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1. A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts

Author

Andrew D. Gillie, Matthew G. Wakeling, Bethan L. Greene, Louise Male, and Paul W. Davies

Subjects
annulation, carbene, gold, imidazolium, nhc, Science, Organic chemistry, QD241-441
Abstract

A polysubstituted 3-aminoimidazo[5,1-b]oxazol-6-ium framework has been accessed from a new nitrenoid reagent by a two-step ynamide annulation and imidazolium ring-formation sequence. Metalation with Au(I), Cu(I) and Ir(I) at the C2 position provides an L-shaped NHC ligand scaffold that has been validated in gold-catalysed alkyne hydration and arylative cyclisation reactions.

Published
2024
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2. Isotopic labelling studies for a gold-catalysed skeletal rearrangement of alkynyl aziridines

Author

Paul W. Davies, Nicolas Martin, and Neil Spencer

Subjects
1,2-aryl shift, cycloisomerisation, gold, isotopic labelling, pyrrole, skeletal rearrangement, Science, Organic chemistry, QD241-441
Abstract

Isotopic labelling studies were performed to probe a proposed 1,2-aryl shift in the gold-catalysed cycloisomerisation of alkynyl aziridines into 2,4-disubstituted pyrroles. Two isotopomers of the expected skeletal rearrangement product were identified using 13C-labelling and led to a revised mechanism featuring two distinct skeletal rearrangements. The mechanistic proposal has been rationalised against the reaction of a range of 13C- and deuterium-labelled substrates.

Published
2011
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3. Synthesis of α-tertiary primary amines and 1,2-amino alcohols from vinyl azides by light induced denitrogenative alkylarylation/dialkylation

Author

Wei Shu, Sifan Li, Hai-Wu Du, and Paul W. Davies

Abstract

Sterically congested α-tertiary primary amines are ubiquitous substructures in pharmaceutical and agrochemical agents yet are challenging to access. Herein, a straightforward photoredox-catalyzed access to structurally diverse α,α,α-trisubstituted primary amines from denitrogenative alkylarylation or dialkylation of vinyl azides with NHPI esters and cyanoarenes or aryl aldehydes has been developed. The use of vinyl azides as a precursor of primary amines was enabled by the dual role of Hantzsch ester to form electron donor-acceptor (EDA) complexes and to serve as a sacrificial reductant. This strategy provides a modular synthesis of α-tertiary primary amines, including unprotected 1,2-amino alcohols, from simple materials with excellent functional group tolerance. The synthetic applicability of this method was demonstrated by streamlined access to 2,2-disubstituted tetrahydroquinolines. Preliminary investigations support two parallel reductive photocatalytic cycles allowing for the denitrogenative alkylarylation or dialkylation of vinyl azides via decarboxylative radical addition followed by hetero-radical cross-coupling between α-amino radicals and aryl anion radicals or ketyl anion radicals.

Published
2023
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4. Gold‐Catalyzed Annulations with Nucleophilic Nitrenoids Enabled by Heteroatom‐Substituted Alkynes

Author

Paul W. Davies

Subjects
chemistry.chemical_classification, Annulation, 010405 organic chemistry, General Chemical Engineering, Nitrene, Alkyne, Context (language use), General Chemistry, 010402 general chemistry, Triple bond, 01 natural sciences, Biochemistry, Combinatorial chemistry, 0104 chemical sciences, chemistry.chemical_compound, chemistry, Nucleophile, Materials Chemistry, Carbenoid, Oxazole
Abstract

The combination of a nucleophilic nitrene equivalent, a triple bond and a π-acid catalyst has underpinned numerous efficient transformations for the preparation of azacycles. This personal account details our efforts in developing an annulation strategy. Adding a nucleophilic nitrenoid to an activated alkyne can generate carbenoid character that is then quenched by a cyclisation onto the nitrenoid substituent. The use and development of N-acyl and N-heterocyclic pyridinium-N-aminides as 1,3-N,O and 1,3-N,N-dipole equivalents is discussed in the context of oxazole and heterocycle-fused imidazole formation, respectively. The resulting processes are highly efficient, practically straightforward, and tolerate considerable structural and functional group variation. Our use of heteroatom-substituted alkynes as enabling tools for reaction discovery is discussed. The reactivity accessed from the strong donor-like properties of ynamides is complemented by that obtained from alkynyl thioethers, which are emerging as interesting substrates for π-acid catalysis.

Published
2021
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5. A Radical-Initiated Fragmentary Rearrangement Cascade of Ene-Ynamides to [1,2]-Annulated Indoles via Site-Selective Cyclization

Author

Wei Shu, Weiliang Shi, Yibo Lei, Yu Wang, Zi-Bo Wu, Paul W. Davies, and Sifan Li

Subjects
chemistry.chemical_compound, Cascade reaction, Chemistry, Stereochemistry, Aryl, Organic Chemistry, Intramolecular cyclization, Site selective, Rapid access, Physical and Theoretical Chemistry, Bond formation, Biochemistry, Ene reaction
Abstract

Straightforward access to [1,2]-annulated indoles, key substructures in natural products, is highly desirable yet challenging. Herein, a radical triggered fragmentary cyclization cascade reaction of ene-ynamides is presented, providing a rapid access into [1,2]-annulated indoles by an intermolecular radical addition, intramolecular cyclization, desulfonylative aryl migration, and site-selective C(sp2)-N cyclization sequence. DFT calculations support oxidation of N-centered radical species to cations prior to the C-N bond formation, followed by an unusual aza-Nazarov cyclization.

Published
2021
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6. Gold(I)-Catalyzed Synthesis of 3-Sulfenyl Pyrroles and Indoles by a Regioselective Annulation of Alkynyl Thioethers

Author

Paul W. Davies, Peter E. Simm, Prakash Sekar, and Jeffery Richardson

Subjects
Annulation, Letter, 010405 organic chemistry, Chemistry, Regioselectivity, Heterocycle synthesis, General Chemistry, gold, nitrenoid, 010402 general chemistry, annulation, 01 natural sciences, Combinatorial chemistry, Catalysis, thioether, 0104 chemical sciences, chemistry.chemical_compound, Nucleophile, indole, pyrroles, Structural isomer, Isoxazole
Abstract

The combination of nucleophilic nitrenoids and π-acid catalysis has emerged as a powerful tool in heterocycle synthesis. Accessing more varied heterocycle-substitution patterns by maintaining the same reaction pathways across different alkynes remains a challenge. Here we show that Au(I) catalysis of isoxazole-based nitrenoids with alkynyl thioethers provides controlled access to (3 + 2) annulation by a regioselective addition β to the sulfenyl group. The reaction with isoxazole-containing nitrenoids delivers sulfenylated pyrroles and indoles as single regioisomers bearing useful functional groups and structural variety.

Published
2021

7. Gold-Catalysed Cycloisomerisation of Ynamides To Access 2,2-Disubstituted Tetrahydrothiophene Motifs

Author

Parmjit Heer Kaur and Paul W. Davies

Subjects
chemistry.chemical_compound, chemistry, 010405 organic chemistry, Organic Chemistry, Regioselectivity, Sulfoxide, 010402 general chemistry, 01 natural sciences, Tetrahydrothiophene, Combinatorial chemistry, Isomerization, 0104 chemical sciences
Abstract

Ynamides bearing a tethered allyl sulfoxide undergo a gold-catalysed cycloisomerisation to afford tetrahydrothiophene-2-carboxamides and their benzo-fused analogues. The reactions are initiated by a formal 7-endo-dig cyclisation and accommodate a range of different substituents. The use of N-allyl ynamides provided a route into novel spirocyclic ε-lactam structures.

Published
2021
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8. Gold-Catalyzed Intermolecular Alkyne Oxyarylation for C3 Functionalization of Benzothiophenes

Author

Paul W. Davies, Richard S. Grainger, and Paige A Rist

Subjects
chemistry.chemical_classification, 010405 organic chemistry, Chemistry, Aryl, Organic Chemistry, Alkyne, Regioselectivity, Benzothiophene, Sulfoxide, 010402 general chemistry, 01 natural sciences, Biochemistry, Combinatorial chemistry, 0104 chemical sciences, Catalysis, chemistry.chemical_compound, Surface modification, Physical and Theoretical Chemistry, Alkyl
Abstract

C3-selective C-C bond formation on benzothiophenes is challenging, and few direct functionalization methods are available. A gold-catalyzed reaction of alkynes with benzothiophene S-oxides provides regioselective entry into C3-alkylated benzothiophenes with the C7-alkylated isomer as the minor product. This oxyarylation reaction works with alkyl and aryl alkynes and substituted and unsubstituted benzothiophenes. Mechanistic studies identify that sulfoxide inhibits the catalyst [DTBPAu(PhCN)]SbF6, which also degrades and forms the unreactive complex [(DTBP)2Au]SbF6.

Published
2021
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9. Modular synthesis of α-arylated carboxylic acids, esters and amides

Author

Sifan, Li, Paul W, Davies, and Wei, Shu

Abstract

α-Arylated carboxylic acids, esters and amides are widespread motifs in bioactive molecules and important building blocks in chemical synthesis. Thus, straightforward and rapid access to such structures is highly desirable. Here we report an organophotocatalytic multicomponent synthesis of α-arylated carboxylic acids, esters and amides from exhaustive defluorination of α-trifluoromethyl alkenes in the presence of alkyltrifluoroborates, water and nitrogen/oxygen nucleophiles. This operationally simple strategy features a unified access to functionally diverse α-arylated carboxylic acids, esters, and primary, secondary, and tertiary amides through backbone assembly from simple starting materials enabled by consecutive C-F bond functionalization at room temperature. Preliminary mechanistic investigations reveal that the reaction operates through a radical-triggered three-step cascade process, which involves distinct mechanisms for each defluorinative functionalization of the C-F bond.

Published
2022

12. Diagnostic accuracy and added value of qualitative radiological review of 1H-magnetic resonance spectroscopy in evaluation of childhood brain tumors

Author

Adam Oates, Benjamin Pinkey, Karen A Manias, Ben Babourina-Brooks, Simrandip K. Gill, Martin Wilson, Andrew C. Peet, Paul W. Davies, Lesley MacPherson, Nigel P. Davies, and Niloufar Zarinabad

Subjects
medicine.medical_specialty, medicine.diagnostic_test, business.industry, Medicine (miscellaneous), Diagnostic accuracy, Magnetic resonance imaging, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Radiological weapon, medicine, Histopathology, Radiology, Stage (cooking), Medical diagnosis, Radiation treatment planning, Prospective cohort study, business, 030217 neurology & neurosurgery
Abstract

Background 1H-magnetic resonance spectroscopy (MRS) facilitates noninvasive diagnosis of pediatric brain tumors by providing metabolite profiles. Prospective studies of diagnostic accuracy and comparisons with conventional MRI are lacking. We aimed to evaluate diagnostic accuracy of MRS for childhood brain tumors and determine added clinical value compared with conventional MRI. Methods Children presenting to a tertiary pediatric center with brain lesions from December 2015 through 2017 were included. MRI and single-voxel MRS were acquired on 52 tumors and sequentially interpreted by 3 radiologists, blinded to histopathology. Proportions of correct diagnoses and interrater agreement at each stage were compared. Cases were reviewed to determine added value of qualitative radiological review of MRS through increased certainty of correct diagnosis, reduced number of differentials, or diagnosis following spectroscopist evaluation. Final diagnosis was agreed by the tumor board at study end. Results Radiologists’ principal MRI diagnosis was correct in 69%, increasing to 77% with MRS. MRI + MRS resulted in significantly more additional correct diagnoses than MRI alone (P = .035). There was a significant increase in interrater agreement when correct with MRS (P = .046). Added value following radiologist interpretation of MRS occurred in 73% of cases, increasing to 83% with additional spectroscopist review. First histopathological diagnosis was available a median of 9.5 days following imaging, with 25% of all patients managed without conclusive histopathology. Conclusions MRS can improve the accuracy of noninvasive diagnosis of pediatric brain tumors and add value in the diagnostic pathway. Incorporation into practice has the potential to facilitate early diagnosis, guide treatment planning, and improve patient care.

Published
2019
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13. Synthesis of N ‐Acyl Pyridinium‐ N ‐Aminides and Their Conversion to 4‐Aminooxazoles via a Gold‐Catalyzed Formal (3+2)‐Dipolar Cycloaddition

Author

Matthew P. Ball‐Jones, Paul W. Davies, Manuela Brütsch, Estíbaliz Merino, and Cristina Nevado

Subjects
chemistry.chemical_compound, chemistry, 010405 organic chemistry, Pyridinium, 010402 general chemistry, 01 natural sciences, Medicinal chemistry, Cycloaddition, 0104 chemical sciences, Catalysis
Published
2019
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15. Evaluation of the added value of 1H-magnetic resonance spectroscopy for the diagnosis of pediatric brain lesions in clinical practice

Author

Ina Nicklaus-Wollenteit, Simrandip K. Gill, Daniel Ford, Lesley MacPherson, Adam Oates, Jenny Adamski, Paul W. Davies, Martin Wilson, Niloufar Zarinabad, Guirish A. Solanki, Martin English, Karen A Manias, and Andrew C. Peet

Subjects
Pediatrics, medicine.medical_specialty, magnetic resonance imaging (MRI), Medicine (miscellaneous), metabolite profiles, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Biopsy, medicine, Medical diagnosis, Radiation treatment planning, 1H magnetic resonance spectroscopy (MRS), medicine.diagnostic_test, business.industry, pediatric brain tumors, Magnetic resonance imaging, Original Articles, Clinical Practice, Mri diagnosis, Pediatric brain, Histopathology, Radiology, noninvasive diagnosis, business, 030217 neurology & neurosurgery
Abstract

Background Magnetic resonance spectroscopy (MRS) aids noninvasive diagnosis of pediatric brain tumors, but use in clinical practice is not well documented. We aimed to review clinical use of MRS, establish added value in noninvasive diagnosis, and investigate potential impact on patient care. Methods Sixty-nine children with lesions imaged using MRS and reviewed by the tumor board from 2014 to 2016 met inclusion criteria. Contemporaneous MRI diagnosis, spectroscopy analysis, histopathology, and clinical information were reviewed. Final diagnosis was agreed on by the tumor board at study end. Results Five cases were excluded for lack of documented MRI diagnosis. The principal MRI diagnosis by pediatric radiologists was correct in 59%, increasing to 73% with addition of MRS. Of the 73%, 19.1% (95% CI, 9.1%-33.3%) were incorrectly diagnosed with MRI alone. MRS led to a significant improvement in correct diagnosis over all tumor types (P = .012). Of diagnoses correctly made with MRI, confidence increased by 37% when adding MRS, with no patients incorrectly re-diagnosed. Indolent lesions were diagnosed noninvasively in 85% of cases, with MRS a major contributor to 91% of these diagnoses. Of all patients, 39% were managed without histopathological diagnosis. MRS contributed to diagnosis in 68% of this group, modifying it in 12%. MRS influenced management in 33% of cases, mainly through avoiding and guiding biopsy and aiding tumor characterization. Conclusion MRS can improve accuracy and confidence in noninvasive diagnosis of pediatric brain lesions in clinical practice. There is potential to improve outcomes through avoiding biopsy of indolent lesions, aiding tumor characterization, and facilitating earlier family discussions and treatment planning.

Published
2017
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16. Balancing Bulkiness in Gold(I) Phosphino-triazole Catalysis

Author

Benjamin R. Buckley, Tze Jing Sum, Huy V. Nguyen, Paul W. Davies, Fernanda Meloni, John S. Fossey, Yiming Zhao, and Matthew G. Wakeling

Subjects
chemistry.chemical_classification, Triazole, Alkyne, Chloride, Catalysis, chemistry.chemical_compound, chemistry, Phosphorus atom, Polymer chemistry, medicine, Click chemistry, Single crystal, Phosphine, medicine.drug
Abstract

A series of phosphino triazoles are disclosed, within which, the phosphorus atom is appended by one, two or three triazole motifs. Gold(I) chloride complexes of the synthesised ligands were prepared and analysed by techniques including single crystal X-ray diffraction structure determination. SambVca (2.0) was used to determine percentage buried volumes. The effectiveness of these gold(I) chloride complexes to serve as precatalysts for alkyne hydration were assessed.

Published
2019
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17. Diastereoselective sulfur ylide rearrangements from gold catalyzed oxidation of ynamides

Author

Joshua D. Priest, Louise Male, and Paul W. Davies

Subjects
chemistry.chemical_classification, 010405 organic chemistry, Chemistry, Sulfonium, Organic Chemistry, chemistry.chemical_element, Substrate (chemistry), 010402 general chemistry, 01 natural sciences, Biochemistry, Sulfur, Combinatorial chemistry, 0104 chemical sciences, Catalysis, chemistry.chemical_compound, Ylide, Drug Discovery, Allyl Sulfide
Abstract

The [2,3]-sigmatropic rearrangement of sulfonium ylides bearing substituted allyl groups creates two contiguous stereocentres. Low diastereoselectivity is typically observed from commonly used α-diazocarboxylic ester precursors. High diastereoselectivity was previously revealed in a gold-catalyzed multicomponent route into allyl sulfonium ylides by reaction of ynamide, oxidant and allyl sulfides. The effect of substrate modifications on the diastereoselectivity have been studied, with N-phenyl methanesulfonamide derived ynamides proving the most effective. This report includes an enhanced experimental procedure, and a demonstration that the gold-catalyzed process remains highly effective at −78 °C.

Published
2021
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18. A Gold Carbene Manifold to Prepare Fused γ-Lactams by Oxidative Cyclisation of Ynamides

Author

Fernando, Sánchez-Cantalejo, Joshua D, Priest, and Paul W, Davies

Subjects
ynamide, oxidation, Communication, Cyclisation, γ-lactam, gold, Communications
Abstract

Gold‐catalysed oxidative cyclisation reactions of ynamides offer great promise in γ‐lactam synthesis but are limited by preferential over‐oxidation to form α‐keto imides. Evaluating the factors that might limit N‐cyclisation pathways led to effective gold‐catalysed conditions that allow access to different fused γ‐lactams on changing the ynamide N‐substituent and accommodate previously incompatible substitution patterns. New and efficient methods for the synthesis of functionalised 3‐aryl indoles and cyclohepta[c]pyrrol‐1‐one derivatives are presented. These conditions illustrate the complementarity of gold catalysis to other metals.

Published
2018

19. Cancelled operations: a 7-day cohort study of planned adult inpatient surgery in 245 UK National Health Service hospitals

Author

Jennifer Morrish, Emily J Robson, Georgina Ashfield, Karuna Kotur, Jashmin Maria, Charlotte Downes, Shweta Patro, Mark Scrutton, George Gladstone, Andy Burton, Paula Mulligan, Wei Lin Allen, Michael McCusker, Dee Leonard, James Edwards, Sarah Dolling, Katherine Pass, Hywel Garrard, Francis Young, Paul Edgar, Elaine Matthews, Douglas Findlay, Helen Whittle, Aillison MacLean, Chris Levett, Claire-Marie Agius, Kim Porter, Nurse Charlotte White, Bridget Campbell, Gemma Scotland, Patrick Haywood, Liz Shenton, Tom Hatton, Laura McAffrey, Jane Hunt, Jaime Carungcong, Sara Owen, Fiona Christie, Lesley Milne, Liza Tharakan, Ruth Smith, Henry Nash, Timothy Gould, Jodie Fitzgerald, Wael Zghaibe, Mark Gaskell, Dushyanthi Jayasekera, Elana Owen, Kinga Dwornik, Amr Ali, Donna Cotterill, Martyn Cain, Peter Wicks, Daniel West, Catriona Walker, Rebecca Lee, Amanda Isaac, Naresh Rajasekar, Sally Collins, Laura Hammon, Tim Hendra, Yemi Adelaja, Mike Pollard, Ellen L. Brown, Matt Clayton, Rachel Bown, Sally Moore, Keyury Desai, Tony Kinsey, Charlotte Dunn, Li Lian Loh, Emelia Passaro, Timothy Faccini, Stephen Linter, Sumant Shanbhag, David Lee, David Restall, Angela Cook, Simon Ripoll, Rachael Bird, Vicky Murray, Alex Wollaston, Daniel Yarwood, Sonia Bhangu, Sahar Biuk, Jenny Ferry, Alexander Michael Stewart, Ceri Lynch, Lucy Sheppard, Denise Webster, Jamie Allen, Merle Cohen, James Hanison, Shilpa Rawat, Prabhakaran Premraj, Gamunu Ratnayake, Clare Bird, Lorna Filby, Clare Allcock, Babak Sedghi, Celly Weegenaar, Dawn Collier, Sreekanth Rayalu Uppugonduri, Amanda Whileman, Su Ying Ong, Jack Carmichael, Victoria O'Loughlin, Barbara Linklater-Jones, Maria Lackmann, Vitul Manhas, Albert Brennan, Alasdair Waite, Andrew Smallwood, Salvatore Bruni, Catriona Barr, Thomas Murphy, Gemma Hudson, Khalid Hasan, Alison J. Campbell, Radu Chiravasuta, Charlotte Maden, Roddy Chapman, Jon Clark, Nauman Iftikhar, Sarah Hagyard, Denis O'Leary, Steven Forde, Joanne Webb, Ryan W Haines, Andrea Galloway, Richard Siviter, Heidi Lightfoot, Hew D.T. Torrance, Christopher Smith, Hollie Robinson-Perrie, Josh Wall, Carina Cruz, Andrew Song, Stephen T. Webb, Nurse Sara-Beth Sutherland, Carol-Ann Woolley, Susan Martin, S.L.M. Walker, George Koshy, Renee Ford, Mona Mubarak, Robert Stuart, Keshava Reddy Burijinti Chenna, Rizana Ghafoor, Katie Hanlon, Fiona Faulds, Hiba Khaled, Richard Jones, Karin Duckett, Cathryn Matthews, Charles Chan, Sanjeewa Ranaweera, Nurse Rebecca Hinch, Richard Shawyer, Jo Cudlip, Marion Ashe, Steve Harris, Ravi K. Alagar, Jonathan Hetherington, Sara Churchill, Yolanda Baird, Maria Tritean, Gabriela Wong, Dermot Moloney, Lee Tbaily, Jonathan Finnity, Norbert Bokor, Peter Indoe, Lucy Stelfox, Simon Marcus, Bryony Burrill, Ellie Roderick, Carina Lilley, Alex Yusaf, Lucy Corbett, Esther Neilly, Christine Ryan, Amon Wijunamai, Katie Atterbury, Abigail Clarke, Josh Patch, Otto Mohr, Ronan Mukherjee, Asokan Krishnaier, Chen Yun-Han, Prasan Panagoda, Polly Rice, Katherine Jones, James Hudson, Sophie Uren, Peter Sutton, Evangelia Poimenidi, Tracy Marsden, Veronica Barnes, Alice Drysdale, Tara Lawrence, Lisa Sharpe, John G. Francis, N. M. Wharton, Claire Kurasz, Marina Iaverdino, Caradog Thomas, Emma Gold, Raj McNab, Tom E.F. Abbott, Claire Dowse, Jane Hamilton, Tony Sutherland, Robert P. Jones, Peter Alston, Daniel Haslam, Philippa Marshall, Bernadette Tilley, Cathleen Chabo, Adam Carpenter, Steve Cole, Nicholas Hooper, Kate Arrow, Alka Shah, Rosie Furness, Susie Chapman, Sachini Dhamaratne, Constandinos Papageorgiou, Michael Girgis, Sandra Pearson, Andrew W. Wood, Jaya Nariani, Sonia White, Christopher Godden, Mary Bellamy, Indra Chadbourn, Laura Parker, Peter Knowlden, Cat Griffiths, Jeanette Smith, David Brooks, Jonathan Smith-Williams, Elizabeth Barnes, Sunil Jamadarkhana, Andrew Feneley, Maria Croft, Tom Disney, Paramesh Kumara, Anna Warrington, Seetal Aggarwal, Zackriah Badsha, Suman Biswas, Suzanne Shuttleworth, Ben Jones, Jose Lourtie, Mark Stubbington, Asya Mussad, Patrick Johnson, Sister Amanda Cowton, James Spargo, Kelly Hard, Annette Fraine, William Weston, Farrukh Ameer, Andrew Prenter, Lisa Bacon, Sunil kumar Chaurasia, Claire Nicholas, Amy Kitching, Sneha Prasad, Catriona Ferguson, Martin P. Huntley, Claire Cameron, Hugh Cutler, Anne Harrison, Kunal Joshi, Anna Cormack, Rebecca Jones, Martin Paul, Jean Bage, Stephen Cole, Usman Razaque, Robert Lewis, David O'Callaghan, Samantha Strong, Victoria Frost, Peter Ip, Victoria Male, Mat Molyneux, Christopher Worth, Michael Brett, Megan Smith, Shayan Arshed, Timothy McMillan, Lorri James, Frances Lay, Jennifer Bennett-Britton, Patrick Colhoun, Alison Shaw, Michael Stewart, Maie Templeton, Karin Gupwell, Mujeeb Khan, Elena Stanton, Chandini Chuni, Janette Brown, Mariam Latif, Rebecca L. Wilson, Felix Fombon, Jo Novaga, Cindy Persad, Matthew Thomas, Maryna Garmash, Metod Oblak, Sarah Maher, Rahul Muddanyake, Morgan Foster, Kris Parker, Tim Sutton, Ndi Ekwere, Samuel Armanious, Mohammad Bhatti, Steve Phillips, Maria Rivero-Bosch, Nick Spittle, David Harding, Henry Hammerbeck, Rose Buckley, Jonathan Hatton, Ahmed Gilani, Ali Watts, Neeraj Bhardwaj, Lesley McShane, Simon Ridler, Martin Murphy, Vandana Goel, S Ramani Moonesinghe, Sophie Scutt, Sanniah Hussain, Hannah Donaldson, Tom Bennett, Helen Boys, David Steven Davies, Bev Hammond, Bryan Yates, Victoria Hawley, Chris Gibb, Ulrika Winstone, Keith Couper, Benedict Williams, Louise Duncan, Georgina Wilson, Anil Hormis, Emily Dana, Jens Full, Amina Chohan, Amanda Ebejer, Sian McKillop, Tomas Bakonyi, Georgina Bird, George Davies, Christina Penny, Helen Thornley, Karen Jewers, Kingsin Ang, Mishell Cunningham, Conny Blunt, Ronald Carrera, Kay Finney, Alvin Soosay, Nagaraj Rao, Jason Mann, Carol Edwards, Richard Lowe, Paul Stevens, Hilary Ashton, Rachel Codling, Rhys Davies, Muthuraj Kanakaraj, Zoe Apple, Kirsty Meats, Tammy Smith, Charmaine Beirnes, John Gardner, Peter Featherstone, Claire Williams, Rohit Mittal, Emma Shinn, Alex Moore, Michael Whitear, Hannah Rose, Paul Kelly, Megan Thomas, Matthew Gibbins, Jack Reid, Caroline Clarke, Victoria Irvine, Bhavesh Pratap, Ella Buchanan, Nurse Francesca Wright, Vatsharlan Santhirapala, Richard Gould, Dionne Dervin, Behzad Sohail, Lauren Duraman, Thecla Scully, Adnaan Qureshi, Muditha Peiris, Thomas Ratcliffe-Law, Samuel J. Clark, Ben Vowles, Sam Keable, Hoda Abou Ghoneim, Becky Morris, Aidan Hulbert, Rachael Craven, Ashish Kundu, Emma M. Casely, Maya Kommer, Tom Poulton, Greg Nussbaum, Ahmad Huda, Caroline Davis, Suzanne Gleeson, Paul Clements, Matt Willis, Isobel Amey, David J. Perry, Rachel Harford, Bianca Hulance, Kirsty Baron, Charlotte Grove, Sergio Dominguez, Susanna Richie-Mclean, John Stones, Ioana Simionescu, Khaled Razouk, Cristina Niciu, Ben Hyams, Mark Doran, Carolyn Colvin, Jonathan Rivers, Raluca Ene, Rebecca Jackson, Jonathan Edgar, Ben Robinson, Lisa Wilkinson-Guy, Aji Mathew, Christopher Patrick, Gauhar Sharih, Ismail Tariq, Andrea Kay, Joshua O'Donnell, Dafydd Watterson, Lail Zaheer, Fiona Reed, Tom Johnson, Christopher Oscier, Mirain Phillips, Edmund Gerrans, Joanna Hackney, Sally M. Dunlop, Elizabeth Willetts, Jiang Yuchen, Lizzie Ashton, Theresa Cooper, Paul W. Davies, Carly Brown, James Small, Julie Lowe, Amarjeet Patil, Filipe Helder, Joshua Cuddihy, Faisal Sheikh, Hayley Tarft, Enid Leung, Adrian Percuin, Paolo Mazzone, Rochelle Rhodes, Jane Pilsbury, Kerry Cullis, Peter Brook, Helen McNamara, Carin Swanevelder, Claire Frith, Adrian Clarke, Stuart Watson, Glenn Vetuz, Zoe Riddell, Drew Welch, Geoff Warnock, Lalani Induruwage, Paul Mallett, Elizabeth Cervi, Santinder Dalay, Supriya Antrolikar, Sinead O'Kane, Toby Hoskins, Stephen Duberley, Sophie Parcell, Jayne Sutherland, Lynn Fairless, Dave Parkinson, Matron Beryl Davis, Abigail Patrick, Jithu Jayan, Nicola Harvey, Catherine Pitman, Donata Banni, Samuel Passey, Omar Alex Pemberton, Becky Sands, Hon Sum Liu, Alexandra Mudd, Sheldon Zhang, Ange Lise John-Baptiste, Thomas Clayton, Charlotte Marriot, Tom Reevell, Nicola Mackenzie, Temitope Aiyedun, Andy Cruickshanks, Jacqueline Gunn, Alison Moss, Martyn Clark, Swetha Rambhatla, Claire Matata, Ben Cracknell, Pauline Mercer, Matthew Morgans, Catrin Williams, Shareef Madhi, Jane Montgomery, George Kohler, Yasir Hameed, Muneeba Ahmed, Glenn Saunders, Anand Kulkarni, Craig Pinner, Lauren Pearce, Vishnu Bhardwa, Judi Ramsey, Meghna Sharma, Rob Hull, Srinivasan Perumal, Julia Critchley, Stephen Hill, Bethany Fitzmaurice, Robert Crichton, Cormac O'Connor, M. Dickinson, Alison Pearce-Smith, Julie Toms, Kathleen Horan, Ammy Dodd, Rachel Crone, Graeme Finnie, Suman Shrestha, Saul Sundayi, Shamini Sivakumaran, Robert Collin, Janine Musselwhite, Yuvaraj Kummur, Mariana Bernardo, Amrinda Sayan, Gabrielle De Selincourt, Laura Bridge, Melissa Rosbergen, Philip Barclay, Garry Davenport, Daniel Murrell, Andrew Drummond, Eireann Allen, Emma Fadden, Subha Arunachalam, David Robinson, Stephanie Dukes, Catherine Jardine, Sunny Bhat, Hemantha Shiva, Amy Kerr, Henry Elms, Anam Asif, Sandra Evans, Girish Rangaswamy, Laura Thomson, Asad Javed, Jenny Shuttleworth Davies, Maren Kleine-Brueggeney, Sian Edwards, Jean-Paul Zahra, Jo simpson, Priya Verma, Bhamini Tharmalingam, Matthew Edmunds, Stephen Adshead, Hannah Luckhurst, Lara Allen, Colin Merrill, Fiona Lyle, Falguni Choksey, Mohyman El Habishi, Holly Notman, Lisa Murthen, Christiana Georgiou, Georgina Singleton, Tim Cook, Melba Knighton, Shirley Pyke, Amit Gadre, Maria Rehnstrom, Helen Hothersall, Anja Kuttler, Anita Boltres, Sarah Williams, Sarah Welch, Yamuna Madhu, Pramod Nalwaya, Alistair Coleman, Jeanie Worthington, Jasmine Samuel, Rajashekar Gowni, Karen Burt, Shamim Haque, Reynard Knoetze, Hakeem Yusuff, Tom Taylor, Val Parkinson, Sheik Pahary, Jonathan Fortune, Natalie Long, David Gilhooly, Karthick Duraisamy, Duncan Baines, Shondipon Laha, Marie Appleby, Jyothi Hosahalli, Christine Catley, Jasmine Jose, Damien Mantle, Dinkar Gowda, Permendra Singh, Ramesh Khoju, Carol Bradbury, Sarah Hazeldine, Karan Kanal, Sonal Lodhi, James Craig, Rachel Wong, Teresa Ferreira, Charis Banks, Ben Chandler, Asia Sarwar, Sivaprakash Vaitheeswaran, Sam Bews, Katie Hunter, Sohan Bisonoothan, Lauren Hunt, Melony Hayes, Nilesh Chauhan, Janet Pickett, Sharon Dealing, Jamie Plumb, Thomas Hollins, Claire Hill, Claire Hindmoor, Nicolas Hooker, Hannah Davis, Laura Mee, Elizabeth Thomas, James Self, Jenny May-Ling Cheung, Jane Varin, Manish Kakkar, Anuj Wali, Omar Siddique, Sophie Earl, Elizabeth Longdon, Alison Meadows, Shafi Ahmed, David MacPherson, Shaima Elnour, Suzi Hale, Ramez Ibrahim, Fei Long, Orlanda Allen, Alice Groves, Mohammed Wahid, Angela Stevens, Carl Ilyas, Richard Robley, Nichola Bleasby, Peter Havalda, Ursula McHugh, Judith Brade, Georgia Monantera, Stuart Younie, Brian Johnston, Jamie Brookes, Linda Park, Graeme Wilson, Mark Greasley, Lohita Nanda, Vineetha Jayakumar, Ian M. Lyons, Ayman Abdu, Paul Athanasopoulos, Justin Woods, Kariem El-Boghdadly, Diane Simpson, Georgina Williamson, Jonathan McCarter, Anil Golhar, Alicia Waite, Claire Halligan, Sarah Anne Leir, Joanne Turner, Matthew O'Meara, Claire Atkinson, Adam Yarnold, Mark Fernie, Rhiann Marie O'Shaughnessy, Jamie Elwood, Laura Harvey, Ali Atrah, Helen Terrett, Sam Scholes, Rebecca E. Saunders, Vin Vyapury, Amir Rafi, Peter Bradley, Srikant Ganesh, Zehrin Nassa, Ulf Buhmann, Laura Carrick, Natalie Rogers, Said Seifalan, Ian Ryder, Jennifer Partridge, Tim Lovell, Martin Priestley, Caroline Wrey Brown, Joanna Moore, Vidhya Nagaratnam, Saba Iqbal, Francesca Mazzola, Samantha Weller, Laura Gould, Helen Johnston, Jenny Spimpolo, Carmen Scott, Stephen J. Brett, Paul Cripps, Amit Kurani, Alexander Knight, Nirav Shah, Pushkar Patankar, Fraser Waterson, Sarah Martindale, Johannes Mellinghoff, Joanne Wootton, Sarah McCormick, Sameer Somanath, Bilal Yasin, Christopher Skeoch, Toby Jacobs, Katrina Eaton, Lynne Connell, Harry Soar, Yvonne Bramma, Tom Gately, Renjith Joseph, Anish Gupta, Lucie Hobson, Charindri Wariyapola, Maryam Zaky, Nimu Varsani, Gerhardus Van Rensberg, Jackie Evans, Rosahn Saleh, William Sutcliffe, Louise Potter, Harvey Dymond, Catherine (Katie) Patton, Andrew Selman, Stephen Traynor, Kate Tizzard, Rumyana Nyathi, Caroline Reavley, Saima Hashmi, Kerry Hughes, Isabelle Sykes, Kate Slade, Anne Troy, David Castillo, Jennifer Quinton, Anne Adams, Joanne Gresty, Stella Wright, Victoria Christenssen, Iain Mooney, Fiqry Fadhlillah, Seema Pai, Gabor Debreceni, Aleinmar Winthein, Denise Griffin, Hannah Beadle, Elisa Kam, Marie Williams, Helen Howes, Tariq Tabiner, Saxon Prentice, James Bedford, Emma Craig, Peter Standen, Stephen Petley, Janaki Pearson, Cheryl Marriott, Harry Barclay, Alexandra Matson, Michael P.W. Grocott, Alison Thorne, Joanne Humphreys, Vishal Patil, Nick Greenwood, Richard Wassall, S.K. Harris, Valpuri Luoma, Dancho Ignatov, Rebecca Fry, Anamika Sehgal, Antonio Paredes-Guerra, Manjula Yadagiri, Yuvraj Doriaswami, Benjamin O'Donovan, Adam Mounce, Stephanie Wright, Linda Webber, Tracy Hazelton, Ethan Bateson, Theresa Garrett, Chris Honstvet, John Scriven, Rahul Dimber, Phillip Lo, Jenny Stead, Catherine Plowright, Rachel Morris, Pallavbhai Desai, Nicola Johnson, Neil Muchatuta, Vijayakumar Gopal, Sherma Turner, Karina Fitzgibbon, John B. Davis, Sarah Patch, Erica Jolly, Rob Gregory, Christopher Lochrin, Geoffrey Ryder, Sam Michlig, Liana Zucco, Susan Nimmo, Jessica Whiston, Sarah Goellner, Rohan Babla, Deborah Skelton, Lucy Mcmanoman, Darcy Pearson, Diane Forrest, Sanjeev Garg, Joanne Bradley-Potts, Joel Perfitt, Danny J.N. Wong, Mike Weisz, Caroline Lowrie, Timothy Alce, Alice Michell, Charlotte Soulsby, Dominic Hayes, Arnab Mandal, Stephanie Ridgway, Angela Willberry, Alka Grover, Simran Minhas, Kerwei Tan, Sharon Jones, Sam Marcangelo, Ben Millette, Hilary Thatcher, Greg Foster, Krishna Balachandar, Megan McAtear, Richard Shellard, Chris Littler, Thunga Setty, Kavita Sasi-Kumar, Theodore Floyd, Duncan Adshead, Stephen Hickey, South Yorkshire Hospitals Audit, Amy Barker, Ewen Cameron, Dawn Trodd, Wendy Nichols, Beth Farr, Mike Salmon, Naomi Fleming, Umairali Ikram, Ben Straughan, Peter J O'Brien, Laura Purandare, Janine Thomas, Elizabeth Wood, Kate Bosworth, Stewart Mckie, Samantha Evans, Tamilselvan Rajamanickam, Srinivasan Dhileepan, Paul Hindmarch, Colin Bergin, Sange Mansoor, Lisa Armstrong, Nagendra Natarajan, Irmeet Banga, Fiona Osborne, Lynne Williams, Pieter Bothma, Jade Woolley, Joanne Finn, Bernd Oliver Rose, Shaman Jhanji, Bennur Katyayani, Gillian Robertson, Laura Bird, Pauline Fitzell, Sally Anne Smith, Serena Yen, Stuart Clelland, Thomas Urwin, Luff Delme, Rocio Ochoa Ferraro, Nurse Cheryl Padilla Harris, Asad Naqvi, Andy Cumpstey, Natalie C. Wood, Samar Al-Rawi, Pulak Padhi, Claire Botfield, Bhavesh Raithatha, Michael Briskoe, Jolyon Cohen, Ben Gibbison, John John, Stephen Washington, Jayne Foot, Karen Chadwick, Naomi Cochrane, Sophie Spencer, Alexandra Gatehouse, Susan Smolen, Aaron D'Sa, John Sturrock, Christopher P Bourdeaux, Kumud Bhandari, Neil Kellie, Elizabeth Denman, Samson Tou, Laura Kettley, Alex Eros, Stuart McLellan, Nicola Ball, Emily Kirk, Sue Smyth, Kim Gibson, Oliver Barker, Mohammad Masood, Dabeeruddeen Ahmed, Geoff Thorning, Jennifer Van Ross, Esme Elloway, Kat Rhead, Sei Nishimura, Maximiliane Kellner, Benjamin Jacobs, Sanjoy Shah, Matthew Stubbs, Faye Moore, Greg Cox, Nishita Patel, Ashok Nair, Elizabeth Hawes, A Espinosa, Kavita Wankhade, Vladimir Bashliyski, Carina Bautista, Susan Lyjko, Michelle Rowe, Nikita Whotton, Julie Temple, Inthu Kangesan, Gemma McIntosh, Samir Nazir, R. N. Kumar, Jen Warren, Alex Coombs, Marilyn Boampomaa, Kaya Jeyarajah, Heather Savill, Claudette Jones, Vinayak Vanjari, Caroline Tierney, Santhana Kannan, Jennifer Aston, Helen Melsom, Valantine Woodham, Nichola White, Niraj Barot, Paolo Perella, Mayumi Vianzon, Padmanabhan Vatsala, Claire Boynton, Alexandra Edwards, Elisa Masoni, Jayne Edwards, Julie Edwards, Thomas Garth, Amanda Skinner, Kate Blethyn, Jonathan Chambers, Katie Ramm, Rosada Jackson, Thomas Coleman, Tracey White, Emma McKenna, Kanchan Umbarje, Thomas Sheppard, Deepa Jumani, Emma Murphy, Peter Lawley, David Howe, Daisy Alston, Ania Dean, Prasun Mukerjee, Julian Hood, Mahmoud Alkholany, Sarah Goff, Gillian Rennie, Bridget Fuller, Ciara Walker, Jonathan Pipe, Alex Eeles, Wai Soon, Catherine McMillan, Martha Wrigley, Neil Brown, Peter Sandbach, Claire McCahill, Anna Wilson Charlotte Yates, Paul Sampson, Natasha Muzengi, Colum Slorach, Moyra Hynd, Arjun Ardeshna, Trish Boateng, James C. Geoghegan, Rhys Williams, Karoline Middleton, Brian Campbell, Srikanth Chukkambotla, Daniel Leslie, Sherrie Samuels, Michael Allan, Ruth Clarke, Christopher Nutt, Kirsten Reid, Hannah Smith, Surabhi Jain, Stephanie Reed, Hywel Evans, Irene Gardner, Ben Griffiths, Guy Shinner, Marek Frenkiel, Jacek Zeber, Gary Minto, Simon Parrington, Louise Harrison, Carlos Kidel, Hawa Desai, Lois Steuart, Claire Hirst, Johann Harten, Marc Slorach, Angela Christofides, Claire Macey, Helen Moore, Chantal Busby, Andrew Robertson, Leanne Milner, Catherine Chapman, Rebecca Reeves, Lawrence Wilson, Alice Aarvold, Lizzie Irvine, Narayanan Suresh, Kirsteen Brown, James Dalton, Sam Miller, Yasir Rashid, Andrew Swain, Liliana Czukowska, Natasha Permall, Carys Durie, Peter Carroll, Lauren Cooper, Prerna Mehrotra, Sarah Clayton, Martina McMonagle, Sarah Buckley, Enoch Onya, Elizabeth Perritt, Domonique Georgiou, Manjeet Save, Lauren Friedman, David W. Hewson, Katherine McAndrew, Simon Morton, James Morgan, Susan Underwood, Helen Bowyer, Avninder Chana, Lucy Sootheran, Kieron Rooney, Pooja Patel, Jessica Summers, Laura Farmer, Kiran Keshvara, Victoria Richardson, Hannah Crowther, Geejo Rappai, Adam E. Green, Sarah Willcock, Smitangshu Mukherjee, Samuel Tyrrell, Geraldine Landers, Claire McAteer, Jennifer Awolesi, Sarah Higgin, Orla O'Neill, Chrissie Chevis, Paul Winwright, Vikram Malhotra, Jonathan Ogor, Maria Muelmenstaedt, Richard Stead, Lindsay Roughley, Sara Balliston, Nevena Kalcheva, Marc Wittenberg, Adrian Taylor, Lydia Shatanda, Anjali Soodan, Angela Moon, Sarah Elgarf, Matthew Roche, Sanchita Bhatia, Clare Howcroft, Emma Butterfield, Emily Gannon, Matthew Needham, Jacqueline McCormick, Daniel Bendel, Victoria Martinson, David Hall, Richard A. Armstrong, Lara Herbert, Beverly Kilner, Kathy Dent, Victoria Thwaites, Issy Thomas, Maggie Peat, Lisa Macbeth, Alex James, Rachel Flight, Nick Black, Elizabeth Boyd, Catherine Gedling, Suzanne Body, Nadine Farrell, Samantha Clayton, Paula Hiltout, Richard Haddon, Bethany Philpott, Victoria A Burgess, John Jackson, Anita Patil, Chris Platt, Lindsey Iles, Chrissy Braybrook, Katherine Morris, Emma Karsten, Minna Meritahti, Anastasia Lynn-Smith, Dorothy Hutchinson, Rebecca Darbyshire, Joanne Riches, Astri Luoma, Andy Gibson, Dushanthi Thurairasa, Roisin Baker, Xantha Holmwood, Alda Remegoso, Trusha Mistry, Sarah Hennell, Suganthi Joachim, Stephen Harris, Sam Eggleston, Melanie Morrison, Boon Ang, Natalie Jackson, Nicola Jones, Zena Haslam, Beata Iwanicka, Laura Graham, King Dhar, Melanie Kent, Daniel Wirth, Umakanth Kempanna, Laura Troth, Robert Orme, D. Campbell, Raquel Duarte, Muzaffar Sheik, Robert Maher, Jon Bramall, Rebecca Coates, Tracey Cosier, Sarah Vest, Kajan Kamalanathan, Graeme Foggo, Amanda Mohabir, Ritoo Kapoor, Precious Basvi, Jamie McCanny, Christian Frey, Bruce Emerson, Anantharaman Venkataraman, Karen Burns, Gail Pottinger, Mohamed Elwkhiee, Farkhunda Waqas, Alison Loftus, Amanda Kirrage, Ilma Songaile, Craig Smith, Jo Mullender, Hannah McPhee, Miriam Namih, Linda Gregson, Rachel K. Walker, Iain K. Moppett, Christine Adamson, Katie Flower, Tina Stoycheva, Beena Parker, Caroline Thompson, Kootharajan Kamraj, Vignesh Ashok, Ranjit Gidda, Istvan Koczka, Sadie Perkin, Vandita Ralhan, Arun Sengottaiyans, Ruth Hodgson, Peter Valentine, David Nunn, John Hickman, Molly Waldron, Lauren Elliott, Irene Echaveznaguicni, Lisa Dunlop, Julian Sonksen, Robert Fallon, Huw Griffiths, Thoy Ruth, Olivia Clancy, Lucy Dudgeon, Alicia Rodgers, Pamela Oracki, Phoebe Syme, Maria Newton, Stuart P. D. Gill, Julie Foxton, Jane Perez, Liam Gleeson, Richard Green, Sally Beer, Rohit Juneja, Loretta Barnett, Alex Bonner, Eunice Emeakaroha, Andrew V. Bradley, Ravishankar Jakkala Saibaba, Dipali Verma, J. Joseph Kinsella, Swee Ang Tung, Anju Raina, Verity Calder, Andrea Ortu, Chris Walmsley, Suneal Sharma, Michelle Reichman, Tom Stocks, Annika Smith, Ross Cruikshank, Sharon Storton, Matyas Andorka, Abhishek Kakkar, Allison Daniels, Priya Datar, Nichola Wakeford, Sheila Black, Usman Choudhry, Stephen Hackett, Huw Wilkins, Kirtida Mukherjee, Tim Green, Rebecca Hill, Ishan Dharmarathna, Jennifer Crooks, Serah Mungai, Luisa Howlett, Niveen El-Wahab, Linda Prasad, Amy Sadler, David Sharpley, Daphne Varveris, Victoria Ashton, Rajeev Jeevananthan, Safia Begum, Helen Anderson, Katherine Nahajski, Vanessa Linnett, Laura Morland, Stephen Mowat, Nenette Abano, Kathryn James, Ian Butler, Madelaine Ocampo, D. Williams, Gabriella Frunza, Wendy Deamer, Dominic Espitalier-Noel, Sian Liddle, Jane McConniffe, Anthony E. Pickering, Lisha Aju, Catherine Morgan, Hao Ern Tan, Jemma Tate, Emma Dooks, Anna Moore, Alison Hardwick, Liam Scott, Zak Rob, Rajeev Jha, Sujesh Bansal, Lynda Connor, Seliat Sanusi, Sophie Mason, Nipun Agarwal, James Woodier, Julian Giles, Lauren Collis, Jill Brown, Natalie Constable, Nichola Cahill, Anne Cowley, Mai Wakatsuki, Kelly Mintrim, Glenn Arnold, Donna Doyle, Ryhs Millington, Richard Dobson, Monica Serrano, Saqib Naji, Walid Hammad, Jacob Osbourne-Wylde, David Rollins, Claudia Paoloni, Nathan Anderson, Rachel Ingham, Alison Whitcher, Vicky Hills, Nina Toms, Jon Witby, Amy Nash, Marcus Fletcher, Jane Gibson, Martin Warin, Katherine McDowall, William Malein, Madhurima Das, Wael Abdelrhamen, Tom Neal, Sister Jenny Ritzema, James Collins, Chandana Rao, Joyce Yeung, Nadeem Shakir, Andrea Weigert, Atideb Mitra, Hari Arunachalam, Amy Morgan, Richard J. Jackson, Julie Chadwick, Debbie Callaghan, Frank Swinton, Lorraine Lock, Rahul Wakhle, Krish Kapoor, Ryan Humphries, Sarah Beavis, John-Paul Cutts, Julie Wilson, Keith Kelly, James Gill, Angela Loughlin, Rhys Rhidian, Christopher McGovern, Tom Hickish, Rachel Campbell, James Pennington, James Tozer, Philip Coakley, Lynn Fenner, Sally Tomkins, Lester Ribeiro, Shabir Qadri, Hristina Petkova, Christina Timmons, Katy Smith, Jonathan Perry, Stephen Crotty, Tanmay Patil, Mayavan Abayalingam, Ahmed Foly, Anna Wahed, Lewys Winfield-Young, Naomi Goodwin, Mark Verlander, Clare Donovan, Milena Vannahme, David Helm, Murali Vallabhaneni, Clare Ingram, Neil Moreland, Lorraine Stephenson, Jenny Jackson, Lindsay McOwat, Sathya Visvendra, Rhiannon Jones, Sarah Bird, M. H. Nathanson, Beryl Jones, Claire Davies, Beena David, Ian Sheldrake, Jeremy Guilford, Sister Bryony Storey, Rajeev Mishra, Irina Halfacree, Kiran Rait, Sameer Ahmed, Victoria Poyntz, Pamela Birks, Tom Kennedy, Angiy Michael, Michael McEvoy, Ian Davies, James Chan, Sajjad Ahmed, Laura Sweeney, Anne Whaley, Andrew Moores, Stella Gillies, Gearoid Crosbie, Antoinette Wilson, Iain Walker, Fiona Brailsford, Virginia Solanki, Elizabeth Turnbull, Lyndon Harkett, Sarah Ramsay, Thomas Syratt, Pushpaj Gajendragadkar, Cathal Small, Joanna Poole, Annabelle Whapples, Raghavendran Krishnaiyan, Elizabeth Smee, Richard Pierson, Taslima Rabbi, Alexandra Murphy, Angela Rooney, Sarah Crawford, Peter Bamford, Stephen Worthy, Sarah Munsie, Lucy Venyo, Henry Wang, Aditya Kuravi, Dennis Barnes, Ruth Han, Benjamin Gupta, Nurse Lynn Wren, Robert Hartley, Emma Edmunds, Laura Blood, Valerie J. Page, Thomas Judd, Puvan Suppiah, Emma Jenkins, Kate Gallagher, Fionnuala Lenehen, Rashidat Adeniba, Julius Cranshaw, Julie Wollaston, Kathryn Allison, Richard Kirkdale, Samantha Griffith-Norris, Jenna Kelly, Snehasish Guha, Stefan Schraag, Joy Dearden, Elizabeth Bell, Stephen Smith, Sarah Longhurst, Elizabeth Wilby, Annaliza Sevillano, Raksha Mistry, Aalisha Mariam Karimi, Kaung Pyae, Sarang Puranik, Maggie Collingborn, Karen Cranmer, Chandrashekhar Vaidyanath, M. Chincholkar, Narendra Siddaiah, Gillian Bell, Edward Rintoul, Nicki Devooght-Johnson, Tom Lovejoy, Eleanor Roscoe, Zoe Neilson, Joanne Hill, Kamal Sharif, Sharon Meehan, Bassey Nkanang, Thomas Georgiou, Martin Goodman, Prashant Kakodkar, Rebecca Martin, Philip Roddam, Evanna McEvoy, Peter Tsim, Janakan Anandarajah, Shub Gupta, Oliver Pratt, Yang Ng, Francesca Th'ng, Linda Kent, Graham Soulsby, Danielle Kirk, Ramana Govindaraju, Rebecca McClean, Samantha Harkett, Obaid Tarin, Shalini Chinna, Susan Gallagher, Laura Gardiner, Marc Turnbull, James Briscoe, Anna McSkeane, Melanie Claridge, Gillian Fleming, Thomas Huttley, Elaine Spruce, Lianne Hufton, Susan Hendy, Adrian Barry, Jeremy Drake, Cody Allen, James Hillier, Manju Patel, C. Gray, Nasreen Iqbal, Karen Markwell, Linzi Heaton, Michelle Nicholas, Gary Lau, Laura Catchpole, Nurse Sonia Walia, Kerry Elliott, Jake Hartford-Beynon, Amee Samani, Kathryn King, José William Martínez, Skylar Paulich, Ifan Patchell, Killian McCourt, Rebekah Rodgers, Christine Wood, Richard Wan, Karan Verma, H. W. Cain, Eleonore Quinn, Lisa Richardson, Muhammad Usman Latif, Nicholas Hingley, Rajesh Gilla, Roopa McCrossan, Mayeth Recto, Russell Hedley, Lucy McClelland, Suzie Marriott, Deepak Seharawat, Gururaj Mudimadagu, Claire Jones, Michelle Yare, Sophia Henderson, Rupinder Kaur, Emily Spence, David Wright, Bhaskar Dutta, Tom Pettigrew, Vikki Atkinson, Lorna Sissons, Segun Oladele, Sue Thomas, Hani Ali, Rebecca Robson, David Buckley, Kevin Hamilton, Amanda Hall, Anaesthetic Audit, Anna Watkin, Donna Kelly, Graham White, Sarah Sanders, Henry Boyle, Joao Galente, Thomas Williams, Justin Ang, Sarah Horton, Abdelrahman Soliman, Vijay Jeganath, Kavita Upadhyaya, Plamen Stoyanov, Murray Geddes, Alan Pope, Khaled Ellisy, Thomas Walker, Emma Finlay, Penny Parsons, McDonald Mupudzi, Adam Duffen, James Goodwin, Rob Penson, Laura O'Sullivan, Vinesh Mistry, Ravindra Mallavalli, Krzysztos Guz, Deepti Bhuwanee, Eleanor Andrews, Justine Burns, Sarah Kirk, Faith Kibutu, Sam Stafford, Julia Blackburn, Joellene Mitchell, Robert Spencer, Helen Williams, Karen Riley, Gabbie Young, Tom Williams, James Wu, Emma Wheatley, Alistair Johnstone, Rachel Stoeter, Timothy Cominos, Guy Coady, Ruth Mawhinney, Sam Spinney, ruthy Arumugam, Myura Nagendram, Jason Lie, Sian Hughes, Linda Bairkdar, Peter Evans, Daniel Pygall, Graeme Brown, Susan Livingstone, Norbert Skarbit, Amit Pruthi, Zakaulla Belagodu, Ben Linton-Willoughby, Richard A Cowan, Helena Prady, Mike Raffles, Sonia Rasoli, Katherine Cullen, Jessica Lees, Peter Lax, Ashok Puttapa, Fran Millinchamp, Aneta Oborska, Benita Adams, Kathryn Newton, Mrutyunjaya Rao Rambhatla, Sunny Nayee, Madlena Ivanova Vrazhalska, Jonathan Clarke, Aariana Sohal, Siobhan King, James Bain, Jessica Wilson, Anthony Carver, Jack Davies, Lucy Connolly, Samuel Morrish, Robyn Lee, Lucia Stancombe, Satyanarayan Jakkampudi, Kath Rosedale, Philip Hopkins, Clovis Rau, Katherine Hunter, Amy Farrow, Kathleen Holding, Elizabeth Vassell, Oliver Boney, Julia Icke, Ewa Prusack, Osi Egole, Fiona Linton, Suresh Eapen, Wendy Goddard, Ayda Borjian Boroojeny, Simon J. Davies, Jackie Terry, Fiona Graham, Thomas Pratt, Hanzla Naeem, Viv Colclough, Yeng Yap, Tejuswi Patel, Susan Midgley, Mark MacGregor, Ben Marshall, Talitha Devries, Cheng Ong, Katie Molloy, Kat Walker, Katy Irwin, Abbas Majeed, Mark Pinkerton, Nicki Russell, Sibtain Anwar, Ian A Jenkins, Lucy Allen, Elaine Coulborn, Ganesh Nair, Stewart Brown, Melissa Addy, Matt Milner, Amr Hassan, Victoria Millar, Sarah Turner, Gary Baigel, Amanda Lyle, Simon Young, Kathy Malinovszky, Heather Short, Mary Newmarch, Colin McAdam, Andrew Robert Bailey, Kevin Draper, Michael Agyemang, Kieran Oglesby, Clare Mewies, Ruth Ugochukwu, Shibu Jacob, Susan O'Connell, Charlotte Topham, Xiao Zhao, Shay Willoughby, Ossian Aukland Child, Manish Torne, Ben Wetherell, Divya Veluvolu, Dominic Wu, Elizabeth Evans, Daniel Eden, Suzannah Peggler, Lucy Emmett, Romit Samanta, Ravi Parekh, Jane Hermanowski, Will Shankey-Smith, Sam Papadopoullos, Julie Camsooksai, Sara Mistry, James Wigley, Anna Todd, Bally Purewal, Natalie Baldry, Kate Wilkinson, Aalia Sange, Kirsty Baillie, Joanne Topliffe, Denise McSorland, Saheli Das, Nikki Staines, Catherine Harris, Anna-Marie Boniface, Gemma Milne, Tessa Rowlands, Leanne Quinn, Svetlana Kulikouskaya, Christopher Bull, Angus Sutherland, Mihir Desai, Hannah Goodhand, Meenal Rana, John Bugo, Maria Chazapis, Sarah Kent, Sarah Siew, Marcin Pachucki, Tim Forsyth-Jones, John McKenna, Sarah Driscoll, Laura Hunter, Penny Bedoes, Natasha Santana-Vaz, Sandra Latham, Robert Coe, Sharon Christie, Lawrence R Kidd, Katy Redington, Alastair Sawyer, Abdalla Ali, Rekha Jayapal, Manfred Staber, Emma Pearson, Stuart Reilley, Tom Bird, Kristofor Inkpin, Annette Haines, Manish Verma, Naomi Wee, Ozerah Choudhry, Daniel Tucker, Euan Campbell, Aaron Stokes, Ashley Allan, Emma Reeves, Helen Fenner, Melanie Cockroft, Tom Nicholls, Sinan Bahlool, Sharon Drake, Nalini Sethia, Lesley Jordan, Martin Northey, Paul Glyn Jones, Lara Jeanes, Emma Simpson, Julia Brown, Samantha Coetzee, James Nicholas, Adam Samways, Ritesh Ganesh, Martin Ward Platt, Mizan Khondoker, Helen Wibberley, Lauren Simmonds, Sunita Agarwal, Linda Titinchi, Fran O'Higgins, David Pritchard, Laura Beard, Yvonne Lester, Charlotte Hirst, Louise Wills, Kevin Windsor, Haren Jyothiraj, Carmela Martella, Stephanie Bell, Christopher Nwaefulu, Hemamangala Venkatesh, Camilla Stagg, Soumi Ghosh, Thomas Dawes, Jennifer Lockhart, Stavros Papadopoulos, Nanci Doyle, Gillian Whalley, Rachael Britton, James Goddin, Maggie Dawson, Carole Holder, Elaine Morsman, Rachel Lovatt, Venu Mehta, John J.B. Allen, Anna Perham, Stephanie Wallis, Dmitry Zabauski, Peter Hart, Tracy Sharp, Martin Pope, Jo Knight, Jane Wright, Nageena Hussain, Josie Snell, Thomas Knight, Philippa Hill, Nic Martins, Robin Williams, Beverley Stidolph, Beth Peers, Brian Lafferty, Alicja A'Court, Joanna Collins, Charlie Kennedy, Andy Bates, Graham Walkden, Mia Marsden, Lauren Shillito, Poonam Bopanna, Raheel Ahmed, Ada Ezihe-Ejiofor, Kate Driver, Mevan Gooneratne, Carolyn Smith, Caroline Abernethy, Kathy Shammas, Chanice Alcock, Yin Yong Choo, Mark Vertue, Ratna Makker, Victoria C. Smith, Sachin Mehta, Clare Denford, Wint Mon, Jose Miguel Sabugueiro, Liz Varghese, Mohamed Ahmed, Rebekah Chan, Alexandra Williams, Stephanie Pauling, Maria Faulkner, Ryan Wilkins, Sara Stevenson, Kathryn Simpson, Moiz Alibhai, Patricia Williams, Pascal Defeyter, Siva Sangaralingham, Lucy Evans, Shirley Cocks, Simon Dyer, William Rea, Caroline Renton, Karl Braid, Ranjit Bains, Holly Owen, Sue Brixey, Calum Taylor, Laura Coleman, Andrew Peeling, Daniel Solomon, Christopher Perman, Roisin McCallum, Helen Church, Martin Watson, Amy Bamford, Elizabeth Bradshaw, Elizabeth Turner, Owen Vale, Suneetha Ramani Moonesinghe, Preeti Mahidik, Lynsey Cubitt, Catherine Hunter, Eleanor Warwick, Sam McAleer, Suresh Singaravelu, James Hilton, Rebecca Aspinall, Icel Souleimanova, Muna Elsheikh Idris, Wei Teo, Sarah El-Sheika, Adrienne Stewart, Sadia Habib, Emily Wade, Liesl Despy, Sharmin Shohelly, Colin Williams, Louise Shaw, Shree Voralia, Dafydd Lloyd, Barbara A. Crooks, Laura D Howe, Una Gunter, Edward Hare, Louise Nimako, Ruth Young, Helen Doherty, Sock Huang Koh, Stephen Merron, Martina Coulding, Agilan Kaliappan, Clare Bolton-Hill, Jill Wain, Maria O'Callaghan, Catherine Cartmell, Nicola Pemberton, Hannah Bennett, Lynda Garcia, Riquella Abbott, Sally Jeffrey, Thomas McLoughlin, Andrew Gratrix, Christopher Harrison, Matt Mackenzie, Jayshree Gracey, Chris Moore, Benjamin Parsons, Nehal Patel, Stephanie Brooks, Catherine Riley, Jemma Gilmore, Ilya Kantsedikas, Simon Whiteley, Emily Pallister, Angie Organ, Yohinee Rajendran, Gopinath Selvraj, Priya Thorat, Ilona Schmidt, Pauline Austin, Nitin Madhukar Sadavarte, James Haddock, Alastair Duncan, Richard Bateman, Elaine Chinery, Martin Gray, Felicity Corcoran, Shanelle Tharuka Wijesuria, Bryany Bond, Charlene Otieno, Sion Lewis, Cieron Roe, Dan Freshwater-Turner, Annette Bolger, Sarah Steynberg, Louie Saclot, Charlotte Busby, Jack Roberts, Richard Dagnan, Jasna Comara, Krishnakar Melachuri, Sian Gibson, Joanne Taylor, Manju Agarwal, Mark Sheils, Matthew Bell, Rosemary Anna Lewis, Kiran Patel, Mansoor Siddiqui, Christopher J. Groves, Mini Thankachen, Sharon Turney, Viral Dalal, Pele Banugo, Andrew Baird, Euan Kerr, Simon Tomlins, Laura Osbourne, Nicola Pattison, Stuart Joy, Susan Merotra, Lorna Ryan, Lisa-Jayne Cottam, Chye Siaw, Keelan Jerram, Nurse Diane Scarletta, Carole Paley, Jennie Smith, Will Gatfield, Stephen Alderson, Claire Swarbrick, Amelia van Manen, Stephan Clements, Sophia Strong-Sheldrake, Jake Drinkwater, John McLenachan, Lucinda Williams, Dianne Heaton, Sandor Orosz, Chloe O'Hara, Nina Barratt, Justine Elliot, Michael Gardner, Nicola Crowther, Bharati Rajdev, Linda Hall, Youssef Girgis, Michael Kinsella, Alison Potter, Matthew Martin, Rosie Reece-Anthony, Richard Pugh, Tracey Taylor, Esme Marshall, Wendy Stoker, Helen Worrell, Kay Housley, Rebecca Leslie, Helen Jewitt, Sandeep Sharma, Maire Gallagher, Jon Fenn, Jade Harrison, Hannah Watson, Natalie Morris, Lewis Schofield, Nisha Pattni, Charlotte Thomas, Eleanor Walshe, Richard Snooks, Ruth Murphy, Emily Pickford, Gnanshree Krishnamurthy, Donna McIntosh, Rachel Dolan, Emma Stoddard, Kelly Goffin, Shady Elhallous, Adrian Butler, Ildiko Nemeth, Hannah Wilson, James Sylvester, Melanie Sahni, James Wardlow, Ann Lachana, Emma Barr, Kayleigh Gilbert, Yazzim Hammoud, Peter Csabi, Maqsood Bajwa, James D Turner, Alex Hunt, Samantha Moore, Stephanie Hii, Philip Atkinson, Michelle Walter, Elizabeth Bailey, Frances Tait, Annie Newby, Jane Martin, Greg Forshaw, Bert Quartermain, Sally Humphreys, Aoife Hegarty, Caroline Bennett, Satyajeet Ghatge, Charles Prior, Kribashnie Nundlall, Priaykam Chowdhury, Jill Fitchett, Daiva Bernotaitis, Sandeep Varma, Alex Dunn, Rebecca Dooley, Mahamed Mostafa, Shelly Wood, James Humphreys, Anna Celnik, John Bailes, Mark Snazelle, Christina McCarroll, Matthew Govier, Emert White, Matthew Taylor, Alastair Rose, Brigid Hairsine, Natalie Whybro, Allen George, Robin Wilson, Filipe Vieira, Leon Cohen, Jonathan Womack, Thomas Woodward, Nimali Lochanie, Ben Howes, Joshua Nelson, Preea Gill, Gayle Clifford, Lushani Suntharanathan, Duncan Wagstaff, Steve Pryn, Lalindra Bandara, Sneh Shah, Nowfal Rahman, Iolo Roberts, Mirriam Sangombe, Shaik Subhani, Hannah Phelan, William Udall, Katy Allan, Nicola Zondo, Tim J Peters, James Roe, Catherine Addleton, Angus McKnight, James McCaul, Flora Kormendy, Anil Rao, Luke Vamplew, Andrew Rees, Jeanette Gilbert, Mandy Austin, Thomas Hunt, Sian Birch, Catherine Lloyd, Stewart D'Sylva, Jill Smith, Wendy Lum Hee, Michael Munro, Jean Denton, Julia Hindle, Alice Brown, Ursula Kirwan, Dinithi Yogya, Maria Mclaughlin, Nurse Louise Moran, Larysa Duniec, Sophie Benoliel, Gail Evans, Linda Bailey, Colin Hall, Katie Rowland, Krupali Patel, Ashwini Keshkamat, Zorba Begum, Resti Varquez, Victoria Apps, Giles Bond-Smith, Shirin Dastur, Andy Chapman, Amy Smith, Sarada Gurung, Ruth Delascasas, Nicole Issit, Pauline Sibley, Jaina Parmar, George Madden, Eveliina Nurmi, Katja van de Snepscheut-Jones, Louise Peacock, Vanja Srbljak, Kellie Allen, Andy Chamberlain, Suhail Zaidi, Andrew Boyle, Daniel Stolady, Rita Saha, Mark Clayton, Mitul Patel, Emily King, Hannah Oliver, Ewa Werpachowska, Holly Coles, John Dereix, Agnieszka Kubisz-Pudelko, Clare Watkinson, David Rogerson, Laurence Inman, Jaspreet Rayet, Jenny Finch, Emma Stewart, K. E. Wilson, Emma Tyson, Asif Gani, Reni Jacob, Neil Smith, Johnny Holland, Max Richardson, Mark Chen, Richard George, Helen Laycock, Anoushka Winton, Emily Hignell, Li Fang, Emma Welfare, Rochelle Velho, Fayaz Baba, Finbar O'Sullivan, Lisa Zeidan, N. Beauchamp, Neil Rasburn, Guy Rousseau, Victoria Roberts, Hollie Bancroft, Holly Maguire, Mechele Couch-Upite, Rahul Kumar, Chandra Bhimarasetty, Matt Lovell, Sujata Anipindi, Charlotte Small, Matthew Faulds, Alex Mattin, Alice O'Donnell, James Jack, Richard Boulding, Tarek Mostafa, Rhian Bull, Corinne Pawley, Ruth Killen, Jessica Lowe, Frances Taylor, Ethel Black, Michael F. M. James, Jenny Child, Lisa Emery, Kim Hoyland, David Hay, Janet Cotta, Josephine Stewart, Sue Spearritt, Laura MacNally, Fatma Lahloub, Katie Welham, Sanjoy Bhattacharyya, Shanteela McCooty, Heena Bidd, Hugo Buckley, Ervin Shpuza, Zaid Ahmed, Emily Craven, Amanda Cook, Caroline Dixon, Tara Pauley, Tariq Azad, Helena Barcraft-Barnes, Sindy Lee, Kate Penhaligon, Bernice Dudkowsky, Karen Ellis, Laura Montague, Ching Pang, Elsie Bickmore, Veronica Marsh, Toby Winterbottom, Marta Campbell, Rhys Hughes, Issie Gardner, Elizabeth Steel, Ramai Santhirapala, Katie Sweet, Michelle Scott, John Ekpa, Bhavia Janardhana, Catriona Frankling, Julia Ottaway, Alexander Middleditch, Elna Cifre, Annabel Pearson, Amanda Cotterill, Sarah Raut, Hannah Blanshard, Sara Eddy, Garry Henry, Elizabeth Hood, Maria Loy, Matthew Campbell, Marc Gimenez, Jessica Thrush, Jeremy Henning, Vlad Kushakavsky, Nikolaos Makris, Deborah Fradkin, Karen Fan, Fiona Hammonds, Kathryn Jackson, John Hadfield, Pyda Venkatesh, David Read, Daniel Zeinali, Ryan Hynd, James Carvell, Richard McCormick, Emily Dodds, Sana Rizvi, Amelia Daniel, Dan Sellers, Thomas E. Miller, Daniel Haigh, Nicky Moss, Patrick Dill-Russell, Priya Shekar, Teresa Melody, Randeep Dhaliwal, Nigel Hollister, Andrew Burtenshaw, Adrian Wagstaff, Ben Scoones, Eduardo Osorio, Joanna Allison, Lucy Willsher, Carol McArthur, Stephan Dalchow, Elaine Winkley, Eleanor Reeves, Ben Eden Green, Andrea Ingham, Mohammad Auldin, Freda Amoakwa-Adu, Jonathan Adams, Fiona Oglesby, Charlotte Steeds, Nurse Sara Greig, Obla Suganthi, Puja Chhaniyara, Clare De'Ath, Chandrakant Gosavi, Bart Ordys, Adele Flowerdew, Doug Tunney, Rachel Alexander, Oliver Griffith, Thomas Saunders, Matthew Maton-Howarth, Gabi Metiu, Akmal Shakoor, Elizabeth Willard, Katherine Russell, Matthew Robinson, Emma O'Kane, Meera Raja, Phillippa Falkner, Kerry Colling, Natasha Joshi, Laura Pearse, Tim J. Smith, Anitha James, Mona Mohamed, Richard Kennedy, Samson Ma, Tasmeen Ghafoor, Matthew N. Davies, Henry Lewith, Samuel Mindel, Sarah-Jane Dunn, Hemangini Barot, Sadie Diamond-Fox, Jenny Macallan, Arun Menon, Helen Farrah, Emma Plunkett, Brendon Spooner, Sorana White, Katie Samuel, David Crabtree, Katherine Cheshire, Gareth Harrop, Dionne Wortley, Tim Warrener, Joanne Mullen, Peter Taysum, John Whitaker, Kathy Wilkinson, Jean Dent, Nicola Farmer, Thelma Darian, Guru Hosdurga, Phillipa Wakefield, Christopher W Horner, Julie Steen, Elena Teh, Helen Gerrish, Betty Travasso, Mhairi Jhugursing, Michelle Gardener, Alexandra Crook, Edward W. Miles, Patricia Doble, Ashok Raj, Hanna Wong, Kay Protheroe, Chiraag Talati, Banher Sandhu, Cara Marshall, Matt Holl, Julie Sheriff, Frances Forrest, Adam Mitchell, Hindusha Keerthikumar, Mohamad Mahmoud, Simon Ben-Nathan, Janice Hartley, Danielle Ormandy, Hayleigh Morris, Steven Tran, Imogen Hayes, Trudy Smith, Kirsty Duell, Jennifer Cunningham, Richard Appleton, Lucy Pippard, Debroah Beeby, Hayley Bridger, Manuel Pinto, Susan Beames, Huiqi Wang, Cain Hunter, Flora Darch, Debbie Weller, Jonathan Hulme, Jacqueline Howes, Michael Kriger, Badrinath Manikundalam, D.J.N. Wong, Tim Arnold, Belinda Wroath, Rachel McKendry, Harry Knight, Caroline Bushell, Victoria Siddons, Louise Humphries, Joanne Vere, Vinanti Cherian, Janine Birch, Kate Blyth, Tatyana Bolonenkova, Meredith Harris, Alice Sisson, Sarah Clark, Sandeep Saxena, Samira Green, Amit Ranjan, Gillian Bennett, Chris Smales, Laura Ferguson, Ash Bharti, Francisca Mautadin, Katherine Brown, Lydia Jones, Christopher Adeney, Nikkita Carden, Sanjay Behl, Sonia Sathe, Elizabeth Neale, Helen French, Charlotte Mundy, Anna Batchelor, David Morris, Nithin Roy, Evelyn Philip, P.A.-A. Marc Hastie, Andrea Cole, Edmund Quak, Claire Totten, Karen McIntosh, Fiona Davis, Søren Kudsk-Iversen, Vanessa Unsworth, Andrew McIndoe, Jeremy Bewley, Sarbpreet Sarao, Laura Wood, Elaine Walker, Egidio Da Silva, Danielle Gilmour, Richard Yardley, Zara Eagle, Vijay Ragothaman, Sean Rayappu, Moira Tait, Alex Hamilton, Chris Gillett, Adeel Majeed, John Elton, Arlo Whitehouse, Fiona Robertson, Tim Martindale, Kin So, Kathryn Dixon, Toby Shipway, Fiona Mcneela, Simon Cousins, Brian Conway, Merate Place, Phil Duggleby, Rhian Morgan, Racquel Carpio, Carina Casey, Edward Mew, Jo Han Gan, Caroline Clark, Natasha Sharma, Kay Anne Mak, Gahan Bose, Chris Ford, Ruoling Yan, Anand Sathiapillai, Panagiotis Sgardelis, Sue Redhead, Arjun Alva, Cathy Jones, Vincent Hamlyn, Gemma Squires, Karen Smallshaw, John Whitwell, Sarah Shaw, Paul Watson, Michelle Cheeseman, Kimberley Netherton, Juneenath Karattuparambil, Niyesa Ranasinghe, Jeet Patel, Rob Lyons, Gemma Bown, Helen Bromhead, Zhana Ignatova, Kudakwashe Nyangoni, Linden Baxter, Thomas Moody, Sachin Valap, Esme Sleap, Mario Fernandes, Kinga Bodo, Jane Silk, Charlie Pope, Donna Ferraioli, Chloe Billingham, Rachel Butterworth, Andrew Kelly, Lesley Hawkins, Issac Gill, Hannah Greenlee, Sue Kirby, Jessica Giles, Anna Pierson, Roxana Sandhar, Claire Smyth, Rhona Younger, Ciara Coary, Arif Qureshi, Tahir Abbas, Corinne Rimmer, James Evans, Ida Ponce, Fenner Christoper, Buzz Shephard, Sophie Tang, Lauren Milian, Joanne Hiden, Dhania Haron, Jamie Calderwood, David Freeman, Virginia McTaggart, Carla Lewis, Chai Obeysekera, Alan H. Cohen, Melvin Leong, Jenni Law, Noor Elahi, Kim Holland, Victor Maduekwe, James Garwood, Lizzie Dawson, Virginia Iqbal, Thomas J Craig, Daniel Shuttleworth, Anand Perumal, Mahmood Saad, Seema Charters, Bethany Tookey, P Gunning, Suresh Panchakshariah, I.J. Wrench, Mayur Murali, Susan McInerney, Paul Foley, Charlotte Perkins, Marie-Louise Svensson, Karen Birnie, Samantha Hagan, Emily Hetherington, Anna-Marie Love, Annette Woods, Karen Green, Steve Hillier, Hannah Conway, Rebecca Reilly, Laura Bubb, Amy Ashford, Andrew Savva, Melody MacGregor, Stephen Lord, Ahmed Hassanin, Ramdas Howard, Laura Ashton, Arihant Jain, Simon Williams, Michael Shaw, Jill Deane, Abbie Singleton, Catriona Routley, Christopher Hall, Robin Webber, Tressy Pitt-Kerby, Stuart M. White, Shannon Gawley, Nick Heseltine, Christina Lalani, Claudia Dulea, Arindam Biswas, Rebecca Harris, Aislinn Brown, Nicholas Francis, Ben Holst, Ryan Perry, Cathie Melvin, Mark Darbyshire, Stephen Mulvany, Amy Ashton, Petrus Fourie, Emma Temlett, Jason Cupitt, Vanisha Patel, Alice Trimble, Andrew Brammar, Sarah Grayland, Eleanor Pett, Tom Standley, Carly Webb, Manamohan Rangaiah, Laura Peltola, Leanne Darwin, Yvonne Grimes, Elizabeth Brodier, Scott Berwick, Adam Janeczko, Madeleine McKee, Katherine Davidson, Jan Woodward, Saurabh Mehotra, Tara Keogh, Kofi Mensah, Joyce Guy, James King, Matt Aldridge, Nicolas Price, Alaine Done, Teresa Jones, Julia Sampson, Smita Bapat, Lauren Perkins, Tamas Szelei, Ryan Kingan, Suleman Mulla, Celia Montgomery, Alex Belcher, Salma Kadiri, Bryan Singizi, Peter Chater-Lea, Jennifer Claire Taylor, Lauren Oswald, Stephanie L. Lee, Rhys Griffiths, Samuel Pestell, John Livesy, Sarah Ciechanowicz, Alexander Stephen Harrison, Richard Partridge, Alex Daniels, Beth Penhaligan, Lyndsay Bibb, Jonathan Little, Margaret Cullen, Anya Eijk, Charlotte Earnshaw, Elena Lynes, Nicholas Jenkins, Inthekab Mohammed Ali, Madhu Balasubramaniam, Vusumuzi Shabangu, Paul-Simon Whitney, Rebecca Denyer, Kathryn Potts, Andrew Ray, Jonny Guy, Mike (Stephen) Kinsella, Pearl Baker, Olga Fernandez, Julian Berry, Callum Forbes, Southcoast Peri-operative Audit, Rebecca Rice, Lisa Horner, Sally Pitts, Kirat Panesar, Joe Stevens, Timothy Molitor, Oon Chiu, Piers Murphy, Sudeshkumar Muniyappa, David George, Jonathan Veitch, Shifa Yaruk, Lynn O'Donohoe, Theresa Murray, Laura Tasker, Johanna Wales, Diane Mellers, Robert Sparrow, Olivia Ward, Emma Shacklock, Janet Middle, Sarah MacLennan, Martin Knight, Lindsay Dawson, Teodora Orasanu, Jo Fletcher, Sarah Martin, Pnt Laloë, Gregor Imrie, Harriet Pudge, Tamsin Gregory, Andrea Wood, Colin Christie, James Penketh, Mia Andrews, Nicky Ford, Ellie Fisher, Sophie Robin, Richard Stewart, Steve Williams, Harriet Gardiner, Alison Evans, Guanmei Luo, Urmila Ratnasabapathy, Ruth Joslyn, R. Sneyd, John Westwood, Naomi Cassells, Olivia Kay, Jordi Margalef, S Butler, Hari Nageswaran, Chloe Searles, Geoffrey Wright, Thomas Potter, Drew Norwood-Green, Jonathan Ramsden, Sarah Bean, Emma Sadler, Anaesthetic Trainees, Stephanie Lewis, Kevin E. Thorpe, Sarah MacLean, Paul Ogle, Mary O'Sullivan, Diane Whitehouse, Mandy Oakley, Rachel Coathup, Harisg Venkatesh, Lisa Burgess, Daniela Smith, Kimberley Plummer, Hilary Robb, Jeanette Grocott, Rebecca Mairs, Helen Gilfillan, Moira Morrison, Sharon Garner, and Tammy Towers

Subjects
Adult, medicine.medical_specialty, Adolescent, State Medicine, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, 030202 anesthesiology, Pregnancy, Risk Factors, Neoplasms, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Young adult, Prospective cohort study, health care economics and organizations, Aged, Aged, 80 and over, Health Facility Size, Postoperative Care, Models, Statistical, business.industry, Incidence (epidemiology), Incidence, Health services research, Operating room management, Odds ratio, Middle Aged, Confidence interval, United Kingdom, Surgery, Obstetrics, Anesthesiology and Pain Medicine, Hospital Bed Capacity, General Surgery, Female, business, Emergency Service, Hospital, human activities, Cohort study
Abstract

Background: cancellation of planned surgery impacts substantially on patients and health systems. This study describes the incidence and reasons for cancellation of inpatient surgery in the UK NHS. Methods: we conducted a prospective observational cohort study over 7 consecutive days in March 2017 in 245 NHS hospitals. Occurrences and reasons for previous surgical cancellations were recorded. Using multilevel logistic regression, we identified patient- and hospital-level factors associated with cancellation due to inadequate bed capacity. Results: we analysed data from 14 936 patients undergoing planned surgery. A total of 1499 patients (10.0%) reported previous cancellation for the same procedure; contemporaneous hospital census data indicated that 13.9% patients attending inpatient operations were cancelled on the day of surgery. Non-clinical reasons, predominantly inadequate bed capacity, accounted for a large proportion of previous cancellations. Independent risk factors for cancellation due to inadequate bed capacity included requirement for postoperative critical care [odds ratio (OR)=2.92; 95% confidence interval (CI), 2.12–4.02; PConclusions: a significant proportion of patients presenting for surgery have experienced a previous cancellation for the same procedure. Cancer surgery is relatively protected, but bed capacity, including postoperative critical care requirements, are significant risk factors for previous cancellations.

Published
2018

20. Nucleophilic Nitrenoids Through π-Acid Catalysis: Providing a Common Basis for Rapid Access into Diverse Nitrogen Heterocycles

Author

Paul W. Davies and Miguel Garzón

Subjects
chemistry.chemical_compound, Acid catalysis, chemistry, Nucleophile, Organic Chemistry, Functional group, Organic chemistry, Reactivity (chemistry), Triple bond, Carbene, Combinatorial chemistry, Cycloaddition, Catalysis
Abstract

Nitrogen heterocycles are some of the most important and sought-after structural motifs in synthetic chemistry. General methods that can be applied towards a structurally diverse range of different scaffolds are rare. This Focus Review discusses an emerging area with the field of π-acid catalysis based on the activation of carbon-carbon triple bonds in conjunction with nucleophilic nitrenoids. The resulting approach provides ready access into α-imino metal carbene reactivity patterns that can be employed in a number of quenching processes to realize a variety of powerful new transformations. The resulting methods are characterized by high efficiency, simple and straightforward reaction set ups, mild conditions, and excellent functional group tolerance. In this Focus Review the different nucleophilic nitrenoid types are explored showing how they can be used across a range of (poly)cyclization and formal cycloaddition processes to provide an alternative and direct disconnection pathway in the generation of N-heterocyclic motifs.

Published
2015
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21. Alkynyl sulfoxides as α-sulfinyl carbene equivalents: gold-catalysed oxidative cyclopropanation

Author

Ghulam F. Khan, Paul W. Davies, Richard S. Grainger, and Matthew J. Barrett

Subjects
010405 organic chemistry, Cyclopropanation, Chemistry, Synthon, Metals and Alloys, General Chemistry, Oxidative phosphorylation, 010402 general chemistry, 01 natural sciences, Catalysis, 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, chemistry.chemical_compound, Materials Chemistry, Ceramics and Composites, Organic chemistry, Carbene
Abstract

Alkynyl sulfoxides are shown to act as α-sulfinyl metallocarbene synthons under oxidative gold catalysis, enabling reactions that are not available from diazo-precursors. This strategy is exemplified in the synthesis of fused α-sulfinyl cyclopropanes.

Published
2017

25. π-Acid Mediated Insertion of Alkynes into Carbon–Heteroatom σ-Bonds

Author

Paul W. Davies and Holly V. Adcock

Subjects
chemistry.chemical_classification, Nucleophilic addition, Organic Chemistry, Heteroatom, Alkyne, Sigmatropic reaction, Medicinal chemistry, Catalysis, chemistry.chemical_compound, chemistry, Nucleophile, Functional group, Reactivity (chemistry), Oxonium ion
Abstract

The rapidly expanding field of gold and platinum π-acid catalysis has led to the discovery of diverse transformations that are initiated with nucleophilic attack onto a metal-activated alkyne. This review brings together those reactions which employ a heteroatom nucleophile bearing a functional group that can subsequently migrate to effect a formal insertion of the alkyne into a carbon–heteroatom­ σ-bond. This reactivity profile is encountered in a range of efficient and powerful cycloisomerisations for the preparation of carbo- and heterocycles. 1 Introduction 2 1,2-Addition of Carbon–Heteroatom Bonds across Alkynes 2.1 Heteroatom-to-Carbon Allyl Migrations 2.2 Accessing Sigmatropic Rearrangements 2.3 Related Palladium-Catalysed 1,2-Carboalkoxylations and Carboaminations 2.4 Beyond Allyl Migration in the 1,2-Carbofunctionalisation of Alkynes 2.5 Oxonium Ion Migration 2.6 Migrating Centres at Higher Oxidation Levels 2.7 Migration of Heteroatoms 3 1,5 Heteroatom-to-Carbon Migrations 3.1 Alkynyl Benzoates as Alkylating Agents 4 Internal versus External Migrations 4.1 Internal Migrations of Oxonium Species 5 1,1-Carbofunctionalisations 6 Application in Natural Products 7 Summary and Conclusions

Published
2012
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26. Septo-Optic Dysplasia: Antenatal Risk Factors and Clinical Features in a Regional Study

Author

John R. Ainsworth, Paul W. Davies, Navoda Atapattu, Manoj Parulekar, Claire Miller, Lesley MacPherson, Harry E. Willshaw, and Jeremy Kirk

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Pathology, Adolescent, Pituitary Diseases, Endocrinology, Diabetes and Metabolism, Hemorrhage, Hypopituitarism, Antenatal risk factors, Paternal Age, Endocrinology, Septo-Optic Dysplasia, Pregnancy, Risk Factors, medicine, Humans, Child, Optic nerve hypoplasia, business.industry, Pregnancy Complications, Hematologic, Infant, Septo-optic dysplasia, medicine.disease, United Kingdom, Clinical trial, Pregnancy Trimester, First, Dysplasia, Child, Preschool, Pediatrics, Perinatology and Child Health, Etiology, Female, business, Diabetes Insipidus, Maternal Age
Abstract

Background: Septo-optic dysplasia (SOD) is a disorder with postulated environmental and genetic aetiology. This study delineates clinical features and potential perinatal environmental factors along with epidemiology in SOD children. Methods: Assessment of patients with SOD triad features in the UK West Midlands region. Results: Of 227 patients identified between 1998 and 2009 with 1 or more feature of the triad, 55 had midline defects, 149 had optic nerve hypoplasia and 132 had hypopituitarism. Eighty-eight children (52% males; incidence 8.3/100,000 live births) had SOD defined as 2 out of 3 features and 21 (24%) had all 3. Sixty-one percent had anterior pituitary deficiency and 21.5% had diabetes insipidus. Median maternal/paternal ages in SOD were 21 and 23.5 years, compared to UK means of 29.3 and 32.4 years (p < 0.001). First trimester bleeding was markedly increased at 12/48 (25%) compared to 0.07% in the UK (p < 0.001). Ethnicity showed a non-significant higher prevalence in Afro-Caribbean and mixed race groups, and significantly lower prevalence (p = 0.004) in South Asian groups compared to West Midland and Birmingham city data: 8% versus 2.5 and 6.7%, 9% versus 1.8 and 3.2% and 3% versus 8.4 and 21%, respectively. Conclusions: SOD is associated with younger maternal and paternal age, primigravida births and ethnic differences. Increased first trimester bleeding may indicate that SOD is a vascular disruption sequence.

Published
2012
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28. Intermolecular and Selective Synthesis of 2,4,5-Trisubstituted Oxazoles by a Gold-Catalyzed Formal [3+2] Cycloaddition

Author

Alex Cremonesi, Paul W. Davies, and Lidia Dumitrescu

Subjects
Chemistry, Intermolecular force, Organic chemistry, Homogeneous catalysis, General Medicine, General Chemistry, Catalysis, Cycloaddition
Abstract

Trisubstituted 1,3-oxazoles are smoothly prepared by the intermolecular reaction of pyridine-N-aminides with ynamides tolerating a variety of functional groups.

Published
2011
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29. An efficient and selective synthesis of 2,5-substituted pyrroles by gold-catalysed ring expansion of alkynyl aziridines

Author

Nicolas Martin and Paul W. Davies

Subjects
chemistry.chemical_classification, Range (particle radiation), Chemistry, Organic Chemistry, Ring (chemistry), Biochemistry, Combinatorial chemistry, Catalysis, Inorganic Chemistry, chemistry.chemical_compound, Materials Chemistry, Physical and Theoretical Chemistry, Counterion, Pyrrole
Abstract

A range of substituted alkynyl aziridines undergo a ring expansion to afford 2,5-substituted pyrroles under gold catalysis. While effective conditions can be generated from other gold sources, a combination of Ph 3 PAuCl and AgOTs generate a catalyst system that provides extremely clean cycloisomerisation reactions requiring minimal work-up and purification.

Published
2011
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30. Alkynes as 'masked' ylides under noble-metal catalysis

Author

Paul W. Davies

Subjects
Chemistry, General Chemical Engineering, Atom economy, engineering, chemistry.chemical_element, Organic chemistry, Noble metal, General Chemistry, engineering.material, Photochemistry, Platinum, Sulfur, Catalysis
Abstract

Our development of noble-metal-catalyzed reactions that involve the preparation of sulfur ylides directly from alkynes, without employing sacrificial functionality, is reviewed.

Published
2010
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32. Impact of nutrient density of nocturnal enteral feeds on appetite: a prospective, randomised crossover study

Author

Ian W. Booth, Anne Daly, Sharon Evans, Anita MacDonald, and Paul W. Davies

Subjects
Male, medicine.medical_specialty, Home Nursing, media_common.quotation_subject, Appetite, Nocturnal, Enteral administration, Nutrient density, Eating, Enteral Nutrition, Animal science, Nutrient, Internal medicine, Dietary Carbohydrates, Humans, Medicine, Prospective Studies, Child, media_common, Food, Formulated, Cross-Over Studies, Anthropometry, business.industry, Infant, Dietary Fats, Crossover study, Parenteral nutrition, Endocrinology, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, Original Article, Dietary Proteins, Child Nutritional Physiological Phenomena, Energy Intake, business
Abstract

Objective: To determine whether the energy density of isocaloric nocturnal enteral feeds (NEF) influences daily nutrient intake in children. Method: In a 6 week, randomised, crossover trial, the impact on spontaneous nutrient intake of manipulating the energy density of two isocaloric overnight feeds (1.0 kcal/ml and 1.5 kcal/ml) was compared in a group of 32 children aged 1–10 years (or 8–25 kg body weight) on long term, overnight enteral feeding at home. Total daily oral energy, protein, fat and carbohydrate intake were assessed using 3 day food diaries. Anthropometric data were also recorded during the study. Results: Spontaneous intakes of energy, protein, fat and carbohydrate from food were 20–30% greater when receiving the lower nutrient density feed (1 kcal/ml). This was due to a gender effect; males consumed twice as much protein from food than females and had slightly higher (but not significant) energy and fat intakes when on the larger volume feed. All children increased in weight, height and mid-upper arm circumference in the 6 week period. Conclusions: Children appear to tolerate and grow equally well, irrespective of the nutrient density and volume of NEF taken. However, it appears that children will consume a more energy and nutrient dense oral diet when given their NEF as a higher volume/lower nutrient density feed. This is particularly so for boys, while for girls the volume of NEF or feed concentration appeared to have no impact on quantity of oral diet taken. However, further blinded studies with larger subject numbers would be useful to support these findings.

Published
2007
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34. Catalytic Carbophilic Activation: Catalysis by Platinum and Gold π Acids

Author

Paul W. Davies and Alois Fürstner

Subjects
chemistry.chemical_classification, Chemistry, chemistry.chemical_element, General Chemistry, Carbocation, Combinatorial chemistry, Catalysis, Coordination complex, Cycloisomerization, Organogold chemistry, Electrophile, Organic chemistry, Reactivity (chemistry), Platinum
Abstract

The ability of platinum and gold catalysts to effect powerful atom-economic transformations has led to a marked increase in their utilization. The quite remarkable correlation of their catalytic behavior with the available structural data, coordination chemistry, and organometallic reactivity patterns, including relativistic effects, allows the underlying principles of catalytic carbophilic activation by pi acids to be formulated. The spectrum of reactivity extends beyond their utility as catalytic and benign alternatives to conventional stoichiometric pi acids. The resulting reactivity profile allows this entire field of catalysis to be rationalized, and brings together the apparently disparate electrophilic metal carbene and nonclassical carbocation explanations. The advances in coupling, cycloisomerization, and structural reorganization--from the design of new transformations to the improvement to known reactions--are highlighted in this Review. The application of platinum- and gold-catalyzed transformations in natural product synthesis is also discussed.

Published
2007
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36. ChemInform Abstract: Regioselective Functionalization of Dibenzothiophenes Through Gold-Catalyzed Intermolecular Alkyne Oxyarylation

Author

Paul W. Davies, Matthew J. Barrett, and Richard S. Grainger

Subjects
chemistry.chemical_classification, Chemistry, Intermolecular force, Alkyne, Regioselectivity, Organic chemistry, Surface modification, General Medicine, Catalysis
Abstract

An efficient procedure is elaborated for the Au-catalyzed synthesis of 4-substituted dibenzothiophenes from S-oxides (I) and alkynes (II).

Published
2015
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37. ChemInform Abstract: Nucleophilic Nitrenoids Through π-Acid Catalysis: Providing a Common Basis for Rapid Access into Diverse Nitrogen Heterocycles

Author

Paul W. Davies and Miguel Garzón

Subjects
chemistry.chemical_compound, Acid catalysis, chemistry, Nucleophile, Functional group, Reactivity (chemistry), General Medicine, Triple bond, Carbene, Combinatorial chemistry, Cycloaddition, Catalysis
Abstract

Nitrogen heterocycles are some of the most important and sought-after structural motifs in synthetic chemistry. General methods that can be applied towards a structurally diverse range of different scaffolds are rare. This Focus Review discusses an emerging area with the field of π-acid catalysis based on the activation of carbon-carbon triple bonds in conjunction with nucleophilic nitrenoids. The resulting approach provides ready access into α-imino metal carbene reactivity patterns that can be employed in a number of quenching processes to realize a variety of powerful new transformations. The resulting methods are characterized by high efficiency, simple and straightforward reaction set ups, mild conditions, and excellent functional group tolerance. In this Focus Review the different nucleophilic nitrenoid types are explored showing how they can be used across a range of (poly)cyclization and formal cycloaddition processes to provide an alternative and direct disconnection pathway in the generation of N-heterocyclic motifs.

Published
2015
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38. Divergent C-H Insertion-Cyclization Cascades of N-Allyl Ynamides

Author

Holly V. Adcock, Paul W. Davies, and Elli Chatzopoulou

Subjects
Molecular complexity, Cyclization Reactions, Cyclopropanation, Stereochemistry, Communication, cyclopropanation, General Chemistry, gold, Combinatorial chemistry, Catalysis, Communications, Ketenimine, Isotopic labeling, carbenes, chemistry.chemical_compound, chemistry, Pyridine, ynamides, Reactivity (chemistry), nitrogen heterocycles, Selectivity, Carbene
Abstract

Gold carbene reactivity patterns were accessed by ynamide insertion into a C(sp3)—H bond. A substantial increase in molecular complexity occurred through the cascade polycyclization of N‐allyl ynamides to form fused nitrogen‐heterocycle scaffolds. Exquisite selectivity was observed despite several competing pathways in an efficient gold‐catalyzed synthesis of densely functionalized C(sp3)‐rich polycycles and a copper‐catalyzed synthesis of fused pyridine derivatives. The respective gold–keteniminium and ketenimine activation pathways have been explored through a structure–reactivity study, and isotopic labeling identified turnover‐limiting C—H bond‐cleavage in both processes.

Published
2015

39. Regioselective functionalisation of dibenzothiophenes through gold-catalysed intermolecular alkyne oxyarylation

Author

Richard S. Grainger, Paul W. Davies, and Matthew J. Barrett

Subjects
chemistry.chemical_classification, Organic Chemistry, Intermolecular force, Alkyne, Regioselectivity, Sulfoxide, Bond formation, Biochemistry, Combinatorial chemistry, Catalysis, chemistry.chemical_compound, chemistry, Organic chemistry, Physical and Theoretical Chemistry
Abstract

A protocol has been developed for direct Csp(3)-Csp(2) bond formation at the 4- and 6-positions of dibenzothiophenes using a gold(I) catalyst with terminal alkynes and dibenzothiophene-S-oxides. The sulfoxide acts as a traceless directing group to avoid the need to prefunctionalise at carbon. The iterative use of this protocol is possible and has been employed in the preparation of novel macrocyclic structures. In addition, a cascade process shows how oxyarylations can be combined with other processes resulting in complex, highly efficient transformations.

Published
2015

40. ChemInform Abstract: A Direct Route into Fused Imidazo-Diazines and Imidazo-Pyridines Using Nucleophilic Nitrenoids in a Gold-Catalyzed Formal [3 + 2]-Dipolar Cycloaddition

Author

Paul W. Davies and Miguel Garzón

Subjects
chemistry.chemical_compound, Direct route, chemistry, Nucleophile, Regioselectivity, General Medicine, Pyridinium, Combinatorial chemistry, Cycloaddition, Catalysis
Abstract

Pyridinium N-(heteroaryl)aminides can be employed as robust and practical synthetic equivalents of nucleophilic 1,3-N,N-dipoles in a formal cycloaddition onto electron-rich alkynes under gold catalysis. Convergent and regioselective access to five types of imidazo-fused heteroaromatics is provided from the appropriate aminide. The efficient transformation accommodates significant structural variation around the aminide, ynamide, or indolyl-alkyne reactants and tolerates sensitive functional groups.

Published
2015
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41. Bidentate Ruthenium Vinylcarbene Catalysts Derived from Enyne Metathesis

Author

Alois Fürstner, Christian W. Lehmann, and Paul W. Davies

Subjects
Silylation, Organic Chemistry, Substituent, chemistry.chemical_element, Metathesis, Enyne metathesis, Silyl ether, Ruthenium, Inorganic Chemistry, chemistry.chemical_compound, chemistry, Phenylacetylene, Polymer chemistry, Moiety, Organic chemistry, Physical and Theoretical Chemistry
Abstract

The preparation, structure, and catalytic activity of a series of bidentate η1-vinylcarbene ruthenium complexes derived from the standard metathesis catalysts 1, 2, or 4 by enyne metathesis with phenylacetylene derivatives bearing an isopropoxy substituent at their ortho position are described. Terminal as well as non-terminal phenylacetylene derivatives react with similar ease, thus providing ample opportunity for the preparation of catalysts with tailor-made properties. Use of the silyl propargyl ether derivative 13b as the substrate results in the formation of complex 15, in which the silyl ether moiety rather than the isopropoxy substituent ligates the metal center. The structures of the new chelate complexes 6, 7, 9, 14, and 15 in the solid state were determined by X-ray crystallography.

Published
2005
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42. Protein substitute dosage in PKU: how much do young patients need?

Author

Ian W. Booth, Kate Hall, Paul W. Davies, Anupam Chakrapani, Anita MacDonald, Christian J. Hendriksz, Anne Daly, and D Asplin

Subjects
Male, medicine.medical_specialty, Evening, Phenylalanine, Blood phenylalanine, Washout period, Phenylketonurias, Internal medicine, Diet, Protein-Restricted, Humans, Medicine, Prospective Studies, Child, Cross-Over Studies, Dose-Response Relationship, Drug, business.industry, Low dose, Carbohydrate, Crossover study, Endocrinology, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, Original Article, Dietary Proteins, business
Abstract

Background: The optimal dose of protein substitute has not been determined in children with phenylketonuria (PKU). Aim: To determine if a lower dose of protein substitute could achieve the same or better degree of blood phenylalanine control when compared to the dosage recommended by the UK MRC. 1 Methods: In a six week randomised, crossover study, two doses of protein substitute (Protocol A: 2 g/kg/day of protein equivalent; Protocol B: 1.2 g/kg/day protein equivalent) were compared in 25 children with well controlled PKU aged 2–10 years (median 6 years). Each dose of protein substitute was taken for 14 days, with a 14 day washout period in between. Twice daily blood samples (fasting pre-breakfast and evening, at standard times) for plasma phenylalanine were taken on day 8–14 of each protocol. The median usual dose of protein substitute was 2.2 g/kg/day (range 1.5–3.1 g/kg/day). Results: When compared with control values, median plasma phenylalanine on the low dose of protein substitute increased at pre-breakfast by 301 μmol/l (95% CI 215 to 386) and in the evening by 337 μmol/l (95% CI 248 to 431). On the high dose of protein substitute, plasma phenylalanine concentrations remained unchanged when compared to control values. However, wide variability was seen between subjects. Conclusions: A higher dosage of protein substitute appeared to contribute to lower blood phenylalanine concentrations in PKU, but it did have a variable and individual impact and may have been influenced by the carbohydrate (+/− fat) content of the protein substitute.

Published
2005
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43. Protein substitutes for PKU: What's new?

Author

D Asplin, A. MacDonald, Paul W. Davies, S. K. Hall, Anupam Chakrapani, Anne Daly, and G. Rylance

Subjects
chemistry.chemical_classification, medicine.medical_specialty, Dose, biology, Novel protein, business.industry, Phenylalanine, Blood phenylalanine, Protein S, Amino acid, Endocrinology, chemistry, Phenylketonurias, Internal medicine, Dietary Supplements, Genetics, medicine, biology.protein, Humans, Treatment strategy, Dietary Proteins, Patient compliance, business, Genetics (clinical)
Abstract

Summary: Protein substitutes are an essential component in the management of phenylketonuria. A series of studies at Birmingham Children's Hospital have investigated their optimal dosage, timing and practical administration as well as the efficacy and tolerance of novel protein substitutes. The key findings are as follows. (1) Lower dosages of protein substitute (1.2 g/kg per day of protein equivalent) adversely affect blood phenylalanine control in children aged 1–10 years. (2) There is wide variability in 24 h blood phenylalanine concentrations. (3) Adjusting protein substitute timing during daytime does not reduce blood phenylalanine variability. (4) Repeated 4 h administration of protein substitute throughout 24 h markedly reduces phenylalanine variability and leads to lower phenylalanine concentrations. (5) The new, concentrated, low-volume protein substitutes and amino acid tablet preparations are efficacious and well tolerated by patients. (6) Administration of protein substitute as a gel or paste has reduced difficulties with administration of protein substitute in children. These findings are important in rationalizing treatment strategies, improving patient compliance and overall in improving blood phenylalanine control.

Published
2004
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44. Site-specific introduction of gold-carbenoids by intermolecular oxidation of ynamides or ynol ethers

Author

Nicolas Martin, Alex Cremonesi, and Paul W. Davies

Subjects
Carboxylic acid, Stereoisomerism, Imides, Catalysis, chemistry.chemical_compound, Nucleophile, Materials Chemistry, Organic chemistry, Molecule, Reactivity (chemistry), chemistry.chemical_classification, Molecular Structure, Chemistry, Intermolecular force, Metals and Alloys, Esters, General Chemistry, Amides, Combinatorial chemistry, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Ceramics and Composites, Ynol, Gold, Methane, Oxidation-Reduction, Ethers
Abstract

Ynamides and ynol ethers undergo intermolecular gold-catalysed reaction with a nucleophilic oxidant to access metal-carbenoid reactivity patterns. A site-specific oxidation/1,2-insertion cascade is used for a general access to functionalised α,β-unsaturated carboxylic acid derivatives and vinylogous carbimates.

Published
2011
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47. A direct route into fused imidazo-diazines and imidazo-pyridines using nucleophilic nitrenoids in a gold-catalyzed formal [3 + 2]-dipolar cycloaddition

Author

Miguel, Garzón and Paul W, Davies

Abstract

Pyridinium N-(heteroaryl)aminides can be employed as robust and practical synthetic equivalents of nucleophilic 1,3-N,N-dipoles in a formal cycloaddition onto electron-rich alkynes under gold catalysis. Convergent and regioselective access to five types of imidazo-fused heteroaromatics is provided from the appropriate aminide. The efficient transformation accommodates significant structural variation around the aminide, ynamide, or indolyl-alkyne reactants and tolerates sensitive functional groups.

Published
2014

48. A gold-catalysed fully intermolecular oxidation and sulfur-ylide formation sequence on ynamides

Author

Mickaël, Dos Santos and Paul W, Davies

Abstract

An efficient C-O, C-S and C-C bond-forming sequence leads to functionalised compounds bearing sulfur-substituted quaternary carbons. Ynamides are employed as diazo-equivalents to access the [2,3]-sigmatropic rearrangements of allyl sulfonium ylides by a three-component chemoselective oxidation and intermolecular ylide formation.

Published
2014

49. 1,2-N-migration in a gold-catalysed synthesis of functionalised indenes by the 1,1-carboalkoxylation of ynamides

Author

Holly V, Adcock, Thomas, Langer, and Paul W, Davies

Subjects
carbenes, Indenes, Molecular Structure, cycloisomerisation, regioselectivity, ynamides, Stereoisomerism, Gold, Amides, Skeletal Rearrangements, Catalysis, Communications
Abstract

Unique α-hemiaminal ether gold carbene intermediates were accessed by a gold-catalysed 1,1-carboalkoxylation strategy and evolved through a highly selective 1,2-N-migration. This skeletal rearrangement gave functionalised indenes, and isotopic labelling confirmed the rare C–N bond cleavage of the ynamide moiety. The effect of substituents on the migration has been explored, and a model is proposed to rationalise the observed selectivity.

Published
2014

50. Stereochemistry on the shores

Author

Paul W. Davies

Subjects
Stereochemistry, Chemistry, General Chemical Engineering, Carbon chemistry, Supramolecular chemistry, Organic chemistry, Nanotechnology, General Chemistry
Abstract

The annual Burgenstock conference brings together a select band of chemists to talk about the many different facets of stereochemistry, and the unique format of the meeting encourages plenty of discussion and debate alongside the traditional lectures and poster presentations.

Published
2010
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