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1. Supreme Court Holds That Constitutional Limits On Permit Conditions Apply To Both Legislative And Administrative Actions

Author

Craig, Darren A.

Subjects
United States. Supreme Court -- Cases, Impact fees -- Cases, Eminent domain (Law) -- Cases, Land use -- Licensing, certification and accreditation -- Cases -- California, Judicial opinions -- Cases, Company legal issue, Business, international, United States Constitution. 5th Amendment, clause 6
Abstract

Sheetz v. County. of El Dorado, California, 144 S. Ct. 893 (Apr. 12, 2024) In Sheetz v. County of El Dorado, the U.S. Supreme Court held that conditions imposed on [...]

Published
2024

2. Supreme Court Rejects Bright-Line Preemption Standard Under The National Bank Act

Author

Craig, Darren A.

Subjects
United States. Supreme Court -- Cases, Banking law -- Cases, Exclusive and concurrent legislative powers -- Cases, Company legal issue, Business, international, National Bank Act
Abstract

Cantero v. Bank of Am., N. A., 144 S. Ct. 1290 (May 30, 2024) In Cantero v. Bank of America, the U.S. Supreme Court held that state laws are preempted [...]

Published
2024

3. Novel morphological and physiological scaling relationships in the southern red wood ant

Author

Perl, Craig Darren

Subjects
570, QL0568.F7 Formicidae (Ants), QL0799 Morphology
Abstract

Red wood ants (Formica rufa) are visual navigators whose colonies contain workers that differ substantially in size. By investigating the allometry of the ants' compound eyes, and the regions within them, I showed that facets in particular regions scaled differently: both grade and slope shifts occurred. Facets in some eye regions were absolutely larger than others, while other facet regions scaled at different rates with body size. I next compared eye scaling between nests from the same population. Nevertheless, the method by which ants increased their eye size differed between nests. I found that ants from some nests primarily increased eye size through facet number and others through facet diameter. This showed that scaling rules at the cellular levels can differ even within a single population. Comparisons among Formica species revealed that differential eye scaling was not restricted to just F. rufa. Differential scaling was found in F. sanguinea but not F. lugubris or F. fusca. Surprisingly, scaling between facet diameter and number was conserved across all four species, demonstrating that whole-organ scaling among species can be conservative whilst differing vastly between organ-regions. Moving beyond morphology, I next investigated whether physiological scaling was equally as variable among nests. Metabolic rate scaling was negatively allometric and the same among four nests. Respiratory water loss was found to be determined solely by metabolic rate. Metabolic rate co-varies with different ventilation types, however, switches in ventilation type are driven by movement. This demonstrates that increases in metabolic rate are not sufficient to explain changes in ventilation type but are sufficient to explain respiratory water loss.

Published
2018

4. Large scale pattern detection in videos and images from the wild

Author

Henderson, Craig Darren Mark

Subjects
006.4, Electronic engineering and computer science, Large Scale Pattern Detection
Abstract

Pattern detection is a well-studied area of computer vision, but still current methods are unstable in images of poor quality. This thesis describes improvements over contemporary methods in the fast detection of unseen patterns in a large corpus of videos that vary tremendously in colour and texture definition, captured "in the wild" by mobile devices and surveillance cameras. We focus on three key areas of this broad subject; First, we identify consistency weaknesses in existing techniques of processing an image and it's horizontally reflected (mirror) image. This is important in police investigations where subjects change their appearance to try to avoid recognition, and we propose that invariance to horizontal reflection should be more widely considered in image description and recognition tasks too. We observe online Deep Learning system behaviours in this respect, and provide a comprehensive assessment of 10 popular low level feature detectors. Second, we develop simple and fast algorithms that combine to provide memory- and processing-efficient feature matching. These involve static scene elimination in the presence of noise and on-screen time indicators, a blur-sensitive feature detection that finds a greater number of corresponding features in images of varying sharpness, and a combinatorial texture and colour feature matching algorithm that matches features when either attribute may be poorly defined. A comprehensive evaluation is given, showing some improvements over existing feature correspondence methods. Finally, we study random decision forests for pattern detection. A new method of indexing patterns in video sequences is devised and evaluated. We automatically label positive and negative image training data, reducing a task of unsupervised learning to one of supervised learning, and devise a node split function that is invariant to mirror reflection and rotation through 90 degree angles. A high dimensional vote accumulator encodes the hypothesis support, yielding implicit back-projection for pattern detection.

Published
2017

6. Studies in acute liver failure

Author

Craig, Darren George Norman

Abstract

Acute liver failure (ALF) is a devastating condition with a high associated mortality rate. Paracetamol hepatotoxicity remains the leading cause of ALF in the developed world. The studies outlined in this thesis explore the current management of ALF, and systematically review the prognostic tests currently used in paracetamol-induced ALF. Using a database of over 900 acute liver injury patients, the impact of unintentional paracetamol overdose is retrospectively analysed, demonstrating a strong association between this mode of paracetamol overdose and adverse clinical outcomes, including the requirement for emergency orthotopic liver transplantation. Current prognostic tests for severe paracetamol-induced hepatotoxicity have been criticised for their relatively low sensitivity, with the result that not all patients who might benefit from tertiary level care are identified. This thesis demonstrates that the development of the Systemic Inflammatory Response Syndrome (SIRS) or extrahepatic organ failure is strongly associated with death following paracetamol overdose. Due to their very high sensitivity in this condition, both the SIRS and Sequential Organ Failure Assessment scores have potential as future gatekeepers to improve the triage of paracetamol overdose patients, thereby delivering tertiary level care to those most likely to require emergency transplantation. A greater understanding of the pathophysiological links between the initial hepatic injury and development of the SIRS could help to identify novel biomarkers for ALF, and help guide future therapeutic avenues. Using serum samples from a prospectively collected cohort of acute liver injury patients, this thesis identifies two novel biomarkers, serum ferritin and the long pentraxin PTX3, which show a strong association with outcome following paracetamol hepatotoxicity. These biomarkers illustrate the importance that the innate immune system plays in the pathogenesis of paracetamol-induced ALF, and identifies several exciting areas for future cellular and animal-based studies.

Published
2012

7. Defining characteristics and outcomes for patients with non-alcoholic fatty liver disease admitted to hospital with decompensated cirrhosis

Author

Tavabie, Oliver D., Abbott, Jane, Abeysekera, Kushala WM., Balachandrakumar, Vinay K., Bennett, Kris, Brennan, Paul, Buchanan, Ryan, Dhaliwal, Amritpal, Galanakis, Vasileios, Hardy, Tim, Harris, Rebecca, Kronsten, Victoria T., Leighton, Jess, Li, Wenhao, Yin, James Liu, Macken, Lucia, Marjot, Thomas, Maurice, James B., McDowell, Hannah, Navaratnam, Janardhan, Pohl, Keith, Nayagam, Jeremy S., Saunsbury, Emma, Scott, Jennifer, Sheth, Abhishek, Sinharay, Ricky, Sheiybani, Giovanna, Subhani, Mohsan, Turner, Lucy, White, Helen, Zakeri, Nekisa, Cook, Charlotte, Abbas, Nadir, Abbasi, Abdullah, Abdul, Rahman, Abdulaziz, Mohamed, Abduljabbar, Duaa, Adamson, Robbie, Adebayo, Danielle, Adhikarla, Aditya Kumar, Adler, Maciej, Ahmad, Salman, Ahmed, Shayan, Afifi, Mostafa, Akram, Ali, Al Radhi, Balqees, Al-Talib, Ismaeel, Alele, Jolomi, Ali, Alaa Mohammed, Almusai, Safa, Appleby, Victoria, Asmat, Huma, Astbury, Sarah, Atkinson, Ali, Badrulhisham, Fakhirah, Ball, Alexandra, Banfa, Moses, Barn, Jeevan, Begum, Shahnaz, Belfield, Katherine, Bendall, Oliver, Bhandari, Rajan, Bhatti, Prashan, Bradley, Meg, Brown, Edward, Bryce, Kathleen, Burke, Laura, Campbell, Roisin, Cargill, Tamsin, Carroll, Geraldine, Cartledge, James, Chatterjee, Devnandan, Chaundry, Rayan, Choudhry, Zeshan, Clare, Kathleen, Cobbold, Jeremy, Coburn, Robert, Corvan, Fintan, Cox, Rebecca, Craig, Darren, Creamer, John, Curran, Christopher, De Silva, Shanika, Dean, Laurence, Dillon, Jayne, Dunn, Rebecca, Eckersley, Robert, Eike, Gidveig, Elagib, Amul, Elkholi, Ayman, Elshaarawy, Omar, Faloon, Sarah, Fan, Francis, Fazili, Mohammad, Fernandes, Denzil, Fox, James, Foxton, Matthew, Gaba, Waqas, Gaikwad, Girish, Gairola, Abishek, Gallaher, Charles, Gautam, Nisham, Germain, Lewis, Giles, Ben, Gill, Ceri, Glover, Ben, Glover, John, Gomez, David, Gomez, Michael, Gordon, Victoria, Gormley, Sarah, Goulder, John, Goyal, Simran, Greenham, Olivia, Guthrie, Sarah, Hackett, Richard, Haddadin, Yazan, Hadjinicolaou, Andreas, Hall, Jonathan, Haque, Tasnuma, Hart, Catherine, Hasnain Nadir, Syed Mujtaba, Hassall, James, Hasan, Sundas, Hawker-Bond, George, Hawkyard, Jake, Healey, Scott, Hornby, Catherine, Hamza, Mohammed, Humayun, M.D., Hutchison, John, Iftikhar, Zahra, Ismail, Asem, James, Joel, Jopson, Laura, Juthani, Dipal, Kaina, Philippa, Karim, Aadil, Karim, Syed Misbah, Kashyap, Vaishnavi, Kassab, Mohamed, Katarey, Dev, Kenny, Lee, Kerry, Georgina, Khan, Adnan, Khan, Ayesha, Khan, Azab, Khan, Muhammad Taha, Khan, Tahir, Khatib, Aseil, Khattak, Mohammad Fawad, King, Ji Jade, Korani, Mohammed, Kotha, Sreelakshmi, Kooner, Emily, Lam, Wai Liam, Lateef, Mohammed, Leith, Damien, Liaros, Angela, Lourenco, Floyd, Lyles, Annabel, Mahenthiran, Midusa, Magee, Ciaran, Maggs, Daniel, Mahalingam, Aarani, Mahmood, Rizwan, Mandour, Mandour Omer, Manocha, Namita, Mansour, Dina, Marks, Daniella, Martin, Ciara, Martin, Harry, Martin, Iana, Martin, Katherine, Maruthan, Sachan, Masin, Rhys, Mason, Denise, Matthews, Charmaine, Mavrou, Athina, Maxan, Ema, Maxfield, Dominic, McAvoy, Emma, McColl, Kirsty, McCaughan, Hannah, McCorry, Roger, McGoran, John, McDonald, Stewart, McIlwane, Stewart, Meakin, Olivia, Mebarek, Leila, Merrill, Hannah, Michail, Stephanie, Modarres, Pedram, Mohamedali, Alaa, Mohammed, Yaser, Mohammed, Zakiuddin, Mohan, Jaiganesh, Monnier, Chloe, Moran, Eilis, Morrison, Gary, Moroni, Francesca, Msaddi, Anas, Mutar, Sarah, Neto-Pereira, Luis, Nahed, Ismail, Ng, Jennifer, Nwoguh, Chinonso, O’Kane, Rebecca, Omar, Sohail, Ososanya, Abosede, Parambil, Jessiya Veliyankodan, Patel, Jay, Pericleous, Marinos, Pervais, Zeshan, Phoolchund, Anju, Pietrzycki, Julian, Pillay, Lushen, Prabhu, Kiran, Putri, Yesita Rizky F., Qazi, Umang, Rafique, Khizar Khalid, Raman, Krithivasan, Ranade, Vaishali, Rastelli, Francesca, Ratcliffe, Elizabeth, Rattehalli, Deepa, Raza, Tufail, Razak, Amir, Raghuraman, Arun, Read, George, Robins, Anne, Rushbrook, Simon, Salama, Mohamed, St. Aimee, Louise, Saravan, Ramasamy, Sarkar, Srishti, Serna, Solange, Shahzad, Hassnain, Shamsaldeen, Mohammed, Sharip, Mohammed, Shearer, Jessica, Sheikh, Adam, Sherwin, Michelle, Shintre, Nidhi, Singhal, Saket, Sinha, Rohit, Smith, Gloria, Smith, Ria, Spicer, Joanne, Spoor, Johannes, Sreenivasan, Shiva, Srinivasa, Amar, Srivastava, Ankur, Stagg, Georgia, Stanley, Jatinder, Stevenson, Jason, Stokes, Daniel, Stroud, Robert, Suliman, Hiba, Sultana, Marium, Summers, Nikki, Sutherland, Chloe, Swann, Rachael, Sykes, Lynne, Taha, Mostafa, Tan, Kwei Eng, Tariq, Zohaib, Ming Tay, Joshua Jun, Taylor, Alison, Thakor, Amit, Tsang, James, Tyler, Zaccharie, Unitt, Esther, Volcek, Edward, Wischhusen, Jack, Watson, Iona, Watters, Chris, Wells, Gemma, Widlak, Monika, Williams, Matthew, Woodland, Hazel, Wren, Louise, Xyda, Souzana, Yeh, Julian, Young, Alison, Jie Yuan, Jack Shie, Aithal, Guruprasad, Bernal, William, Dillon, John, Hogan, Brian, McPherson, Stuart, Jones, Rebecca, Rowe, Ian, and Snowdon, Victoria

Published
2023
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9. Regional variation in characteristics of patients with decompensated cirrhosis admitted to hospitals in the UK

Author

Tavabie, Oliver D, Abeysekera, Kushala WM, Brennan, Paul N, Marjot, Thomas, Kronsten, Victoria T, Li, Wenhao, Nayagam, Jeremy S, Dhaliwal, Amritpal, Hardy, Tim, Maurice, James B, Zakeri, Nekisa, Abbas, Nadir, Abbasi, Abdullah, Abbott, Jane, Abdul, Rahman, Abdulaziz, Mohamed, Abduljabbar, Duaa, Adamson, Robbie, Adebayo, Danielle, Adhikarla, Aditya Kumar, Adler, Maciej, Afifi, Mostafa, Ahmad, Salman, Ahmed, Shayan, Aithal, Guruprasad, Akram, Ali, Al Radhi, Balqees, Al-Talib, Ismaeel, Alele, Jolomi, Ali, Alaa Mohammed, Almusai, Safa, Appleby, Victoria, Asmat, Huma, Astbury, Sarah, Atkinson, Ali, Badrulhisham, Fakhirah, Balachandrakumar, Vinay K, Ball, Alexandra, Banfa, Moses, Barn, Jeevan, Begum, Shahnaz, Belfield, Katherine, Bendall, Oliver, Bennett, Kris, Bernal, William, Bhandari, Rajan, Bhatti, Prashan, Bradley, Meg, Brown, Edward, Bryce, Kathleen, Buchanan, Ryan, Burke, Laura, Campbell, Roisin, Cargill, Tamsin, Carroll, Geraldine, Cartledge, James, Chatterjee, Devnandan, Chaundry, Rayan, Choudhry, Zeshan, Clare, Kathleen, Cobbold, Jeremy, Coburn, Robert, Cook, Charlotte, Corvan, Fintan, Cox, Rebecca, Craig, Darren, Creamer, John, Curran, Christopher, De Silva, Shanika, Dean, Laurence, Dillon, Jayne, Dillon, John, Dunn, Rebecca, Eckersley, Robert, Eike, Gidveig, Elagib, Amul, Elkholi, Ayman, Elshaarawy, Omar, Faloon, Sarah, Fan, Francis, Fazili, Mohammad, Fernandes, Denzil, Fox, James, Foxton, Matthew, Gaba, Waqas, Gaikwad, Girish, Gairola, Abishek, Galanakis, Vasileios, Gallaher, Charles, Gautam, Nisham, Germain, Lewis, Giles, Ben, Gill, Ceri, Glover, Ben, Glover, John, Gomez, David, Gomez, Michael, Gordon, Victoria, Gormley, Sarah, Goulder, John, Goyal, Simran, Greenham, Olivia, Guthrie, Sarah, Hackett, Richard, Haddadin, Yazan, Hadjinicolaou, Andreas, Hall, Jonathan, Hamza, Mohammed, Haque, Tasnuma, Harris, Rebecca, Hart, Catherine, Hasan, Sundas, Hasnain Nadir, Syed Mujtaba, Hassall, James, Hawker-Bond, George, Hawkyard, Jake, Healey, Scott, Hogan, Brian, Hornby, Catherine, Humayun, MD, Hutchison, John, Iftikhar, Zahra, Ismail, Asem, James, Joel, Jones, Rebecca, Jopson, Laura, Juthani, Dipal, Kaina, Philippa, Karim, Aadil, Karim, Syed Misbah, Kashyap, Vaishnavi, Kassab, Mohamed, Katarey, Dev, Kenny, Lee, Kerry, Georgina, Khan, Adnan, Khan, Ayesha, Khan, Azab, Khan, Muhammad Taha, Khan, Tahir, Khatib, Aseil, Khattak, Mohammad Fawad, King, Ji Jade, Kooner, Emily, Korani, Mohammed, Kotha, Sreelakshmi, Lam, Wai Liam, Lateef, Mohammed, Leighton, Jess, Leith, Damien, Liaros, Angela, Liu Yin, James, Lourenco, Floyd, Lyles, Annabel, Macken, Lucia, Magee, Ciaran, Maggs, Daniel, Mahalingam, Aarani, Mahenthiran, Midusa, Mahmood, Rizwan, Mandour, Mandour Omer, Manocha, Namita, Mansour, Dina, Marks, Daniella, Martin, Ciara, Martin, Harry, Martin, Iana, Martin, Katherine, Maruthan, Sachan, Masin, Rhys, Mason, Denise, Matthews, Charmaine, Mavrou, Athina, Maxan, Ema, Maxfield, Dominic, McAvoy, Emma, McCaughan, Hannah, McColl, Kirsty, McCorry, Roger, McDonald, Stewart, McDowell, Hannah, McGoran, John, McIlwane, Stewart, McPherson, Stuart, Meakin, Olivia, Mebarek, Leila, Merrill, Hannah, Michail, Stephanie, Modarres, Pedram, Mohamedali, Alaa, Mohammed, Yaser, Mohammed, Zakiuddin, Mohan, Jaiganesh, Monnier, Chloe, Moran, Eilis, Moroni, Francesca, Morrison, Gary, Msaddi, Anas, Mutar, Sarah, Nahed, Ismail, Navaratnam, Janardhan, Neto-Pereira, Luis, Ng, Jennifer, Nwoguh, Chinonso, O'Kane, Rebecca, Omar, Sohail, Ososanya, Abosede, Parambil, Jessiya Veliyankodan, Patel, Jay, Pericleous, Marinos, Pervais, Zeshan, Phoolchund, Anju, Pietrzycki, Julian, Pillay, Lushen, Pohl, Keith, Prabhu, Kiran, Putri, Yesita Rizky F., Qazi, Umang, Rafique, Khizar Khalid, Raghuraman, Arun, Raman, Krithivasan, Ranade, Vaishali, Rastelli, Francesca, Ratcliffe, Elizabeth, Rattehalli, Deepa, Raza, Tufail, Razak, Amir, Read, George, Robins, Anne, Rowe, Ian, Rushbrook, Simon, Salama, Mohamed, Saravan, Ramasamy, Sarkar, Srishti, Saunsbury, Emma, Scott, Jennifer, Serna, Solange, Shahzad, Hassnain, Shamsaldeen, Mohammed, Sharip, Mohammed, Shearer, Jessica, Sheikh, Adam, Sheiybani, Giovanna, Sherwin, Michelle, Sheth, Abhishek, Shintre, Nidhi, Singhal, Saket, Sinha, Rohit, Sinharay, Ricky, Smith, Gloria, Smith, Ria, Snowdon, Victoria, Spicer, Joanne, Spoor, Johannes, Sreenivasan, Shiva, Srinivasa, Amar, Srivastava, Ankur, St. Aimee, Louise, Stagg, Georgia, Stanley, Jatinder, Stevenson, Jason, Stokes, Daniel, Stroud, Robert, Subhani, Mohsan, Suliman, Hiba, Sultana, Marium, Summers, Nikki, Sutherland, Chloe, Swann, Rachael, Sykes, Lynne, Taha, Mostafa, Tan, Kwei Eng, Tariq, Zohaib, Tay, Joshua Jun Ming, Taylor, Alison, Thakor, Amit, Tsang, James, Turner, Lucy, Tyler, Zaccharie, Unitt, Esther, Volcek, Edward, Watson, Iona, Watters, Chris, Wells, Gemma, White, Helen, Widlak, Monika, Williams, Matthew, Wischhusen, Jack, Woodland, Hazel, Wren, Louise, Xyda, Souzana, Yeh, Julian, Young, Alison, and Yuan, Jack Shie Jie

Published
2023
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11. Scientific Challenges, Opportunities and Priorities for the U.S. Fusion Energy Sciences Program

Author

Baker, Charles, Prager, Stewart, Abdou, Mohamed, Berry, Lee, Betti, Riccardo, Chan, Vincent, Craig, Darren, Dahlburg, Jill, Davidson, Ronald, Drake, James, Hawryluk, Richard, Hill, David, Hubbard, Amanda, Logan, Grant, Marmar, Earl, Mauel, Michael, McCarthy, Kathryn, Parker, Scott, Sauthoff, Ned, Stambaugh, Ronald, Ulrickson, Michael, Dam, James Van, Wurden, Glen, Zarnstorff, Michael, and Zinkle, Steven

Published
2005
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20. Appellate civil case law update.

Author

Smith, Maggie L. and Craig, Darren A.

Subjects
Civil procedure -- Surveys, Indiana. Supreme Court -- Surveys
Published
2009

22. Appellate civil case law update.

Author

Smith, Maggie L. and Craig, Darren A.

Subjects
Appellate procedure -- Surveys, Civil procedure -- Surveys
Published
2008

23. Appellate civil case law update.

Author

Smith, Maggie L. and Craig, Darren A.

Subjects
Appellate procedure -- Surveys, Civil procedure -- Surveys
Published
2007

27. Appellate civil case law update.

Author

Smith, Maggie L. and Craig, Darren A.

Subjects
Appellate procedure -- Surveys, Civil procedure -- Surveys
Published
2006

29. Markedly Increased High-Mobility Group Box 1 Protein in a Patient with Small-for-Size Syndrome

Author

Craig, Darren G., Lee, Patricia, Pryde, E. Anne, Hidalgo, Ernest, Hayes, Peter C., Wigmore, Stephen J., Forbes, Stuart J., and Simpson, Kenneth J.

Subjects
Article Subject
Abstract

Background. Small-for-size syndrome (SFSS) occurs in the presence of insufficient liver mass to maintain normal function after liver transplantation. Murine mortality following 85% hepatectomy can be reduced by the use of soluble receptor for advanced glycation end products (sRAGE) to scavenge damage-associated molecular patterns and prevent their engagement with membrane-bound RAGE. Aims. To explore serum levels of sRAGE, high-mobility group box-1 (HMGB1) protein, and other soluble inflammatory mediators in a fatal case of SFSS. Methods. Serum levels of HMGB1, sRAGE, IL-18, and other inflammatory mediators were measured by ELISA in a case of SFSS, and the results were compared with 8 patients with paracetamol-induced acute liver failure (ALF) and 6 healthy controls (HC). Results. HMGB1 levels were markedly higher in the SFSS patient (92.1 ng/mL) compared with the ALF patients (median (IQR) 11.4 (3.7–14.8) ng/mL) and HC (1.42 (1.38–1.56) ng/mL). In contrast, sRAGE levels were lower in the SFSS patient (1.88 ng/mL) compared with the ALF patients (3.53 (2.66–12.37) ng/mL) and were similar to HC levels (1.40 (1.23–1.89) ng/mL). Conclusion. These results suggest an imbalance between pro- and anti-inflammatory innate immune pathways in SFSS. Modulation of the HMGB1-RAGE axis may represent a future therapeutic avenue in this condition.

Published
2014
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31. The systemic inflammatory response syndrome (SIRS) and sequential organ failure assessment (SOFA) scores are effective triage markers following paracetamol overdose

Author

Craig, Darren George Norman, Reid, Thomas WDJ, Martin, Kirsty G, Davidson, Janice S, Hayes, Peter C, Simpson, K J, Scottish Liver Transplantation Unit, Royal Infirmary of Edinburgh, University of Edinburgh, Division of Clinical and Surgical Sciences, and Centre for Liver and Digestive Disorders

Subjects
Medicine
Abstract

International audience; BACKGROUND: The Systemic Inflammatory Response Syndrome (SIRS) and Sequential Organ Failure Assessment (SOFA) scores are widely used as prognostic markers in critical care settings and could improve triage of high-risk paracetamol (acetaminophen) overdose patients. AIM: To evaluate the prognostic accuracy of the SIRS and SOFA scores following single time point paracetamol overdose. METHODS Analysis of 100 single time-point paracetamol overdoses admitted to a tertiary liver centre, with subsequent prospective validation of identified thresholds. Individual laboratory samples were correlated with the corresponding clinical parameters in relation to time post-overdose, and the daily SOFA and SIRS scores calculated. RESULTS A total of 74 (74%) patients developed the SIRS, which occurred significantly earlier in patients who died (n=21) compared with spontaneous survivors (n=53, p=0.05). The SIRS occurred in 70 (70%) patients by 96 hours post-overdose, with a 30% mortality rate; compared with 0% mortality in the 30 non-SIRS patients (p=0.001). Median SOFA scores were significantly higher in non-survivors at 48 (p=0.009), 72 (p7 during the first 96 hours post-overdose predicted death/transplantation with a sensitivity of 95.0 (95% CI 78.5-99.1) and specificity of 70.5 (95% CI 66.3-71.6). A validation cohort of 38 single time-point paracetamol overdoses confirmed the extremely high negative predictive value of both the SIRS and SOFA thresholds. CONCLUSIONS The absence of either a SOFA score >7 or a SIRS response during the first 96 hours following paracetamol overdose could improve triage and reduce transfers of lower risk patients to tertiary liver centres.

Published
2011
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32. Overdose pattern and outcome in paracetamol-induced acute severe hepatotoxicity

Author

Craig, Darren G N, Bates, Caroline M, Davidson, Janice S, Martin, Kirsty G, Hayes, Peter C, and Simpson, Kenneth J

Subjects
Adult, Male, Pharmacoepidemiology, Contraindications, Suicide, Attempted, Analgesics, Non-Narcotic, Liver Failure, Acute, Middle Aged, Prognosis, Liver Transplantation, Humans, Female, Drug Overdose, Epidemiologic Methods, Acetaminophen, Aged
Abstract

Paracetamol (acetaminophen) hepatotoxicity is the commonest cause of acute liver failure (ALF) in the UK. Conflicting data regarding the outcomes of paracetamol-induced ALF resulting from different overdose patterns are reported.Using prospectively defined criteria, we have analysed the impact of overdose pattern upon outcome in a cohort of 938 acute severe liver injury patients admitted to the Scottish Liver Transplantation Unit.Between 1992 and 2008, 663 patients were admitted with paracetamol-induced acute severe liver injury. Of these patients, 500 (75.4%) had taken an intentional paracetamol overdose, whilst 110 (16.6%) had taken an unintentional overdose. No clear overdose pattern could be determined in 53 (8.0%). Unintentional overdose patients were significantly older, more likely to abuse alcohol, and more commonly overdosed on compound narcotic/paracetamol analgesics compared with intentional overdose patients. Unintentional overdoses had significantly lower admission paracetamol and alanine aminotransferase concentrations compared with intentional overdoses. However, unintentional overdoses had greater organ dysfunction at admission, and subsequently higher mortality (unintentional 42/110 (38.2%), intentional 128/500 (25.6%), P0.001). The King's College poor prognostic criteria had reduced sensitivity in unintentional overdoses (77.8%, 95% confidence intervals (CI) 62.9, 88.8) compared with intentional overdoses (89.9%, 95% CI 83.4, 94.5). Unintentional overdose was independently predictive of death or liver transplantation on multivariate analysis (odds ratio 1.91 (95% CI 1.07, 3.43), P = 0.032).Unintentional paracetamol overdose is associated with increased mortality compared with intentional paracetamol overdose, despite lower admission paracetamol concentrations. Alternative prognostic criteria may be required for unintentional paracetamol overdoses.

Published
2011

33. Systematic review and meta-analysis: Prognostic tests of paracetamol-induced acute liver failure

Author

Craig, Darren George Norman, Ford, Alexander, Hayes, Peter C, Simpson, K J, Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Department of Academic Medicine, and St James's University Hospital

Subjects
Medicine
Abstract

International audience; Background: Paracetamol toxicity remains the leading cause of acute liver failure (ALF) in the developed world. In the UK, the recently modified King's College Criteria (KCC) are used to list patients for emergency liver transplantation, but these criteria have been criticised for their low sensitivity and for spectrum bias in their application. Aim: To critically evaluate existing prognostic criteria for predicting death without transplantation in paracetamol-induced ALF. Methods: MEDLINE, EMBASE and CINAHL were searched to identify studies containing adult patients with paracetamol-induced ALF. Selected studies were evaluated, and data were pooled if appropriate, to calculate sensitivity, specificity, and diagnostic odds ratios (DORs) of applied prognostic tests. Results: Of 6507 studies identified, 14 were eligible for inclusion, evaluating 1960 patients. The original KCC had a pooled sensitivity of 58.2% and specificity of 94.6%, with a DOR of 27.7. Addition of arterial lactate to the KCC reduced the DOR to 26.1. Several other clinical and laboratory variables had higher DORs than the KCC, but were only evaluated in single studies of limited quality. Conclusion: The original KCC remain well validated criteria with high prognostic accuracy. Other potential prognostic variables should be prospectively assessed in multi-centre studies to further refine the criteria.

Published
2010
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37. Breeding habitat of poorly studied humpback whales (Megaptera novaeangliae) in Boa Vista, Cape Verde.

Author

RYAN, CONOR, CRAIG, DARREN, LÓPEZ-SUÁREZ, PEDRO, PEREZ, JOSE VAZQUEZ, O'CONNOR, IAN, and BERROW, SIMON D.

Subjects
*HUMPBACK whale, *MATING grounds, *PARTURITION grounds, *COASTS, *DEMOGRAPHIC surveys
Abstract

The waters surrounding Cape Verde comprise one of two known breeding grounds for humpback whales in the North Atlantic. The population remains very small and has apparently failed to recover since the cessation of whaling there. During the breeding seasons of 2011 and 2012, sighting surveys were carried out for humpback whales off Boa Vista, the easternmost island of the Cape Verde Island archipelago. The distribution and relative abundance of humpback whales and mother-calf pairs was investigated by plotting effort-corrected sightings using a 2km2 grid-square. The study area, a 206km2 region from the coastline up to 8km offshore, covered the western half of Boa Vista where whales have previously been regularly recorded. Following 1,954km of search effort, 117 sightings of humpback whales were made. An encounter rate of 0.11 whales per km was recorded for both years. It is hoped that these data may assist in implementing conservation measures to protect humpback whales and the habitat of Baia Sal Rei, which appears to be the single most important bay for winter breeding, calving and nursing humpback whales in the eastern North Atlantic. [ABSTRACT FROM AUTHOR]

Published
2013

41. Local measurements of plasma ion dynamics with optical probes.

Author

Kuritsyn, Alexey, Craig, Darren, Fiksel, Gennady, Miller, Matt, Cylinder, David, and Yamada, Masaaki

Subjects
*PLASMA gases, *PLASMA probes, *PLASMA devices, *ELECTRONIC probes, *IONS
Abstract

Two insertable optical probes have been constructed to measure local ion temperature and flow velocity using the idea proposed by Fiksel et al. [Rev. Sci. Instrum. 69, 2024 (1998)]. The light from plasma is collected by an optical fiber bundle and transported to a high resolution spectrometer. Spatial resolution of a few centimeters is achieved by using a collimator and a view dump. One ion dynamics spectroscopy (IDS) probe is employed in the edge plasma of Madison Symmetric Torus reversed field pinch in combination with the high throughput (f/4.5) and high resolution (0.15 nm/mm) IDS-II spectrometer. It has provided local ion temperature measurements of carbon and helium impurities with temporal resolution of 10 μs and accuracy of about 5 eV. The second instrument is used on the Magnetic Reconnection eXperiment, where the local temperature of helium ions (∼10 eV) has been measured with 1 eV accuracy. Details of the designs, calibrations, and data analysis are described. [ABSTRACT FROM AUTHOR]

Published
2006
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42. The toxicity lies not with the alcohol, but with the mixers.

Author

Simpson, Ken and Craig, Darren

Subjects
*HEPATITIS, *ALCOHOL drinking, *ETIOLOGY of diseases, *ANTISEPTICS, *DIETHYL phthalate
Abstract

The authors discuss a study on cholestatic hepatitis cases in Russia that was caused by consumption of alcohol in the form of the antiseptic liquid Extracept-1. They say that the consumption of non-beverage alcohols in the country continues to increase because they are cheaper. The authors stress that the study showed that exposure to toxins in non-beverage alcohols could result to mortality and morbidity. They also reveal that Extracept-1 contains diethyl phthalate (DEP), which is associated with mitochondrial abnormalities.

Published
2011
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43. MOMMY DEAREST.

Author

Craig, Darren

Subjects
LETTERS to the editor, MARRIAGE
Abstract

Presents a letter to the editor regarding underwater wedding.

Published
2005

47. Molecular forms of HMGB1 and keratin-18 as mechanistic biomarkers for mode of cell death and prognosis during clinical acetaminophen hepatotoxicity

Author

Antoine, Daniel J., Jenkins, Rosalind E., Dear, James W., Williams, Dominic P., McGill, Mitchell R., Sharpe, Matthew R., Craig, Darren G., Simpson, Kenneth J., Jaeschke, Hartmut, and Park, B. Kevin

Subjects
*KERATIN, *BIOMARKERS, *CELL death, *PROGNOSIS, *HEPATOTOXICOLOGY, *ALANINE aminotransferase, *ACETAMINOPHEN
Abstract

Background & Aims: Full length keratin-18 (FL-K18) and High Mobility Group Box-1 (HMGB1) represent circulating indicators of necrosis during acetaminophen (APAP) hepatotoxicity in vivo. In addition, the caspase-cleaved fragment of K18 (cK18) and hyper-acetylated HMGB1 represent serum indicators of apoptosis and immune cell activation, respectively. The study aim was to assess their mechanistic utility to establish the balance between apoptosis, necrosis, and immune cell activation throughout the time course of clinical APAP hepatotoxicity. Methods: HMGB1 (total, acetylated) and K18 (apoptotic, necrotic) were identified and quantified by novel LC–MS/MS assays in APAP overdose patients (n=78). Results: HMGB1 (total; 15.4±1.9ng/ml, p <0.01, acetylated; 5.4±2.6ng/ml, p <0.001), cK18 (5649.8±721.0U/L, p <0.01), and FL-K18 (54770.2±6717.0U/L, p <0.005) were elevated in the sera of APAP overdose patients with liver injury compared to overdose patients without liver injury and healthy volunteers. HMGB1 and FL-K18 correlated with alanine aminotransferase (ALT) activity (R2 =0.60 and 0.58, respectively, p <0.0001) and prothrombin time (R2 =0.62 and 0.71, respectively, p <0.0001). Increased total and acetylated HMGB1 and FL-K18 were associated with worse prognosis (King’s College Criteria) or patients that died/required liver transplant compared to spontaneous survivors (all p <0.05–0.001), a finding not reflected by ALT and supported by ROC analysis. Acetylated HMGB1 was a better predictor of outcome than the other markers of cell death. Conclusions: K18 and HMGB1 represent blood-based tools to investigate the cell death balance clinical APAP hepatotoxicity. Activation of the immune response was seen later in the time course as shown by the distinct profile of acetylated HMGB1 and was associated with worse outcome. [ABSTRACT FROM AUTHOR]

Published
2012
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48. Cyclophilin A Is a Damage-Associated Molecular Pattern Molecule That Mediates Acetaminophen-Induced Liver Injury.

Author

Dear, James W., Simpson, Kenneth J., Nicolai, Melianthe P. J., Catterson, James H., Street, Jonathan, Huizinga, Tineke, Craig, Darren G., Dhaliwal, Kevin, Webb, Sheila, Bateman, D. Nicholas, and Webb, David J.

Subjects
*CYCLOPHILINS, *ACETAMINOPHEN, *LIVER failure, *CELL death, *LIVER cells, *IMMUNE system
Abstract

The immune system is alerted to cell death by molecules known as damage-associated molecular patterns (DAMPs). These molecules partly mediate acetaminophen-induced liver injury, an archetypal experimental model of sterile cell death and the commonest cause of acute liver failure in the western world. Cyclophilin A (CypA) is an intracellular protein that is proinflammatory when released by cells. We hypothesized that CypA is released from necrotic liver cells and acts as a DAMP to mediate acetaminophen-induced liver injury. Our data demonstrated that mice lacking CypA (Ppia-/-) were resistant to acetaminophen toxicity. Antagonism of the extracellular receptor for CypA (CD147) also reduced acetaminophen-induced liver injury. When injected into a wild-type mouse, necrotic liver from Ppia-/- mice induced less of an inflammatory response than did wild-type liver. Conversely, the host inflammatory response was increased when CypA was injected with necrotic liver. Antagonism of CD147 also reduced the inflammatory response to necrotic liver. In humans, urinary CypA concentration was significantly increased in patients with acetaminophen-induced liver injury. In summary, CypA is a DAMP that mediates acetaminophen poisoning. This mechanistic insight presents an opportunity for a new therapeutic approach to a disease that currently has inadequate treatment options. [ABSTRACT FROM AUTHOR]

Published
2011
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50. Identification of nuclear export inhibitors with potent anticancer activity in vivo.

Author

Mutka SC, Yang WQ, Dong SD, Ward SL, Craig DA, Timmermans PB, and Murli S

Subjects
Active Transport, Cell Nucleus drug effects, Animals, Apoptosis drug effects, Bone Neoplasms drug therapy, Bone Neoplasms metabolism, Cell Cycle drug effects, Cell Line, Tumor, Cell Nucleus metabolism, Fatty Acids, Unsaturated chemistry, Fatty Acids, Unsaturated pharmacology, Female, Fibroblasts cytology, Fibroblasts drug effects, HCT116 Cells, Humans, Lung cytology, Lung drug effects, Mice, Mice, Inbred C57BL, Mice, Nude, Osteosarcoma drug therapy, Osteosarcoma metabolism, Tumor Suppressor Protein p53 biosynthesis, Xenograft Model Antitumor Assays, Exportin 1 Protein, Antibiotics, Antineoplastic chemistry, Antibiotics, Antineoplastic pharmacology, Cell Nucleus drug effects, Karyopherins antagonists & inhibitors, Receptors, Cytoplasmic and Nuclear antagonists & inhibitors
Abstract

The export protein CRM1 is required for the nuclear export of a wide variety of cancer-related "cargo" proteins including p53, c-Abl, and FOXO-3A. Leptomycin B (LMB) is a highly specific inhibitor of CRM1 with significant in vitro potency but limited in vivo efficacy due to toxicity. We now report a series of semisynthetic LMB derivatives showing substantially improved therapeutic windows. Exposure of cancer cells to these compounds leads to a rapid and prolonged block of nuclear export and apoptosis. In contrast to what is observed in cancer cells, these agents induce cell cycle arrest, but not apoptosis, in normal lung fibroblasts. These new nuclear export inhibitors (NEI) maintain the high potency of LMB, are up to 16-fold better tolerated than LMB in vivo, and show significant efficacy in multiple mouse xenograft models. These NEIs show the potential of CRM1 inhibitors as novel and potent anticancer agents.

Published
2009
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