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Michael O'Brien

Ashang Luwang Laiva, Rosanne M Raftery, Michael B Keogh, Fergal J O'Brien
Ensuring an adequate angiogenic response during wound healing is a prevailing clinical challenge in biomaterials science. To address this, we aimed to develop a pro-angiogenic gene-activated scaffold (GAS) that could activate MSCs to produce paracrine factors and influence angiogenesis and wound repair. A non-viral polyethyleneimine (PEI) nanoparticles carrying a gene encoding for stromal derived factor-1 alpha (SDF-1α) was combined with a collagen-chondroitin sulfate scaffold to produce the GAS. The ability of this platform to enhance the angiogenic potential of mesenchymal stem cells (MSCs) was then assessed...
March 16, 2018: International Journal of Pharmaceutics
Maro Ohanian, Ana Tari Ashizawa, Guillermo Garcia-Manero, Naveen Pemmaraju, Tapan Kadia, Elias Jabbour, Farhad Ravandi, Gautam Borthakur, Michael Andreeff, Marina Konopleva, Miranda Lim, Sherry Pierce, Susan O'Brien, Yesid Alvarado, Srdan Verstovsek, William Wierda, Hagop Kantarjian, Jorge Cortes
BACKGROUND: Activating mutations of tyrosine kinases are common in leukaemias. Oncogenic tyrosine kinases use the growth factor receptor-bound protein 2 (Grb2) for signal transduction, leading to activation of mitogen-activated protein kinase (MAPK) 1 and MAPK3 (ERK2 and ERK1). We hypothesised that inhibition of Grb2 would suppress ERK1 and ERK2 activation and inhibit leukaemia progression. To inhibit Grb2, a liposome-incorporated antisense oligodeoxynucleotide that blocks Grb2 protein expression, BP1001, was developed...
March 14, 2018: Lancet Haematology
Byron J Schneider, Zachary McCormick, David O'Brien, Michael Bunch, Clark C Smith
No abstract text is available yet for this article.
March 14, 2018: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Luis R Peraza, Ruth Cromarty, Xenia Kobeleva, Michael J Firbank, Alison Killen, Sara Graziadio, Alan J Thomas, John T O'Brien, John-Paul Taylor
Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) require differential management despite presenting with symptomatic overlap. Currently, there is a need of inexpensive DLB biomarkers which can be fulfilled by electroencephalography (EEG). In this regard, an established electrophysiological difference in DLB is a decrease of dominant frequency (DF)-the frequency with the highest signal power between 4 and 15 Hz. Here, we investigated network connectivity in EEG signals acquired from DLB patients, and whether these networks were able to differentiate DLB from healthy controls (HCs) and associated dementias...
March 15, 2018: Scientific Reports
Michael Hallek, Bruce D Cheson, Daniel Catovsky, Federico Caligaris-Cappio, Guillermo Dighiero, Hartmut Döhner, Peter Hillmen, Michael Keating, Emili Montserrat, Nicholas Chiorazzi, Stephan Stilgenbauer, Kanti R Rai, John C Byrd, Barbara Eichhorst, Susan O'Brien, Tadeusz Robak, John F Seymour, Thomas J Kipps
In 2008, International Workshop on CLL (iwCLL) published consensus guidelines for the design and conduct of clinical trials for patients with chronic lymphocytic leukemia (CLL) that were revised from those previously published by the National Cancer Institute-sponsored Working Group. These guidelines provided definitions intended to standardize the assessment of patients that were adopted by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the evaluation of new drugs. Since the publication of these guidelines there have been major advances in the biology and treatment of patients with CLL, prompting the iwCLL to evaluate and revise the 2008 criteria...
March 14, 2018: Blood
Michael J Martens, Brent R Logan
Competing risks endpoints arise when patients can fail therapy from several causes. Analyzing these outcomes allows one to assess directly the benefit of treatment on a primary cause of failure in a clinical trial setting. Regression models can be used in clinical trials to adjust for residual imbalances in patient characteristics, improving the power to detect treatment differences. But, none of the competing risks methods currently available for use in group sequential trials adjust for covariates. We propose a group sequential test for treatment effect that, because it is based on the Fine-Gray model, permits adjustment for covariates...
March 13, 2018: Biometrics
Matthew Cox, Catherine O'Connor, Katie Biggs, Daniel Hind, Oscar Bortolami, Matthew Franklin, Barbara Collins, Stephen Walters, Allan Wailoo, Julie Channell, Paul Albert, Ursula Freeman, Stephen Bourke, Michael Steiner, Jon Miles, Tom O'Brien, David McWilliams, Terry Schofield, John O'Reilly, Rodney Hughes
BACKGROUND: Chronic obstructive pulmonary disease (COPD) affects > 3 million people in the UK. Acute exacerbations of COPD (AECOPD) are the second most common reason for emergency hospital admission in the UK. Pulmonary rehabilitation is usual care for stable COPD but there is little evidence for early pulmonary rehabilitation (EPR) following AECOPD, either in hospital or immediately post discharge. OBJECTIVE: To assess the feasibility of recruiting patients, collecting data and delivering EPR to patients with AECOPD to evaluate EPR compared with usual care...
March 2018: Health Technology Assessment: HTA
Mark H Yazer, Nancy M Dunbar, Claudia Cohn, Jessica Dillon, Howida Eldib, Bryon Jackson, Richard Kaufman, Michael F Murphy, Kerry O'Brien, Jay S Raval, Jansen Seheult, Julie Staves, Jonathan H Waters
BACKGROUND: Bleeding emergencies can complicate pregnancies. Understanding the disposition of the products that are issued in this clinical setting can help inform inventory levels at hospitals where obstetric patients are seen. STUDY DESIGN AND METHODS: Patients who had an obstetric hemorrhage of any etiology between January 2013 and June 2017, and whose resuscitation began with uncrossmatched red blood cells (RBCs) or emergency-issued plasma or platelets (PLT), were included...
March 7, 2018: Transfusion
Heather J Tarbet, Lee Dolat, Timothy J Smith, Brett M Condon, E Timothy O'Brien, Raphael H Valdivia, Michael Boyce
Intermediate filaments (IF) are a major component of the metazoan cytoskeleton and are essential for normal cell morphology, motility, and signal transduction. Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy. Despite this pathophysiological significance, how cells regulate IF structure, dynamics, and function remains poorly understood. Here, we show that site-specific modification of the prototypical IF protein vimentin with O-linked β- N -acetylglucosamine (O-GlcNAc) mediates its homotypic protein-protein interactions and is required in human cells for IF morphology and cell migration...
March 7, 2018: ELife
Eanna P Connaughton, Serika Naicker, Shirley A Hanley, Stephanie M Slevin, John K Eykelenboom, Noel F Lowndes, Timothy O'Brien, Rhodri Ceredig, Matthew D Griffin, Michael C Dennedy
Human blood monocytes are sub-classified as classical, intermediate and non-classical. In this study, it was shown that conventionally-defined human intermediate monocytes (IM) can be divided into two distinct subpopulations with mid- and high-level surface expression of HLA-DR (referred to as DRmid and DRhi IM). These IM subpopulations were phenotypically and functionally characterized in healthy adult blood by flow cytometry, migration assays and lipoprotein uptake assays. Their absolute numbers and proportions were then compared in blood samples from obese and non-obese adults...
March 5, 2018: Immunology and Cell Biology
Michael Creane, Mary Mc Elroy, Aoife Duffy, Chaansha Shaik Dawood, Timothy O'Brien
Critical limb ischemia (CLI) represents the severest manifestation of peripheral arterial disease and is a major unmet medical need. This disease occurs when the arterial blood supply within the limb fails to meet the metabolic demands of the resting muscle or tissue, resulting in chronic ischemic rest pain and/or tissue necrosis. Human mesenchymal stromal cells, termed hMSCs, represent an exciting therapeutic modality for the treatment of this disease due to their immunomodulatory and tissue reparative functions...
January 1, 2018: Toxicologic Pathology
Michael F Robuck, Christine M O'Brien, Kelsi M Knapp, Sheila Shay, James D West, J M Newton, James C Slaughter, Bibhash Paria, Jeff Reese, Jennifer L Herington
In mouse models used to study parturition or pre-clinical therapeutic testing, measurement of uterine contractions is limited to either ex vivo isometric tension or operative IUP. The goal of this study was to: 1) develop a method for transcervical insertion of a pressure catheter to measure in vivo intrauterine contractile pressure during mouse pregnancy, 2) determine whether this method can be utilized numerous times in a single mouse pregnancy without affecting the timing of delivery or fetal outcome, and 3) compare the in vivo contractile activity between mouse models of term and preterm labor (PTL)...
March 2, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
Solventa Krakauskaite, Corey Thibeault, James LaVangie, Mateo Scheidt, Leo Martinez, Danielle Seth-Hunter, Amanda Wu, Michael O'Brien, Fabien Scalzo, Seth J Wilk, Robert B Hamilton
OBJECTIVE: To determine normal ranges for traditional transcranial Doppler (TCD) measurements for two age groups (14-19 and 20-29 years) and compare to existing literature results. The development of a normal range for TCD measurements will be required for the development of diagnostic and prognostic tests in the future. MATERIALS AND METHODS: We performed TCD on the middle cerebral artery on 147 healthy subjects aged 18.9 years (SD = 2.1) and calculated mean cerebral blood flow velocity (mCBFV) and pulsatility index (PI)...
2018: Acta Neurochirurgica. Supplement
Henrik Hartmann, Catarina F Moura, William R L Anderegg, Nadine K Ruehr, Yann Salmon, Craig D Allen, Stefan K Arndt, David D Breshears, Hendrik Davi, David Galbraith, Katinka X Ruthrof, Jan Wunder, Henry D Adams, Jasper Bloemen, Maxime Cailleret, Richard Cobb, Arthur Gessler, Thorsten E E Grams, Steven Jansen, Markus Kautz, Francisco Lloret, Michael O'Brien
Accumulating evidence highlights increased mortality risks for trees during severe drought, particularly under warmer temperatures and increasing vapour pressure deficit (VPD). Resulting forest die-off events have severe consequences for ecosystem services, biophysical and biogeochemical land-atmosphere processes. Despite advances in monitoring, modelling and experimental studies of the causes and consequences of tree death from individual tree to ecosystem and global scale, a general mechanistic understanding and realistic predictions of drought mortality under future climate conditions are still lacking...
April 2018: New Phytologist
Maria Kelly, Katie M O'Brien, Michael Lucey, Kerri Clough-Gorr, Ailish Hannigan
BACKGROUND: Analysing linked, routinely collected data may be useful to identify characteristics of patients with suspected lung cancer who could benefit from early assessment for palliative care. The aim of this study was to compare characteristics of newly diagnosed lung cancer patients dying within 30 days of diagnosis (short term survivors) with those surviving more than 30 days. To identify indicators for early palliative care assessment we distinguished between characteristics available at diagnosis (age, gender, smoking status, marital status, comorbid disease, admission type, tumour stage and histology) from those available post diagnosis...
February 26, 2018: BMC Palliative Care
Kylie B O'Brien, Anjail Z Sharrief, Eric J Nordstrom, Anthony J Travanty, Mailee Huynh, Megan P Romero, Katie C Bittner, Michael T Bowser, Frank H Burton
Tics and compulsions in comorbid Tourette's syndrome (TS) and obsessive-compulsive disorder (OCD) are associated with chronic hyperactivity of parallel cortico/amygdalo-striato-thalamo-cortical (CSTC) loop circuits. Comorbid TS- & OCD-like behaviors have likewise been observed in D1CT-7 mice, in which an artificial neuropotentiating transgene encoding the cAMP-elevating intracellular subunit of cholera toxin (CT) is chronically expressed selectively in somatosensory cortical & amygdalar dopamine (DA) D1 receptor-expressing neurons that activate cortico/amygdalo-striatal glutamate (GLU) output...
February 23, 2018: Journal of Chemical Neuroanatomy
Paolo Strati, Alessandra Ferrajoli, William G Wierda, Nitin Jain, Philip A Thompson, Susan M O'Brien, Katy Rezvani, Hagop M Kantarjian, Jan A Burger, Christina O Hinojosa, Michael J Keating, Zeev Estrov
No abstract text is available yet for this article.
February 20, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Ales Tichy, Sylwia Kabacik, Grainne O'Brien, Jaroslav Pejchal, Zuzana Sinkorova, Adela Kmochova, Igor Sirak, Andrea Malkova, Caterina Gomila Beltran, Juan Ramon Gonzalez, Jakub Grepl, Matthaeus Majewski, Elizabeth Ainsbury, Lenka Zarybnicka, Jana Vachelova, Alzbeta Zavrelova, Marie Davidkova, Marketa Markova Stastna, Michael Abend, Eileen Pernot, Elisabeth Cardis, Christophe Badie
The increasing risk of acute large-scale radiological/nuclear exposures of population underlines the necessity of developing new, rapid and high throughput biodosimetric tools for estimation of received dose and initial triage. We aimed to compare the induction and persistence of different radiation exposure biomarkers in human peripheral blood in vivo. Blood samples of patients with indicated radiotherapy (RT) undergoing partial body irradiation (PBI) were obtained soon before the first treatment and then after 24 h, 48 h, and 5 weeks; i...
2018: PloS One
Donna T Chen, Tomohiro M Ko, Ashleigh A Allen, Richard J Bonnie, Colleen E Suratt, Paul S Appelbaum, Edward V Nunes, Peter D Friedmann, Joshua D Lee, Michael S Gordon, Ryan McDonald, Donna Wilson, Tamara Y Boney, Sean M Murphy, Charles P O'Brien
Individuals must feel free to exert personal control over decisions regarding research participation. We present an examination of participants' perceived personal control over, as well as reported pressures and threats from others, influencing their decision to join a study assessing the effectiveness of extended-release naltrexone in preventing opioid dependence relapse. Most participants endorsed a strong sense of control over the decision; few reported pressures or threats. Although few in number, participants' brief narrative descriptions of the pressures and threats are illuminating and provide context for their perceptions of personal control...
February 1, 2018: Journal of Empirical Research on Human Research Ethics: JERHRE
Michael Kardas, Ed O'Brien
Modern technologies such as YouTube afford unprecedented access to the skilled performances of other people. Six experiments ( N = 2,225) reveal that repeatedly watching others can foster an illusion of skill acquisition. The more people merely watch others perform (without actually practicing themselves), the more they nonetheless believe they could perform the skill, too (Experiment 1). However, people's actual abilities-from throwing darts and doing the moonwalk to playing an online game-do not improve after merely watching others, despite predictions to the contrary (Experiments 2-4)...
February 1, 2018: Psychological Science
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