361 results on '"James Shepherd"'
Search Results
2. A shortcut to the thermodynamic limit for quantum many-body calculations of metals
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Laura Weiler, Andreas Grüneis, Tobias Schäfer, James Shepherd, Sai Kumar Ramadugu, and Tina Mihm
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Computer Networks and Communications ,0103 physical sciences ,Computer Science (miscellaneous) ,02 engineering and technology ,021001 nanoscience & nanotechnology ,010306 general physics ,0210 nano-technology ,01 natural sciences ,Computer Science Applications - Abstract
Computationally efficient and accurate quantum mechanical approximations to solve the many-electron Schrödinger equation are crucial for computational materials science. Methods such as coupled cluster theory show potential for widespread adoption if computational cost bottlenecks can be removed. For example, extremely dense k-point grids are required to model long-range electronic correlation effects, particularly for metals. Although these grids can be made more effective by averaging calculations over an offset (or twist angle), the resultant cost in time for coupled cluster theory is prohibitive. We show here that a single special twist angle can be found using the transition structure factor, which provides the same benefit as twist averaging with one or two orders of magnitude reduction in computational time. We demonstrate that this not only works for metal systems but also is applicable to a broader range of materials, including insulators and semiconductors.
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- 2021
3. 1897. The Decline of Respiratory Viruses During the SARS-CoV-2 Pandemic: Public Health Interventions vs. Viral Competition?
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Waleed Malik, Ritche Hao, and James Shepherd
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Infectious Diseases ,Oncology - Abstract
Background With the spread of the SARS-CoV-2 pandemic in 2020 and the attendant global precautions such as masking, travel restrictions and social distancing, the WHO FluNet data indicated a decline in flu rates. The CDC data for the 2020-2021 season showed the same decline in US flu as well as other respiratory viruses. Two hypotheses to explain the observed phenomenon are the impact of non-pharmaceutical interventions (NPI) to prevent SARS-CoV-2 infection and suppression of other respiratory viruses by SARS-CoV-2 through a form of resource competition. Methods We conducted a study using the EPIC Slicer Dicer analytics tool and the Yale Internal Medicine COVID-19 Database to retrieve data from the Yale New Haven Health System (YNHHS). We tabulated the total number of positive and negative tests for SARS-CoV-2 and a panel of respiratory viruses from September 2, 2018 to April 30, 2022 to cover pre- and peri-pandemic periods. These results were divided into three age groups: ≤12, 13-59, and ≥60. Epidemic curves of each virus with respect to each other, the season, and the introduction of NPIs were constructed to help differentiate between the two hypotheses. Results Pre-pandemic data from 09/2018 to 02/2020 revealed seasonal spikes in influenza A and B with 254 positive weekly influenza A/B tests from 11/2018 to 02/2019 for a positivity rate of 7.97% and 481 positive weekly tests (10.53% positivity rate [PR]) from November 2019 to February 2020. There were only 0.35 positive weekly influenza A/B tests (0.05% PR) from 11/2020 to 02/2021 with 2018 positive weekly tests (6.45% PR) for SARS-CoV-2 over the same period. From 11/2020 to 02/2021, there were 56 positive weekly influenza A/B tests (1.44% PR) and 4347 positive weekly SARS-CoV-2 tests (10.35% PR). From 07/2021 to 11/2021, there was an increased rate of positive RSV tests (82 per week, 15.76% PR) and rhinovirus tests (58 per week, 18.73% PR). There were 803 positive weekly tests (2.53% positivity rate) for SARS-CoV-2 over this same period. Conclusion Since the start of the SARS-CoV-2 pandemic, the number of positive tests for influenza A/B and seasonal respiratory viruses have not reached pre-pandemic levels across the YNHHS. However, rates of influenza and other respiratory viruses have increased since the relaxation of NPIs. Disclosures All Authors: No reported disclosures.
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- 2022
4. Descriptive comparison of admission characteristics between pandemic waves and multivariable analysis of the association of the Alpha variant (B.1.1.7 lineage) of SARS-CoV-2 with disease severity in inner London
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Keith Morris, Judith Breuer, NgeeKeong Tan, Eric Witele, Sophie Hunter, Monica Panca, Aleks Marek, Paul Flowers, Gaia Nebbia, Sam Haldenby, Jacqui Prieto, Gee Yen Shin, Fiona Mapp, Andrew Copas, Mark Hopkins, Oliver Stirrup, Adam Witney, Kenneth Laing, May Rabuya, Vasa Curcin, Alison Holmes, Mohammad Raza, Wenjuan Wang, Rachel Williams, David Robertson, Julie Samuel, Rory Gunson, Helen Wheeler, Alexander J Keeley, Paul Randell, Cariad Evans, Tabassum Khan, Michelle Ramsay, Darren Smith, James Price, Sarah Francis, Shazaad Ahmad, Finola Higgins, Eleni Nastouli, Abhinav Kumar, Katie Johnson, Sharon Glaysher, Scott Elliott, Rebecca Gregory, Matthew D Parker, Helen Umpleby, Emanuela Pelosi, Emma Thomson, Anna Riddell, Yanzhong Wang, David Harrington, Alexandra Bailey, Nikunj Mahida, Charlotte Williams, Tanzina Haque, David G Partridge, Yusri Taha, Adrienn Angyal, Catherine Houlihan, James Shepherd, Hayley Colton, Chris Davis, Adela Alcolea-Medina, Themoula Charalampous, Beatrix Kele, Irene Monahan, Guy Mollett, Sunando Roy, Joshua Taylor, Sophie Weller, Eleri Wilson-Davies, Joseph Hughes, Tabitha Mahungu, Cassie Pope, Samuel Robson, Kordo Saeed, Luke Snell, James Blackstone, Leanne Hockey, Georgia Marley, Christine Peters, Flavia Flaviani, Bindi Patel, Rahul Batra, Jennifer Hart, Nadua Bayzid, Marius Cotic, Luke Green, Amy State, Alison Cope, Peijun Zhang, Max Whiteley, Marta Gallis Ramalho, Stella Christou, Paige Wolverson, Joe Heffer, Nikki Smith, Salman Goudarzi, Kate Cook, Katie Loveson, Buddhini Samaraweera, Stephen Aplin, Sarah Jeremiah, Matthew Harvey, Thea Sass, Dan Frampton, Matt Byott, Judith Heaney, Ana da Silva Filipe, Thushan de Silva, Jonathan Edgeworth, Luke B Snell, Leonardo de Jongh, Teresa Cutino-Moguel, Raghavendran Kulasegaran-Shylini, Claire E. Broad, Dola Owoyemi, Clare Coffey, Martina Cummins, Tyrra D’Souza, Emily Goldstein, Emilie Shepherd, Katherine Smollett, Alice Broos, Stephen Carmichael, Nicholas Suarez, Sreenu Vattipally, Ioulia Tsatsani, Jacqueline McTaggart, Stephanie McEnhill, Adela Medina, Jörg Saßmannshausen, Sulekha Gurung, Anu Augustine, Sid Mookerjee, Krystal Johnson, Thilipan Thaventhiran, Damien Mine, Isa Ahmad, Anitha Ramanathan, Anu Chawla, Alistair Derby, Becky Taylor, Charles Numbere, Jenifer Mason, Nicholas Machin, Julie Cawthorne, Ryan George, James Montgomery, Deborah McKew, Angela Cobb, Maria Leader, Shirelle Burton-Fanning, Lydia Taylor, Matthew Bashton, Matthew Crown, Matthew Loose, Patrick McClure, Mitch Clarke, Elaine Baxter, Carl Yates, Irfan Aslam, Vicki Fleming, Michelle Lister, Johnny Debebe, Nadine Holmes, Christopher Moore, Matt Carlile, Dianne Irish-Tavares, Mia De Mesa, Vicky Pang, Jelena Heaphy, Wendy Chatterton, Monika Pusok, Tranprit Saluja, Zahira Maqsood, Angie Williams, Debbie Devonport, Lucy Palinkas, Diane Thomlinson, Julie Booth, Ashok Dadrah, Amanda Symonds, Cassandra Craig, Benjamin B Lindsey, Benjamin H Foulkes, Stavroula F Louka, Phillip Ravencroft, Sharon Hsu, Nasar Ali, Rasha Raghei, Samantha E Hansford, Hailey R Hornsby, Phil Wade, Kay Cawthron, Maqsood Khan, Amber Ford, Imogen Wilson, Kate Harrington, Nic Tinker, Sally Nyinza, Adhyana Mahanama, Siona Silviera, Christopher Fearn, Claudia Cardosa Pereira, Vaz Malik, Gema Martinez-Garcia, Leila Hail, Ndifreke Atang, Helen Francis, Milica Rajkov, Rachel McComish, Alyson MacNeil, Alif Tamuri, Stefan Piatek, Snell, Luke B [0000-0002-6263-9497], Wang, Wenjuan [0000-0002-1879-7332], Charalampous, Themoula [0000-0002-8914-5868], Nebbia, Gaia [0000-0002-7524-1947], Wang, Yanzhong [0000-0002-0768-1676], and Apollo - University of Cambridge Repository
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SARS-CoV-2 ,public health ,B100 ,COVID-19 ,General Medicine ,A300 ,Severity of Illness Index ,virology ,B900 ,London ,Medicine ,Humans ,RNA, Viral ,epidemiology ,Pandemics - Abstract
BackgroundThe Alpha variant (B.1.1.7 lineage) of SARS-CoV-2 emerged and became the dominant circulating variant in the UK in late 2020. Current literature is unclear on whether the Alpha variant is associated with increased severity. We linked clinical data with viral genome sequence data to compare admitted cases between SARS-CoV-2 waves in London and to investigate the association between the Alpha variant and the severity of disease.MethodsClinical, demographic, laboratory and viral sequence data from electronic health record systems were collected for all cases with a positive SARS-CoV-2 RNA test between 13 March 2020 and 17 February 2021 in a multisite London healthcare institution. Multivariate analysis using logistic regression assessed risk factors for severity as defined by hypoxia at admission.ResultsThere were 5810 SARS-CoV-2 RNA-positive cases of which 2341 were admitted (838 in wave 1 and 1503 in wave 2). Both waves had a temporally aligned rise in nosocomial cases (96 in wave 1 and 137 in wave 2). The Alpha variant was first identified on 15 November 2020 and increased rapidly to comprise 400/472 (85%) of sequenced isolates from admitted cases in wave 2. A multivariate analysis identified risk factors for severity on admission, such as age (OR 1.02, 95% CI 1.01 to 1.03, for every year older; pConclusionsOur analysis is the first in hospitalised cohorts to show increased severity of disease associated with the Alpha variant. The number of nosocomial cases was similar in both waves despite the introduction of many infection control interventions before wave 2.
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- 2022
5. DIY Fraud Investigation and Access to Justice: A Case Study
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David William James Shepherd
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Political science ,050901 criminology ,0502 economics and business ,05 social sciences ,Justice (ethics) ,0509 other social sciences ,Criminology ,Law ,050203 business & management - Abstract
Access to justice for fraud victims remains an enduring problem in the UK. Law enforcement agencies have limited capacity and capabilities for delivering criminal justice. Civil justice is so expensive that it is only an option for those with deep pockets or lucky enough to find competent professionals who are willing to work under a conditional fee arrangement (no-win-no-fee). This article describes the progress of a fraud case from a victim’s perspective through both the criminal and civil justice systems in the UK. The experiences describe incompetence in law enforcement, dishonesty and incompetence amongst lawyers and other professionals, and fractured, self-centred justice systems that poorly serve the public in England and Wales.
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- 2020
6. The media, personal digital criminal legacies and the experience of offenders convicted of occupational fraud and corruption
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Mark Button, Dean Blackbourn, Emma Beatty, and David William James Shepherd
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Coping (psychology) ,Health (social science) ,Public Administration ,Sociology and Political Science ,Social Psychology ,Digital era ,media_common.quotation_subject ,medicine.medical_treatment ,corruption ,050801 communication & media studies ,Prison ,Criminology ,Health(social science) ,Newspaper ,0508 media and communications ,Political science ,medicine ,offenders ,media_common ,Rehabilitation ,business.industry ,050901 criminology ,05 social sciences ,Public sector ,media impact ,resettlement ,White-collar crime ,white-collar crime ,Content analysis ,fraud ,0509 other social sciences ,business ,Law - Abstract
Purpose The purpose of this paper is to explore the impact of media coverage on offenders convicted of occupational fraud and corruption in the UK. It examines the extent of media coverage and provides insights into the experiences of offenders. Design/methodology/approach The study is based upon interviews with 17 convicted offenders, and on a content analysis of one national and two regional newspapers in the UK. Findings The findings suggest that offenders convicted of occupational crime and corruption are more likely to experience media coverage than previously assumed and that personal digital criminal legacies create long-term labels which lead to economic strains and social fractures that hinder productive reintegration into society. Research limitations/implications The research is limited by a small sample frame in the UK. Nevertheless, the findings suggest further research is required as they have important implications for privacy and rehabilitation. Practical implications In particular, offenders and their families need support in dealing with their personal digital criminal legacies, accessing their privacy rights and coping with the strains created by online stigmatisation. From a policy perspective, the existing regulatory framework that supports rehabilitation in the UK, especially the increasingly archaic Rehabilitation of Offenders Act 1974, requires close examination and debate to ensure it is fit for the digital era. The findings also suggest that policies, practices and responsibilities of the public sector in employing offenders need to be examined. Originality/value It is a rare study of white-collar offenders after their release from prison. The findings are of relevance to criminal justice policy makers, rehabilitation services and academics.
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- 2019
7. Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant
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Mohammad Raza, Alison E. Mather, Gilberto Betancor, Ian Merrick, Ben Taylor, Mathew A. Beale, Helen Ward, Samir Dervisevic, Michelle Cronin, Aaron R. Jeffries, Louise Smith, Steven Rudder, Mara K. N. Lawniczak, Sascha Ott, Ashok Dadrah, Luke Bedford, Gabrielle Vernet, Erik M. Volz, Rahul Batra, Johnny Debebe, Caoimhe McKerr, Samantha McGuigan, Oliver Megram, Katie Jones, Mailis Maes, Rebecca Dewar, Emma Swindells, Robert E. Johnson, Myra Hosmillo, Wen C Yew, Vineet Patel, Scott Aj Thurston, Matthew Bashton, Luke B Snell, Lynn Monaghan, David Buck, Gregory R Young, Garren Scott, Louis du Plessis, Sara Kumziene-Summerhayes, David M. Aanensen, Carl Jones, Nadine Holmes, Bernardo Gutierrez, Elizabeth Wastenge, Stavroula F Louka, Dennis Wang, Richard I. Gregory, M. Estée Török, Alistair C. Darby, Ulf Schaefer, Marc Niebel, David Robertson, E. Thomson, Carol Churcher, Patrick C McClure, Scott Elliott, Sarah Jeremiah, Katerina Galai, Matthew W. Loose, Megan Mayhew, Adhyana I K Mahanama, Angeliki Karamani, Naomi R Park, David J. Williams, Lance Turtle, Lucy R. Frost, Alicia Thornton, Jennifier Liddle, M Morgan, Tim Wyatt, Paul W Bird, Chloe Bishop, Esther Robinson, Alasdair MacLean, Inigo Martincorena, Bridget A. Knight, Emma Meader, Thomas R. Connor, Hermione J. Webster, Peter Muir, Sarah Walsh, Stephanie W. Lo, Andrew Bosworth, Hannah E Bridgewater, David Simpson, Radoslaw Poplawski, Angus I. Best, David Baker, Laura Letchford, Cassie Breen, Yann Bourgeois, Matthew Gemmell, Nikki Smith, Alison Holmes, Iliana Georgana, Christophe Fraser, Natasha Jesudason, Johnathan M Evans, Rachael Stanley, Lesley-Anne Williams, Jessica Lynch, Hannah Lowe, Eleri Wilson-Davies, Paul A. Baker, Alex Makunin, James Bonfield, Helen Adams, Christopher Fearn, Peter J. Diggle, Harry D Wilson, Carmen F. Manso, Nichola Duckworth, D Haw, Anna L. Casey, Audrey Farbos, Sam Haldenby, Vicki Chalker, Roberto Amato, Elen De Lacy, Ben Farr, Eric Witele, Buddhini Samaraweera, G MacIntyre-Cockett, Husam Osman, Jane Greenaway, Justin O'Grady, Sally Forrest, Andrew Nelson, Monika Pusok, A Lloyd, Edward Barton, James W. Harrison, Sophie Palmer, Amanda Symmonds, James Shepherd, Nazreen F. Hadjirin, Stephen L. Michell, Mohammed O Hassan-Ibrahim, Fiona Ashcroft, Daniel Mair, Richard H. Myers, Dianne Irish-Tavares, Hannah C. Howson-Wells, Jacqui Prieto, Christine Sambles, Andrew Hesketh, Alp Aydin, Sónia Gonçalves, Tabitha Mahungu, Tanzina Haque, Nicholas Ellaby, Karen Oliver, Hannah Paul, Joanne Watts, Claire McMurray, Lisa J Levett, Darren Smith, Simon Cottrell, Joanna Warwick-Dugdale, Pinglawathee Madona, Matthew J. Dorman, Lizzie Meadows, Ali R Awan, Leanne M Kermack, Jennifer Hart, Angie Lackenby, Carol Scott, Michael Spencer Chapman, Lucille Rainbow, Kyriaki Nomikou, Julianne R Brown, Juan Ledesma, Adam P Westhorpe, Giri Shankar, Karlie Fallon, Tim J Sloan, Joanne Watkins, Robert Impey, Sue Edwards, Rebecca C H Brown, Robin J Moll, Karla Spellman, Laura Gifford, Jamie Young, Adrienn Angyal, Graham Phillip Taylor, Robin Manley, Gavin Dabrera, Michelle Wantoch, Rachel Williams, David Heyburn, Mirko Menegazzo, Derrick W. Crook, Gaia Nebbia, Rachel Nelson, Elaine O'Toole, Luke Foulser, Katherine L Harper, Fatima Downing, Hassan Hartman, Nathan Moore, Gemma L. Kay, Matthew Wyles, Thanh Le-Viet, Edith Vamos, John Sillitoe, Lesley Shirley, Nicholas J. Loman, Iona Willingham, Elihu Aranday-Cortes, Ian B Vipond, Jeremy Mirza, Alberto C Cerda, Michelle L Michelsen, Steven Riley, Alison Cox, Igor Siveroni, Nadua Bayzid, Shavanthi Rajatileka, Giselda Bucca, Benjamin J Cogger, Tim Boswell, Matthew J. Bull, Stephen Carmichael, Lisa Berry, Frances Bolt, Kylie E. C. Ainslie, Martyn Guest, Sarojini Pandey, Katherine L. Bellis, Shane A. McCarthy, Christopher Ruis, Fei Sang, David Bonsall, Danni Weldon, Alex Alderton, Lee Graham, Amy Trebes, Sally Corden, Adrian W Signell, Tanya Golubchik, Huw Gulliver, Rocio Martinez Nunez, Dinesh Aggarwal, Tanya Curran, Jonathan K. Ball, Sharif Shaaban, Paul Randell, Jillian Durham, Alec Birchley, Matilde Mori, Joana Dias, Katherine A Twohig, Grant Hall, Antony D Hale, Alan McNally, Jonathan D. Edgeworth, Safiah Afifi, Andrew Rambaut, Katherine Smollett, David N. Lee, Tamyo Mbisa, Shahjahan Miah, Steven Rushton, Grace Taylor-Joyce, Hannah M Pymont, Chloe L Fisher, Cordelia Langford, Alex G. Richter, Jane A. H. Masoli, Michael Gallagher, Vicki M. Fleming, Kathleen A. Williamson, Anna Price, Holli Carden, Khalil Abudahab, Joanne D. Stockton, Meera Unnikrishnan, Jennifer Collins, Emma Moles-Garcia, Michaela John, Christine Kitchen, Tranprit Saluja, Ian Harrison, Lily Tong, Thomas G. Thompson, Thomas Helmer, Amita Patel, Siona Silveira, Deborah Ashby, Claire M Bewshea, Anita Justice, Brendan A I Payne, Alexander J. Trotter, Nikos Manesis, Katie F. Loveson, Cristina V. Ariani, Wendy Chatterton, Robert J. Munn, Julian A. Hiscox, Robert Beer, Judith Breuer, Caroline E. Walters, Liam Crawford, Ara Darzi, Will P. M. Rowe, Cariad Evans, Matthew Parker, Tammy V Merrill, Louise Aigrain, Joshua Quick, Leigh M Jackson, Samuel M. Nicholls, Jonathan W. Moore, John A Hartley, Graham P. Taylor, Cherian Koshy, Shirelle Burton-Fanning, Sheila Waugh, Catherine Moore, Danielle C. Groves, Peijun Zhang, Sahar Eldirdiri, Derek Fairley, Tim E. A. Peto, Jack Cd Lee, Sharon Glaysher, Liam Prestwood, Hannah Dent, Anita Kenyon, Stephen P. Kidd, Nick Levene, Igor Starinskij, Joseph G. Chappell, Steve Paterson, Gary Eltringham, Laia Fina, Angela Marchbank, Daniel Bradshaw, Marina Escalera Zamudio, Scott Goodwin, Andrew D Beggs, Seema Nickbakhsh, Trevor Robinson, Christina Atchison, David K. Jackson, Kathy Li, Rory Gunson, Sunando Roy, Graham S Cooke, Steven Liggett, Yasmin Chaudhry, Anoop Chauhan, Ben Temperton, Mariateresa de Cesare, Paul E Brown, Li Xu-McCrae, Martin P McHugh, Catherine Ludden, Wendy Smith, Danielle Leek, Divya K. Shah, Judith Heaney, Dominic P. Kwiatkowski, Kate M. Johnson, Robin Howe, Malorie Perry, Tetyana I. Vasylyeva, David F. Bibby, Haowei Wang, Steve Palmer, Nicholas W Machin, Charlotte A Williams, Bree Gatica-Wilcox, Angie Green, John A. Todd, Paul Elliott, Noel Craine, Jeffrey K. J. Cheng, Kate Templeton, Jonathan Hubb, Joshua Maksimovic, Christl A. Donnelly, Monique Andersson, Christopher Holmes, Dimitris Grammatopoulos, Christopher B. Williams, David G Partridge, Aminu S Jahun, Alexander Adams, Marius Cotic, Sarah Essex, Christopher J. Moore, Trudy Workman, Nicola Sheriff, Helen L Lowe, Ewan M. Harrison, Dorota Jamrozy, Rachel Jones, Ellen Higginson, Erwan Acheson, Christopher R. Jones, Oliver G. Pybus, Francesc Coll, Sian Morgan, Paul J. Parsons, Patawee Asamaphan, Veena Raviprakash, Andrew R. Bassett, Declan Bradley, Laura Atkinson, Anthony Underwood, Graciela Sluga, Sally Kay, Ellena Brooks, Oliver Eales, Andrew Whitwham, Surendra Parmar, Angela Cowell, Nicole Pacchiarini, Theocharis Tsoleridis, Jason Coombes, Robert Davies, Flavia Flaviani, Benita Percival, Jenna Nichols, Natasha M. Johnson, Salman Goudarzi, Hibo Asad, Amanda Bradley, Hannah Jones, Chrystala Constantinidou, Georgina M McManus, Minal Patel, Steven Leonard, Rebecca Williams Bmbs, Andrew J. Page, Christoph Puethe, Nicola Reynolds, Amy Ash, John Danesh, Corin Yeats, Claudia Wierzbicki, Kordo Saeed, John Boyes, Michael A. Quail, Sharon J. Peacock, Nabil-Fareed Alikhan, Jon-Paul Keatley, Claudio Fronterre, Garry Scarlett, James McKenna, Thushan I de Silva, Malte L Pinckert, Kate B. Cook, Amy Gaskin, Rajiv Shah, Matthew T. G. Holden, Sophie J Prosolek, Nathaniel Storey, Ryan P George, Lindsay Coupland, Jenifer Mason, Matthew Carlile, Thomas D Stanton, Guy Mollett, Siddharth Mookerjee, Mary Ramsay, Steven Platt, Stephen W Attwood, Susanne Stonehouse, Sophie Jones, Venkat Sivaprakasam, Amy Plimmer, Mark Whitehead, Catherine Bresner, Stefanie V Lensing, Louissa R Macfarlane-Smith, Colin P. Smith, Wendy Hogsden, Charlotte Nelson, Ian Johnston, Jeffrey C. Barrett, Joshua B Singer, Samuel Robson, Zoltán Molnár, Emma L. Wise, Sian Ellard, Kim S Smith, Alice Broos, Manjinder Khakh, Kathryn A Jackson, Claire Cormie, Rachel Tucker, Ian Goodfellow, S.E. Moses, Nicola Cumley, Meera Chand, Debra Padgett, Cassandra S Malone, James V. Price, Themoula Charalampous, Ronan A Lyons, Natalie Groves, Stefan Rooke, Rebekah E Wilson, Stephen Bonner, Richard Stark, Sharon Campbell, Michelle Lister, Carlos Balcazar, Ana da Silva Filipe, Ben Warne, Thomas N. Williams, Marta Gallis, Lauren Gilbert, Rose K Davidson, Angela Helen Beckett, Ember Hilvers, Kathryn McCluggage, Eileen Gallagher, Charlotte Beaver, Nick Cortes, Alisha Davies, Yusri Taha, Leah Ensell, Emanuela Pelosi, Elias Allara, Cressida Auckland, Eleanor Drury, Richard Eccles, Adela Alcolea-Medina, William L Hamilton, Rich Livett, Rachel Blacow, Margaret Hughes, Sarah François, Melisa Louise Fenton, Liz Ratcliffe, Verity Hill, Stephanie Hutchings, Kathryn Ann Harris, Emma Betteridge, William D. Fuller, Sophia T Girgis, Louise Berry, Gemma Clark, Nicholas M Redshaw, Richard Hopes, Leonardo de Oliveira Martins, Alexander J Keeley, Beth Blane, Wendy S. Barclay, Victoria Wright, Anita Lucaci, Luke R. Green, Fenella D. Halstead, Sarah Wyllie, Iraad F. Bronner, Áine O'Toole, Ravi Gupta, Leanne Kane, Clare M. McCann, Michael R Chapman, David W Eyre, Kelly Bicknell, Aileen G. Rowan, Sara Rey, Shazaad Ahmad, Diana Rajan, S Taylor, Sarah J. O'Brien, Alessandro M Carabelli, Amelia Joseph, Max Whiteley, Riaz Jannoo, Victoria Blakey, Martin D. Curran, David J. Studholme, Harmeet K Gill, Thomas R. A. Davis, Sushmita Sridhar, Clive Graham, Julian Tang, Clare Pearson, Mark Kristiansen, Miren Iturriza-Gomara, National Institute for Health Research, and UK Research and Innovation
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Delta ,Adult ,Male ,2019-20 coronavirus outbreak ,COVID-19 Vaccines ,Vaccination Coverage ,Coronavirus disease 2019 (COVID-19) ,Adolescent ,General Science & Technology ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Vaccine Efficacy ,Biology ,Young Adult ,Exponential growth ,Ethnicity ,Prevalence ,Humans ,Child ,Aged ,Family Characteristics ,Multidisciplinary ,High prevalence ,COVID-19 Genomics UK (COG-UK) Consortium11‡ ,SARS-CoV-2 ,Age Factors ,COVID-19 ,Middle Aged ,Virology ,Hospitalization ,England ,Socioeconomic Factors ,COVID-19 Nucleic Acid Testing ,Child, Preschool ,Female ,Self Report - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were rising during early summer 2021 in many countries as a result of the Delta variant. We assessed reverse transcription polymerase chain reaction swab positivity in the Real-time Assessment of Community Transmission–1 (REACT-1) study in England. During June and July 2021, we observed sustained exponential growth with an average doubling time of 25 days, driven by complete replacement of the Alpha variant by Delta and by high prevalence at younger, less-vaccinated ages. Prevalence among unvaccinated people [1.21% (95% credible interval 1.03%, 1.41%)] was three times that among double-vaccinated people [0.40% (95% credible interval 0.34%, 0.48%)]. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination.
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- 2021
8. The SARS-CoV-2 Alpha variant is associated with increased clinical severity of COVID-19 in Scotland: a genomics-based retrospective cohort analysis
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Alasdair Campbell, David Robertson, Samantha Lycett, John Haughney, Ruth Forrester, James Shepherd, Martin P McHugh, David J Pascall, Sharif Shabaan, Ben Parcell, Katherine Smollett, Rachel M Blacow, Rory Gunson, Guy Mollett, Ludmila Fjodorova, Emily Goldstein, Ana Da Silva Filipe, Noha El Sakka, Naomi Bulteel, Matthew T. G. Holden, Eddie A. James, Chris Davis, Patrick Honour, Joseph Hughes, Sarah Clifford, Tim Lewis, Yusuke Onishi, and Robyn Campbell
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medicine.medical_specialty ,Lineage (genetic) ,business.industry ,Transmission (medicine) ,Internal medicine ,Severity of illness ,Medicine ,Alpha (ethology) ,Clinical severity ,Odds ratio ,Disease ,business ,Viral load - Abstract
Background The B.1.1.7 (Alpha) SARS-CoV-2 variant of concern was associated with increased transmission relative to other variants present at the time of its emergence and several studies have shown an association between the B.1.1.7 lineage infection and increased 28-day mortality. However, to date none have addressed the impact of infection on severity of illness or the need for oxygen or ventilation. Methods In this prospective clinical cohort sub-study of the COG-UK consortium, 1475 samples from hospitalised and community cases collected between the 1st November 2020 and 30th January 2021 were collected. These samples were sequenced in local laboratories and analysed for the presence of B.1.1.7-defining mutations. We prospectively matched sequence data to clinical outcomes as the lineage became dominant in Scotland and modelled the association between B.1.1.7 infection and severe disease using a 4-point scale of maximum severity by 28 days: 1. no support, 2. oxygen, 3. ventilation and 4. death. Additionally, we calculated an estimate of the growth rate of B.1.1.7-associated infections following introduction into Scotland using phylogenetic data. Results B.1.1.7 was responsible for a third wave of SARS-CoV-2 in Scotland, and rapidly replaced the previously dominant second wave lineage B.1.177) due to a significantly higher transmission rate (∼5 fold). Of 1475 patients, 364 were infected with B.1.1.7, 1030 with B.1.177 and 81 with other lineages. Our cumulative generalised linear mixed model analyses found evidence (cumulative odds ratio: 1.40, 95% CI: 1.02, 1.93) of a positive association between increased clinical severity and lineage (B.1.1.7 versus non-B.1.1.7). Viral load was higher in B.1.1.7 samples than in non-B.1.1.7 samples as measured by cycle threshold (Ct) value (mean Ct change: -2.46, 95% CI: -4.22, -0.70). Conclusions The B.1.1.7 lineage was associated with more severe clinical disease in Scottish patients than co-circulating lineages. Funding COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute. Funding was also provided by UKRI through the JUNIPER consortium (grant number MR/V038613/1). Sequencing and bioinformatics support was funded by the Medical Research Council (MRC) core award (MC UU 1201412).
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- 2021
9. Author response: Rapid feedback on hospital onset SARS-CoV-2 infections combining epidemiological and sequencing data
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Aleksandra Marek, Alexander J Keeley, Oliver Stirrup, Thushan I de Silva, Judith Breuer, Joshua B Singer, Matthew Parker, Asif U. Tamuri, Benjamin B Lindsey, Christine Peters, David G Partridge, James Blackstone, E. Thomson, Joseph Hughes, Francesc Coll, and James Shepherd
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medicine.medical_specialty ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Epidemiology ,Sequencing data ,medicine ,business ,Virology - Published
- 2021
10. White Collar Criminals’ Experience of Imprisonment in England and Wales: Revisiting the ‘special Sensitivity’ Debate
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David William James Shepherd, Dean Blackbourn, Mark Button, and Dennis Gough
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White (horse) ,History ,Sociology and Political Science ,Social Psychology ,050901 criminology ,05 social sciences ,Criminology ,Collar ,Clinical Psychology ,0501 psychology and cognitive sciences ,0509 other social sciences ,Imprisonment ,Law ,050104 developmental & child psychology - Abstract
This article explores white collar criminals’ experience of imprisonment in England and Wales. Based upon interviews with 13 convicted offenders after they had completed their imprisonment, it is the first study to date of this kind in England and Wales (all others have been based in prison). It offers a unique impartial insight of prisoners’ experience, beyond the influence of the prison walls. The paper explores the experience around the largely American ‘special sensitivity’ debate, over whether such offenders are more sensitive to prison. The research uncovers both positive experiences, labelled ‘good’, but also negative, labelled ‘bad’ (non-violent experiences) and ‘ugly’ (violent experiences). Overall the findings reveal it is difficult to apply the special sensitivity hypothesis universally to this group of offenders.
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- 2019
11. Genetic epidemiology of SARS-CoV-2 transmission in renal dialysis units - a high risk community-hospital interface
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Joseph Hughes, Oliver Stirrup, Alison Taylor, Natasha Johnson, Kathy Li, Rory Gunson, James Shepherd, Josh Singer, Jennifer S Lees, Yasmin A Parr, Judith G Breuer, Aislynn Taggart, Timothy Willem Jones, Y. Mun Woo, David Robertson, Patrick B. Mark, Igor Starinskij, Vattipally B. Sreenu, Marc Niebel, E. Thomson, Elihu Aranday-Cortes, Scott T W Morris, Ana da Silva Filipe, Natasha Jesudason, Daniel Mair, Jamie P. Traynor, Rajiv Shah, Kyriaki Nomikou, Antonia Ho, Zoe Cousland, Kirstyn Brunker, Alasdair MacLean, Colin C. Geddes, Peter C. Thomson, Sarah E. McDonald, Stephen Carmichael, Jonathan Price, Jenna Nichols, Carlos Varon Lopez, Patawee Asamaphan, Lily Tong, Katherine Smollett, Mair, Daniel [0000-0001-7169-9080], Nomikou, Kyriaki [0000-0002-7013-1853], Niebel, Marc [0000-0003-2515-6151], Shah, Rajiv [0000-0002-2827-5108], Jones, Timothy PW [0000-0001-6147-6748], Starinskij, Igor [0000-0001-8585-5929], Mark, Patrick B [0000-0003-3387-2123], and Apollo - University of Cambridge Repository
- Subjects
medicine.medical_specialty ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Infection control ,Renal Dialysis ,Epidemiology ,medicine ,Humans ,Molecular Epidemiology ,SARS-CoV-2 ,business.industry ,Transmission (medicine) ,fungi ,COVID-19 ,Outbreak ,Bayes Theorem ,Renal dialysis unit ,Hospitals ,Community hospital ,Rapid sequencing ,Haemodialysis ,Increased risk ,Genetic epidemiology ,Emergency medicine ,Dialysis unit ,Nosocomial ,business - Abstract
ObjectivesPatients requiring haemodialysis are at increased risk of serious illness with SARS-CoV-2 infection. To improve the understanding of transmission risks in six Scottish renal dialysis units, we utilised the rapid whole-genome sequencing data generated by the COG-UK consortium.MethodsWe combined geographical, temporal and genomic sequence data from the community and hospital to estimate the probability of infection originating from within the dialysis unit, the hospital or the community using Bayesian statistical modelling and compared these results to the details of epidemiological investigations.ResultsOf 671 patients, 60 (8.9%) became infected with SARS-CoV-2, of whom 16 (27%) died. Within-unit and community transmission were both evident and an instance of transmission from the wider hospital setting was also demonstrated.ConclusionsNear-real-time SARS-CoV-2 sequencing data can facilitate tailored infection prevention and control measures, which can be targeted at reducing risk in these settings.
- Published
- 2021
12. Iron-Catalyzed Halogen Exchange of Trifluoromethyl Arenes
- Author
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Florence Williams, James Shepherd, Hayley Petras, Emily Landgreen, and Andreas Dorian
- Abstract
We report the facile production of ArCF2X and ArCX3 from ArCF3 using catalytic iron(III)halides, which constitutes the first iron-catalyzed halogen exchange for non-aromatic CF bonds. Theoretical calculations suggest direct activation of C–F bonds by iron coordination. ArCX3 and ArCF2X products of the reaction are synthetically valuable due to their diversification potential. In particular, bromo-, chloro-, and iododifluoromethyl arenes (ArCF2Br, ArCF2Cl, ArCF2I, respectively) provide access to a myriad of difluoromethyl arene derivatives (ArCF2R). To optimize for mono-halogen exchange, a statistical method called Design of Experiments was used. Optimized parameters were successfully applied to electron rich and electron deficient aromatic substrates, and to the late stage diversification of flufenoxuron, a commercial insecticide.
- Published
- 2021
13. Epidemic waves of COVID-19 in Scotland: a genomic perspective on the impact of the introduction and relaxation of lockdown on SARS-CoV-2
- Author
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Rachel M. Colquhoun, David Robertson, Stephen Carmichael, Gianluigi Rossi, Tom Stanton, Andrew Rambaut, James Shepherd, Stefan Rooke, Ana da Silva Filipe, Amy Shepherd, Alasdair MacLean, Elihu Aranday-Cortes, Carlos E Balcazar-Lopez, Verity Hill, Igor Starinskij, Lu Lu, Katherine Smollett, Kathy Li, Michael Gallagher, Kathleen A. Williamson, John T. McCrone, Rory Gunson, Ben Jackson, Thomas C Williams, Rebecca Dewar, Kirstyn Brunker, Rhys Inward, Sharif Shaaban, Martin P McHugh, Kate Templeton, Seb Cotton, Mark E. J. Woolhouse, Daniel Balaz, Alice Broos, Sarah E. McDonald, Rajiv Shah, Jenna Nichols, Lily Tong, Thomas Doherty, Rowland R. Kao, Áine O'Toole, Natasha Johnson, Patawee Asamaphan, Yasmin A Parr, Vattipally B. Sreenu, E. Thomson, Marc Niebel, Natasha Jesudason, Daniel Mair, Kyriaki Nomikou, Emily Scher, Matthew T. G. Holden, Samantha Lycett, and Joseph Hughes
- Subjects
medicine.medical_specialty ,education.field_of_study ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Public health ,Population ,National health service ,Quarter (United States coin) ,Geography ,Epidemiology ,medicine ,Health board ,education ,Demography - Abstract
The second SARS virus, SARS-CoV-2, emerged in December 2019, and within a month was globally distributed. It was first introduced into Scotland in February 2020 associated with returning travellers and visitors. By March it was circulating in communities across the UK, and to control COVID-19 cases, and prevent overwhelming of the National Health Service (NHS), a ‘lockdown’ was introduced on 23rd March 2020 with a restriction of people’s movements. To augment the public health efforts a large-scale genome epidemiology effort (as part of the COVID-19 Genomics UK (COG-UK) consortium) resulted in the sequencing of over 5000 SARS-CoV-2 genomes by 18th August 2020 from Scottish cases, about a quarter of the estimated number of cases at that time. Here we quantify the geographical origins of the first wave introductions into Scotland from abroad and other UK regions, the spread of these SARS-CoV-2 lineages to different regions within Scotland (defined at the level of NHS Health Board) and the effect of lockdown on virus ‘success’. We estimate that approximately 300 introductions seeded lineages in Scotland, with around 25% of these lineages composed of more than five viruses, but by June circulating lineages were reduced to low levels, in line with low numbers of recorded positive cases. Lockdown was, thus, associated with a dramatic reduction in infection numbers and the extinguishing of most virus lineages. Unfortunately since the summer cases have been rising in Scotland in a second wave, with >1000 people testing positive on a daily basis, and hospitalisation of COVID-19 cases on the rise again. Examining the available Scottish genome data from the second wave, and comparing it to the first wave, we find that while some UK lineages have persisted through the summer, the majority of lineages responsible for the second wave are new introductions from outside of Scotland and many from outside of the UK. This indicates that, while lockdown in Scotland is directly linked with the first wave case numbers being brought under control, travel-associated imports (mostly from Europe or other parts of the UK) following the easing of lockdown are responsible for seeding the current epidemic population. This demonstrates that the impact of stringent public health measures can be compromised if following this, movements from regions of high to low prevalence are not minimised.
- Published
- 2021
14. Victims of Cybercrime: Understanding the Impact Through Accounts
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Lisa Sugiura, Dean Blackbourn, Mark Button, David William James Shepherd, Victoria Wang, and Richard Kapend
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Cybercrime ,Continuum (measurement) ,Technological change ,media_common.quotation_subject ,Subject (philosophy) ,Sociology ,Paper based ,Criminology ,Seriousness ,Hacker ,media_common - Abstract
The technological changes of the last 30 years have facilitated a substantial increase in cybercrimes. The impact of these crimes on victims has not been the subject of extensive research. This paper based upon a British Home Office funded study draws upon the experience of 52 victims of computer misuse crime, which can be broadly grouped under hacking and computer virus related crimes. Drawing upon the interviews with these victims the researchers identified a continuum of three components founded upon the seriousness of the incident and the impact on the victim. These three categories included: incidents of inconvenience, crimes of inconvenience and serious crimes of personal violation or significant financial loss or fear of. The paper provides depth accounts of 15 of the 52 victims interviewed to illustrate this continuum.
- Published
- 2021
15. Remdesivir induced viral RNA and subgenomic RNA suppression, and evolution of viral variants in SARS-CoV-2 infected patients
- Author
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Juanita Pang, Myerson P, de Silva Ti, Köeglmeier J, Judith Breuer, Caroline Dalton, Matthew Parker, E. Thomson, Rachel Williams, Grandjean L, Timothy Best, Florencia A T Boshier, Bynoe Pd, Richard A. Goldstein, Nele Alders, Stephanie Grunewald, Justin Penner, Alasdair Bamford, James Shepherd, Sunando Roy, Claire Frauenfelder, Joseph Hughes, and James Hatcher
- Subjects
Viral replication ,Viral evolution ,Superinfection ,medicine ,RNA ,Drug resistance ,Biology ,medicine.disease_cause ,Virology ,Viral load ,Deep sequencing ,Subgenomic mRNA - Abstract
While changes in SARS-CoV-2 viral load over time have been documented, detailed information on the impact of remdesivir and how it might alter intra-host viral evolution is limited. Sequential viral loads and deep sequencing of SARS-CoV-2 recovered from the upper respiratory tract of hospitalised children revealed that remdesivir treatment suppressed viral RNA levels in one patient but not in a second infected with an identical strain. Evidence of drug resistance to explain this difference was not found. Reduced levels of subgenomic (sg) RNA during treatment of the second patient, suggest an additional effect of remdesivir on viral replication that is independent of viral RNA levels. Haplotype reconstruction uncovered persistent SARS-CoV-2 variant genotypes in four patients. We conclude that these are likely to have arisen from within-host evolution, and not co-transmission, although superinfection cannot be excluded in one case. Sample-to-sample heterogeneity in the abundances of variant genotypes is best explained by the presence of discrete viral populations in the lung with incomplete population sampling in diagnostic swabs. Such compartmentalisation is well described in serious lung infections caused by influenza and Mycobacterium tuberculosis and has been associated with poor drug penetration, suboptimal treatment and drug resistance. Our data provide evidence that remdesivir is able to suppress SARS-CoV-2 replication in vivo but that its efficacy may be compromised by factors reducing penetration into the lung. Based on data from influenza and Mycobacterium tuberculosis lung infections we conclude that early use of remdesivir combined with other agents should now be evaluated.Summary SentenceDeep sequencing of longitudinal samples from SARS-CoV-2 infected paediatric patients identifies evidence of remdesivir-associated inhibition of viral replication in vivo and uncovers evidence of within host evolution of distinct viral genotypes.
- Published
- 2020
16. Detection of Southern Beech Heavy Flowering Using Sentinel-2 Imagery
- Author
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Ben Jolly, James Shepherd, Jan Schindler, John Dymond, and Terry Greene
- Subjects
General Earth and Planetary Sciences - Abstract
The southern beech (genus Fuscospora and Lophozonia) forest in New Zealand periodically has “mast” years, during which very large volumes of seeds are produced. This excessive seed production results in a population explosion of rodents and mustelids, which then puts pressure on native birds. To protect the birds, extra pest controls, costing in the order of NZD 20 million, are required in masting areas. To plan pest control and keep it cost-effective, it would be helpful to have a map of the masting areas. In this study, we developed a remote sensing method for the creation of a national beech flowering map. It used a temporal sequence of Sentinel-2 satellite imagery to determine areas in which a yellow index, which was based on red and green reflectance (red-green)/(red + green), was higher than normal in spring. The method was used to produce national maps of heavy beech flowering for the years 2017 to 2021. In 2018, which was a major beech masting year, of the 4.1 million ha of beech forest in New Zealand, 27.6% was observed to flower heavily. The overall classification accuracy of the map was 90.8%. The method is fully automated and could be used to help to identify areas of potentially excessive seed fall across the whole of New Zealand, several months in advance of when pest control would be required.
- Published
- 2022
17. COVID-19 and telemedicine
- Author
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James Shepherd
- Subjects
2019-20 coronavirus outbreak ,Telemedicine ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,medicine ,Medical emergency ,medicine.disease ,business - Published
- 2021
18. periscope: sub-genomic RNA identification in SARS-CoV-2 Genomic Sequencing Data
- Author
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Lily Tong, Elihu Aranday-Cortes, Chris Davis, Danielle C. Groves, Abha Chopra, Laura Carrilero, David G Partridge, Simon B. Mallal, Dennis Wang, James Shepherd, E. Thomson, Joe Heffer, Jenna Nichols, Matthew Wyles, T.I. de Silva, Shay Leary, Alexander J Keeley, Luke R. Green, Mohammad Raza, Cariad Evans, Sahan Bennett, Alain Kohl, Nikki Smith, Benjamin B Lindsey, Rachel Tucker, Parker, Karen C. Johnson, Ana da Silva Filipe, Paul J. Parsons, Adrienn Angyal, Silvana Gaudieri, and Rebecca Brown
- Subjects
Untranslated region ,Open reading frame ,Start codon ,Regulatory sequence ,Transcription (biology) ,RNA ,Computational biology ,Biology ,Genome ,Subgenomic mRNA - Abstract
We have developed periscope, a tool for the detection and quantification of sub-genomic RNA (sgRNA) in SARS-CoV-2 genomic sequence data. The translation of the SARS-CoV-2 RNA genome for most open reading frames (ORFs) occurs via RNA intermediates termed “sub-genomic RNAs”. sgRNAs are produced through discontinuous transcription which relies on homology between transcription regulatory sequences (TRS-B) upstream of the ORF start codons and that of the TRS-L which is located in the 5’ UTR. TRS-L is immediately preceded by a leader sequence. This leader sequence is therefore found at the 5’ end of all sgRNA. We applied periscope to 1,155 SARS-CoV-2 genomes from Sheffield, UK and validated our findings using orthogonal datasets and in vitro cell systems. Using a simple local alignment to detect reads which contain the leader sequence we were able to identify and quantify reads arising from canonical and non-canonical sgRNA. We were able to detect all canonical sgRNAs at expected abundances, with the exception of ORF10. A number of recurrent non-canonical sgRNAs are detected. We show that the results are reproducible using technical replicates and determine the optimum number of reads for sgRNA analysis. In VeroE6 ACE2+/− cell lines, periscope can detect the changes in the kinetics of sgRNA in orthogonal sequencing datasets. Finally, variants found in genomic RNA are transmitted to sgRNAs with high fidelity in most cases. This tool can be applied to all sequenced COVID-19 samples worldwide to provide comprehensive analysis of SARS-CoV-2 sgRNA.
- Published
- 2020
19. Co-offending and bribery: the recruitment of participants to corrupt schemes and the implications for prevention
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David William James Shepherd, Mark Button, and Dean Blackbourn
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Corruption ,Prevention ,Strategy and Management ,media_common.quotation_subject ,05 social sciences ,Co offending ,Criminology ,Public domain ,Bribery ,050501 criminology ,0501 psychology and cognitive sciences ,Business ,Resident pathogen theory ,Law ,Safety Research ,050104 developmental & child psychology ,0505 law ,media_common - Abstract
This paper explores the rarely researched areas of co-offending and bribery. Based upon interviews with six persons convicted of bribery-related offences and other cases in the public domain, the paper explores how previously ‘clean’ persons are recruited to corrupt schemes. In doing so, the paper draws on Reason’s resident pathogen theory on safety and uniquely applies it to bribery. The paper also identifies common recruitment techniques used by corruptors and proposes pathogen network analysis as a novel method for enhancing bribery prevention.
- Published
- 2018
20. 'The Higher You Fly, the Further You Fall': White-Collar Criminals, 'Special Sensitivity' and the Impact of Conviction in the United Kingdom
- Author
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Mark Button, Dean Blackbourn, and David William James Shepherd
- Subjects
050402 sociology ,Health (social science) ,media_common.quotation_subject ,white collar offenders ,Prison ,Criminology ,Pathology and Forensic Medicine ,Collar ,0504 sociology ,special sensitvity ,Applied Psychology ,0505 law ,media_common ,White (horse) ,05 social sciences ,embargoover12 ,Mental health ,conviction ,impact ,050501 criminology ,Conviction ,Psychological resilience ,Psychology ,Law ,Sentence ,Criminal justice - Abstract
The resilience of some high-profile white-collar criminals in the media gaze after prison may lead some to conclude, particularly as some research also supports this notion, that this group of offenders generally manages well after conviction. Research in this area is, however, small and largely American. The authors seek to add to this small body of research by offering findings on the impact of conviction on 17 UK convicted white-collar criminals after completion of their sentence. It provides a unique insight into the consequences of conviction, showing that although there were some offenders who did experience limited impact and coped well, there was also a significant group who suffered a decline in status, financial losses, negative media coverage, and relationship and mental health problems, to name some. The authors argue more research is needed on this group and their needs as they are often neglected by the criminal justice system.
- Published
- 2017
21. Derivation and external validation of a risk score for predicting HIV-associated tuberculosis to support case finding and preventive therapy scale-up: A cohort study
- Author
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Tefera Agizew, Yasmeen Hanifa, Heather Alexander, Unami Mathebula-Modongo, Yuliang Liu, Anand Date, Rosanna Boyd, Andrew D. Kerkhoff, Andrew F. Auld, Robin Wood, George Bicego, Anikie Mathoma, Goabaone Rankgoane-Pono, Alison D. Grant, Salome Charalambous, Alyssa Finlay, Pontsho Pono, Katherine Fielding, Tedd V. Ellerbrock, James Shepherd, Ray W. Shiraishi, and Christopher Serumola
- Subjects
Bacterial Diseases ,Male ,Epidemiology ,Economics ,Antitubercular Agents ,Social Sciences ,HIV Infections ,Economic Geography ,Logistic regression ,Biochemistry ,Machine Learning ,Medical Conditions ,Mathematical and Statistical Techniques ,Risk Factors ,Preventive Health Services ,Medicine and Health Sciences ,Prevalence ,Mass Screening ,Public and Occupational Health ,Subclinical infection ,Clinical Trials as Topic ,Botswana ,Framingham Risk Score ,Geography ,Coinfection ,Statistics ,General Medicine ,Middle Aged ,Prognosis ,Vaccination and Immunization ,Infectious Diseases ,Anti-Retroviral Agents ,Physical Sciences ,Medicine ,Tuberculosis Diagnosis and Management ,Low and Middle Income Countries ,Female ,Fast track ,Research Article ,Cohort study ,Adult ,Computer and Information Sciences ,medicine.medical_specialty ,Tuberculosis ,Immunology ,Antiretroviral Therapy ,Research and Analysis Methods ,Risk Assessment ,HIV Long-Term Survivors ,Antiviral Therapy ,Artificial Intelligence ,Diagnostic Medicine ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Hemoglobin ,Statistical Methods ,Medical prescription ,business.industry ,Biology and Life Sciences ,Proteins ,Reproducibility of Results ,Tropical Diseases ,medicine.disease ,Early Diagnosis ,Medical Risk Factors ,Earth Sciences ,Preventive Medicine ,business ,Body mass index ,Mathematics ,Forecasting - Abstract
Background Among people living with HIV (PLHIV), more flexible and sensitive tuberculosis (TB) screening tools capable of detecting both symptomatic and subclinical active TB are needed to (1) reduce morbidity and mortality from undiagnosed TB; (2) facilitate scale-up of tuberculosis preventive therapy (TPT) while reducing inappropriate prescription of TPT to PLHIV with subclinical active TB; and (3) allow for differentiated HIV–TB care. Methods and findings We used Botswana XPRES trial data for adult HIV clinic enrollees collected during 2012 to 2015 to develop a parsimonious multivariable prognostic model for active prevalent TB using both logistic regression and random forest machine learning approaches. A clinical score was derived by rescaling final model coefficients. The clinical score was developed using southern Botswana XPRES data and its accuracy validated internally, using northern Botswana data, and externally using 3 diverse cohorts of antiretroviral therapy (ART)-naive and ART-experienced PLHIV enrolled in XPHACTOR, TB Fast Track (TBFT), and Gugulethu studies from South Africa (SA). Predictive accuracy of the clinical score was compared with the World Health Organization (WHO) 4-symptom TB screen. Among 5,418 XPRES enrollees, 2,771 were included in the derivation dataset; 67% were female, median age was 34 years, median CD4 was 240 cells/μL, 189 (7%) had undiagnosed prevalent TB, and characteristics were similar between internal derivation and validation datasets. Among XPHACTOR, TBFT, and Gugulethu cohorts, median CD4 was 400, 73, and 167 cells/μL, and prevalence of TB was 5%, 10%, and 18%, respectively. Factors predictive of TB in the derivation dataset and selected for the clinical score included male sex (1 point), ≥1 WHO TB symptom (7 points), smoking history (1 point), temperature >37.5°C (6 points), body mass index (BMI) 10) yielded TB prevalence of 1%, 1%, 2%, and 6% in the lowest risk group and 33%, 22%, 26%, and 32% in the highest risk group for XPRES, XPHACTOR, TBFT, and Gugulethu cohorts, respectively. At clinical score ≥2, the number needed to screen (NNS) ranged from 5.0 in Gugulethu to 11.0 in XPHACTOR. Limitations include that the risk score has not been validated in resource-rich settings and needs further evaluation and validation in contemporary cohorts in Africa and other resource-constrained settings. Conclusions The simple and feasible clinical score allowed for prioritization of sensitivity and NPV, which could facilitate reductions in mortality from undiagnosed TB and safer administration of TPT during proposed global scale-up efforts. Differentiation of risk by clinical score cutoff allows flexibility in designing differentiated HIV–TB care to maximize impact of available resources., Andrew Auld and colleagues evaluate a clinical score for active tuberculosis in persons with HIV infection., Author summary Why was this study done? Tuberculosis (TB) remains the most common cause of death among people living with HIV (PLHIV) and is often undiagnosed at time of death. Rapid scale-up of tuberculosis preventive therapy (TPT) to 13 million PLHIV in low- and middle-income countries (LMICs) has been proposed for 2021; however, active TB is commonly asymptomatic and therefore missed by current WHO-recommended 4-symptom TB screening rules. Therefore, more sensitive TB screening tools are needed to better facilitate early TB diagnosis and safer scale-up of TPT to PLHIV by avoiding TPT prescription to clients with asymptomatic active TB, who need TB treatment. What did the researchers do and find? We derived a TB risk score for PLHIV from XPRES trial data and validated the score on 3 external datasets. We prioritized high sensitivity and ability to correctly rule out TB (i.e., high negative predictive value (NPV)) at key time points in care such as HIV clinic enrollment and before TPT prescription. Both logistic regression and random forest machine learning approaches were used to identify the 6 most important predictors, commonly available in LMIC clinic settings. In the external datasets, TB risk score ≥2 had higher sensitivity (87% to 97%) than WHO 4-symptom screening rule and increased NPV by 0.3% to 1.7%. Three risk groups were identified by the score, with active TB prevalence in external datasets ranging from 1% to 6% in the lowest to 22% to 32% in the highest risk groups. What do these findings mean? Following further validation, this clinical score could improve early detection of active TB to reduce morbidity and mortality from undiagnosed TB. Use of the clinical score cutoff of ≥2 during the proposed TPT scale-up for 13 million PLHIV could potentially avoid many thousands of PLHIV with active TB being inappropriately prescribed TPT. By differentiating 3 risk groups, the score also allows for the development of differentiated service delivery models suitable for LMIC.
- Published
- 2021
22. Phylogenetic diversity of Mycobacterium tuberculosis in two geographically distinct locations in Botswana - The Kopanyo Study
- Author
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Chawangwa Modongo, Nicola M. Zetola, Alyssa Finlay, Xiao Jun Wen, James Shepherd, Joyce Basotli, Patrick K. Moonan, John E. Oeltmann, Rosanna Boyd, and Eleanor S. Click
- Subjects
0301 basic medicine ,Microbiology (medical) ,Veterinary medicine ,Genotype ,Lineage (evolution) ,030106 microbiology ,Population ,Microbiology ,Mycobacterium tuberculosis ,03 medical and health sciences ,South Africa ,Genetics ,Cluster Analysis ,Humans ,Tuberculosis ,education ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Phylogeny ,education.field_of_study ,Molecular Epidemiology ,Botswana ,biology ,Phylogenetic tree ,Molecular epidemiology ,Genetic Variation ,biology.organism_classification ,Bacterial Typing Techniques ,Interspersed Repetitive Sequences ,Variable number tandem repeat ,Phylogenetic diversity ,030104 developmental biology ,Infectious Diseases ,Mycobacterium tuberculosis complex ,Tandem Repeat Sequences - Abstract
Mycobacterium tuberculosis complex (MTBC) is divided into several major phylogenetic lineages, with differential distribution globally. Using population-based data collected over a three year period, we performed 24-locus Mycobacterial Interspersed Repeat Unit – Variable Number Tandem Repeat (MIRU-VNTR) genotyping on all culture isolates from two districts of the country that differ in tuberculosis (TB) incidence (Gaborone, the capital, and Ghanzi in the Western Kalahari). The study objective was to characterize the molecular epidemiology of TB in these districts. Overall phylogenetic diversity mirrored that reported from neighboring Republic of South Africa, but differences in the two districts were marked. All four major lineages of M. tuberculosis were found in Gaborone, but only three of the four major lineages were found in Ghanzi. Strain diversity was lower in Ghanzi, with a large proportion (38%) of all isolates having an identical MIRU-VNTR result, compared to 6% of all isolates in Gaborone with the same MIRU-VNTR result. This study demonstrates localized differences in strain diversity by two districts in Botswana, and contributes to a growing characterization of MTBC diversity globally.
- Published
- 2019
23. Mathematical modelling of the pre-oxidation of a uranium carbide fuel pellet
- Author
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Bruce C. Hanson, Michael Fairweather, James Shepherd, and Peter J. Heggs
- Subjects
Materials science ,Differential equation ,General Chemical Engineering ,Nuclear engineering ,Radiochemistry ,Radius ,010402 general chemistry ,010403 inorganic & nuclear chemistry ,7. Clean energy ,01 natural sciences ,0104 chemical sciences ,Computer Science Applications ,chemistry.chemical_compound ,chemistry ,Mass transfer ,Pellet ,Uranium oxide ,Uranium carbide ,Limiting oxygen concentration ,Current (fluid) - Abstract
Uranium carbide is a candidate fuel for future nuclear reactors. However, for it to be implemented in a closed fuel cycle, an outline for its reprocessing is necessary. One proposed method is to oxidise the uranium carbide into uranium oxide which can then be reprocessed using current infrastructure. A mathematical model describing the heat and mass transfer processes involved in such an oxidation has been constructed. The available literature was consulted for reaction coefficients and information on reaction products. A stable and convergent numerical solution has been developed using a combination of finite-difference approximations of the differential equations. Completion times of approximately 3-30h are predicted given a spherical pellet with a radius of 9.35mm under varying initial conditions. The transient temperature distribution throughout the system is predicted, with a maximum temperature of 1458°C observed from an initial temperature of 500°C at an oxygen concentration of 3.15mol m‾³.
- Published
- 2015
24. The Barriers to the Opening of Government Data in the UK – A View From the Bottom
- Author
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Mark Button, Victoria Wang, and David William James Shepherd
- Subjects
impression management ,Open Government Data (OGD) ,EP/N027825/1 ,Public Administration ,Sociology and Political Science ,Public administration ,privacy ,Civil servants ,UK government ,Sociology ,benefit paradox ,Open government ,Government ,business.industry ,Communication ,RCUK ,EPSRC ,Publishing ,Impression management ,Position (finance) ,business ,EP/N028139/1 ,Library and Information Science ,Information Systems - Abstract
This paper explores some of the key barriers to Open Government Data (OGD) that responsible civil servants in the UK face as they try to comply with the UK-led OGD initiative. Empirically, we provide a quantitative analysis of the resources published on the government’s central OGD portal, data.gov.uk, and a unique insight into the publishing of OGD in the UK based on 22 interviews with responsible individuals at the operational level of publishing OGD. Our findings reveal that while the barriers to open government information have been substantially reduced, the barriers to open government data persist. Even the most enthusiastic responsible individuals face considerable obstacles in publishing OGD. Further, a key barrier to OGD in the UK is its impression management strategy based on its informational rather than data orientation. Due to the UK’s pioneering position in the OGD initiative, these findings are relevant to understanding and improving OGD programmes at local, national and international levels. The findings may subsequently lead to evidence-based strategies and policies.
- Published
- 2018
25. Tuberculosis incidence after 36 months’ isoniazid prophylaxis in HIV-infected adults in Botswana
- Author
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Zegabriel Tedla, James Shepherd, Samba Nyirenda, Thabisa Sibanda, Nong Shang, Tefera Agizew, Taraz Samandari, Barudi Mosimaneotsile, Oaitse I. Motsamai, and Charles E. Rose
- Subjects
Adult ,Male ,medicine.medical_specialty ,Tuberculosis ,Immunology ,Antitubercular Agents ,Placebo-controlled study ,Tuberculin ,HIV Infections ,Article ,law.invention ,Placebos ,Double-Blind Method ,Randomized controlled trial ,law ,Internal medicine ,Isoniazid ,Humans ,Immunology and Allergy ,Medicine ,Botswana ,business.industry ,Incidence ,Incidence (epidemiology) ,Hazard ratio ,medicine.disease ,Confidence interval ,Surgery ,Infectious Diseases ,Cohort ,Female ,Pre-Exposure Prophylaxis ,business - Abstract
Objective Thirty-six months of isoniazid preventive therapy (36IPT) was superior to 6 months of IPT (6IPT) in preventing tuberculosis (TB) among HIV-infected adults in Botswana. We assessed the posttrial durability of this benefit. Design A 36-month double-blind placebo controlled trial (1 : 1 randomization) with recruitment between November 2004 and July 2006 and observation until June 2011. Methods One thousand, nine hundred and ninety-five participants were followed in eight public health clinics. Twenty-four percent had a tuberculin skin test ≥5 mm (TST-positive). A minimum CD4 lymphocyte count was not required for enrolment. Antiretroviral therapy (ART) was provided in accordance with Botswana guidelines; 72% of participants retained by June 2011 had initiated ART. Multivariable analysis using Cox regression analysis included treatment arm, TST status, ART as a time-dependent variable and CD4 cell count at baseline and updated at 36 months. Results In the posttrial period, 2.13 and 2.14 per 100 person-years accumulated, whereas 0.93 and 1.13% TB incidence rates were observed in the 36IPT and 6IPT arms, respectively (P = 0.52). The crude hazard ratio of TB during the trial and posttrial was 0.57 [95% confidence intervals (CI) 0.33, 0.99] and 0.82 (95% CI 0.46, 1.49), and when restricted to TST-positive participants was 0.26 (95% CI 0.08, 0.80) and 0.40 (95% CI 0.15, 1.08), respectively. Multivariable analysis showed that ART use was associated with reduced death (adjusted hazard ratio 0.36, 95% CI 0.17-0.75) but not TB (0.92, 95% CI 0.55-1.53) in the posttrial period. Conclusion The benefit of 36IPT for TB prevention declined posttrial in this cohort. Adjunctive measures are warranted to prevent TB among HIV-infected persons receiving long-term ART in TB-endemic settings.
- Published
- 2015
26. Increase in anti-tuberculosis drug resistance in Botswana: results from the fourth National Drug Resistance Survey
- Author
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Joconiah Chirenda, Heather J. Menzies, R. Makombe, James Shepherd, O. Kachuwaire, Kevin P. Cain, T. Maribe, B. Kim, K. Radisowa, C. Sentle, V. Anisimova, S. El-Halabi, Marcus A. Bachhuber, E. Bile, Taraz Samandari, G. Moalosi, Victoria M. Gammino, and J. Basotli
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Time Factors ,Tuberculosis ,Adolescent ,Antitubercular Agents ,Microbial Sensitivity Tests ,Drug resistance ,Article ,Mycobacterium tuberculosis ,Young Adult ,Anti tuberculosis ,Drug Resistance, Multiple, Bacterial ,Internal medicine ,Tuberculosis, Multidrug-Resistant ,Humans ,Medicine ,Young adult ,Child ,Tuberculosis, Pulmonary ,Aged ,Aged, 80 and over ,Botswana ,biology ,business.industry ,Transmission (medicine) ,Mycobacterial culture ,Sputum ,Middle Aged ,biology.organism_classification ,medicine.disease ,Surgery ,Treatment Outcome ,Infectious Diseases ,Child, Preschool ,Health Care Surveys ,Female ,medicine.symptom ,business - Abstract
Setting Although approximately 0.5 million cases of multidrug-resistant tuberculosis (MDR-TB) occur globally each year, surveillance data are limited. Botswana is one of the few high TB burden countries to have carried out multiple anti-tuberculosis drug resistance surveys (in 1995-1996, 1999 and 2002). Objective In 2007-2008, we conducted the fourth national survey of anti-tuberculosis drug resistance in Botswana to assess anti-tuberculosis drug resistance, including trends over time. In the previous survey, 0.8% (95%CI 0.4-1.5) of new patients and 10.4% (95%CI 5.6-17.3) of previously treated patients had MDR-TB. Design During the survey period, eligible specimens from all new sputum-smear positive TB patients and from all TB patients with history of previous anti-tuberculosis treatment underwent mycobacterial culture and anti-tuberculosis drug susceptibility testing (DST). Results Of 924 new TB patients and 137 with previous anti-tuberculosis treatment with DST results, respectively 23 (2.5%, 95%CI 1.6-3.7) and 9 (6.6%, 95%CI 3.3-11.7) had MDR-TB. The proportion of new TB patients with MDR-TB has tripled in Botswana since the previous survey. Conclusion Combatting drug-resistant TB will require the scale-up of MDR-TB diagnosis and treatment to prevent the transmission of MDR-TB and strengthening of general TB control to prevent the emergence of resistance.
- Published
- 2014
27. Evaluating the case for greater use of private prosecutions in England and Wales for fraud offences
- Author
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Alison Wakefield, David William James Shepherd, Graham Brooks, Chris Lewis, and Mark Button
- Subjects
Sociology and Political Science ,Law ,Political science ,Political Science and International Relations ,Sanctions ,Criminology ,Sentencing ,Policing-and-criminal-investigations ,Private prosecution - Abstract
This paper considers the challenges and opportunities that exist in England and Wales for the use of private prosecutions for Fraud. It considers the need for sanctions against fraudsters: looks at the prosecution landscape as it has evolved, especially during the 21st century: considers the legal basis for private prosecution and gives a brief history of its extent. The advantages and disadvantages associated with private prosecution are considered and recommendations made on the changes needed before there could be significant developments in the use of private prosecutions.
- Published
- 2014
28. Housing benefit for service charges in sheltered housing schemes: an exercise in semantics or an application of reality?
- Author
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James Shepherd and Paul Sandford
- Subjects
Advanced and Specialized Nursing ,Community and Home Care ,Service (business) ,Health (social science) ,Housing Benefit ,Public economics ,business.industry ,Level of service ,Rehabilitation ,Legislation ,Public relations ,Semantics ,Tribunal ,Sheltered housing ,Value (economics) ,business - Abstract
PurposeThis paper aims to give guidance on the level of service charges that can be claimed by residents in sheltered housing as part of their housing benefit claims.Design/methodology/approachThe paper reviews the relevant legislation and recent opinions and rulings of both the Upper Tribunal and the Supreme Court.FindingsA broad based non arithmetical approach must be taken, particularly as many key words are not statutorily defined.Originality/valueClaimants, advocates and decision makers should use the guidance outlined when considering housing benefit claims by sheltered housing residents.
- Published
- 2012
29. A Novel Electrical Based Breach Detection System for Flexible Pipe
- Author
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William James Shepherd, Phil Nott, John Mcnab, Syed Zakir Ahmed, and Phil Harley
- Subjects
Steady state (electronics) ,Computer science ,business.industry ,Mechanical engineering ,Structural engineering ,business ,Corrosion - Abstract
An outer shield breach is the most common form of damage that can occur to a subsea flexible pipe during both installation and operation. Definitive and accurate detection and location of such damage is imperative in triggering the appropriate repair response. The overall aim is to minimise corrosion damage to the carbon steel strength elements in the pipe annulus, which occurs from the resulting ingress of seawater. GE Oil & Gas, in collaboration with Photon Fire Ltd have developed a new method of detecting seawater in a subsea flexible pipe annulus. This paper describes a novel breach detection system developed to monitor pipes using very low energy electrical signals appropriate for use in hazardous areas. The technique provides an enduring record of the occurrence of a breach and the extent of the subsequent flooding. A brief outline of the development programme is presented. The work involved determining the sensing technique used, development of appropriate electronic instrumentation, the optimised method for installing the sensor into the riser, and bespoke connection to the instrumentation. A prototype system, approved for use in Hazardous Area ATEX zone zero has been implemented on midscale pipe samples and the transient and steady state ‘scans’ of the pipe have been investigated. A summary of the test results and a proposed testing regime is presented. Results show that using this technique can accurately determine that a breach has occurred in the wall of the riser and the extent of the flooding.
- Published
- 2016
30. Drilling Safe Wells Through Efficient, Rapid and Site Specific Planningto Manage Risks & Improve Performance
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Muhammad R. Tayab, Suhail Valappil, Sultan Al Yammani, and James Shepherd
- Published
- 2016
31. Are you ready?—lessons learned from the Fort Hood shooting in Texas
- Author
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L. Gill Naul, James Shepherd, Clint Gerdes, and Michael L. Nipper
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Time Factors ,business.industry ,Communication ,Mass casualty event ,Trauma center ,Poison control ,Radiology, Interventional ,medicine.disease ,Texas ,Triage ,Suicide prevention ,Occupational safety and health ,Mass-casualty incident ,Military personnel ,Emergency Medicine ,medicine ,Humans ,Mass Casualty Incidents ,Radiology, Nuclear Medicine and imaging ,Medical emergency ,business - Abstract
On November 5, 2009, a US Army psychiatrist allegedly opened fire with one or more handguns, killing 12 military personnel and one civilian at Fort Hood in Killeen, Texas. The most severely wounded casualties were transported to Scott and White Memorial Hospital, a Level I trauma center and tertiary care teaching hospital in Temple, Texas associated with the Texas A&M University College of Medicine. Ten victims arrived in a 1-h period with another two arriving in the second hour, necessitating an emergency response to a mass casualty event. Our radiology department's response was largely unplanned and was therefore the result of many spontaneous actions and ideas. We share our experiences and from them formulate guidelines for a general radiology surge model for mass casualty events. It is our hope to raise awareness and help other radiology departments to prepare for such an unexpected event.
- Published
- 2010
32. Comparison of 80 versus 10 mg of Atorvastatin on Occurrence of Cardiovascular Events After the First Event (from the Treating to New Targets [TNT] Trial)
- Author
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Prakash Deedwania, Nanette K. Wenger, David A. DeMicco, Andrei Breazna, John C. LaRosa, Heiner Greten, and James Shepherd
- Subjects
medicine.medical_specialty ,Heart Diseases ,Atorvastatin ,Coronary Disease ,Drug Administration Schedule ,law.invention ,Coronary Restenosis ,Diabetes Complications ,Double-Blind Method ,Randomized controlled trial ,Risk Factors ,law ,Internal medicine ,Clinical endpoint ,Humans ,Medicine ,Pyrroles ,Disease burden ,Aged ,Heart Failure ,Metabolic Syndrome ,business.industry ,Anticholesteremic Agents ,Hazard ratio ,Type 2 Diabetes Mellitus ,medicine.disease ,Treatment Outcome ,Heptanoic Acids ,Relative risk ,Cardiology ,Metabolic syndrome ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Analyses of randomized clinical trials are usually restricted to examination of time to first event. However, because many patients have multiple events, this approach precludes much potentially useful clinical and economic data. To assess the effect on overall disease burden in the Treating to New Targets (TNT) study, we evaluated the effect of treatment with atorvastatin 80 versus 10 mg in the period after the occurrence of a first cardiovascular event. In TNT, 10,001 patients with stable coronary heart disease received double-blind therapy with atorvastatin 80 or 10 mg and were followed for 4.9 years. Post hoc time-to-event analysis was used to estimate separate hazard ratios for time to any first, second, third, fourth, and fifth recurrent cardiovascular events. During TNT, 3,082 patients had a first recurrent cardiovascular event, with 1,516, 698, 345, and 197 developing second, third, fourth, and fifth recurrent events, respectively. In patients receiving atorvastatin 80 mg, the relative risk of a first recurrent event was significantly decreased compared to those receiving atorvastatin 10 mg. Significant benefit with the 80-mg dose was also observed for second, third, fourth, and fifth recurrent events. Similar findings were recorded in 5,854 patients with type 2 diabetes mellitus and/or metabolic syndrome and in 3,809 patientsor = 65 years of age compared to younger patients. In conclusion, treatment with atorvastatin 80 mg continued to significantly decrease the risk of any cardiovascular event over time compared to atorvastatin 10 mg in patients who had survived previous events. In TNT, analyses limited to the primary end point significantly underestimated the decrease in total cardiovascular disease burden achieved by intensive low-density lipoprotein cholesterol lowering.
- Published
- 2010
33. Mycobacterium tuberculosisof the elbow joint
- Author
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Quintin Liao, James Shepherd, and Sulman Hasnie
- Subjects
030222 orthopedics ,medicine.medical_specialty ,Tuberculosis ,Bursitis ,biology ,business.industry ,Elbow ,Arthritis ,General Medicine ,medicine.disease ,biology.organism_classification ,Mycobacterium tuberculosis ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Rare Disease ,Cellulitis ,Internal medicine ,medicine ,Synovial fluid ,030212 general & internal medicine ,Flucloxacillin ,business ,medicine.drug - Abstract
Mycobacterium tuberculosis(TB) affecting the elbow joint is rarely reported in the developed world. We present the case of an 85-year-old Caucasian female who complained of a chronically discharging and painful wound across her left elbow during her admission for an ischaemic stroke. This was initially deemed to be either a bursitis or local manifestation of amyloid by her general practitioner and dermatologist respectively prior to admission. She was commenced on flucloxacillin by the medical team for presumed cellulitis with minimal response. A synovial fluid sample and repeated wound swabs yielded no growth from routine bacterial culture. Radiological assessment together with knowledge of her husband having previous TB raised the possibility of TB arthritis. Synovial fluid aspirate was subsequently sent for acid–alcohol fast bacilli microscopy and mycobacterial culture that confirmed M. tuberculosis. She was consequently started on multidrug TB therapy, over a year after the onset of her symptoms.
- Published
- 2017
34. Apolipoprotein B Metabolism in Man
- Author
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James Shepherd and Christopher J. Packard
- Subjects
medicine.medical_specialty ,Apolipoprotein B ,biology ,business.industry ,Hyperlipidemias ,Metabolism ,Lipoproteins, VLDL ,Hyperlipoproteinemia Type II ,Endocrinology ,Biochemistry ,Internal medicine ,Hyperlipoproteinemia Type III ,Internal Medicine ,medicine ,biology.protein ,Humans ,business ,Triglycerides ,Apolipoproteins B - Published
- 2009
35. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial
- Author
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Antonio M. Gotto, Peter Libby, James T. Willerson, Wolfgang Koenig, Paul M. Ridker, Alberto J. Lorenzatti, Børge G. Nordestgaard, John J.P. Kastelein, Jacques Genest, Robert J. Glynn, Eleanor Danielson, Jean G. MacFadyen, James Shepherd, Francisco Ah Fonseca, ACS - Amsterdam Cardiovascular Sciences, and Vascular Medicine
- Subjects
Male ,medicine.medical_specialty ,Sensitivity and Specificity ,Disease-Free Survival ,Statistics, Nonparametric ,chemistry.chemical_compound ,Double-Blind Method ,Internal medicine ,JUPITER trial ,medicine ,Humans ,Rosuvastatin ,Prospective Studies ,cardiovascular diseases ,Rosuvastatin Calcium ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,Sulfonamides ,biology ,Unstable angina ,Cholesterol ,business.industry ,Incidence ,Hazard ratio ,C-reactive protein ,nutritional and metabolic diseases ,Cholesterol, LDL ,General Medicine ,Middle Aged ,medicine.disease ,Fluorobenzenes ,C-Reactive Protein ,Pyrimidines ,Treatment Outcome ,Endocrinology ,chemistry ,Cardiovascular Diseases ,HMG-CoA reductase ,Cardiology ,biology.protein ,Female ,lipids (amino acids, peptides, and proteins) ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,medicine.drug - Abstract
Background Statins lower high-sensitivity C-reactive protein (hsCRP) and cholesterol concentrations, and hypothesis generating analyses suggest that clinical outcomes improve in patients given statins who achieve hsCRP concentrations less than 2 mg/L in addition to LDL cholesterol less than 1.8 mmol/L ( = 1.8 mmol/L or
- Published
- 2009
36. Valvular Heart Disease
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Rachel K. Y. Hung, Ross Fitzgerald, David E. Newby, James Shepherd, Shruti Daga, and J. Garreth S. Callaghan
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business.industry ,030204 cardiovascular system & hematology ,medicine.disease_cause ,medicine.disease ,Microbiology ,03 medical and health sciences ,0302 clinical medicine ,Staphylococcus aureus ,Infective endocarditis ,Induced platelet aggregation ,medicine ,030212 general & internal medicine ,Cardiology and Cardiovascular Medicine ,business - Published
- 2009
37. Genetic variation at the PCSK9 locus moderately lowers low-density lipoprotein cholesterol levels, but does not significantly lower vascular disease risk in an elderly population
- Author
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J. Wouter Jukema, Ernst J. Schaefer, Brendan M. Buckley, Eliana Polisecki, James Shepherd, Chris J. Packard, Rudi G. J. Westendorp, Michele Robertson, Gerard J. Blauw, Jose M. Ordovas, Stella Trompet, Inga Peter, Anton J. M. de Craen, Ian Ford, Alex D. McMahon, and Michael B. Murphy
- Subjects
Male ,medicine.medical_specialty ,Population ,Coronary Disease ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Article ,chemistry.chemical_compound ,Internal medicine ,Odds Ratio ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,education ,Aged ,Pravastatin ,Aged, 80 and over ,education.field_of_study ,Vascular disease ,Cholesterol ,PCSK9 ,Serine Endopeptidases ,Cholesterol, LDL ,Odds ratio ,medicine.disease ,Endocrinology ,chemistry ,Female ,lipids (amino acids, peptides, and proteins) ,Proprotein Convertases ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Proprotein Convertase 9 ,Cardiology and Cardiovascular Medicine ,medicine.drug - Abstract
Caucasian carriers of the T allele at R46L in the proprotein convertase subtilisin/kexin type 9 (PCSK9) locus have been reported to have 15% lower low density lipoprotein (LDL) cholesterol (C) levels and 47% lower coronary heart disease (CHD) risk. Our objective was to examine two PCSK9 single nucleotide polymorphisms (SNPs), R46L and E670G, in 5,783 elderly participants in PROSPER (Prospective Study of Pravastatin in the Elderly at Risk), of whom 43% had a history of vascular disease at baseline, and who were randomized to pravastatin or placebo with followup. In this population 3.5% were carriers of the T allele at R46L, and these subjects had significantly (p
- Published
- 2008
38. Genetic variation at the LDL receptor and HMG-CoA reductase gene loci, lipid levels, statin response, and cardiovascular disease incidence in PROSPER
- Author
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J. Wouter Jukema, Inga Peter, Hind Muallem, Rudi G. J. Westendorp, Eliana Polisecki, Ernst J. Schaefer, James Shepherd, Ian Ford, Chris J. Packard, Anton J. M. de Craen, Michele Robertson, Alex D. McMahon, Jose M. Ordovas, Brendan M. Buckley, and Nobuyo Maeda
- Subjects
Male ,medicine.medical_specialty ,Statin ,Apolipoprotein B ,medicine.drug_class ,Population ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,Article ,chemistry.chemical_compound ,Risk Factors ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,cardiovascular diseases ,education ,Triglycerides ,Aged ,Pravastatin ,Aged, 80 and over ,education.field_of_study ,biology ,Cholesterol ,Cholesterol, HDL ,nutritional and metabolic diseases ,Cholesterol, LDL ,Endocrinology ,Receptors, LDL ,chemistry ,Cardiovascular Diseases ,HMG-CoA reductase ,LDL receptor ,biology.protein ,Female ,Hydroxymethylglutaryl CoA Reductases ,lipids (amino acids, peptides, and proteins) ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,medicine.drug - Abstract
Our purpose was to evaluate associations of single nucleotide polymorphisms (SNPs) at the low density lipoprotein (LDL) receptor (LDLR C44857T, minor allele frequency (MAF) 0.26, and A44964G, MAF 0.25, both in the untranslated region) and HMG-CoA reductase (HMGCR i18T>G, MAF 0.019) gene loci with baseline lipid values, statin induced LDL- cholesterol (C) lowering response, and incident coronary heart disease (CHD) and cardiovascular disease on trial (CVD). Our population consisted of 5804 elderly men and women with vascular disease or one or more vascular disease risk factors, who were randomly allocated to pravastatin or placebo. Other risk factors and apolipoprotein (apo) E phenotype were controlled for in the analysis. Despite a prior report, no relationships with the HMGCR SNP were noted. For the LDLR SNPs C44857T and A44964G we noted significant associations of the rare alleles with baseline LDL-C and triglyceride levels, a modest association of the C44857T with LDL-C lowering to pravastatin in men, and significant associations with incident CHD and CVD of both SNPs, especially in men on pravastatin. Our data indicate that genetic variation at the LDLR locus can affect baseline lipids, response to pravastatin, and CVD risk in subjects placed on statin treatment.
- Published
- 2008
39. Intensive Lipid-Lowering With Atorvastatin for Secondary Prevention in Patients After Coronary Artery Bypass Surgery
- Author
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Sanjiv J. Shah, John J.P. Kastelein, David A. DeMicco, Andrei Breazna, David D. Waters, Nanette K. Wenger, John C. LaRosa, James Shepherd, Philip J. Barter, ACS - Amsterdam Cardiovascular Sciences, and Vascular Medicine
- Subjects
Adult ,Male ,medicine.medical_specialty ,Atorvastatin ,Coronary Artery Disease ,law.invention ,Coronary Restenosis ,chemistry.chemical_compound ,Coronary artery bypass surgery ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Pyrroles ,cardiovascular diseases ,Myocardial infarction ,Coronary Artery Bypass ,Stroke ,Triglycerides ,Aged ,Cholesterol ,business.industry ,Anticholesteremic Agents ,Graft Occlusion, Vascular ,Cholesterol, LDL ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Treatment Outcome ,chemistry ,Heptanoic Acids ,Cardiology ,lipids (amino acids, peptides, and proteins) ,Female ,business ,Cardiology and Cardiovascular Medicine ,medicine.drug ,Artery - Abstract
OBJECTIVES: The aim of this post hoc analysis from the TNT (Treating to New Targets) trial is to determine whether patients with previous coronary artery bypass grafting (CABG) surgery achieved clinical benefit from intensive low-density lipoprotein (LDL)-cholesterol lowering. BACKGROUND: The development and progression of atherosclerosis is accelerated in coronary venous bypass grafts. METHODS: A total of 10,001 patients with documented coronary disease, including 4,654 with previous CABG, were randomized to atorvastatin 80 or 10 mg/day and were followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event (cardiac death, nonfatal myocardial infarction, resuscitated cardiac arrest, or stroke). RESULTS: A first major cardiovascular event occurred in 11.4% of the patients with prior CABG and 8.5% of those without prior CABG (p < 0.001). In CABG patients, mean LDL-cholesterol levels at study end were 79 mg/dl in the 80-mg arm and 101 mg/dl in the 10-mg arm, and the primary event rate was 9.7% in the 80-mg arm and 13.0% in the 10-mg arm (hazard ratio 0.73, 95% confidence interval 0.62 to 0.87, p = 0.0004). Repeat revascularization during follow-up, either CABG or percutaneous coronary intervention, was performed in 11.3% of the CABG patients in the 80-mg arm and 15.9% in the 10-mg arm (hazard ratio 0.70, 95% confidence interval 0.60 to 0.82, p < 0.0001). CONCLUSIONS: Intensive LDL-cholesterol lowering to a mean of 79 mg/dl with atorvastatin 80 mg/day in patients with previous CABG reduces major cardiovascular events by 27% and the need for repeat coronary revascularization by 30%, compared with less intensive cholesterol-lowering to a mean of 101 mg/dl with atorvastatin 10 mg/day. (A Study to Determine the Degree of Additional Reduction in CV Risk in Lowering LDL Below Minimum Target Levels [TNT]; NCT00327691)
- Published
- 2008
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40. Intensive Lipid Lowering With Atorvastatin in Patients With Coronary Heart Disease and Chronic Kidney Disease
- Author
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Andrea Zuckerman, Daniel J. Wilson, John J.P. Kastelein, James Shepherd, Prakash Deedwania, Stephen Dobson, Andrei Breazna, Nanette K. Wenger, Vera Bittner, Tnt Trial Investigators, ACS - Amsterdam Cardiovascular Sciences, and Vascular Medicine
- Subjects
medicine.medical_specialty ,education.field_of_study ,Cholesterol ,business.industry ,Atorvastatin ,Population ,Hazard ratio ,Renal function ,medicine.disease ,Gastroenterology ,Comorbidity ,Surgery ,chemistry.chemical_compound ,chemistry ,Internal medicine ,Relative risk ,medicine ,education ,business ,Cardiology and Cardiovascular Medicine ,Kidney disease ,medicine.drug - Abstract
Intensive Lipid Lowering With Atorvastatin in Patients With Coronary Heart Disease and Chronic Kidney Disease: The TNT (Treating to New Targets) Study James Shepherd, John J. P. Kastelein, Vera Bittner, Prakash Deedwania, Andrei Breazna, Stephen Dobson, Daniel J. Wilson, Andrea Zuckerman, Nanette K. Wenger, for the TNT (Treating to New Targets) Investigators In 9,656 patients with stable coronary heart disease (CHD) and low-density lipoprotein cholesterol levels
- Published
- 2008
- Full Text
- View/download PDF
41. Effect of pravastatin on the development of diabetes and adiponectin production
- Author
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Tohru Funahashi, Toshiyuki Takagi, Iichiro Shimomura, Muriel J. Caslake, Atsunori Fukuhara, Hironori Kobayashi, Manabu Abe, Morihiro Matsuda, Alex D. McMahon, James Shepherd, Ryutaro Komuro, and Shinji Kihara
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,Glucose uptake ,Adipose tissue ,Mice ,Diabetes mellitus ,Internal medicine ,Adipocytes ,Diabetes Mellitus ,polycyclic compounds ,Animals ,Humans ,Medicine ,Obesity ,Pravastatin ,biology ,Adiponectin ,business.industry ,Insulin ,Glucose transporter ,nutritional and metabolic diseases ,medicine.disease ,Disease Models, Animal ,Glucose ,Endocrinology ,HMG-CoA reductase ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
In the West of Scotland Coronary Prevention Study (WOSCOPS), treatment of hypercholesterolemic men with pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, reduced their likelihood to progress to diabetes mellitus by 30%. However, the mechanism of this effect of pravastatin has not been investigated. In the current study, we examined the effect of pravastatin on the development of diabetes in obese diabetic mice, and on the insulin-induced glucose uptake and adiponectin production. Pravastatin treatment attenuated the development of diabetes in db/db and high fat/high sucrose diet-fed C57BL/6J mice. An in vivo glucose transport assay showed that pravastatin upregulated glucose uptake in adipose tissue. Insulin-stimulated glucose uptake was enhanced in primary adipocytes isolated from pravastatin-treated mice. Pravastatin treatment increased adiponectin production in 3T3-L1 adipocytes. Plasma adiponectin levels were significantly increased in pravastatin-treated mice. Analyses of plasma samples from the WOSCOPS biobank indicated a significant increase of plasma adiponectin levels with pravastatin treatment (placebo -0.28+/-0.34 microg/ml versus pravastatin +1.47+/-0.33 microg/ml, p=0.0003). Taken together, our findings suggest that pravastatin may have beneficial effects on adipose tissue, which may partly explain the reduction of the development of diabetes by pravastatin treatment.
- Published
- 2008
42. Association of the Trp719Arg Polymorphism in Kinesin-Like Protein 6 With Myocardial Infarction and Coronary Heart Disease in 2 Prospective Trials
- Author
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Carmen H. Tong, Marc A. Pfeffer, Olga Iakoubova, James Shepherd, Frank M. Sacks, Charles M. Rowland, Chris J. Packard, Thomas J. White, Hannia Campos, Dov Shiffman, James J. Devlin, Todd G. Kirchgessner, Eugene Braunwald, Marc S. Sabatine, Bradford A. Young, and Andre R. Arellano
- Subjects
medicine.medical_specialty ,business.industry ,Proportional hazards model ,Hazard ratio ,Absolute risk reduction ,Odds ratio ,medicine.disease ,Surgery ,Internal medicine ,Cohort ,medicine ,KIF6 ,Myocardial infarction ,Cardiology and Cardiovascular Medicine ,business ,Pravastatin ,medicine.drug - Abstract
Objectives We asked whether 35 genetic polymorphisms, previously found to be associated with cardiovascular disease, were associated with myocardial infarction (MI) in the CARE (Cholesterol and Recurrent Events) trial and with coronary heart disease (CHD) in the WOSCOPS (West of Scotland Coronary Prevention Study) trial and whether the risk associated with these polymorphisms could be reduced by pravastatin treatment. Background Identification of genetic polymorphisms associated with CHD may improve assessment of CHD risk and understanding of disease pathophysiology. Methods We tested the association between genotype and recurrent MI in the CARE study and between genotype and primary CHD in the WOSCOPS trial using regression models that adjusted for conventional risk factors: Cox proportional hazards models for the CARE study and conditional logistic regression models for a nested case-control study of the WOSCOPS trial. Results We found that Trp719Arg (rs20455) in KIF6 was associated with coronary events. KIF6 encodes kinesin-like protein 6, a member of the molecular motor superfamily. In placebo-treated patients, carriers of the KIF6 719Arg allele (59.4% of the CARE trial cohort) had a hazard ratio of 1.50 (95% confidence interval [CI] 1.05 to 2.15) in the CARE trial and an odds ratio of 1.55 (95% CI 1.14 to 2.09) in the WOSCOPS trial. Among carriers, the absolute risk reduction by pravastatin was 4.89% (95% CI 1.81% to 7.97%) in the CARE trial and 5.49% (95% CI 3.52% to 7.46%) in the WOSCOPS trial. Conclusions In both the CARE and the WOSCOPS trials, carriers of the KIF6 719Arg allele had an increased risk of coronary events, and pravastatin treatment substantially reduced that risk.
- Published
- 2008
43. Association Between Apolipoprotein E4 and Cognitive Decline in Elderly Adults
- Author
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Allan Gaw, Ian Ford, James Shepherd, Peter W. Macfarlane, Rudi G. J. Westendorp, Michael E. Hyland, J. Wouter Jukema, Jellemer Jolles, Gerard J. Blauw, Edward L.E.M. Bollen, Brian Sweeney, Ivan J. Perry, David J. Stott, Stuart M. Cobbe, Adriaan M. Kamper, Brendan M. Buckley, C. Twomey, Heather Murray, Chris J. Packard, Mike Murphy, and Muriel J. Caslake
- Subjects
Geriatrics ,Apolipoprotein E ,Gerontology ,medicine.medical_specialty ,Recall ,Cross-sectional study ,business.industry ,Cognitive disorder ,medicine.disease ,medicine ,Geriatrics and Gerontology ,Cognitive decline ,business ,Stroop effect ,Cohort study - Abstract
OBJECTIVE: To determine the influence of apolipoproteinEoncognitivedeclineinacohortofelderlymenandwomen.DESIGN: Prospective study.SETTING: Scotland, Ireland, and the Netherlands.PARTICIPANTS: Five thousand eight hundred four subjectsaged70to 82fromtheProspectiveStudy of PravastatinintheElderly at Risk (PROSPER).MEASUREMENTS: Subjects were assessed at baselineand over a mean 3.2-year (range 0.7–4.2) follow-upfor memory (Picture-Word Recall), speed of informationprocessing (Stroop and Letter-Digit Coding), global cogni-tive function (Mini-Mental State Examination), and activ-ities of daily living.RESULTS: At baseline, subjects with apolipoprotein E
- Published
- 2007
44. Effect of Intensive Lipid Lowering with Atorvastatin on Renal Function in Patients with Coronary Heart Disease
- Author
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John J.P. Kastelein, James Shepherd, Prakash Deedwania, Andrei Breazna, Andrea Zuckerman, Vera Bittner, Stephen Dobson, Nanette K. Wenger, Daniel J. Wilson, ACS - Amsterdam Cardiovascular Sciences, and Vascular Medicine
- Subjects
Adult ,Male ,medicine.medical_specialty ,Epidemiology ,Atorvastatin ,Renal function ,Blood Pressure ,Coronary Disease ,Kidney ,urologic and male genital diseases ,Critical Care and Intensive Care Medicine ,law.invention ,chemistry.chemical_compound ,Double-Blind Method ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Pyrroles ,In patient ,Aged ,Transplantation ,Cholesterol ,business.industry ,Anticholesteremic Agents ,Cholesterol, HDL ,Cholesterol, LDL ,Middle Aged ,Coronary heart disease ,chemistry ,Heptanoic Acids ,Nephrology ,Creatinine Measurement ,Cardiology ,Female ,Kidney Diseases ,Lipid lowering ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,Glomerular Filtration Rate ,medicine.drug - Abstract
BACKGROUND AND OBJECTIVES: Data suggest that atorvastatin may be nephroprotective. This subanalysis of the Treating to New Targets study investigated how intensive lipid lowering with 80 mg of atorvastatin affects renal function when compared with 10 mg in patients with coronary heart disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 10,001 patients with coronary heart disease and LDL cholesterol levels of or = 60 ml/min per 1.73 m2 in significantly more patients and declined to < 60 ml/min per 1.73 m2 in significantly fewer patients than in the 10-mg arm. CONCLUSIONS: The expected 5-yr decline in renal function was not observed. Estimated GFR improved in both treatment groups but was significantly greater with 80 mg than with 10 mg, suggesting this benefit may be dosage related
- Published
- 2007
45. Valves in the Heart of the Big Apple V: Evaluation and Management of Valvular Heart Diseases 2007.Third Annual Scientific Session: Heart Valve Society of America, New York City, N.Y., April 12–14, 2007
- Author
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Kurt Boman, Harun Evrengul, E. Vizzardi, Jacob Goldstein, M. Metra, Daniel P. Shmorhun, Yu Shu Li, Chia-Ti Tsai, Pei-Leun Kang, Ke Ping Yang, Kai Mortensen, Gerhard Blazek, Claudia Stöllberger, Christopher Gans, Rodolfo Ventura, Debabrata Mukherjee, J. Kogias, Holger Diedrichs, Sena Tokay, Sungha Park, Seyhan Tanriverdi, James Blasetto, Adam Torbicki, David Köhler, Ken-ichi Sugimoto, Joško Osredkar, C. Fiorina, Akira Suda, Pablo Ancillo, Ahmet Oktay, Se-Jung Yoon, D. Tanne, Gertrud Wüstefeld, Refik Erdim, Matthias Pfisterer, Teiichi Yamane, Anthony Roselli, Daniel Petrovič, Chi Young Shim, Erol Saygili, Xue-Bing Li, H. Asuman Kaftan, Muhammet Ali Aydin, Uwe Nixdorff, Barbara Lewis, Susan Harris, Zaza Iakobishvili, Dariusz A. Kosior, Ulrich Keller, Renata Verhovec, Basil S. Lewis, Lutz Klinghammer, V. Boyko, V. Caldir, Ronen Jaffe, Basheer Karkabi, Daniel Seidensticker, Robert H. G. Schwinger, Shih Kai Lin, Tsutomu Yoshikawa, S. Behar, John Kao, Midori Yamakawa, Andreas Schuchert, Yung-Zu Tseng, Mona Olofsson, Ronen Rubinshtein, Miodrag Filipovic, Kimiaki Komukai, U. Guray, Yuichiro Maekawa, Gabriele Pfitzer, Ling-Ping Lai, Zenon S. Kyriakides, Hiroyuki Hazeyama, Ralph Stephan von Bardeleben, Manfred D. Seeberger, Konrad Frank, Josef Finsterer, Kamran Aghasadeghi, S. Kormaz, Chanmi Park, Hartwig Wolburg, Hemender S. Vats, Elinor Miller, M. Haim, Yohei Ohno, Param P. Sharma, Takashi Kohno, U. Goldbourt, Hiromichi Hara, Hyun Young Park, Joji Urata, Taro Date, Ming-Ren Chen, S. Nodari, Shye-Jao Wu, Nurullah Tuzun, Shiro Iwanaga, A. Serdar Fak, Donald G. Vidt, S. Cay, Chun-Peng Liu, Doron Zahger, Holger K. Eltzschig, Mojca Globočnik Petrovič, Ing-Sh Chiu, Namsik Chung, Yasar Enli, Juey-Jen Hwang, S. Sideris, David J. Moliterno, Jonathan Rosen, Toshihisa Anzai, H. Sasmaz, Esra Saygili, Yuan-Sheng Liu, Halil Tanriverdi, K. Tsatiris, David Hasdai, Toshihide Shinozaki, M.B. Yilmaz, Mei-Hwan Wu, R. Zimlichman, Borut Peterlin, Gautam Nayak, M. Bonios, Fu-Tien Chiang, Moshe Y. Flugelman, L. Dei Cas, Knut Gjesdal, Maria Winkler-Dworak, Susanne Mohr-Kahaly, Carsten Zobel, Amir Aslani, Grzegorz Opolski, Tobias Eckle, Guang Yuan Mar, Omur Kuru, Y. Guray, Dan Edebro, Fernando Arós, Pedro Morillas, David A. Halon, Rita Dictiar, Tao Yu Lee, Deniz Seleci, Takashi Sakamoto, Raban Jeger, Stephanie Zug, Jochen Müller-Ehmsen, Ping Zhang, Hai-Cheng Zhang, Bermseok Oh, Hidehiro Kaneko, Zhi-Hong Zhao, Shmuel Gottlieb, Chuen-Wang Chiou, Thomas Meinertz, Z. Matas, Hung-Chi Lue, Jiunn-Lee Lin, Dan Atar, Yangsoo Jang, José Luis Priego Bermejo, Gökmen Gemici, Karin Klingel, Alex I. Malinin, George Arealis, Hakan Tezcan, Savvas Nikolidakis, Young Guk Ko, Daisuke Utsunomiya, Donghoon Choi, Birgit Bölck, Satoshi Ogawa, Kotaro Naito, Arne Warth, Solomon Behar, Pedro Pabón, John J. Hayes, Yuan Xu, M. Benderly, Humberto Vidaillet, Ming Hua Luo, Hui-Chong Li, Avital Porter, Yasushi Asakura, C. Melexopoulou, Stephan Willems, Jou-Kou Wang, Yasuo Sugano, Taiji Nishiharu, Marion Faigle, P. Exarchos, Seibu Mochizuki, Haim Hammerman, Yasuyuki Yamashita, Robert J. Goldberg, Shih Hung Hsiao, Hung Tae Kim, Nevzat Karabulut, Carmen Fernández, Hanoch Hod, Michael Koutouzis, Vicente Bertomeu, Obaida R. Rana, Hannes Reuter, Kazuo Awai, James Shepherd, Ikuo Taniguchi, Victor L. Serebruany, Chuen-Den Tseng, and Ji-Hong Guo
- Subjects
medicine.medical_specialty ,medicine.anatomical_structure ,business.industry ,Internal medicine ,General surgery ,Cardiology ,Medicine ,Pharmacology (medical) ,Heart valve ,Session (computer science) ,Cardiology and Cardiovascular Medicine ,business - Published
- 2007
46. Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study
- Author
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Jasbir S. Moore, S. W. Brouilette, Alex D. McMahon, Ian Ford, Nilesh J. Samani, John R. Thompson, Chris J. Packard, and James Shepherd
- Subjects
Male ,Aging ,medicine.medical_specialty ,Blood Pressure ,Coronary Disease ,Polymerase Chain Reaction ,chemistry.chemical_compound ,Risk Factors ,Internal medicine ,medicine ,Humans ,Pravastatin ,Framingham Risk Score ,Cholesterol ,business.industry ,Case-control study ,General Medicine ,Odds ratio ,Middle Aged ,Telomere ,Surgery ,Blood pressure ,Scotland ,chemistry ,Ageing ,Case-Control Studies ,Nested case-control study ,Cardiology ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,Follow-Up Studies ,medicine.drug - Abstract
Summary Background Inter-individual differences in biological ageing could affect susceptibility to coronary heart disease. Our aim was to determine whether mean leucocyte telomere length is a predictor of the development of coronary heart disease. Methods We compared telomere lengths at recruitment in 484 individuals in the West of Scotland Primary Prevention Study (WOSCOPS) who went on to develop coronary heart disease events with those from 1058 matched controls who remained event free. We also investigated whether there was any association between telomere length and observed clinical benefit of statin treatment in WOSCOPS. Findings Mean telomere length decreased with age by 9% per decade (95% CI 3·6–14·1; p=0·001) in controls; much the same trend was seen in cases (−5·9% per decade, −3·1 to 14·1; p=0·1902). Individuals in the middle and the lowest tertiles of telomere length were more at risk of developing a coronary heart disease event than were individuals in the highest tertile (odds ratio [OR] for coronary heart disease: 1·51, 95% CI 1·15–1·98; p=0·0029 in the middle tertile; 1·44, 1·10–1·90, p=0·0090 in the lowest). In placebo-treated patients, the risk of coronary heart disease was almost double in those in the lower two tertiles of telomere length compared with those in the highest tertile (1·93, 1·33–2·80, p=0·0005 in the middle tertile; 1·94, 1·33–2·84, p=0·0006 in the lowest). By contrast, in patients treated with pravastatin, the increased risk with shorter telomeres was substantially attenuated (1·12, 0·75–1·69, p=0·5755 in the middle tertile; 1·02, 0·68–1·52, p=0·9380 in the lowest). Interpretation Mean leucocyte telomere length is a predictor of future coronary heart disease events in middle-aged, high-risk men and could identify individuals who would benefit most from statin treatment. Our findings lend support to the hypothesis that differences in biological ageing might contribute to the risk—and variability in age of onset—of coronary heart disease.
- Published
- 2007
47. Effect of high-dose atorvastatin on the cardiovascular risk associated with individual components of metabolic syndrome: a subanalysis of the Treating to New Targets (TNT) study
- Author
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Andrei Breazna, Prakash Deedwania, David A. DeMicco, and James Shepherd
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Atorvastatin ,Blood sugar ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Gastroenterology ,Body Mass Index ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,High-density lipoprotein ,Double-Blind Method ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,Medicine ,Humans ,Triglycerides ,Aged ,Metabolic Syndrome ,Dose-Response Relationship, Drug ,business.industry ,Cholesterol ,Anticholesteremic Agents ,Cholesterol, HDL ,nutritional and metabolic diseases ,Cholesterol, LDL ,Fasting ,Middle Aged ,medicine.disease ,chemistry ,Cardiovascular Diseases ,Low-density lipoprotein ,Hypertension ,lipids (amino acids, peptides, and proteins) ,Female ,Metabolic syndrome ,business ,medicine.drug ,Lipoprotein - Abstract
Aims To investigate the impact of intensive lipid-lowering with high-dose atorvastatin on the cardiovascular risk associated with individual metabolic syndrome components [high body mass index (BMI), elevated triglycerides, low high-density lipoprotein (HDL) cholesterol, hypertension and elevated fasting glucose] in patients with coronary heart disease (CHD). Methods Patients with clinically evident, stable CHD and low-density lipoprotein (LDL) cholesterol
- Published
- 2015
48. Dextran Sulphate Adsorption: Effects on Coronary Heart Disease
- Author
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Ross Lorimer, James Shepherd, Graeme W. Tait, Christopher J. Packard, and Ian Hutton
- Subjects
medicine.medical_specialty ,Adsorption ,Dextran sulphate ,Chemistry ,Internal medicine ,Cardiology ,medicine ,Coronary heart disease - Published
- 2015
49. Genetic Determinants of Apolipoprotein B Metabolism
- Author
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Thomas Demant, Dorothy Bedford, Christopher Packard, and James Shepherd
- Subjects
Apolipoprotein E ,medicine.medical_specialty ,Very low-density lipoprotein ,Apolipoprotein B ,biology ,Catabolism ,Metabolism ,medicine.disease ,Lipoprotein lipase deficiency ,Endocrinology ,Internal medicine ,Genotype ,medicine ,Cardiology ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Allele - Abstract
In this thesis the influence of genetic factors on the apolipoprotein B metabolism in humans was investigated. The phenotype of the apolipoprotein E polymorphism was determined for normolipidaemic subjects (n = 1600). The metabolism of apolipoprotein B in fifteen subjects, homozygous for apoE3, apoE4 or apoE2, was examined by VLDL-turnover studies, using trace-labelled VLDL1 (Sf 60-400) and VLDL2 (Sf 20-60). Results were used for computer modelling of the apoB metabolism, which enabled quantitative comparisons between the three study groups. In apoE2/2 subjects, clearance of VLDL1 and VLDL2 as well as transfer from IDL into LDL was found to be delayed and in apoE4/4 subjects the LDL-FCR was reduced as compared to apoE3/3 normolipidaemics. These observations explain the correlation between apoE phenotypes and plasma cholesterol levels, which had been observed previously by others and were confirmed in the present study. The Xbal restriction site polymorphism of the apoB gene was analysed in nineteen hypercholesterolaemic patients and correlated with fractional catabolic rates for LDL as defined by LDL-turnover studies. The X2 allele was found to be linked with a decreased LDL-FCR, in line with previous reports of a correlation between X2X2 genotype and increased plasma cholesterol concentrations. In addition to these studies of common genetic determinants of apoB metabolism, five patients with rare inherited disorders of lipoprotein metabolism were investigated. These conditions were homozygous familial hypercholesterolaemia, lipoprotein lipase deficiency and hepatic lipase deficiency. VLDL-turnovers in these subjects revealed the significance of the LDL-receptor and the two lipolytic enzymes for apolipoprotein B metabolism. Finally, some conclusions were drawn about metabolic heterogeneity within the VLDL subfraction and about apoB synthesis.
- Published
- 2015
50. Urinary Mevalonic Acid and Plasma Lathosterol: Responses to Simvastatin Therapy
- Author
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J. Philip Stewart, Christopher J. Packard, Anuradha S. Pappu, James Shepherd, Allan Gaw, and D. Roger Illingworth
- Subjects
medicine.medical_specialty ,business.industry ,Urinary system ,Lathosterol ,Mevalonic acid ,Pharmacology ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Simvastatin ,Internal medicine ,medicine ,business ,medicine.drug - Published
- 2015
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