The GOAL study: a prospective examination of the impact of factor V Leiden and ABO(H) blood groups on haemorrhagic and thrombotic pregnancy outcomes

Factor V Leiden (FVL) and ABO(H) blood groups are the common influences on haemostasis and retrospective studies have linked FVL with pregnancy complications. However, only one sizeable prospective examination has taken place. As a result, neither the impact of FVL in unselected subjects, any interaction with ABO(H) in pregnancy, nor the utility of screening for FVL is defined. A prospective study of 4250 unselected pregnancies was carried out. A venous thromboembolism (VTE) rate of 1·23/1000 was observed, but no significant association between FVL and pre-eclampsia, intra-uterine growth restriction or pregnancy loss was seen. No influence of FVL and/or ABO(H) on ante-natal bleeding or intra-partum or postpartum haemorrhage was observed. However, FVL was associated with birth-weights >90th centile [odds ratio (OR) 1·81; 95% confidence interval (CI<sub>95</sub>) 1·04–3·31] and neonatal death (OR 14·79; CI<sub>95</sub> 2·71–80·74). No association with ABO(H) alone, or any interaction between ABO(H) and FVL was observed. We neither confirmed the protective effect of FVL on pregnancy-related blood loss reported in previous smaller studies, nor did we find the increased risk of some vascular complications reported in retrospective studies

Common themes and challenges in hemophilia care: a multinational perspective

This is an Accepted Manuscript of an article published by Taylor & Francis in Hematology on 3 Aug 2018, available online: https://doi.org/10.1080/10245332.2018.150522

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

First prospective report on immune tolerance in poor risk haemophilia A inhibitor patients with a single factor VIII/von Willebrand factor concentrate in an observational immune tolerance induction study.

Development of neutralizing inhibitors against factor VIII (FVIII) is a major complication of haemophilia A treatment. The ongoing, international, open-label, uncontrolled, observational immune tolerance induction (ObsITI) study evaluates ITI, the standard of care in patients with inhibitors. Forty-eight prospective patients in this interim analysis received a single plasma-derived, von Willebrand factor-stabilized, FVIII concentrate (pdFVIII/VWF) for ITI. According to recommended Bonn protocol, 'low responders' at ITI start ( Forty of 48 patients (83.3%), had at least one risk factor for poor ITI-prognosis at ITI start (i.e. age ≥7 years, >2 years since inhibitor diagnosis, inhibitor titre ≥10 BU at the start of ITI, or prior ITI failure). Nonetheless, 34 patients (70.8%) achieved complete success, 3 (6.3%) partial success, 1 (2.1%) partial response; ITI failed in 10 patients (20.8%), all with poor prognosis factors. All six low responders achieved complete success. ITI outcome was significantly associated with inhibitor titre level at ITI start (P = 0.0068), number of poor prognosis factors for ITI success (P = 0.0187), monthly bleeding rate during ITI (P = 0.0005) and peak inhibitor titre during ITI (P = 0.0007). Twenty-two of 35 high responder patients (62.9%) with ≥1 poor prognosis factor achieved complete success. Treatment with a single pdFVIII/VWF concentrate, mainly according to the Bonn protocol, resulted in a high ITI success rate in haemophilia A patients with inhibitors and poor prognosis for ITI success