Genome-wide association analysis of red blood cell traits in African Americans: the COGENT Network

Laboratory red blood cell (RBC) measurements are clinically important, heritable and differ among ethnic groups. To identify genetic variants that contribute to RBC phenotypes in African Americans (AAs), we conducted a genome-wide association study in up to ∼16 500 AAs. The alpha-globin locus on chromosome 16pter [lead SNP rs13335629 in ITFG3 gene; P < 1E−13 for hemoglobin (Hgb), RBC count, mean corpuscular volume (MCV), MCH and MCHC] and the G6PD locus on Xq28 [lead SNP rs1050828; P < 1E − 13 for Hgb, hematocrit (Hct), MCV, RBC count and red cell distribution width (RDW)] were each associated with multiple RBC traits. At the alpha-globin region, both the common African 3.7 kb deletion and common single nucleotide polymorphisms (SNPs) appear to contribute independently to RBC phenotypes among AAs. In the 2p21 region, we identified a novel variant of PRKCE distinctly associated with Hct in AAs. In a genome-wide admixture mapping scan, local European ancestry at the 6p22 region containing HFE and LRRC16A was associated with higher Hgb. LRRC16A has been previously associated with the platelet count and mean platelet volume in AAs, but not with Hgb. Finally, we extended to AAs the findings of association of erythrocyte traits with several loci previously reported in Europeans and/or Asians, including CD164 and HBS1L-MYB. In summary, this large-scale genome-wide analysis in AAs has extended the importance of several RBC-associated genetic loci to AAs and identified allelic heterogeneity and pleiotropy at several previously known genetic loci associated with blood cell traits in AAs

Autologous adoptive T-cell therapy for recurrent or drug-resistant cytomegalovirus complications in solid organ transplant recipients: a single-arm open-label phase I clinical trial

Background:Opportunistic infections including cytomegalovirus (CMV) are a major cause of morbidity and mortality in solid organ transplant (SOT) recipients. The recurrent and protracted use of antiviral drugs with eventual emergence of drug resistance represents a significant constraint to therapy. Although adoptive T-cell therapy has been successfully used in hematopoietic stem cell transplant recipients, its extension to the SOT setting poses a considerable challenge because of the inhibitory effects of immunosuppressive drugs on the virus-specific T-cell response in vivo and the perceived risk of graft rejection. Methods:In this prospective study, 22 SOT recipients (13 renal and 8 lung and 1 heart transplants) with recurrent or ganciclovir-resistant CMV infection were recruited, and 13 of them were treated with in vitro-expanded autologous CMV-specific T cells. These patients were monitored for safety, clinical symptoms, and immune reconstitution. Results:Autologous CMV-specific T-cell manufacture was attempted for 21 patients, and was successful in 20. The use of this adoptive immunotherapy was associated with no therapy-related serious adverse events. Eleven (84%) of the 13 treated patients showed improvement in symptoms, including complete resolution or reduction in DNAemia and CMV-associated end-organ disease and/or the cessation or reduced use of antiviral drugs. Furthermore, four of these patients showed coincident increased frequency of CMV-specific T cells in peripheral blood after completion of T-cell therapy. Conclusions:The data presented here demonstrate for the first time the clinical safety of CMV-specific adoptive T-cell therapy and its potential therapeutic benefit for SOT recipients with recurrent and/or drug-resistant CMV infection or disease. Clinical Trials Registration:ACTRN12613000981729.Corey Smith, Leone Beagley, Sweera Rehan, Michelle A. Neller ... Mark D. Holmes ... Chien-Li Holmes-Liew ... et al

Effect of zeolite catalysts on pyrolysis liquid oil

The aim of this study was to determine the quality and applications of liquid oil produced by thermal and catalytic pyrolysis of polystyrene (PS) plastic waste by using a small pilot scale pyrolysis reactor. Thermal pyrolysis produced maximum liquid oil (80.8%) with gases (13%) and char (6.2%), while catalytic pyrolysis using synthetic and natural zeolite decreased the liquid oil yield (52%) with an increase in gases (17.7%) and char (30.1%) production. The lower yield but improved quality of liquid oil through catalytic pyrolysis are due to catalytic features of zeolites such as microporous structure and high BET surface area. The liquid oils, both from thermal and catalytic pyrolysis consist of around 99% aromatic hydrocarbons, as further confirmed by GC-MS results. FT-IR analysis further showed chemical bonding and functional groups of mostly aromatic hydrocarbons, which is consistent with GC-MS results. The produced liquid oils can be suitable for energy generation and heating purposes after the removal of acid, solid residues and contaminants. Further upgrading of liquid oil and blending with diesel is required for its potential use as a transport fuel

Retained Austenite Transformation during Heat Treatment of a 5 Wt Pct Cr Cold Work Tool Steel

Retained austenite transformation was studied for a 5 wt pct Cr cold work tool steel tempered at 798 K and 873 K (525 degrees C and 600 degrees C) followed by cooling to room temperature. Tempering cycles with variations in holding times were conducted to observe the mechanisms involved. Phase transformations were studied with dilatometry, and the resulting microstructures were characterized with X-ray diffraction and scanning electron microscopy. Tempering treatments at 798 K (525 degrees C) resulted in retained austenite transformation to martensite on cooling. The martensite start (M-s) and martensite finish (M-f) temperatures increased with longer holding times at tempering temperature. At the same time, the lattice parameter of retained austenite decreased. Calculations from the Ms temperatures and lattice parameters suggested that there was a decrease in carbon content of retained austenite as a result of precipitation of carbides prior to transformation. This was in agreement with the resulting microstructure and the contraction of the specimen during tempering, as observed by dilatometry. Tempering at 873 K (600 degrees C) resulted in precipitation of carbides in retained austenite followed by transformation to ferrite and carbides. This was further supported by the initial contraction and later expansion of the dilatometry specimen, the resulting microstructure, and the absence of any phase transformation on cooling from the tempering treatment. It was concluded that there are two mechanisms of retained austenite transformation occurring depending on tempering temperature and time. This was found useful in understanding the standard tempering treatment, and suggestions regarding alternative tempering treatments are discussed. (C) The Author(s) 2017.Funders: Uddeholm AB</p