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Jeffrey L Carson

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https://www.readbyqxmd.com/read/29259756/vu6010608-a-novel-mglu7-nam-from-a-series-of-n-2-1h-1-2-4-triazol-1-yl-5-trifluoromethoxy-phenyl-benzamides
#1
Carson W Reed, Kevin M McGowan, Paul K Spearing, Branden J Stansley, Hanna F Roenfanz, Darren W Engers, Alice L Rodriguez, Eileen M Engelberg, Vincent B Luscombe, Matthew T Loch, Daniel H Remke, Jerri M Rook, Anna L Blobaum, P Jeffrey Conn, Colleen M Niswender, Craig W Lindsley
Herein, we report the structure-activity relationships within a series of mGlu7 NAMs based on an N-(2-(1H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl)benzamide core with excellent CNS penetration (Kp 1.9-5.8 and Kp,uu 0.4-1.4). Analogues in this series displayed steep SAR. Of these, VU6010608 (11a) emerged with robust efficacy in blocking high frequency stimulated long-term potentiation in electrophysiology studies.
December 14, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29115020/glycosylphosphatidylinositol-gpi-anchored-protein-deficiency-serves-as-a-reliable-reporter-of-pig-a-gene-mutation-support-from-an-in-vitro-assay-based-on-l5178y-tk-cells-and-the-cd90-2-antigen
#2
Jeffrey C Bemis, Svetlana L Avlasevich, Carson Labash, Page McKinzie, Javier Revollo, Vasily N Dobrovolsky, Stephen D Dertinger
Lack of cell surface glycosylphosphatidylinositol (GPI)-anchored protein(s) has been used as a reporter of Pig-a gene mutation in several model systems. As an extension of this work, our laboratory initiated development of an in vitro mutation assay based on the flow cytometric assessment of CD90.2 expression on the cell surface of the mouse lymphoma cell line L5178Y/Tk(+/-) . Cells were exposed to mutagenic and nonmutagenic compounds for 24 hr followed by washout and incubation for an additional 7 days. Following this mutant manifestation time, cells were labeled with fluorescent antibodies against CD90...
November 8, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28953438/indications-for-and-adverse-effects-of-red-cell-transfusion
#3
REVIEW
Jeffrey L Carson, Darrell J Triulzi, Paul M Ness
New England Journal of Medicine, Volume 377, Issue 13, Page 1261-1272, September 2017.
September 28, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28882834/anemia-and-bleeding-in-thrombocytopenic-patients
#4
Jeffrey L Carson, Simon J Stanworth
No abstract text is available yet for this article.
September 7, 2017: Blood
https://www.readbyqxmd.com/read/28833575/in-vivo-pig-a-and-micronucleus-study-of-the-prototypical-aneugen-vinblastine-sulfate
#5
Svetlana L Avlasevich, Carson Labash, Dorothea K Torous, Jeffrey C Bemis, James T MacGregor, Stephen D Dertinger
The Pig-a assay is being used in regulatory studies to evaluate the potential of agents to induce somatic cell gene mutations and an OECD test guideline is under development. A working group involved with establishing the guideline recently noted that representative aneugenic agents had not been evaluated, and to help fill this data gap Pig-a mutant phenotype and micronucleated reticulocyte frequencies were measured in an integrated study design to assess the mutagenic and cytogenetic damage responses to vinblastine sulfate exposure...
August 19, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28135150/phase-iii-randomized-study-of-4-weeks-of-high-dose-interferon-%C3%AE-2b-in-stage-t2bno-t3a-bno-t4a-bno-and-t1-4n1a-2a-microscopic-melanoma-a-trial-of-the-eastern-cooperative-oncology-group-american-college-of-radiology-imaging-network-cancer-research-group-e1697
#6
RANDOMIZED CONTROLLED TRIAL
Sanjiv S Agarwala, Sandra J Lee, Waiki Yip, Uma N Rao, Ahmad A Tarhini, Gary I Cohen, Douglas S Reintgen, Terry L Evans, Joanna M Brell, Mark R Albertini, Michael B Atkins, Shaker R Dakhil, Robert M Conry, Jeffrey A Sosman, Lawrence E Flaherty, Vernon K Sondak, William E Carson, Michael G Smylie, Alberto S Pappo, Richard F Kefford, John M Kirkwood
Purpose To test the efficacy of 4 weeks of intravenous (IV) induction with high-dose interferon (IFN) as part of the Eastern Cooperative Oncology Group regimen compared with observation (OBS) in patients with surgically resected intermediate-risk melanoma. Patients and Methods In this intergroup international trial, eligible patients had surgically resected cutaneous melanoma in the following categories: (1) T2bN0, (2) T3a-bN0, (3) T4a-bN0, and (4) T1-4N1a-2a (microscopic). Patients were randomly assigned to receive IFN α-2b at 20 MU/m(2)/d IV for 5 days (Monday to Friday) every week for 4 weeks (IFN) or OBS...
March 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28004771/spatially-resolved-proteomics-rapid-quantitative-analysis-of-laser-capture-microdissected-alveolar-tissue-samples
#7
Geremy Clair, Paul D Piehowski, Teodora Nicola, Joseph A Kitzmiller, Eric L Huang, Erika M Zink, Ryan L Sontag, Daniel J Orton, Ronald J Moore, James P Carson, Richard D Smith, Jeffrey A Whitsett, Richard A Corley, Namasivayam Ambalavanan, Charles Ansong
Laser capture microdissection (LCM)-enabled region-specific tissue analyses are critical to better understand complex multicellular processes. However, current proteomics workflows entail several manual sample preparation steps and are challenged by the microscopic mass-limited samples generated by LCM, impacting measurement robustness, quantification and throughput. Here, we coupled LCM with a proteomics workflow that provides fully automated analysis of proteomes from microdissected tissues. Benchmarking against the current state-of-the-art in ultrasensitive global proteomics (FASP workflow), our approach demonstrated significant improvements in quantification (~2-fold lower variance) and throughput (>5 times faster)...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27852723/regional-versus-general-anesthesia-for-promoting-independence-after-hip-fracture-regain-protocol-for-a-pragmatic-international-multicentre-trial
#8
Mark D Neuman, Susan S Ellenberg, Frederick E Sieber, Jay S Magaziner, Rui Feng, Jeffrey L Carson
INTRODUCTION: Hip fractures occur 1.6 million times each year worldwide, with substantial associated mortality and losses of independence. At present, anaesthesia care for hip fracture surgery varies widely within and between countries, with general anaesthesia and spinal anaesthesia representing the 2 most common approaches. Limited randomised evidence exists regarding potential short-term or long-term differences in outcomes between patients receiving spinal or general anaesthesia for hip fracture surgery...
November 15, 2016: BMJ Open
https://www.readbyqxmd.com/read/27739152/red-blood-cell-transfusion-2016-clinical-practice-guidelines-from-aabb
#9
Aaron A R Tobian, Nancy M Heddle, Theresa L Wiegmann, Jeffrey L Carson
No abstract text is available yet for this article.
October 2016: Transfusion
https://www.readbyqxmd.com/read/27732721/clinical-practice-guidelines-from-the-aabb-red-blood-cell-transfusion-thresholds-and-storage
#10
Jeffrey L Carson, Gordon Guyatt, Nancy M Heddle, Brenda J Grossman, Claudia S Cohn, Mark K Fung, Terry Gernsheimer, John B Holcomb, Lewis J Kaplan, Louis M Katz, Nikki Peterson, Glenn Ramsey, Sunil V Rao, John D Roback, Aryeh Shander, Aaron A R Tobian
Importance: More than 100 million units of blood are collected worldwide each year, yet the indication for red blood cell (RBC) transfusion and the optimal length of RBC storage prior to transfusion are uncertain. Objective: To provide recommendations for the target hemoglobin level for RBC transfusion among hospitalized adult patients who are hemodynamically stable and the length of time RBCs should be stored prior to transfusion. Evidence Review: Reference librarians conducted a literature search for randomized clinical trials (RCTs) evaluating hemoglobin thresholds for RBC transfusion (1950-May 2016) and RBC storage duration (1948-May 2016) without language restrictions...
November 15, 2016: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/27731885/transfusion-thresholds-and-other-strategies-for-guiding-allogeneic-red-blood-cell-transfusion
#11
REVIEW
Jeffrey L Carson, Simon J Stanworth, Nareg Roubinian, Dean A Fergusson, Darrell Triulzi, Carolyn Doree, Paul C Hebert
BACKGROUND: There is considerable uncertainty regarding the optimal haemoglobin threshold for the use of red blood cell (RBC) transfusions in anaemic patients. Blood is a scarce resource, and in some countries, transfusions are less safe than others because of a lack of testing for viral pathogens. Therefore, reducing the number and volume of transfusions would benefit patients. OBJECTIVES: The aim of this review was to compare 30-day mortality and other clinical outcomes in participants randomized to restrictive versus liberal red blood cell (RBC) transfusion thresholds (triggers) for all conditions...
October 12, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27112994/red-blood-cell-transfusion-strategies-in-adult-and-pediatric-patients-with-malignancy
#12
REVIEW
Nareg Roubinian, Jeffrey L Carson
Anemia in patients with malignancy is common as a consequence of their disease and treatment. Substantial progress has been made in the management of anemia with red blood cell transfusion in acute conditions, such as bleeding and infection, through the performance of large clinical trials. These trials suggest that transfusion at lower hemoglobin thresholds (restrictive transfusion ∼7-8 g/dL) is safe and in some cases superior to higher transfusion thresholds (liberal transfusion ∼9-10 g/dL). However, additional studies are needed in patients with malignancy to understand best practice in relation to quality of life as well as clinical outcomes...
June 2016: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27076078/ampk-is-essential-to-balance-glycolysis-and-mitochondrial-metabolism-to-control-t-all-cell-stress-and-survival
#13
Rigel J Kishton, Carson E Barnes, Amanda G Nichols, Sivan Cohen, Valerie A Gerriets, Peter J Siska, Andrew N Macintyre, Pankuri Goraksha-Hicks, Aguirre A de Cubas, Tingyu Liu, Marc O Warmoes, E Dale Abel, Allen Eng Juh Yeoh, Timothy R Gershon, W Kimryn Rathmell, Kristy L Richards, Jason W Locasale, Jeffrey C Rathmell
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy associated with Notch pathway mutations. While both normal activated and leukemic T cells can utilize aerobic glycolysis to support proliferation, it is unclear to what extent these cell populations are metabolically similar and if differences reveal T-ALL vulnerabilities. Here we show that aerobic glycolysis is surprisingly less active in T-ALL cells than proliferating normal T cells and that T-ALL cells are metabolically distinct. Oncogenic Notch promoted glycolysis but also induced metabolic stress that activated 5' AMP-activated kinase (AMPK)...
April 12, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27070726/clinical-features-and-associated-likelihood-of-primary-ciliary-dyskinesia-in-children-and-adolescents
#14
Margaret W Leigh, Thomas W Ferkol, Stephanie D Davis, Hye-Seung Lee, Margaret Rosenfeld, Sharon D Dell, Scott D Sagel, Carlos Milla, Kenneth N Olivier, Kelli M Sullivan, Maimoona A Zariwala, Jessica E Pittman, Adam J Shapiro, Johnny L Carson, Jeffrey Krischer, Milan J Hazucha, Michael R Knowles
RATIONALE: Primary ciliary dyskinesia (PCD), a genetically heterogeneous, recessive disorder of motile cilia, is associated with distinct clinical features. Diagnostic tests, including ultrastructural analysis of cilia, nasal nitric oxide measurements, and molecular testing for mutations in PCD genes, have inherent limitations. OBJECTIVES: To define a statistically valid combination of systematically defined clinical features that strongly associates with PCD in children and adolescents...
August 2016: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/26856665/right-atrial-pressure-pulmonary-artery-wedge-pressure-ratio-a-more-specific-predictor-of-survival-in-pulmonary-arterial-hypertension
#15
Wassim H Fares, Lavanya Bellumkonda, Adriano R Tonelli, Shannon S Carson, Paul M Hassoun, Terence K Trow, Erica L Herzog, Naftali Kaminski, Cyrus A Kholdani, Lixia Zhang, Yi Zhou, Jeffrey P Hammel, Raed A Dweik
BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive, fatal disease. Current prognostic models are not ideal, and identifying more accurate prognostic variables is needed. The objective of this study was to evaluate the relative prognostic value of the right atrial pressure/pulmonary artery wedge pressure (RAP/PAWP) ratio in PAH patients. We hypothesized that the RAP/PAWP ratio is more predictive of survival than any of the other measured or calculated hemodynamic variables...
June 2016: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/26722906/strong-loophole-free-test-of-local-realism
#16
Lynden K Shalm, Evan Meyer-Scott, Bradley G Christensen, Peter Bierhorst, Michael A Wayne, Martin J Stevens, Thomas Gerrits, Scott Glancy, Deny R Hamel, Michael S Allman, Kevin J Coakley, Shellee D Dyer, Carson Hodge, Adriana E Lita, Varun B Verma, Camilla Lambrocco, Edward Tortorici, Alan L Migdall, Yanbao Zhang, Daniel R Kumor, William H Farr, Francesco Marsili, Matthew D Shaw, Jeffrey A Stern, Carlos Abellán, Waldimar Amaya, Valerio Pruneri, Thomas Jennewein, Morgan W Mitchell, Paul G Kwiat, Joshua C Bienfang, Richard P Mirin, Emanuel Knill, Sae Woo Nam
We present a loophole-free violation of local realism using entangled photon pairs. We ensure that all relevant events in our Bell test are spacelike separated by placing the parties far enough apart and by using fast random number generators and high-speed polarization measurements. A high-quality polarization-entangled source of photons, combined with high-efficiency, low-noise, single-photon detectors, allows us to make measurements without requiring any fair-sampling assumptions. Using a hypothesis test, we compute p values as small as 5...
December 18, 2015: Physical Review Letters
https://www.readbyqxmd.com/read/26553764/nccn-oncology-research-program-s-investigator-steering-committee-and-nccn-best-practices-committee-molecular-profiling-surveys
#17
MULTICENTER STUDY
Razelle Kurzrock, A Dimitrios Colevas, Anthony Olszanski, Wallace Akerley, Carlos L Arteaga, William E Carson, Jeffrey W Clark, John F DiPersio, David S Ettinger, Robert J Morgan, Lee S Schwartzberg, Alan P Venook, Christopher D Gocke, Jonathan Tait, F Marc Stewart
BACKGROUND: With advances such as next-generation sequencing (NGS) increasing understanding of the basis of cancer and its response to treatment, NCCN believes it is important to understand how molecular profiling/diagnostic testing is being performed and used at NCCN Member Institutions and their community affiliates. METHODS: The NCCN Oncology Research Program's Investigator Steering Committee and the NCCN Best Practices Committee gathered baseline information on the use of cancer-related molecular testing at NCCN Member Institutions and community members of the NCCN Affiliate Research Consortium through 2 separate surveys distributed in December 2013 and September 2014, respectively...
November 2015: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/26357928/a-comparison-of-cpap-and-cpapflex-in-the-treatment-of-obstructive-sleep-apnea-in-world-trade-center-responders-study-protocol-for-a-randomized-controlled-trial
#18
RANDOMIZED CONTROLLED TRIAL
Indu Ayappa, Jag Sunderram, Kathleen Black, Akosua Twumasi, Iris Udasin, Denise Harrison, Jeffrey L Carson, Shou-En Lu, David M Rapoport
BACKGROUND: Following the World Trade Center disaster, a large number of individuals involved in rescue and recovery activity were exposed to significant amounts of dust, and reported symptoms of chronic nasal and sinus inflammation. An unusually high prevalence of obstructive sleep apnea (OSA) has also been observed in this World Trade Center Responder population. This project aims to examine the relationship between nasal pathology and OSA. Our hypothesis is that increased nasal resistance due to nasal inflammation predisposes to OSA in this population...
September 10, 2015: Trials
https://www.readbyqxmd.com/read/26352420/the-shifting-paradigm-for-transfusion-of-red-blood-cells
#19
Jeffrey L Carson
No abstract text is available yet for this article.
March 2015: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/26232429/proteolytic-cleavage-of-ampk%C3%AE-and-intracellular-mmp9-expression-are-both-required-for-tlr4-mediated-mtorc1-activation-and-hif-1%C3%AE-expression-in-leukocytes
#20
Zhiyong Zhang, Louis F Amorosa, Susette M Coyle, Marie A Macor, Sara E Lubitz, Jeffrey L Carson, Morris J Birnbaum, Leonard Y Lee, Beatrice Haimovich
LPS-induced TLR4 activation alters cellular bioenergetics and triggers proteolytic cleavage of AMPKα and HIF-1α expression in leukocytes. In human leukocytes, and more specifically neutrophils, AMPKα cleavage yields 55- and 35-kDa protein fragments. In this study, we address the mechanism by which AMPKα is cleaved and its relevance to human health. Our data indicate that AMPKα cleavage is linked to MMP9 expression and that both are required for mammalian target of rapamycin complex-1 and S6K1 activation and HIF-1α expression in LPS-stimulated human and mice leukocytes...
September 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
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