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Alan Brown

Michelle Addison, Ruth Mcgovern, Colin Angus, Frauke Becker, Alan Brennan, Heather Brown, Simon Coulton, Lisa Crowe, Eilish Gilvarry, Matthew Hickman, Denise Howel, Elaine Mccoll, Colin Muirhead, Dorothy Newbury-Birch, Muhammad Waqas, Eileen Kaner
Aims: There is a clear association between alcohol use and offending behaviour and significant police time is spent on alcohol-related incidents. This study aimed to test the feasibility of a trial of screening and brief intervention in police custody suites to reduce heavy drinking and re-offending behaviour. Short summary: We achieved target recruitment and high brief intervention delivery if this occurred immediately after screening. Low rates of return for counselling and retention at follow-up were challenges for a definitive trial...
June 8, 2018: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
Craig A Nash, Loren M Brown, Sundeep Malik, Xiaodong Cheng, Alan V Smrcka
In cardiac myocytes activation of an exchange factor activated by cAMP (Epac) leads to activation of phospholipase Cε (PLCε)-dependent hydrolysis of phosphatidylinositol 4-phosphate (PI4P) in the Golgi apparatus a process critical for development of cardiac hypertrophy. Here we show that β-adrenergic receptor (βAR) stimulation does not stimulate this pathway in the presence of the broad spectrum phosphodiesterase (PDE) inhibitor IBMX, but selective PDE3 inhibition revealed βAR-dependent PI4P depletion...
June 6, 2018: Journal of Molecular and Cellular Cardiology
Tiffany J Callahan, Alan E Bauck, David Bertoch, Jeff Brown, Ritu Khare, Patrick B Ryan, Jenny Staab, Meredith N Zozus, Michael G Kahn
Objective: To compare rule-based data quality (DQ) assessment approaches across multiple national clinical data sharing organizations. Methods: Six organizations with established data quality assessment (DQA) programs provided documentation or source code describing current DQ checks. DQ checks were mapped to the categories within the data verification context of the harmonized DQA terminology. To ensure all DQ checks were consistently mapped, conventions were developed and four iterations of mapping performed...
June 12, 2017: EGEMS
Vanessa I Francis, Elaine M Waters, Sutharsan E Finton-James, Andrea Gori, Aras Kadioglu, Alan R Brown, Steven L Porter
Bacteria and many non-metazoan Eukaryotes respond to stresses and threats using two-component systems (TCSs) comprising sensor kinases (SKs) and response regulators (RRs). Multikinase networks, where multiple SKs work together, detect and integrate different signals to control important lifestyle decisions such as sporulation and virulence. Here, we study interactions between two SKs from Pseudomonas aeruginosa, GacS and RetS, which control the switch between acute and chronic virulence. We demonstrate three mechanisms by which RetS attenuates GacS signalling: RetS takes phosphoryl groups from GacS-P; RetS has transmitter phosphatase activity against the receiver domain of GacS-P; and RetS inhibits GacS autophosphorylation...
June 7, 2018: Nature Communications
Justin C Brown, Sui Zhang, Donna Niedzwiecki, Leonard B Saltz, Robert J Mayer, Rex B Mowat, Renaud Whittom, Alexander Hantel, Al Benson, Daniel Atienza, Michael Messino, Hedy Kindler, Alan Venook, Shuji Ogino, Yanping Li, Xuehong Zhang, Kimmie Ng, Walter C Willett, Edward L Giovannucci, Charles S Fuchs, Jeffrey A Meyerhardt
Background: Energy balance-related risk factors for colon cancer recurrence and mortality-type II diabetes, hyperinsulinemia, inflammation, and visceral obesity-are positively correlated with consumption of refined grains and negatively correlated with consumption of whole grains. We examined the relationship between the consumption of refined and whole grains with cancer recurrence and mortality in a cohort of patients with colon cancer. Methods: We conducted a prospective observational study of 1024 patients with stage III colon cancer who participated in a randomized trial of postoperative chemotherapy...
February 2018: JNCI cancer spectrum
Jean-Philippe Krieger, Ellen Paula Santos da Conceição, Graciela Sanchez-Watts, Myrtha Arnold, Klaus G Pettersen, Mazher Mohammed, Salvatore Modica, Pius Lossel, Shaun F Morrison, Christopher J Madden, Alan G Watts, Wolfgang Langhans, Shin J Lee
Endogenous intestinal glucagon-like peptide-1 (GLP-1) controls satiation and glucose metabolism via vagal afferent neurons (VAN). Recently, VAN have received increasing attention for their role in brown adipose tissue (BAT) thermogenesis. It is however unclear whether VAN GLP-1 receptor (GLP-1R) signaling affects BAT thermogenesis and energy expenditure (EE), and whether this VAN mechanism contributes to energy balance. First, we tested the effect of the GLP-1R agonist Exendin-4 (Ex4, 0.3 μg/kg IP) on EE and BAT thermogenesis, and whether these effects require VAN GLP-1R signaling, using a rat model with a selective Glp1r knockdown (kd) in VAN...
May 30, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Yunfei Zhang, Lev Bromberg, Zhou Lin, Paul Brown, Troy Van Voorhis, T Alan Hatton
We introduce 10,12-Pentacosadiynoic acid conjugated with pyridine-2-aldoxime (pralidoxime, PAM) as a positively charged amphiphilic molecule capable of forming a polymer with polydiacetylene (PDA-PAM) via 1,4-addition photopolymerization of self-assembled PAM-modified monomers. Colloidally stabilized vesicles formed by PDA-PAM and unmodified pentacosadiynoic acid via electrostatic interactions in a basic aqueous medium exhibit a colorimetric transition in the presence of malathion. The malathion detection limit, through color change observed by the naked eye, is in the mM range (liquid suspension) or at nmol/cm2 levels (solid membrane); the response to exposure to malathion was rapid, within seconds...
April 27, 2018: Journal of Colloid and Interface Science
Moshrik Abd Alamir, Michael Goyfman, Adib Chaus, Firas Dabbous, Leslie Tamura, Veit Sandfort, Alan Brown, Mathew Budoff
Background: The extent of coronary artery calcium (CAC) improves cardiovascular disease (CVD) risk prediction. The association between common dyslipidemias (combined hyperlipidemia, simple hypercholesterolemia, metabolic Syndrome (MetS), isolated low high-density lipoprotein cholesterol, and isolated hypertriglyceridemia) compared with normolipidemia and the risk of multivessel CAC is underinvestigated. Objectives: To determine whether there is an association between common dyslipidemias compared with normolipidemia, and the extent of coronary artery involvement among MESA participants who were free of clinical cardiovascular disease at baseline...
2018: Journal of Lipids
Julie Vercelloni, Sam Clifford, M Julian Caley, Alan R Pearse, Ross Brown, Allan James, Bryce Christensen, Tomasz Bednarz, Ken Anthony, Manuel González-Rivero, Kerrie Mengersen, Erin E Peterson
Aesthetic value, or beauty, is important to the relationship between humans and natural environments and is, therefore, a fundamental socio-economic attribute of conservation alongside other ecosystem services. However, beauty is difficult to quantify and is not estimated well using traditional approaches to monitoring coral-reef aesthetics. To improve the estimation of ecosystem aesthetic values, we developed and implemented a novel framework used to quantify features of coral-reef aesthetics based on people's perceptions of beauty...
April 2018: Royal Society Open Science
Alexander Bean, Rasika Sunnadeniya, Neda Akhavan, Annabelle Campbell, Matthew Brown, Alan Lloyd
The key enzymatic step in betalain biosynthesis involves conversion of l-3,4-dihydroxyphenylalanine (l-DOPA) to betalamic acid. One class of enzymes capable of this is 3,4-dihydroxyphenylalanine 4,5-dioxygenase (DODA). In betalain-producing species, multiple paralogs of this gene are maintained. This study demonstrates which paralogs function in the betalain pathway and determines the residue changes required to evolve a betalain-nonfunctional DODA into a betalain-functional DODA. Functionalities of two pairs of DODAs were tested by expression in beets, Arabidopsis and yeast, and gene silencing was performed by virus-induced gene silencing...
May 13, 2018: New Phytologist
Wesley H Self, Matthew W Semler, Rinaldo Bellomo, Samuel M Brown, Bennett P deBoisblanc, Matthew C Exline, Adit A Ginde, Colin K Grissom, David R Janz, Alan E Jones, Kathleen D Liu, Stephen P J Macdonald, Chadwick D Miller, Pauline K Park, Lora A Reineck, Todd W Rice, Jay S Steingrub, Daniel Talmor, Donald M Yealy, Ivor S Douglas, Nathan I Shapiro
Prompt intravenous fluid therapy is a fundamental treatment for patients with septic shock. However, the optimal approach for administering intravenous fluid in septic shock resuscitation is unknown. Two competing strategies are emerging: a liberal fluids approach, consisting of a larger volume of initial fluid (50 to 75 mL/kg [4 to 6 L in an 80-kg adult] during the first 6 hours) and later use of vasopressors, versus a restrictive fluids approach, consisting of a smaller volume of initial fluid (≤30 mL/kg [≤2 to 3 L]), with earlier reliance on vasopressor infusions to maintain blood pressure and perfusion...
May 9, 2018: Annals of Emergency Medicine
Sophia S Wang, Mary Carrington, Sonja I Berndt, Susan L Slager, Paige M Bracci, Jenna Voutsinas, James R Cerhan, Karin Ekström Smedby, Henrik Hjalgrim, Joseph Vijai, Lindsay M Morton, Roel Vermeulen, Ora Paltiel, Claire M Vajdic, Martha S Linet, Alexandra Nieters, Silvia de Sanjosé, Wendy Cozen, Elizabeth E Brown, Jennifer Turner, John J Spinelli, Tongzhang Zheng, Brenda M Birmann, Christopher R Flowers, Nikolaus Becker, Elizabeth A Holly, Eleanor Kane, Dennis Weisenburger, Marc Maynadie, Pierluigi Cocco, Demetrius Albanes, Stephanie J Weinstein, Lauren R Teras, W Ryan Diver, Stephanie J Lax, Ruth C Travis, Rudolf Kaaks, Elio Riboli, Yolanda Benavente, Paul Brennan, James D McKay, Marie Helene Delfau-Larue, Brian K Link, Corrado Magnani, Maria G Ennas, Giancarlo Latte, Andrew L Feldman, Nicole Wong Doo, Graham G Giles, Melissa C Southey, Roger L Milne, Kenneth Offit, Jacob Muskinsky, Alan A Arslan, Mark P Purdue, Hans-Olov Adami, Mads Melbye, Bengt Glimelius, Lucia Conde, Nicola J Camp, Martha Glenn, Karen Curtin, Jacqueline Clavel, Alain Monnereau, David G Cox, Hervé Ghesquières, Gilles Salles, Paolo Boffetta, Lenka Foretova, Anthony Staines, Scott Davis, Richard K Severson, Qing Lan, Angela Brooks-Wilson, Martyn T Smith, Eve Roman, Anne Kricker, Yawei Zhang, Peter Kraft, Stephen J Chanock, Nathaniel Rothman, Patricia Hartge, Christine F Skibola
A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for: 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent...
May 7, 2018: Cancer Research
Tristan Glatard, Gregory Kiar, Tristan Aumentado-Armstrong, Natacha Beck, Pierre Bellec, Rémi Bernard, Axel Bonnet, Shawn T Brown, Sorina Camarasu-Pop, Frédéric Cervenansky, Samir Das, Rafael Ferreira da Silva, Guillaume Flandin, Pascal Girard, Krzysztof J Gorgolewski, Charles R G Guttmann, Valérie Hayot-Sasson, Pierre-Olivier Quirion, Pierre Rioux, Marc-Étienne Rousseau, Alan C Evans
We present Boutiques, a system to automatically publish, integrate and execute command-line applications across computational platforms. Boutiques applications are installed through software containers described in a rich and flexible JSON language. A set of core tools facilitate the construction, validation, import, execution, and publishing of applications. Boutiques is currently supported by several distinct virtual research platforms, and it has been used to describe dozens of applications in the neuroinformatics domain...
March 23, 2018: GigaScience
Andrew Tutt, Holly Tovey, Maggie Chon U Cheang, Sarah Kernaghan, Lucy Kilburn, Patrycja Gazinska, Julie Owen, Jacinta Abraham, Sophie Barrett, Peter Barrett-Lee, Robert Brown, Stephen Chan, Mitchell Dowsett, James M Flanagan, Lisa Fox, Anita Grigoriadis, Alexander Gutin, Catherine Harper-Wynne, Matthew Q Hatton, Katherine A Hoadley, Jyoti Parikh, Peter Parker, Charles M Perou, Rebecca Roylance, Vandna Shah, Adam Shaw, Ian E Smith, Kirsten M Timms, Andrew M Wardley, Gregory Wilson, Cheryl Gillett, Jerry S Lanchbury, Alan Ashworth, Nazneen Rahman, Mark Harries, Paul Ellis, Sarah E Pinder, Judith M Bliss
Germline mutations in BRCA1/2 predispose individuals to breast cancer (termed germline-mutated BRCA1/2 breast cancer, gBRCA-BC) by impairing homologous recombination (HR) and causing genomic instability. HR also repairs DNA lesions caused by platinum agents and PARP inhibitors. Triple-negative breast cancers (TNBCs) harbor subpopulations with BRCA1/2 mutations, hypothesized to be especially platinum-sensitive. Cancers in putative 'BRCAness' subgroups-tumors with BRCA1 methylation; low levels of BRCA1 mRNA (BRCA1 mRNA-low); or mutational signatures for HR deficiency and those with basal phenotypes-may also be sensitive to platinum...
April 30, 2018: Nature Medicine
Mayenaaz Sidhu, David J Tate, Lobke Desomer, Gregor Brown, Luke F Hourigan, Eric Y T Lee, Alan Moss, Spiro Raftopoulos, Rajvinder Singh, Stephen J Williams, Simon Zanati, Nicholas Burgess, Michael J Bourke
No abstract text is available yet for this article.
April 26, 2018: Endoscopy
Bruce C V Campbell, Peter J Mitchell, Leonid Churilov, Nawaf Yassi, Timothy J Kleinig, Richard J Dowling, Bernard Yan, Steven J Bush, Helen M Dewey, Vincent Thijs, Rebecca Scroop, Marion Simpson, Mark Brooks, Hamed Asadi, Teddy Y Wu, Darshan G Shah, Tissa Wijeratne, Timothy Ang, Ferdinand Miteff, Christopher R Levi, Edrich Rodrigues, Henry Zhao, Patrick Salvaris, Carlos Garcia-Esperon, Peter Bailey, Henry Rice, Laetitia de Villiers, Helen Brown, Kendal Redmond, David Leggett, John N Fink, Wayne Collecutt, Andrew A Wong, Claire Muller, Alan Coulthard, Ken Mitchell, John Clouston, Kate Mahady, Deborah Field, Henry Ma, Thanh G Phan, Winston Chong, Ronil V Chandra, Lee-Anne Slater, Martin Krause, Timothy J Harrington, Kenneth C Faulder, Brendan S Steinfort, Christopher F Bladin, Gagan Sharma, Patricia M Desmond, Mark W Parsons, Geoffrey A Donnan, Stephen M Davis
BACKGROUND: Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion. METHODS: We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0...
April 26, 2018: New England Journal of Medicine
Kenneth T Shelton, Jason Qu, Federico Bilotta, Emery N Brown, Gaston Cudemus, David A D'Alessandro, Hao Deng, Alan DiBiasio, Jacob A Gitlin, Eunice Y Hahm, Lauren E Hobbs, Timothy T Houle, Reine Ibala, Marco Loggia, Kara J Pavone, Shahzad Shaefi, George Tolis, M Brandon Westover, Oluwaseun Akeju
INTRODUCTION: Delirium, which is prevalent in postcardiac surgical patients, is an acute brain dysfunction characterised by disturbances in attention, awareness and cognition not explained by a pre-existing neurocognitive disorder. The pathophysiology of delirium remains poorly understood. However, basic science and clinical studies suggest that sleep disturbance may be a modifiable risk factor for the development of delirium. Dexmedetomidine is a α-2A adrenergic receptor agonist medication that patterns the activity of various arousal nuclei similar to sleep...
April 20, 2018: BMJ Open
Scott E Collibee, Gustave Bergnes, Alexander Muci, William F Browne, Marc Garard, Aaron C Hinken, Alan J Russell, Ion Suehiro, James Hartman, Raja Kawas, Pu-Ping Lu, Kenneth H Lee, David Marquez, Matthew Tomlinson, Donghong Xu, Adam Kennedy, Darren Hwee, Julia Schaletzky, Kwan Leung, Fady I Malik, David J Morgans, Bradley P Morgan
The identification and optimization of the first activators of fast skeletal muscle are reported. Compound 1 was identified from high-throughput screening (HTS) and subsequently found to improve muscle function via interaction with the troponin complex. Optimization of 1 for potency, metabolic stability, and physical properties led to the discovery of tirasemtiv ( 25 ), which has been extensively characterized in clinical trials for the treatment of amyotrophic lateral sclerosis.
April 12, 2018: ACS Medicinal Chemistry Letters
Robert Freedman, Alan S Brown, Tyrone D Cannon, Benjamin G Druss, Felton J Earls, Javier Escobar, Yasmin L Hurd, David A Lewis, Carlos López-Jaramillo, Joan Luby, Helen S Mayberg, Terrie E Moffitt, Maria Oquendo, Roy H Perlis, Daniel S Pine, A John Rush, Carol A Tamminga, Mauricio Tohen, Eduard Vieta, Katherine L Wisner, Yu Xin
No abstract text is available yet for this article.
April 16, 2018: American Journal of Psychiatry
Shin J Lee, Graciela Sanchez-Watts, Jean-Philippe Krieger, Angelica Pignalosa, Puck N Norell, Alyssa Cortella, Klaus G Pettersen, Dubravka Vrdoljak, Matthew R Hayes, Scott Kanoski, Wolfgang Langhans, Alan G Watts
OBJECTIVE: Glucagon-like peptide-1 (GLP-1) neurons in the hindbrain densely innervate the dorsomedial hypothalamus (DMH), a nucleus strongly implicated in body weight regulation and the sympathetic control of brown adipose tissue (BAT) thermogenesis. Therefore, DMH GLP-1 receptors (GLP-1R) are well placed to regulate energy balance by controlling sympathetic outflow and BAT function. METHODS: We investigate this possibility in adult male rats by using direct administration of GLP-1 (0...
May 2018: Molecular Metabolism
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