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139 results on '"Hepworth, David"'

107. Beyond caring?

Author

Hepworth, David

Subjects
Caregivers -- Services, Social work with minorities -- Management, Psychology and mental health, Sociology and social work
Abstract

UK local authorities tend to overlook the needs of black and ethnic minority carers, according to research undertaken by the social policy research unit at the University of York and CNA North of England. There is poor consultation with this group of carers, with some local authorities adopting a generalist approach that does not consider the requirements of ethnic minorities.

Published
2001

110. Effect of novel bio-derived nanoplatelets on the hydration of Portland cement: Reactive molecular dynamics simulations and experimental characterization

Author

Chi, Yin, Huang, Bo, Saafi, Mohamed, Fullwood, Nigel, Lambert, Colin, Whale, Eric, Hepworth, David, and Jianqiao Ye

Subjects
Density Function Theory (DFT), Reactive Molecular Dynamics Simulation, Cement Hydration, Tricalcium Silicate, Carrot Nanosheet, 13. Climate action
Abstract

Ordinary Portland cement (OPC) is the binding element in concrete materials and, CO2 emissions associated with its manufacturing and use is about 8% of the world's CO2 emissions. When OPC is mixed with water, a large quantity of OPC particles remain unhydrated or partially hydrated. If the dissolution and setting of calcium silicate phases of OPC could be increased, the performance of concrete would be improved, and the consumption of OPC will be decreased and its environmental footprint will be reduced. In this paper, we examine the origin of increased dissolution of tricalcium silicate (C3S) and dicalcium silicate (C2S) phases as a result of their interfacial chemical interactions with newly developed 2D carrot-based bio nanosheets (CNSs). Density-functional theory calculations and reactive molecular dynamics (DFT-MD) simulations were combined with experimental characterization to uncover the molecular chemical phenomena at the CNS/cement interface and understand how they influence the hydration of cement. The DFT-MD simulations results reveal that the observed increase in the degree of hydration of cement is due to the chemical interaction at the CNS/C3S interface. The dissolution of CNS by the highly reactive C3S leads to a series of proton exchange with higher diffusion rate in C3S. This increases the thickness of the hydration shell by as much as 3 nm. The DFT-MD simulations also show that the dissolution of CNS creates new organic compounds that enhance the mobility and dynamics of protons to further promote the dissolution of C3S. The experimental results support the DFT-MD simulation results. They confirm the dissolution of some CNS layers and the subsequent increased dissolution of C3S. The experimental results also show that CNS increases the degree of hydration of C3S and C2S by 6.3% at a maximum CNS concentration of 0.4-wt%. This work demonstrates that the kinetics of reaction of CNS in the cement environment amplify the hydration of OPC for enhanced performance and provides a base for the development of cementitious materials with low carbon footprint using green and renewable 2D nanomaterials.

111. Assessment of 'danger to self and others': a study of the Mental Health Review Tribunal's interpretation of 'dangerousness'

Author

Hepworth, David Robert

Abstract

The general research aim was to examine the process by which the mental health review tribunal decided on the 'dangerousness' of the person before them as a basis for their judgement about release or continued detention. Within the general context of the sociology of law, the research project was concerned with the decision-process as it operated in practice within the established socio-legal framework and its interaction with the concept and causation and social nature of deviance and 'danger'. It was assumed that the formal-structural approach was insufficient to study and explain the decision-process in practice; so the research incorporated the study of the relationship between socio-demographic facts and the tribunal decisions, a study of the way the facts were perceived by the tribunal members, and consideration of the dilemmas and conflicts experienced in practice and innovatory action arising from anomalies in their rules and powers. Various methods of data-collection were adopted in respect of the sample of 150 tribunal hearings held at Rampton Hospital: a) the systematic observation of the hearing, b) the structured interviewing of the legal chairman, and c) structured examination of written records for details of the subject. The findings supported the conclusions that the prescribed rules and powers of the tribunal were insufficient for the task of protecting the individual from unfair detention; and the nature of 'danger' and the social identity of the 'dangerous individual' required a response from the decision-makers beyond objective assessment of observable facts. The decision-process was shown to be a 'human-process' involving emotional and subjective reactions. A more sufficient model of the decision-process in respect of 'danger to self and others' was developed, designed to take account of external restraints and anomalies in the system, and influences which could not be explained in strictly 'objective' terms.

113. Sail Away.

Author

Hepworth, David

Subjects
*POPULAR music, 2011-2020
Published
2017

114. Rolling Stoned.

Author

HEPWORTH, DAVID

Subjects
GRATEFUL Dead (Performer), BAR-Lev, Amir, LONG Strange Trip (Film)
Abstract

The article features the band Grateful Dead, with topics including the documentary film "Long Strange Trip," directed by Amir BAr-Lev, the career development of the band, and their success in independent rock music.

Published
2017

115. The Diary.

Author

Hepworth, David

Subjects
*POPULAR culture, *SOCCER fields
Abstract

The author discusses aspects of British popular culture as of May 26, 2017. Topics covered include the last game of the Tottenham Hotspur Football Club at the White Hart Lane football stadium in London, England, the 40th anniversary of the release of the song "God Save the Queen" by the Sex Pistols, and writer Danny Baker's radio program on BBC Radio 5 Live. Also mentioned are a session about American songwriter Bob Dylan at the Bath Festival and the audio version of the book "Uncommon People."

Published
2017

117. New films.

Author

Hepworth, David

Subjects
MOTION pictures
Abstract

Reviews the motion picture `Pocahontas,' directed by Mike Gabriel .

Published
1995

120. Untitled.

Author

W. F. W. and HEPWORTH, DAVID

Published
1876

121. Rational approach to highly potent and selective apoptosis signal-regulating kinase 1 (ASK1) inhibitors.

Author

Lovering, Frank, Morgan, Paul, Allais, Christophe, Aulabaugh, Ann, Brodfuehrer, Joanne, Chang, Jeanne, Coe, Jotham, Ding, Weidong, Dowty, Heather, Fleming, Margaret, Frisbie, Richard, Guzova, Julia, Hepworth, David, Jasti, Jayasankar, Kortum, Steve, Kurumbail, Ravi, Mohan, Shashi, Papaioannou, Nikolaos, Strohbach, Joseph W., and Vincent, Fabien

Subjects
*APOPTOSIS, *REACTIVE oxygen species, *OXIDATIVE stress, *AMINO acids, *PHARMACOLOGY
Abstract

Many diseases are believed to be driven by pathological levels of reactive oxygen species (ROS) and oxidative stress has long been recognized as a driver for inflammatory disorders. Apoptosis signal-regulating kinase 1 (ASK1) has been reported to be activated by intracellular ROS and its inhibition leads to a down regulation of p38-and JNK-dependent signaling. Consequently, ASK1 inhibitors may have the potential to treat clinically important inflammatory pathologies including renal, pulmonary and liver diseases. Analysis of the ASK1 ATP-binding site suggested that Gln756, an amino acid that rarely occurs at the GK+2 position, offered opportunities for achieving kinase selectivity for ASK1 which was applied to the design of a parallel medicinal chemistry library that afforded inhibitors of ASK1 with nanomolar potency and excellent kinome selectivity. A focused optimization strategy utilizing structure-based design resulted in the identification of ASK1 inhibitors with low nanomolar potency in a cellular assay, high selectivity when tested against kinase and broad pharmacology screening panels, and attractive physicochemical properties. The compounds we describe are attractive tool compounds to inform the therapeutic potential of ASK1 inhibition. [ABSTRACT FROM AUTHOR]

Published
2018
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122. Movies to rent.

Author

Hepworth, David and Nathan, Ian

Subjects
MOTION pictures
Abstract

Reviews the video version of the motion picture `Casper,' directed by Brad Silberling.

Published
1996

123. Video movies to rent.

Author

Hepworth, David and Nathan, Ian

Subjects
MOTION pictures
Abstract

Reviews the videotape of the motion picture `Muriel's Wedding,' directed by P.J. Hogan, starring Toni Collette and Bill Hunter.

Published
1995

124. A Small-Molecule Anti-secretagogue of PCSK9 Targets the 80S Ribosome to Inhibit PCSK9 Protein Translation.

Author

Petersen, Donna N., Hawkins, Julie, Ruangsiriluk, Wanida, Stevens, Kimberly A., Maguire, Bruce A., O’Connell, Thomas N., Rocke, Benjamin N., Boehm, Markus, Ruggeri, Roger B., Rolph, Tim, Hepworth, David, Loria, Paula M., and Carpino, Philip A.

Subjects
*SMALL molecules, *GHRELIN receptors, *TARGETED drug delivery, *RIBOSOMES, *MESSENGER RNA
Abstract

Summary Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that downregulates low-density lipoprotein (LDL) receptor (LDL-R) levels on the surface of hepatocytes, resulting in decreased clearance of LDL-cholesterol (LDL-C). Phenotypic screening of a small-molecule compound collection was used to identify an inhibitor of PCSK9 secretion, (R)- N -(isoquinolin-1-yl)-3-(4-methoxyphenyl)- N -(piperidin-3-yl)propanamide (R-IMPP), which was shown to stimulate uptake of LDL-C in hepatoma cells by increasing LDL-R levels, without altering levels of secreted transferrin. Systematic investigation of the mode of action revealed that R-IMPP did not decrease PCSK9 transcription or increase PCSK9 degradation, but instead caused transcript-dependent inhibition of PCSK9 translation. In support of this surprising mechanism of action, we found that R-IMPP was able to selectively bind to human, but not E. coli , ribosomes. This study opens a new avenue for the development of drugs that modulate the activity of target proteins by mechanisms involving inhibition of eukaryotic translation. [ABSTRACT FROM AUTHOR]

Published
2016
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125. 2D bio-based nanomaterial as a green route to amplify the formation of hydrate phases of cement composites: Atomistic simulations and analytical characterization.

Author

Chi, Yin, Huang, Bo, Saafi, Mohamed, Fullwood, Nigel, Lambert, Colin, Whale, Eric, Hepworth, David, and Ye, Jianqiao

Subjects
*CEMENT composites, *CALCIUM silicates, *PORTLAND cement, *SUGAR beets, *SCANNING electron microscopes, *NANOSTRUCTURED materials, *DIFFERENTIAL scanning calorimetry
Abstract

• Novel 2D CNS reinforcing material synthesized sugar beet waste. • MD and DFT simulations investigated the effect of CNS on hydration. • MD and DFT uncovered new positive effects of CNS on hydration. • The CNS amplified the hydration of cement. • A hydration mechanism for the new cementitious composites is proposed. Ordinary Portland cement (OPC) is the binding element in concrete materials and, CO 2 emissions associated with its manufacturing and use is about 8% of the world's CO 2 emissions. The engineering properties of hardened concrete depend on the amount of the hydrate phases in OPC. If the growth of the hydrate phases could be increased, the performance of concrete would be significantly improved, and the consumption of OPC will be decreased, and its environmental footprint will be reduced. In this paper, we present a new green approach for controlling the growth of the hydrate phases in OPC using bio flakes composed of staked carrot-based two-dimensional (2D) nanosheets (CNSs) synthesized from carrot waste. Density-functional theory and reactive molecular dynamics (DFT-MD) simulations were carried out in conjunction with analytical characterization to examine the interfacial interaction between CNS with tricalcium silicate Ca 3 SiO 5 (C 3 S), the main constituent of OPC and understand how they influence the growth of the hydrate phases in OPC. The DFT-MD simulations results show the 2D CNS dissolves due to its interfacial interaction with the highly reactive C 3 S, leading to a series of fast proton exchange in C 3 S. This in return accelerates the dissolution rate of C 3 S thereby amplifying the growth of the hydrate phases. The DFT-MD simulations also show that the dissolution of the 2D CNS creates new several organic compounds that enhance the mobility and dynamics of protons that further amplify the dissolution rate of C 3 S. The analytical results from scanning electron microscope (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), and thermography analysis (TGA) and differential scanning calorimetry (DSC) show a significant growth of the hydrate products in OPC due to interfacial dissolution of C 3 S and some CNS thus, confirming the DFT-MD results. This work demonstrates that the growth of the hydrate products in OPC can be amplified by the addition of green and renewable 2D bio-based nanomaterials. This green approach provides a base for the design and development of low-carbon cementitious materials. [ABSTRACT FROM AUTHOR]

Published
2021
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129. Postoperative continuous positive airway pressure to prevent pneumonia, re-intubation, and death after major abdominal surgery (PRISM): a multicentre, open-label, randomised, phase 3 trial

Author

Rupert Pearse, Marco Ranieri, Tom Abbott, Mari-Liis Pakats, Edoardo Piervincenzi, Akshaykumar Patel, Brennan Kahan, Andrew Rhodes, Priyanthi Dias, Russell Hewson, Ib Jammer, Michelle Chew, Cesar Aldecoa, Reitze Rodseth, Bruce Biccard, Tim Stephens, Sara Payne, David Hepworth, Soeren Pischke, Joerund Asvall, John Hausken, Shaman Jhanji, Martin Rooms, Neil Flint, Dawn Hales, Tamas Szakmany, Andrew Leitch, Savino Spadaro, Davide Chiumello, Paul Johnston, Joyce Yeung, Guglielmo Tellan, Tonny Veenith, Josep Macmillan, Pierpaolo Terragni, Caroline Sander, Vidya Kasipandian, Tahania Ahmad, Aaron Lee, Marcello Tammaro, Danny McAuley, Simon Skene, Ravinder Vohra, Matt Wilson, Mark Edwards, Ewen Griffiths, Naomi Pritchard, Claudia Filippini, Tor Aasmundstad, Einar Aksnes, Lise-Merete Alpers, Andreas Barratt-Due, Anita Dahl, Linda Feldt, Elisa Figari, Eva Flåten, Karen Granheim, Minna Hagring, Håkon Haugaa, Gisle Kjoesen, Inge Klaevahaugen, Harald Lenz, Marianne Myhre, Hilde Orrem, Emily Stitt, Tor Inge Toennessen, Samuel Al-Kadhimi, Robert Anker, Mihaela Balint, Lauren Barraclough, Ethel Black, Matt Clayton, Leonora Conneely, Zara Edwards, Alex Eeles, Matthew Evans, Michelle Gerstman, Nicole Greenshields, Eleanor Harvey, Aoife Hegarty, Natalie Hester, Jenna Hutchinson, Ramanathan Kasivisvanathan, Helen Lawrence, Veronica Marsh, Laura Matthews, Francesca Mazzola, Jamie McCanny, Ben Morrison, Michelle O'Mahony, Ching Ling Pang, David Parkinson, Katrina Pirie, Ravishankar Rao Baikady, Louisa Shovel, Lorna Smith, Kate Tatham, Peter Thomas, Sophie Uren, Susanna Walker, Alasdair Wills, Prematie Andreou, Alex Howson, Jasmin Kaur, Adam Lewszuk, Esther Molina, Nirmalabaye Ramsamy, Emma Roberts, Vanessa Amaral, Salma Begum, Soliana Bekele, Richard Cashmore, Carmen Correia, Steven Dunkley, Maria Fernandez, Alexander Fowler, Amaia Garcia, Maria Della Giovampaola, Kathryn Greaves, Bethan Griffiths, Ryan Haines, Richard Haslop, Ying Hu, Sarah Hui, Marta Januszewska, Vasi Manon, Tim Martin, Shaun May, Annamaria Minicozzi, Edyta Niebrzegowska, Monica Oliveira, Katherine Pates, Filipa Santos, Tasnin Shahid, Paolo Simili, Alastair Somerville, Emily Subhedar, Ruzena Uddin, Sophie Walker, Yize Wan, Jan Whalley, Parjam Zolfaghari, Una Gunter, Gemma Hodkinson, Gwenllian Howe, Valentina Baratozzi, Giulia Casotto, Giulia Darai, Erica Ferrari, Giovanni Mistraletti, Valentina Palmaverdi, Stefano Furlani, Paolo Priani, Riccardo Ragazzi, Marco Salmaso, Marco Verri, Carlo Volta, Chris Nutt, Emma McKay, Orla O'Neill, Jaimin Patel, Katie Atterbury, Sarah Ballinger, Natalie Carling, Kaytie Ellis, Jo Gresty, Teresa Melody, Jade Monk, Chloe Norman, Eleanor Reeves, Julia Sampson, Peter Sutton, Marie Thomas, Amy Bamford, Colin Bergin, Ronald Carrera, Lauren Cooper, Liesl Despy, Karen Ellis, Emma Fellows, Stephanie Goundry, Samantha Harkett, Peter Ip, Tracy Mason, Christopher McGhee, Aisling McLaughlin, Aoife Neal, Martin Pope, Stephanie Porter, Hazel Smith, Catherine Snelson, Elaine Spruce, Ylenia Vigo, Arlo Whitehouse, Tony Whitehouse, Maria Donatiello, Sergio Gazzanelli, Mario Mezzapesa, Martina Savino, Giacomo Settesoldi, Gudrun Kunst, Sian Birch, Louise Greig, Harriet Noble, Evita Pappa, Bethany Penhaligon, Andrea Cossu, Leda Floris, Davide Piredda, Alberto Racca, Olof Brattstrom, Bente Heggelund, Magnus Flodberg, Sandra Månsson, Mamoona Ahmed, Jonathan Allen, Paula Bell, Roman Genetu, Julia Glennon, Janice Hanley, Katy Jenner, Summayyah Jogi, Parisa Mahjoob, Clare McGovern, Anthony Murphy, Roonak Nazari, Jacki Routledge, Trishna Uttamlal, Sinead Ward, Giorgio Iotti, Raffaella Picchioni, Silvia Poma, Paolo Navalesi, Andrea Bruni, Brunella De Leonardis, Eugenio Garofalo, Panna Patel, Carol McArthur, Karen Burns, Steven Peters, Giuseppe Foti, Serena Calcinati, Alice Grassi, Silvia Villa, John Berridge, Muthuraj Kanakaraj, Hazel Cahill, Greg Forshaw, Andy Gibson, Lia Grainger, Kate Howard, Katherine James, Zoe Murphy, Helen Sweeting, Rebecca Tait, Danielle Wilcock, David Yates, Sean Cope, Ashley Allan, Rebecca Betts, Sarah Cornell, Julie Sheriff, Lindsey Woods, Giacomo Grasselli, Matteo Brioni, Luigi Castagna, Richard von Rahden, Zane Farina, Samantha Green, Simphiwe Gumede, Chantal Rajah, Arisha Ramkillawan, Susan Moug, David Alcorn, Carol Dalton, Natalie Dickinson, Jennifer Edwards, Steven Henderson, Erin McIlveen, Richard Ramsaran, Joanne Bell, Lorna Fleming, Kathleen Monks, Jane Parker, Sean Stamper, Jo Stokes-Denson, Elisa Elías, Yessica Guerra, Jesus Rico-Feijoo, Carlos Kidel, Helder Filipe, Gretchelle Asis, Yvonne Gleeson, Alice Harvey, Christine Jackson, Margaret McNeil, Sara Mingo, Glykeria Pakou, Manuel Pinto, Stephen Wright, Maite Babio-Galan, David Buckley, Verity Calder, Ahmad Chishti, Joseph Cosgrove, Katherine Cullen, Leigh Dunn, Matthew Faulds, Jonathan Fortune, Matthew Gardner, Abigail Harrison, Carole Hays, Gerry Jones, Caroline Macfie, Iain Mccullagh, Ian Nesbitt, Suzanne O'Neil, Catherine Phoenix, Girish Rangaswamy, Craig Samson, Carmen Scott, Tara Shrestha, Rita Singh, Graham Soulsby, Jon Walton, Kimberley Zwiggelaar, Ceri Lynch, Heidi Clarke, Bethan Deacon, Helen Ivatt, Leanne Jones, Ahmed Latif, Shaun Oram, Chris Perman, Lisa Roche, Rowan Duys, Margot Flint, Kamal Bhagwan, Ettienne Coetzee, Ivan Joubert, Felipe Montoya-Pelaez, Pradeep Navsaria, Guy Picken, Owen Porrill, Grant Strathie, Thembinkosi Zungu, Sireesha Aluri, Simon Chau, Deborah Cooper, Mishell Cunningham, Allison Daniels, Susan Hope, Alice Nicholson, Laura Walker, Antonino Giarratano, Giuseppe Accurso, Santi Raineri, Giuseppe Tricoli, Richard Innes, Patricia Doble, Joanne Hutter, Corinne Pawley, Moira Tait, Mark Hamilton, Edward Andrade, Veronica Barnes, Claire Dalton, Carlos Delgado, Sarah Farnell-Ward, Helen Farrah, Geraldine Gray, Luisa Howlett, Gipsy Joseph, Monika Krupa, Susannah Leaver, Joao Macedo, Karen Maher, Johannes Mellinghoff, Rachel Oguntimehin, Joel Pereira, Frances Robinson, Christine Ryan, Nirav Shah, Paula Shirley, Alexandra Torborg, Thuli Biyase, Leanne Drummond, Belinda Kusel, Mbalenhle Mbuyisa, Sivuyisiwe Solala, Jenna Taylor, Adanma Ezihe-Ejiofor, Maame Aduse-Poku, Gary Colville, Louise Davies, Soo Kang, Alex Phillips, Justin Kirk-Bayley, Leigh Kelliher, Paula Carvelli, Gokce Daysal, Matthew Dickinson, Nancileigh Doyle, Christina Hughes, Laura Montague, Elizabeth Potter, Armorel Salberg, Sheena Sibug, Sinduja Sivarajan, Milo Thomson, Nichola Wakeford, Monica Rocco, Daniela Alampi, Daniel Conway, Richard Clark, Jashmin Maria, Fiona Pomeroy, Tanviha Quraishi, Abigail Williams, Srikanth Chukkambotla, Caroline Aherne, Donna Harrison-Briggs, Jill Fitchett, Stephen Duberley, Andrea Zanoni, Daniela Cardinale, Claudia Righi, Mark Blunt, Tracy Fuller, Ruth Hodgson, Melissa Rosbergen, Andrew Brennan, Louise Akeroyd, Victoria Boardman, Christopher Bull, Mike Carrick, Ian Chadderton, Sarah Cooper, Sarah Goellner, Laura Graham, Carl Ilyas, James King, Muhammad Laklouk, Tom Lawton, Christopher Macrow, Michael Munro, Adam Neep, Martin Northey, Victoria Peacock, Kate Pye, Lydia Radley, James Sira, Beth Smithson, Stuart Syddall, David Tooth, Thomas White, Sindre Hoel, Elin Aakre, Monica Bakke, Tone Hoivik, Arystarch Makowski, Harry Alcock, Sean Cardoso, Samantha Coetzee, Mary Everett, Mohamed Ibrahim, Christina Kouridaki, Vongayi Ogbeide, Elisabetta Bertellini, Valentina Bertolotti, Antonio Buono, Maria Fanigliulo, Ram Kumar, Nicole Richards, Alisha Allana, Samantha Bacciarelli, Helen Barker, Jessica De Bois, Isabel Bradley, Jennifer Crooks, Peter Daum, Alex Feben, Lizzie Gannon, Sarah Kipling, Andrew Peetamsingh, Charlotte Quamina, Sahiba Sethi, Harry Sivadhas, Kathryn Sollesta, Andrew Swain, Evalyn Tan, Joan Willis, Maggie Zou, Julius Cranshaw, Nina Barratt, Katie Bowman, Debbie Branney, Maria Letts, Sally Pitts, Christopher Day, Sarah Benyon, Sara Eddy, Adam Green, Anna Grice, Sinéad Kelly, Daisy Mackle, Victor Mariano, Linda Park, Pauline Sibley, William Spencer, Elena Bignami, Valentina Bellini, Francesco Forfori, Maria Curci, Alessandra Leo, Matthew Jackson, Jennifer Awolesi, Sheila Hodgkinson, Alissa Kent, Dee Leonard, Claire Stapleton, Clare Tibke, Farhad Alexander-Sefre, Lorraine Campey, Kathryn Hall, Jennifer Spimpolo, Malin Nilsson, Helen Didriksson, Emma Hamilton, Mandy Carnahan, Chris Mowatt, Jo Stickley, Antonio Corcione, Giuseppe Rossi, Hege Fladby, Nina Andersen, Gunhild Bjoernå, Mads Reite, Linda Roertveit, Philipp Seidel, Glenn Arnold, Melissa Benavente, Anjalee Chattersingh, Nyasha Chironga, Gillian Hornzee, Joyce Kibaru, Ihtisham Malik, Laura McLeavy, Byiravey Pathmanathan, Florence Prior, Rhea Strudwick, Marios Vezyrgiannis, Aneeta Sinha, Sheeba Babu, Bisanth Batuwitage, Zoe Daly, Katharine Ellinor, Elizabeth Hawes, Ann Holmes, Karen Hudson, Jeremy Nightingale, Alison Le Poidevin, Lindsey Roberts, Agnieszka Kubisz-Pudelko, Joanna Allison, Lucy Pippard, Vincent Hamlyn, Angie Organ, Thaventhran Prabhahar, Hayley Bridger, Lee Dvorkin, Vitul Manhas, Rachel Vincent, Shondipon Laha, Terri-Louise Cromie, Donna Doyle, Rachel Howarth, Mark Verlander, Ailsa Watt, Alexandra Williams, Massimo Antonelli, Salvatore Cutuli, Luca Montini, Juan Graterol, Benita Adams, Sarah Bean, Karen Burt, Fiona Hammonds, Suyogi Jigajinni, Laura Fulton, Stephen Kinghorn, Jost Mullenheim, Kirsty Baillie, Martyn Cain, Kerry Colling, Carol Hannaway, Ruggero Corso, Morena Calli, Carlos Ferrando, Esther Romero, Pablo Jorge-Monjas, María Soria-García, José Gómez-Herreras, Rita Rodríguez-Jiménez, Blanca De Prada-Martín, Pearse, Rupert, Ranieri, Marco, Abbott, Tom, Pakats, Mari-Lii, Piervincenzi, Edoardo, Patel, Akshaykumar, Kahan, Brennan, Rhodes, Andrew, Dias, Priyanthi, Hewson, Russell, Jammer, Ib, Chew, Michelle, Aldecoa, Cesar, Rodseth, Reitze, Biccard, Bruce, Stephens, Tim, Payne, Sara, Hepworth, David, Pischke, Soeren, Asvall, Joerund, Hausken, John, Jhanji, Shaman, Rooms, Martin, Flint, Neil, Hales, Dawn, Szakmany, Tama, Leitch, Andrew, Spadaro, Savino, Chiumello, Davide, Johnston, Paul, Yeung, Joyce, Tellan, Guglielmo, Veenith, Tonny, Macmillan, Josep, Terragni, Pierpaolo, Sander, Caroline, Kasipandian, Vidya, Ahmad, Tahania, Lee, Aaron, Tammaro, Marcello, McAuley, Danny, Skene, Simon, Vohra, Ravinder, Wilson, Matt, Edwards, Mark, Griffiths, Ewen, Pritchard, Naomi, Filippini, Claudia, Aasmundstad, Tor, Aksnes, Einar, Alpers, Lise-Merete, Barratt-Due, Andrea, Dahl, Anita, Feldt, Linda, Figari, Elisa, Flåten, Eva, Granheim, Karen, Hagring, Minna, Haugaa, Håkon, Kjoesen, Gisle, Klaevahaugen, Inge, Lenz, Harald, Myhre, Marianne, Orrem, Hilde, Stitt, Emily, Toennessen, Tor Inge, Al-Kadhimi, Samuel, Anker, Robert, Balint, Mihaela, Barraclough, Lauren, Black, Ethel, Clayton, Matt, Conneely, Leonora, Edwards, Zara, Eeles, Alex, Evans, Matthew, Gerstman, Michelle, Greenshields, Nicole, Harvey, Eleanor, Hegarty, Aoife, Hester, Natalie, Hutchinson, Jenna, Kasivisvanathan, Ramanathan, Lawrence, Helen, Marsh, Veronica, Matthews, Laura, Mazzola, Francesca, McCanny, Jamie, Morrison, Ben, O'Mahony, Michelle, Pang, Ching Ling, Parkinson, David, Pirie, Katrina, Rao Baikady, Ravishankar, Shovel, Louisa, Smith, Lorna, Tatham, Kate, Thomas, Peter, Uren, Sophie, Walker, Susanna, Wills, Alasdair, Andreou, Prematie, Howson, Alex, Kaur, Jasmin, Lewszuk, Adam, Molina, Esther, Ramsamy, Nirmalabaye, Roberts, Emma, Amaral, Vanessa, Begum, Salma, Bekele, Soliana, Cashmore, Richard, Correia, Carmen, Dunkley, Steven, Fernandez, Maria, Fowler, Alexander, Garcia, Amaia, Della Giovampaola, Maria, Greaves, Kathryn, Griffiths, Bethan, Haines, Ryan, Haslop, Richard, Hu, Ying, Hui, Sarah, Januszewska, Marta, Manon, Vasi, Martin, Tim, May, Shaun, Minicozzi, Annamaria, Niebrzegowska, Edyta, Oliveira, Monica, Pates, Katherine, Santos, Filipa, Shahid, Tasnin, Simili, Paolo, Somerville, Alastair, Subhedar, Emily, Uddin, Ruzena, Walker, Sophie, Wan, Yize, Whalley, Jan, Zolfaghari, Parjam, Gunter, Una, Hodkinson, Gemma, Howe, Gwenllian, Baratozzi, Valentina, Casotto, Giulia, Darai, Giulia, Ferrari, Erica, Mistraletti, Giovanni, Palmaverdi, Valentina, Furlani, Stefano, Priani, Paolo, Ragazzi, Riccardo, Salmaso, Marco, Verri, Marco, Volta, Carlo, Nutt, Chri, McKay, Emma, O'Neill, Orla, Patel, Jaimin, Atterbury, Katie, Ballinger, Sarah, Carling, Natalie, Ellis, Kaytie, Gresty, Jo, Melody, Teresa, Monk, Jade, Norman, Chloe, Reeves, Eleanor, Sampson, Julia, Sutton, Peter, Thomas, Marie, Bamford, Amy, Bergin, Colin, Carrera, Ronald, Cooper, Lauren, Despy, Liesl, Ellis, Karen, Fellows, Emma, Goundry, Stephanie, Harkett, Samantha, Ip, Peter, Mason, Tracy, McGhee, Christopher, McLaughlin, Aisling, Neal, Aoife, Pope, Martin, Porter, Stephanie, Smith, Hazel, Snelson, Catherine, Spruce, Elaine, Vigo, Ylenia, Whitehouse, Arlo, Whitehouse, Tony, Donatiello, Maria, Gazzanelli, Sergio, Mezzapesa, Mario, Savino, Martina, Settesoldi, Giacomo, Kunst, Gudrun, Birch, Sian, Greig, Louise, Noble, Harriet, Pappa, Evita, Penhaligon, Bethany, Cossu, Andrea, Floris, Leda, Piredda, Davide, Racca, Alberto, Brattstrom, Olof, Heggelund, Bente, Flodberg, Magnu, Månsson, Sandra, Ahmed, Mamoona, Allen, Jonathan, Bell, Paula, Genetu, Roman, Glennon, Julia, Hanley, Janice, Jenner, Katy, Jogi, Summayyah, Mahjoob, Parisa, McGovern, Clare, Murphy, Anthony, Nazari, Roonak, Routledge, Jacki, Uttamlal, Trishna, Ward, Sinead, Iotti, Giorgio, Picchioni, Raffaella, Poma, Silvia, Navalesi, Paolo, Bruni, Andrea, De Leonardis, Brunella, Garofalo, Eugenio, Patel, Panna, McArthur, Carol, Burns, Karen, Peters, Steven, Foti, Giuseppe, Calcinati, Serena, Grassi, Alice, Villa, Silvia, Berridge, John, Kanakaraj, Muthuraj, Cahill, Hazel, Forshaw, Greg, Gibson, Andy, Grainger, Lia, Howard, Kate, James, Katherine, Murphy, Zoe, Sweeting, Helen, Tait, Rebecca, Wilcock, Danielle, Yates, David, Cope, Sean, Allan, Ashley, Betts, Rebecca, Cornell, Sarah, Sheriff, Julie, Woods, Lindsey, Grasselli, Giacomo, Brioni, Matteo, Castagna, Luigi, von Rahden, Richard, Farina, Zane, Green, Samantha, Gumede, Simphiwe, Rajah, Chantal, Ramkillawan, Arisha, Moug, Susan, Alcorn, David, Dalton, Carol, Dickinson, Natalie, Edwards, Jennifer, Henderson, Steven, McIlveen, Erin, Ramsaran, Richard, Bell, Joanne, Fleming, Lorna, Monks, Kathleen, Parker, Jane, Stamper, Sean, Stokes-Denson, Jo, Elías, Elisa, Guerra, Yessica, Rico-Feijoo, Jesu, Kidel, Carlo, Filipe, Helder, Asis, Gretchelle, Gleeson, Yvonne, Harvey, Alice, Jackson, Christine, McNeil, Margaret, Mingo, Sara, Pakou, Glykeria, Pinto, Manuel, Wright, Stephen, Babio-Galan, Maite, Buckley, David, Calder, Verity, Chishti, Ahmad, Cosgrove, Joseph, Cullen, Katherine, Dunn, Leigh, Faulds, Matthew, Fortune, Jonathan, Gardner, Matthew, Harrison, Abigail, Hays, Carole, Jones, Gerry, Macfie, Caroline, Mccullagh, Iain, Nesbitt, Ian, O'Neil, Suzanne, Phoenix, Catherine, Rangaswamy, Girish, Samson, Craig, Scott, Carmen, Shrestha, Tara, Singh, Rita, Soulsby, Graham, Walton, Jon, Zwiggelaar, Kimberley, Lynch, Ceri, Clarke, Heidi, Deacon, Bethan, Ivatt, Helen, Jones, Leanne, Latif, Ahmed, Oram, Shaun, Perman, Chri, Roche, Lisa, Duys, Rowan, Flint, Margot, Bhagwan, Kamal, Coetzee, Ettienne, Joubert, Ivan, Montoya-Pelaez, Felipe, Navsaria, Pradeep, Picken, Guy, Porrill, Owen, Strathie, Grant, Zungu, Thembinkosi, Aluri, Sireesha, Chau, Simon, Cooper, Deborah, Cunningham, Mishell, Daniels, Allison, Hope, Susan, Nicholson, Alice, Walker, Laura, Giarratano, Antonino, Accurso, Giuseppe, Raineri, Santi, Tricoli, Giuseppe, Innes, Richard, Doble, Patricia, Hutter, Joanne, Pawley, Corinne, Tait, Moira, Hamilton, Mark, Andrade, Edward, Barnes, Veronica, Dalton, Claire, Delgado, Carlo, Farnell-Ward, Sarah, Farrah, Helen, Gray, Geraldine, Howlett, Luisa, Joseph, Gipsy, Krupa, Monika, Leaver, Susannah, Macedo, Joao, Maher, Karen, Mellinghoff, Johanne, Oguntimehin, Rachel, Pereira, Joel, Robinson, France, Ryan, Christine, Shah, Nirav, Shirley, Paula, Torborg, Alexandra, Biyase, Thuli, Drummond, Leanne, Kusel, Belinda, Mbuyisa, Mbalenhle, Solala, Sivuyisiwe, Taylor, Jenna, Ezihe-Ejiofor, Adanma, Aduse-Poku, Maame, Colville, Gary, Davies, Louise, Kang, Soo, Phillips, Alex, Kirk-Bayley, Justin, Kelliher, Leigh, Carvelli, Paula, Daysal, Gokce, Dickinson, Matthew, Doyle, Nancileigh, Hughes, Christina, Montague, Laura, Potter, Elizabeth, Salberg, Armorel, Sibug, Sheena, Sivarajan, Sinduja, Thomson, Milo, Wakeford, Nichola, Rocco, Monica, Alampi, Daniela, Conway, Daniel, Clark, Richard, Maria, Jashmin, Pomeroy, Fiona, Quraishi, Tanviha, Williams, Abigail, Chukkambotla, Srikanth, Aherne, Caroline, Harrison-Briggs, Donna, Fitchett, Jill, Duberley, Stephen, Zanoni, Andrea, Cardinale, Daniela, Righi, Claudia, Blunt, Mark, Fuller, Tracy, Hodgson, Ruth, Rosbergen, Melissa, Brennan, Andrew, Akeroyd, Louise, Boardman, Victoria, Bull, Christopher, Carrick, Mike, Chadderton, Ian, Cooper, Sarah, Goellner, Sarah, Graham, Laura, Ilyas, Carl, King, Jame, Laklouk, Muhammad, Lawton, Tom, Macrow, Christopher, Munro, Michael, Neep, Adam, Northey, Martin, Peacock, Victoria, Pye, Kate, Radley, Lydia, Sira, Jame, Smithson, Beth, Syddall, Stuart, Tooth, David, White, Thoma, Hoel, Sindre, Aakre, Elin, Bakke, Monica, Hoivik, Tone, Makowski, Arystarch, Alcock, Harry, Cardoso, Sean, Coetzee, Samantha, Everett, Mary, Ibrahim, Mohamed, Kouridaki, Christina, Ogbeide, Vongayi, Bertellini, Elisabetta, Bertolotti, Valentina, Buono, Antonio, Fanigliulo, Maria, Kumar, Ram, Richards, Nicole, Allana, Alisha, Bacciarelli, Samantha, Barker, Helen, De Bois, Jessica, Bradley, Isabel, Crooks, Jennifer, Daum, Peter, Feben, Alex, Gannon, Lizzie, Kipling, Sarah, Peetamsingh, Andrew, Quamina, Charlotte, Sethi, Sahiba, Sivadhas, Harry, Sollesta, Kathryn, Swain, Andrew, Tan, Evalyn, Willis, Joan, Zou, Maggie, Cranshaw, Juliu, Barratt, Nina, Bowman, Katie, Branney, Debbie, Letts, Maria, Pitts, Sally, Day, Christopher, Benyon, Sarah, Eddy, Sara, Green, Adam, Grice, Anna, Kelly, Sinéad, Mackle, Daisy, Mariano, Victor, Park, Linda, Sibley, Pauline, Spencer, William, Bignami, Elena, Bellini, Valentina, Forfori, Francesco, Curci, Maria, Leo, Alessandra, Jackson, Matthew, Awolesi, Jennifer, Hodgkinson, Sheila, Kent, Alissa, Leonard, Dee, Stapleton, Claire, Tibke, Clare, Alexander-Sefre, Farhad, Campey, Lorraine, Hall, Kathryn, Spimpolo, Jennifer, Nilsson, Malin, Didriksson, Helen, Hamilton, Emma, Carnahan, Mandy, Mowatt, Chri, Stickley, Jo, Corcione, Antonio, Rossi, Giuseppe, Fladby, Hege, Andersen, Nina, Bjoernå, Gunhild, Reite, Mad, Roertveit, Linda, Seidel, Philipp, Arnold, Glenn, Benavente, Melissa, Chattersingh, Anjalee, Chironga, Nyasha, Hornzee, Gillian, Kibaru, Joyce, Malik, Ihtisham, McLeavy, Laura, Pathmanathan, Byiravey, Prior, Florence, Strudwick, Rhea, Vezyrgiannis, Mario, Sinha, Aneeta, Babu, Sheeba, Batuwitage, Bisanth, Daly, Zoe, Ellinor, Katharine, Hawes, Elizabeth, Holmes, Ann, Hudson, Karen, Nightingale, Jeremy, Le Poidevin, Alison, Roberts, Lindsey, Kubisz-Pudelko, Agnieszka, Allison, Joanna, Pippard, Lucy, Hamlyn, Vincent, Organ, Angie, Prabhahar, Thaventhran, Bridger, Hayley, Dvorkin, Lee, Manhas, Vitul, Vincent, Rachel, Laha, Shondipon, Cromie, Terri-Louise, Doyle, Donna, Howarth, Rachel, Verlander, Mark, Watt, Ailsa, Williams, Alexandra, Antonelli, Massimo, Cutuli, Salvatore, Montini, Luca, Graterol, Juan, Adams, Benita, Bean, Sarah, Burt, Karen, Hammonds, Fiona, Jigajinni, Suyogi, Fulton, Laura, Kinghorn, Stephen, Mullenheim, Jost, Baillie, Kirsty, Cain, Martyn, Colling, Kerry, Hannaway, Carol, Corso, Ruggero, Calli, Morena, Ferrando, Carlo, Romero, Esther, Jorge-Monjas, Pablo, Soria-García, María, Gómez-Herreras, José, Rodríguez-Jiménez, Rita, and De Prada-Martín, Blanca

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_treatment, Population, NO, 03 medical and health sciences, 0302 clinical medicine, CPAP, Abdomen, Settore MED/41 - ANESTESIOLOGIA, Intubation, Intratracheal, medicine, Humans, Intubation, 030212 general & internal medicine, Continuous positive airway pressure, Adverse effect, education, education.field_of_study, Continuous Positive Airway Pressure, business.industry, respiratory complications, continuous positive airway pressure, major abdominal surgery, Pneumonia, Middle Aged, medicine.disease, respiratory tract diseases, Intratracheal, Treatment Outcome, 030228 respiratory system, Respiratory failure, Anesthesia, Vomiting, medicine.symptom, Respiratory Insufficiency, business, Abdominal surgery
Abstract

BackgroundRespiratory complications are an important cause of postoperative morbidity. We aimed to investigate whether continuous positive airway pressure (CPAP) administered immediately after major abdominal surgery could prevent postoperative morbidity.MethodsPRISM was an open-label, randomised, phase 3 trial done at 70 hospitals across six countries. Patients aged 50 years or older who were undergoing elective major open abdominal surgery were randomly assigned (1:1) to receive CPAP within 4 h of the end of surgery or usual postoperative care. Patients were randomly assigned using a computer-generated minimisation algorithm with inbuilt concealment. The primary outcome was a composite of pneumonia, endotracheal re-intubation, or death within 30 days after randomisation, assessed in the intention-to-treat population. Safety was assessed in all patients who received CPAP. The trial is registered with the ISRCTN registry, ISRCTN56012545.FindingsBetween Feb 8, 2016, and Nov 11, 2019, 4806 patients were randomly assigned (2405 to the CPAP group and 2401 to the usual care group), of whom 4793 were included in the primary analysis (2396 in the CPAP group and 2397 in the usual care group). 195 (8·1%) of 2396 patients in the CPAP group and 197 (8·2%) of 2397 patients in the usual care group met the composite primary outcome (adjusted odds ratio 1·01 [95% CI 0·81-1·24]; p=0·95). 200 (8·9%) of 2241 patients in the CPAP group had adverse events. The most common adverse events were claustrophobia (78 [3·5%] of 2241 patients), oronasal dryness (43 [1·9%]), excessive air leak (36 [1·6%]), vomiting (26 [1·2%]), and pain (24 [1·1%]). There were two serious adverse events: one patient had significant hearing loss and one patient had obstruction of their venous catheter caused by a CPAP hood, which resulted in transient haemodynamic instability.InterpretationIn this large clinical effectiveness trial, CPAP did not reduce the incidence of pneumonia, endotracheal re-intubation, or death after major abdominal surgery. Although CPAP has an important role in the treatment of respiratory failure after surgery, routine use of prophylactic post-operative CPAP is not recommended.FundingNational Institute for Health Research, Barts Charity, Intersurgical, Association of Anaesthetists, and Sapienza Università di Roma.

130. Everyone can draw: An inclusive and transformative activity for conceptualization of topographic anatomy.

Author

Horne CA, Hepworth D, Saunders E, and Keenan ID

Subjects
Humans, Female, Male, Young Adult, Models, Anatomic, Adult, Surveys and Questionnaires, Education, Medical, Undergraduate methods, Learning, Comprehension, Femur anatomy & histology, Adolescent, United Kingdom, Curriculum, Concept Formation, Anatomy education, Students, Medical psychology, Students, Medical statistics & numerical data
Abstract

Anatomical drawing traditionally involves illustration of labeled diagrams on two-dimensional surfaces to represent topographical features. Despite the visual nature of anatomy, many learners perceive that they lack drawing skills and do not engage in art-based learning. Recent advances in the capabilities of technology-enhanced learning have enabled the rapid and inexpensive production of three-dimensional anatomical models. This work describes a "drawing on model" activity in which learners observe and draw specific structures onto three-dimensional models. Sport and exercise sciences (SES, n = 79) and medical (MED, n = 156) students at a United Kingdom medical school completed this activity using heart and femur models, respectively. Learner demographics, their perceptions of anatomy learning approaches, the value of the activity, and their confidence in understanding anatomical features, were obtained via validated questionnaire. Responses to 7-point Likert-type and free-text items were analyzed by descriptive statistics and semi-quantitative content analysis. Learners valued art-based study (SES mean = 5.94 SD ±0.98; MED = 5.92 ± 1.05) and the "drawing on model" activity (SES = 6.33 ± 0.93; MED = 6.21 ± 0.94) and reported enhanced confidence in understanding of cardiac anatomy (5.61 ± 1.11), coronary arteries (6.03 ± 0.83), femur osteology (6.07 ± 1.07), and hip joint muscle actions (5.80 ± 1.20). Perceptions of learners were independent of both their sex and their art-based study preferences (p < 0.05). Themes constructed from free-text responses identified "interactivity," "topography," "transformative," and "visualization," as key elements of the approach, in addition to revealing some limitations. This work will have implications for anatomy educators seeking to engage learners in an inclusive, interactive, and effective learning activity for supporting three-dimensional anatomical understanding., (© 2024 The Author(s). Anatomical Sciences Education published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Published
2024
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131. Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells.

Author

Offensperger F, Tin G, Duran-Frigola M, Hahn E, Dobner S, Ende CWA, Strohbach JW, Rukavina A, Brennsteiner V, Ogilvie K, Marella N, Kladnik K, Ciuffa R, Majmudar JD, Field SD, Bensimon A, Ferrari L, Ferrada E, Ng A, Zhang Z, Degliesposti G, Boeszoermenyi A, Martens S, Stanton R, Müller AC, Hannich JT, Hepworth D, Superti-Furga G, Kubicek S, Schenone M, and Winter GE

Subjects
Humans, Ligands, Protein Binding, Proteome metabolism, Ubiquitin-Protein Ligases metabolism, Drug Discovery, Machine Learning, Proteomics methods, Small Molecule Libraries chemistry
Abstract

Chemical modulation of proteins enables a mechanistic understanding of biology and represents the foundation of most therapeutics. However, despite decades of research, 80% of the human proteome lacks functional ligands. Chemical proteomics has advanced fragment-based ligand discovery toward cellular systems, but throughput limitations have stymied the scalable identification of fragment-protein interactions. We report proteome-wide maps of protein-binding propensity for 407 structurally diverse small-molecule fragments. We verified that identified interactions can be advanced to active chemical probes of E3 ubiquitin ligases, transporters, and kinases. Integrating machine learning binary classifiers further enabled interpretable predictions of fragment behavior in cells. The resulting resource of fragment-protein interactions and predictive models will help to elucidate principles of molecular recognition and expedite ligand discovery efforts for hitherto undrugged proteins.

Published
2024
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132. Error reporting in a large animal veterinary teaching hospital identifies medication errors occur most often in the prescribing phase of therapy.

Author

Hepworth-Warren KL, Maynard-Swift E, Prange T, Colwell C, Stallings O, Derks KG, Love K, Hepworth DA, and Marks SL

Subjects
Animals, Humans, Retrospective Studies, Medication Errors veterinary, Patient Safety, Hospitals, Animal, Hospitals, Teaching
Abstract

Objective: To identify the rate at which medication errors occurred over a 2-year period in a large animal veterinary teaching hospital and describe the types of errors that occurred., Sample: 226 medication errors over 6,155 large animal visits occurred during the study period. Multiple errors may have affected the same patient., Methods: Medication error reports from March 1, 2021, to March 31, 2023, were reviewed retrospectively and classified by species, type of drug, and month and day of the week the error occurred. Errors were categorized according to multiple previously developed systems to allow for comparison to other studies., Results: 226 medication errors occurred over 6,155 patient visits in a 2-year period: 57.5% (130/226) were identified by a dedicated large animal pharmacist, and 64.2% (145/226) of errors were identified and corrected before reaching the patient. Prescription/medication order errors (58.4% [132/226]) occurred significantly more often than errors in medication preparation (21.7% [49/226]; P < .001) and administration (19.6%; P < .001). Antibiotics (48.7% [110/226]) and NSAIDs (17.7% [40/226]) were the drug classes most involved in errors., Clinical Relevance: Most medication errors in this study occurred in the ordering/prescribing phase. This is similar to reports in human medicine, where standardized medication error reporting strategies exist. Developing and applying similar strategies in veterinary medicine may improve patient safety and outcome.

Published
2023
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133. Designing small molecules for therapeutic success: A contemporary perspective.

Author

Maurer TS, Edwards M, Hepworth D, Verhoest P, and Allerton CMN

Subjects
Drug Design
Abstract

Successful small-molecule drug design requires a molecular target with inherent therapeutic potential and a molecule with the right properties to unlock its potential. Present-day drug design strategies have evolved to leave little room for improvement in drug-like properties. As a result, inadequate safety or efficacy associated with molecular targets now constitutes the primary cause of attrition in preclinical development through Phase II. This finding has led to a deeper focus on target selection. In this current reality, design tactics that enable rapid identification of risk-balanced clinical candidates, translation of clinical experience into meaningful differentiation strategies, and expansion of the druggable proteome represent significant levers by which drug designers can accelerate the discovery of the next generation of medicines., Competing Interests: Declaration of Interests C.M.N.A., D.H., T.S.M., and P.V. are employed by Pfizer Inc., M.E. was previously employed by Pfizer Inc., and some or all may hold Pfizer shares., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2022
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134. Corrigendum: The promise and peril of chemical probes.

Author

Arrowsmith CH, Audia JE, Austin C, Baell J, Bennett J, Blagg J, Bountra C, Brennan PE, Brown PJ, Bunnage ME, Buser-Doepner C, Campbell RM, Carter AJ, Cohen P, Copeland RA, Cravatt B, Dahlin JL, Dhanak D, Edwards AM, Frederiksen M, Frye SV, Gray N, Grimshaw CE, Hepworth D, Howe T, Huber KV, Jin J, Knapp S, Kotz JD, Kruger RG, Lowe D, Mader MM, Marsden B, Mueller-Fahrnow A, Müller S, O'Hagan RC, Overington JP, Owen DR, Rosenberg SH, Ross R, Roth B, Schapira M, Schreiber SL, Shoichet B, Sundström M, Superti-Furga G, Taunton J, Toledo-Sherman L, Walpole C, Walters MA, Willson TM, Workman P, Young RN, and Zuercher WJ

Published
2015
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135. The promise and peril of chemical probes.

Author

Arrowsmith CH, Audia JE, Austin C, Baell J, Bennett J, Blagg J, Bountra C, Brennan PE, Brown PJ, Bunnage ME, Buser-Doepner C, Campbell RM, Carter AJ, Cohen P, Copeland RA, Cravatt B, Dahlin JL, Dhanak D, Edwards AM, Frederiksen M, Frye SV, Gray N, Grimshaw CE, Hepworth D, Howe T, Huber KV, Jin J, Knapp S, Kotz JD, Kruger RG, Lowe D, Mader MM, Marsden B, Mueller-Fahrnow A, Müller S, O'Hagan RC, Overington JP, Owen DR, Rosenberg SH, Roth B, Ross R, Schapira M, Schreiber SL, Shoichet B, Sundström M, Superti-Furga G, Taunton J, Toledo-Sherman L, Walpole C, Walters MA, Willson TM, Workman P, Young RN, and Zuercher WJ

Subjects
Biomedical Research instrumentation, Humans, Intellectual Property, Internet, Molecular Probes pharmacology, Molecular Weight, Sensitivity and Specificity, Small Molecule Libraries pharmacology, Biomedical Research methods, Information Dissemination ethics, Molecular Probes chemistry, Small Molecule Libraries chemistry
Published
2015
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136. Shaping a screening file for maximal lead discovery efficiency and effectiveness: elimination of molecular redundancy.

Author

Bakken GA, Bell AS, Boehm M, Everett JR, Gonzales R, Hepworth D, Klug-McLeod JL, Lanfear J, Loesel J, Mathias J, and Wood TP

Subjects
Computer Simulation, Drug Design, Models, Molecular, Probability, Quantitative Structure-Activity Relationship, Algorithms, Drug Discovery, Small Molecule Libraries chemistry
Abstract

High Throughput Screening (HTS) is a successful strategy for finding hits and leads that have the opportunity to be converted into drugs. In this paper we highlight novel computational methods used to select compounds to build a new screening file at Pfizer and the analytical methods we used to assess their quality. We also introduce the novel concept of molecular redundancy to help decide on the density of compounds required in any region of chemical space in order to be confident of running successful HTS campaigns.

Published
2012
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137. Variations in the morphology of wood structure can explain why hardwood species of similar density have very different resistances to impact and compressive loading.

Author

Hepworth DG, Vincent JF, Stringer G, and Jeronimidis G

Subjects
Absorption, Cellulose ultrastructure, Hardness, Microfibrils ultrastructure, Microscopy, Electron, Scanning Transmission, Tensile Strength, Water chemistry, Cellulose chemistry, Stress, Mechanical, Wood
Abstract

A clear relationship has been established between the impact resistance and density of softwoods. However, there are hardwood species that have the same density but very different impact resistance. Softwoods are largely composed of tracheid cells (30-50 microm across); hardwoods have smaller fibre cells and also contain vessels (50-500 microm across). We examined white oak, beech, hickory and spruce. Compressive deformation was identified as the main mechanism for energy absorption in the type of impact test used. The disparate size of different wood cells in the hardwoods results in heterogeneous compressive deformation. During compression, large vessels cause smaller surrounding cells to be deformed more than in regions without vessels, increasing the energy absorbed. However, vessels that are too close together initiate kink banding at low loads and less energy is absorbed. The different morphologies of hardwoods are probably responsible for the variation in impact resistance between species of similar density. Drilling small holes along the grain of spruce, which naturally lacks vessels, mimicked the effect of vessels and did not reduce the energy-absorbing capabilities of the wood, despite the density being reduced. These findings could be used to increase the energy-absorbing capacity of synthetic foam materials.

Published
2002
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138. The Chemistry and Biology of Alkannin, Shikonin, and Related Naphthazarin Natural Products.

Author

Papageorgiou VP, Assimopoulou AN, Couladouros EA, Hepworth D, and Nicolaou KC

Abstract

Wound healing properties of plant extracts that contain the naphthoquinone natural products alkannin (1) and shikonin (2) have been known for many centuries. More recently, the biological properties of 1, 2, and related derivatives have been demonstrated experimentally, and their production both by cell cultures and chemical synthesis has been studied extensively., (© 1999 WILEY-VCH Verlag GmbH, Weinheim, Fed. Rep. of Germany.)

Published
1999
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139. Concise and Efficient Total Syntheses of Alkannin and Shikonin.

Author

Nicolaou KC and Hepworth D

Abstract

Two enantiomic natural products with wound-healing properties, alkannin (1) and shikonin (2), are accessible by a short and efficient total synthesis. The success was achieved by a novel protecting system for masking of 5,8-dihydroxy-1,4-naphthoquinones (naphthazarins) and a highly stereoselective ketone reduction., (© 1998 WILEY-VCH Verlag GmbH, Weinheim, Fed. Rep. of Germany.)

Published
1998
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