Harmonic (United States)

BackgroundOsteoarthritis (OA) is a chronic disease characterized by degradation of joint structures including the subchondral bone, the synovium, and cartilage. Aggrecan constitutes a major component of hyaline cartilage and plays an important role for its normal function. In OA, aggrecan is gradually lost, which together with cytokines, proteases, and circulating pro-inflammatory fragments of hyaluronic acid (HA) further accelerates tissue destruction. SB-061 is an aggrecan mimetic, composed of a backbone of chondroitin sulfate conjugated to a HA peptide coating protein. SB-061 is believed to bind HA fragments in the synovium. Hence, SB-061 acts upstream in the inflammatory cascade, thereby potentially reducing both pain as well as structural deterioration [1].ObjectivesTo evaluate the efficacy and safety of intra-articular injections of SB-061 in subjects with knee OA.MethodsThis was a randomized, placebo-controlled, double-blind phase II study comparing quarterly intra-articular injections of SB-061 with placebo (isotonic saline) for 52 weeks (EudraCT No. 2019-004515-31). Eligible subjects had a Kellgren-Lawrence (KL) grade of 2 or 3 on X-ray of the target knee and a Western Ontario and McMasters Osteoarthritis Index (WOMAC) pain score ≥20 out of 50 at screening and baseline visits. Subjects having used any medication known to affect the joints up to 3 months prior to the study or having any other knee condition were excluded. Any use of analgesic medication was prohibited during the study, except for rescue medication (paracetamol/acetaminophen). The primary endpoint was the change from baseline (CFB) in WOMAC pain at Week 8 after first injection. Secondary endpoints were CFB in WOMAC function and total, ICOAP and the Patient Global Assessment (PGA), and 20-meter walk test. Exploratory structural endpoints included CFB in knee cartilage thickness and volume, and bone shape as measured by magnetic resonance imaging (MRI), and CFB in the radiographic minimum joint-space width (JSW).ResultsA total of 288 subjects were randomized to SB-061 (n= 145) or placebo (n=143), and of these 252 (87.5%) completed injections. The two groups were well-balanced in terms of the main clinical and radiographic parameters, and reflective of a typical OA clinical trial population. The primary endpoint was not met, as there was no significant difference in the CFB of the WOMAC pain score (0-50) at Week 8 between the groups (LSmean difference: 0.00, 95% CI -4.33; 4.34, p=0.999, nor at any other time point during the trial (Figure 1). Similarly, neither of the secondary endpoints of changes from baseline in WOMAC function, WOMAC total, ICOAP, PGA, and 20-meter walk test indicated any significant difference between SB-061 and placebo. There was no significant difference between groups in CFB in JSW or any of the MRI parameters. The frequency and type of adverse events was similar between groups receiving SB-061 and placebo. SB-061 was well-tolerated.ConclusionIntra-articular injections of SB-061 administered quarterly for one year in patients with knee OA was safe but did not show any statistically significant effect on knee pain nor on other symptomatic or structural entities compared to placebo.Reference[1]Hauser-Kawaguchi A, Luyt LG, Turley E. Design of peptide mimetics to block pro-inflammatory functions of HA fragments. Matrix Biology. 2019 at https://doi.org/10.1016/j.matbio.2018.01.021.Figure 1.Acknowledgements:NIL.Disclosure of InterestsAsger Reinstrup Bihlet Employee of: Employee and shareholder in Nordic Bioscience., Inger Byrjalsen Employee of: Previous employee in Nordic Bioscience., Kamilla Mundbjerg Employee of: Employee in Nordic Bioscience Clinical Development., Peter Alexandersen Employee of: Part-time employee Nordic Bioscience Clinical Development., Helene Rovsing: None declared, Tobias Axelsen: None declared, Jeppe Ragnar Andersen Employee of: Employee and shareholder in Nordic Bioscience., Anna Metnik Employee of: Employee in Nordic Bioscience Clinical Development., Nathan Bachtell: None declared, Alan Brett Employee of: Employee and shareholder in Stryker., Claus Christiansen Employee of: Shareholder in Nordic Bioscience.

Introduction: Impaired coordination within the shoulder complex is a frequent symptom in post-stroke survivors. However, most devices that have undergone clinical trials are unable to actively assist the full movement of the shoulder girdle. Purpose: In this study, we aim to evaluate the safety of the Harmony robot in post-stroke rehabilitation and to understand the needs of the user and the clinicians. Methods: The Harmony exoskeleton is a bilateral device with seven degrees-of-freedom in each arm, which has an anatomical shoulder mechanism that can provide active assistance for the shoulder girdle. Each subject underwent seven one-hour training sessions in which six arm trajectories based on functional therapeutic exercises were trained with robotic assistance. Position and torque data during movements were captured by the robot’s sensors. Heart rate, blood pressure, and subject pain and safety perception of the robot were measured in each session. Results: Three (3) subjects have completed the study. The mean donning and doffing times were 3’56” and 1’21”, respectively. The mean improvement in Fugl-Meyer UE and Action Research Arm Test scores was 6 and 4.3 points, respectively. The stability of the glenohumeral joint during multi-joint 3D movements was maintained as evaluated by an occupational therapist. All subjects reported their safety perception to be maximal (very safe); no adverse events have been reported. The mean anxiety score of the subjects was 1.4 on a scale from 1 (no anxiety) through 10 (extreme anxiety). The mean heart rate change during a session was 4.1 bpm, suggesting subjects were not showing signs of exhaustion or stress; average variation in heart rate across sessions was 11 bpm. No moderate or severe pain was reported along the experiments. Conclusions: These results suggest that the Harmony exoskeleton can safely assist in the completion of complex upper-limb movements with reasonably short donning-and-doffing times. Our results also suggest that robotic-assisted therapy has great potential to motivate and engage patients in their treatment.

This paper presents the design, construction and performance of an application of shunt tuned passive filters in the medium-voltage side of a distribution system. The results found are encouraging to solve eventual parallel resonances problems detected in this kind of distribution feeder.

Analog fiber links often use externally modulated 1550 nm transmitters and EDFAs to obtain high performance over long distances. The use of differential detection eliminates two signal-degrading effects associated with such transmission phase to amplitude noise conversion, and fiber-induced composite second order distortion (CSO). In addition, the use of differential detection boosts the net carrier-to-noise ratio (CNR) by 3 dB, and enables very high analog performance over distances in excess of 50 km, without the use of optical amplifiers.

We present our study of VoD service optical network using 16-channel DWDM. One approach is a VoD architecture where all video server equipment is centralized and located in the headend. Another option is to deploy servers in several hubs where each has the capability of providing digital VoD service but on a smaller scale. A centralized video server maybe more attractive as it reduces operating cost. DWDM provides a perfect solution for this application because of the high data transport capacity. In a typical DWDM VoD system video programs are stored in MPEG-II format and transported using 64 or 256-QAM modulation. One VoD server in the headend can provide service to several hubs on a fiber ring by allocating wavelengths to these hubs. The number of dropped wavelengths at a particular location depends on the local demand. VoD programs are routed by wavelength to the appropriate hub location. Each wavelength can carry multiple QAM channels. The frequency allocation of these QAM channels depends on the system design. Usually the QAM is inserted in a frequency band above the traditional 50 MHz to 550 MHz broadcast channels. Since QAM signal can be readily decoded by the set top box in customer home, there is no RF conversion required if this QAM signal band originating at the headend matches the set-top box tuner frequency range. At the hubs, the VoD signal can be combined with local channels and the broadcast channels in RF domain and retransmitted for distribution.

Commonly used diode-based third-order distortion generators produce residual second-order distortion signals due to the unmatched statistical characteristics of the diodes. In this paper, a novel circuit technique is presented by which, in theory, the suppression of undesirable residual second-order distortion is achieved. A theoretical analysis of the proposed novel circuit topologies is carried out using Volterra series analysis. The residual second-order intermodulation distortions (IM2) of conventional antiparallel and bridge configurations are compared with the modified versions presented in the paper. Simulated results show that the modified antiparallel configuration possess a maximum residual IM2 46 dB lower than the one produced by the conventional configuration. The modified bridge configuration has a maximum residual IM2 36 dB lower than the one of the conventional configuration. A sensitivity analysis of the modified configurations is also presented. Experimental results indicate that 20 dB cancellation is achievable.

Summary form only given. As the transmitted power and the fiber span increase for the analog CATV systems, the fiber is no longer transparent. The interaction of fiber and the transmitted light degrades the system performance due to chromatic dispersion and non-linear fiber optics, including SCS, SRS and SPM for a single optic channel. In cases of multi-wavelength systems, four wave mixing (FWM), cross phase modulation (XPM), and SRS are more important degradation factor. We discuss the system parameters such as CSO, CTB, CNR, and options/demonstrations of numerous countermeasures that drastically reduce the degradation.

Intense activity and tremendous growth have recently occurred in the field of analog and mixed analog/digilai CATV/FITL transmission and distribution. Several competing/complementing choices of technology have become available for the wide-area distribution and long-haul transport of broadband analog/digital information. In this paper we review and compare the most relevant of those rapidly evolving technologies, addressing basic properties at the component level as well as component integration into subsystems and systems and the resulting performance.

Recent advances in electronic linearization of AM CATV transmitters based on externally modulated diode pumped Nd:YAG lasers are presented. The theoretical principles and practical issues related to the methods of feedforward and predistortion linearization, the factors affecting system performance and the emerging devices, circuits, subsystems, and systems architectures are reviewed. In experiments based on a predistortion linearized system, transmission over two fibers of 30 km each, wherein each fiber carries 80 NTSC channels, is now routinely achieved with a CNR>50 dBc, a CTB<-65 dBc, and a CSO of typically -70 dBc. As the number of channels broadcast over each fiber is reduced from 80 to 60, CNR increases to 52 dBc. The fiber links served by the system under test each have 12-dB link budget, and include four connectors per fiber, with no degradation observed in one link when the connectors were opened on the other link.