Underplating of the Hawaiian Swell : evidence from teleseismic receiver functions

Author Posting. © The Authors, 2010. This article is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in Geophysical Journal International 183 (2010): 313-329, doi:10.1111/j.1365-246X.2010.04720.x.The Hawaiian Islands are the canonical example of an age-progressive island chain, formed by volcanism long thought to be fed from a hotspot source that is more or less fixed in the mantle. Geophysical data, however, have so far yielded contradictory evidence on subsurface structure. The substantial bathymetric swell is supportive of an anomalously hot upper mantle, yet seafloor heat flow in the region does not appear to be enhanced. The accumulation of magma beneath pre-existing crust (magmatic underplating) has been suggested to add chemical buoyancy to the swell, but to date the presence of underplating has been constrained only by local active-source experiments. In this study, teleseismic receiver functions derived from seismic events recorded during the PLUME project were analysed to obtain a regional map of crustal structure for the Hawaiian Swell. This method yields results that compare favourably with those from previous studies, but permits a much broader view than possible with active-source seismic experiments. Our results indicate that the crustal structure of the Hawaiian Islands is quite complicated and does not conform to the standard model of sills fed from a central source. We find that a shallow P-to-s conversion, previously hypothesized to result from the volcano-sediment interface, corresponds more closely to the boundary between subaerial and subaqueous extrusive material. Correlation between uplifted bathymetry at ocean-bottom-seismometer locations and presence of underplating suggests that much of the Hawaiian Swell is underplated, whereas a lack of underplating beneath the moat surrounding the island of Hawaii suggests that underplated crust outward of the moat has been fed from below by dykes through the lithosphere rather than by sills spreading from the island centre. Local differences in underplating may reflect focusing of magma-filled dykes in response to stress from volcanic loading. Finally, widespread underplating adds chemical buoyancy to the swell, reducing the amplitude of a mantle thermal anomaly needed to match bathymetry and supporting observations of normal heat flow.We are grateful to the Ocean Sciences Division of the U.S. National Science Foundation for their support of this project under grants OCE-0002470, OCE-0002552 and OCE-0002819

Perioperative and peripartum prevention of venous thromboembolism in patients with hereditary antithrombin deficiency using recombinant antithrombin therapy

Recombinant human antithrombin (rhAT; ATryn), isolated from the milk of transgenic goats, provides an alternative to human plasma-derived antithrombin (AT) concentrate for perioperative and peripartum prophylaxis of venous thromboembolism (VTE) in patients with hereditary AT deficiency. Optimized rhAT dosing algorithms and improved plasma AT monitoring protocol were used in an open-label, single-arm, multinational, pivotal safety and efficacy study that was conducted in patients with hereditary AT deficiency in perioperative and peripartum settings. Loading and maintenance doses were calculated on the basis of pretreatment AT activity levels. Specific dosing regimens were used for pregnant and surgical patients; rhAT was to be given for at least 3 days and for 14 days or less. The primary efficacy end point was the incidence of any thromboembolic event during rhAT therapy or within 7 days of rhAT discontinuation. Safety and AT activity levels were secondary end points. Six surgical and 12 pregnant patients were treated for a median of 3.2 days (range 0.9–14 days). With the optimized dosing regimens, a median of 1 dose adjustment (range 0–6 dose adjustments) was needed to maintain AT activity levels within 80–120% of normal. No confirmed VTEs occurred during treatment or in the subsequent 7 days. Overall, rhAT was well tolerated, but some bleeding complications occurred after rhAT discontinuation and anticoagulation reinstitution. No antibodies to rhAT or goat milk proteins were detected. Perioperative and peripartum prophylactic rhAT therapy in patients with hereditary AT deficiency is well tolerated and effective in preventing VTE

Efficacy and Safety of ABP 798: Results from the JASMINE Trial in Patients with Follicular Lymphoma in Comparison with Rituximab Reference Product

Introduction!#!ABP 798 is being developed as a biosimilar to rituximab reference product (RP), a CD20-directed cytolytic antibody that is approved in the US and EU for the treatment of non-Hodgkin lymphoma (NHL).!##!Methods!#!This randomized, double-blind, comparative clinical study (JASMINE) evaluated the efficacy and safety of ABP 798 compared with rituximab RP. Adult, anti-CD20 treatment naïve patients diagnosed with grade 1, 2, or 3a follicular B-cell NHL expressing CD20 were randomized 1:1 to receive a 375 mg/m!##!Results!#!Of the 256 randomized patients, 254 were treated with ABP 798 (n = 128; 100%) or rituximab RP (n = 126; 98.4%); 96 (78.0%) patients in the ABP 798 group and 87 (70.2%) in the rituximab RP group had a best ORR by week 28. The point estimate of RD in ORR between ABP 798 and rituximab RP from the adjusted generalized linear model for stratification factors was 7.7%. Clinical equivalence was based on sequential testing of the one-sided 95% lower confidence limits and one-sided 95% upper confidence limits of RD in ORR (- 1.4% and 16.8%, respectively) which was within the prespecified non-inferiority margin (- 15%) and non-superiority margin (35.5%), respectively. Results of sensitivity analyses were consistent with the primary efficacy analysis. ABP 798 was also comparable to rituximab RP across additional secondary endpoints, further supporting the conclusion of similarity, and including: RD of ORR at week 12; trough serum concentrations; percent of patients with complete depletion of CD19+ cell count at day 8; safety; and immunogenicity.!##!Conclusions!#!These results support a conclusion of similar clinical efficacy between ABP 798 and rituximab RP in patients with follicular lymphoma.!##!Nct number!#!NCT02747043; first posted April 21, 2016.!##!Eudract number!#!2013-005,542-11; submitted 14 October, 2014

Outpatient rituximab, ifosfamide, etoposide (R-IE) in patients older than 60 years with relapsed or refractory diffuse large B-cell lymphoma who are not candidates for stem cell transplantation

Patients with relapsed-refractory diffuse large B-cell lymphoma (RR-DLBCL) ineligible for autologous stem cell transplantation (autoSCT) have poor survival. Thirty transplant-ineligible patients older than 60 years were administered rituximab 375 mg/m2 day 1, ifosfamide 1333 mg/m2 days 1 to 3, and etoposide 80 mg/m2 days 1 to 3 (R-IE) every 21 days for 6 cycles plus 2 doses of rituximab. Revised international prognostic index 3–4 was seen in 53% and prior rituximab exposure in 60%. The complete and overall response rates were 55% and 76%, respectively. Median progression free survival (PFS) and overall survival were 23 and 24 months, respectively. Patients relapsing within 12 months of prior treatment had a median PFS of 2.5 months compared to 23 months for those relapsing beyond 12 months. Grade 3–4 thrombocytopenia and neutropenia occurred in one and eight patients, respectively. R-IE is an effective, well tolerated regimen in RR-DLBCL patients not fit for autoSCT.This study was supported by Roche Products Pty Limited and Amgen Pty Limited. This study was also supported by Amgen Australia Pty Ltd

Recommendations for the use of pegylated interferon-α in the treatment of classical myeloproliferative neoplasms

The classical myeloproliferative neoplasms (MPN) are uncommon clonal haemopoietic malignancies characterised by excessive production of mature blood cells. Clinically, they are associated with thrombosis, haemorrhage, varying degrees of constitutional disturbance and a risk of progression to myelofibrosis or acute myeloid leukaemia. Many of the disease manifestations may be ameliorated by treatment with interferon-α (IFN), but its use in Australian MPN patients has been limited due to the inconvenience of frequent injections and side-effects. The pegylated form of IFN is a long-acting preparation, which is better tolerated, and its Pharmaceutical Benefits Scheme listing is likely to lead to increased usage. We review the literature on risks and benefits of IFN treatment for MPN, suggest criteria for patient selection in each of these diseases and discuss strategies to manage the side-effects of pegylated IFN