Factor VIII assay variability in postinfusion samples containing full length and B-domain deleted FVIII

Introduction Although the variability in factor VIII (FVIII):C measurement is well recognized, this has not been widely reported for post-FVIII infusion samples. Aim/Methods Three samples from haemophilia A patients were distributed in a UK National External Quality Assessment Scheme survey, each after treatment with either ReFacto AF, Kogenate FS or Advate. Fifty-two UK haemophilia centres performed FVIII assays using one-stage (n = 46) and chromogenic (n = 10) assays. Centres calibrated assays with the local plasma standard and with ReFacto AF laboratory standard for the ReFacto AF sample. Results/Conclusions Chromogenic assays gave significantly higher results than one-stage assays (P < 0.0001, 32% difference) in the post-Kogenate sample but not in the post-ReFacto AF (11% higher by chromogenic assay, ns) or post-Advate samples (3% lower by chromogenic, ns) when assays were calibrated with plasma standards. Twenty centres used all Instrumentation Laboratory (IL)-activated partial thromboplastin time reagents (Synthasil)/IL deficient plasma/reference plasma) in the one-stage assay and 15 used all Siemens reagents (Actin FS/Siemens deficient plasma/reference plasma); this made a significant difference to results post-ReFacto AF (41% higher by IL reagents, P < 0.0001) and Advate (39% higher by IL reagents, P < 0.0001), but not Kogenate (7% higher by IL, ns) when calibrated with plasma standards. Differences between results obtained with different one-stage assay reagents for monitoring Advate have implications for dosing patients. Furthermore, there was considerable inter-laboratory variation as indicated by CVs in the range 15–26% for chromogenic assay and 12–19% for one-stage assay results. This study suggests that external quality assessment schemes should offer participation in post-FVIII infusion schemes where haemophilic patients are monitored

Clotting and chromogenic factor VIII assay variability in post-infusion and spiked samples containing full-length recombinant FVIII or recombinant factor VIII Fc fusion protein (rFVIIIFc).

INTRODUCTION: Variability in FVIII measurement is a recognized problem. There are limited data for samples containing recombinant Factor VIII Fc fusion protein (rFVIIIFc). Many studies use samples for which factor concentrate has been spiked into FVIII deficient plasma in vitro. This approach requires validation. AIM/METHODS: Four samples were distributed in a UK National External Quality Assessment Scheme for Blood Coagulation (NEQAS BC) survey. One contained Advate (full-length recombinant FVIII) (rFVIII) added to FVIII deficient plasma, one was from a severe haemophilia A patient after infusion of Advate, one was prepared by addition of rFVIIIFc (marketed as Elocta/Eloctate) to FVIII deficient plasma and the fourth was collected from a severe haemophilia A patient following rFVIIIFc (Eloctate) infusion. Fifty-three haemophilia centres (UK and Scandinavia) performed one-stage FVIII assays and 27 performed chromogenic FVIII assays. RESULTS/CONCLUSIONS: One-stage assays gave significantly lower results than chromogenic assays by 7% (P < 0.01) and 13%(P < 0.001) for post-Advate and Advate spiked samples, and by 22% (P < 0.001) and 23% (P < 0.001) for post-rFVIIIFc and rFVIIIFc spiked samples. The interlaboratory variation was similar for all samples, with CVs of 12%-16% (chromogenic) and 10%-13% (one stage). The data indicate that either product can be safely monitored by one-stage or chromogenic assay. Spiked samples behaved in a similar way to post-infusion samples for both products and could be substituted for post-infusion samples for use in proficiency testing exercises (ie, samples were commutable)

Kelyphite textures experimentally reproduced through garnet breakdown in the presence of a melt phase

Complex multiphase reaction rims that form during garnet breakdown are known as kelyphite coronae and are common amongst exhumed mantle xenoliths. It has long been established that a reaction of garnet and olivine produces kelyphite corona consisting of spinel and pyroxenes, and that preservation of high-pressure garnet cores requires sufficiently rapid uplift of material through the spinel lherzolite stability field from depths of at least 60 km.We present new high-pressure, high-temperature experiments of garnet breakdown in the spinel-lherzolite stability field demonstrating that a series of cascading reactions can reproduce the multilayer, multiphase kelyphites seen in nature. In all experiments where breakdown occurred, a melt appears to have moderated the reactions towards equilibrium; we believe this to be the first experimental confirmation of the importance of such melts in garnet breakdown reactions. In our experiments at least three distinct zones of concentric kelyphite growth can occur at a single pressure, temperature condition; we suggest, therefore, that such kelyphites seen in natural samples do not have to be caused by a multistage uplift path as is often assumed.Kelyphitic coronae surrounding garnet have previously been used to estimate uplift rates, however, the lack of kinetic data for relevant exhumation reactions has limited their use for PTt pathway estimations and the understanding of emplacement mechanisms. In order to constrain accurate PTt pathways we use reaction rim thickness as a proxy for reaction progress and present preliminary results for the kinetics of garnet breakdown

Cryogenic Characterization of Commercial SiC Power MOSFETs

The cryogenic performance of two commercially available SiC power MOSFETs are presented in this work. The devices are characterised in static and dynamic tests at 10 K intervals from 20-320 K. Static current-voltage characterisation indicates that at low temperatures threshold voltage, turn-on voltage, on-state resistance, transconductance, and the body diode turn-on voltage all increase while saturation current decreases. Dynamic, 60 V, 3A switching tests within the cryogenic chamber are also reported and the trends of switching speed, losses, and total power losses, which rise at low temperature, are presented. Overall, both MOSFETs are fully operable down to 20 K with both positive and negative changes in behaviour.</p

A Naturally Narrow Positive Parity Theta^+

We present a consistent color-flavor-spin-orbital wave function for a positive parity Theta^+ that naturally explains the observed narrowness of the state. The wave function is totally symmetric in its flavor-spin part and totally antisymmetric in its color-orbital part. If flavor-spin interactions dominate, this wave function renders the positive parity Theta^+ lighter than its negative parity counterpart. We consider decays of the Theta^+ and compute the overlap of this state with the kinematically allowed final states. Our results are numerically small. We note that dynamical correlations between quarks are not necessary to obtain narrow pentaquark widths.Comment: 10 pages, 1 figure, Revtex4, two-column format, version to be published in Phys. Rev. D, includes numerical estimates of decay width

Color Transparency versus Quantum Coherence in Electroproduction of Vector Mesons off Nuclei

So far no theoretical tool for the comprehensive description of exclusive electroproduction of vector mesons off nuclei at medium energies has been developed. We suggest a light-cone QCD formalism which is valid at any energy and incorporates formation effects (color transparency), the coherence length and the gluon shadowing. At medium energies color transparency (CT) and the onset of coherence length (CL) effects are not easily separated. Indeed, although nuclear transparency measured by the HERMES experiment rises with Q^2, it agrees with predictions of the vector dominance model (VDM) without any CT effects. Our new results and observations are: (i) the good agreement with the VDM found earlier is accidental and related to the specific correlation between Q^2 and CL for HERMES kinematics; (ii) CT effects are much larger than have been estimated earlier within the two channel approximation. They are even stronger at low than at high energies and can be easily identified by HERMES or at JLab; (iii) gluon shadowing which is important at high energies is calculated and included; (iv) our parameter-free calculations explain well available data for variation of nuclear transparency with virtuality and energy of the photon; (v) predictions for electroproduction of \rho and \phi are provided for future measurements at HERMES and JLab.Comment: Latex 57 pages and 17 figure

Experimental and Theoretical Challenges in the Search for the Quark Gluon Plasma: The STAR Collaboration's Critical Assessment of the Evidence from RHIC Collisions

We review the most important experimental results from the first three years of nucleus-nucleus collision studies at RHIC, with emphasis on results from the STAR experiment, and we assess their interpretation and comparison to theory. The theory-experiment comparison suggests that central Au+Au collisions at RHIC produce dense, rapidly thermalizing matter characterized by: (1) initial energy densities above the critical values predicted by lattice QCD for establishment of a Quark-Gluon Plasma (QGP); (2) nearly ideal fluid flow, marked by constituent interactions of very short mean free path, established most probably at a stage preceding hadron formation; and (3) opacity to jets. Many of the observations are consistent with models incorporating QGP formation in the early collision stages, and have not found ready explanation in a hadronic framework. However, the measurements themselves do not yet establish unequivocal evidence for a transition to this new form of matter. The theoretical treatment of the collision evolution, despite impressive successes, invokes a suite of distinct models, degrees of freedom and assumptions of as yet unknown quantitative consequence. We pose a set of important open questions, and suggest additional measurements, at least some of which should be addressed in order to establish a compelling basis to conclude definitively that thermalized, deconfined quark-gluon matter has been produced at RHIC.Comment: 101 pages, 37 figures; revised version to Nucl. Phys.

The geology and geophysics of Kuiper Belt object (486958) Arrokoth

The Cold Classical Kuiper Belt, a class of small bodies in undisturbed orbits beyond Neptune, are primitive objects preserving information about Solar System formation. The New Horizons spacecraft flew past one of these objects, the 36 km long contact binary (486958) Arrokoth (2014 MU69), in January 2019. Images from the flyby show that Arrokoth has no detectable rings, and no satellites (larger than 180 meters diameter) within a radius of 8000 km, and has a lightly-cratered smooth surface with complex geological features, unlike those on previously visited Solar System bodies. The density of impact craters indicates the surface dates from the formation of the Solar System. The two lobes of the contact binary have closely aligned poles and equators, constraining their accretion mechanism

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely