Zero incidence of factor VIII inhibitors and successful haemostatic response in previously factor VIII-treated patients with haemophilia A switching to turoctocog alfa in a noninterventional study

Introduction: Turoctocog alfa (NovoEight®) is a B-domain-truncated recombinant factor VIII (FVIII) approved for patients with haemophilia A. Aim: To investigate the long-term safety and efficacy of turoctocog alfa in routine clinical practice. Methods: Guardian 5 was a prospective, multinational, non-interventional, post-authorisation safety study. Male previously treated patients (> 150 exposure days [EDs]) of any age with severe/moderately severe haemophilia A (FVIII ≤ 2%) and a negative inhibitor test prior to first dosing (independent of FVIII-inhibitor history) were included to receive prophylaxis or on-demand treatment. The primary endpoint was the proportion of patients developing FVIII inhibitors (≥.6 Bethesda Units [BU]) after baseline visit, measured as per routine practice of each study site during clinic visits. Secondary endpoints included haemostatic effect, annualised bleeding rate (ABR), and adverse reactions assessment. The study concluded when 50 patients reached 100 EDs/patient minimum. Results: Seventy patients were screened and 68 exposed to turoctocog alfa; 63 (92.6%) were on prophylaxis and five received on-demand treatment. Six (8.8%) patients reported a history of positive inhibitors. During the study, patients were exposed to turoctocog alfa for a mean (standard deviation) of 131.9 (99.0) days/patient. Fifty-five of 58 patients who completed the study were tested for FVIII inhibitors; no positive tests were reported. Overall success rate of turoctocog alfa for treatment of bleeds was 87.3%. Among patients receiving prophylaxis, median (range) ABR was 1.97 (.0–25.5) bleeds/year; estimated ABR (negative binomial model) was 3.65 (95% confidence interval: 2.53–5.25). Conclusion: Turoctocog alfa was safe and efficacious for haemophilia A treatment in routine clinical practice

Bose-Einstein condensation of strongly correlated electrons and phonons in cuprate superconductors

The long-range Froehlich electron-phonon interaction has been identified as the most essential for pairing in high-temperature superconductors owing to poor screening, as is now confirmed by optical, isotope substitution, recent photoemission and some other measurements. I argue that low energy physics in cuprate superconductors is that of superlight small bipolarons, which are real-space hole pairs dressed by phonons in doped charge-transfer Mott insulators. They are itinerant quasiparticles existing in the Bloch states at low temperatures as also confirmed by continuous-time quantum Monte-Carlo algorithm (CTQMC) fully taking into account realistic Coulomb and long-range Froehlich interactions. Here I suggest that a parameter-free evaluation of Tc, unusual upper critical fields, the normal state Nernst effect, diamagnetism, the Hall-Lorenz numbers and giant proximity effects strongly support the three-dimensional (3D) Bose-Einstein condensation of mobile small bipolarons with zero off-diagonal order parameter above the resistive critical temperature Tc at variance with phase fluctuation scenarios of cuprates.Comment: 35 pages, 10 figures, to appear in the special volume of Journal of Physics: Condensed Matte

Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks

Background For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). Objective To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). Methods Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353). Results A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment. Conclusions In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms

The use of in situ X-ray absorption spectroscopy in applied fuel cell research

It is known that polarization-sensitive backscattering images of different objects in turbid media may show better contrasts than usual intensity images. Polarimetric image contrast depends on both target and background polarization properties and typically involves averaging over groups of pixels, corresponding to given areas of the image. By means of numerical modelling we show that the experimental arrangement, namely, the shape of turbid medium container, the optical properties of the container walls, the relative positioning of the absorbing, scattering and reflecting targets with respect to each other and to the container walls, as well as the choice of the image areas for the contrast calculations, can strongly affect the final results for both linearly and circularly polarized light

Atmospheric Plasma Deposition: A New Pathway in the Design of Conducting Polymer-Based Anodes for Hydrogen Fuel Cells

In this study, we explored thin films of nanofibrous functionalised conducting plasma polyaniline (pPANI) with platinum deposited by an atmospheric plasma deposition process for the potential design of anodes for hydrogen fuel cell applications. We observed that the incorporation of such a polymer, characterised by both electronic and ionic conductivity, associated with a catalyst in a 3D porous network, could lead to an increased probability of the three-phase contact to occur. In this context, aniline was mixed with functionalised platinum nanoparticles and used as the precursor. The role of these functionalised nanoparticles was not only to act as the catalyst for fuel cell purposes, but also as nucleation sites promoting the formation of the nanofibrous pPANI thin film during the plasma polymerisation. The morphology of the thin film was analysed by scanning electron microscopy and the efficiency, in terms of energy conversion, was assessed in a single fuel cell test bench

Spatially resolved degradation effects in membrane-electrode-assemblies of vehicle aged polymer electrolyte membrane fuel cell stacks

State of the art MEAs were aged in a fuel cell vehicle and degradation effects analyzed using electron microscopy and electrochemical methods. All cells of the stack showed a performance decay along with a loss in the electrochemical surface area. This could be correlated to particle growth and carbon corrosion observed by electron microscopy. Spatially resolved investigations showed a significant deterioration of the cathode, which is particularly pronounced at the hydrogen inlet. Differences in the cell performance of the aged cells could not be attributed to a variation in the catalyst degradation, but are linked to an altered ohmic resistance in the cells. The ohmic resistance of the cells is likely to be affected by the formation of precipitates in the membrane and seems to be correlated with their size

Dissolution and Migration of Platinum in PEMFCs Investigated for Start/Stop Cycling and High Potential Degradation

Dissolution and migration of platinum due to start/stop degradation and increased cathode potentials were studied for commercial membrane electrode assemblies (MEA). The chosen conditions closely mimic real situations in automotive operation. In start/stop tests, we observed a strongly enhanced platinum dissolution due to the dynamic interplay of repeated cell start-up and consecutive normal fuel cell operation, which is related to platinum oxidation (start-up) and reduction (normal operation) cycles. Consequently, the performed test protocols distinguish between dynamic and static load profiles. Electrochemical investigations before and after degradation monitor the loss in cell performance. Since electron microscopy offers the unique possibility to unravel and distinguish degradation due to carbon corrosion and agglomeration or platinum dissolution, a focus was set on this method. For the start/stop MEA pronounced platinum dissolution accompanied by the formation of large platinum precipitations in the membrane was found. Carbon corrosion was also observed, but did not lead to a significantly reduced porosity and loss in platinum dispersion. In contrast, the MEA which was exposed to high constant potentials exhibited severe damage to the 3D cathode structure due to carbon corrosion. However, no pronounced platinum dissolution was observed and only few Pt precipitations were found in the membrane itself