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Gavin D Merrifield, James Mullin, Lindsay Gallagher, Carl Tucker, Maurits A Jansen, Martin Denvir, William M Holmes
Increasing scientific interest in the zebrafish as a model organism across a range of biomedical and biological research areas raises the need for the development of in vivo imaging tools appropriate to this subject. Development of the embryonic and early stage forms of the subject can currently be assessed using optical based techniques due to the transparent nature of the species at these early stages. However this is not an option during the juvenile and adult stages when the subjects become opaque. Magnetic Resonance Imaging (MRI) techniques would allow for the longitudinal and non-invasive assessment of development and health in these later life stages...
October 14, 2016: Magnetic Resonance Imaging
James P Gavin, Stephen D Myers, Mark E Willems
BACKGROUND: We examined the effect of early-onset of muscle damage and low muscle glycogen on cardiorespiratory and metabolic responses to low-intensity exercise. METHODS: Twelve men cycled for 10 min at 50% maximal oxygen uptake before, and 12 h after a morning downhill run (five, 8 min bouts at -12% gradient, with 2 min rests) under normal (NORM) and lowered glycogen (LOW) conditions, following a cross-over design with conditions separated by six weeks. Cardiorespiratory responses were recorded, with oxidation measures derived from stoichiometry equations...
October 11, 2016: Journal of Sports Medicine and Physical Fitness
Nicolas A Menzies, Gabriela B Gomez, Fiammetta Bozzani, Susmita Chatterjee, Nicola Foster, Ines Garcia Baena, Yoko V Laurence, Sun Qiang, Andrew Siroka, Sedona Sweeney, Stéphane Verguet, Nimalan Arinaminpathy, Andrew S Azman, Eran Bendavid, Stewart T Chang, Ted Cohen, Justin T Denholm, David W Dowdy, Philip A Eckhoff, Jeremy D Goldhaber-Fiebert, Andreas Handel, Grace H Huynh, Marek Lalli, Hsien-Ho Lin, Sandip Mandal, Emma S McBryde, Surabhi Pandey, Joshua A Salomon, Sze-Chuan Suen, Tom Sumner, James M Trauer, Bradley G Wagner, Christopher C Whalen, Chieh-Yin Wu, Delia Boccia, Vineet K Chadha, Salome Charalambous, Daniel P Chin, Gavin Churchyard, Colleen Daniels, Puneet Dewan, Lucica Ditiu, Jeffrey W Eaton, Alison D Grant, Piotr Hippner, Mehran Hosseini, David Mametja, Carel Pretorius, Yogan Pillay, Kiran Rade, Suvanand Sahu, Lixia Wang, Rein M G J Houben, Michael E Kimerling, Richard G White, Anna Vassall
BACKGROUND: The post-2015 End TB Strategy sets global targets of reducing tuberculosis incidence by 50% and mortality by 75% by 2025. We aimed to assess resource requirements and cost-effectiveness of strategies to achieve these targets in China, India, and South Africa. METHODS: We examined intervention scenarios developed in consultation with country stakeholders, which scaled up existing interventions to high but feasible coverage by 2025. Nine independent modelling groups collaborated to estimate policy outcomes, and we estimated the cost of each scenario by synthesising service use estimates, empirical cost data, and expert opinion on implementation strategies...
October 5, 2016: Lancet Global Health
Rein M G J Houben, Nicolas A Menzies, Tom Sumner, Grace H Huynh, Nimalan Arinaminpathy, Jeremy D Goldhaber-Fiebert, Hsien-Ho Lin, Chieh-Yin Wu, Sandip Mandal, Surabhi Pandey, Sze-Chuan Suen, Eran Bendavid, Andrew S Azman, David W Dowdy, Nicolas Bacaër, Allison S Rhines, Marcus W Feldman, Andreas Handel, Christopher C Whalen, Stewart T Chang, Bradley G Wagner, Philip A Eckhoff, James M Trauer, Justin T Denholm, Emma S McBryde, Ted Cohen, Joshua A Salomon, Carel Pretorius, Marek Lalli, Jeffrey W Eaton, Delia Boccia, Mehran Hosseini, Gabriela B Gomez, Suvanand Sahu, Colleen Daniels, Lucica Ditiu, Daniel P Chin, Lixia Wang, Vineet K Chadha, Kiran Rade, Puneet Dewan, Piotr Hippner, Salome Charalambous, Alison D Grant, Gavin Churchyard, Yogan Pillay, L David Mametja, Michael E Kimerling, Anna Vassall, Richard G White
BACKGROUND: The post-2015 End TB Strategy proposes targets of 50% reduction in tuberculosis incidence and 75% reduction in mortality from tuberculosis by 2025. We aimed to assess whether these targets are feasible in three high-burden countries with contrasting epidemiology and previous programmatic achievements. METHODS: 11 independently developed mathematical models of tuberculosis transmission projected the epidemiological impact of currently available tuberculosis interventions for prevention, diagnosis, and treatment in China, India, and South Africa...
October 5, 2016: Lancet Global Health
Eugene V Golanov, James M Shiflett, Gavin W Britz
Diving response (DR) is a powerful integrative response targeted toward survival of the hypoxic/anoxic conditions. Being present in all animals and humans, it allows to survive adverse conditions like diving. Earlier, we discovered that forehead stimulation affords neuroprotective effect, decreasing infarction volume triggered by permanent occlusion of the middle cerebral artery in rats. We hypothesized that cold stimulation of the forehead induces DR in rats, which, in turn, exerts neuroprotection. We compared autonomic [AP, heart rate (HR), cerebral blood flow (CBF)] and EEG responses to the known DR-triggering stimulus, ammonia stimulation of the nasal mucosa, cold stimulation of the forehead, and cold stimulation of the glabrous skin of the tail base in anesthetized rats...
2016: Frontiers in Neurology
Anthony C Gordon, Gavin D Perkins, Mervyn Singer, Daniel F McAuley, Robert M L Orme, Shalini Santhakumaran, Alexina J Mason, Mary Cross, Farah Al-Beidh, Janis Best-Lane, David Brealey, Christopher L Nutt, James J McNamee, Henrik Reschreiter, Andrew Breen, Kathleen D Liu, Deborah Ashby
Background Levosimendan is a calcium-sensitizing drug with inotropic and other properties that may improve outcomes in patients with sepsis. Methods We conducted a double-blind, randomized clinical trial to investigate whether levosimendan reduces the severity of organ dysfunction in adults with sepsis. Patients were randomly assigned to receive a blinded infusion of levosimendan (at a dose of 0.05 to 0.2 μg per kilogram of body weight per minute) for 24 hours or placebo in addition to standard care. The primary outcome was the mean daily Sequential Organ Failure Assessment (SOFA) score in the intensive care unit up to day 28 (scores for each of five systems range from 0 to 4, with higher scores indicating more severe dysfunction; maximum score, 20)...
October 5, 2016: New England Journal of Medicine
Billie Giles-Corti, Anne Vernez-Moudon, Rodrigo Reis, Gavin Turrell, Andrew L Dannenberg, Hannah Badland, Sarah Foster, Melanie Lowe, James F Sallis, Mark Stevenson, Neville Owen
Significant global health challenges are being confronted in the 21st century, prompting calls to rethink approaches to disease prevention. A key part of the solution is city planning that reduces non-communicable diseases and road trauma while also managing rapid urbanisation. This Series of papers considers the health impacts of city planning through transport mode choices. In this, the first paper, we identify eight integrated regional and local interventions that, when combined, encourage walking, cycling, and public transport use, while reducing private motor vehicle use...
September 19, 2016: Lancet
James T Julian, Victoria A Gould, Gavin W Glenney, Robert P Brooks
Few studies have documented seasonal variation of Batrachochytrium dendrobatidis (Bd) infection rates in larval amphibians. We identified 4 natural populations of northern green frogs Lithobates clamitans melanota in Pennsylvania (USA) that contained Bd-infected tadpoles during post-wintering collections in May and June, after hibernating tadpoles had overwintered in wetlands. However, we failed to detect infected tadpoles at those wetlands when pre-wintering collections were made in late July through early September...
September 26, 2016: Diseases of Aquatic Organisms
Gavin Churchyard, Koleka Mlisana, Shelly Karuna, Anna-Lise Williamson, Carolyn Williamson, Lynn Morris, Georgia D Tomaras, Stephen C De Rosa, Peter B Gilbert, Niya Gu, Chenchen Yu, Nonhlanhla N Mkhize, Tandile Hermanus, Mary Allen, Michael Pensiero, Susan W Barnett, Glenda Gray, Linda-Gail Bekker, David C Montefiori, James Kublin, Lawrence Corey
BACKGROUND: The safety and immunogenicity of SAAVI DNA-C2 (4 mg IM), SAAVI MVA-C (2.9 x 109 pfu IM) and Novartis V2-deleted subtype C gp140 (100 mcg) with MF59 adjuvant in various vaccination regimens was evaluated in HIV-uninfected adults in South Africa. METHODS: Participants at three South African sites were randomized (1:1:1:1) to one of four vaccine regimens: MVA prime, sequential gp140 protein boost (M/M/P/P); concurrent MVA/gp140 (MP/MP); DNA prime, sequential MVA boost (D/D/M/M); DNA prime, concurrent MVA/gp140 boost (D/D/MP/MP) or placebo...
2016: PloS One
Guillem Anglada-Escudé, Pedro J Amado, John Barnes, Zaira M Berdiñas, R Paul Butler, Gavin A L Coleman, Ignacio de la Cueva, Stefan Dreizler, Michael Endl, Benjamin Giesers, Sandra V Jeffers, James S Jenkins, Hugh R A Jones, Marcin Kiraga, Martin Kürster, Marίa J López-González, Christopher J Marvin, Nicolás Morales, Julien Morin, Richard P Nelson, José L Ortiz, Aviv Ofir, Sijme-Jan Paardekooper, Ansgar Reiners, Eloy Rodríguez, Cristina Rodrίguez-López, Luis F Sarmiento, John P Strachan, Yiannis Tsapras, Mikko Tuomi, Mathias Zechmeister
At a distance of 1.295 parsecs, the red dwarf Proxima Centauri (α Centauri C, GL 551, HIP 70890 or simply Proxima) is the Sun's closest stellar neighbour and one of the best-studied low-mass stars. It has an effective temperature of only around 3,050 kelvin, a luminosity of 0.15 per cent of that of the Sun, a measured radius of 14 per cent of the radius of the Sun and a mass of about 12 per cent of the mass of the Sun. Although Proxima is considered a moderately active star, its rotation period is about 83 days (ref...
August 24, 2016: Nature
Tanya I Coulter, Anita Chandra, Chris M Bacon, Judith Babar, James Curtis, Nick Screaton, John R Goodlad, George Farmer, Cathal Laurence Steele, Timothy Ronan Leahy, Rainer Doffinger, Helen Baxendale, Jolanta Bernatoniene, J David M Edgar, Hilary J Longhurst, Stephan Ehl, Carsten Speckmann, Bodo Grimbacher, Anna Sediva, Tomas Milota, Saul N Faust, Anthony P Williams, Grant Hayman, Zeynep Yesim Kucuk, Rosie Hague, Paul French, Richard Brooker, Peter Forsyth, Richard Herriot, Caterina Cancrini, Paolo Palma, Paola Ariganello, Niall Conlon, Conleth Feighery, Patrick J Gavin, Alison Jones, Kohsuke Imai, Mohammad A A Ibrahim, Gašper Markelj, Mario Abinun, Frédéric Rieux-Laucat, Sylvain Latour, Isabelle Pellier, Alain Fischer, Fabien Touzot, Jean-Laurent Casanova, Anne Durandy, Siobhan O Burns, Sinisa Savic, D S Kumararatne, Despina Moshous, Sven Kracker, Bart Vanhaesebroeck, Klaus Okkenhaug, Capucine Picard, Sergey Nejentsev, Alison M Condliffe, Andrew James Cant
BACKGROUND: Activated phosphoinositide 3-kinase δ syndrome (APDS) is a recently described combined immunodeficiency resulting from gain-of-function mutations in PIK3CD, the gene encoding the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ). OBJECTIVE: We sought to review the clinical, immunologic, histopathologic, and radiologic features of APDS in a large genetically defined international cohort. METHODS: We applied a clinical questionnaire and performed review of medical notes, radiology, histopathology, and laboratory investigations of 53 patients with APDS...
July 16, 2016: Journal of Allergy and Clinical Immunology
Nardin Samuel, Gavin Wilson, Mathieu Lemire, Badr Id Said, Youliang Lou, Weili Li, Diana Merino, Ana Novokmet, James Tran, Kim E Nichols, Jonathan L Finlay, Sanaa Choufani, Marc Remke, Vijay Ramaswamy, Florence M G Cavalli, Christine Elser, Lynn Meister, Michael D Taylor, Uri Tabori, Meredith Irwin, Rosanna Weksberg, Jonathan D Wasserman, Andrew D Paterson, Jordan R Hansford, Maria Isabel W Achatz, Thomas J Hudson, David Malkin
PURPOSE: Although the link between mutant TP53 and human cancer is unequivocal, a significant knowledge gap exists in clinically actionable molecular targets in Li-Fraumeni syndrome (LFS), a highly penetrant cancer predisposition syndrome associated with germline mutations in TP53. This study surveyed the epigenome to identify functionally and clinically relevant novel genes implicated in LFS. PATIENTS AND METHODS: We performed genome-wide methylation analyses of peripheral blood leukocyte DNA in germline TP53 mutation carriers (n = 72) and individuals with TP53 wild type in whom histologically comparable malignancies developed (n = 111)...
August 22, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Ligia S Antonio, Pia Jeggle, Lesley J MacVinish, James C Bartram, Henry Miller, Gavin E Jarvis, Flávia M Levy, Mariana R Santesso, Aline L Leite, Rodrigo C Oliveira, Marília A R Buzalaf, J Michael Edwardson
High concentrations of fluoride in the body may cause toxic effects. Here, we investigated the effects of fluoride on the structure, function, and proteome of a cortical collecting duct epithelium in vitro. Kidney tubule cells (M-1) were chosen because the concentration of fluoride in the kidney is 4-5-fold higher than that in plasma. Mouse M-1 cell monolayers were incubated in fluoride-containing media, and the amiloride-sensitive short-circuit current and transepithelial resistance were measured. The Young's modulus of the epithelium was determined using atomic force microscopy, and the effect of fluoride on epithelial structure was assessed using scanning and transmission electron microscopy, and immunofluorescence...
August 22, 2016: Environmental Toxicology
Emma Davé, Ralph Adams, Oliver Zaccheo, Bruce Carrington, Joanne E Compson, Sarah Dugdale, Michael Airey, Sarah Malcolm, Hanna Hailu, Gavin Wild, Alison Turner, James Heads, Kaushik Sarkar, Andrew Ventom, Diane Marshall, Mark Jairaj, Tim Kopotsha, Louis Christodoulou, Miren Zamacona, Alastair D Lawson, Sam Heywood, David P Humphreys
An antibody format, termed Fab-dsFv, has been designed for clinical indications that require monovalent target binding in the absence of direct Fc receptor (FcR) binding while retaining substantial serum presence. The variable fragment (Fv) domain of a humanized albumin-binding antibody was fused to the C-termini of Fab constant domains, such that the VL and VH domains were individually connected to the Cκ and CH1 domains by peptide linkers, respectively. The anti-albumin Fv was selected for properties thought to be desirable to ensure a durable serum half-life mediated via FcRn...
August 17, 2016: MAbs
Gavin Shaddick, James V Zidek, Yi Liu
The potential effects of air pollution are a major concern both in terms of the environment and in relation to human health. In order to support both environmental and health policy there is a need for accurate estimates of the exposures that populations might experience. The information for this typically comes from environmental monitoring networks but often the locations of monitoring sites are preferentially located in order to detect high levels of pollution. Using the information from such networks has the potential to seriously affect the estimates of pollution that are obtained and that might be used in health risk analyses...
August 2016: Spatial and Spatio-temporal Epidemiology
Jacquelyn A DuVall, Scott T Cabaniss, Morgan L Angotti, John H Moore, Mayuresh Abhyankar, Nishant Shukla, Daniel L Mills, Bryan G Kessel, Gavin T Garner, Nathan S Swami, James P Landers
Pathogen detection has traditionally been accomplished by utilizing methods such as cell culture, immunoassays, and nucleic acid amplification tests; however, these methods are not easily implemented in resource-limited settings because special equipment for detection and thermal cycling is often required. In this study, we present a magnetic bead aggregation assay coupled to an inexpensive microfluidic fabrication technique that allows for cell phone detection and analysis of a notable pathogen in less than one hour...
October 7, 2016: Analyst
Jingyun Wang, Daniel E Neely, Jay Galli, Joshua Schliesser, April Graves, Tina G Damarjian, Jessica Kovarik, James Bowsher, Heather A Smith, Dana Donaldson, Kathryn M Haider, Gavin J Roberts, Derek T Sprunger, David A Plager
PURPOSE: To compare the effectiveness of intermittent occlusion therapy (IO therapy) using liquid crystal glasses and continuous occlusion therapy using traditional adhesive patches for treating amblyopia. METHODS: Children 3-8 years of age with previously untreated, moderate, unilateral amblyopia (visual acuity of 20/40 to 20/100 in the amblyopic eye) were enrolled in this randomized controlled trial. Amblyopia was associated with strabismus, anisometropia, or both...
August 2016: Journal of AAPOS: the Official Publication of the American Association for Pediatric Ophthalmology and Strabismus
Gavin Rush, Aoife O'Donovan, Laura Nagle, Catherine Conway, AnnMaria McCrohan, Cliona O'Farrelly, James V Lucey, Kevin M Malone
BACKGROUND: Immune system dysfunction is implicated in the pathophysiology of major depression, and is hypothesized to normalize with successful treatment. We aimed to investigate immune dysfunction in melancholic depression and its response to ECT. METHODS: 55 melancholic depressed patients and 26 controls participated. 33 patients (60%) were referred for ECT. Blood samples were taken at baseline, one hour after the first ECT session, and 48h after ECT series completion...
June 17, 2016: Journal of Affective Disorders
Demetrius A Vazquez-Molina, Gavin S Mohammad-Pour, Chain Lee, Matthew W Logan, Xiangfeng Duan, James K Harper, Fernando J Uribe-Romo
Covalent organic frameworks (COFs) usually crystallize as insoluble powders, and their processing for suitable devices is thought to be limited. We demonstrate that COFs can be mechanically pressed into shaped objects having anisotropic ordering with preferred orientation between hk0 and 00l crystallographic planes. Five COFs with different functionality and symmetry exhibited similar crystallographic behavior and remarkable stability, indicating the generality of this processing. Pellets prepared from bulk COF powders impregnated with LiClO4 displayed room temperature conductivity up to 0...
August 10, 2016: Journal of the American Chemical Society
Heather Jackson, David Granger, Gavin Jones, Louisa Anderson, Sarah Friel, Daniel Rycroft, William Fieles, James Tunstead, Michael Steward, Trevor Wattam, Adam Walker, Jeremy Griggs, Muhammad Al-Hajj, Christopher Shelton
UNLABELLED: Aberrant WNT signaling is associated with the formation and growth of numerous human cancer types. The low-density lipoprotein receptor-related protein 6 (LRP6) is the least redundant component of the WNT receptor complex with two independent WNT ligand-binding sites. Using domain antibody (dAb) technology, a bispecific antibody (GSK3178022) to LRP6 was identified that is capable of blocking stimulation in the presence of a range of WNT and R-spondin (RSPO) ligands in vitro GSK3178022 was also efficacious in reducing WNT target gene expression in vivo, in both cancer cell line and patient-derived xenograft models, and delays tumor growth in a patient-derived RSPO fusion model of colorectal cancer...
September 2016: Molecular Cancer Research: MCR
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