Load-Independent Voltage Balancing of Multi-Level Flying Capacitor Converters in Quasi-2-Level Operation

Quasi-2-level (Q2L) operation of multi-level bridge-legs, especially of flying-capacitor converters (FCC), is an interesting option for realizing single-cell power conversion in applications whose system voltages exceed the ratings of available power semiconductors. To ensure equal voltage sharing among a Q2L-FCC’s switches, the voltages of a Q2L-FCC’s minimized flying capacitors (FCs) must always be balanced. Thus, we propose a concept for load-independent FC voltage balancing: For non-zero load current, we use a model predictive control (MPC) approach to identify the commutation sequence of the individual switches within a Q2L transition that minimizes the FC or cell voltage errors. In case of zero load current, we employ a novel MPC-based approach using cell multiple switching (CMS), i.e., the insertion of additional zero-current commutations within a Q2L transition, to exchange charge between the FCs via the charging currents of the switches’ parasitic capacitances. Experiments with a 5-level FCC half-bridge demonstrator confirm the validity of the derived models and verify the performance of the proposed load-independent balancing concept.

Iterative Parameter Optimization for Multiple Switching Control Applied to a Precision Stage for Microfabrication

This paper proposes an iteration procedure to derive optimal parameters for a multiple switching control architecture. Control design is usually a compromise between various performance requirements; therefore, switching between multiple controllers that achieve a particular performance under different conditions can potentially improve the overall system behavior. In this paper, we consider a control-switching mechanism that can automatically switch controllers based on the prediction of future responses, and we develop an iteration procedure that can optimize the mechanism parameters, such as the number of controllers and the prediction horizon. We then implement the proposed mechanism in a long-stroke precision stage, and demonstrate the effectiveness of switching robust control with simulations and experiments. Lastly, we integrate the stage with a two-photon polymerization system to fabricate microlenses. The optical properties confirm that the proposed iterative parameter optimization procedure is effective in improving the performance of microfabrication employing multiple switching control.

Switching from Biosimilar to Biosimilar Adalimumab, Including Multiple Switching, in Crohn’s Disease: A Prospective Study

No data are available regarding the safety and effectiveness of the biosimilar-to-biosimilar switch of adalimumab in any disease, and in particular in Crohn’s disease (CD). The aim of our study was to provide real world data on switching from biosimilar adalimumab to another biosimilar, including multiple switching. We conducted a prospective, single-centre observational study in which we consecutively recruited all CD patients who switched from adalimumab biosimilar ABP 501 to biosimilar SB5 from January to July 2021. Sixty-one patients were included in the final analysis, of whom 43/61 (70.5%) were multiple switches (Humira® → ABP 501 → SB5). After 6 months of follow up, 88.5% (54/61) of patients maintained SB5 on therapy. The success of the switch (defined as no systemic corticosteroids within 6 months, non-discontinuation of SB5, no dose escalation) was achieved by 82.0% (50/61) of patients. At multivariate analysis, C-reactive protein > 5 mg/L predicted switch failure (p = 0.03). Seven patients (11.5%) experienced side effects, compared to one patient (1.6%) in the 6 pre-switch months (p = 0.03). In conclusion, switching from biosimilar to biosimilar of adalimumab did not lead to signs of safety or loss of efficacy other than those already known in the literature for the class of drugs.

Real-time virtual sonography-assisted radiofrequency ablation in liver tumors with conspicuous or inconspicuous images or peritumoral landmarks under ultrasonography

Objectives The objectives of this study were to determine the primary technique effectiveness (PTE), to compare the complete response and local recurrence rates between conspicuous and inconspicuous tumors using single and switching electrodes of real-time virtual sonography (RVS)-assisted radiofrequency ablation (RFA) in conspicuous and inconspicuous hepatic tumors under conventional ultrasonography (US). Subjects and method We compared the complete ablation of inconspicuous tumors with and without anatomical landmark (N = 54) with conspicuous liver tumors (N = 272). Conventional US imaging was done initially, and then these images were fused with CT or MRI arterial-venous-wash-out cross-sectional studies and synchronized with real-time US images. Results RVS-assisted RFA was technically feasible in all patients. The PTE rate after the first ablation was 94% (245/261) for conspicuous tumors, 88% (7/8) in inconspicuous tumors with landmark, and 78% (36/46) in inconspicuous tumors without landmark. The complete response (p = 0.1912 vs. p = 0.4776) and local recurrence rate (p = 0.1557 vs. p = 0.7982) were comparable in conspicuous tumors of both HCC and liver metastasis group when single or multiple switching was used. The cumulative local recurrence in the conspicuous and inconspicuous tumors of the HCC group (p = 0.9999) was almost parallel after 12 (10% vs. 4%) and 24 (13% vs. 4%) months of follow-up. In the liver metastasis group, the cumulative local recurrence for conspicuous tumors (p = 0.9564) was nearly equal after 12 and 24 months of monitoring (24% vs. 27%) while no recurrence was incurred for the inconspicuous tumors. Conclusion RVS-assisted RFA is an effective tool for the treatment of conspicuous and inconspicuous HCC and hepatic metastasis.

Rewritable color nanoprints in antimony trisulfide films

Materials that exhibit large and rapid switching of their optical properties in the visible spectrum hold the key to color-changing devices. Antimony trisulfide (Sb2S3) is a chalcogenide material that exhibits large refractive index changes of ~1 between crystalline and amorphous states. However, little is known about its ability to endure multiple switching cycles, its capacity for recording high-resolution patterns, nor the optical properties of the crystallized state. Unexpectedly, we show that crystalline Sb2S3 films that are just 20 nm thick can produce substantial birefringent phase retardation. We also report a high-speed rewritable patterning approach at subdiffraction resolutions (>40,000 dpi) using 780-nm femtosecond laser pulses. Partial reamorphization is demonstrated and then used to write and erase multiple microscale color images with a wide range of colors over a ~120-nm band in the visible spectrum. These solid-state, rapid-switching, and ultrahigh-resolution color-changing devices could find applications in nonvolatile ultrathin displays.

Biosimilars

Biologic therapy for treatment of rheumatoid arthritis (RA) has evolved considerably over the past 20 years. Biosimilar development continues to accelerate at a frenetic pace worldwide. Initial regulatory efforts were developed within the EU and subsequent guidelines have now evolved in over 20 countries. Biosimilars by definition are highly similar, with ‘comparable quality, safety, and efficacy’ (EMA) and ‘no clinically meaningful differences in safety, purity, and potency’ (FDA) to the reference product. Development and manufacturing are based on reverse engineering of the reference product as only the primary amino acid sequence is known. Testing of primary, secondary, tertiary, and quaternary structure, binding pharmacokinetics, and stability is required. Characterization of post-translational modifications and biologic function, pharmacokinetics, evaluation of immunogenicity, and at least one comparative efficacy clinical trial are major requirements for regulatory approval. Clinical trials to assess biosimilarity are required in only one clinical indication and may be extrapolated to other indications for which the reference product is approved. Both single and multiple switching trials (between biosimilar and reference product) have yielded consistent results across numerous patient populations and diseases, with no evidence of detrimental outcomes. Two prospective large observational series (Danbio and Nor-Switch) have similarly assessed non-medical switching. Several open-label switching studies have revealed equivalent efficacy, safety, and discontinuation rates but real-world studies have raised concerns about potential nocebo responses.

THU0484 FIBROMYALGIA AND MULTIPLE SWITCHING OF BIOLOGICS IN SPONDYLOARTHRITIS

Background:Fibromyalgia (FM) is a condition characterized by chronic widespread pain, tender points, fatigue and disturbed sleep rhythm. Some of these symptoms such as fatigue, tender points and diffuse pain seen in patients with spondylarthritis (SpA). Moreover, FM and SpA can coexist creating a diagnostic challenge, particularly in early disease course and influence clinical disease activity assessment.Objectives:With this cross-sectional study, we aim to estimate the prevalence of FM in SpA and to elaborate its effect on biological treatments.Methods:FM was identified according to the ACR 2010 diagnostic criteria. SpA patients identified according to rheumatologist using various SpA subsets criteria. A review of the electronic medical files for SpA patients attending the rheumatology outpatient clinic and infusion unit at a major tertiary hospital during the period from June to December 2018 were included. Patients’ demographics, socioeconomics, disease characteristics, activity, HLA status and abnormal MRI sacroiliac were explored. Regarding SpA medications, number, frequency and dose of DMARDs and biological agents were obtained.Continuous variables were reported by their mean and standard deviation (SD) and qualitative variables by frequency and percentage. Statistical significance was set at p <0.05. Statistical analysis was performed using SPSS version 23.Results:Of the 305 enrolled SpA patients, 43 (14.1%) had FM. Females represents 57.4% of the patients, mean age was 44.07 ± 11.85 years. Arab ethnicity represents most of our cohort 84.9%, the majority were Emirati 64.6%. Smokers were 8.2% and ex-smokers were 3.3%. Axial SpA represents 38.4% while peripheral SpA 61.6% of our cohort according to ASAS classification.HLA B27 tested in a sample of 180 patients; it was positive in only 17.8%. CRP found to be elevated in 20.3% of the patients at baseline. Abnormal MRI SIJ bone marrow edema changes were found in 10.8%, while other SIJ changes was seen in additional 20.6%. The prevalence of FM showed no statistically significant difference between axial and peripheral SpA. Patients SpA and FM have longer disease duration than SpA alone, P= 0.034. Table.1 show demographics, socioeconomics and clinical data of our cohort.Regarding medication, the use of biologics among SpA patients with FM is more frequent than SpA patients without FM (74.4% vs 51.5 % respectively), P= 0.005. Interestingly, the likelihood ratio testing showed that SpA patient with Fibromyalgia switch more frequently to another biologics than SpA without fibromyalgia, P= 0.015.Cramer’s V test showed that there is a high statistically significant (P= 0.002) and very strong association (> 0.25) between presence of Fibromyalgia and multiple switching of biologics in SpA.There was no difference in the exposure to prednisolone nor conventional DMARDs between SpA patients with or without FM, P= 0.64 & 1 respectively.Gender, Female, n (%)175 (57.4)Age, mean ± SD (min- max), years44.07 ± 11.85 (18- 78)Type of A, n (%)AxialPeripheral117 (38.4)188 (61.6)Fibromyalgia, n (%)FM in axial SpAFM in Peripheral SpA43 (14.1)18 (41.9)25 (58.1)SpA Disease duration (months)FM+, mean ±SDFM-, mean ±SD107.7± 50.486± 57.9Elevated CRP, n (%)62 (20.3)HLA B27 in180 patients, n (%)PositiveNegative32 (17.8)148 (82.2)Abnormal MRI SIJ, n (%)Bone marrow edemaSubchondral sclerosisFatty transformation of bone marrowErosion92 (30.2)33 (10.8)21 (6.9)5 (1.6)2 (0.7)Number of conventional DMARDs ever tired, n (%)NoneOneTwoThree81 (26.6)166 (54.4)46 (15.1)12 (3.9)Frequency of DMARDs usage, n, (%)Conventional DMARDsPrednisoloneBiologic DNARDs224 (73.4)56 (18.4)164 (53.8)Conclusion:FM coexistence with SpA might impact clinical evaluation of disease activity and possibly negatively affect self-measurement of treatment response. In our study, SPA patients exposed to more biologics if they have coexisting FM; Moreover, they are more frequent switchers among biologics including TNFi and IL17i.Acknowledgments:N Elsidig, A Al Marzooqi, N Zamani, A HossainiDisclosure of Interests: :None declared