Double Switch Research Articles

P360 Safety and clinical efficacy of double switch from originator infliximab to biosimilars CT-P13 and SB2 in patients with inflammatory bowel diseases (SCESICS): A multicentre study

Abstract Background Since infliximab (IFX) patent expiry in 2015, several IFX biosimilars have been licensed in EU for all indications, including inflammatory bowel diseases (IBD). IFX biosimilars currently available in Italy include CT-P13 and SB2, both of which demonstrated comparable efficacy, safety and immunogenicity with IFX originator in IBD patients. Safety and clinical efficacy of single switch from originator IFX to CT-P13 have also been confirmed in a prospective clinical trial. On the contrary, data regarding multiple therapeutic switching of IFX originator with CT-P13 and SB2 are currently lacking. Methods This study was aimed to evaluate the safety and efficacy of double switch from IFX originator to CT-P13 and subsequently to SB2 in patients with IBD. From November 2018 to May 2019, patients undergoing IFX double switch in 8 Centres in Lombardy were retrospectively analysed. The overall rate of IFX discontinuation, incidence and type of adverse events (AE) and proportion of patients on clinical remission over time were recorded. Data were compared with a control group of 66 IBD patients single switched from IFX originator to CT-P13. Results Fifty-two double-switched IBD patients were enrolled (63% M, mean age 41 years, 75% Crohn’s disease, 25% ulcerative colitis). Main indications for IFX therapy were moderate to severe disease (50%) and steroid-dependent disease (25%). The overall 24- and 48-week IFX discontinuation rates following second switch (CTP13->SB2) were 2% (95% CI 0–6%) and 14% (95% CI 3–25%), respectively. During a median follow-up of 40 weeks (18–48), 4 patients (12%) experienced a total of 6 AE (2 cutaneous, 2 infectious, 1 articular and 1 immunological), leading to IFX discontinuation in 3 cases (6%). No infusion reactions were observed. At week 24 following second switch, 49 (94%) patients were in clinical remission, the remaining 3 patients not being in remission already at the time of second switch. Only one patient lost response after week 24, 48 (92%) of patients being in clinical remission at the end of follow-up. No differences in IFX discontinuation, AE and clinical remission rates were found between double-switched and single-switched patients. No clinical parameters were found to predict safety and efficacy outcomes. Conclusion The study supports both safety and efficacy of the double switch from IFX originator to CT-P13 and SB2 in patients with IBD, and demonstrates its non-inferiority to a single switch strategy, with potential cost implications.

Left Ventricular Re-training in Transposition: An Evolution in Concepts

Left ventricular (LV) re-training is utilized for patients with D-transposition of the great arteries (D-TGA) who have undergone a previous atrial switch and develop right ventricular failure and a select subset of patients with congenitally corrected transposition (CC-TGA). We have evaluated our experience with LV re-training in both D- and CC-TGA in a series of publications over the past 6 years. The purpose of this paper is to summarize the evolution in concepts that have occurred with regard to LV re-training. This review will bring together the findings of 4 manuscripts that our group has published on the subject of LV re-training in recent years. This summary includes a total of 61 patients, of whom 25 had D-TGA and 36 had CC-TGA. The median age of the D-TGA patients was 15 years and the median age of the CC-TGA patients was 12 months. Thirteen of 25 (52%) of patients with D-TGA underwent LV re-training and subsequently had a double switch. Ten of these 13 patients are mid-term survivors. To date, 31 of the 36 patients with CC-TGA underwent LV re-training and a double switch with 100% survival in this cohort. Two of the 36 patients with CC-TGA are definitive LV re-training failures, while 3 patients are still in the process of evaluation. LV re-training and late arterial switch can be accomplished in the majority of patients with TGA. However, there is a marked disparity in achieving a successful double switch between D- and CC-TGA.

Integrated Multimode Orbital Angular Momentum Antenna Based on RF Switch

This paper proposes an electronically reconfigurable multimode orbital angular momentum (OAM) patch array antenna using single pole double throw radio frequency switch that can complete dynamic switching of three modes (-1,0,1) at 2.4 GHz. As a new type of multiplexing technology, the application value of OAM technology in radar imaging and wireless communication has been continuously verified. Considering that many theoretical algorithms are proposed, a multimode vortex antenna that meets the experimental requirements should be developed. The proposed antenna consists of RF switch, programmable microcontroller, phase-shifted feed network, and $2\times2$ rectangular array. Different feeder networks were selected by controlling the RF switch to generate vortex beams with different modes. The proposed antenna was numerically simulated and physically produced. The feasibility of the design was verified through experiments. The simulation and design results are basically the same. The proposed scheme has simple structure, easy to design and deploy, and has important significance in the design of many mode vortex antenna applications in communication and radar imaging.

A Double-Switch Temperature-Sensitive Controlled Release Antioxidant Film Embedded with Lyophilized Nanoliposomes Encapsulating Rosemary Essential Oils for Solid Food.

In order to match the solid food oxidation during logistics and storage process under severe high temperature, a double-switch temperature-sensitive controlled release antioxidant film embedded with lyophilized nanoliposomes encapsulating rosemary essential oils (REOs) was prepared. The double switch temperature at 35.26 and 56.98 °C was achieved by development of a temperature sensitive polyurethane (TSPU) film. With biaxially oriented polyethylene terephthalate (BOPET) as a barrier layer, the intelligent complex film was prepared via coating the TSPU embedded with lyophilized nanoliposomes encapsulating REOs on BOPET. The results indicate that the REO is well encapsulated in nanoliposomes with encapsulation efficiency (EE) of 67.3%, high stability and lasting antioxidant effect during 60 days. The incorporation of lyophilized nanoliposomes containing REOs into TSPU remains the double-switch temperature-sensitive characteristic of the prepared TSPU. In agreement with porosity and WVTR results, the diffusion coefficient (D) of the antioxidant complex film sharply increases respectively at two switching temperatures, indicating that the intelligent double-switch temperature-sensitive controlled release property is functioning. Furthermore, compared with films directly added with REO, the lower Ds of films added with lyophilized nanoliposomes encapsulating REOs provides a longer-lasting antioxidant activity. Thus, the acquired controlled release antioxidant film sensitive to temperature at 39.56 and 56.00 °C can be potentially applied for protection of solid food during distribution and storage process under severe high temperatures.

The Micro-Miniature Capacitance Sensor Based on Light-Trigger Technology and Its Hardware Design in the Electrical Capacitance Tomography System

Electrical capacitance tomography (ECT) technology can monitor the multi-phase flow in closed pipes or vessels. The monitoring technology has the advantages of anti-intrusion, low manufacturing cost, high-temperature resistance, and simple structure. At present, ECT systems use small-scale sensors for signal capture, but such sensors have problems such as low sensitivity and poor anti-interference, which have attracted the attention of researchers. In this study, a light-trigger sensor was proposed, which was equipped with a special light window to receive optical signals. At the same time, in terms of the problem of electromagnetic shielding and optical window protection, a light window structure that transmitted optical signals and shields electromagnetic waves was designed. Based on the light-trigger sensor, the other modules of the ECT system were designed, considering that the sensor would be interfered by the measurement of stray capacitance, the intra-isoelectric driver cable shielding technology, the double T-type simulation switch matrix, and the digital-mode demodulation technology was introduced. Consequently, the performance of the sensor was tested. During the experiment, the sucrose flow pattern was used as the test object. The results showed that compared with the traditional sensors, the image distortion of the sensor based on the ECT system was lower; while in the performance test of the ECT system, the introduction of the double T-type simulation switch matrix, the digital-analogy demodulation technology, and the bipolar plate excitation mode could further optimize the signal-to-noise ratio index of the image; in the sensitivity test of the ECT system, the introduction of bipolar plate excitation mode could improve the output sensitivity of the capacitance.

Left ventricular retraining in corrected transposition: Relationship between pressure and mass

BackgroundA subset of patients with corrected transposition of the great arteries (CC-TGA) will require left ventricular (LV) retraining before undergoing a double-switch procedure. LV retraining results in an immediate increase in LV pressure but not in LV mass. The purpose of this study was to evaluate the relationship between LV pressure and mass during LV retraining. MethodsThis was a retrospective review of 36 patients with CC-TGA who were enrolled in LV retraining. The median age at enrollment was 12 months. The majority (82%) had an Ebstenoid tricuspid valve or moderate to severe tricuspid valve regurgitation before pulmonary artery banding. ResultsTwenty-seven of the 36 patients underwent LV retraining and a double switch, including 14 patients with a single pulmonary artery band (PAB), 12 patients with 2 PABs, and 1 patient with 3 PABs. There was no early or late mortality associated with these procedures. Ninety percent of the patients demonstrated a linear relationship between LV pressure and mass; however, 3 patients (10%) demonstrated a different LV retraining pattern characterized by excess LV mass compared to LV pressure. Two of these 3 patients are LV retraining failures, whereas the third patient did undergo a double switch. ConclusionsThe data show that the majority of patients enrolled in LV retraining have a predictable relationship between LV mass and pressure. A minority demonstrate an excess accrual of mass with respect to pressure load. These results suggest there may be an important distinction between normal and pathological hypertrophy during the LV retraining process.

High peak optical power of 1ns pulse duration from laser diodes - low voltage thyristor vertical stack.

It is shown that the use of low-voltage GaAs/AlGaAs thyristors as high-speed and high-current switches in vertical stacks with semiconductor lasers ensures the efficient generation of high-power ns-duration laser pulses. The lasing and current dynamics in vertical stacks based on laser diode mini bar emitting at 1060 nm and a single as well as a double thyristor switch is studied. The possibility is demonstrated that a laser diode mini bar (with 3 laser emitters) together with a single thyristor switch can generate laser pulses with a peak power of 6 W with a duration of 950 ps and a peak current of 12 A for an operating voltage of 28 V. The use of a double thyristor switch leads to a broadening of the current pulse due to different delays in turn-on of the thyristor switches, while the peak power and duration of laser pulses increase to 8 W and 1.4 ns, respectively. It is found that the stage of low-speed turn-on of the thyristor limits the efficient generation of current and laser pulses of ns duration at low operating voltages (less than 21V). An efficient generation of current and laser pulses by low-voltage thyristors at control currents of 2-320 mA is ensured by efficient impact ionization in the region of the reverse biased p-n junction at high values of operating voltages (more than 21V).

Smart nonwoven fabric with reversibly dual-stimuli responsive wettability for intelligent oil-water separation and pollutants removal

This work presents the first fabrication of smart nonwoven fabric (DSR-CZPP) with extraordinary reversible double-stimulus responsive wettability, where carboxyl groups of cellulose nanocrystals/zinc oxide (CNC/ZnO) nanohybrids deposited on fabric surface can bond with hydroxyl group of the PDMAEMA-b-PHEMA-b-PMAAAB triblock polymer brushes that was prepared by using methyl methacrylate (HEMA), dimethylaminoethyl methacrylate (DMAEMA) and methacrylamide-azobenzene monomer (MAAAB) via reversible addition–fragmentation chain transfer (RAFT). The peculiar reversible double-stimulus responsive wettability of the DSR-CZPP can be modulated by triggering hydrophilic/hydrophobic transitions and lipophilic/oleophobic transitions under dual-stimulations of pH and UV light irradiation. The special molecular structure of the triblock polymer brushes enabled DSR-CZPP to intelligent modulation of oil-water separation under the control of "UV & pH double switch", meanwhile CNC/ZnO simultaneously can induce the photocatalytic degradation of organic dyes. Moreover, DSR-CZPP can have high removal ratios of various pollutants, such as metal ion (Cu2+) and toxic organic solvent (silicone oil, acetone and chloroform). This smart and multifunctional fabric shows great potentials for treating complicated polluted water from most industrial fields.

Anion-Regulated Molecular Rotor Crystal: The First Case of a Stator-Rotator Double Switch with Relaxation Behavior.

Molecular rotational motion is crucial in artificial molecular machines and is expected to be very significant for the development of an electronic information molecular machine as mentioned in the 2016 Nobel Prize. However, controlling multiple motor modes is a huge challenge. Here, we report a case in which the structural phase transition effectively triggers multiple motor modes by regulating the rotational speed of the cation and/or anion. A novel switchable crystalline supramolecular rotor, [(cyclohexylammonium)(18-crown-6)] FSO3 (1), exhibits prominent temperature-dependent double switching behavior at 157.9 and 389.1 K induced by the variation of the rotational speed of the FSO3- anion (which acts as a super miniature rotator) in response to temperature. Moreover, it exhibits significant relaxation behavior and excellent pyroelectric switch characteristics. To the best of our knowledge, this might be the first discovery of the stator-rotator double switch with a relaxation effect, which could be a promising candidate for a slow/fast responsive double switch over a wide temperature range.

Double Switch Biodegradable Porous Hollow Trinickel Monophosphide Nanospheres for Multimodal Imaging Guided Photothermal Therapy.

Due to the limitation of inorganic nanomaterials in present clinical applications induced by their inherent nonbiodegradability and latent long-term side effects, we successfully prepared double switch degradable and clearable trinickel monophosphide porous hollow nanospheres (NiP PHNPs) modified with bovine serum albumin (BSA). Attributed to their acidic and oxidative double switch degradation capacities, NiP PHNPs can be effectively excreted from mice without long-term toxicity. Moreover, because of the paramagnetic and high molar extinction coefficient property resulting from the strong absorption in the second near-infrared light (NIR II) biowindow, NiP PHNPs have potential to be used for photoacoustic imaging (PAI) and T1-weighted magnetic resonance imaging (MRI) guided photothermal ablation of tumors in the NIR II biowindow. Specifically, it is interesting that the hollow structure and acidic degradation property enable NiP PHNPs to act as intelligent drug carriers with an on-demand release ability. These findings highlight the great potential of NiP PHNPs in the cancer theranostics field and inspire us to further broaden the bioapplications of transition metal phosphides.

Design and performance analysis of double cantilever type capacitive shunt RF MEMS switch

This paper presents a novel structure of capacitance shunt type RF switch for 5G applications. The proposed RF MEMS switch is having Cantilever type designed with optimized dimensions to operate in V-band applications. The electromechanical analysis is done by using the COMSOL tool. The actuation voltage of the proposed switch is 10.5 V with the air gap of 1 µm and gold as a beam material. The proposed switch with the meanders and perforations show the scattering parameters in HFSS software such as insertion loss (S12) of − 0.033 dB and return loss (S11) less than − 48 dB and the isolation (S21) calculated in off-state as − 62 dB at 50 GHz.

Congenitally corrected transposition of the great vessels: Evaluation with cardiac magnetic resonance imaging after double-switch repair

Congenitally corrected transposition of the great vessels implies double discordance: atrioventricular and ventriculoarterial. We present cardiac magnetic resonance images from a 9-year-old girl with congenitally corrected transposition of the great vessels, interventricular communication, and coarctation of the aorta who was treated with pulmonary artery banding, correction of coarctation, and posterior double switch. We also review the disease and the complications that should be evaluated after the surgical intervention.

Anatomic Repair of Corrected Transposition of the Great Arteries: The Double Switch.

The long-term outcome of patients with corrected transposition of the great arteries and associated lesions after physiologic repair is uncertain. Anatomic correction, utilizing the morphologic left ventricle as a systemic pumping chamber and the mitral valve as the systemic atrioventricular valve, is considered the preferred method, especially for patients with either tricuspid valve regurgitation, with Ebstein's malformation of the tricuspid valve, or with right ventricular dysfunction. The double switch employs both an atrial switch and arterial switch to "correct" the atrioventricular and ventriculoarterial discordance. Associated lesions are also repaired. The best outcomes with double switch are achieved with patients in the first few years of life even if reconditioning of morphologic left ventricle is required. However, the long-term function of the conduction system, the aortic valve, and the ventricles is variable and requires close surveillance.

Transposición congénitamente corregida de grandes arterias: valoración por resonancia magnética cardíaca tras corrección anatómica tipo “doble switch”

Congenitally corrected transposition of the great vessels implies double discordance: atrioventricular and ventriculoarterial. We present cardiac magnetic resonance images from a 9-year-old girl with congenitally corrected transposition of the great vessels, interventricular communication, and coarctation of the aorta who was treated with pulmonary artery banding, correction of coarctation, and posterior double switch. We also review the disease and the complications that should be evaluated after the surgical intervention.

Conversions After Sleeve Gastrectomy for Weight Regain: to Single and Double Anastomosis Duodenal Switch and Gastric Bypass at a Single Institution.

With the increase in popularity of laparoscopic sleeve gastrectomy (LSG), the number of patients experiencing weight regain has increased as well. This study aims to demonstrate the outcomes of LSG conversions to Roux-en-Y gastric bypass (RYGB), double anastomosis duodenal switch (DS), and single anastomosis duodeno-ileal sleeve (SADI-S) due to weight regain. A retrospective chart review was performed on 21 patients who underwent a conversion of LSG due to weight regain between March 1, 2013, and April 30, 2017. A longitudinal analysis was performed for the body mass index (BMI) measures, using multilevel model for change. Of 21 patients, 6 underwent a conversion to RYGB, 9 underwent a conversion to SADI-S, and 6 underwent a conversion to double anastomosis DS. Mean percentage of total weight loss was 16.0% at 6months, 20.1% at 12months, 18.8% at 24months, and 21.8% at 36months after the procedure. The final model suggests that preoperative BMI is the most significant indicator for initial status and the rate of change in BMI. Adjusting for preoperative BMI, type of procedure significantly affected the rate of change in BMI. The rate of decrease was fastest in RYGB patients, adjusting for preoperative BMI. One patient was readmitted 26days after the conversion for pulmonary embolism and intraabdominal hematoma, and no patient required a reoperation within 30days after the conversion. Conversions of LSG to RYGB, double anastomosis DS, and SADI-S are safe and can provide significant additional weight loss.

Rotary trigger double spark gap switch for repetitive pulse generator and production of silver nanocolloid

High-voltage, repetitive pulse generation technology plays a key role in underwater discharge applications such as water treatment and metal nanocolloid production. For these applications, a high-voltage, high-speed switching technology was crucial to swiftly transfer the energy stored in the capacitor to the electrodes in water. A rotary-triggered double spark gap switch was developed for this purpose in this study. Two spark gaps dedicated for charge and discharge were arranged in this switch, and they eliminated the irregular and unstable pulse generation due to the simultaneous charging and discharging in the pulse-generating circuits. Using this technique, pulses with 12 kV and 100 ns rise time were generated at a repetition rate of 150 pulses per second and applied to underwater discharge to produce silver nanocolloids.

Outcomes of Anatomic Repair in Patients with Congenitally Corrected Transposition of Great Arteries: Systematic Review and Meta-analysis

Introduction Anatomic repair of congenitally corrected transposition of great arteries (cc-TGA) has long held the promise of prevention of congestive heart failure by restoring the systemic ventricle function to the morphologic left ventricle. However data are limited and variable. We intended to perform a pooled analysis to try and delineate the outcomes after anatomic repair. Methods A comprehensive search of Medline and Scopus databases from inception through Dec 31, 2017 was conducted using predefined criteria. We included studies reporting anatomic repair of minimum 5 cc-TGA patients with a follow-up duration of 2 years or more. Meta-analysis was performed using Comprehensive meta-analysis v3.0 software. Random effects modelling was used because of observational nature of pooled data. Results In 21 eligible studies, 895 patients underwent anatomic repair with a pooled follow-up of 5457.2 person-years (PY). There was an even split between patients treated with the double switch operation and the atrial switch / ventricular re-routing operation. Pooled estimate for operative mortality was 8.3% (95% CI: 6.0-11.4%). 0.2% (CI: 0.1-0.4%) patients required ECMO/LVAD postoperatively and 1.7% (CI: 1.1-2.4%) developed post-operative AV block requiring a pacemaker. Patients surviving initial surgery had a transplant free survival of 92.5%(CI: 89.5-95.4%) per 100 PY and a low rate of need for pacemaker (0.5% / year; CI: 0.2-0.8%). 84.7% patients (CI: 79.6-89.9%) were found to be in NYHA functional class I or II after 100 PY follow up. Total re-intervention rate was 5.3% per year (CI: 3.8-6.8%). Incidence of baffle stenosis, AV valve dysfunction, neo-aortic insufficiency and LVOT obstruction were estimated at 1.1% (CI: 0.8-1.5%); 0.3% (CI: 0.2-0.5%); 0.5% (CI: 0.2-0.9%) and 0.4% (CI: 0.1-0.6%) per year. Rate of development of LV dysfunction was 1.7%/ year (CI: 1.0-2.4%). Conclusions Despite a relatively high operative mortality, our study provides favorable updated estimates for follow-up outcomes after anatomic repair for cc-TGA patients. The pooled data suggests need for active monitoring over the long term for important complications including heart block and worsening ventricular dysfunction despite majority of patients being in NYHA class I/II.

Pentablock Copolymer from Tetracomponent Monomer Mixture Using a Switchable Dizinc Catalyst

Well-defined pentablock copolymers are prepared using a single catalyst, in one pot, from four different monomers: anhydride, epoxide, lactone, and CO2. The dizinc catalyst bridges three distinct polymerization cycles and performs a double switch in polymerization mechanism to produce pentablock copolymers. The new materials are hydroxyl-telechelic and are efficiently postfunctionalized to introduce polar and nonpolar side-chains.

Visual Osteoclast Fusion via A Fluorescence Method

Osteoclasts are multinucleated giant cells. Fusion is an essential element in the formation of osteoclasts. However, the exact cellular events and mechanisms remain largely unknown because of limited and insufficient methods for observing fusion process. In this work, a fluorescence reporter strategy was established to monitor osteoclast fusion. After fusing with cells expressing Cre recombinase, those cells with double fluorescence switch its expression from red to green fluorescent protein. The effect of RANKL and PTH on osteoclast fusion were both quantitatively and visually detected utilizing this strategy. Furthermore, a combination of this strategy with a technique of fluorescence-activated cell sorting revealed two different populations of fused osteoclasts, tdTomato+ GFP+ cells (TG cells) and GFP+ cells (G cells). The results argue for the potential of combining this technique with other bio-technologies to gain more information about osteoclast fusion. Overall, these data demonstrated that this visual fluorescence switch strategy is useful for further analysis of osteoclast fusion mechanisms.

Double Molecular Photoswitch Driven by Light and Collisions.

The shapes of many molecules can be transformed by light or heat. Here we investigate collision- and photon-induced interconversions of EE, EZ, and ZZ isomers of the isolated Congo red (CR) dianion, a double molecular switch containing two ─N═N─ azo groups, each of which can have the E or Z configuration. We find that collisional activation of CR dianions drives a one-way ZZ→EZ→EE cascade towards the lowest-energy isomer, whereas the absorption of a single photon over the 270-600nm range can switch either azo group from E to Z or Z to E, driving the CR dianion to lower- or higher-energy forms. The experimental results, which are interpreted with the aid of calculated statistical isomerization rates, indicate that photoisomerization of CR in the gas phase involves a passage through conical intersection seams linking the excited and ground state potential energy surfaces rather than through isomerization on the ground state potential energy surface following internal conversion.