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JOURNAL ARTICLE
James A Watson, Robert J Commons, Joel Tarning, Julie A Simpson, Alejandro Llanos Cuentas, Marcus V G Lacerda, Justin A Green, Gavin C K W Koh, Cindy S Chu, François H Nosten, Richard N Price, Nicholas P J Day, Nicholas J White
In our recent paper on the clinical pharmacology of tafenoquine (Watson et al., 2022), we used all available individual patient pharmacometric data from the tafenoquine pre-registration clinical efficacy trials to characterise the determinants of anti-relapse efficacy in tropical vivax malaria. We concluded that the currently recommended dose of tafenoquine (300 mg in adults, average dose of 5 mg/kg) is insufficient for cure in all adults, and a 50% increase to 450 mg (7.5 mg/kg) would halve the risk of vivax recurrence by four months...
February 7, 2024: ELife
#22
JOURNAL ARTICLE
Oliver W Meldrum, Gavin C Donaldson, Jayanth Kumar Narayana, Fransiskus Xaverius Ivan, Tavleen K Jaggi, Micheál Mac Aogáin, Lydia J Finney, James P Allinson, Jadwiga A Wedzicha, Sanjay H Chotirmall
RATIONALE: Progressive lung function loss is recognized in COPD; however, no study concurrently evaluates how accelerated lung function decline relates to mucus properties and the microbiome in COPD. OBJECTIVE: Longitudinal assessment of mucus and microbiome changes accompanying accelerated lung function decline in COPD patients. METHODS: Prospective, longitudinal assessment of the London COPD cohort exhibiting the greatest FEV1 decline (n=30; "accelerated decline"; 156 mL/year FEV1 loss) and with no FEV1 decline (n=28; "non-decline"; 49 mL/year FEV1 gain) over time...
February 5, 2024: American Journal of Respiratory and Critical Care Medicine
#23
JOURNAL ARTICLE
Beatrix Theobald, Regis Risani, Lloyd Donaldson, James H Bridson, Joanne M Kingsbury, Olga Pantos, Louise Weaver, Gavin Lear, Xavier Pochon, Anastasija Zaiko, Dawn A Smith, Ross Anderson, Ben Davy, Steph Davy, Fraser Doake, Hayden Masterton, Francois Audrezet, Stefan D M Maday, Jessica A Wallbank, Maxime Barbier, Angelique F Greene, Kate Parker, Jessica Harris, Grant L Northcott, Robert Abbel
The fragmentation of plastic debris is a key pathway to the formation of microplastic pollution. These disintegration processes depend on the materials' physical and chemical characteristics, but insight into these interrelationships is still limited, especially under natural conditions. Five plastics of known polymer/additive compositions and processing histories were deployed in aquatic environments and recovered after six and twelve months. The polymer types used were linear low density polyethylene (LLDPE), oxo-degradable LLDPE (oxoLLDPE), poly(ethylene terephthalate) (PET), polyamide-6 (PA6), and poly(lactic acid) (PLA)...
January 23, 2024: Science of the Total Environment
#24
Sairam Behera, Severine Catreux, Massimiliano Rossi, Sean Truong, Zhuoyi Huang, Michael Ruehle, Arun Visvanath, Gavin Parnaby, Cooper Roddey, Vitor Onuchic, Daniel L Cameron, Adam English, Shyamal Mehtalia, James Han, Rami Mehio, Fritz J Sedlazeck
Research and medical genomics require comprehensive and scalable solutions to drive the discovery of novel disease targets, evolutionary drivers, and genetic markers with clinical significance. This necessitates a framework to identify all types of variants independent of their size (e.g., SNV/SV) or location (e.g., repeats). Here we present DRAGEN that utilizes novel methods based on multigenomes, hardware acceleration, and machine learning based variant detection to provide novel insights into individual genomes with ∼30min computation time (from raw reads to variant detection)...
January 6, 2024: bioRxiv
#25
JOURNAL ARTICLE
Keith Couper, Chen Ji, Ranjit Lall, Charles D Deakin, Rachael Fothergill, John Long, James Mason, Felix Michelet, Jerry P Nolan, Henry Nwankwo, Tom Quinn, Anne-Marie Slowther, Michael A Smyth, Alison Walker, Loraine Chowdhury, Chloe Norman, Laurille Sprauve, Kath Starr, Sara Wood, Steve Bell, Gemma Bradley, Martina Brown, Shona Brown, Karl Charlton, Alison Coppola, Charlotte Evans, Christine Evans, Theresa Foster, Michelle Jackson, Justin Kearney, Nigel Lang, Adam Mellett-Smith, Ria Osborne, Helen Pocock, Nigel Rees, Robert Spaight, Belinda Tibbetts, Gregory A Whitley, Jason Wiles, Julia Williams, Adam Wright, Gavin D Perkins
AIMS: The PARAMEDIC-3 trial evaluates the clinical and cost-effectiveness of an intraosseous first strategy, compared with an intravenous first strategy, for drug administration in adults who have sustained an out-of-hospital cardiac arrest. METHODS: PARAMEDIC-3 is a pragmatic, allocation concealed, open-label, multi-centre, superiority randomised controlled trial. It will recruit 15,000 patients across English and Welsh ambulance services. Adults who have sustained an out-of-hospital cardiac arrest are individually randomised to an intraosseous access first strategy or intravenous access first strategy in a 1:1 ratio through an opaque, sealed envelope system...
March 2024: Resuscitation plus
#26
Joseph Farris, Cheryl Khanna, James B Smadbeck, Sarah H Johnson, Erick Bothun, Tyler Kaplan, Francis Hoffman, Katarzyna Polonis, Gavin Oliver, Linda M Reis, Elena V Semina, Laura Rust, Nicole L Hoppman, George Vasmatzis, Cherisse A Marcou, Lisa A Schimmenti, Eric W Klee
Axenfeld-Rieger Syndrome (ARS) type 1 is a rare autosomal dominant condition characterized by anterior chamber anomalies, umbilical defects, dental hypoplasia, and craniofacial anomalies, with Meckel's diverticulum in some individuals. Here, we describe a clinically ascertained female of childbearing age with ARS for whom clinical targeted sequencing and deletion/duplication analysis followed by clinical exome and genome sequencing resulted in no pathogenic variants or variants of unknown significance in PITX2 or FOXC1...
January 17, 2024: American Journal of Medical Genetics. Part A
#27
JOURNAL ARTICLE
Ayesha Shah, Michael P Jones, Gavin Callaghan, Thomas Fairlie, Xiaomin Ma, Emma L Culver, Katherine Stuart, Peter De Cruz, James O'Beirne, James H Tabibian, Axel Dignass, Ali Canbay, Gregory J Gores, Gerald J Holtmann
BACKGROUND: Primary sclerosing cholangitis (PSC) is an immune-mediated, chronic cholestatic liver disease. Currently, liver transplantation is the only established life-saving treatment. Several studies have evaluated the effect of different biologic therapies on PSC with inconclusive findings. We conducted a systematic review and meta-analysis to assess the effects of biologics in PSC and associated inflammatory bowel disease (IBD). METHODS: MEDLINE, Scopus, and Embase were searched up to July 31, 2023, for studies reporting the effects of biologics in patients with PSC-IBD...
January 1, 2024: Hepatology Communications
#28
JOURNAL ARTICLE
Roberto Mansilla, Gavin Long, Simon Welham, John Harvey, Evgeniya Lukinova, Georgiana Nica-Avram, Gavin Smith, David Salt, Andrew Smith, James Goulding
Plant-based product replacements are gaining popularity. However, the long-term health implications remain poorly understood, and available methods, though accurate, are expensive and burdensome, impeding the study of sufficiently large cohorts. To identify dietary transitions over time, we examine anonymised loyalty-card shopping records from Co-op Food, UK. We focus on 10,626 frequent customers who directly replaced milk with alternative milk. We then use product nutritional information to estimate weekly nutrient intake before and after the transition...
January 10, 2024: Scientific Reports
#29
Valentina Cipriani, Letizia Vestito, Emma F Magavern, Julius Ob Jacobsen, Gavin Arno, Elijah R Behr, Katherine A Benson, Marta Bertoli, Detlef Bockenhauer, Michael R Bowl, Kate Burley, Li F Chan, Patrick Chinnery, Peter Conlon, Marcos Costa, Alice E Davidson, Sally J Dawson, Elhussein Elhassan, Sarah E Flanagan, Marta Futema, Daniel P Gale, Sonia García-Ruiz, Cecilia Gonzalez Corcia, Helen R Griffin, Sophie Hambleton, Amy R Hicks, Henry Houlden, Richard S Houlston, Sarah A Howles, Robert Kleta, Iris Lekkerkerker, Siying Lin, Petra Liskova, Hannah Mitchison, Heba Morsy, Andrew D Mumford, William G Newman, Ruxandra Neatu, Edel A O'Toole, Albert Cm Ong, Alistair T Pagnamenta, Shamima Rahman, Neil Rajan, Peter N Robinson, Mina Ryten, Omid Sadeghi-Alavijeh, John A Sayer, Claire L Shovlin, Jenny C Taylor, Omri Teltsh, Ian Tomlinson, Arianna Tucci, Clare Turnbull, Albertien M van Eerde, James S Ware, Laura M Watts, Andrew R Webster, Sarah K Westbury, Sean L Zheng, Mark Caulfield, Damian Smedley
To discover rare disease-gene associations, we developed a gene burden analytical framework and applied it to rare, protein-coding variants from whole genome sequencing of 35,008 cases with rare diseases and their family members recruited to the 100,000 Genomes Project (100KGP). Following in silico triaging of the results, 88 novel associations were identified including 38 with existing experimental evidence. We have published the confirmation of one of these associations, hereditary ataxia with UCHL1 , and independent confirmatory evidence has recently been published for four more...
December 21, 2023: medRxiv
#30
Cree Kachelski, Kelsey Gavin, Hayden Head, Danielle Horton, James Anderst
Abusive head trauma (AHT) is a leading cause of abusive deaths in children under age one. AHT can include intracranial hemorrhages, hypoxic ischemic injury, or parenchymal lacerations. Most infants with parenchymal lacerations present with acute neurological symptoms. There has been some published literature on lucid intervals in cases of AHT; however, there has not been a described lucid interval with parenchymal lacerations. Parenchymal lacerations typically present with acute symptomatology such as seizures, alteration in mental status, or increased fussiness/lethargy given the damage to neurons and brain structure...
December 26, 2023: Journal of Forensic and Legal Medicine
#31
JOURNAL ARTICLE
Andrew I Ritchie, Gavin C Donaldson, Eric A Hoffman, James P Allinson, Chloe I Bloom, Charlotte E Bolton, Gourab Choudhury, Sarah E Gerard, Junfeng Guo, Luana Alves-Moreira, Lorcan McGarvey, Elizabeth Sapey, Robert A Stockley, K P Yip, Dave Singh, Tom Wilkinson, Malin Fageras, Kristoffer Ostridge, Olaf Jöns, Enrica Bucchioni, Chris H Compton, Paul Jones, Karen Mezzi, Jørgen Vestbo, Peter M A Calverley, Jadwiga A Wedzicha
RATIONALE: Chronic obstructive pulmonary disease (COPD) due to tobacco smoking commonly presents when extensive lung damage has occurred. OBJECTIVES: We hypothesised that structural change would be detected early in the natural history of COPD and would relate to loss of lung function with time. METHODS: We recruited 431 current smokers (median age 39 years, 16 pack-years smoked) and recorded symptoms by the COPD Assessment Test (CAT), spirometry and quantitative thoracic CT (QCT) scans at study entry...
January 4, 2024: American Journal of Respiratory and Critical Care Medicine
#32
JOURNAL ARTICLE
Holger Babbe, Thomas B Sundberg, Mark Tichenor, Mark Seierstad, Genesis Bacani, James Berstler, Wenying Chai, Leon Chang, De Michael Chung, Kevin Coe, Bernard Collins, Michael Finley, Alexander Guletsky, Christopher T Lemke, Puiying A Mak, Ashok Mathur, Eduardo V Mercado-Marin, Shailesh Metkar, Donald D Raymond, Marie-Laure Rives, Michele Rizzolio, Paul L Shaffer, Russell Smith, Jacqueline Smith, Ruth Steele, Helena Steffens, Javier Suarez, Gaochao Tian, Nathan Majewski, Laurie P Volak, Jianmei Wei, Prerak T Desai, Luvena L Ong, Tatiana Koudriakova, Steven D Goldberg, Gavin Hirst, Virendar K Kaushik, Tatiana Ort, Nilufer Seth, Daniel B Graham, Scott Plevy, Jennifer D Venable, Ramnik J Xavier, Jennifer E Towne
The salt-inducible kinases (SIK) 1-3 are key regulators of pro- versus anti-inflammatory cytokine responses during innate immune activation. The lack of highly SIK-family or SIK isoform-selective inhibitors suitable for repeat, oral dosing has limited the study of the optimal SIK isoform selectivity profile for suppressing inflammation in vivo. To overcome this challenge, we devised a structure-based design strategy for developing potent SIK inhibitors that are highly selective against other kinases by engaging two differentiating features of the SIK catalytic site...
January 2, 2024: Proceedings of the National Academy of Sciences of the United States of America
#33
JOURNAL ARTICLE
Stefanie Croghan, Robert Malcolm, Hugh Flood, Stuart Mealing, Brooke Avey, Gavin Leonard, James Wright, Niall Davis, Michael Walsh
AIMS: Intraurethral catheter balloon inflation is a substantial contributor to significant catheter-related urethral injury. A novel safety valve has been designed to prevent these balloon-inflation injuries. The purpose of this evaluation was to assess the cost-effectiveness of urethral catheterisation with the safety valve added to a Foley catheter versus the current standard of care (Foley catheter alone). MATERIALS AND METHODS: The analysis was conducted from the UK public payer perspective on a hypothetical cohort of adults requiring transurethral catheterization...
December 21, 2023: Journal of Medical Economics
#34
JOURNAL ARTICLE
Stephen P H Alexander, Doriano Fabbro, Eamonn Kelly, Alistair A Mathie, John A Peters, Emma L Veale, Jane F Armstrong, Elena Faccenda, Simon D Harding, Jamie A Davies, Laura Amarosi, Catriona M H Anderson, Philip M Beart, Stefan Broer, Paul A Dawson, Gergely Gyimesi, Bruno Hagenbuch, James R Hammond, Jules C Hancox, Michal Hershfinkel, Ken-Ichi Inui, Yoshikatsu Kanai, Stephan Kemp, Edmund R S Kunji, Gavin Stewart, Sotiria Tavoulari, David T Thwaites, Tiziano Verri
The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties...
October 2023: British Journal of Pharmacology
#35
JOURNAL ARTICLE
Adam H Dyer, Helena Dolphin, Antoinette O'Connor, Laura Morrison, Gavin Sedgwick, Aoife McFeely, Emily Killeen, Conal Gallagher, Naomi Davey, Eimear Connolly, Shane Lyons, Conor Young, Christine Gaffney, Ruth Ennis, Cathy McHale, Jasmine Joseph, Graham Knight, Emmet Kelly, Cliona O'Farrelly, Nollaig M Bourke, Aoife Fallon, Sean O'Dowd, Sean P Kennelly
INTRODUCTION: Alzheimer's disease and other dementias affect >50 million individuals globally and are characterised by broad clinical and biological heterogeneity. Cohort and biobank studies have played a critical role in advancing the understanding of disease pathophysiology and in identifying novel diagnostic and treatment approaches. However, further discovery and validation cohorts are required to clarify the real-world utility of new biomarkers, facilitate research into the development of novel therapies and advance our understanding of the clinical heterogeneity and pathobiology of neurodegenerative diseases...
December 9, 2023: BMJ Open
#36
JOURNAL ARTICLE
Bärbel Hönisch, Dana L Royer, Daniel O Breecker, Pratigya J Polissar, Gabriel J Bowen, Michael J Henehan, Ying Cui, Margret Steinthorsdottir, Jennifer C McElwain, Matthew J Kohn, Ann Pearson, Samuel R Phelps, Kevin T Uno, Andy Ridgwell, Eleni Anagnostou, Jacqueline Austermann, Marcus P S Badger, Richard S Barclay, Peter K Bijl, Thomas B Chalk, Christopher R Scotese, Elwyn de la Vega, Robert M DeConto, Kelsey A Dyez, Vicki Ferrini, Peter J Franks, Claudia F Giulivi, Marcus Gutjahr, Dustin T Harper, Laura L Haynes, Matthew Huber, Kathryn E Snell, Benjamin A Keisling, Wilfried Konrad, Tim K Lowenstein, Alberto Malinverno, Maxence Guillermic, Luz María Mejía, Joseph N Milligan, John J Morton, Lee Nordt, Ross Whiteford, Anita Roth-Nebelsick, Jeremy K C Rugenstein, Morgan F Schaller, Nathan D Sheldon, Sindia Sosdian, Elise B Wilkes, Caitlyn R Witkowski, Yi Ge Zhang, Lloyd Anderson, David J Beerling, Clara Bolton, Thure E Cerling, Jennifer M Cotton, Jiawei Da, Douglas D Ekart, Gavin L Foster, David R Greenwood, Ethan G Hyland, Elliot A Jagniecki, John P Jasper, Jennifer B Kowalczyk, Lutz Kunzmann, Wolfram M Kürschner, Charles E Lawrence, Caroline H Lear, Miguel A Martínez-Botí, Daniel P Maxbauer, Paolo Montagna, B David A Naafs, James W B Rae, Markus Raitzsch, Gregory J Retallack, Simon J Ring, Osamu Seki, Julio Sepúlveda, Ashish Sinha, Tekie F Tesfamichael, Aradhna Tripati, Johan van der Burgh, Jimin Yu, James C Zachos, Laiming Zhang
The geological record encodes the relationship between climate and atmospheric carbon dioxide (CO2 ) over long and short timescales, as well as potential drivers of evolutionary transitions. However, reconstructing CO2 beyond direct measurements requires the use of paleoproxies and herein lies the challenge, as proxies differ in their assumptions, degree of understanding, and even reconstructed values. In this study, we critically evaluated, categorized, and integrated available proxies to create a high-fidelity and transparently constructed atmospheric CO2 record spanning the past 66 million years...
December 8, 2023: Science
#37
RANDOMIZED CONTROLLED TRIAL
Emma Kwan-Yee Ho, Ralph Jasper Mobbs, James Montague van Gelder, Ian Andrew Harris, Gavin Davis, Ralph Stanford, David John Beard, Christopher Gerard Maher, Joanna Prior, Michael Knox, David Barrett Anderson, Rachelle Buchbinder, Manuela Loureiro Ferreira
Although placebo-controlled trials are considered the gold standard for evaluating the efficacy of healthcare interventions, they can be perceived to be controversial and challenging to conduct for surgical treatments. The SUcceSS trial is the first placebo-controlled trial of lumbar decompression surgery for symptomatic lumbar canal stenosis. The SUcceSS trial has experienced common issues affecting the implementation of randomised placebo-controlled surgery trials, accentuated by the COVID-19 pandemic. Using the SUcceSS trial as an example, we discuss key challenges and mitigation strategies specific to the conduct of a randomised placebo-controlled surgical trial...
December 6, 2023: Trials
#38
JOURNAL ARTICLE
Alexandra M Zaborowski, Katie Doogan, Siobhan Clifford, Gavin Dowling, Farah Kazi, Karina Delaney, Himanshu Yadav, Aaron Brady, James Geraghty, Denis Evoy, Jane Rothwell, Damian McCartan, Anna Heeney, Mitchel Barry, Siun M Walsh, Maurice Stokes, Malcolm R Kell, Michael Allen, Colm Power, Arnold D K Hill, Elizabeth Connolly, Dhafir Alazawi, Terence Boyle, Mark Corrigan, Peter O'Leary, Ruth S Prichard
BACKGROUND: The necessity of performing a sentinel lymph node biopsy in patients with clinically and radiologically node-negative breast cancer after neoadjuvant chemotherapy has been questioned. The aim of this study was to determine the rate of nodal positivity in these patients and to identify clinicopathological features associated with lymph node metastasis after neoadjuvant chemotherapy (ypN+). METHODS: A retrospective multicentre study was performed. Patients with cT1-3 cN0 breast cancer who underwent sentinel lymph node biopsy after neoadjuvant chemotherapy between 2016 and 2021 were included...
December 6, 2023: British Journal of Surgery
#39
Suzanne A Aleksander, Anna V Anagnostopoulos, Giulia Antonazzo, Valerio Arnaboldi, Helen Attrill, Andrés Becerra, Susan M Bello, Olin Blodgett, Yvonne M Bradford, Carol J Bult, Scott Cain, Brian R Calvi, Seth Carbon, Juancarlos Chan, Wen J Chen, J Michael Cherry, Jaehyoung Cho, Madeline A Crosby, Jeffrey L De Pons, Peter D'Eustachio, Stavros Diamantakis, Mary E Dolan, Gilberto Dos Santos, Sarah Dyer, Dustin Ebert, Stacia R Engel, David Fashena, Malcolm Fisher, Saoirse Foley, Adam C Gibson, Varun R Gollapally, L Sian Gramates, Christian A Grove, Paul Hale, Todd Harris, G Thomas Hayman, Yanhui Hu, Christina James-Zorn, Kamran Karimi, Kalpana Karra, Ranjana Kishore, Anne E Kwitek, Stanley J F Laulederkind, Raymond Lee, Ian Longden, Manuel Luypaert, Nicholas Markarian, Steven J Marygold, Beverley Matthews, Monica S McAndrews, Gillian Millburn, Stuart Miyasato, Howie Motenko, Sierra Moxon, Hans-Michael Muller, Christopher J Mungall, Anushya Muruganujan, Tremayne Mushayahama, Robert S Nash, Paulo Nuin, Holly Paddock, Troy Pells, Norbert Perrimon, Christian Pich, Mark Quinton-Tulloch, Daniela Raciti, Sridhar Ramachandran, Joel E Richardson, Susan Russo Gelbart, Leyla Ruzicka, Gary Schindelman, David R Shaw, Gavin Sherlock, Ajay Shrivatsav, Amy Singer, Constance M Smith, Cynthia L Smith, Jennifer R Smith, Lincoln Stein, Paul W Sternberg, Christopher J Tabone, Paul D Thomas, Ketaki Thorat, Jyothi Thota, Monika Tomczuk, Vitor Trovisco, Marek A Tutaj, Jose-Maria Urbano, Kimberly Van Auken, Ceri E Van Slyke, Peter D Vize, Qinghua Wang, Shuai Weng, Monte Westerfield, Laurens G Wilming, Edith D Wong, Adam Wright, Karen Yook, Pinglei Zhou, Aaron Zorn, Mark Zytkovicz
The Alliance of Genome Resources (Alliance) is an extensible coalition of knowledgebases focused on the genetics and genomics of intensively-studied model organisms. The Alliance is organized as individual knowledge centers with strong connections to their research communities and a centralized software infrastructure, discussed here. Model organisms currently represented in the Alliance are budding yeast, C. elegans , Drosophila , zebrafish, frog, laboratory mouse, laboratory rat, and the Gene Ontology Consortium...
November 22, 2023: bioRxiv
#40
JOURNAL ARTICLE
James R Gavin, Richard M Abaniel, Naunihal S Virdi
BACKGROUND: Therapeutic inertia leading to delays in insulin initiation or intensification is a major contributor to lack of optimal diabetes care. This report reviews the literature summarizing data on therapeutic inertia and delays in insulin intensification in the management of type 2 diabetes. METHODS: A literature search was conducted of the Allied & Complementary Medicine, BIOSIS Previews, Embase, EMCare, International Pharmaceutical Abstracts, MEDLINE, and ToxFile databases for clinical studies, observational research, and meta-analyses from 2012 to 2022 using search terms for type 2 diabetes and delay in initiating/intensifying insulin...
2023: Diabetes Spectrum: a Publication of the American Diabetes Association
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