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1. Assessing teams in endoscopy : does good non-technical skills performance correlate with good clinical outcomes?

Author: Hitchins, Charlotte Ruth
Subjects: 616.33, endoscopy, gastrointestinal endoscopy, non-technical skills, team training, non-technical skills assessment
Abstract: Background Failures in non-technical skills (NTS) contribute to adverse events in healthcare. Previous research has explored the assessment and training of these skills, and yet there is a lack of evidence for their impact on clinical outcomes. Gastrointestinal endoscopy is a high-pressure specialty, but to date there is little on the role of NTS in this area, or a method for their assessment. This MD project aims to measure NTS in endoscopy, explore their relationship with clinical outcomes, and identify those specific to this area of healthcare. Methods An observational study of endoscopy teams in real time, using the Oxford NOTECHS II assessment tool. Comparison of NTS performance with procedure outcomes and patient satisfaction. A qualitative interview study with staff members to establish the NTS specifically relevant to working in gastrointestinal endoscopy. Results Reliability of the Oxford NOTECHS II tool by a single rater in this environment was good. Positive relationships were found between NTS scores and polyp detection, scope withdrawal time and completion of items on a safety checklist. However, relationships with other outcomes, including patient satisfaction were weak, or inconclusive. The themes identified relating to NTS in gastrointestinal endoscopy were leadership, working together as a team, situation awareness, making decisions, the patient and communication. Conclusions Although few conclusive relationships were found between NTS performance and procedure outcomes, those positive associations found seem logical as they are likely to reflect increased care and vigilance. This may have been affected by a lack of variation in scores. The NTS relevant to this area are similar to other areas of healthcare. However, the interaction with and around the awake patient is unique to endoscopy and an important influence on the NTS that staff must possess. There is scope to develop a more specific tool for the assessment of NTS in endoscopy.
Published: 2018

2. Posttraumatic growth as a discursive resource for managing identity after breast cancer : implications for theory, and counselling psychology practice

Author: Hitchins, Jennifer Marie
Subjects: 362.19699, 610 Medicine & health
Abstract: Previous research conceptualises posttraumatic growth (PTG) as a phenomenon experienced by some people after breast cancer. In this thesis, I consider an alternative understanding of PTG; as discursive identity performance in the context of breast cancer survivorship. First, a critical review of literature on PTG after cancer is presented, with attention to rigour and methodological diversity and also with regard to the fit between existing research and counselling psychology values. It is concluded that much of the existing research is framed within a realist perspective, and accordingly, accounts of PTG are viewed as stable internal beliefs rather than socially constructed ways of managing identity. The social context in which survivorship occurs has not been adequately explored and there is a paucity of work from within the UK, and especially from amongst counselling psychologists, who, arguably, have a significant contribution to make within the psycho-oncology arena. An area for research is marked out, from the epistemological position of social construction, to explore women's accounts of life after cancer, and how they orient to and make use of PTG in this context. Following consideration of the approach taken (a synthesis of two forms of discourse analysis), I present my research with four women who were interviewed about their experiences of life after breast cancer. The analysis highlights the fine grained features of the women's talk as they manage their post-cancer identities discursively negotiating the social and moral obligation to survive well. A number of discourses, including the ‘PTG discourse’ are drawn upon, making a number of subject positions available. Notably, the PTG discourse closes down talk of troubles. Implications for theory, and for counselling psychology practice within psycho-oncology, are discussed.
Published: 2015

3. Oakland Schools New Teacher's Manual.

Author: Oakland Schools, Waterford, MI., Fletcher, Barbara, Hitchins, Renee, Kramp, Robert, Moase-Burke, Jackie, and Pinho, Jason
Abstract: This guide for beginning teachers provides assistance in the following areas: (1) "Physical Environment and Materials" (e.g., room arrangement and bulletin boards); (2) "Setting Expectations" (e.g., rules and consequences and early parent communication); (3) "First Days of School" (e.g., activities and teacher daily reflection log); (4) "Establishing a Positive Environment" (e.g., building community and building self-esteem); (5) "Parent Communication" (e.g., parent-teacher night and positive versus negative language); (6) "Evaluating" (evaluating students and evaluating teachers); (7) "Quick Teaching Tips" (e.g., time saving tips and homework tips); (8) "Employee Information" (school roster and union information); (9) "Resources" (teachers' stores, Oakland Schools, and Internet resources); and (10) "Appendix" (e.g., sample first day letter to parents, sponge activities, sample lesson plans, conference letter samples, substitute information, secondary student information sheet, informal cooperative learning, tips for involving parents, and legal information). (SM)
Published: 1998

4. The influence of the audio engineer on the development of Jamaican popular music

Author: Hitchins, Raymond A.
Subjects: 781.629697292
Abstract: This ethnomusicology-based study investigates the influence of audio engineers on the development of Jamaican popular music. An analysis of audio engineering practice from Jamaica's earliest recording studios to present day has shown how audio engineers have understood and used new technologies, adapting and applying them on their own terms, and how this has had a profound impact on the development of Jamaican music. The thesis provides a new perspective and significant additional information and insights on the formative years of the Jamaican recording industry. This includes the way in which music was consumed, the role of recording studios, the way in which they were accessed and the significance of the first post-mento recordings, categorised into two distinct recorded products of exclusive sound-system acetates and commercial records. Analysis of these products includes the first detailed description of a seminal 1958 recording session that marked a major transition in Jamaican recording models. This thesis demonstrates how emphasised bass and the riddlrn- production method emerged as audio-engineered elements in the Jamaican music-production system. The thesis introduces a new graphical mixing- analysis tool that demonstrates how engineered sounds, rhythms and performance-mixing, based on spontaneity, groove and vibe, became integral parts of that system. This thesis argues that audio engineers and musicians often play the role of producer, but also demonstrates the way in which audio engineering practice became integrated into the work of the multi-role producer. This thesis questions prevalent themes in the literature, such as t~e concept of a 'digital revolution' and argues that this and other claims are not supported by the analysis of actual recording practice, especially when considered in the context of the social, political and economic forces that characterise the music industry in Jamaica. Finally, an ethnographic study and analysis of a recording session, demonstrates how the audio engineer continues to have a profound influence on Jamaican popular music today.
Published: 2011

5. Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Author: Spiers, H, Kouli, O, Ahmed, W, Varley, R, Ahari, D, Argus, L, Mclean, K, Kamarajah, S, Coe, P, Griffiths, E, Chan, A, Macutkiewicz, C, Jamdar, S, Wilson, M, Fullwood, C, Toogood, G, Gilchrist, A, Goldsworthy, M, Rashid, M, Pockney, P, Varela, J, Brindl, N, Ramirez, J, Marafante, C, Iwao, Y, Ghzawi, A, Elhadi, M, Gacaferi, H, Varghese, C, Adeyeye, A, Alser, O, Teh, C, Prieto, M, Hasan, A, Al-Naggar, H, Salgado, R, Veracierto, F, Lancelotti, T, Solinas, D, Oddi, R, Garcia, F, Mazza Diez, E, Andrade Ramirez, M, Bracco, R, Fernandez, D, Maraschio, M, Obeide, L, Giordano, E, Alcaraz, A, Marani, M, Aguirre, N, Luna, F, Francesconi, M, Chiham, F, Ramos Cossio, R, Alvarez, F, Pantoja Pachajoa, D, Mandojana, F, Merlo, I, Gonzalez, M, Cervelo, G, Puma, R, Vardaro, G, Davis, A, Jurat, D, Guenoff, C, Raubenheimer, K, Goddard, K, Brown, K, Wegrecki, K, Cheung, H, Yang, M, Siddiqui, J, Ahn, J, Huynh, R, Lam, Y, Afzal, M, Ong, B, Chua, M, Ly, K, Thomson, J, Watson, D, Dawson, A, Drane, A, Van Ruyven, S, Lun, E, Ferguson, M, Jeong, J, De Silva, C, Wills, V, Gundara, J, Mccourt, E, Bong, C, Tabone, R, Wong, W, Gray, A, Koh, D, Pollock, M, Singhal, S, Smith, R, Dudi-Venkata, N, Kanhere, H, Stranz, C, Seow, W, Mansour, L, Wormald, J, Loveday, B, Thomson, B, O'Donnell, T, Milenkovski, N, Herath, M, Trochsler, M, Farfus, A, Maddern, G, Bunjo, Z, Kuan, L, Atanasov, G, Samadov, E, Namazov, I, Asgarov, M, Ibrahimli, A, Srinivasan, M, Saeed, M, Aljawder, H, Juma, I, Coimbra, F, Marques, N, Casteleins, W, Petruzziello, A, Jabur, G, Rodriguez, J, Buso, P, Mackenzie, S, Hsiao, M, Sljivic, I, Tecson, A, Karanicolas, P, Roke, R, Moon, J, Butler, E, Riquelme, F, Yanez, M, Catan, F, Uribe, M, Carriel, F, Oppliger, F, Paredes, A, Daroch, D, Aguayo, J, Perez Rivera, C, Acosta Buitrago, L, Kadamani Abiyomaa, A, Mosquera Paz, M, Cabrera, P, Corso, J, Ozcay, N, Ozant, A, Arslan, K, Besim, H, Almezghwi, H, Azzam, A, Bessa, S, El-Sayes, I, Badawy, A, Wael, M, El-Gendi, A, Azab, M, Fayed, M, El Kassas, M, Gamal, M, Tawheed, A, Al Shafie, A, Emile, S, Elfallal, A, Elfeki, H, Shalaby, M, Sakr, A, Elbahnasawy, M, Shama, M, Abdel-Elsalam, W, Abd-Elsalam, S, Escobar Dominguez, J, Medrano, F, Gaitan, S, Escalon Gonzalez, O, Alfaro Varela, J, Cea, M, Interiano, M, Cabrera, B, Lakkis, Z, Georges, P, Antonot, C, Magnin, J, Kamphues, C, Lauscher, J, Schineis, C, Loch, F, Lee, L, Beyer, K, Bouchagier, K, Galanis, I, Bartziotas, D, Lostoridis, E, Tourountzi, P, Nagorni, E, Charalabopoulos, A, Baili, E, Kyros, E, Vagios, I, Skotsimara, A, Liakakos, T, Alexandrou, A, Papalampros, A, Papadopolous, V, Tooulias, A, Kentarchos, I, Christou, C, Tsoulfas, G, Tale-Rosales, L, Lopez Muralles, I, Melendez, H, Bran, G, Monroy Mahecha, F, Contreras, J, Porras, D, Paiz, E, Soto, E, Ixcayau Hernandez, J, Gupta, A, Rajput, D, Kumar, N, Mani, R, Kant, R, Sonkar, A, Anand, A, Agrawal, M, Gaurav, K, Tripathi, M, Sikora, S, Bharathy, K, Kumar Rangapa, M, Khuller, D, Bhojwwani, R, Ayyar, S, Jain, N, Mehraj, A, Hussain, F, Nazir, I, Shah, M, Chowdri, N, Hilmi, A, Argenio, G, Atelli, P, Palladino, E, Armellino, M, Tamini, N, Nespoli, L, Degrate, L, Angrisani, M, Carissimi, F, Bordoni, P, Fleres, F, Clarizia, G, Spolini, A, Franzini, M, Cucinotta, E, Badessi, G, Mazzeo, C, Viscosi, F, Pintabona, G, Campagnaro, T, Poletto, E, Turri, G, Ruzzenente, A, Conci, S, Guglielmi, A, Feo, C, Fabbri, N, Fazzin, M, Giaccari, S, Massani, M, Pelizzo, P, Colella, M, Tutino, R, Cappellacci, F, Medas, F, Canu, G, Erdas, E, Calo, P, Porcu, A, Perra, T, Scanu, A, Fancellu, A, Germani, P, Giunta, C, Biloslavo, A, Abdallah, H, Aizza, G, Barberis, A, Belli, F, Santoliquido, M, Filauro, M, Canonico, G, Nelli, T, Di Martino, C, Capezzuoli, L, Anastasi, A, Bressan, L, Cortinovis, S, Nagliati, C, Colombo, F, Ferrario, L, Bondurri, A, Guerci, C, Maffioli, A, Catena, F, Perrone, G, Giuffrida, M, Morini, A, Annicchiarico, A, Gallo, G, Carpino, A, Ferrari, F, De Paola, G, Sammarco, G, Callari, C, Licari, L, Sorce, V, Di Miceli, D, Lovisetto, F, Zonta, S, Chessa, A, Fiorini, A, De Manzoni Garberini, A, Angelini, E, Moggia, E, Murgese, A, Mungo, S, Birolo, S, Garino, M, Pipitone Federico, N, Muratore, A, Lunghi, E, Calabro, M, Cianci, P, Enrico, R, Capuzzolo, S, Cafagna, L, Minafra, M, Sasia, D, Gattolin, A, Migliore, M, Rimonda, R, Travaglio, E, De Marco, G, Elter, C, Bargellini, T, D'Amico, S, Zambonin, D, Caponi, A, Calini, G, Puggioni, A, Bresadola, V, Zalla, T, Cantafio, S, Feroci, F, Romoli, L, Giudicissi, R, Picciariello, A, Papagni, V, Dibra, R, Altomare, D, Pinotti, E, Montuori, M, Baronio, G, Tonini, V, Sartarelli, L, Gori, A, Cervellera, M, Lapolla, P, Sapienza, P, Brachini, G, Cirillo, B, Zambon, M, Mingoli, A, Pascariello, A, Boccia, L, Benedetti, S, Mantovani, G, De Angelis, M, Ferrara, F, Testa, V, Borghi, F, Maione, F, Pruiti Ciarello, V, Giraudo, G, Agresta, F, Cestaro, G, Prando, D, Cavallo, F, Zese, M, Cillara, N, Sechi, R, Cardia, R, Cannavera, A, Putzu, G, Frongia, F, Pisanu, A, Delogu, D, Esposito, G, Podda, M, Iossa, A, De Angelis, F, Boru, C, Silecchia, G, Palini, G, Garulli, G, Veneroni, S, Tammaro, P, Maida, P, Leake, P, Wanliss, M, Sato, K, Chiyonobu, N, Imamura, H, Yamazaki, S, Watanabe, M, Qasem, A, Ayasra, F, Al Dahabrh, S, Khaled, A, Alsaafin, S, Al-Thunaibat, A, Olaywah, D, Alqudah, S, Alqawasmi, S, Khamees, A, Guboug, A, Es Salim, M, Althwabteh, T, Bani Khaled, H, El-Hammuri, N, Aljesrawi, A, Alamaadany, F, Eljareh, M, Al Gasi, A, Alsaeiti, S, Alkhafeefi, A, Suliaman, T, Alanasri, A, Haroun, A, Haron, A, Kilani, A, Ahmed, M, Alawami, M, Alawami, A, Albashri, M, Abusannuga, M, Malek, A, Jwaili, N, Aldenfria, A, Elzwawi, F, Almugaddami, A, Egdeer, A, Masoud, M, Alazzabi, B, Alezabi, B, Shuwayyah, A, Alkamkhe, A, Aboulqasim, I, Atiyah, H, Alfagi, R, Abdulmula, A, Bouhuwaish, A, Samer, A, Salim, R, Aboazamazem, H, Almiqlash, B, Biala, M, Alganimi, W, Ghamgh, R, Ben Omar, N, Alsoufi, A, Aldreawi, M, Saleim, N, Sowan, F, Saleem, H, Ahmed, A, Samalavicius, N, Aliosin, O, Dailidenas, S, Dulskas, A, Buckus, B, Kuliesius, Z, Bradunaite, R, Dominguez-Rosado, I, Buerba, G, Posadas-Trujillo, O, Alfaro-Goldaracena, A, Cortes, R, Mercado, M, Beristain-Hernandez, J, Mora-Munoz, V, Mena-Bedolla, J, Palacios Ramirez, A, Astorga Medina, M, Van Aert, G, Ombashi, S, Spillenaar Bilgen, R, Vos, D, Besselink, M, Alberts, V, Busch, O, Bemelman, W, Boermeester, M, Daams, F, Gordinou De Gouberville, M, Van Duijvendijk, P, De Graaff, M, Baaij, J, Gans, S, Bos, K, Goudsmit, B, Den Dekker, B, Braat, A, Kuijpers, A, Breukers, S, Borel Rinkes, I, Andel, D, Hayes, T, Carson, D, Bhat, S, Van Der Have, J, Anderson, C, Bissett, I, Windsor, J, Elliott, B, Scowcroft, H, Mclauchlan, J, Ritchie, D, Jeffery, F, Connor, S, Xu, W, Mashlan, H, Thirayan, V, Ly, J, Mcguinness, M, Ferguson, L, Watt, I, Harmston, C, Akinmade, A, Enoch, E, Kayode-Nissi, V, Ogundele, I, Ayoade, B, Adekoya, A, Nwokoro, C, Opadeyi, A, Yusuf, A, Ojajuni, A, Adepoju, O, Muhammad Dauda, M, Keffi Mubarak, M, Lawal, K, Muhammad, D, Salonga, D, Sael, N, Rey, C, Pestano, M, Tan, D, Bangayan, N, Sy, D, Ang, D, Bernardo, E, Chua, J, Alharthi, M, Bukhari, W, Bakier Mohammed, K, Al Athath, S, Ghunaim, M, Saiedi, H, Sultan, N, Farsi, A, Basendowah, M, Malibary, N, Jaloun, H, Altalhi, D, Organjee, A, Moamena, M, Al Zaidi, T, Alyami, M, Alqannas, M, Al-Urfan, M, Elawad, A, Alawadhi, A, Alalawi, Y, Alqarni, A, Alqahtani, B, Alayed, A, Alsobaie, K, Adi, H, Elhaj, M, Dehlawi, A, Behairy, G, Khaled, I, Kmezic, S, Radenkovic, D, Aleksic, L, Markovic, V, Pejovic, I, Antic, A, Kalkan, M, Vujanovic Gadjanski, O, Dusan, S, Marcetic, B, Thiruchelvam, N, Chiow, A, Mun, D, Tan, E, Koh, Y, Loh, W, Wang, Z, Chan, C, Kloppers, C, Almgla, N, Bernon, M, Kahn, M, Karimbocus, N, Roldan Villavicencio, J, Goitia, V, Gutierrez Rios, R, Garcia Ruiz, S, Lopez Deogracias, M, Turrado-Rodriguez, V, Morales, X, Hessheimer, A, Termes Serra, R, Beltran De Heredia, J, Trujillo-Diaz, J, Herreros-Rodriguez, J, Montes-Manrique, M, De Andres-Asenjo, B, Beltran-Heredia, J, Gimenez Maurel, T, Utrilla Fornals, A, Martin Anoro, L, Cortese, S, Perez Diaz, M, Ballon, M, Morote, M, Cebolla Rojas, L, Oliver Guillen, J, Lopez De Fernandez, A, Del Campo Lavilla, M, Mora-Guzman, I, Escartin, A, Pinillos, A, Vela Polanco, F, Jara Quezada, J, Muriel Alvarez, P, Tur-Martinez, J, Camps, J, Herrero, E, Garcia-Domingo, M, Cugat Andorra, E, Crespi Mir, A, Claramonte Bellmunt, O, Vicens Arbona, J, Fernandez Burgos, I, Sarriugarte Lasarte, A, Marin, H, Tellaeche De La Iglesia, M, Ocerin Alganza, O, Salinas Gomez, J, Ramos-Martin, P, Urbieta, A, Nasimi Sabbagh, R, Castell Gomez, J, Serrablo, A, Paterna -Lopez, S, GutiCrossed D SignCopyrightrrez-Diez, M, Abadia-Forcen, M, Serradilla-Martin, M, Duran Munoz-Cruzado, V, Pareja Ciuro, F, Perea Del Pozo, E, Aparicio Sanchez, D, Dios-Barbeito, S, Marenco De La Cuadra, B, Retamar Gentil, M, Reguera-Rosal, J, Infantes Ormad, M, Lopez-Ruiz, J, Landaluce-Olavarria, A, Zevallos-Quiroz, J, Barrutia Leonardo, J, Emaldi, A, Begona, E, Balciscueta Coltell, I, Sebastian, M, Martinez Ramos, S, Martinez Alcaide, S, Lorenzo Perez, J, Martinez Insfran, L, Lopez-Morales, P, Gimenez Frances, C, Rahy-Martin, A, Pelloni, M, Ortiz-Lopez, D, Benet-Munoz, O, Pinero-Gonzalez, L, Alconchel, F, Nicolas-Lopez, T, Rodrigues, K, Cascales Campos, P, Gomez-Bosch, F, Ramirez Romero, P, Ibrahim, M, Hamid, H, Idres, R, Idris, M, Mohammed, O, Ayran, S, Sinan, A, Ozben, V, Aytac, E, Aliyeva, Z, Mutlu, A, Bilgin, I, Karahasanoglu, T, Hamzaoglu, I, Bozkirli, B, Uprak, T, Kotan, T, Coskun, M, Kara, Y, Somuncu, E, Kocatas, A, Bozkurt, M, Demirli Atici, S, Kaya, T, Sert, I, Emiroglu, M, Jaffar, M, Younis, M, Aziz, T, Ikram, F, Sandal, M, Al Madhloum Al Suwaidi, F, Alshaikh, M, Saber, A, Khammas, A, Nessa, A, Jardine, R, Nicol, L, Clark, C, Mcgee, A, Alkari, B, Feretis, M, Antakia, R, Georgiades, F, Moneim, J, O'Neill, R, Balakrishnan, A, Lunevicius, R, Sud, A, Moutsos, I, Gomez, D, Shahid, S, Majeed, T, Ibrahim, W, Kadum, K, Melia, R, Magee, C, Chicken, D, Kumar, S, Alshibshoubi, M, Van Laarhoven, S, Dewi, F, Williams, J, Byrne, B, Wilkerson, P, Tang, C, Farhangmehr, N, Jonas, A, Charavanamuttu, V, Almeida, K, Efthimiou, E, Boardley, J, White, A, Butt, M, Menzies, D, Gundkalli, Z, Hassanzadeh-Baboli, D, Jones, O, Mistry, P, Saha, S, Gerrard, A, Evans, J, Rajeev, S, Ali, W, Ross, E, Gilliam, A, Hitchins, C, Emslie, K, Spellar, K, Sked, H, Briggs, C, Brown, L, A Hemadasa, N, Apollos, J, Belgaumkar, A, Tawfik, A, Brewin, L, Oyewole, B, Wadhawan, H, Massie, E, Rutherford, D, Mcgivern, K, Mcelroy, L, De'Ath, H, Tobbal, M, Nagendram, S, Patel, P, Handa, S, Houghton, G, Sundaralingam, S, Parker, J, Morgan, R, Gala, T, Ibrahim, S, Harby, R, Abdelkarim, M, Holroyd, D, Thomas, R, Mclennan, E, Boardley, R, Jamieson, N, Ebied, H, Gossage, J, Davies, A, Wheatstone, S, Jawad, Z, Jiao, L, Rajagopal, P, Sodergren, M, Lami, M, Wiberg, A, Bond-Smith, G, Gemmill, E, Lenzi, E, Sapre, D, Herrod, P, Boyd-Carson, H, Garcea, G, Issa, E, Jackson, A, Fashina, T, Pan, H, Farquharson, B, Shafiq, H, Emanuel, O, Mahdi, S, Jeyarajah, S, Finch, L, Whiting, G, Pigott, L, Martin, J, Siriwardena, A, Beatson, K, Abawi, L, Lam, W, Rea, W, Andrews, B, Al-Sarireh, B, Soliman, F, Burridge, J, Jenvey, C, Hammoda, M, Hollyman, M, Merker, L, Richards, J, Sukumaran, V, Rogers, S, Payne, C, Bibi, S, Raza, K, Ul Ain, N, Dronamraju, S, Patil, S, Nachimuthu, S, Ravindran, S, Patel, S, Ivanov, B, Patel, M, Ejtehadi, F, Jebamani, J, Akhter Rahman, M, Woodun, H, De Prendergast, A, Afzal, A, Bota, E, Abdul, S, Karmarkar, R, Crockett, E, Evans, L, Appleton, B, Dada, O, Kulkarni, R, Albirnawi, H, Gravestock, P, Vincenti, C, Taribagil, S, Dent, B, Tse, C, Clayton, B, Burdekin, E, Bannister, L, Alam, I, Gray, J, Mactier, M, Pollock, A, Gough, V, Kanchustambam, S, Ridgway, M, Arujunan, K, Gopalswamy, S, Monteiro De Barros, J, Lyons, T, Griffith, D, Awan, A, Latif, J, Bandlamudi, N, Bhatti, I, Raptis, D, Machairas, N, Pissanou, T, Mestre-Costa, J, Hidalgo Salinas, C, Pollok, J, Al-Ardah, M, Watson-Jones, E, Rontree-Carey, T, Boyce, T, Hawkin, P, Elmaradny, A, Ross, K, Adu-Peprah, E, Pinto, K, Dunne, D, Mccready, R, Nita, G, Szatmary, P, Tay, V, Rajput, K, Rajendran, I, Chaudhury, M, Zambas, G, Swaminathan, C, Atif, Q, Barrow, T, Williams, O, Malik, A, Conroy, S, Lindley, S, Gilmore, K, Boden, E, Richards, S, Hraishawi, I, Polak, P, Mclaughlin, D, Deeny, D, Shuttleworth, R, Harris, A, Peilober-Richardson, A, Morris, G, Sara, X, Almourad, H, Ang, Y, Smyth, R, Ding, D, Foster, J, Bond, A, Kumar, Y, Ahmad, A, Radoi, D, Alkaili-Alyamani, A, Balakrishnan, S, Satchidanand, R, Danwaththa Liyanage, A, Blake, I, Ransome, M, Weerasinghe, C, Kenington, C, Mayo, K, Mohammed, M, Cockbain, A, Peckham-Cooper, A, Mccauley, G, Gordon, C, Smith, A, Hawkins, W, Chakravartty, S, Baillie, C, Kenny, R, Kumar, A, Koimtzis, G, Bellamy, E, Menon, A, Kanakala, A, Nevins, E, Madhavan, A, Thulasiraman, S, France, K, O'Connor, A, Idama, D, Raslan, C, Sridhar, S, Parveen, M, Mubashar, T, Jarvis, S, Cakmak, I, Wright, C, Andrews, S, Abdelsaid K Abdul Aal, Y, Jayasankar, B, Morilla, J, Shehata, M, Subba, N, Tewari, N, El-Sayed, C, Somaie, D, Beheiry, N, Douka, E, Arumugam, S, Wijetunga, I, Leivers, E, Ibrahim, B, Khan, K, Wheat, J, Christopher, J, Barnett, R, Elberm, H, Booker, J, Ashai, S, Berry, D, Luhmann, A, Sgro, A, Galea, M, Jeyakumar, J, Marriott, P, Zafar, S, Baker, A, Yershov, D, Galanopoulos, G, Jordan, R, Peinado Garcia, C, Anyaugo, N, Bath, M, Omatseye, J, Roberts, L, Argyriou, E, Machesney, M, Parmar, C, Clark, S, Khalil, H, Unsworth, S, Mlotshwa, M, Ayoub, N, Aboelkhair, A, Iosif, E, Mohamed, N, Reynolds, E, Mackender, E, Robinson, D, Mufti, W, Fischkoff, K, Coleman, N, Anantha Sathyanarayana, S, Deutsch, G, Giangola, M, Lin, D, Weiss, M, Chung, C, Nguyen, A, Mueller, J, Dabit, M, Gordon, J, Mcguire, E, Rashid, O, Georgi, E, Gallo, M, Kunstman, J, Peters, N, O'Connor, R, Bhattacharya, B, Onkendi, E, Santos, A, Richmond, R, Warren, M, Zhang, K, Broderick, R, Clary, B, Horgan, S, Doucet, J, Liepert, A, Harmon, L, Mccall, C, Sham, J, Williams, E, Labadie, K, Clark, N, Dickerson, L, Hammill, C, Williams, G, Kushner, B, Cos, H, Zarate Rodriguez, J, Bailey, K, Al-Raimi, I, Al-Zazay, K, Ahmed Mohammed Al-Mahdi, S, Mohammed Aldowbli, S, Al-Shehari, M, Shream, S, Al-Ameri, S, Aeed, M, Aldawbali, M, Alsayadi, R, Alsayadi, M, Spiers H. V. M., Kouli O., Ahmed W. U., Varley R., Ahari D., Argus L., McLean K. A., Kamarajah S. K., Coe P., Griffiths E. A., Chan A. K. C., Macutkiewicz C., Jamdar S., Wilson M., Fullwood C., Toogood G., McLean K., Ahmed W., Gilchrist A., Goldsworthy M., Rashid M., Pockney P., Varela J., Brindl N., Ramirez J., Marafante C., Iwao Y., Ghzawi A., Elhadi M., Gacaferi H., Varghese C., Adeyeye A., Alser O., Teh C., Prieto M., Hasan A., Al-Naggar H., Salgado R., Veracierto F., Lancelotti T., Solinas D., Oddi R., Garcia F. W., Mazza Diez E., Andrade Ramirez M. R., Bracco R., Fernandez D., Maraschio M. A., Obeide L., Giordano E., Alcaraz A., Marani M. A., Aguirre N., Luna F., Francesconi M., Chiham F., Ramos Cossio R., Alvarez F. A., Pantoja Pachajoa D. A., Mandojana F., Merlo I. G., Gonzalez M. H., Cervelo G., Puma R., Vardaro G. F., Davis A., Jurat D., Guenoff C., Raubenheimer K., Goddard K., Brown K., Wegrecki K. J., Cheung H. Y. C., Yang M., Cheung H., Siddiqui J., Ahn J. H., Huynh R., Lam Y. H., Afzal M., Ong B. S., Chua M. Y. M., Ly K., Thomson J. E., Watson D., Dawson A. C., Drane A., Van Ruyven S., Lun E. W. Y., Ferguson M., Jeong J. Y., De Silva C., Wills V., Gundara J., McCourt E., Bong C., Tabone R., Wong W. J., Gray A., Koh D., Pollock M., Singhal S., Smith R., Dudi-Venkata N. N., Kanhere H., Stranz C., Seow W., Mansour L. T., Wormald J., Loveday B. P. T., Thomson B., O'Donnell T., Milenkovski N., Herath M., Trochsler M., Farfus A., Maddern G., Bunjo Z., Kuan L. L., Atanasov G., Dawson A., Lun E., Samadov E., Namazov I., Asgarov M., Ibrahimli A., Srinivasan M., Saeed M. F., Aljawder H., Juma I., Coimbra F. J., Marques N., Casteleins W. A., Petruzziello A., Jabur G., Rodriguez J. F. P., Buso P. L., Mackenzie S., Hsiao M., Sljivic I., Tecson A., Karanicolas P. J., Roke R., Moon J., Butler E. V., Riquelme F., Yanez M., Catan F., Uribe M., Carriel F., Oppliger F., Paredes A., Daroch D., Aguayo J. C., Perez Rivera C. J., Acosta Buitrago L. M., Kadamani Abiyomaa A., Mosquera Paz M. S., Cabrera P., Corso J., Ozcay N., Ozant A., Arslan K., Besim H., Almezghwi H., Azzam A. Y., Bessa S., El-Sayes I., Badawy A., Wael M., El-Gendi A., Azab M. A., Fayed M., El Kassas M., Gamal M., Tawheed A., Al Shafie A., Emile S., Elfallal A., Elfeki H., Shalaby M., Sakr A., Elbahnasawy M., Shama M., Abdel-Elsalam W., Abd-Elsalam S., Escobar Dominguez J. E., Medrano F., Gaitan S., Escalon Gonzalez O. M., Alfaro Varela J. C., Cea M., Interiano M., Cabrera B., Lakkis Z., Georges P., Antonot C., Magnin J., Kamphues C., Lauscher J. C., Schineis C., Loch F. N., Lee L. D., Beyer K., Bouchagier K., Galanis I., Bartziotas D., Lostoridis E., Tourountzi P., Nagorni E. A., Charalabopoulos A., Baili E., Kyros E., Vagios I., Skotsimara A., Liakakos T., Alexandrou A., Papalampros A., Papadopolous V., Tooulias A., Kentarchos I., Christou C., Tsoulfas G., Tale-Rosales L. F., Lopez Muralles I., Melendez H., Bran G., Monroy Mahecha F. A., Contreras J. R., Porras D. E., Paiz E., Soto E. R., Ixcayau Hernandez J. R., Gupta A., Rajput D., Kumar N., Mani R., Kant R., Sonkar A. A., Anand A., Agrawal M. K., Gaurav K., Tripathi M., Sikora S., Bharathy K., Kumar Rangapa M., Khuller D. S., Bhojwwani R., Ayyar S., Jain N., Mehraj A., Hussain F., Nazir I., Shah M., Chowdri N. A., Hilmi A., Argenio G., Atelli P., Palladino E., Armellino M. F., Tamini N., Nespoli L. C., Degrate L., Angrisani M., Carissimi F., Bordoni P., Fleres F., Clarizia G., Spolini A., Franzini M., Cucinotta E., Badessi G., Mazzeo C., Viscosi F., Pintabona G., Campagnaro T., Poletto E., Turri G., Ruzzenente A., Conci S., Guglielmi A., Feo C., Fabbri N., Fazzin M., Giaccari S., Feo C. V., Massani M., Pelizzo P., Colella M., Tutino R., Cappellacci F., Medas F., Canu G. L., Erdas E., Calo P. G., Porcu A., Perra T., Scanu A. M., Feo C. F., Fancellu A., Germani P., Giunta C., Biloslavo A., Abdallah H., Aizza G., Barberis A., Belli F., Santoliquido M., Filauro M., Canonico G., Nelli T., Di Martino C., Capezzuoli L., Anastasi A., Bressan L., Cortinovis S., Nagliati C., Colombo F., Ferrario L., Bondurri A., Guerci C., Maffioli A., Catena F., Perrone G., Giuffrida M., Morini A., Annicchiarico A., Gallo G., Carpino A., Ferrari F., De Paola G., Sammarco G., Callari C., Licari L., Sorce V., Di Miceli D., Lovisetto F., Zonta S., Chessa A., Fiorini A., De Manzoni Garberini A., Angelini E., Moggia E., Murgese A., Mungo S., Birolo S. L., Garino M., Pipitone Federico N. S., Muratore A., Lunghi E. G., Calabro M., Cianci P., Enrico R., Capuzzolo S., Cafagna L., Minafra M., Sasia D., Gattolin A., Migliore M., Rimonda R., Travaglio E., De Marco G., Elter C., Bargellini T., D'Amico S., Zambonin D., Caponi A., Calini G., Puggioni A., Bresadola V., Zalla T., Cantafio S., Feroci F., Romoli L., Giudicissi R., Picciariello A., Papagni V., Dibra R., Altomare D. F., Pinotti E., Montuori M., Baronio G., Tonini V., Sartarelli L., Gori A., Cervellera M., Lapolla P., Sapienza P., Brachini G., Cirillo B., Zambon M., Mingoli A., Pascariello A., Boccia L., Benedetti S., Mantovani G., De Angelis M., Ferrara F., Testa V., Borghi F., Maione F., Pruiti Ciarello V., Giraudo G., Agresta F., Cestaro G., Prando D., Cavallo F., Zese M., Cillara N., Sechi R., Cardia R., Cannavera A., Putzu G., Frongia F., Pisanu A., Delogu D., Esposito G., Podda M., Iossa A., De Angelis F., Boru C., Silecchia G., Palini G. M., Garulli G., Veneroni S., Tammaro P., Maida P., Leake P. A., Wanliss M. G., Sato K., Chiyonobu N., Imamura H., Yamazaki S., Watanabe M., Qasem A., Ayasra F., Al Dahabrh S., Khaled A., Alsaafin S., Al-Thunaibat A., Olaywah D., Alqudah S., Alqawasmi S., Khamees A., Guboug A., Es Salim M., Althwabteh T., Bani Khaled H., El-Hammuri N., Aljesrawi A., Alamaadany F., Eljareh M., Al Gasi A. E. J., Alsaeiti S., Alkhafeefi A. S., Suliaman T., Alanasri A. H. A., Haroun A. B. A., Haron A., Kilani A. I., Ahmed M., Alawami M., Alawami A., Albashri M., Abusannuga M., Malek A., Jwaili N., Aldenfria A., Elzwawi F., Almugaddami A., Egdeer A. S. A., Masoud M., Alazzabi B., Alezabi B., Shuwayyah A., Alkamkhe A. A. S., Aboulqasim I., Atiyah H., Alfagi R. A. A., Abdulmula A., Bouhuwaish A., Samer A., Salim R., Aboazamazem H., Almiqlash B., Biala M., Alganimi W., Ghamgh R., Ben Omar N., Alsoufi A., Aldreawi M., Saleim N., Sowan F., Saleem H., Ahmed A., Samalavicius N. 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D., Garcia Ruiz S., Lopez Deogracias M., Turrado-Rodriguez V., Morales X., Hessheimer A., Termes Serra R., Beltran De Heredia J., Trujillo-Diaz J., Herreros-Rodriguez J., Montes-Manrique M., De Andres-Asenjo B., Beltran-Heredia J., Gimenez Maurel T., Utrilla Fornals A., Martin Anoro L. F., Cortese S., Perez Diaz M. D., Ballon M., Morote M., Cebolla Rojas L., Oliver Guillen J. R., Lopez De Fernandez A., Del Campo Lavilla M., Mora-Guzman I., Escartin A., Pinillos A., Vela Polanco F. F., Jara Quezada J. H., Muriel Alvarez P., Tur-Martinez J., Camps J., Herrero E., Garcia-Domingo M. I., Cugat Andorra E., Crespi Mir A., Claramonte Bellmunt O., Vicens Arbona J. C., Fernandez Burgos I. R., Sarriugarte Lasarte A., Marin H., Tellaeche De La Iglesia M., Ocerin Alganza O., Salinas Gomez J., Ramos-Martin P., Urbieta A., Nasimi Sabbagh R., Castell Gomez J. T., Serrablo A., Paterna -Lopez S., GutiCrossed D SignCopyrightrrez-Diez M., Abadia-Forcen M. T., Serradilla-Martin M., Duran Munoz-Cruzado V. M., Pareja Ciuro F., Perea Del Pozo E., Aparicio Sanchez D., Dios-Barbeito S., Marenco De La Cuadra B., Retamar Gentil M., Reguera-Rosal J., Infantes Ormad M., Lopez-Ruiz J. A., Landaluce-Olavarria A., Zevallos-Quiroz J. C., Barrutia Leonardo J., Emaldi A., Begona E., Balciscueta Coltell I., Sebastian M., Martinez Ramos S., Martinez Alcaide S., Lorenzo Perez J., Martinez Insfran L. A., Lopez-Morales P., Gimenez Frances C., Rahy-Martin A., Pelloni M., Ortiz-Lopez D., Benet-Munoz O., Pinero-Gonzalez L., Alconchel F., Nicolas-Lopez T., Rodrigues K., Cascales Campos P. A., Gomez-Bosch F., Ramirez Romero P., Ibrahim M., Hamid H. K. S., Idres R., Idris M., Mohammed O., Ayran S., Sinan A. H., Ozben V., Aytac E., Aliyeva Z., Mutlu A. U., Bilgin I. A., Karahasanoglu T., Hamzaoglu I., Bozkirli B., Uprak T. K., Kotan T., Coskun M., Kara Y., Somuncu E., Kocatas A., Bozkurt M. A., Demirli Atici S., Kaya T., Sert I., Emiroglu M., Jaffar M., Younis M. U., Aziz T., Ikram F., Sandal M., Al Madhloum Al Suwaidi F., Alshaikh M. O., Saber A., Khammas A., Nessa A., Jardine R., Nicol L., Clark C., McGee A., Alkari B., Feretis M., Antakia R., Georgiades F., Moneim J., O'Neill R., Balakrishnan A., Lunevicius R., Sud A., Moutsos I., Gomez D., Shahid S., Majeed T., Ibrahim W. K. G., Kadum K., Melia R., Magee C., Chicken D. W., Kumar S., Alshibshoubi M., Van Laarhoven S., Dewi F., Williams J., Byrne B., Wilkerson P., Tang C. B., Farhangmehr N., Jonas A., Charavanamuttu V., Almeida K., Efthimiou E., Boardley J., White A., Butt M. A., Menzies D., Gundkalli Z., Hassanzadeh-Baboli D., Jones O., Mistry P., Saha S., Gerrard A., Evans J., Rajeev S., Ali W., Ross E., Gilliam A., Hitchins C., Emslie K., Spellar K., Sked H., Briggs C., Brown L., A Hemadasa N., Apollos J. R., Belgaumkar A., Tawfik A., Brewin L., Oyewole B., Wadhawan H., Massie E., Rutherford D., McGivern K., McElroy L., De'Ath H. D., Tobbal M., Nagendram S., Patel P., Handa S., Houghton G., Sundaralingam S. S., Parker J., Morgan R., Gala T., Ibrahim S., Harby R., Abdelkarim M., Holroyd D., Thomas R., McLennan E., Boardley R., Jamieson N. B., Ebied H., Gossage J., Davies A., Wheatstone S., Jawad Z., Jiao L., Rajagopal P., Sodergren M., Lami M., Wiberg A., Bond-Smith G., Gemmill E., Lenzi E., Sapre D., Herrod P., Boyd-Carson H., Garcea G., Issa E., Jackson A., Fashina T., Pan H., Farquharson B., Shafiq H., Emanuel O., Mahdi S., Jeyarajah S., Finch L., Whiting G., Pigott L., Martin J., Siriwardena A. K., Beatson K., Abawi L., Lam W., Rea W., Andrews B., Al-Sarireh B., Soliman F., Burridge J., Jenvey C., Hammoda M., Hollyman M., Merker L., Richards J., Sukumaran V., Rogers S., Payne C., Bibi S., Raza K., Ul Ain N., Dronamraju S., Patil S., Nachimuthu S., Ravindran S., Patel S., Ivanov B., Patel M., Ejtehadi F., Jebamani J., Akhter Rahman M. M., Woodun H., De Prendergast A., Afzal A., Bota E., Abdul S. R., Karmarkar R., Crockett E., Evans L., Appleton B., Griffiths E., Dada O., Kulkarni R., Albirnawi H., Gravestock P., Vincenti C., Taribagil S., Dent B., Tse C., Clayton B., Burdekin E., Bannister L., Alam I., Gray J., Mactier M., Pollock A., Gough V., Kanchustambam S. R., Ridgway M., Arujunan K., Gopalswamy S., Monteiro De Barros J., Lyons T., Griffith D., Awan A. K., Latif J., Bandlamudi N., Bhatti I., Raptis D. A., Machairas N., Pissanou T., Mestre-Costa J., Hidalgo Salinas C., Pollok J. M., Al-Ardah M., Watson-Jones E., Rontree-Carey T., Boyce T., Hawkin P., Elmaradny A., Ross K., Adu-Peprah E., Pinto K., Dunne D., McCready R., Nita G., Szatmary P., Tay V. L., Rajput K., Rajendran I., Chaudhury M., Zambas G., Swaminathan C., Atif Q. A. A., Barrow T., Williams O., Malik A., Conroy S., Lindley S., Gilmore K., Boden E., Richards S. K., Hraishawi I., Polak P., McLaughlin D., Deeny D., Shuttleworth R., Harris A., Peilober-Richardson A., Morris G. C., Sara X., Almourad H., Ang Y., Smyth R., Ding D., Foster J., Bond A., Kumar Y., Ahmad A., Radoi D., Alkaili-Alyamani A., Balakrishnan S., Satchidanand R. Y., Danwaththa Liyanage A. S., Blake I., Ransome M., Weerasinghe C., Kenington C., Mayo K., Mohammed M., Cockbain A. J., Peckham-Cooper A., McCauley G., Gordon C., Smith A., Hawkins W., Chakravartty S., Baillie C., Kenny R., Kumar A., Koimtzis G., Bellamy E., Menon A., Kanakala A., Nevins E. J., Madhavan A., Thulasiraman S., France K., O'Connor A., Idama D., Raslan C., Sridhar S., Parveen M., Mubashar T., Jarvis S., Cakmak I., Wright C., Andrews S., Abdelsaid K Abdul Aal Y., Jayasankar B., Morilla J., Shehata M., Subba N., Tewari N., El-Sayed C., Somaie D., Beheiry N., Douka E., Arumugam S., Wijetunga I., Leivers E., Ibrahim B., Khan K., Wheat J., Christopher J., Barnett R., Elberm H., Booker J., Ashai S., Berry D., Luhmann A., Sgro A., Rashid M. M., Galea M., Jeyakumar J., Marriott P., Zafar S., Baker A., Yershov D., Galanopoulos G., Jordan R., Peinado Garcia C., Anyaugo N., Bath M. F., Omatseye J., Roberts L., Argyriou E. O., Machesney M., Parmar C., Clark S., Khalil H., Unsworth S., Mlotshwa M., Ayoub N., Aboelkhair A., Iosif E., Mohamed N., Reynolds E., Mackender E., Robinson D., Mufti W., Fischkoff K., Coleman N., Anantha Sathyanarayana S., Deutsch G., Giangola M., Lin D., Weiss M., Chung C., Nguyen A., Mueller J., Dabit M., Gordon J., McGuire E., Rashid O., Georgi E., Gallo M., Kunstman J. W., Peters N. V., O'Connor R., Bhattacharya B., Onkendi E., Santos A. P., Richmond R., Warren M., Zhang K., Broderick R., Clary B., Horgan S., Doucet J., Liepert A., Harmon L., McCall C., Sham J. G., Williams E., Labadie K. P., Clark N. M., Dickerson L. K., Hammill C. W., Williams G., Kushner B., Cos H., Zarate Rodriguez J., Bailey K., Al-Raimi I. M. 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V. M., Kouli O., Ahmed W. U., Varley R., Ahari D., Argus L., McLean K. A., Kamarajah S. K., Coe P., Griffiths E. A., Chan A. K. C., Macutkiewicz C., Jamdar S., Wilson M., Fullwood C., Toogood G., McLean K., Ahmed W., Gilchrist A., Goldsworthy M., Rashid M., Pockney P., Varela J., Brindl N., Ramirez J., Marafante C., Iwao Y., Ghzawi A., Elhadi M., Gacaferi H., Varghese C., Adeyeye A., Alser O., Teh C., Prieto M., Hasan A., Al-Naggar H., Salgado R., Veracierto F., Lancelotti T., Solinas D., Oddi R., Garcia F. W., Mazza Diez E., Andrade Ramirez M. R., Bracco R., Fernandez D., Maraschio M. A., Obeide L., Giordano E., Alcaraz A., Marani M. A., Aguirre N., Luna F., Francesconi M., Chiham F., Ramos Cossio R., Alvarez F. A., Pantoja Pachajoa D. A., Mandojana F., Merlo I. G., Gonzalez M. H., Cervelo G., Puma R., Vardaro G. F., Davis A., Jurat D., Guenoff C., Raubenheimer K., Goddard K., Brown K., Wegrecki K. J., Cheung H. Y. C., Yang M., Cheung H., Siddiqui J., Ahn J. H., Huynh R., Lam Y. H., Afzal M., Ong B. S., Chua M. Y. M., Ly K., Thomson J. E., Watson D., Dawson A. C., Drane A., Van Ruyven S., Lun E. W. Y., Ferguson M., Jeong J. Y., De Silva C., Wills V., Gundara J., McCourt E., Bong C., Tabone R., Wong W. J., Gray A., Koh D., Pollock M., Singhal S., Smith R., Dudi-Venkata N. N., Kanhere H., Stranz C., Seow W., Mansour L. T., Wormald J., Loveday B. P. T., Thomson B., O'Donnell T., Milenkovski N., Herath M., Trochsler M., Farfus A., Maddern G., Bunjo Z., Kuan L. L., Atanasov G., Dawson A., Lun E., Samadov E., Namazov I., Asgarov M., Ibrahimli A., Srinivasan M., Saeed M. F., Aljawder H., Juma I., Coimbra F. J., Marques N., Casteleins W. A., Petruzziello A., Jabur G., Rodriguez J. F. P., Buso P. L., Mackenzie S., Hsiao M., Sljivic I., Tecson A., Karanicolas P. J., Roke R., Moon J., Butler E. V., Riquelme F., Yanez M., Catan F., Uribe M., Carriel F., Oppliger F., Paredes A., Daroch D., Aguayo J. C., Perez Rivera C. J., Acosta Buitrago L. M., Kadamani Abiyomaa A., Mosquera Paz M. S., Cabrera P., Corso J., Ozcay N., Ozant A., Arslan K., Besim H., Almezghwi H., Azzam A. Y., Bessa S., El-Sayes I., Badawy A., Wael M., El-Gendi A., Azab M. A., Fayed M., El Kassas M., Gamal M., Tawheed A., Al Shafie A., Emile S., Elfallal A., Elfeki H., Shalaby M., Sakr A., Elbahnasawy M., Shama M., Abdel-Elsalam W., Abd-Elsalam S., Escobar Dominguez J. E., Medrano F., Gaitan S., Escalon Gonzalez O. M., Alfaro Varela J. C., Cea M., Interiano M., Cabrera B., Lakkis Z., Georges P., Antonot C., Magnin J., Kamphues C., Lauscher J. C., Schineis C., Loch F. N., Lee L. D., Beyer K., Bouchagier K., Galanis I., Bartziotas D., Lostoridis E., Tourountzi P., Nagorni E. A., Charalabopoulos A., Baili E., Kyros E., Vagios I., Skotsimara A., Liakakos T., Alexandrou A., Papalampros A., Papadopolous V., Tooulias A., Kentarchos I., Christou C., Tsoulfas G., Tale-Rosales L. F., Lopez Muralles I., Melendez H., Bran G., Monroy Mahecha F. A., Contreras J. 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F., Fancellu A., Germani P., Giunta C., Biloslavo A., Abdallah H., Aizza G., Barberis A., Belli F., Santoliquido M., Filauro M., Canonico G., Nelli T., Di Martino C., Capezzuoli L., Anastasi A., Bressan L., Cortinovis S., Nagliati C., Colombo F., Ferrario L., Bondurri A., Guerci C., Maffioli A., Catena F., Perrone G., Giuffrida M., Morini A., Annicchiarico A., Gallo G., Carpino A., Ferrari F., De Paola G., Sammarco G., Callari C., Licari L., Sorce V., Di Miceli D., Lovisetto F., Zonta S., Chessa A., Fiorini A., De Manzoni Garberini A., Angelini E., Moggia E., Murgese A., Mungo S., Birolo S. L., Garino M., Pipitone Federico N. S., Muratore A., Lunghi E. 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E., Aliosin O., Dailidenas S., Dulskas A., Buckus B., Kuliesius Z., Bradunaite R., Dominguez-Rosado I., Buerba G. A., Posadas-Trujillo O. E., Alfaro-Goldaracena A., Cortes R., Mercado M. A., Beristain-Hernandez J. L., Mora-Munoz V. S., Mena-Bedolla J. M., Palacios Ramirez A. R., Astorga Medina M. M., Van Aert G., Ombashi S., Spillenaar Bilgen R., Vos D., Besselink M., Alberts V., Busch O., Bemelman W., Boermeester M., Daams F., Gordinou De Gouberville M., Van Duijvendijk P., De Graaff M., Baaij J., Gans S., Bos K., Goudsmit B., Den Dekker B., Braat A., Kuijpers A., Breukers S., Borel Rinkes I., Andel D., Hayes T., Carson D., Bhat S., Van Der Have J., Anderson C., Bissett I., Windsor J., Elliott B. M., Scowcroft H., McLauchlan J., Ritchie D., Jeffery F., Connor S., Xu W., Mashlan H., Thirayan V., Ly J., McGuinness M. J., Ferguson L., Watt I., Harmston C., Akinmade A., Enoch E., Kayode-Nissi V., Ogundele I., Ayoade B. A., Adekoya A., Nwokoro C., Opadeyi A., Yusuf A., Ojajuni A., Adepoju O., Muhammad Dauda M., Keffi Mubarak M., Lawal K., Muhammad D., Salonga D., Sael N. A., Rey C. M., Pestano M., Tan D., Bangayan N. R., Sy D. K., Ang D., Bernardo E., Chua J. P., Alharthi M., Bukhari W., Bakier Mohammed K., Al Athath S., Ghunaim M., Saiedi H., Sultan N., Farsi A., Basendowah M., Malibary N., Jaloun H., Altalhi D., Organjee A., Moamena M., Al Zaidi T. M., Alyami M., Alqannas M., Al-Urfan M., Elawad A., Alawadhi A., Alalawi Y., Alqarni A., Alqahtani B., Alayed A., Alsobaie K., Adi H., Elhaj M., Dehlawi A., Behairy G., Khaled I., Kmezic S., Radenkovic D., Aleksic L., Markovic V., Pejovic I., Antic A., Kalkan M., Vujanovic Gadjanski O., Dusan S., Marcetic B., Thiruchelvam N., Chiow A. K. H., Lee L. S., Mun D. Y. C., Tan E. K., Koh Y. X., Loh W. L., Wang Z., Chan C. Y., Kloppers C., Almgla N., Bernon M., Kahn M., Karimbocus N., Roldan Villavicencio J. I., Goitia V., Gutierrez Rios R. D., Garcia Ruiz S., Lopez Deogracias M., Turrado-Rodriguez V., Morales X., Hessheimer A., Termes Serra R., Beltran De Heredia J., Trujillo-Diaz J., Herreros-Rodriguez J., Montes-Manrique M., De Andres-Asenjo B., Beltran-Heredia J., Gimenez Maurel T., Utrilla Fornals A., Martin Anoro L. F., Cortese S., Perez Diaz M. D., Ballon M., Morote M., Cebolla Rojas L., Oliver Guillen J. R., Lopez De Fernandez A., Del Campo Lavilla M., Mora-Guzman I., Escartin A., Pinillos A., Vela Polanco F. F., Jara Quezada J. H., Muriel Alvarez P., Tur-Martinez J., Camps J., Herrero E., Garcia-Domingo M. I., Cugat Andorra E., Crespi Mir A., Claramonte Bellmunt O., Vicens Arbona J. C., Fernandez Burgos I. R., Sarriugarte Lasarte A., Marin H., Tellaeche De La Iglesia M., Ocerin Alganza O., Salinas Gomez J., Ramos-Martin P., Urbieta A., Nasimi Sabbagh R., Castell Gomez J. T., Serrablo A., Paterna -Lopez S., GutiCrossed D SignCopyrightrrez-Diez M., Abadia-Forcen M. T., Serradilla-Martin M., Duran Munoz-Cruzado V. M., Pareja Ciuro F., Perea Del Pozo E., Aparicio Sanchez D., Dios-Barbeito S., Marenco De La Cuadra B., Retamar Gentil M., Reguera-Rosal J., Infantes Ormad M., Lopez-Ruiz J. A., Landaluce-Olavarria A., Zevallos-Quiroz J. C., Barrutia Leonardo J., Emaldi A., Begona E., Balciscueta Coltell I., Sebastian M., Martinez Ramos S., Martinez Alcaide S., Lorenzo Perez J., Martinez Insfran L. A., Lopez-Morales P., Gimenez Frances C., Rahy-Martin A., Pelloni M., Ortiz-Lopez D., Benet-Munoz O., Pinero-Gonzalez L., Alconchel F., Nicolas-Lopez T., Rodrigues K., Cascales Campos P. A., Gomez-Bosch F., Ramirez Romero P., Ibrahim M., Hamid H. K. S., Idres R., Idris M., Mohammed O., Ayran S., Sinan A. H., Ozben V., Aytac E., Aliyeva Z., Mutlu A. U., Bilgin I. A., Karahasanoglu T., Hamzaoglu I., Bozkirli B., Uprak T. K., Kotan T., Coskun M., Kara Y., Somuncu E., Kocatas A., Bozkurt M. A., Demirli Atici S., Kaya T., Sert I., Emiroglu M., Jaffar M., Younis M. U., Aziz T., Ikram F., Sandal M., Al Madhloum Al Suwaidi F., Alshaikh M. O., Saber A., Khammas A., Nessa A., Jardine R., Nicol L., Clark C., McGee A., Alkari B., Feretis M., Antakia R., Georgiades F., Moneim J., O'Neill R., Balakrishnan A., Lunevicius R., Sud A., Moutsos I., Gomez D., Shahid S., Majeed T., Ibrahim W. K. G., Kadum K., Melia R., Magee C., Chicken D. W., Kumar S., Alshibshoubi M., Van Laarhoven S., Dewi F., Williams J., Byrne B., Wilkerson P., Tang C. B., Farhangmehr N., Jonas A., Charavanamuttu V., Almeida K., Efthimiou E., Boardley J., White A., Butt M. A., Menzies D., Gundkalli Z., Hassanzadeh-Baboli D., Jones O., Mistry P., Saha S., Gerrard A., Evans J., Rajeev S., Ali W., Ross E., Gilliam A., Hitchins C., Emslie K., Spellar K., Sked H., Briggs C., Brown L., A Hemadasa N., Apollos J. R., Belgaumkar A., Tawfik A., Brewin L., Oyewole B., Wadhawan H., Massie E., Rutherford D., McGivern K., McElroy L., De'Ath H. D., Tobbal M., Nagendram S., Patel P., Handa S., Houghton G., Sundaralingam S. S., Parker J., Morgan R., Gala T., Ibrahim S., Harby R., Abdelkarim M., Holroyd D., Thomas R., McLennan E., Boardley R., Jamieson N. B., Ebied H., Gossage J., Davies A., Wheatstone S., Jawad Z., Jiao L., Rajagopal P., Sodergren M., Lami M., Wiberg A., Bond-Smith G., Gemmill E., Lenzi E., Sapre D., Herrod P., Boyd-Carson H., Garcea G., Issa E., Jackson A., Fashina T., Pan H., Farquharson B., Shafiq H., Emanuel O., Mahdi S., Jeyarajah S., Finch L., Whiting G., Pigott L., Martin J., Siriwardena A. K., Beatson K., Abawi L., Lam W., Rea W., Andrews B., Al-Sarireh B., Soliman F., Burridge J., Jenvey C., Hammoda M., Hollyman M., Merker L., Richards J., Sukumaran V., Rogers S., Payne C., Bibi S., Raza K., Ul Ain N., Dronamraju S., Patil S., Nachimuthu S., Ravindran S., Patel S., Ivanov B., Patel M., Ejtehadi F., Jebamani J., Akhter Rahman M. M., Woodun H., De Prendergast A., Afzal A., Bota E., Abdul S. R., Karmarkar R., Crockett E., Evans L., Appleton B., Griffiths E., Dada O., Kulkarni R., Albirnawi H., Gravestock P., Vincenti C., Taribagil S., Dent B., Tse C., Clayton B., Burdekin E., Bannister L., Alam I., Gray J., Mactier M., Pollock A., Gough V., Kanchustambam S. R., Ridgway M., Arujunan K., Gopalswamy S., Monteiro De Barros J., Lyons T., Griffith D., Awan A. K., Latif J., Bandlamudi N., Bhatti I., Raptis D. A., Machairas N., Pissanou T., Mestre-Costa J., Hidalgo Salinas C., Pollok J. M., Al-Ardah M., Watson-Jones E., Rontree-Carey T., Boyce T., Hawkin P., Elmaradny A., Ross K., Adu-Peprah E., Pinto K., Dunne D., McCready R., Nita G., Szatmary P., Tay V. L., Rajput K., Rajendran I., Chaudhury M., Zambas G., Swaminathan C., Atif Q. A. A., Barrow T., Williams O., Malik A., Conroy S., Lindley S., Gilmore K., Boden E., Richards S. K., Hraishawi I., Polak P., McLaughlin D., Deeny D., Shuttleworth R., Harris A., Peilober-Richardson A., Morris G. C., Sara X., Almourad H., Ang Y., Smyth R., Ding D., Foster J., Bond A., Kumar Y., Ahmad A., Radoi D., Alkaili-Alyamani A., Balakrishnan S., Satchidanand R. Y., Danwaththa Liyanage A. S., Blake I., Ransome M., Weerasinghe C., Kenington C., Mayo K., Mohammed M., Cockbain A. J., Peckham-Cooper A., McCauley G., Gordon C., Smith A., Hawkins W., Chakravartty S., Baillie C., Kenny R., Kumar A., Koimtzis G., Bellamy E., Menon A., Kanakala A., Nevins E. J., Madhavan A., Thulasiraman S., France K., O'Connor A., Idama D., Raslan C., Sridhar S., Parveen M., Mubashar T., Jarvis S., Cakmak I., Wright C., Andrews S., Abdelsaid K Abdul Aal Y., Jayasankar B., Morilla J., Shehata M., Subba N., Tewari N., El-Sayed C., Somaie D., Beheiry N., Douka E., Arumugam S., Wijetunga I., Leivers E., Ibrahim B., Khan K., Wheat J., Christopher J., Barnett R., Elberm H., Booker J., Ashai S., Berry D., Luhmann A., Sgro A., Rashid M. M., Galea M., Jeyakumar J., Marriott P., Zafar S., Baker A., Yershov D., Galanopoulos G., Jordan R., Peinado Garcia C., Anyaugo N., Bath M. F., Omatseye J., Roberts L., Argyriou E. O., Machesney M., Parmar C., Clark S., Khalil H., Unsworth S., Mlotshwa M., Ayoub N., Aboelkhair A., Iosif E., Mohamed N., Reynolds E., Mackender E., Robinson D., Mufti W., Fischkoff K., Coleman N., Anantha Sathyanarayana S., Deutsch G., Giangola M., Lin D., Weiss M., Chung C., Nguyen A., Mueller J., Dabit M., Gordon J., McGuire E., Rashid O., Georgi E., Gallo M., Kunstman J. W., Peters N. V., O'Connor R., Bhattacharya B., Onkendi E., Santos A. P., Richmond R., Warren M., Zhang K., Broderick R., Clary B., Horgan S., Doucet J., Liepert A., Harmon L., McCall C., Sham J. G., Williams E., Labadie K. P., Clark N. M., Dickerson L. K., Hammill C. W., Williams G., Kushner B., Cos H., Zarate Rodriguez J., Bailey K., Al-Raimi I. M. N., Al-Zazay K., Ahmed Mohammed Al-Mahdi S., Mohammed Aldowbli S., Al-Shehari M., Shream S., Al-Ameri S., Aeed M., Aldawbali M., Alsayadi R., and Alsayadi M.
Abstract: https://www.scopus.com/record/display.uri?eid=2-s2.0-85138595712&origin=inward&txGid=728c82ff11b9726b5d443216a91e7ffa#:~:text=Background: This study,of this pandemic.
Published: 2022

6. Identification and characterisation of genes from the Angelman and Prader-Willi syndrome region of chromosome 15q11-13

Author: Hitchins, Megan P.
Subjects: 618.92
Abstract: Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are clinically distinct neurobehavioural disorders which map to 15ql 1.2-12. AS is characterised by mental retardation, seizures, ataxia, absent speech, excessive laughter, and distinctive EEG. PWS involves poor suck reflex and hypotonia in infancy, short stature, microgenitalia, and hyperphagia leading to obesity. Chromosome 15ql 1.2-12 is subject to genomic imprinting whereby certain genes are functionally active or silent depending on their parental origin of inheritance. AS and PWS are caused by various mechanisms including cytogenetic deletion, uniparental disomy and altered epigenetic modification, with the common factor being lack of a maternal contribution to 15ql 1.2-12 in AS, and loss of expression of genes on the paternally derived allele in PWS. Approximately 25% of AS patients, including familial cases, are due to mutations of an imprinted gene within 15ql 1.2-12, which is expressed from the maternal allele. The UBE3A gene has been implicated in AS. The lack of a similar category of patients in PWS suggests that this is a contiguous gene disorder. In order to identify genes which may be involved in the pathogenesis of either AS or PWS, positional cloning studies were performed in the AS and distal portion of the PWS candidate regions. UBE3A was located to the AS region, and a novel expressed sequence identified through direct cDNA selection was shown to represent an extended 3' untranslated region of UBE3A. No additional genes were identified in the AS region. USES A was screened for mutations in cases of familial and sporadic AS in which the genetic aetiology of the disease remained unidentified. Pathogenic mutations were identified in 3/5 familial and 4/21 sporadic cases, indicating that UBE3A mutations cause AS in a proportion of patients. Two novel transcripts, '395-H22' and '123-E19', were identified from the PWS region. 395- H22 was found to be expressed solely from the paternal allele in an in vitro imprinting assay system, indicating that it may represent an additional gene involved in the PWS phenotype.
Published: 1999

7. POLE-Mutant Colon Cancer Treated with PD-1 Blockade Showing Clearance of Circulating Tumor DNA and Prolonged Disease-Free Interval.

Author: Bikhchandani, Mihir, Bikhchandani, Mihir, Amersi, Farin, Hendifar, Andrew, Gangi, Alexandra, Osipov, Arsen, Zaghiyan, Karen, Atkins, Katelyn, Cho, May, Aguirre, Francesca, Hazelett, Dennis, Alvarez, Rocio, Zhou, Lisa, Hitchins, Megan, Gong, Jun, Bikhchandani, Mihir, Bikhchandani, Mihir, Amersi, Farin, Hendifar, Andrew, Gangi, Alexandra, Osipov, Arsen, Zaghiyan, Karen, Atkins, Katelyn, Cho, May, Aguirre, Francesca, Hazelett, Dennis, Alvarez, Rocio, Zhou, Lisa, Hitchins, Megan, and Gong, Jun
Abstract: Colon cancer with high microsatellite instability is characterized by a high tumor mutational burden and responds well to immunotherapy. Mutations in polymerase ɛ, a DNA polymerase involved in DNA replication and repair, are also associated with an ultra-mutated phenotype. We describe a case where a patient with POLE-mutated and hypermutated recurrent colon cancer was treated with pembrolizumab. Treatment with immunotherapy in this patient also led to the clearance of circulating tumor DNA (ctDNA). ctDNA is beginning to emerge as a marker for minimal residual disease in many solid malignancies, including colon cancer. Its clearance with treatment suggests that the selection of pembrolizumab on the basis of identifying a POLE mutation on next-generation sequencing may increase disease-free survival in this patient.
Published: 2023

8. Conceiving systems

Author: Hitchins, Derek K.
Subjects: 005, TA Engineering (General). Civil engineering (General)
Abstract: The thesis is concerned with the development of innovative, robust design concepts for a class of systems called Information Decision Action (IDA) Systems. IDA systems are typified by Command and Control (C2) and Command, Control, Communications and Intelligence (C3I) systems as used by police, emergency services and the military - the two titles refer respectively to the human activity and the technological systems. The class of systems is much wider, however, and includes, financial, traffic control, business and even governmental systems where information is gathered, used as a basis for human decision-forming, and results in action, all in real, or near-real time. IDA system complexity stems largely from the dominance of robust human activity systems within the overall system, and also from the employment of often-rigid, technology-based, decision support systems which are unable to adapt as swiftly as the humans they serve. The thesis is in two parts. In the first part, the author presents a perspective on "hard" and "soft" systems and the gradual move by so-called "hard" systems engineers towards softer concepts in the search for more satisfactory IDA systems. This progression is presented partly by anecdote, supported by some of the author's papers showing the development of his contribution to understanding of, and partly by an exposition of the essential themes inherent in, IDA systems. Keynote papers in the first part are: MOSAIC: Concepts for the Deployment of Air Power in Europe and The Human Element in C3 I: The first of these presents a highly-survivable alternative to the present force and C2 deployment approaches which have evolved little since World War IT; the second considers the human and his social behaviour as keys to understanding IDA systems. Other papers develop the themes and show their application to systems in which the author has had major involvement The second part is concerned with the process of conceiving and creating IDA systems and it too draws on published papers as direct support for the thesis. Keynote papers here are A General Theory of Command and Control, a unique recent paper which proposes a set of design axioms for an idealized IDA system, the award-winning Managing Systems Creation which presents an engineering framework for Creating Systems, and SEAMS (Systems Engineering, Analysis and Management Support) which signals a major design initiative to develop engineering frameworks into company-wide IT environments. The second part also introduces a complete Conceiving System, called the Seven-Step Continuum (SSC), describes some prototype tools developed by the author to perform some of the tasks of design conception and - in Chapter 9, which is a paper within the thesis - shows results from using the SSC, its methods and tools, in practice. The second part closes with a look forward to the building of flexible future systems which can adapt to their environment.
Published: 1990

9. A Concise History of Romania

Author: Hitchins, Keith
Published: 2014
Full Text: View/download PDF

10. Circulating tumor DNA dynamics and response to immunotherapy in colorectal cancer.

Author: Gong, Jun, Gong, Jun, Aguirre, Francesca, Hazelett, Dennis, Alvarez, Rocio, Zhou, Lisa, Hendifar, Andrew, Osipov, Arsen, Zaghiyan, Karen, Cho, May, Gangi, Alexandra, Hitchins, Megan, Gong, Jun, Gong, Jun, Aguirre, Francesca, Hazelett, Dennis, Alvarez, Rocio, Zhou, Lisa, Hendifar, Andrew, Osipov, Arsen, Zaghiyan, Karen, Cho, May, Gangi, Alexandra, and Hitchins, Megan
Abstract: Circulating tumor DNA (ctDNA) is increasingly being investigated as a tool to detect minimal residual disease in resected, stage I-III colorectal cancer. Recent ctDNA studies have indicated that detection of ctDNA following surgery for resectable colorectal cancer confers a significantly higher risk of recurrence than those with negative ctDNA postoperatively. In those with postoperative ctDNA positivity, clearance of minimal residual disease with adjuvant chemotherapy is a positive prognostic indicator. Lastly, ctDNA has demonstrated superior sensitivity to the conventional blood tumor marker carcinoembryonic antigen (CEA) and can offer median lead times of up to 11 months for radiographic detection of recurrence during the surveillance of resected, stage I-III colorectal cancer. In metastatic colorectal cancer (mCRC), there is growing evidence to suggest that plasma ctDNA can be used to monitor tumor response to conventional chemotherapy as well. The present case series demonstrated that plasma ctDNA is a predictor of tumor response to immunotherapy in patients with mCRC that are microsatellite stable or microsatellite instability high. Plasma ctDNA could serve as a dynamic marker of immunotherapy response even in colorectal tumors that were CEA non-producers. Overall, these findings add to ongoing efforts to establish the role of plasma ctDNA in monitoring response to immunotherapy in CRC.
Published: 2022

11. Improving outcomes for patients with lymphoma: design and development of the Australian and New Zealand Lymphoma and Related Diseases Registry

Author: Anderson, MA, Berkahn, L, Cheah, C, Dickinson, M, Gandhi, MK, Giri, P, Hawkes, EA, Johnston, A, Keane, C, McQuilten, ZK, Mulligan, SP, Opat, S, Talaulikar, D, Trotman, J, Williams, J, Wood, EM, Armytage, T, Barraclough, A, Carradice, D, Chong, G, Cochrane, T, Hamad, N, Ku, M, Lee, D, Morgan, S, Mutsando, H, Narayana, M, Prince, HM, Ratnasingam, S, Wight, J, Badoux, X, Cull, G, Kuss, B, Marlton, P, Tam, C, Casan, J, Cushion, T, Tedjaseputra, A, Birch, S, Brown, C, Ellis, D, Harvey, Y, Hitchins, S, Jain, S, Jessup, P, Juneja, S, Kearney, D, Kumar, B, Lade, S, Lee, K, Leslie, C, Long, E, Morey, A, Nath, L, Norris, D, Parker, A, Parry, J, Chen, FP-Y, Chung, E, Morison, J, Rowsell, L, St George, G, Thu, C, Waters, N, Wellard, C, Zheng, M, Anderson, MA, Berkahn, L, Cheah, C, Dickinson, M, Gandhi, MK, Giri, P, Hawkes, EA, Johnston, A, Keane, C, McQuilten, ZK, Mulligan, SP, Opat, S, Talaulikar, D, Trotman, J, Williams, J, Wood, EM, Armytage, T, Barraclough, A, Carradice, D, Chong, G, Cochrane, T, Hamad, N, Ku, M, Lee, D, Morgan, S, Mutsando, H, Narayana, M, Prince, HM, Ratnasingam, S, Wight, J, Badoux, X, Cull, G, Kuss, B, Marlton, P, Tam, C, Casan, J, Cushion, T, Tedjaseputra, A, Birch, S, Brown, C, Ellis, D, Harvey, Y, Hitchins, S, Jain, S, Jessup, P, Juneja, S, Kearney, D, Kumar, B, Lade, S, Lee, K, Leslie, C, Long, E, Morey, A, Nath, L, Norris, D, Parker, A, Parry, J, Chen, FP-Y, Chung, E, Morison, J, Rowsell, L, St George, G, Thu, C, Waters, N, Wellard, C, and Zheng, M
Abstract: BACKGROUND: Lymphoma is a malignancy of lymphocytes and lymphoid tissues comprising a heterogeneous group of diseases, with up to 80 entities now described. Lymphoma is the 6th most common cancer in Australia, affecting patients of all ages, with rising incidence rates. With the proliferation of efficacious novel agents, therapeutic strategies are increasingly diverse and survival is improving. There is a clear need for contemporary robust and detailed data on diagnostic, investigational and management strategies for this disease in Australia, New Zealand and worldwide, to inform and benchmark local and international standards of care. Clinical quality registries can provide these data, and support development of strategies to address variations in management, including serving as platforms for clinical trials and other research activities. The Lymphoma and Related Diseases Registry (LaRDR) was developed to capture details of patient demographics, disease characteristics, and management throughout their disease course and therapy and to develop outcome benchmarks nationally and internationally for lymphoma. This report describes the aims, development and implementation of the LaRDR, as well as challenges addressed in the process. METHODS: The LaRDR was established in 2016 as a multicentre, collaborative project at sites across Australia with a secure online database which collects prospective data on patients with a new diagnosis of lymphoma or chronic lymphocytic leukaemia (CLL). LaRDR development required multidisciplinary participation including specialist haematology, information technology, and biostatistical support, as well as secure funding. Here we describe the database development, data entry, ethics approval process, registry governance and support for participating sites and the coordinating centre. RESULTS: To date more than 5,300 patients have been enrolled from 28 sites in Australia and New Zealand. Multiple challenges arose during the development, wh
Published: 2022

12. Large Cancer Pedigree Involving Multiple Cancer Genes including Likely Digenic MSH2 and MSH6 Lynch Syndrome (LS) and an Instance of Recombinational Rescue from LS.

Author: Vogelaar, Ingrid P, Vogelaar, Ingrid P, Greer, Stephanie, Wang, Fan, Shin, GiWon, Lau, Billy, Hu, Yajing, Haraldsdottir, Sigurdis, Alvarez, Rocio, Hazelett, Dennis, Nguyen, Peter, Aguirre, Francesca P, Guindi, Maha, Hendifar, Andrew, Balcom, Jessica, Leininger, Anna, Fairbank, Beth, Ji, Hanlee, Hitchins, Megan P, Vogelaar, Ingrid P, Vogelaar, Ingrid P, Greer, Stephanie, Wang, Fan, Shin, GiWon, Lau, Billy, Hu, Yajing, Haraldsdottir, Sigurdis, Alvarez, Rocio, Hazelett, Dennis, Nguyen, Peter, Aguirre, Francesca P, Guindi, Maha, Hendifar, Andrew, Balcom, Jessica, Leininger, Anna, Fairbank, Beth, Ji, Hanlee, and Hitchins, Megan P
Abstract: Lynch syndrome (LS), caused by heterozygous pathogenic variants affecting one of the mismatch repair (MMR) genes (MSH2, MLH1, MSH6, PMS2), confers moderate to high risks for colorectal, endometrial, and other cancers. We describe a four-generation, 13-branched pedigree in which multiple LS branches carry the MSH2 pathogenic variant c.2006G>T (p.Gly669Val), one branch has this and an additional novel MSH6 variant c.3936_4001+8dup (intronic), and other non-LS branches carry variants within other cancer-relevant genes (NBN, MC1R, PTPRJ). Both MSH2 c.2006G>T and MSH6 c.3936_4001+8dup caused aberrant RNA splicing in carriers, including out-of-frame exon-skipping, providing functional evidence of their pathogenicity. MSH2 and MSH6 are co-located on Chr2p21, but the two variants segregated independently (mapped in trans) within the digenic branch, with carriers of either or both variants. Thus, MSH2 c.2006G>T and MSH6 c.3936_4001+8dup independently confer LS with differing cancer risks among family members in the same branch. Carriers of both variants have near 100% risk of transmitting either one to offspring. Nevertheless, a female carrier of both variants did not transmit either to one son, due to a germline recombination within the intervening region. Genetic diagnosis, risk stratification, and counseling for cancer and inheritance were highly individualized in this family. The finding of multiple cancer-associated variants in this pedigree illustrates a need to consider offering multicancer gene panel testing, as opposed to targeted cascade testing, as additional cancer variants may be uncovered in relatives.
Published: 2022

13. Methylated SEPTIN9 plasma test for colorectal cancer detection may be applicable to Lynch syndrome.

Author: Hitchins, Megan P, Hitchins, Megan P, Vogelaar, Ingrid P, Brennan, Kevin, Haraldsdottir, Sigurdis, Zhou, Nianmin, Martin, Brock, Alvarez, Rocio, Yuan, Xiaopu, Kim, Sungjin, Guindi, Maha, Hendifar, Andrew E, Kalady, Matthew F, DeVecchio, Jennifer, Church, James M, de la Chapelle, Albert, Hampel, Heather, Pearlman, Rachel, Christensen, Maria, Snyder, Carrie, Lanspa, Stephen J, Haile, Robert W, Lynch, Henry T, Hitchins, Megan P, Hitchins, Megan P, Vogelaar, Ingrid P, Brennan, Kevin, Haraldsdottir, Sigurdis, Zhou, Nianmin, Martin, Brock, Alvarez, Rocio, Yuan, Xiaopu, Kim, Sungjin, Guindi, Maha, Hendifar, Andrew E, Kalady, Matthew F, DeVecchio, Jennifer, Church, James M, de la Chapelle, Albert, Hampel, Heather, Pearlman, Rachel, Christensen, Maria, Snyder, Carrie, Lanspa, Stephen J, Haile, Robert W, and Lynch, Henry T
Abstract: ObjectiveThe plasma-based methylated SEPTIN9 (mSEPT9) is a colorectal cancer (CRC) screening test for adults aged 50-75 years who are at average risk for CRC and have refused colonoscopy or faecal-based screening tests. The applicability of mSEPT9 for high-risk persons with Lynch syndrome (LS), the most common hereditary CRC condition, has not been assessed. This study sought preliminary evidence for the utility of mSEPT9 for CRC detection in LS.DesignFirstly, SEPT9 methylation was measured in LS-associated CRC, advanced adenoma, and subject-matched normal colorectal mucosa tissues by pyrosequencing. Secondly, to detect mSEPT9 as circulating tumor DNA, the plasma-based mSEPT9 test was retrospectively evaluated in LS subjects using the Epi proColon 2.0 CE assay adapted for 1mL plasma using the "1/1 algorithm". LS case groups included 20 peri-surgical cases with acolonoscopy-based diagnosis of CRC (stages I-IV), 13 post-surgical metastatic CRC, and 17 pre-diagnosis cases. The control group comprised 31 cancer-free LS subjects.ResultsDifferential hypermethylation was found in 97.3% (36/37) of primary CRC and 90.0% (18/20) of advanced adenomas, showing LS-associated neoplasia frequently produce the mSEPT9 biomarker. Sensitivity of plasma mSEPT9 to detect CRC was 70.0% (95% CI, 48%-88%)in cases with a colonoscopy-based CRC diagnosis and 92.3% (95% CI, 64%-100%) inpost-surgical metastatic cases. In pre-diagnosis cases, plasma mSEPT9 was detected within two months prior to colonoscopy-based CRC diagnosis in 3/5 cases. Specificity in controls was 100% (95% CI 89%-100%).ConclusionThese preliminary findings suggest mSEPT9 may demonstrate similar diagnostic performance characteristics in LS as in the average-risk population, warranting a well-powered prospective case-control study.
Published: 2019

14. Clinical Applications of Minimal Residual Disease Assessments by Tumor-Informed and Tumor-Uninformed Circulating Tumor DNA in Colorectal Cancer.

Author: Gong, Jun, Gong, Jun, Hendifar, Andrew, Gangi, Alexandra, Zaghiyan, Karen, Atkins, Katelyn, Nasseri, Yosef, Murrell, Zuri, Figueiredo, Jane C, Salvy, Sarah, Haile, Robert, Hitchins, Megan, Gong, Jun, Gong, Jun, Hendifar, Andrew, Gangi, Alexandra, Zaghiyan, Karen, Atkins, Katelyn, Nasseri, Yosef, Murrell, Zuri, Figueiredo, Jane C, Salvy, Sarah, Haile, Robert, and Hitchins, Megan
Abstract: Emerging data suggest that circulating tumor DNA (ctDNA) can detect colorectal cancer (CRC)-specific signals across both non-metastatic and metastatic settings. With the development of multiple platforms, including tumor-informed and tumor-agnostic ctDNA assays and demonstration of their provocative analytic performance to detect minimal residual disease, there are now ongoing, phase III randomized clinical trials to evaluate their role in the management paradigm of CRC. In this review, we highlight landmark studies that have formed the basis for ongoing studies on the clinically applicability of plasma ctDNA assays in resected, stage I-III CRC and metastatic CRC. We discuss clinical settings by which ctDNA may have the most immediate impact in routine clinical practice. These include the potential for ctDNA to (1) guide surveillance and intensification or de-intensification strategies of adjuvant therapy in resected, stage I-III CRC, (2) predict treatment response to neoadjuvant therapy in locally advanced rectal cancer inclusive of total neoadjuvant therapy (TNT), and (3) predict response to systemic and surgical therapies in metastatic disease. We end by considering clinical variables that can influence our ability to reliably interpret ctDNA dynamics in the clinic.
Published: 2021

15. Air Board, Canadian Air Force and Royal Canadian Air Force

Author: F. H. Hitchins and F. H. Hitchins
Published: 2020

16. Pancreatic cancer 'mismatch' in Lynch syndrome.

Author: Hendifar, Andrew E, Hendifar, Andrew E, Larson, Brent K, Rojansky, Rebecca, Guan, Michelle, Gong, Jun, Placencio, Veronica, Tuli, Richard, Hitchins, Megan, Hendifar, Andrew E, Hendifar, Andrew E, Larson, Brent K, Rojansky, Rebecca, Guan, Michelle, Gong, Jun, Placencio, Veronica, Tuli, Richard, and Hitchins, Megan
Abstract: ObjectiveImmune therapy with the PD1 inhibitor pembrolizumab has been approved to treat unresectable/metastatic solid tumours exhibiting mismatch repair (MMR) deficiency. Lynch syndrome (LS), caused by autosomal dominant germline mutations of a MMR gene, predisposes to the development of MMR-deficient cancers. We report a case of MSH2-LS with an MMR-intact pancreatic ductal adenocarcinoma (PDAC) ineligible for treatment with pembrolizumab.DesignImmunohistochemistry of MMR proteins was performed in each malignancy developed in a MSH2-LS patient to determine MMR status.ResultsThe patient carried a pathogenic MSH2 germline mutation and had a history of LS-type cancers, including endometrial carcinoma, colorectal adenocarcinoma, urothelial carcinoma of the bladder and PDAC. Three malignancies (endometrial, colorectal, urothelial) lacked MSH2 and MSH6 expression, consistent with MSH2-associated tumorigenesis. However, MSH2 and MSH6 expression were intact in the PDAC, suggesting the sporadic occurrence of the pancreatic tumour unrelated to the germline MSH2 mutation. These inconsistent MMR statuses among the tumours rendered the patient ineligible for the immunotherapy pembrolizumab.ConclusionTesting for MMR protein expression is recommended for each tumour in patients with LS, especially pancreatic, as discordant results may have profound effects on treatment opportunities. To our knowledge, this is the first documented case of MMR-intact PDAC in a patient with MSH2-LS.
Published: 2019

17. The technology of CO2 sequestration by mineral carbonation: current status and future prospects

Author: Wang F., Dreisinger D. B., Hitchins T., Jarvis M., Wang F., Dreisinger D. B., Hitchins T., and Jarvis M.
Abstract: A review is presented of developments in, current status of, and future prospects for, gas-aqueous-solid Mg- and Ca-silicate mineral-carbonation (MC) processes - which are naturally exothermic - for converting carbon dioxide gas into stable Mg and Ca carbonates with silica as by-product. In-situ MC by basalts and peridotite is described including two pilot projects, CarbFix in Icelandic basalts and Big Sky Regional Partnership in Columbia River Basalt, USA, estimation of carbon dioxide by passive peridotite carbonation at an Omani site and development of in-situ high-pressure X-ray diffraction and in-situ infrared spectroscopy for underground MC monitoring. Ex-situ direct MC research studies such as development of Energy Reactor, in-situ grinding concept, evaluation of catalysts (e.g. NaHCO3/NaCl mixtures or carbonic anhydrase) and use as a pre-treatment to enhance Ni extraction from olivine are discussed. Ex-situ indirect MC research investigations and MC by industrial wastes (e.g. coal fly ash, metallurgical slags, waste gypsum and waste concrete) are surveyed. The results of the researches indicate that the efficiency of MC processes increases with increasing carbon dioxide pressure, increasing temperature, decreasing particle size and use of catalysts., A review is presented of developments in, current status of, and future prospects for, gas-aqueous-solid Mg- and Ca-silicate mineral-carbonation (MC) processes - which are naturally exothermic - for converting carbon dioxide gas into stable Mg and Ca carbonates with silica as by-product. In-situ MC by basalts and peridotite is described including two pilot projects, CarbFix in Icelandic basalts and Big Sky Regional Partnership in Columbia River Basalt, USA, estimation of carbon dioxide by passive peridotite carbonation at an Omani site and development of in-situ high-pressure X-ray diffraction and in-situ infrared spectroscopy for underground MC monitoring. Ex-situ direct MC research studies such as development of Energy Reactor, in-situ grinding concept, evaluation of catalysts (e.g. NaHCO3/NaCl mixtures or carbonic anhydrase) and use as a pre-treatment to enhance Ni extraction from olivine are discussed. Ex-situ indirect MC research investigations and MC by industrial wastes (e.g. coal fly ash, metallurgical slags, waste gypsum and waste concrete) are surveyed. The results of the researches indicate that the efficiency of MC processes increases with increasing carbon dioxide pressure, increasing temperature, decreasing particle size and use of catalysts.
Published: 2018

18. Primary constitutional MLH1 epimutations: a focal epigenetic event

Author: Dámaso, E, Castillejo, A, Arias, Mdm, Canet-Hermida, J, Navarro, M, Del Valle, J, Campos, O, Fernández, A, Marín, F, Turchetti, D, García-Díaz, Jd, Lázaro, C, Genuardi, Maurizio, Rueda, D, Alonso, Á, Soto, Jl, Hitchins, M, Pineda, M, Capellá, G., Genuardi M (ORCID:0000-0002-7410-8351), Dámaso, E, Castillejo, A, Arias, Mdm, Canet-Hermida, J, Navarro, M, Del Valle, J, Campos, O, Fernández, A, Marín, F, Turchetti, D, García-Díaz, Jd, Lázaro, C, Genuardi, Maurizio, Rueda, D, Alonso, Á, Soto, Jl, Hitchins, M, Pineda, M, Capellá, G., and Genuardi M (ORCID:0000-0002-7410-8351)
Abstract: BACKGROUND: Constitutional MLH1 epimutations are characterised by monoallelic methylation of the MLH1 promoter throughout normal tissues, accompanied by allele-specific silencing. The mechanism underlying primary MLH1 epimutations is currently unknown. The aim of this study was to perform an in-depth characterisation of constitutional MLH1 epimutations targeting the aberrantly methylated region around MLH1 and other genomic loci. METHODS: Twelve MLH1 epimutation carriers, 61 Lynch syndrome patients, and 41 healthy controls, were analysed by Infinium 450 K array. Targeted molecular techniques were used to characterise the MLH1 epimutation carriers and their inheritance pattern. RESULTS: No nucleotide or structural variants were identified in-cis on the epimutated allele in 10 carriers, in which inter-generational methylation erasure was demonstrated in two, suggesting primary type of epimutation. CNVs outside the MLH1 locus were found in two cases. EPM2AIP1-MLH1 CpG island was identified as the sole differentially methylated region in MLH1 epimutation carriers compared to controls. CONCLUSION: Primary constitutional MLH1 epimutations arise as a focal epigenetic event at the EPM2AIP1-MLH1 CpG island in the absence of cis-acting genetic variants. Further molecular characterisation is needed to elucidate the mechanistic basis of MLH1 epimutations and their heritability/reversibility.
Published: 2018

19. Skeletal muscle microvascular-linked improvements in glycemic control from resistance training in individuals with type 2 diabetes

Author: Russell, Ryan D, Hu, Donghua, Greenaway, Timothy, Blackwood, Sarah J, Dwyer, Renee M, Sharman, James E, Jones, Graeme, Squibb, Kathryn A, Brown, Aascha A, Otahal, Petr, Boman, Meg, Al-Aubaidy, Hayder, Premilovac, Dino, Roberts, Christian K, Hitchins, Samuel, Richards, Stephen M, Rattigan, Stephen, Keske, Michelle A, Russell, Ryan D, Hu, Donghua, Greenaway, Timothy, Blackwood, Sarah J, Dwyer, Renee M, Sharman, James E, Jones, Graeme, Squibb, Kathryn A, Brown, Aascha A, Otahal, Petr, Boman, Meg, Al-Aubaidy, Hayder, Premilovac, Dino, Roberts, Christian K, Hitchins, Samuel, Richards, Stephen M, Rattigan, Stephen, and Keske, Michelle A
Published: 2017

20. SNP rs16906252C>T Is an Expression and Methylation Quantitative Trait Locus Associated with an Increased Risk of Developing MGMT-Methylated Colorectal Cancer

Author: Kuroiwa-Trzmielina, J, Wang, F, Rapkins, RW, Ward, RL, Buchanan, DD, Win, AK, Clendenning, M, Rosty, C, Southey, MC, Winship, IM, Hopper, JL, Jenkins, MA, Olivier, J, Hawkins, NJ, Hitchins, MP, Kuroiwa-Trzmielina, J, Wang, F, Rapkins, RW, Ward, RL, Buchanan, DD, Win, AK, Clendenning, M, Rosty, C, Southey, MC, Winship, IM, Hopper, JL, Jenkins, MA, Olivier, J, Hawkins, NJ, and Hitchins, MP
Abstract: PURPOSE: Methylation of the MGMT promoter is the major cause of O6-methylguanine methyltransferase deficiency in cancer and has been associated with the T variant of the promoter enhancer SNP rs16906252C>T. We sought evidence for an association between the rs16906252C>T genotype and increased risk of developing a subtype of colorectal cancer featuring MGMT methylation, mediated by genotype-dependent epigenetic silencing within normal tissues. EXPERIMENTAL DESIGN: By applying a molecular pathologic epidemiology case-control study design, associations between rs16906252C>T and risk for colorectal cancer overall, and colorectal cancer stratified by MGMT methylation status, were estimated using multinomial logistic regression in two independent retrospective series of colorectal cancer cases and controls. The test sample comprised 1,054 colorectal cancer cases and 451 controls from Sydney, Australia. The validation sample comprised 612 colorectal cancer cases and 245 controls from the Australasian Colon Cancer Family Registry (ACCFR). To determine whether rs16906252C>T was linked to a constitutively altered epigenetic state, quantitative allelic expression and methylation analyses were performed in normal tissues. RESULTS: An association between rs16906252C>T and increased risk of developing MGMT-methylated colorectal cancer in the Sydney sample was observed [OR, 3.3; 95% confidence interval (CI), 2.0-5.3; P < 0.0001], which was replicated in the ACCFR sample (OR, 4.0; 95% CI, 2.4-6.8; P < 0.0001). The T allele demonstrated about 2.5-fold reduced transcription in normal colorectal mucosa from cases and controls and was selectively methylated in a minority of normal cells, indicating that rs16906252C>T represents an expression and methylation quantitative trait locus. CONCLUSIONS: We provide evidence that rs16906252C>T is associated with elevated risk for MGMT-methylated colorectal cancer, likely mediated by constitutive epigenetic repression of the T allele. Clin Cancer
Published: 2016

21. Rumania, 1866-1947

Author: Hitchins, Keith, 1931, Hitchins, Keith, 1931, Hitchins, Keith, 1931, and Hitchins, Keith, 1931
Abstract: Reprint. Originally published: 1994., Electronic access restricted; authentication may be required, 9780198221265, American Council of Learned Societies History E-Book Project, (heb) heb05006.0001.001, http://hdl.handle.net/2027/heb.05006, Permission must be received for any subsequent distribution in print or electronically. Please contact info@hebook.org for more information.
Published: 2007

22. Effects of season and management of irrigated cotton fields on Collembola (Hexapoda) in New South Wales, Australia

Author: Lytton-Hitchins, James A., Greenslade, Penelope, Wilson, Lewis J., Lytton-Hitchins, James A., Greenslade, Penelope, and Wilson, Lewis J.
Abstract: The effects of production practices on the relative abundance of springtails (Collembola) in irrigated cotton fields of northern New South Wales (NSW) were studied over 2 yr to examine effects of farmmanagement on these decomposer organisms. Pitfall trapping and soil core extraction was undertaken in both pseudoreplicated plots within whole fields on cotton farms and on experimental replicate plots of Envirofeast cotton and Lucerne. The relative abundance of surface-active springtails in cotton rows and densities of soil species from the rhizosphere were calculated. Twenty-three species of Collembola were collected from 5 fields, 19 in pitfall traps, and 11 in soil cores. Five species, Setogaster sp., Proisotoma minuta, Entomobrya unostrigata, Entomobrya multifasciata grp, and Lepidobrya sp. were numerically dominant on the ground at 86-96% of individuals and Mesaphorura sp., Folsomides parvulus, and Hemisotoma thermophila grp dominant in the soil. Native grassland samples contained 15 species of which a probable 10 were native and 8 were not found in cotton. Nineteen species of the 24 species identified from cotton were predominantly fungal feeders. Highest catches of Collembola occurred after flowering and soil Collembola increased with depth and during cotton growth on unsprayed plots but decreased on sprayed plots. Surface soil moistures affected daily catch rates with decomposing residues, crop stage, predator abundance, and season as secondary factors. Insecticide (endosulfan, pyrethroid, carbamate, and organophosphate) and predator effects were either negligible or unclear depending on the factor involved. Springtails appear to be predominately food limited during times of adequate soilmoisture in cotton fields.
Published: 2015

23. Art as history, history as art. Jheronimus Bosch and Pieter Bruegel the Elder, assembling knowledge not setting puzzles

Author: Koldeweij, A.M., Hitchins, S.G., Koldeweij, A.M., and Hitchins, S.G.
Abstract: Radboud Universiteit Nijmegen, 27 november 2014, Promotor : Koldeweij, A.M., Contains fulltext : 132856.pdf (publisher's version ) (Open Access)
Published: 2014

24. The MLH1 c.-27C>A and c.85G>T variants are linked to dominantly inherited MLH1 epimutation and are borne on a European ancestral haplotype

Author: Kwok, C.T., Vogelaar, I.P., Zelst-Stams, W.A.G. van, Mensenkamp, A.R., Ligtenberg, M.J.L., Rapkins, R.W., Ward, R.L., Chun, N., Ford, J.M., Ladabaum, U., McKinnon, W.C., Greenblatt, M.S., Hitchins, M.P., Kwok, C.T., Vogelaar, I.P., Zelst-Stams, W.A.G. van, Mensenkamp, A.R., Ligtenberg, M.J.L., Rapkins, R.W., Ward, R.L., Chun, N., Ford, J.M., Ladabaum, U., McKinnon, W.C., Greenblatt, M.S., and Hitchins, M.P.
Abstract: Contains fulltext : 136957.pdf (publisher's version ) (Closed access), Germline mutations of the DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2, and deletions affecting the EPCAM gene adjacent to MSH2, underlie Lynch syndrome by predisposing to early-onset colorectal, endometrial and other cancers. An alternative but rare cause of Lynch syndrome is constitutional epimutation of MLH1, whereby promoter methylation and transcriptional silencing of one allele occurs throughout normal tissues. A dominantly transmitted constitutional MLH1 epimutation has been linked to an MLH1 haplotype bearing two single-nucleotide variants, NM_000249.2: c.-27C>A and c.85G>T, in a Caucasian family with Lynch syndrome from Western Australia. Subsequently, a second seemingly unrelated Caucasian Australian case with the same MLH1 haplotype and concomitant epimutation was reported. We now describe three additional, ostensibly unrelated, cancer-affected families of European heritage with this MLH1 haplotype in association with constitutional epimutation, bringing the number of index cases reported to five. Array-based genotyping in four of these families revealed shared haplotypes between individual families that extended across A and c.85G>T variants are borne on a European ancestral haplotype and provide conclusive evidence for its pathogenicity via a mechanism of epigenetic silencing of MLH1 within normal tissues. Additional descendants bearing this founder haplotype may exist who are also at high risk of developing Lynch syndrome-related cancers.
Published: 2014

25. Epigenetic changes associated with disease progression in a mouse model of childhood allergic asthma

Author: Collison, A, Siegle, JS, Hansbro, NG, Kwok, CT, Herbert, C, Mattes, J, Hitchins, M, Foster, PS, Kumar, RK, Collison, A, Siegle, JS, Hansbro, NG, Kwok, CT, Herbert, C, Mattes, J, Hitchins, M, Foster, PS, and Kumar, RK
Abstract: Development of asthma in childhood is linked to viral infections of the lower respiratory tract in early life, with subsequent chronic exposure to allergens. Progression to persistent asthma is associated with a Th2-biased immunological response and structural remodelling of the airways. The underlying mechanisms are unclear, but could involve epigenetic changes. To investigate this, we employed a recently developed mouse model in which self-limited neonatal infection with a pneumovirus, followed by sensitisation to ovalbumin via the respiratory tract and low-level chronic challenge with aerosolised antigen, leads to development of an asthmatic phenotype. We assessed expression of microRNA by cells in the proximal airways, comparing changes over the period of disease progression, and used target prediction databases to identify genes likely to be up- or downregulated as a consequence of altered regulation of microRNA. In parallel, we assessed DNA methylation in pulmonary CD4+ T cells. We found that a limited number of microRNAs exhibited marked up- or downregulation following early-life infection and sensitisation, for many of which the levels of expression were further changed following chronic challenge with the sensitizing antigen. Targets of these microRNAs included genes involved in immune or inflammatory responses (e.g. Gata3, Kitl) and in tissue remodelling (e.g. Igf1, Tgfbr1), as well as genes for various transcription factors and signalling proteins. In pulmonary CD4+ T cells, there was significant demethylation at promoter sites for interleukin-4 and interferon-γ, the latter increasing following chronic challenge. We conclude that, in this model, progression to an asthmatic phenotype is linked to epigenetic regulation of genes associated with inflammation and structural remodelling, and with T-cell commitment to a Th2 immunological response. Epigenetic changes associated with this pattern of gene activation might play a role in the development of childhood
Published: 2013

26. The role and molecular characteristics of constitutional MLH1 epimutation in young-onset cancer.

Author: Hitchins, Megan, Clinical School - Prince of Wales Hospital, Faculty of Medicine, UNSW, Stirzaker, Clare, Garvan Institute of Medical Research, Faculty of Medicine, UNSW, Kwok, Chau-To, Clinical School - Prince of Wales Hospital, Faculty of Medicine, UNSW, Hitchins, Megan, Clinical School - Prince of Wales Hospital, Faculty of Medicine, UNSW, Stirzaker, Clare, Garvan Institute of Medical Research, Faculty of Medicine, UNSW, and Kwok, Chau-To, Clinical School - Prince of Wales Hospital, Faculty of Medicine, UNSW
Abstract: Lynch syndrome, the commonest form of familial young-onset cancer, is typically caused by germline sequence mutations within the DNA mismatch repair genes, usually MLH1 or MSH2. Constitutional MLH1 epimutation, characterised by monoallelic promoter methylation and transcriptional silencing throughout normal somatic tissues, is an alternative cause of cancer predisposition in mutation-negative cases.This study aimed to further define the role of MLH1 epimutations in cancer causation and their molecular basis. Mutation-negative Lynch syndrome cases with MLH1-deficient tumours were screened for constitutional epimutation and allelic expression imbalance (AEI) of MLH1 using new CpG and allele-quantification pyrosequencing assays. This led to the identification of a novel intronic splice mutation in one patient demonstrating AEI, and new cases with an MLH1 epimutation. Loss-of-heterozygosity of the normal allele was demonstrated in their tumours. In one sporadic case, the epimutation arose de novo. The other cases were familial, and their epimutations demonstrated dominant inheritance linked to a particular ancestral founder genetic haplotype, indicative of a cis genetic-based defect. A single nucleotide variant within the 5'UTR, c.-27C>A, was investigated as the underlying cause. This epimutation was mosaic, as indicated by variable AEI among carriers. Furthermore, it was erased in spermatozoa and reset in the next generation.The molecular characteristics of constitutional MLH1 epimutations were examined in the cell lines from carriers to better characterise the epigenetic modifications associated with this defect. Allele-specific chromatin immunoprecipitation assays were developed at polymorphic sites within the MLH1 promoter to determine the histone profile associated with each allele. Elevated levels of repressive modifications were associated with the epimutant alleles, whereas the unmethylated alleles retained transcriptionally permissive moieties. Treatment with e
Published: 2013

27. Reengineering Systems Engineering

Author: Systems Engineering, Kasser, Joseph, Hitchins, Derek, Huynh, Thomas V., Systems Engineering, Kasser, Joseph, Hitchins, Derek, and Huynh, Thomas V.
Abstract: This paper documents (1) the early phases of using systems engineering to develop a conceptual system – the system being developed is a systems engineering body of knowledge (SEBoK) and (2) the findings and opportunities generated in those early phases. The approach was based on identifying activities specific to systems engineering, as opposed to the broad raft of activities that systems engineers might undertake, according to their role. An activity-based definition of systems engineering vs. non-systems engineering role-based definition was developed. The second part of the paper identifies five types of systems engineers, discusses the evolution of systems engineering in terms of those five types, and hypothesizes that a major cause of the failure of systems engineering is the allocation of inappropriate types of systems engineers to early lifecycle phase systems engineering activities. The paper concludes with some insights and recommendations for further study.
Published: 2009

28. A long-term review of posterior colporrhaphy with Vypro 2 mesh.

Author: Barry C., Rane A., Lim Y.N., Muller R., Corstiaans A., Hitchins S., Barry C., Rane A., Lim Y.N., Muller R., Corstiaans A., and Hitchins S.
Abstract: The objective is to study the long-term outcomes of posterior colporrhaphy with composite polyglactin 910-polypropylene mesh (Vypro 2, Ethicon, Somerville, NJ, USA) utilizing an overlay technique. Seventy-eight patients involved in our previous study were contacted 3 years after their initial operation for follow-up (Lim YN, Rane A, Muller R, Int Urogynecol J 16:126-131, 2005). Thirty-seven (47%) returned for follow-up and completed a standardized questionnaire survey, whereas a further 16 (20%) returned their postal questionnaires. Mean age was 61.3 (SD 10.8) years, and follow-up was 35.7 (SD 4.5) months. There were statistically significant improvements in vaginal lump sensation and constipation (p<0.001) but no differences with defecatory difficulties or dyspareunia. De novo dyspareunia was reported in 27%. On examination, the incidences of mesh vaginal erosion and rectocele recurrence were 30% and 22%, respectively. It appears that posterior colporrhaphy incorporating Vypro 2 mesh with an overlay method is associated with unacceptably high incidence of complications. © International Urogynecology Journal 2007.
Published: 2008

29. Differentiation in History: gifted learners, what can we do?

Author: Hitchins, Penny and Hitchins, Penny
Published: 2008

30. Experimental Study of the Deposition of Combustion Aerosols in the Human Respiratory Tract

Author: Morawska, Lidia, Hofmann, Werner, Hitchins-Loveday, Jane, Swanson, Cheryl, Mengersen, Kerrie, Morawska, Lidia, Hofmann, Werner, Hitchins-Loveday, Jane, Swanson, Cheryl, and Mengersen, Kerrie
Abstract: The total deposition of environmental tobacco smoke (ETS), diesel and petrol smoke in the respiratory tract of 14 non-smokers between the ages of 20 and 30 was determined experimentally. A scanning mobility particle sizer (SMPS) measuring a size range of 0.016–0.626 micrometres was used to characterise the inhaled and exhaled aerosol during relaxed nasal breathing over a period of 10 min. The ETS, diesel, and petrol particles had average count median diameter (and geometric standard deviation) of 0.183 micrometres (1.7), 0.125 micrometres (1.7), and 0.069 micrometres (1.7), respectively. The average total number deposition of ETS was 36% (standard deviation 10%), of diesel smoke 30% (standard deviation 9%), and of petrol smoke 41% (standard deviation 8%). The analysis of the deposition patterns as a function of particle size for the three aerosols in each individual showed that there is a significant difference between each aerosol for a majority of individuals (12 out of 14). This is an important result as it indicates that differences persist regardless of inter-subject variability.
Published: 2005

31. Investigation of UBE3A and MECP2 in Angelman syndrome (AS) and patients with features of AS.

Author: Hitchins, M.P., Rickard, S., Dhalla, F., Vries, L.B.A. de, Winter, R., Pembrey, M.E., Malcolm, S., Hitchins, M.P., Rickard, S., Dhalla, F., Vries, L.B.A. de, Winter, R., Pembrey, M.E., and Malcolm, S.
Abstract: Item does not contain fulltext, Angelman syndrome (AS) is an imprinted neurobehavioral disorder characterized by mental retardation, absent speech, excessive laughter, seizures, ataxia, and a characteristic EEG pattern. Classical lesions, including deletion, paternal disomy, or epigenetic mutation, are confirmatory of AS diagnoses in 80% of cases. Loss-of-function mutations of the UBE3A gene have been identified in approximately 8% of AS cases, failing to account for the remaining patient population, and there appears to be a higher prevalence of mutations in familial than sporadic cases. We screened UBE3A in 45 index cases of AS without obvious 15q11-13 abnormalities. Pathological mutations were identified in 3/6 (50%) familial and 4/39 (>10%) sporadic cases. By combining our data with those of the literature, we demonstrate statistically that the frequency of UBE3A mutations is significantly higher in the familial than sporadic subsets of AS. This indicates that an independent molecular mechanism or 'phenocopy' exists for the sporadic group. Rett syndrome (RS), caused by mutations of the MECP2 gene, and patients with deletions of 22q13.3 --> qter, have overlapping clinical features with AS. We screened 24 of the sporadic AS cases without detectable UBE3A mutations for mutations of MECP2, but found none. A separate cohort of 43 atypical patients with features common to AS and RS, in whom 15q11-13 lesions and 22q13.3 --> qter deletion had been ruled out, were also screened for MECP2 mutations. One male patient was mosaic for a frameshift mutation of this gene (previously reported). While MECP2 mutations can cause a phenotype reminiscent of AS in rare cases, they fail to account for the excess of sporadic patients with a definitive clinical diagnosis of AS.
Published: 2004

32. Contribution from Indoor Sources to Particle Number and Mass Concentrations in Residential Houses

Author: He, Congrong, Morawska, Lidia, Hitchins, Jane, Gilbert, Dale, He, Congrong, Morawska, Lidia, Hitchins, Jane, and Gilbert, Dale
Abstract: As part of a large study investigating indoor air in residential houses in Brisbane, Australia, the purpose of this work was to quantify emission characteristics of indoor particle sources in 15 houses. Submicrometer particle number and approximation of PM2.5 concentrations were measured simultaneously for more than 48 h in the kitchen of all the houses by usinga condensation particle counter (CPC) and a photometer (DustTrak), respectively. In addition, characterizations of particles resultingfrom cookingconducted in an identical way in all the houses were measured by usinga scanningmobility particle sizer (SMPS), an aerodynamic particle sizer (APS) and a DustTrak. All the events of elevated particle concentrations were linked to indoor activities usinghouse occupants diary entries, and catalogued into 21 different types of indoor activities. This enabled quantification of the effect of indoor sources on indoor particle concentrations as well as quantification of emission rates from the sources. For example, the study found that frying, grilling, stove use, toasting, cooking pizza, cooking, candle vaporizing eucalyptus oil and fan heater use, could elevate the indoor submicrometer particle number concentration levels by more than five times, while PM2.5 concentrations could be up to 3, 30 and 90 times higher than the background levels during smoking, frying and grilling, respectively. r 2004 Elsevier Ltd. All rights reserved.
Published: 2004

33. Multiparameter Investigations of Air Pollutant levels Contributing Sources in Residential Houses in Brisbane

Author: Clean Air Society of Australia and New Zealand, Morawska, Lidia, He, Congrong, Ayoko, Godwin, Hargreaves, Megan, Hitchins, Jane, Parappukkaran, Sandhya, Gilbert, D, Clean Air Society of Australia and New Zealand, Morawska, Lidia, He, Congrong, Ayoko, Godwin, Hargreaves, Megan, Hitchins, Jane, Parappukkaran, Sandhya, and Gilbert, D
Published: 2002

34. Dispersion of particles from vehicle emissions

Author: Hitchins, Jane and Hitchins, Jane
Published: 2001

35. Particle emissions from compressed natural gas engines

Author: Ristovski, Zoran, Morawska, Lidia, Hitchins, Jane, Thomas, Stephen B., Greenway, Chriss, Gilbert, Dale, Ristovski, Zoran, Morawska, Lidia, Hitchins, Jane, Thomas, Stephen B., Greenway, Chriss, and Gilbert, Dale
Abstract: This paper presents the results of measurements conducted to determine particle and gas emissions from two large compressed natural gas (CNG) spark ignition (SI) engines. Particle size distributions in the range from 0.01}30 km, and gas composition were measured for five power settings of the engines: 35, 50, 65, 80 and 100% of full power. Particle emissions in the size range between 0.5 and 30 km, measured by the aerodynamic particle sizer (APS), were very low at a level below two particles cm~3. These concentrations were comparable with average ambient concentration, and were not considered in the succeeding analysis. Both engines produce signifcant amounts of particles in the size range between 0.015 and 0.7 km, measured by the scanning mobility particle sizer (SMPS). Maximum number of concentrations of about 1]107 particles cm~3 were very similar for both engines. The CMDs were in the range between 0.020 and 0.060 km. The observed levels of particulate emission are in terms of number of the same order as emissions from heavy duty diesel engines (Morawska et al., Environ. Sci. Tech. 32, 2033}2042). On the other hand, emissions of CO and NOx of 5.53 and 3.33 g kWh~1, respectively, for one of the tested engines, were considerably lower than set by the standards. According to the specifications for the gas emissions, provided by the US EPA (US EPA, 1997), this engine can be considered as a "low-emission" engine, although emissions of submicrometer particles are of the same order as heavy-duty diesel vehicles.
Published: 2000

36. Concentration of submicrometre particles from vehicle emissions near a major road.

Author: Hitchins, Jane, Morawska, Lidia, Wolff, Rodney C., Gilbert, Dale, Hitchins, Jane, Morawska, Lidia, Wolff, Rodney C., and Gilbert, Dale
Abstract: As part of a program of study to assess the exposure risks related to particulate matter in the outdoor environment, number concentrations of particles from vehicle emissions were measured at increasing distances from a major road. Particles in the size range from 0.015 – 0.697 µm were measured with the Scanning Mobility Particle Sizer (SMPS) and in the size range from 0.5 – 20 µm, with the Aerodynamic Particle Sizer (APS). In addition to number concentration measurements, an approximation of PM2.5 fraction was obtained using a DustTrak (simple photometer). The measurements conducted at distances from the road ranging from 15 to 375 m showed, that for conditions where the wind is blowing directly from the road, the concentration of fine and ultrafine particles decays to around half of the maximum (measured at the closest point to the road) at a distance of approximately 100 - 150 m from the road. For the wind blowing parallel to the road, the reduction to half of the concentration occurs at 50 – 100 m. There is no effect on total particle number concentration at a distance greater than 15 m from the road when the wind is blowing towards the road and away from the sampling points. Total number concentrations of larger particles measured were not significantly higher than the average values for the urban environment, and decrease with distance from the road, reaching about 60% at 150 m from the road for wind from the road. PM2.5 levels also decrease with distance to around 75% for wind from the road and to 65% for wind parallel to the road, at a distance of 375 m.
Published: 2000

37. Elemental Composition of Combustion Emissions from Spark Ignition Vehicles

Author: Ristovski, Zoran, Agranovski, Victoria, Bostrom, Thor, Thomas, Stephen, Hitchins, Jane, Morawska, Lidia, Ristovski, Zoran, Agranovski, Victoria, Bostrom, Thor, Thomas, Stephen, Hitchins, Jane, and Morawska, Lidia
Abstract: In petrol engines, solid particle phases are formed as a result of incomplete combustion. In emissions from combustion processes such as petrol, natural gas or diesel, concentration of particles smaller than 1 µm could be several orders of magnitude higher than those which are larger than 1 µm. Due to their physical properties, submicrometer particles have a high probability of deposition in the deeper parts of the respiratory tract. It is known that petrol particles are mutagenic and carriers of hydrocarbons (and other compounds) adsorbed on the particulate and as a result represent a serious health hazard if inhaled. The present paper reports on some measurements of particle size distribution and composition of the bulk aerosol, as well as on morphological and elemental information from individual particles. The study was performed on non-diluted petrol exhaust obtained under different engine operation conditions. The bulk aerosol chemistry study has been performed. The concentrations of the following trace elements were measured: Boron, Calcium, Titanium, Chromium, Manganese, Iron, Cobalt, Nickel, Copper, Zinc, Cadmium, Barium, and Lead. The petrol particles have been found to be spherical. The most abandon elements were Fe, Ca, and Zn that have their origin from the additives in lubricating oil. It is interesting to note that although particle concentrations increased for 3 orders of magnitude from 40 to 120 km/h, emissions of metals did not significantly increase. This would indicate that most of the particle emission at higher loads comes from the unburned fuel and consists mainly of carbon either in elemental or organic form.
Published: 1999

38. Submicron Particle Emissions from Compressed Natural Gas Engines

Author: Ristovski, Zoran, Morawska, Lidia, Thomas, Stephen, Hitchins, Jane, Greenaway, Chris, Gilbert, Dale, Ristovski, Zoran, Morawska, Lidia, Thomas, Stephen, Hitchins, Jane, Greenaway, Chris, and Gilbert, Dale
Published: 1999

39. Submicrometer and Supermicrometer Particulate Emission from Spark Ignition Vehicles

Author: Ristovski, Zoran, Morawska, Lidia, Bofinger, Neville, Hitchins, Jane, Ristovski, Zoran, Morawska, Lidia, Bofinger, Neville, and Hitchins, Jane
Abstract: Particulate emissions from 11 gasoline powered and 2 liquefied petroleum (LPG) powered passenger vehicles were characterised during the Accelerated Simulation Mode driving cycles on a chassis dynamometer. The test fleet consisted of 10 catalyst-equipped vehicles operated with unleaded gasoline (5 Ford Falcons and 5 Holden Commodores), 2 LPG powered vehicles (both Ford Falcons), and 1 older type noncatalyst vehicle operated with leaded gasoline. Particulate characterisation included determination of total particulate number concentration and size distribution using the Scanning Mobility Particle Sizer (SMPS) and the Aerodynamic Particle Sizer (APS). The average particle number concentrations in the SMPS range for all modes was lower for Ford Falcons and somewhat higher for Commodores, with values of 1.5x104 and 4.1x104 cm-3, respectively. This difference is significant and was observed for all modes. The number concentration levels were higher for the LPG fuelled cars (8.4x104 cm-3) and for the leaded gasoline powered vehicle (7.9x105 cm-3). There was not a significant variation in particle count median diameter in the SMPS and the APS ranges, either for different operating conditions of the vehicles investigated, or between different vehicle groups. The observed size distributions were bimodal with average values of CMD ranged from 39.1 to 60.2nm in the SMPS range and from 0.9 to 1.4µm in the APS range. The results obtained from this study can be used as a first order estimation towards emission inventories for vehicle groups included in the investigations.
Published: 1998

40. An analysis of catch per unit effort data from the new Natal Parks Board shore patrol form

Author: Govender, A., Beckley, L.E., Bill, C., Chale, B., Chichwadia, Z., Hall, G.P., Hitchins, D., Koen, P., McKenzie, A., Naidoo, A.D., Pfotenhaner, T., Scott, G., Tooley, J., Trotter, D., White, C., Govender, A., Beckley, L.E., Bill, C., Chale, B., Chichwadia, Z., Hall, G.P., Hitchins, D., Koen, P., McKenzie, A., Naidoo, A.D., Pfotenhaner, T., Scott, G., Tooley, J., Trotter, D., and White, C.
Published: 1995

41. The Rumanian national movement in Transylvania, 1780-1849

Author: Hitchins, Keith, 1931, Hitchins, Keith, 1931, Hitchins, Keith, 1931, and Hitchins, Keith, 1931
Abstract: Based on the author's thesis, Harvard, 1964., Electronic access restricted; authentication may be required, American Council of Learned Societies History E-Book Project, (heb) heb05007.0001.001, http://hdl.handle.net/2027/heb.05007, Permission must be received for any subsequent distribution in print or electronically. Please contact info@hebook.org for more information.
Published: 1969

42. Principles Of Procedures Composition

Author: Riesbeck, Christopher K., Riesbeck, Christopher K., Hitchins, Ehwin L., Riesbeck, Christopher K., Riesbeck, Christopher K., and Hitchins, Ehwin L.
Published: 1982

43. The Eagle zone gold-tungsten sheeted vein porphyry deposit and related mineralisation, Dublin Gulch, Yukon Territory.

Author: Hitchins A.C., Orssich C.N., Hitchins A.C., and Orssich C.N.
Abstract: The deposit is hosted by the Cretaceous Dublin Gulch biotite granodiorite stock. It has been drill-tested over an area of 1 000 m by 500 m to a depth of 150 m. Mineralisation consists of parallel grey and white quartz veins with accessory gold, arsenopyrite, pyrite, pyrrhotite, chalcopyrite, native bismuth, bismuthinite and scheelite. Most veins have potassic and/or phyllic alteration envelopes. Alteration of the granodiorite becomes pervasive as vein densities increase. Mineralisation outside the Eagle zone, but spatially related to the Dublin Gulch stock, includes scheelite-bearing sheeted quartz vein zones, a swarm of Au-bearing quartz-sulphide veins, the Mar scheelite skarn and cassiterite-bearing breccias. A geological potential resource of 64 500 000 tonnes at a grade of 1.03 g/t Au has been estimated for the Eagle zone from widely spaced core and reverse circulation drill holes., The deposit is hosted by the Cretaceous Dublin Gulch biotite granodiorite stock. It has been drill-tested over an area of 1 000 m by 500 m to a depth of 150 m. Mineralisation consists of parallel grey and white quartz veins with accessory gold, arsenopyrite, pyrite, pyrrhotite, chalcopyrite, native bismuth, bismuthinite and scheelite. Most veins have potassic and/or phyllic alteration envelopes. Alteration of the granodiorite becomes pervasive as vein densities increase. Mineralisation outside the Eagle zone, but spatially related to the Dublin Gulch stock, includes scheelite-bearing sheeted quartz vein zones, a swarm of Au-bearing quartz-sulphide veins, the Mar scheelite skarn and cassiterite-bearing breccias. A geological potential resource of 64 500 000 tonnes at a grade of 1.03 g/t Au has been estimated for the Eagle zone from widely spaced core and reverse circulation drill holes.

44. Prediction of air core diameters for hydrocyclones.

Author: Steffens P.R., Appleby S., Hitchins J., Whiten W.J., Steffens P.R., Appleby S., Hitchins J., and Whiten W.J.
Abstract: The flow split between the products of a hydrocyclone is one of the least understood aspects of hydrocyclone operation. The split is greatly influenced by the air core diameter and an understanding of the air core behaviour would assist in predicting flow splits. Combined theoretical and experimental investigations of the factors which control the air core in a hydrocyclone have been carried out. Rietema type simplifications of the Navier Stokes equations were extended to include the prediction of air core diameter. The equations which are indirect in their original form were converted to give a direct solution for the dimensionless pressure and air core diameter ratio. Experimental studies obtained pressure drop, air core diameter and velocity profile data for a range of operating conditions. The data is being used to improve the theoretical analysis. The aim is to produce simple relations to improve simulations and provide guidance in hydrocyclone design., The flow split between the products of a hydrocyclone is one of the least understood aspects of hydrocyclone operation. The split is greatly influenced by the air core diameter and an understanding of the air core behaviour would assist in predicting flow splits. Combined theoretical and experimental investigations of the factors which control the air core in a hydrocyclone have been carried out. Rietema type simplifications of the Navier Stokes equations were extended to include the prediction of air core diameter. The equations which are indirect in their original form were converted to give a direct solution for the dimensionless pressure and air core diameter ratio. Experimental studies obtained pressure drop, air core diameter and velocity profile data for a range of operating conditions. The data is being used to improve the theoretical analysis. The aim is to produce simple relations to improve simulations and provide guidance in hydrocyclone design.

45. An examination of pulp viscosity in tubes at higher shear rates.

Author: Whiten W., Hitchins J., Steffens P., Whiten W., Hitchins J., and Steffens P.
Abstract: Deficiencies in the description of pulp properties is a major factor limiting improvements in the modelling of the flow within many mineral processing separation devices such as jigs and cyclones. Two factors severely hamper the development of accurate descriptions of pulp rheology: the large number of variables which influence pulp behaviour and the difficulty of making accurate measurements of pulp viscosity. Many factors make measurements of pulp viscosity difficult, including wall effects, turbulence, settling and the physical size of particles, particularly at high shear rates. An examination is presented of the measurement of pulp viscocity using capillary viscometers and in particular the high shear rate regions for which turbulent flow (or the transition to turbulent flow) occurs. The results show a marked difference in the behaviour of the pulps in this regime compared to Newtonian fluids. This is significant for hydrodynamic simulations of pulps at high shear rates., Deficiencies in the description of pulp properties is a major factor limiting improvements in the modelling of the flow within many mineral processing separation devices such as jigs and cyclones. Two factors severely hamper the development of accurate descriptions of pulp rheology: the large number of variables which influence pulp behaviour and the difficulty of making accurate measurements of pulp viscosity. Many factors make measurements of pulp viscosity difficult, including wall effects, turbulence, settling and the physical size of particles, particularly at high shear rates. An examination is presented of the measurement of pulp viscocity using capillary viscometers and in particular the high shear rate regions for which turbulent flow (or the transition to turbulent flow) occurs. The results show a marked difference in the behaviour of the pulps in this regime compared to Newtonian fluids. This is significant for hydrodynamic simulations of pulps at high shear rates.

46. The role of the Research Funding Officer in building robust and dynamic foundations for impact.

Author: Hitchins, Casper, Bayley, Julie, Hitchins, Casper, and Bayley, Julie
Abstract: The Research Funding Officer role is increasingly fundamental to impact, growing in importance as bidding becomes more competitive and the impact stakes get higher. Casper Hitchins and Julie Bayley argue that the dramatic elevation of impact in funding applications demands more insightful planning. Focus at the funding application stage not only generates more competitive bids, but also secures resources for the activities underpinning a solid REF submission. With funding schemes like Horizon 2020 already prioritising impact, Research Funding Officers can play a direct role in coordinating clear plans for impact.

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