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John Byrd

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https://www.readbyqxmd.com/read/28874529/synchronous-volcanic-eruptions-and-abrupt-climate-change-%C3%A2-17-7-ka-plausibly-linked-by-stratospheric-ozone-depletion
#1
Joseph R McConnell, Andrea Burke, Nelia W Dunbar, Peter Köhler, Jennie L Thomas, Monica M Arienzo, Nathan J Chellman, Olivia J Maselli, Michael Sigl, Jess F Adkins, Daniel Baggenstos, John F Burkhart, Edward J Brook, Christo Buizert, Jihong Cole-Dai, T J Fudge, Gregor Knorr, Hans-F Graf, Mackenzie M Grieman, Nels Iverson, Kenneth C McGwire, Robert Mulvaney, Guillaume Paris, Rachael H Rhodes, Eric S Saltzman, Jeffrey P Severinghaus, Jørgen Peder Steffensen, Kendrick C Taylor, Gisela Winckler
Glacial-state greenhouse gas concentrations and Southern Hemisphere climate conditions persisted until ∼17.7 ka, when a nearly synchronous acceleration in deglaciation was recorded in paleoclimate proxies in large parts of the Southern Hemisphere, with many changes ascribed to a sudden poleward shift in the Southern Hemisphere westerlies and subsequent climate impacts. We used high-resolution chemical measurements in the West Antarctic Ice Sheet Divide, Byrd, and other ice cores to document a unique, ∼192-y series of halogen-rich volcanic eruptions exactly at the start of accelerated deglaciation, with tephra identifying the nearby Mount Takahe volcano as the source...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28864640/spotlight-on-ibrutinib-in-pcnsl-adding-another-feather-to-its-cap
#2
Aparna Lakshmanan, John C Byrd
In this issue Grommes and colleagues elegantly show that the irreversible inhibitor of Bruton tyrosine kinase, ibrutinib, promotes a high proportion of durable responses in primary central nervous system lymphoma, a type of diffuse large B-cell lymphoma (DLBCL), and also in secondary DLBCL relapsing to the central nervous system. Mutations in the B-cell antigen receptor-associated protein CD79B with upregulation of the MTOR pathway were associated with diminished response, but preclinical combination of PIK3CA and PIK3CD inhibitors synergized with ibrutinib to overcome this resistance mechanism, providing opportunity for further targeted therapy of this difficult-to-treat disease...
September 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28751558/characterization-of-atrial-fibrillation-adverse-events-reported-in-ibrutinib-randomized-controlled-registration-trials
#3
Jennifer R Brown, Javid Moslehi, Susan O' Brien, Paolo Ghia, Peter Hillmen, Florence Cymbalista, Tait D Shanafelt, Graeme Fraser, Simon Rule, Thomas J Kipps, Steven Coutre, Marie-Sarah Dilhuydy, Paula Cramer, Alessandra Tedeschi, Ulrich Jaeger, Martin Dreyling, John C Byrd, Angela Howes, Michael Todd, Jessica Vermeulen, Danelle F James, Fong Clow, Lori Styles, Rudy Valentino, Mark Wildgust, Michelle Mahler, Jan A Burger
The first-in-class Bruton's tyrosine kinase inhibitor ibrutinib has proven clinical benefit in B-cell malignancies; however, atrial fibrillation has been reported in 6-16% of ibrutinib patients. We pooled data from 1505 chronic lymphocytic leukemia and mantle cell lymphoma patients enrolled in four large, randomized, controlled studies to characterize atrial fibrillation with ibrutinib and its management. Atrial fibrillation incidence was 6.5% (95% CI: 4.8, 8.5) for ibrutinib at 16.6-months (vs. 1.6% [95% CI: 0...
July 27, 2017: Haematologica
https://www.readbyqxmd.com/read/28724544/mica-expressing-monocytes-enhance-natural-killer-cell-fc-receptor-mediated-antitumor-functions
#4
Amanda R Campbell, Megan C Duggan, Lorena P Suarez-Kelly, Neela Bhave, Kallan S Opheim, Elizabeth L McMichael, Prashant Trikha, Robin Parihar, Eric Luedke, Adrian Lewis, Bryant Yung, Robert Lee, David Raulet, Susheela Tridandapani, Veronika Groh, Lianbo Yu, Vedat Yildiz, John C Byrd, Michael A Caligiuri, William E Carson
Natural killer (NK) cells are large granular lymphocytes that promote the antitumor response via communication with other cell types in the tumor microenvironment. Previously, we have shown that NK cells secrete a profile of immune stimulatory factors (e.g., IFNγ, MIP-1α, and TNFα) in response to dual stimulation with the combination of antibody (Ab)-coated tumor cells and cytokines, such as IL12. We now demonstrate that this response is enhanced in the presence of autologous monocytes. Monocyte enhancement of NK cell activity was dependent on cell-to-cell contact as determined by a Transwell assay...
September 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28715249/durable-molecular-remissions-in-chronic-lymphocytic-leukemia-treated-with-cd19-specific-chimeric-antigen-receptor-modified-t-cells-after-failure-of-ibrutinib
#5
Cameron J Turtle, Kevin A Hay, Laïla-Aïcha Hanafi, Daniel Li, Sindhu Cherian, Xueyan Chen, Brent Wood, Arletta Lozanski, John C Byrd, Shelly Heimfeld, Stanley R Riddell, David G Maloney
Purpose We evaluated the safety and feasibility of anti-CD19 chimeric antigen receptor-modified T (CAR-T) cell therapy in patients with chronic lymphocytic leukemia (CLL) who had previously received ibrutinib. Methods Twenty-four patients with CLL received lymphodepleting chemotherapy and anti-CD19 CAR-T cells at one of three dose levels (2 × 10(5), 2 × 10(6), or 2 × 10(7) CAR-T cells/kg). Nineteen patients experienced disease progression while receiving ibrutinib, three were ibrutinib intolerant, and two did not experience progression while receiving ibrutinib...
September 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28714866/ibrutinib-treatment-improves-t-cell-number-and-function-in-cll-patients
#6
Meixiao Long, Kyle Beckwith, Priscilla Do, Bethany L Mundy, Amber Gordon, Amy M Lehman, Kami J Maddocks, Carolyn Cheney, Jeffrey A Jones, Joseph M Flynn, Leslie A Andritsos, Farrukh Awan, Joseph A Fraietta, Carl H June, Marcela V Maus, Jennifer A Woyach, Michael A Caligiuri, Amy J Johnson, Natarajan Muthusamy, John C Byrd
BACKGROUND: Ibrutinib has been shown to have immunomodulatory effects by inhibiting Bruton's tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK). The relative importance of inhibiting these 2 kinases has not been examined despite its relevance to immune-based therapies. METHODS: Peripheral blood mononuclear cells from chronic lymphocytic leukemia (CLL) patients on clinical trials of ibrutinib (BTK/ITK inhibitor; n = 19) or acalabrutinib (selective BTK inhibitor; n = 13) were collected serially...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28688082/circulating-myeloid-derived-suppressor-cells-increase-in-patients-undergoing-neo-adjuvant-chemotherapy-for-breast-cancer
#7
Robert Wesolowski, Megan C Duggan, Andrew Stiff, Joseph Markowitz, Prashant Trikha, Kala M Levine, Lynn Schoenfield, Mahmoud Abdel-Rasoul, Rachel Layman, Bhuvaneswari Ramaswamy, Erin R Macrae, Maryam B Lustberg, Raquel E Reinbolt, Ewa Mrozek, John C Byrd, Michael A Caligiuri, Thomas A Mace, William E Carson Iii
This study sought to evaluate whether myeloid-derived suppressor cells (MDSC) could be affected by chemotherapy and correlate with pathologic complete response (pCR) in breast cancer patients receiving neo-adjuvant chemotherapy. Peripheral blood levels of granulocytic (G-MDSC) and monocytic (M-MDSC) MDSC were measured by flow cytometry prior to cycle 1 and 2 of doxorubicin and cyclophosphamide and 1st and last administration of paclitaxel or paclitaxel/anti-HER2 therapy. Of 24 patients, 11, 6 and 7 patients were triple negative, HER2+ and hormone receptor+, respectively...
July 7, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28638738/activation-of-the-fcgammareceptoriiia-on-human-natural-killer-cells-leads-to-increased-expression-of-functional-interleukin-21-receptor
#8
Elizabeth L McMichael, Nicholas B Courtney, Megan C Duggan, Robert Wesolowski, Dionisia Quiroga, Sri Vidya Kondadasula, Lakhvir S Atwal, Neela Bhave, Eric Luedke, Alena Cristina Jaime-Ramirez, Amanda R Campbell, Xiaokui Mo, John C Byrd, William E Carson Iii
Natural killer (NK) cells are innate immune effector cells that play a crucial role in immune surveillance and the destruction of cancer cells. NK cells express a low-affinity receptor for the Fc or constant region of immunoglobulin G (FcγRIIIa) and multiple cytokine receptors that respond to antibody-coated targets and cytokines in the tumor microenvironment. In the present work, microarray gene expression analysis revealed that the IL-21 receptor (IL-21R) was strongly upregulated following FcR stimulation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28613270/a-socio-ecological-examination-of-weight-related-characteristics-of-the-home-environment-and-lifestyles-of-households-with-young-children
#9
Virginia Quick, Jennifer Martin-Biggers, Gayle Alleman Povis, Nobuko Hongu, John Worobey, Carol Byrd-Bredbenner
Home environment and family lifestyle practices have an influence on child obesity risk, thereby making it critical to systematically examine these factors. Thus, parents (n = 489) of preschool children completed a cross-sectional online survey which was the baseline data collection conducted, before randomization, in the HomeStyles program. The survey comprehensively assessed these factors using a socio-ecological approach, incorporating intrapersonal, interpersonal and environmental measures. Healthy intrapersonal dietary behaviors identified were parent and child intakes of recommended amounts of 100% juice and low intakes of sugar-sweetened beverages...
June 14, 2017: Nutrients
https://www.readbyqxmd.com/read/28591523/completion-dissection-or-observation-for-sentinel-node-metastasis-in-melanoma
#10
RANDOMIZED CONTROLLED TRIAL
Mark B Faries, John F Thompson, Alistair J Cochran, Robert H Andtbacka, Nicola Mozzillo, Jonathan S Zager, Tiina Jahkola, Tawnya L Bowles, Alessandro Testori, Peter D Beitsch, Harald J Hoekstra, Marc Moncrieff, Christian Ingvar, Michel W J M Wouters, Michael S Sabel, Edward A Levine, Doreen Agnese, Michael Henderson, Reinhard Dummer, Carlo R Rossi, Rogerio I Neves, Steven D Trocha, Frances Wright, David R Byrd, Maurice Matter, Eddy Hsueh, Alastair MacKenzie-Ross, Douglas B Johnson, Patrick Terheyden, Adam C Berger, Tara L Huston, Jeffrey D Wayne, B Mark Smithers, Heather B Neuman, Schlomo Schneebaum, Jeffrey E Gershenwald, Charlotte E Ariyan, Darius C Desai, Lisa Jacobs, Kelly M McMasters, Anja Gesierich, Peter Hersey, Steven D Bines, John M Kane, Richard J Barth, Gregory McKinnon, Jeffrey M Farma, Erwin Schultz, Sergi Vidal-Sicart, Richard A Hoefer, James M Lewis, Randall Scheri, Mark C Kelley, Omgo E Nieweg, R Dirk Noyes, Dave S B Hoon, He-Jing Wang, David A Elashoff, Robert M Elashoff
BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group)...
June 8, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28547802/the-power-of-exclusion-using-automated-osteometric-sorting-pair-matching
#11
Jeffrey James Lynch, John Byrd, Carrie B LeGarde
This study compares the original pair-matching osteometric sorting model (J Forensic Sci 2003;48:717) against two new models providing validation and performance testing across three samples. The samples include the Forensic Data Bank, USS Oklahoma, and the osteometric sorting reference used within the Defense POW/MIA Accounting Agency. A computer science solution to generating dynamic statistical models across a commingled assemblage is presented. The issue of normality is investigated showing the relative robustness against non-normality and a data transformation to control for normality...
May 26, 2017: Journal of Forensic Sciences
https://www.readbyqxmd.com/read/28526658/nonclinical-pharmacology-and-toxicology-of-the-first-biosimilar-insulin-glargine-drug-product-basaglar-%C3%A2-abasaglar-%C3%A2-approved-in-the-european-union
#12
Richard A Byrd, Rebecca A Owens, Jamie L Blackbourne, David E Coutant, Mark W Farmen, M Dodson Michael, Julie S Moyers, A Eric Schultze, Michael K Sievert, Niraj K Tripathi, John L Vahle
Basaglar(®)/Abasaglar(®) (Lilly insulin glargine [LY IGlar]) is a long-acting human insulin analogue drug product granted marketing authorisation as a biosimilar to Lantus(®) (Sanofi insulin glargine [SA IGlar]) by the European Medicines Agency. We assessed the similarity of LY IGlar to the reference drug product, European Union-sourced SA IGlar (EU-SA IGlar), using nonclinical in vitro and in vivo studies. No biologically relevant differences were observed for receptor binding affinity at either the insulin or insulin-like growth factor-1 (IGF-1) receptors, or in assays of functional or de novo lipogenic activity...
May 17, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28515090/nf-%C3%AE%C2%BAb-p50-nfkb1-contributes-to-pathogenesis-in-the-e%C3%AE-tcl1-mouse-model-of-chronic-lymphocytic-leukemia
#13
LETTER
Timothy L Chen, Minh Tran, Aparna Lakshmanan, Bonnie K Harrington, Nikhil Gupta, Virginia M Goettl, Amy M Lehman, Stephen Trudeau, David M Lucas, Amy J Johnson, John C Byrd, Erin Hertlein
No abstract text is available yet for this article.
July 20, 2017: Blood
https://www.readbyqxmd.com/read/28473620/prognostic-and-biologic-significance-of-long-non-coding-rna-profiling-in-younger-adults-with-cytogenetically-normal-acute-myeloid-leukemia
#14
Dimitrios Papaioannou, Deedra Nicolet, Stefano Volinia, Krzysztof Mrózek, Pearlly Yan, Ralf Bundschuh, Andrew J Carroll, Jessica Kohlschmidt, William Blum, Bayard L Powell, Geoffrey L Uy, Jonathan E Kolitz, Eunice S Wang, Ann-Kathrin Eisfeld, Shelley J Orwick, David M Lucas, Michael A Caligiuri, Richard M Stone, John C Byrd, Ramiro Garzon, Clara D Bloomfield
Long non-coding ribonucleic acids (RNAs) are a novel class of RNA molecules, which are increasingly recognized as important molecular players in solid and hematologic malignancies. Herein we investigated whether long non-coding RNA expression is associated with clinical and molecular features, as well as outcome of younger adults (aged <60 years) with de novo cytogenetically normal acute myeloid leukemia. Whole transcriptome profiling was performed in a training (n=263) and a validation set (n=114). Using the training set, we identified 24 long non-coding RNAs associated with event-free survival...
August 2017: Haematologica
https://www.readbyqxmd.com/read/28442452/homestyles-a-web-based-childhood-obesity-prevention-program-for-families-with-preschool-children-protocol-for-a-randomized-controlled-trial
#15
Carol Byrd-Bredbenner, Jennifer Martin-Biggers, Mallory Koenings, Virginia Quick, Nobuko Hongu, John Worobey
BACKGROUND: The home environment is where young children spend most of their time, and is critically important to supporting behaviors that promote health and prevent obesity. However, the home environment and lifestyle patterns remain understudied, and few interventions have investigated parent-led makeovers designed to create home environments that are supportive of optimal child health and healthy child weights. OBJECTIVE: The aim of the HomeStyles randomized controlled trial (RCT) is to determine whether the Web-based HomeStyles intervention enables and motivates parents to shape the weight-related aspects of their home environments and lifestyle behavioral practices (diet, exercise, and sleep) to be more supportive of their preschool children's optimal health and weight...
April 25, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28421968/chronic-toxicology-studies-of-basal-insulin-peglispro-in-rats-and-dogs-a-novel-pegylated-insulin-lispro-analog-with-a-prolonged-duration-of-action
#16
Richard A Byrd, Jamie L Blackbourne, Mary Pat Knadler, Albert E Schultze, John L Vahle
Basal insulin peglispro (BIL) consists of insulin lispro with a 20-kDa polyethylene glycol (PEG) moiety covalently attached to lysine B28. Because chronic parenteral administration of PEGylated proteins to animals has sometimes resulted in PEG vacuolation of tissue macrophages, renal tubular cells, and choroid plexus ependymal cells, we investigated whether chronic subcutaneous (sc) injection of BIL in rats (52 weeks) and dogs (39 weeks) was associated with systemic toxicities or other changes, including vacuolation of tissue macrophages, renal tubular cells, and ependymal cells...
April 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28418267/btk-c481s-mediated-resistance-to-ibrutinib-in-chronic-lymphocytic-leukemia
#17
RANDOMIZED CONTROLLED TRIAL
Jennifer A Woyach, Amy S Ruppert, Daphne Guinn, Amy Lehman, James S Blachly, Arletta Lozanski, Nyla A Heerema, Weiqiang Zhao, Joshua Coleman, Daniel Jones, Lynne Abruzzo, Amber Gordon, Rose Mantel, Lisa L Smith, Samantha McWhorter, Melanie Davis, Tzyy-Jye Doong, Fan Ny, Margaret Lucas, Weihong Chase, Jeffrey A Jones, Joseph M Flynn, Kami Maddocks, Kerry Rogers, Samantha Jaglowski, Leslie A Andritsos, Farrukh T Awan, Kristie A Blum, Michael R Grever, Gerard Lozanski, Amy J Johnson, John C Byrd
Purpose Therapeutic targeting of Bruton tyrosine kinase (BTK) with ibrutinib in chronic lymphocytic leukemia has led to a paradigm shift in therapy, and relapse has been uncommon with current follow-up. Acquired mutations in BTK and PLCG2 can cause relapse, but data regarding the prevalence and natural history of these mutations are limited. Patients and Methods Patients accrued to four sequential studies of ibrutinib were included in these analyses. Deep sequencing for BTK and PLCG2 was performed retrospectively on patients who experienced relapse and prospectively on a screening population...
May 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28397242/use-of-anticoagulants-and-antiplatelet-in-patients-with-chronic-lymphocytic-leukaemia-treated-with-single-agent-ibrutinib
#18
RANDOMIZED CONTROLLED TRIAL
Jeffrey A Jones, Peter Hillmen, Steven Coutre, Constantine Tam, Richard R Furman, Paul M Barr, Stephen J Schuster, Thomas J Kipps, Ian W Flinn, Ulrich Jaeger, Jan A Burger, Mei Cheng, Joi Ninomoto, Danelle F James, John C Byrd, Susan M O'Brien
Bleeding events have been observed among a subgroup of chronic lymphocytic leukaemia (CLL) patients treated with ibrutinib. We analysed data from two studies of single-agent ibrutinib to better characterize bleeding events and pattern of anticoagulation and antiplatelet use. Among 327 ibrutinib-treated patients, concomitant anticoagulation (11%) or antiplatelet use (34%) was common, but major bleeding was infrequent (2%). Bleeding events were primarily grade 1, and infrequently (1%) led to discontinuation. Among 175 patients receiving concomitant anticoagulant or antiplatelet agents, 5 had major bleeding events (3%)...
July 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28373262/impact-of-ibrutinib-dose-adherence-on-therapeutic-efficacy-in-patients-with-previously-treated-cll-sll
#19
Paul M Barr, Jennifer R Brown, Peter Hillmen, Susan O'Brien, Jacqueline C Barrientos, Nishitha M Reddy, Steven Coutre, Stephen P Mulligan, Ulrich Jaeger, Richard R Furman, Florence Cymbalista, Marco Montillo, Claire Dearden, Tadeusz Robak, Carol Moreno, John M Pagel, Jan A Burger, Samuel Suzuki, Juthamas Sukbuntherng, George Cole, Danelle F James, John C Byrd
Ibrutinib, an oral inhibitor of Bruton's tyrosine kinase (BTK), at a once-daily dose of 420 mg achieved BTK active-site occupancy in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) that was maintained at 24 hours. It is unknown if intermittent interruption of ibrutinib therapy contributes to altered clinical outcomes. We therefore evaluated the effect of ibrutinib dose adherence on patient outcomes in the phase 3 RESONATE trial. The overall mean dose intensity (DI) was 95% with median treatment duration of ∼9 months...
May 11, 2017: Blood
https://www.readbyqxmd.com/read/28299881/the-regulation-of-tumor-suppressive-microrna-mir-126-in%C3%A2-chronic-lymphocytic-leukemia
#20
Daphne Guinn, Amy Lehman, Catherine Fabian, Lianbo Yu, Kami Maddocks, Leslie A Andritsos, Jeffrey A Jones, Joseph M Flynn, Samantha M Jaglowski, Jennifer A Woyach, John C Byrd, Amy J Johnson
The introduction of miR profiling of chronic lymphocytic leukemia (CLL) patients with different cytogenetic profiles and responses to therapy has allowed incorporation of important miR-mRNA interactions into the understanding of disease biology. In this study, we performed miR expression analysis using NanoString nCounter to discover differentially regulated miRs after therapy with the Bruton tyrosine kinase inhibitor ibrutinib. Of the differentially regulated miRs in the discovery set, miR-29c and miR-126 were confirmed using real-time PCR to be upregulated in CLL patient cells with ibrutinib therapy...
April 2017: Cancer Medicine
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