Novel flame retardant thermoset resin blends derived from a free-radically cured vinylbenzylated phenolic novolac and an unsaturated polyester for marine composites

A phenolic novolac resin has been chemically reacted with 4-vinylbenzyl chloride to introduce polymerizable vinyl benzyl groups. The modified novolac spontaneously polymerizes like styrene, is physically and chemically compatible with a typical unsaturated polyester (UP) resin, and can be free-radically cured (crosslinked) alone and in mixtures with UP using styrene as a reactive diluent. The cured vinylbenzylated novolac and co-cured blends of it with UP show superior flame retardance to cured UP alone and have potential applications as matrix resins in glass-reinforced composite laminates especially for marine structures

Complement-Binding Donor-Specific Anti-HLA Antibodies and Risk of Primary Graft Failure in Hematopoietic Stem Cell Transplantation

AbstractDetection of donor-specific anti-HLA antibodies (DSA) has been associated with graft rejection in all forms of transplantation. The mechanism by which DSA increase the risk of graft failure remains unclear. We hypothesized that complement-binding DSA are associated with engraftment failure in hematopoietic stem cell transplantation (HSCT) and analyzed 122 haploidentical transplant recipients tested prospectively for DSA. Retrospective analysis to detect C1q binding DSA (C1q+DSA) was performed on 22 allosensitized recipients. Twenty-two of 122 patients (18%) had DSA, 19 of which were women (86%). Seven patients with DSA (32%) rejected the graft. Median DSA level at transplant for patients who failed to engraft was 10,055 mean fluorescence intensity (MFI) versus 2065 MFI for those who engrafted (P = .007). Nine patients with DSA were C1q positive in the initial samples with median DSA levels of 15,279 MFI (range, 1554 to 28,615), compared with 7 C1q-negative patients with median DSA levels of 2471 MFI (range, 665 to 12,254) (P = .016). Of 9 patients who were C1q positive in the initial samples, 5 patients remained C1q positive at time of transplant (all with high DSA levels [median, 15,279; range, 6487 to 22,944]) and experienced engraftment failure, whereas 4 patients became C1q negative pretransplant and all engrafted the donor cells (P = .008). In conclusion, patients with high DSA levels (>5000 MFI) and complement-binding DSA antibodies (C1q positive) appear to be at much higher risk of primary graft failure. The presence of C1q+DSA should be assessed in allosensitized patients before HSCT. Reduction of C1q+DSA levels might prevent engraftment failure in HSCT

Changes in the Treatment Responses to Artesunate-Mefloquine on the Northwestern Border of Thailand during 13 Years of Continuous Deployment

Background: Artemisinin combination treatments (ACT) are recommended as first line treatment for falciparum malaria throughout the malaria affected world. We reviewed the efficacy of a 3-day regimen of mefloquine and artesunate regimen (MAS ), over a 13 year period of continuous deployment as first-line treatment in camps for displaced persons and in clinics for migrant population along the Thai-Myanmar border. Methods and Findings: 3,264 patients were enrolled in prospective treatment trials between 1995 and 2007 and treated with MAS. The proportion of patients with parasitaemia persisting on day-2 increased significantly from 4.5% before 2001 to 21.9% since 2002 (p<0.001). Delayed parasite clearance was associated with increased risk of developing gametocytaemia (AOR = 2.29; 95% CI, 2.00-2.69, p = 0.002). Gametocytaemia on admission and carriage also increased over the years (p = 0.001, test for trend, for both). MAS efficacy has declined slightly but significantly (Hazards ratio 1.13; 95% CI, 1.07-1.19, p<0.001), although efficacy in 2007 remained well within acceptable limits: 96.5% (95% CI, 91.0-98.7). The in vitro susceptibility of P. falciparum to artesunate increased significantly until 2002, but thereafter declined to levels close to those of 13 years ago (geometric mean in 2007: 4.2 nM/l; 95% CI, 3.2-5.5). The proportion of infections caused by parasites with increased pfmdr1 copy number rose from 30% (12/ 40) in 1996 to 53% (24/45) in 2006 (p = 0.012, test for trend). Conclusion: Artesunate-mefloquine remains a highly efficacious antimalarial treatment in this area despite 13 years of widespread intense deployment, but there is evidence of a modest increase in resistance. Of particular concern is the slowing of parasitological response to artesunate and the associated increase in gametocyte carriage. © 2009 Carrara et al

Fire and mechanical properties of a novel free-radically cured phenolic resin based on a methacrylate-functional novolac and of its blends with an unsaturated polyester resin

A novel phenolic novolac resin bearing methacrylate functional groups has been synthesized by reaction of the novolac with methacryloyl chloride. This resin has been mixed with styrene and cured (crosslinked) free-radically under the relatively low temperature conditions used to cure unsaturated polyester/styrene mixtures, i.e. there is no need to employ the high temperatures and pressures that are required to cure conventional phenolic resins. Homogeneous cured blends of the methacrylated novolac with unsaturated polyester and styrene have been prepared also. The cured methacrylated novolac, and its blends with unsaturated polyester, are rigid materials with good mechanical strength, and have glass transition temperatures, thermal stabilities and flame retardancies superior to those of cured unsaturated polyester alone. Fire and mechanical properties of a novel free-radically cured phenolic resin based on a methacrylate-functional novolac and of its blends with an unsaturated polyester resin

Two new rotenoid glycosides from the rhizomes of <i>Stemona curtisii</i> Hook. f

Two new rotenoid glycosides named stemonal 11-O-β-D-glucopyranoside and 6-O-methylstemonal 11-O-β-D-glucopyranoside together with ten known metabolites were isolated from the rhizomes of Stemona curtisii. The chemical structures of the new compounds were elucidated based on the analysis of their 1D and 2D NMR and HRESIMS, while the sugar unit and absolute configuration were determined by chemical hydrolysis and ECD analysis. Among the tested compounds for anti-α-glucosidase assay, stemonal showed an inhibitory effect (IC50 = 38.67 µM), which is 2.4-fold more potent than acarbose. Cytotoxic evaluation against the lung adenocarcinoma A549 cell line indicated that none of the compounds were strongly active to suppress the cancer cell growth at 100 µM. This work describes the occurrence of rotenoids bearing a sugar moiety, which are reported for the first time in the genus Stemona. The isolated compound’s α-glucosidase inhibitory potential provides insight for further investigation of natural rotenoids as anti-diabetic agents.</p

Haploidentical Donors in Addition to Transplantation in Chronic Phase Associate with Improved Gvhd-Free Relapse-Free Survival (GRFS) for Patients with Advanced CML

Abstract Introduction: Despite the successes of treatment with tyrosine kinase inhibitors (TKIs) in patients with CML, allogeneic hematopoietic stem cell transplantation (ASCT) continues to be a potentially curative option for patients with advanced disease of who fail TKI therapy. Here we analyzed outcomes of patients with advanced CML (aCML) (beyond first chronic phase-CP1) who received an ASCT at our institution to identify factors associated with improved survival. Methods:207 consecutive patients withaCML treated at The University of Texas MD Anderson Cancer Center after year 2000 were included. The median age was 44 years (range 2-70 years), 135 (65%) were male, 77% had less than 5% bone marrow (BM) blasts, 129 (65%) had persistentPh-chromosome positive, and 176 patients (85%) were less than a major molecular response at transplant. Forty of 114 tested patients (35%) had resistant BCR-ABL mutations and 10 patients (8.7%) had T315I mutation at transplant. Conditioning regimen wasmyeloablative (MAC) in 140 patients (68%). Donors were matched related (MRD), matched unrelated (MUD),haploidentical (HAPLO), mismatched unrelated (MMUD), umbilical cord blood (UCB) and 1Ag mismatched related (MMRD) in 79 (38%), 75 (36%), 18 (9%), 17 (8%), 11 (5%) and 7 (3%) patients, respectively. The median time from diagnosis to transplant was 27 months (range 1-318 months) while the median follow-up duration was 20 months (range 1-194 months). Results:At 30 days post-transplant, 180 of 200 tested patients (90%) and 134 of 201 tested patients (67%) achieved a complete cytogenetic and at least a major molecular response, respectively. The response to transplant by day 30assessment correlated significantly with the disease status before transplant. A higher percentage of patients who experienced cytogenetic response before transplant experienced molecular response post-transplant (77%) compared with those who did not (61%; p=0.027). For the entire group, the 1-year cumulative incidence (CI) of acute GVHD (aGVHD) grade II-IV and grade III-IV were 41% and 15%, respectively; 5-year CI of extensive chronic GVHD (cGVHD) was 31%.Haploidentical transplant patients had lesscGVHD compared with HLA matched donor transplants (14% vs. 32% for HLA matched transplants). The CI of non-relapse mortality at 100 days and 1 year was 14% and 30%, respectively. Sixty-five patients (31%) had molecular relapse after transplant, which correlated with the degree of disease control before transplant. The CI of cytogenetic and molecular relapse at 5 years was 22% and 31%, respectively. Overall the 5-year survival (OS), progression free survival (PFS) and GVHD-free, relapse-free survival (GRFS)was49%, 34%, and 22%, respectively. Adjusting for all significant measures, percentage of BM blasts before transplant and donor type were significantly associated with PFS and GRFS (Table1, Figure 1).Haplodenticaltransplant patients had longer PFS and GRFS compared with other donor types including matched related or unrelated donor (5-year GRFS for HAPLO, MRD, MUD, MMUD, UCB and MMRD were 53%, 19%, 23%, 29%, 9%, and 0%, respectively; p=0.033) (Table 1, Figure 1). Cytogenetic and molecular response before transplant as well as year of transplant did not predict survival after transplant. Conclusions: ASCT is curative for a proportion of patients withaCML. PFS and GRFS are favorably influenced by percentage of BM blasts and donor type, withhaploidentical donor having at least as good outcomes as HLA matched donors, while molecular and cytogenetic response before transplant do not appear to correlate with survival post-transplant. Table 1 Multivariable analysis for PFS and GRFS Table 1. Multivariable analysis for PFS and GRFS Figure 1 PFS and GRFS based on percentage of BM blasts before transplant and donor types Figure 1. PFS and GRFS based on percentage of BM blasts before transplant and donor types Disclosures Cortes: Arog: Research Funding; Teva: Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Astellas: Research Funding; Ambit: Research Funding. Champlin:Intrexon: Equity Ownership, Patents & Royalties; Ziopharm Oncology: Equity Ownership, Patents & Royalties. Ciurea:Spectrum Pharmaceuticals: Other: Advisory Board; Cyto-Sen Therapeutics: Equity Ownership

Impact of a novel prognostic model, hematopoietic cell transplant-composite risk (HCT-CR), on allogeneic transplant outcomes in patients with acute myeloid leukemia and myelodysplastic syndrome

Outcomes after allogeneic stem-cell transplantation (AHSCT) are influenced by both disease- and patient-related factors. Here, we developed a novel prognostic model, hematopoietic cell transplant-composite risk (HCT-CR), by combining the refined disease risk index (DRI-R) and hematopoietic stem-cell transplant comorbidity/age index (HCT-CI/Age) to predict post-transplant survival for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The analysis included 942 AML/MDS patients treated with AHSCT. Patients were stratified into 4 HCT-CR risk groups: Low-risk-patients with low/intermediate DRI-R and HCT-CI/Age ≤3 (N = 272); Intermediate-risk-patients with low/intermediate DRI-R and HCT-CI/Age &gt;3 (N = 168); High-risk-patients with high/very high DRI-R and HCT-CI/Age ≤3 (N = 284); and Very high-risk-patients with high/very high DRI-R and HCT-CI/Age &gt;3 (N = 184). Compared with the low-risk group, intermediate, high, and very high-risk groups had a significantly increased risk of death [adjusted HR of 1.37 (P &lt; 0.04), 2.08 (P &lt; 0.001), and 2.92 (P &lt; 0.001), respectively]. The concordance test showed that the HCT-CR model provided better discriminative capacity for OS prediction compared with all prior models independently, including cytogenetic risk group, DRI-R, and HCT-CI/Age model (C-indices: 0.62, 0.55, 0.60, and 0.54, respectively) (P &lt; 0.001). In conclusion, combining disease- and patient-related factors provides better survival stratification for patients with AML/MDS receiving AHSCT

Impact of monosomal karyotype and FLT3 status on post-transplant relapse in acute myeloid leukemia (AML)

7010 Background: Relapse remains the major cause of treatment failure in AML patients (pts) undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT). We aimed to identify prognostic factors for relapse and leukemia free survival (LFS) after allo-HCT in AML pts. Methods: We retrospectively analyzed 987 consecutive pts who underwent their first allo-HCT for AML between January 2001 and June 2012. 124 pts had monosomal karyotype (MK+), 440 had other cytogenetic abnormalities (core-binding factor [CBF] n=67; MK-, n=373). 113 pts had diploid cytogenetics and FLT3 mutations (CN-FLT3+), 235 were diploid without FLT3 mutations (CN-FLT3-); FLT3 data was unavailable for 75 CN pts. Pts were stratified based on disease status at HCT: complete remission (CR, n=627) and active disease (n=360). Results: In this cohort, median age was 52 years (range: 19 – 76) and 191 pts (20%) had secondary AML (sAML). Conditioning intensity was non-myeloablative in 230 pts (23%). On multivariate analysis in pts with CR at HCT (adjusted for age, donor type and conditioning intensity) factors that predicted inferior LFS included: sAML (HR=1.5, 95% CI=1.1-2.2, p=0.009), >=CR2 vs. CR1 (HR=1.6, 95% CI=1.2-2.1, p=0.002), CN-FLT3+ (HR=1.7, 95% CI=1.1-2.5, p=0.02), MK- (HR=1.4, 95% CI=1.1-2.0, p=0.04) and MK+ disease (HR=2.1, 95% CI=1.4-3.2, p <0.001). Three-year LFS rates for CN-FLT3+ and MK+ were 45.3% and 34% vs. 53.3% for CN-FLT3- pts. For pts with active disease; CN-FLT3+ (HR=2.6, 95% CI= 1.5-4.2, p<0.001) and MK+ (HR=2.3, 95% CI= 1.5-3.5, p<0.001) predicted worse 3-year LFS: 10% and 6% vs. 30.8% in pts with CN-FLT3- . For CR pts, cumulative incidence of relapse (CIR) was higher for those with CN–FLT3+ (HR=1.9, 95% CI=1.1-3.1, p=0.01) and MK+ disease (HR=2.1, 95% CI=1.2-3.5, p=0.005). Among active disease pts, CN-FLT3+ (HR=2.5, 95% CI=1.4-4.3, p=0.002) and MK+ (HR=1.9, 95% CI=1.2-3.0, p=0.009) also predicted for higher CIR. Conclusions: Although pts with CN-FLT3+ and MK+ represent a high risk group for decreased LFS with increased relapse incidence after allo-HCT, they may still enjoy LFS of 30% - 45% if transplanted in CR. Post-transplant strategies to minimize the risk of relapse should be investigated in this setting