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Michael O'Brien

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https://www.readbyqxmd.com/read/28199897/real-world-utility-of-whole-exome-sequencing-with-targeted-gene-analysis-for-focal-epilepsy
#1
Piero Perucca, Ingrid E Scheffer, A Simon Harvey, Paul A James, Sebastian Lunke, Natalie Thorne, Clara Gaff, Brigid M Regan, John A Damiano, Michael S Hildebrand, Samuel F Berkovic, Terence J O'Brien, Patrick Kwan
OBJECTIVE: Driven by advances in genomic technology and reduction in costs, next-generation sequencing (NGS) is venturing into routine clinical care. The 'real-world' clinical utility of NGS remains to be determined in focal epilepsies, which account for 60% of all epilepsies and for which the importance of genetic factors is just beginning to emerge. We investigated the diagnostic yield and management implications of whole exome sequencing (WES)-based screening of selected genes in the routine care of common focal epilepsies suspected to have a genetic basis...
February 7, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28199403/comparison-of-microbiological-diagnosis-of-urinary-tract-infection-in-young-children-by-routine-health-service-laboratories-and-a-research-laboratory-diagnostic-cohort-study
#2
Kate Birnie, Alastair D Hay, Mandy Wootton, Robin Howe, Alasdair MacGowan, Penny Whiting, Michael Lawton, Brendan Delaney, Harriet Downing, Jan Dudley, William Hollingworth, Catherine Lisles, Paul Little, Kathryn O'Brien, Timothy Pickles, Kate Rumsby, Emma Thomas-Jones, Judith Van der Voort, Cherry-Ann Waldron, Kim Harman, Kerenza Hood, Christopher C Butler, Jonathan A C Sterne
OBJECTIVES: To compare the validity of diagnosis of urinary tract infection (UTI) through urine culture between samples processed in routine health service laboratories and those processed in a research laboratory. POPULATION AND METHODS: We conducted a prospective diagnostic cohort study in 4808 acutely ill children aged <5 years attending UK primary health care. UTI, defined as pure/predominant growth ≥105 CFU/mL of a uropathogen (the reference standard), was diagnosed at routine health service laboratories and a central research laboratory by culture of urine samples...
2017: PloS One
https://www.readbyqxmd.com/read/28198872/high-extinction-ratio-integrated-photonic-filters-for-silicon-quantum-photonics
#3
Mateusz Piekarek, Damien Bonneau, Shigehito Miki, Taro Yamashita, Mikio Fujiwara, Masahide Sasaki, Hirotaka Terai, Michael G Tanner, Chandra M Natarajan, Robert H Hadfield, Jeremy L O'Brien, Mark G Thompson
We present the generation of quantum-correlated photon pairs and subsequent pump rejection across two silicon-on-insulator photonic integrated circuits. Incoherently cascaded lattice filters are used to provide over 100 dB pass-band to stop-band contrast with no additional external filtering. Photon pairs generated in a microring resonator are successfully separated from the input pump, confirmed by temporal correlations measurements.
February 15, 2017: Optics Letters
https://www.readbyqxmd.com/read/28197323/novel-2-substituted-7-azaindole-and-7-azaindazole-analogues-as-potential-antiviral-agents-for-the-treatment-of-influenza
#4
Upul K Bandarage, Michael P Clark, Emanuele Perola, Huai Gao, Marc D Jacobs, Alice Tsai, Jeffery Gillespie, Joseph M Kennedy, François Maltais, Mark W Ledeboer, Ioana Davies, Wenxin Gu, Randal A Byrn, Kwame Nti Addae, Hamilton Bennett, Joshua R Leeman, Steven M Jones, Colleen O'Brien, Christine Memmott, Youssef Bennani, Paul S Charifson
JNJ-63623872 (2) is a first-in-class, orally bioavailable compound that offers significant potential for the treatment of pandemic and seasonal influenza. Early lead optimization efforts in our 7-azaindole series focused on 1,3-diaminocyclohexyl amide and urea substitutions on the pyrimidine-7-azaindole motif. In this work, we explored two strategies to eliminate observed aldehyde oxidase (AO)-mediated metabolism at the 2-position of these 7-azaindole analogues. Substitution at the 2-position of the azaindole ring generated somewhat less potent analogues, but reduced AO-mediated metabolism...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28197322/discovery-of-novel-orally-bioavailable-%C3%AE-amino-acid-azaindole-inhibitors-of-influenza-pb2
#5
Luc J Farmer, Michael P Clark, Michael J Boyd, Emanuele Perola, Steven M Jones, Alice Tsai, Marc D Jacobs, Upul K Bandarage, Mark W Ledeboer, Tiansheng Wang, Hongbo Deng, Brian Ledford, Wenxin Gu, John P Duffy, Randy S Bethiel, Dean Shannon, Randal A Byrn, Joshua R Leeman, Rene Rijnbrand, Hamilton B Bennett, Colleen O'Brien, Christine Memmott, Kwame Nti-Addae, Youssef L Bennani, Paul S Charifson
In our efforts to develop novel small-molecule inhibitors for the treatment of influenza, we utilized molecular modeling and the X-ray crystal structure of the PB2 subunit of the influenza polymerase to optimize a series of acyclic β-amino acid inhibitors, highlighted by compound 4. Compound 4 showed good oral exposure in both rat and mouse. More importantly, it showed strong potency versus multiple influenza-A strains, including pandemic 2009 H1N1 and avian H5N1 strains and showed a strong efficacy profile in a mouse influenza model even when treatment was initiated 48 h after infection...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28192618/intra-annual-plasticity-of-growth-mediates-drought-resilience-over-multiple-years-in-tropical-seedling-communities
#6
Michael J O'Brien, Robert Ong, Glen Reynolds
Precipitation patterns are changing across the globe causing more severe and frequent drought for many forest ecosystems. Although research has focused on the resistance of tree populations and communities to these novel precipitation regimes, resilience of forests is also contingent on recovery following drought, which remains poorly understood, especially in aseasonal tropical forests. We used rainfall exclusion shelters to manipulate the inter-annual frequency of drought for diverse seedling communities in a tropical forest and assessed resistance, recovery and resilience of seedling growth and mortality relative to everwet conditions...
February 13, 2017: Global Change Biology
https://www.readbyqxmd.com/read/28190549/comparing-del-nido-and-conventional-cardioplegia-in-infants-and-neonates-in-congenital-heart-surgery
#7
Kamal K Pourmoghadam, Mark Ruzmetov, Michael C O'Brien, Kurt D Piggott, Gary Plancher, Sukumar Suguna Narasimhulu, Tavya Benjamin, William M Decampli
BACKGROUND: The aim of this study was to evaluate outcome measures after the use of del Nido (dN) cardioplegia compared with conventional multidose high-potassium (non-dN) cardioplegia in neonates and infants. METHODS: We retrospectively analyzed data in patients, aged younger than 1 year, undergoing cardiopulmonary bypass (CPB) from January 2012 to August 2015. We changed our cardioplegia protocol from non-dN to dN administered in a single or infrequently dosed strategy in September 2013...
February 9, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28185995/study-protocol-community-links-to-establish-alcohol-recovery-clear-for-women-leaving-jail
#8
Jennifer E Johnson, Yael Chatav Schonbrun, Bradley Anderson, Megan Kurth, Christine Timko, Michael Stein
PURPOSE: This article describes the protocol for a randomized effectiveness trial of a method to link alcohol use disordered women who are in pretrial jail detention with post-release 12-step mutual help groups. BACKGROUND: Jails serve 15 times more people per year than do prisons and have very short stays, posing few opportunities for treatment or treatment planning. Alcohol use is associated with poor post-jail psychosocial and health outcomes including sexually transmitted diseases and HIV, especially for women...
February 7, 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28174896/patternmarkers-gwcogaps-for-novel-data-driven-biomarkers-via-whole-transcriptome-nmf
#9
Genevieve L Stein-O'Brien, Jacob L Carey, Wai-Shing Lee, Michael Considine, Alexander V Favorov, Emily Flam, Theresa Guo, Sijia Li, Luigi Marchionni, Thomas Sherman, Shawn Sivy, Daria A Gaykalova, Ronald D McKay, Michael F Ochs, Carlo Colantuoni, Elana J Fertig
No abstract text is available yet for this article.
February 8, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28171709/long-term-outcomes-for-patients-with-chronic-lymphocytic-leukemia-who-discontinue-ibrutinib
#10
Preetesh Jain, Philip A Thompson, Michael Keating, Zeev Estrov, Alessandra Ferrajoli, Nitin Jain, Hagop Kantarjian, Jan A Burger, Susan O'Brien, William G Wierda
BACKGROUND: Ibrutinib is a Bruton tyrosine kinase inhibitor and is approved for the treatment of patients with chronic lymphocytic leukemia (CLL) in frontline and relapsed/refractory settings. The authors previously reported poor outcomes for patients who discontinued ibrutinib; however, long-term outcomes were not reported. METHODS: Data from 320 patients who received ibrutinib on clinical studies between 2010 and 2015 at The University of Texas MD Anderson Cancer Center were retrospectively analyzed...
February 7, 2017: Cancer
https://www.readbyqxmd.com/read/28164300/risk-of-exposure-to-blood-products-during-pregnancy-guidance-for-zika-and-other-donor-deferral-policies
#11
Malia S Q Murphy, Nadine Shehata, Jo Ann Colas, Michaël Chassé, Dean A Fergusson, Sheila F O'Brien, Mindy Goldman, Alan Tinmouth, Alan J Forster, Kumanan Wilson
BACKGROUND: Exposure to blood products during pregnancy carries a potential risk of transfusion transmission of infectious agents. Blood agencies have historically sought optimal deferral and testing strategies to protect blood supplies in part to ensure the protection of pregnant women and their unborn infants. The Zika virus outbreak of 2016 has heightened attention to these concerns. In the current context of the recent Zika outbreak, and also more broadly, data are needed to shed light on the likelihood of exposure to blood products throughout pregnancy to inform policy...
February 5, 2017: Transfusion
https://www.readbyqxmd.com/read/28158967/high-virulence-sub-populations-in-pseudomonas-aeruginosa-long-term-cystic-fibrosis-airway-infections
#12
Siobhán O'Brien, David Williams, Joanne L Fothergill, Steve Paterson, Craig Winstanley, Michael A Brockhurst
BACKGROUND: Pseudomonas aeruginosa typically displays loss of virulence-associated secretions over the course of chronic cystic fibrosis infections. This has led to the suggestion that virulence is a costly attribute in chronic infections. However, previous reports suggest that overproducing (OP) virulent pathotypes can coexist with non-producing mutants in the CF lung for many years. The consequences of such within-patient phenotypic diversity for the success of this pathogen are not fully understood...
February 3, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28138560/leukemia-cell-proliferation-and-death-in-chronic-lymphocytic-leukemia-patients-on-therapy-with-the-btk-inhibitor-ibrutinib
#13
Jan A Burger, Kelvin W Li, Michael J Keating, Mariela Sivina, Ahmed M Amer, Naveen Garg, Alessandra Ferrajoli, Xuelin Huang, Hagop Kantarjian, William G Wierda, Susan O'Brien, Marc K Hellerstein, Scott M Turner, Claire L Emson, Shih-Shih Chen, Xiao-Jie Yan, Dominik Wodarz, Nicholas Chiorazzi
BACKGROUND. Ibrutinib is an effective targeted therapy for patients with chronic lymphocytic leukemia (CLL) that inhibits Bruton's tyrosine kinase (BTK), a kinase involved in B cell receptor signaling. METHODS. We used stable isotopic labeling with deuterated water ((2)H2O) to measure directly the effects of ibrutinib on leukemia cell proliferation and death in 30 patients with CLL. RESULTS. The measured average CLL cell proliferation ("birth") rate before ibrutinib therapy was 0.39% of the clone per day (range 0...
January 26, 2017: JCI Insight
https://www.readbyqxmd.com/read/28135054/integrated-analysis-of-genetic-variation-and-gene-expression-reveals-novel-variant-for-increased-warfarin-dose-requirement-in-african-americans
#14
Wenndy Hernandez, Eric R Gamazon, Keston Aquino-Michaels, Erin Smithberger, Travis J O'Brien, Arthur F Harralson, Matthew Tuck, April Barbour, Larisa H Cavallari, Minoli A Perera
BACKGROUND: Warfarin is commonly used to control and prevent thromboembolic disorders. However, due to warfarin's complex dose-requirement relationship, safe and effective use is challenging. Pharmacogenomics-guided warfarin dosing algorithms that include the well-established VKORC1 and CYP2C9 polymorphisms explain only a small proportion of inter-individual variability in African Americans (AAs). OBJECTIVES: We aimed to assess whether transcriptomic analyses could be used to identify regulatory variants associated with warfarin dose response in AAs...
January 30, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28130399/constitutive-phosphorylation-of-stat3-by-the-ck2-blnk-cd5-complex
#15
Uri Rozovski, David M Harris, Ping Li, Zhiming Liu, Preetesh Jain, Ivo Veletic, Alessandra Ferrajoli, Jan Burger, Susan O'Brien, Prithviraj Bose, Philip Thompson, Nitin Jain, William Wierda, Michael J Keating, Zeev Estrov
: In chronic lymphocytic leukemia (CLL), STAT3 is constitutively phosphorylated on serine 727 and plays a role in the pathobiology of CLL. However, what induces constitutive phosphorylation of STAT3 is currently unknown. Mass spectrometry was used to identify casein kinase 2 (CK2), a serine/threonine kinase that co-immunoprecipitated with serine phosphorylated STAT3 (pSTAT3). Furthermore, activated CK2 incubated with recombinant STAT3 induced phosphorylation of STAT3 on serine 727. Although STAT3 and CK2 are present in normal B- and T-cells, STAT3 is not constitutively phosphorylated in these cells...
January 27, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28128343/rna-sequencing-of-synaptic-and-cytoplasmic-upf1-bound-transcripts-supports-contribution-of-nonsense-mediated-decay-to-epileptogenesis
#16
Claire M Mooney, Eva M Jimenez-Mateos, Tobias Engel, Catherine Mooney, Mairead Diviney, Morten T Venø, Jørgen Kjems, Michael A Farrell, Donncha F O'Brien, Norman Delanty, David C Henshall
The nonsense mediated decay (NMD) pathway is a critical surveillance mechanism for identifying aberrant mRNA transcripts. It is unknown, however, whether the NMD system is affected by seizures in vivo and whether changes confer beneficial or maladaptive responses that influence long-term outcomes such the network alterations that produce spontaneous recurrent seizures. Here we explored the responses of the NMD pathway to prolonged seizures (status epilepticus) and investigated the effects of NMD inhibition on epilepsy in mice...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28118557/brucellosis-transmission-between-wildlife-and-livestock-in-the-greater-yellowstone-ecosystem-inferences-from-dna-genotyping
#17
Michael P O'Brien, Albano Beja-Pereira, Neil Anderson, Ruben M Ceballos, William H Edwards, Beth Harris, Rick L Wallen, Vânia Costa
The wildlife of the Greater Yellowstone Ecosystem carries brucellosis, which was first introduced to the area by cattle in the 19th Century. Brucellosis transmission between wildlife and livestock has been difficult to study due to challenges in culturing the causative agent, Brucella abortus . We examined B. abortus transmission between American bison ( Bison bison ), Rocky Mountain elk ( Cervus elaphus nelsoni), and cattle ( Bos taurus ) using variable number tandem repeat (VNTR) markers on DNA from 98 B...
January 24, 2017: Journal of Wildlife Diseases
https://www.readbyqxmd.com/read/28115169/development-of-a-bimolecular-luminescence-complementation-assay-for-rgs-g-protein-interactions-in-cells
#18
Christopher R Bodle, Michael P Hayes, Joseph B O'Brien, David L Roman
Cell based assessment tools and screening platforms are the preferred paradigm for small molecule identification and validation due to selectively identifying molecules with cellular activity and validation of compound activity against target proteins in their native environment. With respect to Regulator of G Protein Signaling (RGS) proteins, current cell based methodologies are either low throughput or monitor downstream signaling consequences. The increasing number of reports indicating RGS function in various disease pathogeneses highlights the need for a robust RGS inhibitor discovery and characterization paradigm...
January 20, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28103426/analytical-characterization-and-pharmacological-evaluation-of-the-new-psychoactive-substance-4-fluoromethylphenidate-4%C3%A2-f-mph-and-differentiation-between-the-%C3%A2-threo-and-%C3%A2-erythro-diastereomers
#19
Gavin McLaughlin, Noreen Morris, Pierce V Kavanagh, John D Power, Geraldine Dowling, Brendan Twamley, John O'Brien, Gary Hessman, Brian Murphy, Donna Walther, John S Partilla, Michael H Baumann, Simon D Brandt
Misuse of (±)-threo-methylphenidate (methyl-2-phenyl-2-(piperidin-2-yl)acetate; Ritalin®, MPH) has long been acknowledged, but the appearance of MPH analogs in the form of 'research chemicals' has only emerged in more recent years. 4-Fluoromethylphenidate (4 F-MPH) is one of these recent examples and this study presents the identification and analytical characterization of two powdered 4 F-MPH products that were obtained from an online vendor in 2015. Interestingly, the products appeared to have originated from two distinct batches given that one product consisted of (±)-threo-4 F-MPH isomers whereas the second sample consisted of a mixture of (±)-threo and (±)-erythro 4 F-MPH...
January 19, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28096418/multi-institute-analysis-of-carbapenem-resistance-reveals-remarkable-diversity-unexplained-mechanisms-and-limited-clonal-outbreaks
#20
Gustavo C Cerqueira, Ashlee M Earl, Christoph M Ernst, Yonatan H Grad, John P Dekker, Michael Feldgarden, Sinéad B Chapman, João L Reis-Cunha, Terrance P Shea, Sarah Young, Qiandong Zeng, Mary L Delaney, Diane Kim, Ellena M Peterson, Thomas F O'Brien, Mary Jane Ferraro, David C Hooper, Susan S Huang, James E Kirby, Andrew B Onderdonk, Bruce W Birren, Deborah T Hung, Lisa A Cosimi, Jennifer R Wortman, Cheryl I Murphy, William P Hanage
Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to the antibiotic era. Multiple different species can exhibit resistance due to many different mechanisms, and many different mobile elements are capable of transferring resistance between lineages. We prospectively sampled CRE from hospitalized patients from three Boston-area hospitals, together with a collection of CRE from a single California hospital, to define the frequency and characteristics of outbreaks and determine whether there is evidence for transfer of strains within and between hospitals and the frequency with which resistance is transferred between lineages or species...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
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