Modeling and experiments of O-band transmission over G.654.C optical fiber.

We address the potential application of G.654.C optical fiber for O-band transmission in the wavelength range of 1270 nm to 1330 nm. Fiber samples at the extreme upper end of the cable cutoff manufacturing distribution are chosen for modeling and experimentation. Modeling of multipath interference (MPI) generation in bend conditions representative of cable deployment suggests minimal to negligible penalty and transmission experiments at 100 Gb/s and 400 Gb/s with commercial IMDD transceivers demonstrate longer transmission with increased power margin compared to standard G.652 fiber due to lower O-band attenuation and no adverse impacts from MPI.

DESTINATION: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the long-term safety and tolerability of tezepelumab in adults and adolescents with severe, uncontrolled asthma.

BACKGROUND: Tezepelumab is a human monoclonal antibody that blocks the activity of the epithelial cytokine thymic stromal lymphopoietin. The efficacy, safety and oral corticosteroid-sparing potential of tezepelumab are being investigated in two ongoing, phase 3, randomized, double-blind, placebo-controlled studies (NAVIGATOR [NCT03347279] and SOURCE [NCT03406078]). DESTINATION (NCT03706079) is a long-term extension (LTE) of these studies. METHODS: DESTINATION is a randomized, double-blind, placebo-controlled LTE study in adults (18-80 years old) and adolescents (12-17 years old) with severe, uncontrolled asthma who are receiving treatment with medium- or high-dose inhaled corticosteroids plus at least one additional controller medication with or without oral corticosteroids. The study population will comprise patients who complete the 52- and 48-week NAVIGATOR and SOURCE studies, respectively. Patients who were randomized to receive tezepelumab 210 mg every 4 weeks (Q4W) in either predecessor study will continue to receive this regimen for 1 year; those who were previously randomized to receive placebo will be re-randomized (1:1) to receive either tezepelumab 210 mg Q4W or placebo for 1 year. Patients will receive their prescribed controller medications throughout DESTINATION and study physicians will have the opportunity to down- or up-titrate dosage of these medications, if appropriate. The primary objective is to evaluate the long-term safety and tolerability of tezepelumab over 104 weeks (inclusive of the treatment period of either predecessor study). The secondary objective is to assess the long-term effect of tezepelumab on asthma exacerbations. Patients recruited from SOURCE will be followed up post-treatment for 12 weeks. Patients recruited from NAVIGATOR who complete 100 weeks of tezepelumab treatment will be eligible for either 12 weeks of follow-up or a 36-week extended follow-up during which the clinical benefit of tezepelumab after treatment cessation will be investigated. DISCUSSION: DESTINATION will evaluate the long-term safety, tolerability and efficacy of tezepelumab versus placebo with continued dosing for up to 2 years. DESTINATION will also evaluate the clinical effect of tezepelumab after treatment cessation. This LTE study aims to elucidate the long-term safety implications of receiving tezepelumab and to assess its potential long-term treatment benefits in patients with severe, uncontrolled asthma. TRIAL REGISTRATION: NCT03706079 (ClinicalTrials.gov). Registered 15 October 2018.

CASCADE: a phase 2, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the effect of tezepelumab on airway inflammation in patients with uncontrolled asthma.

BACKGROUND: Patients with severe, uncontrolled asthma, particularly those with a non-eosinophilic phenotype, have a great unmet need for new treatments that act on a broad range of inflammatory pathways in the airway. Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, an epithelial cytokine. In the PATHWAY phase 2b study (NCT02054130), tezepelumab reduced exacerbations by up to 71% in adults with severe, uncontrolled asthma, irrespective of baseline eosinophilic inflammatory status. This article reports the design and objectives of the phase 2 CASCADE study. METHODS: CASCADE is an ongoing exploratory, phase 2, randomized, double-blind, placebo-controlled, parallel-group study aiming to assess the anti-inflammatory effects of tezepelumab 210 mg administered subcutaneously every 4 weeks for 28 weeks in adults aged 18-75 years with uncontrolled, moderate-to-severe asthma. The primary endpoint is the change from baseline to week 28 in airway submucosal inflammatory cells (eosinophils, neutrophils, T cells and mast cells) from bronchoscopic biopsies. Epithelial molecular phenotyping, comprising the three-gene-mean technique, will be used to assess participants' type 2 (T2) status to enable evaluation of the anti-inflammatory effect of tezepelumab across the continuum of T2 activation. Other exploratory analyses include assessments of the impact of tezepelumab on airway remodelling, including reticular basement membrane thickening and airway epithelial integrity. At the onset of the COVID-19 pandemic, the protocol was amended to address the possibility that site visits would be limited. The amendment allowed for: at-home dosing of study drug by a healthcare professional, extension of the treatment period by up to 6 months so patients are able to attend an onsite visit to undergo the end-of-treatment bronchoscopy, and replacement of final follow-up visits with a virtual or telephone visit. DISCUSSION: CASCADE aims to determine the mechanisms by which tezepelumab improves clinical asthma outcomes by evaluating the effect of tezepelumab on airway inflammatory cells and remodelling in patients with moderate-to-severe, uncontrolled asthma. An important aspect of this study is the evaluation of the anti-inflammatory effect of tezepelumab across patients with differing levels of eosinophilic and T2 inflammation. TRIAL REGISTRATION: NCT03688074 (ClinicalTrials.gov). Registered 28 September 2018.

Transmission of wireless signals using space division multiplexing in few mode fibers.

Evolution of next generation wireless networks brings challenges to efficiently transmit a large amount of data from a base station to a remote antenna unit. We investigate a space division multiplexing technique that employs few mode fibers (FMFs) to transmit 3 × 3 MIMO wireless signals, aiming to employ a common digital signal processing (DSP) unit to equalize both the fiber and wireless channel. We optimize system parameters and obtain above 28 dB and 23 dB signal-to-interference and noise ratio (SINR) for 3 meters wireless systems with 500 m and 2 km FMF, which correspond to the transmission capacity of 578 Mb/s and 468 Mb/s using a 20 MHz bandwidth, respectively. Moreover, we analyze that the nonlinear spectrum distortion due to the combined effect of nonlinearity in the directly modulated laser and the differential mode delay in multimode fibers and validate it by simulations.

Measurements and modeling of multipath interference at wavelengths below cable cut-off in a G.654 optical fiber span.

Transmission below the cable cut-off wavelength may be a concern in some systems, especially for an optical supervisory channel (OSC) operating below the signal transmission band in systems built with G.654 fiber. In this work, we constructed a cabled span of G.654-compliant fiber and measured the multipath interference (MPI) generated during propagation through the span at a range of wavelengths below the cable cut-offs of the constituent fibers. Measurements were made under a range of conditions including different splice losses and the presence or absence of higher order mode filters placed around the splices. MPI levels were found to be sufficiently low at wavelengths far below the average cable cut-off such that OSC transmission was penalty-free. We compare the experimental results to modeling predictions and find very good agreement.

Rising trends of endogenous Klebsiella pneumoniae endophthalmitis in Australia.

BACKGROUND: Endogenous Klebsiella pneumoniae endophthalmitis (EKPE) is a well-known entity in South-East Asia. We demonstrate a range of differing clinical features and outcomes of EKPE, and highlight the increasing incidence of EKPE in major centres in Sydney and Melbourne, Australia. DESIGN: Retrospective observational case study and case series in the hospital setting. PARTICIPANTS: Four cases of EKPE. METHODS: EKPE cases from 2005 to 2015 were identified through established endophthalmitis databases as well as hospital-based microbiological searches. MAIN OUTCOME MEASURES: EKPE cases were confirmed with positive K. pneumoniae intraocular samples. RESULTS: Rising trends of EKPE were noted in major centres in Australia. Six eyes of four patients with EKPE from January 2011 to December 2015 are reported. The mean age was 49 years (range 43-58 years). Two patients had bilateral involvement. There were systemic symptoms up to 10 days prior to ocular symptoms. The source of sepsis in all cases was a hepatic abscess. Two patients had diabetes mellitus. Five eyes had hypopyon panuveitis on presentation. All eyes underwent vitrectomy. The patient with the most delayed presentation underwent enucleation following globe perforation. Final best corrected visual acuity (BCVA) in one patient with bilateral EKPE was light perception (LP) only. The other three eyes had BCVA in at least one eye of 6/24 or better. CONCLUSIONS: EKPE is an emerging condition in Australia. Although rare, EKPE is a sight-threatening and potentially life-threatening emergency that can initially present to ophthalmologists. One should suspect EKPE in septic patients with a B-scan showing a vitreous or retinal abscess.

Long-haul quasi-single-mode transmissions using few-mode fiber in presence of multi-path interference.

We study long-haul Quasi-Single-mode (QSM) systems in which signals are transmitted in the fundamental modes of a few-mode fiber (FMF) while keeping other system components such as amplifiers and receivers are kept single-moded. The large-effective-area nature of the FMF fundamental modes improves system nonlinear tolerance in the expense of mode coupling along FMF transmissions which induces multi-path interference (MPI) and needs to be compensated. We analytically investigate 6-spatial-polarization mode QSM transmission systems in presence of MPI and show that in the weak coupling regime, the QSM channel is a Gaussian random process in frequency. MPI compensation filters are derived and performance penalties due to MPI and signal loss from higher-order modes are characterized. We also experimentally demonstrate 256 Gb/s polarization multiplexed (PM)-16-QAM QSM transmissions over a record distance of 2600 km with 100-km span using decision directed least mean square (DD-LMS) algorithm for MPI compensation.

Unrepeatered 256 Gb/s PM-16QAM transmission over up to 304 km with simple system configurations.

We study unrepeatered transmission of 40x256 Gb/s systems with polarization-multiplexed 16-quadrature amplitude modulation (PM-16QAM) channels using simple coherent optical system configurations. Three systems are investigated with either a homogeneous fiber span, or simple two-segment hybrid fiber designs. Each system relies primarily on ultra-low loss, very large effective area fiber, while making use of only first-order backward pumped Raman amplification and no remote optically pumped amplifier (ROPA). For the longest span studied, we demonstrate unrepeatered 256 Gb/s transmission over 304 km with the additional aid of nonlinear compensation using digital backpropagation. We find an average performance improvement in terms of the Q-factor of 0.45 dB by using digital backpropagation compared to the case of using chromatic dispersion compensation alone for an unrepeatered span system.

Study of EDFA and Raman system transmission reach with 256 Gb/s PM-16QAM signals over three optical fibers with 100 km spans.

We compare the transmission performance of three different optical fibers in separate 256 Gb/s PM-16QAM systems amplified with erbium doped fiber amplifiers (EDFAs) and distributed Raman amplification. The span length in each system is 100 km. The fibers studied include standard single-mode fiber, single-mode fiber with ultra-low loss, and ultra-low loss fiber with large effective area. We find that the single-mode fiber with ultra-low loss and the large effective area fiber with ultra-low loss afford reach advantages of up to about 31% and 80%, respectively, over standard fiber measured at distances with 3 dB margin over the forward error correction (FEC) threshold. The Raman amplified systems provide about 50% reach length enhancement over the EDFA systems for all three fibers in the experimental set-up. For the best performing fiber with large effective area and ultra-low loss, the absolute reach lengths with 3 dB margin are greater than 1140 km and 1700 km for the for EDFA and Raman systems, respectively.

Ultra-long-haul 112 Gb/s PM-QPSK transmission systems using longer spans and Raman amplification.

Ultra-long-haul transmission at distances greater than 10,000 km is investigated for 112 Gb/s PM-QPSK signals using span lengths of 75 km and 100 km and all-Raman amplification. Two different ultra-low loss and large effective area optical fibers are studied. We demonstrate a reach length of 10,200 km for a 40 channel system using a fiber with effective area 112 µm(2) with 100 km spans, and a reach length of 13,288 km for a system with 75 km spans using a fiber with effective area of 134 µm(2).

112 Gb/s PM-QPSK transmission up to 6000 km with 200 km amplifier spacing and a hybrid fiber span configuration.

We demonstrate transmission of 112 Gb/s PM-QPSK signals over a system with 200 km span lengths. Amplification is provided by hybrid backward-pumped Raman/EDFA amplifiers and reach lengths up to 6000 km for an 8 channel system and 5400 km for a 32 channel system are shown. As a means of maximizing OSNR, a simple hybrid fiber span configuration is used that combines two ultra-low loss fibers, one having very large effective area.

Transmission of 112 Gb/s PM-QPSK signals over up to 635 km of multimode optical fiber.

We investigate transmission of 112 Gb/s PM-QPSK signals over 50 µm core diameter OM3 multimode fiber using the center launch approach. We demonstrate successful transmission of 16 DWDM channels over a distance of 635 km for a capacity-distance product of 1016 Tb/s-km. The limiting impairment appears due to mode coupling and multipath interference effects.

Pulse shaping for 112 Gbit/s polarization multiplexed 16-QAM signals using a 21 GSa/s DAC.

The implications of increasing the symbol rate for a given digital-to-analog converter (DAC) sampling rate are investigated by considering the generation of 112 Gbit/s PM 16-QAM signals (14 Gsym/s) using a 21 GSa/s DAC with 6-bit resolution.

Successful surgical management of interlenticular membrane by vitreoretinal interlenticular membranectomy (VIM).

The formation of a light scattering interlenticular membrane (ILM) is a known complication of polypseudophakia and has been particularly noted with the use of dual intracapsular Alcon AcrylSof intraocular lenses (IOLs). The treatment options for this condition have largely been restricted to either Nd:YAG laser membranotomy or explantation of the dual IOL complex. In this case report, we describe an unusual case of ILM in a 76-year-old woman whose ILM had formed between her primary intracapsular IOL and her piggyback sulcal IOL. Furthermore, we describe vitreoretinal interlenticular membranectomy (VIM), a novel technique involving a translimbal anterior interlenticular membranectomy using vitreoretinal instrumentation. There were no intraoperative or postoperative complications. Postoperative best-corrected visual acuity was 6/4, maintained for 3 years of follow-up. VIM is offered as a management option for surgeons to address ILM when Nd:YAG laser therapy fails, and the IOLs cannot be safely explanted.

Presentation and surgical management of a superficial temporal artery pseudoaneurysm: A case report.

INTRODUCTION AND IMPORTANCE: A Superficial Temporal Artery Pseudoaneurysm is an uncommon, but important, differential diagnosis for masses in the head and neck region. This work has been reported in line with SCARE 2020 criteria [1]. CASE PRESENTATION: An 81-year-old male presented to the Oral and Maxillofacial Department with a facial swelling that had been present for a duration of three weeks. A provisional diagnosis of a haematoma was made and an ultrasound carried out to confirm diagnosis. Ultrasonography and CT Angiography confirmed a pseudoaneurysm arising from the left superficial temporal artery. CLINICAL DISCUSSION: Although this is a relatively uncommon diagnosis it is important to be aware of the key diagnostic tools used to identify a pseudoaneurysm. Specifically, their potential to exclude a pseudoaneurysm prior to diagnosing a simple post-traumatic haematoma. This is important as the treatment strategies for the two pathologies differ considerably. Useful learning points from this case include diagnostic aids such as the unique pulsatile nature of the mass and the role of ultrasonography and CT Angiography in confirming diagnosis and guiding surgical management. CONCLUSION: Pseudoaneurysms are an important consideration as a differential diagnosis of masses in the head and neck region. This case report may impact upon management of future similar cases by highlighting significant aspects of their clinical diagnosis and surgical management, enabling early identification and appropriate management.

Tezepelumab Pharmacokinetics, Safety, and Tolerability After Administration via Vial-and-syringe, Accessorized Prefilled Syringe, or Autoinjector: A Randomized Trial in Healthy Volunteers.

PURPOSE: Tezepelumab is an anti-thymic stromal lymphopoietin monoclonal antibody therapeutic in development for patients with severe, uncontrolled asthma. In ongoing Phase III studies, tezepelumab is administered via subcutaneous (SC) injections using a vial-and-syringe (V-S). This study compared the pharmacokinetic (PK) parameters, safety, and tolerability of tezepelumab administered subcutaneously via V-S versus via an accessorized prefilled syringe (APFS) or autoinjector (AI). METHODS: This single-center, randomized, open-label, parallel-group study was conducted in healthy volunteers aged 18-65 years. Participants, stratified according to weight (50 to <70 kg, 70 to <80 kg, or 80-90 kg), were randomized evenly to 9 groups representing injections to the abdomen, thigh, or upper arm via V-S, APFS, or AI. Tezepelumab PK parameters over 113 days were evaluated after a single 210-mg SC dose. The primary end points were comparison of Cmax and AUC0-∞ between device groups. Further PK parameters, immunogenicity, safety (including injection site reactions [ISRs] and injection site pain [visual analog scale]) were also assessed. FINDINGS: A total of 315 adults were randomized to treatment. Geometric mean ratios for comparisons between device groups of Cmax, AUC0-∞, and AUC0-last were close to 1, with 90% CIs all within the range of 0.8-1.25, meeting bioequivalence criteria. PK variables were also similar between devices across injection sites and weight categories. Across devices, thigh injection resulted in slightly higher exposure than upper arm injection, and abdomen injection resulted in exposure similar to or slightly lower than thigh injection; however, these differences were not clinically meaningful. Treatment-emergent anti-tezepelumab antibodies were present in 3 (2.9%), 1 (1.0%), and 0 participants in the V-S, APFS, and AI groups, respectively. Treatment-related adverse events were reported in 15.0% of participants overall (V-S, 10.7%; APFS, 18.1%; AI, 16.0%), including ISRs in 1 (1.0%), 3 (2.9%), and 3 (2.8%) participants in the V-S, APFS, and AI groups. Median visual analog scale pain score (0-100 mm scale) was 2 mm immediately after injection and was 0 mm at 30 min for all groups. IMPLICATIONS: Tezepelumab PK parameters after a single 210-mg SC dose were comparable when administered via V-S, APFS, or AI. In all groups, immunogenicity rate and injection site pain were low, and ISRs were uncommon. These findings support administration of tezepelumab via APFS or AI, in addition to V-S, providing patients and physicians with greater choice and the potential convenience of at-home use. ClinicalTrials.gov identifier: NCT03989544.

Functionality and Performance of an Accessorized Pre-Filled Syringe and an Autoinjector for At-Home Administration of Tezepelumab in Patients with Severe, Uncontrolled Asthma.

BACKGROUND: Tezepelumab is an anti-thymic stromal lymphopoietin monoclonal antibody in development for the treatment of severe asthma. This study assessed the functionality and performance of an accessorized pre-filled syringe (APFS) and an autoinjector (AI) for administration of tezepelumab in the clinic and at home. METHODS: This phase 3, multicenter, randomized, open-label, parallel-group study (PATH-HOME, ClinicalTrials.gov identifier: NCT03968978) was conducted in patients aged 12-80 years with asthma that was uncontrolled despite treatment with medium- to high-dose inhaled corticosteroids plus at least one additional controller medication. Patients received six subcutaneous doses of tezepelumab 210 mg via APFS or AI. The first dose was administered by a healthcare professional, and patients or caregivers administered subsequent doses. First, second, third and final doses were administered in the clinic; fourth and fifth doses were administered at home. The primary endpoint was the proportion of successful administrations of tezepelumab. Secondary endpoints included the functionality and performance of the devices, Asthma Control Questionnaire (ACQ)-6 score, pharmacokinetics and safety. RESULTS: Overall, 216 patients were randomized (APFS, n=111; AI, n=105). Tezepelumab was successfully administered via APFS by 91.7% of the participants (100/109) and via AI by 92.4% (97/105). Overall, 95.4-97.1% of at-home administrations were successful across device groups. Malfunction occurred in 6 of 655 dispensed APFSs and 5 of 624 dispensed AIs. Clinically meaningful improvements in ACQ-6 score were observed after 24 weeks in 81.1% and 76.2% of the patients in the APFS and AI groups, respectively. Tezepelumab pharmacokinetics were consistent between device groups and with previous studies. The most common adverse event was nasopharyngitis (9.3%). Injection-site reactions occurred in 5.7% and 0% of the patients in the AI and APFS groups, respectively. CONCLUSION: This study demonstrated that the APFS and AI were functional and reliable, and performed equally well at home and in the clinic.

Ultra-low-loss optical fiber enabling purely passive 10 Gb/s PON systems with 100 km length.

We demonstrate time division multiplexing (TDM) and wavelength division multiplexing/TDM (WDM/TDM) long reach 10 Gb/s passive optical network (PON) architectures of 100 km reach with no infield amplification or dispersion compensation. The purely passive nature of the 100 km systems is enabled by the use of ultra-low-loss optical fiber with average attenuation of 0.17 dB/km and downstream transmission with a 10 Gb/s signal modulated with the duobinary format. The high tolerance of duobinary to dispersion, stimulated Brillouin scattering (SBS), and self-phase modulation (SPM) are all key factors to achieving good system performance at this distance, as is the significantly reduced loss from the ultra-low-loss fiber. We show that this combination of fiber and downstream signal format allow split ratios up to 1:128 for both system architectures. The achievable split ratio is reduced for standard single-mode fiber and/or use of an NRZ modulated downstream signal. Standard strength forward error correction (FEC) is used for the WDM/TDM system but is not required for the TDM system.

XPM and SBS nonlinear effects on MLSE with varying uncompensated dispersion.

We investigate the performance of a maximum likelihood sequence estimation (MLSE) receiver at 10.7 Gb/s in the presence of two optical nonlinear impairments, cross-phase modulation (XPM) and stimulated Brillouin scattering (SBS). We find that the tolerance to both nonlinearities decreases with larger levels of uncompensated dispersion. Our results also suggest that the MSLE receiver loses its linear regime advantage in comparison to a standard receiver at some dispersion levels in the presence of the nonlinear effects. We demonstrate that long uncompensated links up to 160 km may show better tolerance to the nonlinear effects with a lower dispersion fiber when using an MLSE receiver.