Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa

Background: This post hoc subanalysis examined outcomes in adult patients with Morquio A (mucopolysaccharidosis IVA) who received enzyme replacement therapy (ERT) with elosulfase alfa over a 120-weeks period. Patients ≥18 years of age evaluated in an open-label, long-term extension study of elosulfase alfa (modified per protocol [MPP], n = 32; intent-to-treat [ITT], n = 37; MOR-005; NCT01415427) were compared with the ≥18-year-old untreated population with 2-years follow-up from a Morquio A natural history study (n = 10; MorCAP; NCT00787995). The MOR-005 MPP population excluded patients who underwent orthopedic surgical procedures or were noncompliant with study protocol (defined as missing ≥20% of ERT infusions). No MorCAP patients underwent orthopedic surgical procedures during the relevant time period. Endurance was assessed by the 6-min walk test (6MWT) and 3-min stair climb test (3MSCT). Activities of daily living (ADLs) were assessed by the MPS Health Assessment Questionnaire (MPS HAQ). / Results: Least squares (LS) mean (SE) 6MWT distances increased by 34.9 (11.7) m (MPP) and 30.5 (10.8) m (ITT) by week 120; LS mean (SE) change in 3MSCT at week 120 was 6.7 (1.8) stairs/min (MPP) and 5.9 (1.7) stairs/min (ITT). MorCAP patients showed no improvement in 6MWT distance or 3MSCT over a similar period of time. Pulmonary function measures remained unchanged in both MOR-005 and MorCAP adults. All MPS HAQ domain scores improved in MOR-005 adults, whereas MorCAP adults had unchanged caregiver assistance and mobility outcomes and worsened self-care outcomes. / Conclusions: Long-term ERT in adult patients with Morquio A was associated with increased endurance and improvement in performance of ADLs. / Trial registration: Trial Registration NCT01415427. Name of registry: Long-Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome). Registered 8 August 2011, retrospectively registered

Compact and Low-Cost 3-D Printed Antennas Metalized Using Spray-Coating Technology for 5G mm-Wave Communication Systems

This letter presents a design of two compact, light, rigid, and low-cost three-dimensionally (3-D) printed millimeter-wave antennas for a fifth-generation (5G) communication system. The proposed antennas consist of a radiating slot that is surrounded by a rectangular cavity and corrugations, which boost the gain performance of the antennas. Furthermore, the proposed antennas are fabricated using 3-D printing technology, and they are metalized using novel, simple, and low-cost techniques, which utilize the commercial conducive spray-coating technology. The proposed antennas operate at a 28 GHz band, where the first design is fed by a waveguide to prove the performance, whereas the second design is fed by a microstrip line to demonstrate the ability to be integrated into a compact structure. Measurement results show a wide impedance bandwidth, which enables the proposed antenna design to be a strong candidate for 5G applications

The eigenvalue problem for the ∞-Bilaplacian

We consider the problem of finding and describing minimisers of the Rayleigh quotient Λ∞:=infu∈W2,∞(Ω)∖{0}∥Δu∥L∞(Ω)∥u∥L∞(Ω), Λ∞:=infu∈W2,∞(Ω)∖{0}‖Δu‖L∞(Ω)‖u‖L∞(Ω), where Ω⊆RnΩ⊆Rn is a bounded C1,1C1,1 domain and W2,∞(Ω)W2,∞(Ω) is a class of weakly twice differentiable functions satisfying either u=0u=0 on ∂Ω∂Ω or u=|Du|=0u=|Du|=0 on ∂Ω∂Ω . Our first main result, obtained through approximation by LpLp -problems as p→∞p→∞ , is the existence of a minimiser u∞∈W2,∞(Ω)u∞∈W2,∞(Ω) satisfying {Δu∞∈Λ∞Sgn(f∞)Δf∞=μ∞ a.e. in Ω, in D′(Ω), {Δu∞∈Λ∞Sgn(f∞) a.e. in Ω,Δf∞=μ∞ in D′(Ω), for some f∞∈L1(Ω)∩BVloc(Ω)f∞∈L1(Ω)∩BVloc(Ω) and a measure μ∞∈M(Ω)μ∞∈M(Ω) , for either choice of boundary conditions. Here Sgn is the multi-valued sign function. We also study the dependence of the eigenvalue Λ∞Λ∞ on the domain, establishing the validity of a Faber–Krahn type inequality: among all C1,1C1,1 domains with fixed measure, the ball is a strict minimiser of Ω↦Λ∞(Ω)Ω↦Λ∞(Ω) . This result is shown to hold true for either choice of boundary conditions and in every dimension

Open issues in mucopolysaccharidosis type I-hurler

Mucopolysaccharidosis I-Hurler (MPS I-H) is the most severe form of a metabolic genetic disease caused by mutations of IDUA gene encoding the lysosomal α-L-iduronidase enzyme. MPS I-H is a rare, life-threatening disease, evolving in multisystem morbidity including progressive neurological disease, upper airway obstruction, skeletal deformity and cardiomyopathy. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the gold standard for the treatment of MPS I-H in patients diagnosed and treated before 2-2.5 years of age, having a high rate of success. Beyond the child's age, other factors influence the probability of treatment success, including the selection of patients, of graft source and the donor type employed. Enzyme replacement therapy (ERT) with human recombinant laronidase has also been demonstrated to be effective in ameliorating the clinical conditions of pre-transplant MPS I-H patients and in improving HSCT outcome, by peri-transplant co-administration. Nevertheless the long-term clinical outcome even after successful HSCT varies considerably, with a persisting residual disease burden. Other strategies must then be considered to improve the outcome of these patients: one is to pursue early pre-symptomatic diagnosis through newborn screening and another one is the identification of novel treatments. In this perspective, even though newborn screening can be envisaged as a future attractive perspective, presently the best path to be pursued embraces an improved awareness of signs and symptoms of the disorder by primary care providers and pediatricians, in order for the patients' timely referral to a qualified reference center. Furthermore, sensitive new biochemical markers must be identified to better define the clinical severity of the disease at birth, to support clinical judgement during the follow-up and to compare the effects of the different therapies. A prolonged neuropsychological follow-up of post-transplant cognitive development of children and residual disease burden is needed. In this perspective, the reference center must guarantee a multidisciplinary follow-up with an expert team. Diagnostic and interventional protocols of reference centers should be standardized whenever possible to allow comparison of clinical data and evaluation of results. This review will focus on all these critical issues related to the management of MPS I-H

Modal analysis of holey fiber mode-selective couplers

Mode Division Multiplexing is currently investigated as a possible way to increase fiber system capacity. With this approach, different modes of the same fiber carry distinct information. One of the problems to be solved in these systems concerns coupling/decoupling of the various modes to/from the same fiber. In this presentation, the mode features of a mode mux/demux based on holey fibers are investigated, with particular emphasis on optimal device design. Some preliminary experimental results will also be presented