic state and the vibrational degrees of freedom of the probe ion.

Cryogenic setup for trapped ion quantum computing.

We report on the design of a cryogenic setup for trapped ion quantum computing containing a segmented surface electrode trap. The heat shield of our cryostat is designed to attenuate alternating magnetic field noise, resulting in 120 dB reduction of 50 Hz noise along the magnetic field axis. We combine this efficient magnetic shielding with high optical access required for single ion addressing as well as for efficient state detection by placing two lenses each with numerical aperture 0.23 inside the inner heat shield. The cryostat design incorporates vibration isolation to avoid decoherence of optical qubits due to the motion of the cryostat. We measure vibrations of the cryostat of less than ±20 nm over 2 s. In addition to the cryogenic apparatus, we describe the setup required for an operation with 40Ca+ and 88Sr+ ions. The instability of the laser manipulating the optical qubits in 40Ca+ is characterized by yielding a minimum of its Allan deviation of 2.4 ⋅ 10-15 at 0.33 s. To evaluate the performance of the apparatus, we trapped 40Ca+ ions, obtaining a heating rate of 2.14(16) phonons/s and a Gaussian decay of the Ramsey contrast with a 1/e-time of 18.2(8) ms.

Plasmonic-organic hybrid (POH) modulators for OOK and BPSK signaling at 40 Gbit/s.

We report on high-speed plasmonic-organic hybrid Mach-Zehnder modulators comprising ultra-compact phase shifters with lengths as small as 19 µm. Choosing an optimum phase shifter length of 29 µm, we demonstrate 40 Gbit/s on-off keying (OOK) modulation with direct detection and a BER < 6 × 10(-4). Furthermore, we report on a 29 µm long binary-phase shift keying (BPSK) modulator and show that it operates error-free (BER < 1 × 10(-10)) at data rates up to 40 Gbit/s and with an energy consumption of 70 fJ/bit.

Influence of local hemostatic and antiplatelet agents on the incidence of bleeding complications in carotid endarterectomies.

BACKGROUND: For the reduction of cardio- and cerebrovascular events in carotid endarterectomies continuation of antiplatelet medication is recommended perioperatively. As a result, this patient population is at increased risk for postoperative bleeding complications. Intraoperative application of local hemostatic agents might reduce the incidence of bleeding complications. MATERIAL AND METHODS: All 565 patients undergoing carotid endarterectomy between January 2005 and January 2011 were analysed retrospectively. Most patients in the earlier cohort years of the study had no perioperative antiplatelet medication. In contrast antiplatelet medication was usually continued perioperatively in the later cohort years. To reduce the risk of perioperative bleeding local hemostatic agents were applied increasingly. RESULTS: Revision surgery, due to postoperative bleeding or massive hematoma, was necessary in 20 cases (3.5 %). Overall, 383 carotid endarterectomies (67.8 %) were performed with perioperative antiplatelet medication. Local hemostatic agents were applied in 259 cases (45.8 %) intraoperatively. Initially, operations performed in patients taking antiplatelet medication resulted in an increased need for surgical revision. Following an accelerated practice of using local hemostatic agents, the need for revision surgeries fell. Nevertheless, when patients from all years were analysed together there was no significant benefit from the application of local hemostatic agents. CONCLUSION: Application of local hemostatic agents might have contributed to a reduction of bleeding complications in carotid endarterectomies. However, this could not be shown of statistical significance. Other confounding factors such as different operative techniques or forms of anesthesia might also have influenced this decline.

Full flex-grid asynchronous multiplexing demonstrated with Nyquist pulse-shaping.

We demonstrate full flex-grid operation with Nyquist frequency division multiplexing. The technique supports high spectral efficiency, asynchronous operation of channels, variable channel loading with different modulation formats and dynamic bandwidth allocation. Data from different sources with different bit and symbol rates are encoded onto electrical Nyquist pulses with different electrical subcarrier frequencies, and then transmitted optically. We give details on the transceiver design with digital signal processing and investigate the implementation penalty as a function of several design parameters such as limited filter length and effective number of bits. Finally, experiments are performed for receivers with direct detection, intradyne and remote heterodyne reception.

Quantum computations on a topologically encoded qubit.

The construction of a quantum computer remains a fundamental scientific and technological challenge because of the influence of unavoidable noise. Quantum states and operations can be protected from errors through the use of protocols for quantum computing with faulty components. We present a quantum error-correcting code in which one qubit is encoded in entangled states distributed over seven trapped-ion qubits. The code can detect one bit flip error, one phase flip error, or a combined error of both, regardless on which of the qubits they occur. We applied sequences of gate operations on the encoded qubit to explore its computational capabilities. This seven-qubit code represents a fully functional instance of a topologically encoded qubit, or color code, and opens a route toward fault-tolerant quantum computing.

Timing, carrier frequency and phase recovery for OFDM and Nyquist signals using a mean modulus algorithm.

Efficient algorithms for timing, carrier frequency and phase recovery of Nyquist and OFDM signals are introduced and experimentally verified. The algorithms exploit the statistical properties of the received signals to efficiently derive the optimum sampling time, the carrier frequency offset, and the carrier phase. Among the proposed methods, the mean modulus algorithm (MMA) shows a very robust performance at reduced computational complexity. This is especially important for optical communications where data rates can exceed 100 Gbit/s per wavelength. All proposed algorithms are verified by simulations and by experiments using optical M-ary QAM Nyquist and OFDM signals with data rates up to 84 Gbit/s.

Silicon-organic hybrid (SOH) frequency comb sources for terabit/s data transmission.

We demonstrate frequency comb sources based on silicon-organic hybrid (SOH) electro-optic modulators. Frequency combs with line spacings of 25 GHz and 40 GHz are generated, featuring flat-top spectra with less than 2 dB power variations over up to 7 lines. The combs are used for WDM data transmission at terabit/s data rates and distances of up to 300 km.

Real-time Nyquist signaling with dynamic precision and flexible non-integer oversampling.

We demonstrate two efficient processing techniques for Nyquist signals, namely computation of signals using dynamic precision as well as arbitrary rational oversampling factors. With these techniques along with massively parallel processing it becomes possible to generate and receive high data rate Nyquist signals with flexible symbol rates and bandwidths, a feature which is highly desirable for novel flexgrid networks. We achieved maximum bit rates of 252 Gbit/s in real-time.

Low-power silicon-organic hybrid (SOH) modulators for advanced modulation formats.

We demonstrate silicon-organic hybrid (SOH) electro-optic modulators that enable quadrature phase-shift keying (QPSK) and 16-state quadrature amplitude modulation (16QAM) with high signal quality and record-low energy consumption. SOH integration combines highly efficient electro-optic organic materials with conventional silicon-on-insulator (SOI) slot waveguides, and allows to overcome the intrinsic limitations of silicon as an optical integration platform. We demonstrate QPSK and 16QAM signaling at symbol rates of 28 GBd with peak-to-peak drive voltages of 0.6 V(pp). For the 16QAM experiment at 112 Gbit/s, we measure a bit-error ratio of 5.1 × 10⁻5 and a record-low energy consumption of only 19 fJ/bit.

Atom-atom entanglement by single-photon detection.

A scheme for entangling distant atoms is realized, as proposed in the seminal paper by [C. Cabrillo et al., Phys. Rev. A 59, 1025 (1999)]. The protocol is based on quantum interference and detection of a single photon scattered from two effectively one meter distant laser cooled and trapped atomic ions. The detection of a single photon heralds entanglement of two internal states of the trapped ions with high rate and with a fidelity limited mostly by atomic motion. Control of the entangled state phase is demonstrated by changing the path length of the single-photon interferometer.

Real-time OFDM or Nyquist pulse generation--which performs better with limited resources?

We investigate the performance and DSP resource requirements of digitally generated OFDM and sinc-shaped Nyquist pulses. The two multiplexing techniques are of interest as they offer highest spectral efficiency. The comparison aims at determining which technology performs better with limited processing capacities of state-of-the-art FPGAs. It is shown that a novel Nyquist pulse shaping technique, based on look-up tables requires lower resource count than equivalent IFFT-based OFDM signal generation while achieving similar performance with low inter-channel guard-bands in ultra-dense WDM. Our findings are based on a resource assessment of selected DSP implementations in terms of both simulations and experimental validations. The experiments were performed with real-time software-defined transmitters using a single or three optical carriers.

Tunable ion-photon entanglement in an optical cavity.

Proposed quantum networks require both a quantum interface between light and matter and the coherent control of quantum states. A quantum interface can be realized by entangling the state of a single photon with the state of an atomic or solid-state quantum memory, as demonstrated in recent experiments with trapped ions, neutral atoms, atomic ensembles and nitrogen-vacancy spins. The entangling interaction couples an initial quantum memory state to two possible light-matter states, and the atomic level structure of the memory determines the available coupling paths. In previous work, the transition parameters of these paths determined the phase and amplitude of the final entangled state, unless the memory was initially prepared in a superposition state (a step that requires coherent control). Here we report fully tunable entanglement between a single (40)Ca(+) ion and the polarization state of a single photon within an optical resonator. Our method, based on a bichromatic, cavity-mediated Raman transition, allows us to select two coupling paths and adjust their relative phase and amplitude. The cavity setting enables intrinsically deterministic, high-fidelity generation of any two-qubit entangled state. This approach is applicable to a broad range of candidate systems and thus is a promising method for distributing information within quantum networks.

512QAM Nyquist sinc-pulse transmission at 54 Gbit/s in an optical bandwidth of 3 GHz.

We demonstrate for the first time transmission of 54 Gbit/s and 48 Gbit/s over 44 km and 150 km, respectively, utilizing an optical bandwidth of only 3 GHz. We used polarization division multiplexed 512QAM and 256QAM modulation formats in combination with Nyquist pulse shaping having virtually zero roll-off. The resulting spectral efficiencies range up to 18 bit/s/Hz and 16 bit/s/Hz, respectively. Taking into account the overhead required for forward error correction, the occupied signal bandwidth corresponds to net spectral efficiencies of 14.4 bit/s/Hz and 15 bit/s/Hz, which could be achieved in a wavelength division multiplexed network without spectral guard bands.

Universal digital quantum simulation with trapped ions.

A digital quantum simulator is an envisioned quantum device that can be programmed to efficiently simulate any other local system. We demonstrate and investigate the digital approach to quantum simulation in a system of trapped ions. With sequences of up to 100 gates and 6 qubits, the full time dynamics of a range of spin systems are digitally simulated. Interactions beyond those naturally present in our simulator are accurately reproduced, and quantitative bounds are provided for the overall simulation quality. Our results demonstrate the key principles of digital quantum simulation and provide evidence that the level of control required for a full-scale device is within reach.

Krefeld CONTRA study: conventional peroral Esophago-Gastro-Duodenoscopy (EGD) vs. transnasal EGD--a prospective and randomised study with independent evaluation of conscious sedation, endoscope diameter, and access path.

BACKGROUND: The guidelines of the German Gastroenterology Society (Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten, DGVS) demand the presence of an additional qualified person solely responsible for patient monitoring during sedated endoscopy. Transnasal esophagogastroduodenoscopy (EGD) allows easy access to the upper gastrointestinal tract and may avoid the complications induced by conscious sedation and reduce medical costs. PATIENT AND METHOD: 120 patients referred to diagnostic EGD were assigned to six groups: group 1, unsedated peroral EGD with normal-caliber endoscope; group 2, unsedated peroral EGD with small-caliber endoscope; group 3, sedated peroral EGD with normal-caliber endoscope; group 4, sedated peroral EGD with small-caliber endoscope; group 5, unsedated transnasal EGD with small-caliber endoscope; group 6, sedated transnasal EGD with small-caliber endoscope. Outcome parameters included objective (duration, oxygen saturation) and subjective measures (standardised visual analogue scales) of the endoscopy staff (handling, insertion, retroflexion, tolerability, overall assessment) and patients (pain, unpleasantness, sore throat, choking, gagging, meteorism, anxiety, acceptability). RESULTS: The patients were comparable according to age, sex, anxiety, and respiratory function before EGD. Sedoanalgesia was without effect on EGD handling and duration, patient tolerability and overall assessment by endoscopists and assistants. Negative effects of sedoanalgesia (decreased oxygen saturation, patient acceptability) were much lower and without significance for transnasal compared to peroral EGD. Patient tolerability and acceptability of the endoscopic staff (handling, insertion, retroflexion) were significantly better for the small-caliber endoscope. Duration of unsedated transnasal EGD was slightly but significantly longer, pain, unpleasantness, and anxiety slightly but significantly higher compared to sedated peroral EGD. However, these differences could no loner be detected seven days after endoscopy. Cost analysis revealed major advantage for transnasal EGD. CONCLUSION: Unsedated transnasal EGD may replace diagnostic peroral EGD, reduces costs with acceptable patient discomfort and has advantagous acceptability of the endoscopic staff.

Absolute frequency measurement of the 40Ca+ 4s(2)S_(1/2)-3d(2)D_(5/2) clock transition.

We report on the first absolute transition frequency measurement at the 10;{-15} level with a single, laser-cooled 40Ca+ ion in a linear Paul trap. For this measurement, a frequency comb is referenced to the transportable Cs atomic fountain clock of LNE-SYRTE and is used to measure the 40Ca+ 4s ;{2}S_{1/2}-3d ;{2}D_{5/2} electric-quadrupole transition frequency. After the correction of systematic shifts, the clock transition frequency nu_{Ca;{+}}=411 042 129 776 393.2(1.0) Hz is obtained, which corresponds to a fractional uncertainty within a factor of 3 of the Cs standard. In addition, we determine the Landé g factor of the 3d;{2}D_{5/2} level to be g_{5/2}=1.200 334 0(3).

Realization of the quantum Toffoli gate with trapped ions.

Gates acting on more than two qubits are appealing as they can substitute complex sequences of two-qubit gates, thus promising faster execution and higher fidelity. One important multiqubit operation is the quantum Toffoli gate that performs a controlled NOT operation on a target qubit depending on the state of two control qubits. Here we present the first experimental realization of the quantum Toffoli gate in an ion trap quantum computer, achieving a mean gate fidelity of 71(3)%. Our implementation is particularly efficient as the relevant logic information is directly encoded in the motion of the ion string.