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Background: Few studies have compared the response to growth hormone (GH) treatment between indications such as isolated growth hormone deficiency (IGHD), born small for gestational age (SGA), idiopathic short stature (ISS), and multiple pituitary hormone deficiency (MPHD). The aim of this analysis of data, collected from two large ongoing observational outcome studies, was to evaluate growth and insulin-like growth factor-I (IGF-I) response data for children of short stature with IGHD, MPHD, SGA, or ISS following two years of treatment with the recombinant GH product Norditropin® (Novo Nordisk A/S, Bagsværd, Denmark). Methods: Analysis of auxologic data from two ongoing prospective observational studies, NordiNet® International Outcomes Study (NordiNet® IOS) and NovoNet®/American Norditropin® Studies: Web-enabled Research (ANSWER) Program®. Results: 4,582 children aged <18 years were included: IGHD, n = 3,298; SGA, n = 678; ISS, n = 334; and MPHD, n = 272. After two years' GH treatment, change in height standard deviation score (SDS) was +1.03 in SGA and +0.84 in ISS vs. +0.97 in IGHD (p=0.047; p<0.001 vs. IGHD, respectively). Height gain was comparable between IGHD and MPHD. In pre-pubertal children vs. total population, height SDS change after two years was: IGHD, +1.24 vs. +0.97; SGA, +1.17 vs. +1.03; ISS, +1.04 vs. +0.84; and MPHD, +1.16 vs. +0.99 (all p<0.001). Conclusions: After two years' GH treatment, change in height SDS was greater in SGA and less in ISS, compared with IGHD; the discrepancy in responses may be due to the disease nature or confounders (i.e. age). Height SDS increase was greatest in pre-pubertal children, supporting early treatment initiation to optimize growth outcomes. [ABSTRACT FROM AUTHOR]

Objective: Bone metastases can occur in many forms of cancer. More than two-thirds of women with metastatic breast cancer may be affected by bone metastasis during the course of their disease. Bisphosphonates, which inhibit osteoclast-mediated bone resorption, are an established standard of care for patients with bone metastases. For patients with cancer and bone metastases, bisphosphonates are associated with a significant reduction in skeletal-related events such as vertebral fractures, non-vertebral fractures as well as increasing the time to skeletal event. The purpose of this study was to quantify the current time involved in the administration of IV bisphosphonates and how this might impact on patient experience and cancer unit capacity.Research design and methods: A pilot audit was initially conducted at the Royal Marsden Hospital (RMH), London (both Chelsea and Sutton sites), and was followed by audits at a further two UK hospital sites: Velindre Hospital, Cardiff and the Royal Surrey County Hospital, Guildford. The study was conducted between December 2005 and September 2006.Results: Overall, 151 forms were completed. Of the total patients audited, approximately 71% had a diagnosis of breast cancer. Where data on the reason for attendance were collected (Velindre and the Royal Surrey County Hospital), over 77% of patients attended hospital for the sole reason of having an IV bisphosphonate administered. The majority of patients (94%) required cannulation prior to infusion and, at the sites where this information was recorded (Royal Surrey County Hospital and Velindre Hospital), almost one-third of patients required two or more attempts before they were successfully cannulated. The time that the patients spent on the unit where the IV bisphosphonates were administered was greater for patients receiving pamidronate compared to those receiving zoledronic acid (2 h 36 min and 1 h 38 min, respectively). The magnitude of the difference was not as great as would be expected considering zoledronic acid should take one-sixth of the time to administer (Royal Marsden Hospital, pamidronate 1 h 29 min, zoledronic acid 18 min: Royal Surrey County Hospital, zoledronic acid 21 min: Velindre Hospital, pamidronate 1 h 42 min, zoledronic acid 17 min).Conclusions: IV bisphosphonates are accepted as standard clinical practice for the management of metastatic bone disease. They are often prescribed for long periods of time, so tolerability and patient acceptability are important factors in therapy. The administration of IV bisphosphonates contributes a substantial time burden for patients travelling to the hospital, considering that in most cases the purpose is for this treatment only. It also places a significant burden on hospital resources, creating capacity planning challenges. Receiving an IV bisphosphonate also has other disadvantages associated with it, such as the need for patients to undergo repeated cannulation. Service redesign, such as home administration of IV bisphosphonates, could help to overcome issues highlighted in this audit. The use of oral alternatives to pamidronate and zoledronic acid which may be more convenient for patients, and perhaps also cost-effective, should also be of ongoing interest. [ABSTRACT FROM AUTHOR]

Abstract??The 1,332?bp phytase gene ofPenicilliumoxalicumPJ3 was inserted into the expression vector, pPICZ?A and expressed in the methylotrophic yeast,Pichia pastorisas an active, extracellular phytase. The recombinant phytase reached a maximum yield of 12?U/ml of medium at 120?h of cultivation after methanol induction under shake-flask conditions. The enzyme was glycosylated, with a molecular mass of about 62.5?kDa. The Michaelis constant (Km) and maximum reaction rate (Vmax) for sodium phytate was 0.37?mM and 526.3?U/mg of protein, respectively. The optimal activity occurred at pH 4.5 and 55?C. [ABSTRACT FROM AUTHOR]

This study investigates the causes of event-dating biases. Two hundred participants provided knowledge ratings and date estimates for 64 news events. Four independent groups dated the same events under different boundary constraints. Analysis across all responses showed that forward telescoping decreased with boundary age, concurring with the boundary-effects model. With guesses removed from the data set, backward telescoping was greatly reduced, but forward telescoping was unaffected by boundaries. This dissociation indicates that multiple factors (e. g., guessing and reconstructive strategies) are responsible for different dating biases and argue against a boundary explanation of forward telescoping. [ABSTRACT FROM AUTHOR]

The increasing demand for improving the high-field (16–22 T) performance of Nb3Sn conductors requires a better understanding of the properties of modern wires much closer to irreversibility field, HIrr. In this study we investigated the impact of Ta, Ti and Hf doping on the high-field pinning properties, the upper critical field, Hc2, and HIrr. We found that the pinning force curves of commercial Ti and Ta doped wires at different temperatures do not scale and that the Kramer extrapolation from low field data, typically used by magnet designers to estimate high-field critical current density and magnet operational margins, is not reliable and significantly overestimates the actual HIrr. In contrast, new laboratory scale conductors made with Nb–Ta–Hf alloy have improved high-field Jc performance and, despite contributions by both grain boundary and point defect pinning mechanisms, have more predictable high-field behavior. Using Extended x-ray Absorption Fine Structure spectroscopy, EXAFS, we found that for the commercial Ta and Ti doped conductors, the Ta site occupancy in the A15 structure gradually changes with the heat treatment temperature whereas Ti is always located on the Nb site with clear consequences for Hc2. This work reveals the still limited understanding of what determines Hc2, HIrr and the high-field Jc performance of Nb3Sn and the complexity of optimizing these conductors so that they can reach their full potential for high-field applications. [ABSTRACT FROM AUTHOR]

Here we show that addition of Hf to Nb4Ta can significantly improve the high field performance of Nb3Sn, making it suitable for dipole magnets for a machine like the 100 TeV Future Circular Collider (FCC). A big challenge of the FCC is that the desired non-Cu critical current density (Jc) target of 1500 A mm−2 (16 T, 4.2 K) is substantially above the best present Nb3Sn conductors doped with Ti or Ta (∼1300 A mm−2 in the very best sample of the very best commercial wire). Recent success with internal oxidation of Nb–Zr precursor has shown significant improvement in the layer Jc of Nb3Sn wires, albeit with the complication of providing an internal oxygen diffusion pathway and avoiding degradation of the irreversibility field HIrr. We here extend the Nb1Zr oxidation approach by comparing Zr and Hf additions to the standard Nb4Ta alloy of maximum Hc2 and HIrr. Nb4Ta rods with 1Zr or 1Hf were made into monofilament wires with and without SnO2 and their properties measured over the entire superconducting range at fields up to 31 T. We found that Group IV alloying of Nb4Ta does raise HIrr, though O2 addition still slightly degrades it. As noted in earlier Nb1Zr work with an O source, the pinning force density Fp is strongly enhanced and its peak value shifted to higher field by internal oxidation. A surprising result of this work is that we found better properties in Nb4Ta1Hf without SnO2, FpMax achieving 2.35 times that of the standard Nb4Ta alloy, while the oxidized Nb4Ta1Zr alloy achieved 1.54 times that of the Nb4Ta alloy. The highest layer Jc (16 T, 4.2 K) of 3700 A mm−2 was found in the SnO2-free wire made with Nb4Ta1Hf alloy. Using a standard A15 cross-section fraction of 60% for modern powder-in-tube and rod restack process wires, we estimated that a non-Cu Jc of 2200 A mm−2 is obtainable in modern conductors, well above the 1500 A mm−2 FCC specification. Moreover, since the best properties were obtained without SnO2, the Nb4Ta1Hf alloy appears to open a straightforward route to enhanced properties in Nb3Sn wires manufactured by virtually all the presently used commercial routes employed today. [ABSTRACT FROM AUTHOR]

Rapid developments in photon-counting and energy-discriminating detectors have the potential to provide an additional spectral dimension to conventional x-ray grayscale imaging. Reconstructed spectroscopic tomographic data can be used to distinguish individual materials by characteristic absorption peaks. The acquired energy-binned data, however, suffer from low signal-to-noise ratio, acquisition artifacts, and frequently angular undersampled conditions. New regularized iterative reconstruction methods have the potential to produce higher quality images and since energy channels are mutually correlated it can be advantageous to exploit this additional knowledge. In this paper, we propose a novel method which jointly reconstructs all energy channels while imposing a strong structural correlation. The core of the proposed algorithm is to employ a variational framework of parallel level sets to encourage joint smoothing directions. In particular, the method selects reference channels from which to propagate structure in an adaptive and stochastic way while preferring channels with a high data signal-to-noise ratio. The method is compared with current state-of-the-art multi-channel reconstruction techniques including channel-wise total variation and correlative total nuclear variation regularization. Realistic simulation experiments demonstrate the performance improvements achievable by using correlative regularization methods. [ABSTRACT FROM AUTHOR]

Dipole magnets for the proposed Future Circular Collider (FCC) demand specifications significantly beyond the limits of all existing Nb3Sn wires, in particular a critical current density (Jc) of more than 1500 A mm−2 at 16 T and 4.2 K with an effective filament diameter (Deff) of less than 20 μm. The restacked-rod-process (RRP®) is the technology closest to meeting these demands, with a Jc (16 T) of up to 1400 A mm−2, residual resistivity ratio > 100, for a sub-element size Ds of 58 μm (which in RRP® wires is essentially the same as Deff). An important present limitation of RRP® is that reducing the sub-element size degrades Jc to as low as 900 A mm−2 at 16 T for Ds = 35 μm. To gain an understanding of the sources of this Jc degradation, we have made a detailed study of the phase evolution during the Cu–Sn ‘mixing’ stages of the wire heat treatment that occur prior to Nb3Sn formation. Using extensive microstructural quantification, we have identified the critical role that the Sn–Nb–Cu ternary phase (Nausite) can play. The Nausite forms as a well-defined ring between the Sn source and the Cu/Nb filament pack, and acts as an osmotic membrane in the 300 °C–400 °C range—greatly inhibiting Sn diffusion into the Cu/Nb filament pack while supporting a strong Cu counter-diffusion from the filament pack into the Sn core. This converts the Sn core into a mixture of the low melting point (408 °C) η phase (Cu6Sn5) and the more desirable ε phase (Cu3Sn), which decomposes at 676 °C. After the mixing stages, when heated above 408 °C towards the Nb3Sn reaction, any residual η liquefies to form additional irregular Nausite on the inside of the membrane. All Nausite decomposes into NbSn2 on further heating, and ultimately transforms into coarse-grain (and often disconnected) Nb3Sn which has little contribution to current transport. Understanding this critical Nausite reaction pathway has allowed us to simplify the mixing heat treatment to only one stage at 350 °C for 400 h which minimizes Nausite formation while encouraging the formation of the higher melting point ε phase through better Cu–Sn mixing. At a Ds of 41 μm, the Nausite control heat treatment increases the Jc at 16 T by 36%, reaching 1300 A mm−2 (i.e. 2980 A mm−2 at 12 T), and moving RRP® closer to the FCC targets. [ABSTRACT FROM AUTHOR]

We present a novel iterative reconstruction method applied to in situ x-ray synchrotron tomographic data of dendrite formation during the solidification of magnesium alloy. Frequently, fast dynamic imaging projection data are undersampled, noisy, of poor contrast and can contain various acquisition artifacts. Direct reconstruction methods are not suitable and iterative reconstruction techniques must be adapted to the existing data features. Normally, an accurate modelling of the objective function can guarantee a better reconstruction. In this work, we design a special cost function where the data fidelity term is based on the Group-Huber functional to minimize ring artifacts and the regularization term is a higher-order variational penalty. We show that the total variation penalty is unsuitable for some cases and higher-order regularization functionals can ensure a better fit to the expected properties of the data. Additionally, we highlight the importance of 3D regularization over 2D for the problematic data. The proposed method shows a promising performance dealing with angular undersampled noisy dynamic data with ring artifacts. [ABSTRACT FROM AUTHOR]

High critical current density (Jc) Nb3Sn A15 multifilamentary wires require a large volume fraction of small grain (SG), superconducting A15 phase, as well as Cu stabilizer with high Residual Resistance Ratio (RRR) to provide electromagnetic stabilization and protection. In powder-in-tube (PIT) wires the unreacted Nb7.5 wt%Ta outer layer of the tubular filaments acts as a diffusion barrier and protects the interfilamentary Cu stabilizer from Sn contamination. A high RRR requirement generally imposes a restricted A15 reaction heat treatment to prevent localized full reaction of the filament that could allow Sn to reach the Cu. In this study we investigate recent high quality PIT wires that achieve a Jc (12 T, 4.2 K) up to ∼2500 A mm−2 and find that the minimum diffusion barrier thickness decreases as the filament aspect ratio increases from ∼1 in the inner rings of filaments to 1.3 in the outer filament rings. We found that just 2–3 diffusion barrier breaches can degrade RRR from 300 to 150 or less. Using progressive etching of the Cu we also found that the RRR degradation is localized near the external filaments where deformation is highest. Consequently minimizing filament distortion during strand fabrication is important for reducing RRR degradation. The additional challenge of developing the highest possible Jc must be addressed by forming the maximum fraction of high Jc SG A15 and minimizing low Jc large-grain (LG) A15 morphologies. In one wire we found that 15% of the filaments had a significantly enhanced SG/LG A15 ratio and no residual A15 in the core, a feature that opens a path to substantial Jc improvement. [ABSTRACT FROM AUTHOR]

As part of the ITER conductor qualification process, 3 m long cable-in-conduit conductors (CICCs) were tested at the SULTAN facility under conditions simulating ITER operation so as to establish the current-sharing temperature, Tcs, as a function of multiple full Lorentz force loading cycles. After a comprehensive evaluation of both the toroidal field (TF) and the central solenoid (CS) conductors, it was found that Tcs degradation was common in long twist pitch TF conductors while short twist pitch CS conductors showed some Tcs increase. However, one kind of TF conductors containing superconducting strand fabricated by the Bochvar Institute of Inorganic Materials (VNIINM) avoided Tcs degradation despite having long twist pitch. In our earlier metallographic autopsies of long and short twist pitch CS conductors, we observed a substantially greater transverse strand movement under Lorentz force loading for long twist pitch conductors, while short twist pitch conductors had negligible transverse movement. With help from the literature, we concluded that the transverse movement was not the source of Tcs degradation but rather an increase of the compressive strain in the Nb3Sn filaments possibly induced by longitudinal movement of the wires. Like all TF conductors this TF VNIINM conductor showed large transverse motions under Lorentz force loading, but Tcs actually increased, as in all short twist pitch CS conductors. We here propose that the high surface roughness of the VNIINM strand may be responsible for the suppression of the compressive strain enhancement (characteristic of long twist pitch conductors). It appears that increasing strand surface roughness could improve the performance of long twist pitch CICCs. [ABSTRACT FROM AUTHOR]

Prototype cable-in-conduit-conductors (CICCs) destined for use in the toroidal field and central solenoid coils of the ITER experimental fusion reactor underwent severe cyclic loading in the SULTAN facility. Their autopsies revealed significant and permanent transverse strand migration due to the large Lorentz forces of the SULTAN test. The movement resulted in a 3%–7% void fraction increase on the low pressure (LP) side of the longer twist pitch CICCs. However, short twist pitch conductors exhibited less than 1% void fraction increase in the LP side, as well as a complete absence of the Nb3Sn filament fractures observed in the longer twist pitch conductors. We report here a detailed strand-to-cable analysis of short and longer ‘baseline’ twist pitch CICCs. It was found that the use of internal tin (IT) strands in the longer ‘baseline’ twist pitch CICCs can be beneficial possibly because of their superior stiffness—which better resist strand movement—while the use of bronze process strands showed more movement and poorer cyclic test performance. This was not the case for the short twist pitch CICC. Such conductor design seems to work well with both strand types. But it was found that despite the absence of filament fractures, the short twist pitch CICC made from the IT strands studied here developed severe strand distortion during cabling which resulted in diffusion barrier breaks and Sn contamination of the Cu stabilizer during the heat treatment. Conversely, the short twist pitch CICC made from bronze process strands preserved diffusion barrier integrity. [ABSTRACT FROM AUTHOR]

Cables made with Nb3Sn-based superconductor strands will provide the 13 T maximum peak magnetic field of the ITER central solenoid (CS) coils and they must survive up to 60 000 electromagnetic cycles. Accordingly, prototype designs of CS cable-in-conduit-conductors (CICC) were electromagnetically tested over multiple magnetic field cycles and warm-up-cool-down scenarios in the SULTAN facility at CRPP. We report here a post-mortem metallographic analysis of two CS CICC prototypes which exhibited some rate of irreversible performance degradation during cycling. The standard ITER CS CICC cable design uses a combination of superconducting and Cu strands, and because the Lorentz force on the strand is proportional to the transport current in the strand, removing the copper strands (while increasing the Cu:SC ratio of the superconducting strands) was proposed as one way of reducing the strand load. In this study we compare the two alternative CICCs, with and without Cu strands, keeping in mind that the degradation after the SULTAN test was lower for the CICC without Cu strands. The post-mortem metallographic evaluation revealed that the overall strand transverse movement was 20% lower in the CICC without Cu strands and that the tensile filament fractures found were less, both indications of an overall reduction in high tensile strain regions. It was interesting to see that the Cu strands in the mixed cable design (with higher degradation) helped reduce the contact stresses on the high pressure side of the CICC, but in either case, the strain reduction mechanisms were not enough to suppress cyclic degradation. Advantages and disadvantages of each conductor design are discussed here aimed to understand the sources of the degradation. [ABSTRACT FROM AUTHOR]

Poly-N-acetyllactosamine (polyLacNAc) is a linear carbohydrate polymer composed of alternating N-acetylglucosamine and galactose residues involved in cellular functions ranging from differentiation to metastasis. PolyLacNAc also serves as a scaffold on which other oligosaccharides such as sialyl Lewis X are displayed. The polymerization of the alternating N-acetylglucosamine and galactose residues is catalyzed by the successive action of UDP-GlcNAc:βGal β-1,3-N-acetylglucosaminyltransferase 1 (B3GNT1) and UDP-Gal:βGlcNAc β-1,4-galactosyltransferase, polypeptide 1 (B4GALT1), respectively. The functional association between these two glycosyltransferases led us to investigate whether the enzymes also associate physically. We show that B3GNT1 and B4GALT1 colocalize by immunofluorescence microscopy, interact by coimmunoprecipitation, and affect each others subcellular localization when one of the two proteins is artificially retained in the endoplasmic reticulum. These results demonstrate that B3GNT1 and B4GALT1 physically associate in vitro and in cultured cells, providing insight into possible mechanisms for regulation of polyLacNAc production. [ABSTRACT FROM AUTHOR]