ALBERT

Description: Journal of the American Chemical Society DOI: 10.1021/jacs.5b05796

Description: Journal of the American Chemical Society DOI: 10.1021/ja5028452

Description: Journal of the American Chemical Society DOI: 10.1021/ja503143p

Description: Journal of the American Chemical Society DOI: 10.1021/ja506176h

Description: Introduction Neonatal AIT (NAIT) is a potentially life-threatening, often severe thrombocytopenia caused by a parental human platelet antigen (HPA) incompatibility resulting in maternal alloantibodies attacking fetal platelets. NAIT affects approximately 1 in 1000 live births and may be accompanied by intracranial hemorrhage (ICH) in 10-20% of cases. Since there is no routine screening for NAIT, it is usually diagnosed after birth of the first affected thrombocytopenic fetus. Mothers of NAIT babies can be treated during subsequent affected pregnancies with IVIG and corticosteroids to increase fetal platelet counts and avoid fetal/neonatal ICH, using fetal blood sampling (FBS) to monitor treatment. Using this approach in previous studies IVIG 1g/kg alone (no steroids) was shown to not be effective in severely thrombocytopenic fetuses with AIT. While FBS allows enhancing therapy (salvage) in poor responders, it is a high-risk procedure associated with adverse fetal outcomes (eg premature delivery and fatal umbilical cord hemorrhage). This study assessed the efficacy, benefits and pitfalls of: a) 2 different regimens in treatment of fetal AIT, both of which are “more” than IVIG 1g/kg alone, and b) an alternative approach, omitting FBS in affected women without a history of ICH in a prior affected sibling and enhancing treatment empirically at 32 weeks, ie treating mothers as if they had undergone FBS and had a low fetal platelet count (FPC). Methods Antenatal treatment in this study compared IVIG 2g/kg/wk (arm A) to IVIG 1g/kg/wk + prednisone (arm B) starting at 20-30 weeks of gestation until delivery, with FBS at 32 weeks. In the alternative treatment arm which was added at the end of the study, all women were treated with IVIG 2g/kg/wk + prednisone 0.5mg/kg (Salvage) after 32 weeks. This prospective multicenter study included 99 mothers and 102 fetuses enrolled from May 2001 to November 2012. All mothers had documented NAIT and those with ICH in a previous child were excluded. FPC, birth platelet count (BPC) and ICH were compared among the 3 treatment regimens outlined above: 1) arm A, 2) arm B, and 3) either Arm A or Arm B followed by empiric salvage without FBS. Results There was no difference in efficacy of treatment between arm A versus arm B; both increased BPC to greater than or equal to 50k in the fetus/neonate in 85% or so of cases (table 1). In 30 pregnancies in which Salvage was used, there were 16 fetuses who did not undergo FBS and 14 who did. Only 2 of the 30 receiving Salvage had BPC 〈 50,000/uL (50k); whereas, 9 of 72 neonates not receiving salvage therapy had a BPC 〈 50k. When only fetuses with an FPC 〈 50k were included, 13/14 receiving Salvage had a BPC 〉 50k whereas only 1 of 5 not on Salvage did (table 2; p=0.006). Overall, of 102 fetuses, 11 had a BPC ≤ 50 (poor responders). Among these 11 poor responders, 0 resulted in ICH, 9 did not receive Salvage treatment (5 in arm A; 4 in Arm B), and 1 of 2 receiving Salvage was only on it for 1.5 weeks. Common adverse effects related to IVIG include headaches, skin rashes, flushing and nausea; these were self-reported by treated mothers and obtained by chart review including nursing records. Also increased hemolysis in mothers with blood type A occurred and was presumed to be caused by anti-A present in IVIG (see separate abstract at this meeting). Conclusions Arms A and B were approximately equally effective; however, both resulted in approximately 15% of low FPC at 32 weeks. These findings support the hypothesis that empiric addition of salvage treatment at approximately 32 weeks of gestation is needed in treating affected cases of NAIT to avoid fetal blood sampling and its substantial attendant complications. The addition of Salvage is highly effective in treating fetal AIT and eliminates risks associated with FBS and greatly reduces the chance of a BPC 〈 50k. However, adverse events have been seen from the increased dosage of IVIG and prolonged prednisone and require careful monitoring. Disclosures: Bussel: Sysmex: Research Funding; Shionogi: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Eisai: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Ligand: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; IgG of America: Research Funding; Genzyme: Research Funding; Cangene: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Amgen: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Symphogen: Membership on an entity’s Board of Directors or advisory committees.

Description: Introduction Hemolysis after IVIG infusion has been observed in clinical trials and case reports. Certain factors seem to place a patient receiving IVIG at higher risk for hemolytic anemia: 1) having blood type A, B, or AB and 2) receiving high doses of IVIG (≥ 2g/kg). IVIG contains isohemagglutinins that coat red blood cells and may cause red cell clearance by the RES (Table 1). Anti-A, Anti-B, and Anti-D titers have been detected in IVIG products at varying concentrations by different IVIG manufacturers. It has been suggested that Anti-A titers 〉 1:16 are more likely to cause clinically significant hemolysis and thus anemia in recipients. 15 summarized studies reported 63 patients who experienced hemolysis after IVIG infusion and showed the higher risk of non-group O recipients to hemolyze with IVIG: In the current study, we sought to explore the degree of anemia as related to ABO blood types in mothers treated with IVIG for fetal alloimmune thrombocytopenia (AIT). Methods A retrospective chart review was conducted on 84 women who had received IVIG for AIT treatment during their pregnancy to increase the fetal platelet count. Women were randomized to receive IVIG 2g/kg/wk (arm A, n=43) or IVIG 1g/kg/wk + prednisone (arm B, n=41) starting at 20-30 weeks of gestation until delivery. One CBC per month was collected from each mother from the start of treatment until delivery. Hemoglobins and mean corpuscular volumes (MCVs) were tracked and development of anemia was compared among women with blood types (BT) A, B, AB and O in each treatment arm. Patients who non-randomly received IVIG 2g/kg/wk + prednisone together as rescuetreatment were excluded from this study. Results 36 of the 84 women had hemoglobins less than 10 on at least one CBC during IVIG treatment. All 36 had MCV values in the normocytic range (80-100). The degree of anemia was significantly greater in Arm A (IVIG 2g/kg) than Arm B (IVIG 1g/kg + pred) (Fisher's exact test, p=0.016; table 3). Among women in arm A (IVIG 2g/kg), BT non-O had a significantly higher incidence of marked anemia (Hg

Description: This National Aeronautics and Space Administration (NASA) Contractor Report summarizes and documents the work performed to investigate technologies that could support long-term aeronautical mobile communications operating concepts for air traffic management (ATM) in the timeframe of 2020 and beyond, and includes the associated findings and recommendations made by ITT Corporation and NASA Glenn Research Center to the Federal Aviation Administration (FAA). The work was completed as the final phase of a multiyear NASA contract in support of the Future Communication Study (FCS), a cooperative research and development program of the United States FAA, NASA, and EUROCONTROL. This final report focuses on an assessment of final five candidate technologies, and also provides an overview of the entire technology assessment process, including final recommendations.

Description: The following NASA Contractor Report documents the in-depth studies on select technologies that could support long-term aeronautical mobile communications operating concepts. This work was performed during the third and final phase of NASA s Technology Assessment for the Federal Aviation Administration (FAA)/EUROCONTROL Future Communications Study (FCS) under a multiyear NASA contract. It includes the associated findings of ITT Corporation and NASA Glenn Research Center to the FAA as of the end of May 2007. The activities documented in this report focus on three final technology candidates identified by the United States, and were completed before sufficient information about two additional technology candidates proposed by EUROCONTROL was made available. A separate report to be published by NASA/CR-2008-215144, entitled Final Report on Technology Investigations for Provision of Future Aeronautical Communications will include an assessment of all five final candidate technologies considered by the U.S. agencies (FAA and NASA) and EUROCONTROL. It will also provide an overview of the entire technology assessment process, including final recommendations. All three phases of this work were performed in compliance with the Terms of Reference for the Action Plan number 17 (AP-17) cooperative research agreement among EUROCONTROL, FAA, and NASA along with the general guidance of the FAA and EUROCONTROL available throughout this study.

Description: This report describes the process, findings, and recommendations of the second of three phases of the Future Communications Study (FCS) technology investigation conducted by NASA Glenn Research Center and ITT Advanced Engineering & Sciences Division for the Federal Aviation Administration (FAA). The FCS is a collaborative research effort between the FAA and Eurocontrol to address frequency congestion and spectrum depletion for safety critical airground communications. The goal of the technology investigation is to identify technologies that can support the longterm aeronautical mobile communication operating concept. A derived set of evaluation criteria traceable to the operating concept document is presented. An adaptation of the analytical hierarchy process is described and recommended for selecting candidates for detailed evaluation. Evaluations of a subset of technologies brought forward from the prescreening process are provided. Five of those are identified as candidates with the highest potential for continental airspace solutions in L-band (P-34, W-CDMA, LDL, B-VHF, and E-TDMA). Additional technologies are identified as best performers in the unique environments of remote/oceanic airspace in the satellite bands (Inmarsat SBB and a custom satellite solution) and the airport flight domain in C-band (802.16e). Details of the evaluation criteria, channel models, and the technology evaluations are provided in appendixes.