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3. Navigating ethics in HIV data and biomaterial management within Black, African, and Caribbean communities in Canada

Author

Rusty Souleymanov, Bolaji Akinyele-Akanbi, Chinyere Njeze, Patricia Ukoli, Paula Migliardi, Linda Larcombe, Gayle Restall, Laurie Ringaert, Michael Payne, John Kim, Wangari Tharao, and Ayn Wilcox

Subjects
HIV community-based testing, Ethical concerns, Ethical considerations, Health data, Secondary use of biomaterials, Medical philosophy. Medical ethics, R723-726
Abstract

Abstract Background This study explored the ethical issues associated with community-based HIV testing among African, Caribbean, and Black (ACB) populations in Canada, focusing on their perceptions of consent, privacy, and the management of HIV-related data and bio-samples. Methods A qualitative community-based participatory research (CBPR) approach was employed to actively engage ACB community members in shaping the research process. The design included in-depth qualitative interviews with 33 ACB community members in Manitoba, Canada. The study was guided by a Community Guiding Circle, which contributed to study design, data analysis, and interpretation. A diverse sample was recruited through community agencies, social media, and flyers, with considerations for variations in age, gender, sexual orientation, and geographical location. The study employed iterative inductive thematic data analysis. Findings Participants expressed significant concerns about the collection, sharing, and use of HIV data from healthcare encounters, revealing mistrust towards institutions like police, child welfare, and immigration accessing their health information. Their worries centered on the handling of biological samples, data misuse, potential human rights violations, HIV criminalization, deportations, challenging consent, privacy, and bodily autonomy principles. While open to contributing to medical research, they unanimously demanded greater transparency, informed consent, and control over the secondary use of their health data. Conclusions The study underscores the need for culturally safe approaches in HIV testing and ethical governance in healthcare for ACB communities. It highlights the importance of prioritizing participant empowerment, ensuring transparency, practicing informed consent, and implementing robust data security measures to balance effective HIV information management with the protection of individual rights.

Published
2025
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4. Are International Students Relatively Resilient? Comparing International and Domestic Students' Levels of Self-Compassion, Mental Health and Wellbeing

Author

Wendy Larcombe, Tracii Ryan, and Chi Baik

Abstract

Because international students encounter unique stressors in addition to those experienced by all higher education students they are often assumed to be at heightened risk for experiencing mental health difficulties. However, empirical studies have consistently found that international students report comparable or lower rates of depression and anxiety than their domestic counterparts. The present study investigates one possible explanation for these unexpected results: are international students relatively resilient? More particularly, we investigate self-compassion (SC) -- an emotion-regulation strategy known to buffer the impact of stressors on mental health. While SC has been associated with positive psycho-social outcomes in the higher education context, existing studies have not disaggregated international and domestic students. The present study addresses that gap by comparing the levels and estimating the effects of SC among international and domestic students. Analyses found that international students on average reported significantly higher SC than their domestic counterparts. Without the protection afforded by those higher levels of SC, we estimated that international students would report higher psychological distress and lower psychological wellbeing than domestic students. Implications for fostering and supporting the mental health and wellbeing of all higher education students are discussed.

Published
2024
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5. CATHETER II: a randomised controlled trial comparing the clinical effectiveness of various washout policies versus no washout policy in preventing catheter-associated complications in adults living with long-term catheters

Author

John Norrie, Graeme Maclennan, David Cooper, Paul Little, Peter Murchie, Phyo Kyaw Myint, Mohamed Abdel-fattah, Mary Kilonzo, Muhammad Imran Omar, Diana Johnson, Sara J Maclennan, James N'Dow, Graham Scotland, Amanda Young, Seonaidh Cotton, James Larcombe, Nikesh Thiruchelvam, Catherine Paterson, Lynda Constable, Hashim Hashim, Sheela Tripathee, Konstantinos Dimitropoulos, Suzanne Evans, and Karen Powell

Subjects
Medicine
Abstract

Objectives Do weekly prophylactic saline or acidic catheter washouts in addition to standard long-term catheter (LTC) care improve the outcomes of adults with LTC compared with standard LTC care only.Design Three-arm superiority open-label randomised controlled trial.Setting UK community-based study.Participants 80 adults with LTC (any type/route) ≥28 days in situ with no plans to discontinue and able to self-manage the washouts/study documentation with/without a carer.Interventions Randomly allocated (26:27:27) to receive standard LTC care with weekly saline or weekly acidic or no prophylactic washouts for up to 24 months.Primary and secondary outcome measures The primary outcome was catheter blockage requiring intervention (per 1000 catheter days). Secondary outcomes were symptomatic catheter-associated urinary tract infection (S-CAUTI) requiring antibiotics, adverse events, participants’ quality of life and day-to-day activities, acceptability and adherence.Results Outcomes reported for 25 saline, 27 acidic and 26 control participants. LTC blockages (per 1000 catheter days) requiring treatment were 9.96, 10.53 and 20.92 in the saline, acidic and control groups, respectively. The incident rate ratio (IRR) favours the washout groups (saline 0.65 (97.5% CI 0.24 to 1.77); p=0.33 and acidic 0.59 (97.5% CI 0.22 to 1.63); p=0.25), although not statistically significant. The S-CAUTI rate (per 1000 catheter days) was 3.71, 6.72 and 8.05 in the saline, acidic and control groups, respectively. The IRR favours the saline group (saline 0.40 (97.5% CI 0.20 to 0.80); p=0.003 and acidic 0.98 (97.5% CI 0.54 to 1.78); p=0.93). The trial closed before reaching target recruitment due to reduced research capacity during the COVID-19 pandemic.Conclusions Early closure and small sample size limits our ability to provide a definite answer. However, the observed non-statistically significant differences over control are favourable for lower rates of LTC blockages without a concomitant rise in S-CAUTI. The results support a multinational randomised controlled trial of catheter washouts in patients with LTC to ascertain their clinical and cost-effectiveness.Trial registration number ISRCTN17116445.

Published
2024
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11. Early moderate prenatal alcohol exposure and maternal diet impact offspring DNA methylation across species

Author

Mitchell Bestry, Alexander N Larcombe, Nina Kresoje, Emily K Chivers, Chloe Bakker, James P Fitzpatrick, Elizabeth J Elliott, Jeffrey M Craig, Evelyne Muggli, Jane Halliday, Delyse Hutchinson, Sam Buckberry, Ryan Lister, Martyn Symons, and David Martino

Subjects
epigeneome, DNA methylation, alcohol, Medicine, Science, Biology (General), QH301-705.5
Abstract

Alcohol consumption in pregnancy can affect genome regulation in the developing offspring but results have been contradictory. We employed a physiologically relevant murine model of short-term moderate prenatal alcohol exposure (PAE) resembling common patterns of alcohol consumption in pregnancy in humans. Early moderate PAE was sufficient to affect site-specific DNA methylation in newborn pups without altering behavioural outcomes in adult littermates. Whole-genome bisulfite sequencing of neonatal brain and liver revealed stochastic influence on DNA methylation that was mostly tissue-specific, with some perturbations likely originating as early as gastrulation. DNA methylation differences were enriched in non-coding genomic regions with regulatory potential indicative of broad effects of alcohol on genome regulation. Replication studies in human cohorts with fetal alcohol spectrum disorder suggested some effects were metastable at genes linked to disease-relevant traits including facial morphology, intelligence, educational attainment, autism, and schizophrenia. In our murine model, a maternal diet high in folate and choline protected against some of the damaging effects of early moderate PAE on DNA methylation. Our studies demonstrate that early moderate exposure is sufficient to affect fetal genome regulation even in the absence of overt phenotypic changes and highlight a role for preventative maternal dietary interventions.

Published
2024
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12. Exposure to biodiesel exhaust is less harmful than exposure to mineral diesel exhaust on blood-brain barrier integrity in a murine model

Author

Michael Nesbit, Colleen Kah Ling Ko, John C. L. Mamo, Virginie Lam, Katherine R. Landwehr, Alexander N. Larcombe, and Ryu Takechi

Subjects
air pollution, diesel exhaust, biodiesel exhaust, blood-brain barrier, neuroinflammation, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Emerging data suggest that air pollution is a persistent source of neuroinflammation, reactive oxygen species (ROS), and neuropathology that contributes to central nervous system (CNS) disorders. Previous research using animal models has shown that exposure to diesel exhaust causes considerable disruption of the blood-brain barrier (BBB), leading to marked neuroinflammation. However, the effects of biodiesel exhaust on cerebrovascular integrity and neuroinflammation have not been explored previously. Therefore, in this study, 8-week-old BALB/c mice were exposed to biodiesel exhaust (derived from canola biodiesel or tallow biodiesel) and compared with control mice that were exposed to air or mineral diesel exhaust. Consistently with previous findings, the integrity of the BBB was significantly disrupted by exposure to mineral diesel exhaust. Tallow and canola biodiesel exhaust exposure resulted in no BBB disruption. Moreover, both tallow and canola biodiesels significantly attenuated oxidative stress in the brain. The data collectively suggest that biodiesel exhaust may exert significantly less detrimental effects on brain function, compared to mineral diesel.

Published
2024
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14. Impact of secreted glucanases upon the cell surface and fitness of Candida albicans during colonisation and infection

Author

Qinxi Ma, Arnab Pradhan, Ian Leaves, Emer Hickey, Elena Roselletti, Ivy Dambuza, Daniel E. Larcombe, Leandro Jose de Assis, Duncan Wilson, Lars P. Erwig, Mihai G. Netea, Delma S. Childers, Gordon D. Brown, Neil A.R. Gow, and Alistair J.P. Brown

Subjects
Candida albicans, Cell wall, Xog1 exoglucanase, Eng1 endoglucanase, β-glucan shaving, Gut colonisation, Cytology, QH573-671
Abstract

Host recognition of the pathogen-associated molecular pattern (PAMP), β-1,3-glucan, plays a major role in antifungal immunity. β-1,3-glucan is an essential component of the inner cell wall of the opportunistic pathogen Candida albicans. Most β-1,3-glucan is shielded by the outer cell wall layer of mannan fibrils, but some can become exposed at the cell surface. In response to host signals such as lactate, C. albicans shaves the exposed β-1,3-glucan from its cell surface, thereby reducing the ability of innate immune cells to recognise and kill the fungus. We have used sets of barcoded xog1 and eng1 mutants to compare the impacts of the secreted β-glucanases Xog1 and Eng1 upon C. albicans in vitro and in vivo. Flow cytometry of Fc-dectin-1-stained strains revealed that Eng1 plays the greater role in lactate-induced β-1,3-glucan masking. Transmission electron microscopy and stress assays showed that neither Eng1 nor Xog1 are essential for cell wall maintenance, but the inactivation of either enzyme compromised fungal adhesion to gut and vaginal epithelial cells. Competitive barcode sequencing suggested that neither Eng1 nor Xog1 strongly influence C. albicans fitness during systemic infection or vaginal colonisation in mice. However, the deletion of XOG1 enhanced C. albicans fitness during gut colonisation. We conclude that both Eng1 and Xog1 exert subtle effects on the C. albicans cell surface that influence fungal adhesion to host cells and that affect fungal colonisation in certain host niches.

Published
2024
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15. Migration and health study: a socio-ecological analysis of sexual health among migrants in Manitoba, Canada

Author

Rusty Souleymanov, Bolaji Akinyele-Akanbi, Chinyere Njeze, Patricia Ukoli, Paula Migliardi, John Kim, Michael Payne, Laurie Ringaert, Gayle Restall, Linda Larcombe, Nathan Lachowsky, Mohammad Nuruzzaman Khan, Robert Lorway, and Fritz Pino

Subjects
Sexual health, Immigrants and refugees, HIV, Manitoba, Canada, Socio-ecological analysis, Public aspects of medicine, RA1-1270
Abstract

Abstract Background To develop effective public health policies, programs, and services tailored to the unique sexual health needs of migrant populations, it is essential to understand the myriad socio-ecological factors that influence their sexual health. This qualitative community-based participatory study aimed to explore factors influencing migrants’ sexual health at different socio-ecological levels in a Canadian setting. Methods Participants (n = 34) from African, Caribbean, Black; Latin American; South Asian; Middle Eastern, as well as East and Southeast Asian communities were recruited across Manitoba using printed flyers, community organizations, and social media. Individual interviews, conducted in English, French, Mandarin, Cantonese, Tagalog, Arabic, Swahili, and Tigrinya languages, explored questions relating to sexual health and experiences with service providers. Data were analyzed using reflexive thematic analysis and socio-ecological systems theory. Results The study uncovered a range of individual, interpersonal, institutional, and socio-structural factors that affect the sexual health of migrants in Manitoba. Individual factors such as sexual health knowledge and testing practices, interpersonal factors like the type of sexual partnerships, institutional factors such as sexual health information needs, language, and service access barriers, and structural-level factors like gender norms and HIV stigma exerted a significant influence on the sexual health practices of study respondents. Sexual health awareness was influenced by various factors including length of time in Canada and involvement in community-based services. Study respondents identified issues related to access to HIV testing and sexual health information, as well as language barriers, racism in healthcare, and HIV stigma. Gender and social norms played a significant role in discouraging communication about sex and safer sex practices. Conclusions The study highlights the complex interplay of factors that influence the sexual health of migrants, and the need for targeted sexual health awareness campaigns and provision of sexual health information in languages spoken by migrants. Public health interventions focused on improving the sexual health outcomes for migrants should consider the socio-ecological elements identified in this study. These findings can inform public health campaigns to increase access to services and address sexual health inequities among migrant communities in Canada.

Published
2023
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18. A prognostic model for use before elective surgery to estimate the risk of postoperative pulmonary complications (GSU-Pulmonary Score): a development and validation study in three international cohorts

Author

Bravo, Laura, Simões, Joana FF, Cardoso, Victor R, Adisa, Adewale, Aguilera, Maria L, Arnaud, Alexis, Biccard, Bruce, Calvache, Jose, Chernbumroong, Saisakul, Elhadi, Muhammed, Ghosh, Dhruv, Gujjuri, Rohan, Harrison, Ewen, Ho, Michael WS, Kasivisvanathan, Veerappan, Kouli, Omar, Lederhuber, Hans, Li, Elizabeth, Löffler, Markus W, Isik, Arda, Marcus, Hani, Martin, Janet, McLean, Kenneth A, Minaya-Bravo, Ana, Modolo, María Marta, Nepogodiev, Dmitri, Pellino, Gianluca, Picciochi, Maria, Pockney, Peter, van Ramshorst, Gabriëlle, Riad, Aya, Sayyed, Raza, Sund, Malin, Gkoutos, Georgios, Bhangu, Aneel A, Glasbey, James C, Bravo, L, Cardoso, V, Glasbey, J, Chernbumroong, S, Nepogodiev, D, Simoes, JFF, Mclean, KA, Bhangu, AA, Gkoutos, G, Kadir, B, Omar, O, Revell, E, Bahrami-Hessari, M, Ahmed, Waheed-Ul-Rahman, Argus, Leah, Ball, Alasdair, Bhangu, Aneel, Bywater, Edward P, Blanco-Colino, Ruth, Brar, Amanpreet, Chaudhry, Daoud, Dawson, Brett E, Duran, Irani, Gujjuri, Rohan R, Jones, Conor S, Harrison, Ewen M, Kamarajah, Sivesh K, Keatley, James M, Lawday, Samuel, Mann, Harvinder, Marson, Ella J, Mclean, Kenneth A, Norman, Lisa, Ots, Riinu, Outani, Oumaima, Santos, Irène, Shaw, Catherine, Taylor, Elliott H, Trout, Isobel M, Varghese, Chris, Venn, Mary L, Xu, William, Dajti, Irida, Gjata, Arben, Kacimi, Salah Eddine Oussama, Boccalatte, Luis, Cox, Daniel, Aigner, Felix, Kronberger, Irmgard Elisabeth, Samadov, Elgun, Alderazi, Amer, Padmore, Greg, van Ramshorst, Gabrielle, Lawani, Ismaïl, Cerovac, Anis, Delibegovic, Samir, Baiocchi, Glauco, Gomes, Gustavo Mendonça Ataíde, Lima Buarque, Igor, Gohar, Muhammad, Slavchev, Mihail, Nwegbu, Chukwuemeka, Agarwal, Arnav, Ng-Kamstra, Joshua, Olivos, Maricarmen, Lou, Wenhui, Ren, Dong-Lin, Calvache, Jose Andres, Perez Rivera, Carlos J, Danic Hadzibegovic, Ana, Kopjar, Tomislav, Mihanovic, Jakov, Avilés Jiménez, Pablo Mijahil, Gouvas, Nikolaos, Klat, Jaroslav, Novysedlák, René, Amisi, Nicolas, Christensen, Peter, El-Hussuna, Alaa, Batista, Sylvia, Lincango-Naranjo, Eddy, Emile, Sameh, Arévalo Sandoval, Danilo Alfonso, Dhufera, Hailu, Hailu, Samuel, Mengesha, Mengistu G, Kauppila, Joonas H, Arnaud, Alexis P, Demetrashvili, Zaza, Albertsmeier, Markus, Löffler, Markus W., Kwesi Acquah, Daniel, Ofori, Bernard, Tabiri, Stephen, Metallidis, Symeon, Tsoulfas, Georgios, Aguilera-Arevalo, Maria-Lorena, Recinos, Gustavo, Mersich, Tamás, Wettstein, Dániel, Ghosh, Dhruva, Kembuan, Gabriele, Brouki Milan, Peiman, Khosravi, Mohammad Hossein, Mozafari, Masoud, Hilmi, Ahmed, Mohan, Helen, Zmora, Oded, Gallo, Gaetano, Pata, Francesco, Fujimoto, Yuki, Kuroda, Naoto, Satoi, Sohei, Abou Chaar, Mohamad K., Ayasra, Faris, Fakhradiyev, Ildar, Hamdun, Intisar Hisham Said, Jin-Young, Jang, Jamal, Mohammad, Karout, Lina, Gulla, Aiste, Rasoaherinomenjanahary, Fanjandrainy, Samison, Luc Hervé, Roslani, April Camilla, Durán Sánchez, Iran Irani, Gonzalez, Diana Samantha, Martinez, Laura, Martínez, María José, Nayen, Alejandra, Ramos-De la Medina, Antonio, Nunez, Jade, Nashidengo, Pueya Rashid, Shrestha, Ashish Lal, Jonker, Pascal, Kruijff, Schelto, Noltes, Milou, Steinkamp, Pieter, Wright, Deborah, Abdur-Rahman, Lukman, Ademuyiwa, Adesoji, Osinaike, Babatunde, Seyi-Olajide, Justina, Williams, Omolara, Williams, Emmanuel, Pejkova, Sofija, Al Balushi, Zainab, Qureshi, Ahmad Uzair, Abo Mohsen, Mustafa, Abukhalaf, Sadi A., Cukier, Moises, Gomez-Fernandez, Hugo, Shu Yip, Sebastian, Vasquez Ojeda, Ximena Paola, Sacdalan, Marie Dione, Major, Piotr, Azevedo, José, Cunha, Miguel F., Zarour, Ahmad, Bonci, Eduard-Alexandru, Negoi, Ionut, Efetov, Sergey, Kochetkov, Viktor, Litvin, Andrey, Allen Ingabire, Jc, Bucyibaruta, Georges, Faustin, Ntirenganya, Habumuremyi, Sosthene, Imanishimwe, Alphonsine, Jean de Dieu, Haragirimana, Munyaneza, Emmanuel, Ncogoza, Isaie, Alameer, Ehab, Ndong, Abdourahmane, Radenkovic, Dejan, Chew, Min Hoe, Koh, Frederick, Ngu, James, Panyko, Arpád, Bele, Uros, Košir, Jurij Aleš, Daoud, Hassan, Minaya Bravo, Ana Maria, Jayarajah, Umesh, Wickramasinghe, Dakshitha, Adam Essa Adam, Mohammed Elmujtba, Rutegård, Martin, Adamina, Michel, Gialamas, Eleftherios, Horisberger, Karoline, Alshaar, Muhammad, Lohsiriwat, Varut, Charles, Shane, Leventoğlu, Sezai, Lekuya, Hervé Monka, Lule, Herman, Kopetskyi, Slava, Alsaadi, Hayder, Alshryda, Sattar, Alser, Osaid, Bankhead-Kendall, Brittany, Breen, Kerry, Kaafarani, Haytham, Mashbari, Hassan, Bonilla Cal, Fernando, Al-Naggar, Hamza, Maimbo, Mayaba, Mazingi, Dennis, Abbott, Tom, Akhbari, Melika, Bhanderi, Shivam, Chakrabortee, Sohini, Costas-Chavarri, Ainhoa, Demetriades, Andreas K, Desai, Anant, Di Saverio, Salomone, Drake, Thomas, Edwards, John, Evans, Jonathan, Fiore, Marco, Ford, Samuel, Fotopoulou, Christina, Fowler, Alexander, Futaba, Kaori, Ganly, Ian, Grace James, Harelimana, Griffiths, Ewen, Hutchinson, Peter, Hyman, Gabriella Yael, Incorvia, Joseph, Jain, Ritu, Jenkinson, Michael, Khan, Tabassum, Knight, Stephen Richard, Kolias, Angelos, Kudsk-Iversen, Søren, Kwan, Tsun Yu, Leung, Elaine, Mayol, Julio, McKay, Siobhan, Meara, John G., Mills, Emily, Moug, Susan, Patel, Akshay, Perinotti, Roberto, Rice, Henry E., Roberts, Keith, Schache, Andrew, Shaw, Richard, Smart, Neil, Stephens, Matthew, Stewart, Grant D., Teasdale, Ella, Vidya, Raghavan, Wright, Naomi, Wuraola, Funmilola, Agastra, Ervis, Thereska, Dariel, Lucchini, Sergio Martin, Laudani, Veronica, Chwat, Carina, Pedraza Salazar, Ivana Ines, Pantoja Pachajoa, Diana Alejandra, Duro, Agustin, Calderón Arancibia, José Alfredo, Bright, Tim, Hollington, Paul, Zhou, Xuanyu, Kroon, Hidde M, Farfus, Anthony, Barker, John, Watson, Eleanor, Stevens, Sean, Latif, Haider, Dawson, Amanda Caroline, Chuan, Alwin, Muralidharan, Vijayaragavan, Wong, Enoch, Ackermann, Travis, Pacilli, Maurizio, Hodgson, Russell, Heriot, Alexander, Choong, Peter, Brown, Wendy, Lidder, Surjit, Yeung, Justin, Traeger, Luke, Regalo, Guillermo, Gourlay, Ralph, Badiani, Sarit, Koh, Cherry, Putnis, Soni, Haider, Fayza, Rahman Mitul, Ashrarur, Komen, Niels, Dhondt, Bert, Cappeliez, Serge, Pigeolet, Manon, Schoneveld, Martijn, Stijns, Jasper, Oosterlinck, Wouter, Flamey, Nicolas, Kpangon, Cyrille, Agbadebo, Mouhamed, Tobome, Sèmèvo Romaric, Vieira Barros, Aldo, Aguiar Júnior, Samuel, Campos, Heloisa Galvão do Amaral, Gross, Jefferson, José Fernandez Coimbra, Felipe, Kowalski, Luiz Paulo, Makdissi, Fabiana, Nakagawa, Suely, Pedreira Duprat Neto, Joao, Vartanian, Jose Guilherme, Yazbek, Guilherme, Zequi, Stenio C, Flumignan, Ronald, Jaworska, Natalia, Dell, Angela, Shanthanna, Harsha, Behzadi, Abdollah, Nessim, Carolyn, Mozel, Michelle, St-germain, Pascal, Russell, Crispin, Groot, Gary, Safieddine, Najib, Wijeysundera, Duminda, Eskander, Antoine, Chadi, Sami, MacKenzie, Shawn, Heredia, Fernando, Villanueva, Julio, Waissbluth, Sofia, Macchiavello, Roberto, Escudero, Mario I, Fuentes, Tyare, Mimica, Ximena, Bolivar Saenz, Dinimo, Caicedo, Lina, Alzate, Juan Pablo, Luna, Joaquin, Pedraza Alonso, Nestor Fabian, Ortiz Silva, Camilo, Rodriguez, Juliana, Silva-Igua, Liliana, Torres, Martha Luz, Trujillo, Lina María, Nieto Calvache, Albaro José, Balanta-Melo, Julián, Figueroa - Casanova, Rafael, García-Montoya, Oscar-Julián, Marulanda Toro, Carlos Andres, Mendoza Arango, Maria Clara, Diaz Martinez, Eneida, Gutiérrez Perdomo, Valentina, Montenegro, Emileth, Rodriguez-Abreu, Julia, Abouelnagah, Galal, Shehata, Sameh, Hossam Eldin Fouad Rida, Ahmed, Hassan, Ramy A., Saad, Mahmoud M., Reda Loaloa, Mohamed, Mostafa, Badr, Qassem, Mohamed, Fahmy, Mohamed, Abozied, Hesham, Azzam, Ahmed Y, Ghozy, Sherief, Sallam, Asser, Shehta, Ahmed, Abdelkhalek, Mohamed, Samaka, Rehab, Morsy, Amr, Sherif, Ahmed Elshawadfy, Abebe, Metasebia, Negussie, Abraham, Fisseha, Tigist, Shumbash, Kibruyisfaw, Yasin, Seid Mohammed, Akililu, Yemisirach Bizuneh, Megersa, Abebe, Tefera, Teshome, Melatework, Atnafu, Bahru, Tsegaye, Bereket, Bezabih, Yoseph Solomon, Sisay, Silamlak, Bekele, Kebebe, Jira, Moa, Derilo, Habtamu, Degefa, Eyueal, Tadesse, Anteneh, Nidaw, Melkamu, Sarjanoja, Elise, Testelin, Sylvie, Boucher, Sophie, Jouffret, Lionel, Lakkis, Zaher, Zarzavadjian Le Bian, Alban, Harper, Luke, Danguy des Déserts, Marc, André, Benoît, Slim, Karem, Verhaeghe, Romain, Police, Andrea, Girard, Edouard, Chebaro, Alexandre, Subayi Nkembi, Armande, Arnalsteen, Laurent, Ballouhey, Quentin, Mege, Diane, Jeandel, Clement, Duchalais, Emilie, Bouche, Pierre-Alban, Manceau, Gilles, Crétolle, Célia, Hervieux, Erik, Girard, Noémie, Seguin-Givelet, Agathe, Gaujoux, Sebastien, De Simone, Belinda, Boisson, Matthieu, Bergeat, Damien, Fredon, Fabien, Nappi, Francesco, Kassir, Radwan, Scalabre, Aurélien, Migliorelli, Federico, Ezanno, Anne-Cecile, Seeliger, Barbara, Vaysse, Charlotte, Charbonneau, Helene, Misrai, Vincent, Abbo, Olivier, Angeles, Martina Aida, Brunaud, Laurent, Modabber, Ali, Wolf, Sebastian, Kamphues, Carsten, Höhn, Philipp, Glowka, Tim R., Rokohl, Alexander Christopher, Bork, Ulrich, Fluegen, Georg, Horch, Raymund E., Schmedding, Andrea, Schnitzbauer, Andreas, Eberbach, Helge, Schlager, Daniel, Spelsberg, Fritz, Keppler, Lena, Hecker, Andreas, Wolfer, Susanne, Ronellenfitsch, Ulrich, Nitschke, Christine, Peiper, Christian, Hakami, Ibrahim, Welter, Stefan, Nikolaieva, Karine, Roth, Andreas, Lindert, Judith, Gousias, Konstantinos, Rissmann, Anke, Linz, Valerie Catherine, Rahbari, Nuh, Rassweiler-Seyfried, Marie-Claire, Gut, Anna Eleonora, Gempt, Jens, Reim, Daniel, Wagner, Arthur, Keppler, Alexander M., Stoleriu, Mircea Gabriel, Saier, Tim, Stadler, Josef, Kaiser, Julia Christina, Brunner, Stefan M., Pfister, Karin, Herzberg, Jonas, Nowak, Kai, Reinhard, Tobias, Stavrou, Gregor A., Königsrainer, Alfred, Konrads, Christian, Quante, Markus, Laban, Simon, Pusch von, Silke, Hirschburger, Markus, Doerner, Johannes, Wiegering, Armin, Tampaki, Ekaterini Christina, Gutiérrez Ruiz, Alitza, Rodas, Alejandra, Portilla, Ana Lucía, Carrera, Jacqueline, Barrios Duarte, Amalia, Lowey, Megan, Barillas, Sabrina, Vaishnav, Dhaivat, Gorantlu Chowdappa, Raghunandan, Madabhavi, Irappa, Bhat, Dhananjaya, Kumar Venkatappa, Sunil, Thakar, Sumit, Jain, Kavitha, Kumar, Aruna, Nagar, Manoj, Mishra, Tushar, Sekar, Arunkumar, Gupta, Anand, Kaman, Lileswar, Karthigeyan, Madhivanan, Tripathi, Manjul, Rammohan, Ashwin, Othiyil vayoth, Sudheer, Rajanbabu, Anupama, Subbian, Anbukkani, Gupta, Rahul, Raut, Monish, Evelyn. R, Nissi, Kannaiyan, Lavanya, Matai, Dr. Anil, Misra, Sanjeev, Bhende, Vishal, Muthu, Sathish, Ghosh, Indranil, Sharma, Abhishek, Bajaj, Ankur, Rajan, Shiv, Agarwal, Gaurav, Pawar, Pranay, Alexander, Philip, Vijayakumar, M, Hameed, BM Zeeshan, L, Badareesh, Chaudhry, Navneet Kumar, Baliarsing, Lipika, Dharap, Satish, Kulkarni, Amruta, Thyavihally, Yuvaraja, Pramesh, C S, Soni, Rajesh, Dube, Surya Kumar, Sharma, Shilpa, Singh, Harvinder, Bains, Lovenish, Ghodke, Rahul, Kumar, Ashwani, Sodhai, Vivek, Maji, Suvendu, Basu, Somprakas, Mahakalkar, Chandrashekhar, Kannan, Ravi, Mehraj, Asif, N, Ranganath, Phadnis, Ashish, Yadev, I, Kavalakat, Alfie, Mittal, Rohin, Vallam, Karthik Chandra, Akhavizadegan, Hamed, Rezghi Maleki, Esmaeil, Yousefzadeh Kandevani, Naser, Ikele, Hilary, McNestry, Catherine, Fleming, Christina, O’Brien, Stephen, Abd Elwahab, Sami, Davis, Niall, Javadpour, Mohsen, McDonnell, Brendan, O Connor, Clare, Bolger, Jarlath, Clancy, Cillian, Croghan, Stefanie M, Donlon, Noel, 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Mathew, Godwin David, Abel, Livingston, Barla, Ravi Kishore, Benjamin, Santosh, Bliss, Jeremy, Ete, Geley, James, Deeptiman, Jesudason, Mark Ranjan, Karnan, Gomathi, Mark Samuel, Vasanth, Nathan, Senthil K, Selvaraj, Daniel, Surendran, Suraj, T D, Hariharan, Thangaraj, Santhosh Kumar, Thomas, Varghese, Dilmy, Mohammad Adya Firmansha, Pratama, Dedy, Sugiarto, Adhrie, Surya, Ilham Utama, Tango, Tamara, Hasyim, Andi, Susanti, Ade, Saputra, Teddy, Syarifuddin, Erwin, Islam, Andi Asadul, Anam, Khoirul, Sugianto, Julius Albert, Lestari, Mayang Indah, Amba, Erick Gamaliel, Apriawan, Tedy, Wathoni, Roidah Taqiyya Zahra, Widyastuti, Yunita, Yun Jufan, Akhmad, Etezadpour, Mohammad, Mehrad-Majd, Hassan, Rajaei, Parisa, Mehdizadeh, Mohammad, Soltani, Mina, Ali Moazami Pour, Gholamreza Azarnia, Alizadeh, Narges, Hossein Mokarami, Tehrani, Shahrzad, Alborzi, Majid, Bagheri, Hamed, Eshraghi, Mohsen, Fatemi manesh, Hassan, Hejazi, Seyed fakhreddin, Pezeshki Modarres, Mahdi, Shafiee, Ali, Vafaeimanesh, 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Francesco Maria, Colombo, Giovanni, De Lucia, Francesca, De Virgilio, Armando, Ferreli, Fabio, La Raja, Carlotta, Milana, Flavio, Rossi, Vanessa, Russo, Elena, Tamburello, Sara, Zerbi, Alessandro, Bona, Davide, Adamoli, Laura, Ansarin, Mohssen, Chu, Francesco, De Berardinis, Rita, Pietrobon, Giacomo, Sedda, Giulia, Caputo, Maria, Cellerino, Paola, Crespi, Michele Achille, Danelli, Piergiorgio, Ferrara, Francesco, Baccellieri, Domenico, Candiani, Massimo, Casiraghi, Arianna, Cipriani, Federica, De Nardi, Paola, Mortini, Pietro, Nocera, Gianluca, Pozzoni, Mirko, Ruffolo, Alessandro Ferdinando, Spina, Alfio, Barberio, Cristina, Beretta, Luigi, Cavenago, Francesca, Fresilli, Stefano, Landoni, Giovanni, Lombardi, Gaetano, Bonomi, Stefano, Guaglio, Marcello, Sala, Laura, Segattini, Silvia, Piccoli, Micaela, Migliore, Marco, Sasia, Diego, Cereda, Marco, Dell’Oro, Cristina, Fogliati, Alessandro, Tamini, Nicolò, Castaldi, Antonio, Bracale, Umberto, Lionetti, Ruggero, Pagano, Gianluca, Peltrini, 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Oseihie, Irowa, Omorodion, Nwashilli, Nnamdi, Obahiagbon, Osarobo, Onyeagwara, Ngozi, Oseghale, Eustace, Osemwegie, Osarenkhoe, Osho, Philip, Akanni, Bolaji, Ezomike, Uchechukwu, Okoro, Kelechukwu, Okwara, Blasius, Abdulsalam, Khalifa, Agida, Eyaofun, Ajibola, Hafees, Benard, Adeka, Buba, Amina, Eniola, Sefiu, Isah, Aliyu, Olute, Anne, Osagie, Olabisi, Pius Ogolekwu, Idoko, Ademola, Samuel, Afuwape, Oludolapo, Daodu, Israel, Egbuchulem, Ifeanyichukwu Kelvin, Nwaorgu, Onyekwere, Obadan, Izegaegbe, Odeyemi, Olubunmi, Ogundoyin, Omowonuola, Okere, Oghenekevwe, Oladiran, Ajibola, Olagunju, Naomi, Olawoye, Olayinka, Olusanya, Adeola, Oyelakin, Oyeleye, Ugwu, Ebere, Atoyebi, Oluwole, Bode, Chris, Chibuike George, Ihediwa, Ezenwankwo, Francis, Fatuga, Adedeji, Ladipo-Ajayi, Oluwaseun, Ojewola, Rufus Wale, Okunowo, Adeyemi, Ugwu, Aloy Okechukwu, Adebara, Idowu, Adeyemo, Olabisi, Banjo, Oluseyi, Obateru, John, Ojo, Owolabi, Oluwafemi, Fatudimu, Adelaja, Aderinsola, Atobatele, Kazeem, Ayodele, Olabamidele, Bello, Funmi, Omisanjo, Olufunmilade, Aderounmu, Adewale, Ajekwu, Temitope, Ajekwu, Samuel, Akeem Aderogba, Adeleke, Balogun, Simon, Ojo, Olugbenga, Olasehinde, Olalekan, Olugbami, Adebayo, Mohammed, Tajudeen, Afolabi, Abdulrahman O., Aremu, Isiaka, Ibraheem, Gbadebo, Odeyemi, Peter Olalekan, Olabinjo, Afusat, Raji, Hadijat Olaide, Salawu, Hafeez, Uche-Okonkwo, Kenechukwu, Anipole, Olalekan, Adesina, Oluwaseyi, Enwerem, Kenneth, Isichei, Mercy, Aghadi, Ifeanyi, Lawal, Jamila, Taingson, Matthew, Yusuf, Nuhu, Takai, Idris Usman, Aji, Sani Ali, Bello-Muhammad, Nafisatu, Garzali, Ibrahim Umar, Hasheem, Muhammad Ghazali, Hassan, Sadiq, Ibrahim Usman, Mustapha, Magashi, Mahmoud Kawu, Mukhtar, Ibrahim Aliyu, Nwachukwu, Callistus, Suleiman, Ibrahim, A, Maryam, Mahmood, Farrukh, Salihu, Mohammed, Alegbeleye, Justina Omoikhefe, Awopeju, Abimbola, Fyneface-Ogan, Sotonye, Kasso, Terhemen, Onwuagha, Ijeoma, Salami, Babatunde, Ajagha, Okeoghene, Awaisu, Mudi, Nwabuoku, Stanley Emeka, 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Khan, Muhammad Osama, Kumari, Sameeta, Malik, Muhammad Jehangir, Mansoor, Maheen, Mubarik, Areeba, Naz, Falak, Qamar, Javeria Bilal, Sadia, Haleema, Safri, Mohammad, Sattar, abida K., Siddiqui, Muhammad Ahsan Iqbal, Waqar, Usama, Ghufran, Muhammad Ali, Memon, Amjad Siraj, Samo, Khursheed Ahmed, Aswani, Manisha, Manzoor, Shahneela, Muhammad, Shoaib, Moin, Inshrah, Najjad, Muhammad Kazim Rahim, Zia, Kashif, Ali Shaikh, Shafqat, Hussaini, Dr, Kamal, Wajahat, Mughal, Zeeshan Uddin, Nadeem, Areeba, Nayyer, Fatima, Nisa, Kanwal, Rauf, Yaseen, Saleem, Shah Masabat, Shah, Aaqil, Siddiqui, Safia, Tariq, Nida, Zamir, Mehroz, Hafiz Muhammad Arif, Ahmed, Ehsan, Ahmed, Jawad, Akbar, Bilal, Ali, Abrar Ashraf, Iqbal, Zafar, Jameel, Muhammad Khurram, Janjua, Muhammad Haris, Janjua, Azwa, Naqi, Syed Asghar, Naumeri, Fatima, Nazir, Umer, Rafi, Yaseen, Saleem, Irfan, Shaukat, Ayesha, Sikandar, Hafiz Saqib, Tu zahara, Fatima, Ali, Ahsan, Jawad, Muhammad, Noman, Hamza, Taha, Dr Hassan, Dr. Gul e Raana, Muhammad Ghulam Qadir, Ali, Imran, Asjad, Muhammad, Ayyaz, Mahmood, Bajwa, Luqman Ali, Bhatti, Samiullah, Butt, Usman, Chishti, Muhammad Haris, Hassan, Muhammad, Hassan, Usman, Hayat, Khizar, Khan, Rohma, Latif, Usman, Majeed, Faizan, Malik, Kiren, Nabi, Muhammad shoaib, Sadiq, Muhammad Hamza, Saeed, Komal, Sarfraz, Kiran, Sohail, Rubina, Syed muhammad, Bilal, Umair, Usama, Wasim, Shafqat, Wasim, Tayyiba, Imran Anwar, Muhammad, Ali, Ammar, Aslam, Muhammad, Sher e Murtaza, Muhammad, Faizi, Fouzia, Khan, Hamza, Akhtar, Muhammad Shaheer, Amin, Hasbi Allah, Ayub, Bakhtawar, Basir, Muhammad, Gul, Hina, Khan, Muhammad faisal, Moeen, Aiman, Mohmand, Obaid, Rahim, Rehana, Shafqat, Tanveer, Ur Rehman, Shams, Daud, Mashal, Abid, Rubaba, Farkhanda, Tallat, Malik, Sobia, Salim, Ruqyyah, Shaheen, Aneela, Ahmed, Faryal, Amjid, Zarafshan, Ishtiaq, Daniyal, Nagra, Ramisha Naseer, Saleem, Maleeha, Saleem, Bushra, Shabbir, Raja Khalid, Shaheen, Azka, Awad, Hadeel, Wafi, Dalia, Al-Slaibi, Ibrahim, I. 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Salam, Chen, Pengchi, Doshi, Neel, Gorgoraptis, Stefanos, Hatim Ali, Ali Asgar, Ng, Benjamin, Risk, Omar Ben Forge, Soleymani majd, Hooman, Ali, Roshneen, Ameen, Abdur-rafee, Belcher, Elizabeth, Ganau, Mario, Hughes, Anne, McNamara, John, Plaha, Puneet, Sravanam, Sanskrithi, Norris, Jonathan, Alasadi, Ala, Donnelly, Lauren, Harding, Thomas, Shum, Christie Hok Yung, Slevin, Zack, Acharya, Shivanie, Amditis, Pantelis, Bashir, Aladdin, Khan, Maham, Marshall-Roberts, Rachel, Miller, Douglas, Miller, Sarah, Nawara, Hossam, Singh, Simran, Smolarek, Sebastian, Yao, Lu, Armstrong, Lara, Lockhart, Jessica, Ashbridge, James, Di Donato, Nadine, Dipper, Matthew, Stefan, Samuel, Khincha, Priyatma, Riaz, Kazim, Shehrazi, S Ali Raza, Anazor, Fitzgerald, Brown, Sarah, Chadha, Radhika, Crawley, Emily, Kulkarni, Avadhut, Lewis, Francesca, Messina, Gianfranco, Bird, Sophie, Chaudhry, Umer, Prakash Narayan, Prabhat, Khan, Karishma, Murali, Sreedutt, Papidze, Ketevan, Ali, Aoun, Haque, Saeef, Mukherjee, Samrat, Wickramarachchi, Lilanthi, Yang, Yu Hsuen, Bitar, Samer, Chelva, Ruth, Gabr, Abdullah, Madni, Abdul, Mohamed, Musheer Hussain, Ramesh, Ashwanth, Ugam, Al-Tamimi, Yahia, Bacon, Andrew, Catto, James, Rominiyi, Ola, Tame, Oliver, Jackson, Richard, Kiely, John, Anjarwalla, Naffis, Kahka, Ehab, Patel, Arjun, Saeid, Sawsan, Samadi, Nilofar, Karar, Shoura, McCullough, Rebekah, Punnen, Aaron Julius, Danwaththa Liyanage, Aloka Suwanna, Aleem, Muhammad, Cathcart, Russell, Cohen, Olivia, Brinkler, Rebecca, Hayat, Zara, Parry, James, Adegbola, Samuel, Yeoh, Clarence, Melissa, Bromage, Stephen, Chatterji, Somashree, George, Suku, George, Smitha, Hunt, Janette, Kujawa, Magda, Munshi, Fatema, Rooney, Joanna, Zakieh, Imad, Zhang, Yuhao, Evans, Daisy, Sachdev, Bobby, Sadia, Uzma, Rajgor, Amarkumar D, Walters, Holt, Dube, Manas, Watson, Nicholas, Ananth, Sankar, Dhillon, Dharminder, Henry, Alastair, Lau, Godfrey, Li, Zoe, Shah, Ketan, Castelhano, Rute, Shah, Vinay, Win, Khine Myat, Davoudi, Kaveh, Foster, Paul, Hunt, Louise, Kamalakannan, Bhavani, Macdonald, Hamish, Morrison, Jo, Newitt, Laura, Parwaiz, Hammad, Slade, George, Stewart, Charles Geoffrey Dermot, Rhee, Jae, Sykes, Rosemary, Dickason, Aubrey, Ekpo, Ekemini, Scott, Rupert, de Rome, Katherine, Sahnan, Kapil, Ismayl, Ghiath, Moores, Thomas, Simmons, Mark, Techaboonanake, Sita, Abdelgalel, Khaled, Amin, Verda, Bhatnagar, Anuj, Charalampakis, Vasileios, Ramcharan, Sean, Galiveeti, Venkat mukund reddy, Massri, Erfan, Hassan, Abdulhakim, Lane, Oliver, McLellan, Morag, Shamim, Sarah, Vinayagam, Raman, Ross, Fiona, Blair, James, Dewan, Varun, Drew, William, Iftikhar, Zainab, Milner, Sean, Rajdev, Kishan, Reid, Jeremy, Thomas, Osmond, Adewusi, Mas’ud, Duckett, Abigail, El Falaha, Sara, Ooi, Chun, Mohamed Salim, Mohamed Ashiq, Ireson, Rebecca, MacDonald, Luisa, Ribeiro, Barbara, Savage, Alistair, Sharma, Tanisha, Swift, Paul, Elswick, Chase, Hemmila, Mark, Wong, Jane J, Amin, Dina, Chabuz, Carolyn, Gergen, Anna, Getz, Anne, Harmon, Laura, McIntyre, Jr., Robert, Meguid, Robert, Rodriguez, Kenny, Scott, Christopher, Steward, Lauren, Stewart, Camille, Thieu, Daniel, Velopulos, Catherine, Vogel, Jon, Bengtson, Erika, Hill, Charles, Holan, Cole, Kay, Hannah, McElhinney, Kathryn, Osterberg, E. Charles, Rossano, Ayane, Trust, Marc, Bigelow, Benjamin, Jain, Amit, Yesantharao, Lekha, Zhang, Bo, Abdou, Hossam, Mazzeffi, Michael, Rock, Peter, Afshar, Salim, Carlson, Laura, Kurtz, Michael, Nathan, Meena, Taghinia, Amir, Williams, Vivian, Cooper, Zara, Mahvi, David, Okafor, Barbara, Roxo, Vanessa, Burks, Ciersten, Jabbour, Nicolette, Sabra, Joseph, Wason, Shaun, Dorken Gallastegi, Ander, Gebran, Anthony, McTague, Michael, Ross, Samuel, Alvarado, Rosalinda, Bhama, Anuradha, Govekar, Henry, Kokosis, George, Millikan, Keith, Myers, Jonathan, Pappas, Sam, Siparsky, Nicole, Tsambarlis, Peter, Quillin, Ralph, Ekrami, Elyad, Kai, Li, Decker, Cassie, Aoun, Salah, Kwon, David, Barbas, Andrew, Dotters-Katz, Sarah K., Ellett, Tressa, Flamant, Etienne, Lazarides, Alexander, Refaat, Motasem, Soderlund, Torre, Velasquez, Camilo, Arrangoiz, Rodrigo, Mijares Olivo, Maria Fernanda, Vasudevan, Vanitha, Katz, Matthew, Nguyen, Huan, Pieretti, Alberto, Roland, Christina L, Baral, Perel, Beahm, D. 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Davies, L, Dwaraknath, M, Farah, Y, Garner, J, Gureviciute, E, Hart, E, Javid, S, Kankam, HK, Kaur Toor, P, Kaz, R, Kermali, M, Khan, I, Mattson, A, McManus, A, Murphy, M, Nair, K, Ngemoh, D, Norton, E, Olabiran, A, Parry, L, Payne, T, Pillai, K, Punjabi, K, Raghunathan, A, Raza, M, Ritehnia, J, Simpson, G, Smith, W, Sodeinde, S, Studd, L, Subramaniam, M, Thomas, J, Towey, S, Tsang, E, Tuteja, D, Vasani, J, Vio, M, Adams, J, Anthony Wilkinson, J, Asvandi, S, Austin, T, Bald, A, Bix, E, Carrick, M, Chander, B, Cooper Drake, B, Crosbie, S, D Portela, S, Francis, D, Gallagher, C, Gillespie, R, Gravett, H, Gupta, P, Ilyas, C, Johny, J, Jones, A, Kinder, F, MacLeod, C, Macrow, C, Maqsood-Shah, A, Mather, J, McCann, L, McMahon, R, Mitham, E, Mohamed, M, Munton, E, Nightingale, K, O‚ÄôNeill, K, Onyemuchara, I, Senior, R, Shanahan, A, Sherlock, J, Spyridoulias, A, Stavrou, C, Stokes, D, Tamang, R, Taylor, E, Trafford, C, Uden, C, Waddington, C, Yassin, D, Zaman, M, Bangi, S, Cheng, T, Hussain, N, Imani-Masouleh, S, Mahasivam, G, McKnight, G, Ng, HL, Ota, HC, Pasha, T, Ravindran, W, Vishnu K, S, Zaman, S, Carr, W, Cope, S, Eagles, EJ, Howarth-Maddison, M, Li, CY, Reed, J, Ridge, A, Stubbs, T, Teasdaled, D, Umar, R, Worthington, J, Dhebri, A, Kalenderov, R, Alattas, A, Arain, Z, Bhudia, R, Chia, D, Daniel, S, Dar, T, Garland, H, Girish, M, Hampson, A, Lehovsky, K, Mullins, W, Omorphos, N, Vasdev, N, Venkatesh, A, Waldock, W, Bhandari, A, Brown, G, Choa, G, Eichenauer, CE, Ezennia, K, Kidwai, Z, Lloyd-Thomas, A, Macaskill Stewart, A, Massardi, C, Sinclair, E, Skajaa, N, Tan, I, Afsheen, N, Anuar, A, Azam, Z, Bhatia, P, Davies-kelly, N, Dickinson, S, Elkawafi, M, Ganapathy, M, Khoury, EG, Licudi, D, Mehta, V, Neequaye, S, Nita, G, Tay, VL, Zhao, S, Botsa, E, Cuthbert, H, Elliott, J, Furlepa, M, Lehmann, J, Mangtani, A, Narayan, A, Shah, D, Shaw, C, Zhao, Z, Beck, C, Caldwell, S, Clements, JM, French, B, Kenny, R, Kirk, S, McClung, A, McLaughlin, N, Watson, S, Whiteside, E, Alyacoubi, S, Arumugam, V, Beg, R, Dawas, K, Garg, S, Lloyd, ER, Mahfouz, Y, Manobharath, N, Moonesinghe, R, Morka, N, Prashar, J, Yip, S, Adeeko, ES, Ajekigbe, F, Bhat, A, Farrugia, A, Gurung, C, Long, T, Malik, B, Manirajan, S, Newport, D, Rayer, J, Ridha, A, Saran, T, Sinker, A, Waruingi, D, Allen, R, Al Sadek, Y, Alves do Canto Brum, H, Asharaf, H, Ashman, M, Balakumar, V, Barrington, J, Baskaran, R, Berry, A, Bhachoo, H, Bilal, A, Boaden, L, Chia, WL, Covell, G, Crook, D, Dadnam, F, Davis, L, De Berker, H, Doyle, C, Fox, C, Gruffydd-Davies, M, Hafouda, Y, Hill, A, Hubbard, E, Hunter, A, Inpadhas, V, Jamshaid, M, Jandu, G, Jeyanthi, M, Kantor, C, Kwak, SY, Malik, N, Matt, R, McNulty, P, Miles, C, Mohomed, A, Myat, P, Niharika, J, Nixon, A, O‚ÄôReilly, D, Parmar, K, Pengelly, S, Price, L, Ramsden, M, Turnor, R, Wales, E, Waring, H, Wu, M, Yang, T, Ye, TTS, Zander, A, Zeicu, C, Bellam, S, Francombe, J, Kawamoto, N, Rahman, MR, Sathyanarayana, A, Tang, HT, Hollingshead, J, Page, V, Sugarman, J, Chiong, J, Fung, E, Kan, SY, Kiang, J, Kok, J, Krahelski, O, Liew, MY, Lyell, B, Sharif, Z, Speake, D, Alim, L, Amakye, NY, Chandrasekaran, J, Chandratreya, N, Drake, J, Owoso, T, Thu, YM, Abou El Ela Bourquin, B, Alberts, J, Chapman, D, Rehnnuma, N, Ainsworth, K, Carpenter, H, Emmanuel, T, Fisher, T, Gabrel, M, Guan, Z, Hollows, S, Hotouras, A, Ip Fung Chun, N, Jaffer, S, Kallikas, G, Lewinsohn, B, Liu, FY, Mohammed, S, Rutherfurd, A, Situ, T, Stammer, A, Taylor, F, Thin, N, Urgesi, E, Zhang, N, Ahmad, MA, Bishop, A, Bowes, A, Dixit, A, Glasson, R, Hatta, S, Hatt, K, Larcombe, S, Preece, J, Riordan, E, Fegredo, D, Haq, MZ, Li, C, McCann, G, Stewart, D, Baraza, W, Bhullar, D, Burt, G, Coyle, J, Deans, J, Devine, A, Hird, R, Ikotun, O, Manchip, G, Ross, C, Storey, L, Tan, WWL, Tse, C, Warner, C, Whitehead, M, Wu, F, Court, EL, Crisp, E, Huttman, M, Mayes, F, Robertson, H, Rosen, H, Sandberg, C, Al Bakry, M, Ashwell, W, Bajaj, S, Bandyopadhyay, D, Browlee, O, Burway, S, Chand, CP, Elsayeh, K, Elsharkawi, A, Evans, E, Ferrin, S, Fort-Schaale, A, Iacob, M, I, K, Impelliziere Licastro, G, Mankoo, AS, Olaniyan, T, Otun, J, Reddy, R, Saeed, D, Simmonds, O, Singhal, G, Tron, K, Wickstone, C, Williams, R, Bradshaw, E, De Kock Jewell, V, Knight, C, Metezai, H, Mirza-Davies, A, Spink, D, and Wischhusen, S

Published
2024
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20. Understanding the experiences of Black birthmothers who have had their child(ren) removed from their care

Author

Larcombe, Francesca

Subjects
black, ethnic minority, global majority, birthmothers, child removal, critical race theory, IPA, qualitative research
Abstract

Research on the experiences of birthmothers who have had their child(ren) removed from their care is scant. Of that which is available, the majority has focused on the experiences of White women. It is well understood that within the UK and internationally, Black children are over-represented in child protection systems when compared to their non-Black peers. Despite this, no research to date has focused on the specific experiences of Black birthmothers. This is in the context of well-known structural and systemic inequalities within the UK and child protection systems, leaving Black families at significant disadvantage. This qualitative study aimed to explore the experiences of Black birthmothers who have had their child(ren) removed from their care. Five women from across England participated in semi-structured interviews exploring how they have made sense of their child being removed; additionally, it sought to better understand potential impacts of their ethnicity on this process. Using Interpretive Phenomenological Analysis, four master themes were identified: ' (M)othering from the margins'; 'Birthmothers vs the state'; "If I looked like you ...": Navigating a racist system' and 'Finding the riverbank'. These themes reflect the recognised disadvantage of the birthmother population, as well as highlighting the additional deleterious impacts of 'race' and racism. Through a Critical Race Theory lens, areas of convergence and divergence with existing literature is identified, and further clinical and research implications discussed.

Published
2022
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21. Acquired uterine arteriovenous malformation—Does it really exist? A case report

Author

Josefina Larcombe, MD and Andrea Stuart, MD

Subjects
Arterial venous malformation, Ultrasound velocity, MRI, Hysterectomy, Invasive placenta disorder, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract

ABSTRACT: Acquired arteriovenous malformations (AVM) of the uterus can cause life-threatening vaginal bleeding and are associated with previous pregnancy, abortion or pelvic trauma. The pathophysiology is not well understood and the diagnosis is usually made by greyscale ultrasound often with nonspecific imaging findings, hence making it difficult to establish a correct diagnosis and therefore also the true incidence. However, case reports have previously described a connection between AVM formation and placental invasive disorders. In this report we demonstrate a case of a woman diagnosed with an AVM by ultrasound, presenting with menorrhagia after a termination of pregnancy, resulting in an emergency hysterectomy where subsequently a vascular malformation was found in conjunction with a remnant of a placenta increta and a placental site nodule. We hence suggest the hypothesis that these conditions are part of the same pathological process in the spectrum of abnormal invasive placental disorders, and that in the setting of previous trophoblastic processes, vascular malformations may mimic AVMs and ought not in fact to be considered as true AVMs.

Published
2023
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22. Multi-omics analysis of hospital-acquired diarrhoeal patients reveals biomarkers of enterococcal proliferation and Clostridioides difficile infection

Author

Marijana Bosnjak, Avinash V. Karpe, Thi Thu Hao Van, Despina Kotsanas, Grant A. Jenkin, Samuel P. Costello, Priscilla Johanesen, Robert J. Moore, David J. Beale, Yogitha N. Srikhanta, Enzo A. Palombo, Sarah Larcombe, and Dena Lyras

Subjects
Science
Abstract

Abstract Hospital-acquired diarrhoea (HAD) is common, and often associated with gut microbiota and metabolome dysbiosis following antibiotic administration. Clostridioides difficile is the most significant antibiotic-associated diarrhoeal (AAD) pathogen, but less is known about the microbiota and metabolome associated with AAD and C. difficile infection (CDI) with contrasting antibiotic treatment. We characterised faecal microbiota and metabolome for 169 HAD patients (33 with CDI and 133 non-CDI) to determine dysbiosis biomarkers and gain insights into metabolic strategies C. difficile might use for gut colonisation. The specimen microbial community was analysed using 16 S rRNA gene amplicon sequencing, coupled with untargeted metabolite profiling using gas chromatography-mass spectrometry (GC-MS), and short-chain fatty acid (SCFA) profiling using GC-MS. AAD and CDI patients were associated with a spectrum of dysbiosis reflecting non-antibiotic, short-term, and extended-antibiotic treatment. Notably, extended antibiotic treatment was associated with enterococcal proliferation (mostly vancomycin-resistant Enterococcus faecium) coupled with putative biomarkers of enterococcal tyrosine decarboxylation. We also uncovered unrecognised metabolome dynamics associated with concomitant enterococcal proliferation and CDI, including biomarkers of Stickland fermentation and amino acid competition that could distinguish CDI from non–CDI patients. Here we show, candidate metabolic biomarkers for diagnostic development with possible implications for CDI and vancomycin-resistant enterococci (VRE) treatment.

Published
2023
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23. A rapid semi-quantitative screening method to assess chemicals present in heated e-liquids and e-cigarette aerosols

Author

N. Anderson, P. Pringle, R. Mead-Hunter, B. Mullins, A. Larcombe, and S. Allard

Subjects
Medicine, Technology (General), T1-995
Abstract

​​​​​​​Electronic cigarettes (e-cigarettes) lack regulatory status as therapeutic products in all jurisdictions worldwide. They are potentially unsafe consumer products, with significant evidence they pose a risk to human health. Therefore, developing rapid, economical test methods to assess the chemical composition of e-liquids in heated and unheated forms and the aerosols produced by e-cigarettes is crucial. Four different e-liquids were heated using two different methods: (1) “typical” vaping using an e-cigarette device, by cycling “on” for 3 s every minute for 2 h (e-liquid obtained from remainder in the tank and aerosol collected in an impinger), and (2) “accelerated” heating, using an e-cigarette coil submerged in e-liquid and heating in short 20 s bursts on then 20 s off for 2 min only (liquid traps aerosol produced). All e-liquids were then analysed to test for the presence and quantity of 13 chemicals by gas chromatography–mass spectrometry and compared to an unheated sample. E-liquids heated with the accelerated method showed a comparable trend to the typical heating method, i.e. increase or decrease in chemical compound quantity, for more than two-thirds of the detected compounds analysed over all e-liquids. Six chemicals were detected as aerosol from the impinger fluid with the typical heating method at negligible levels. We propose that this accelerated version of the typical vaping method could form the basis of a standardized screening tool to test heated e-liquids (and e-cigarette aerosols) for harmful or banned substances. This will ensure that only approved products reach the consumer and reduce potential e-cigarette harm.

Published
2023
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25. Trophic facilitation in forest restoration: Can Nothofagus trees use ectomycorrhizal fungi of the pioneer shrub Leptospermum?

Author

Merissa Strawsine, Laura G. vanGalen, Janice M. Lord, and Matthew J. Larcombe

Subjects
facilitation, home soil advantage, mycorrhizal fungi, Myrtaceae, Nothofagaceae, restoration, Ecology, QH540-549.5
Abstract

Abstract The benefits of plant‐to‐plant facilitation in ecological restoration are well recognized, yet the potential for indirect trophic facilitation remains understudied. Nothofagus (southern beech; Nothofagaceae) is an iconic southern hemisphere tree genus that is frequently the focus of ecological restoration efforts. One aspect of Nothofagus ecology that may limit restoration success is the availability of appropriate ectomycorrhizal fungi. It has been suggested that pioneer dual‐mycorrhizal hosts such as Leptospermum species (Myrtaceae) could facilitate Nothofagus establishment by providing fungal inoculum, but the capacity for Nothofagus to use Leptospermum ectomycorrhizal fungi is unknown. To investigate potential indirect facilitation, we conducted a common garden pot trial to determine if Nothofagus cliffortioides (mountain beech) can use symbionts from Leptospermum scoparium (mānuka) ectomycorrhizal communities. Nothofagus and Leptospermum seedlings were grown in monoculture and mixed pairs with reciprocal “home” and “away” soil fungal inoculum. ITS2 metabarcoding of eDNA from hyphal ingrowth bags revealed that Nothofagus and Leptospermum inoculum contained different ectomycorrhizal fungal communities, but that half of the common ectomycorrhizal taxa identified were found in both soil types, suggesting generalist fungi exist. Nothofagus was able to form associations with some fungal species originating from Leptospermum inoculum, however, probable spore contamination meant that the proportion of root colonization associated with those species was ambiguous. Root ectomycorrhizal colonization rates were positively associated with seedling biomass, and there was some evidence of a home soil inoculum advantage in Nothofagus, but these effects were minor. Additionally, we found evidence that home inoculum provides a protective advantage against drought stress for Leptospermum seedlings. Our results indicate the potential for using Leptospermum to promote Nothofagus establishment in restoration plantings and highlight the possible benefits of considering fungal mutualists in ecological restoration projects.

Published
2024
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27. A study of adaptive prediction in Candida albicans

Author

Larcombe, Daniel E., MacCallum, Donna M., Brown, Alistair J. P., and Gow, Neil A. R.

Subjects
Candida albicans, Mycoses
Abstract

"Adaptive prediction" can evolve in microorganisms that repeatedly encounter the same two environmental stimuli in a conserved temporal order. Over an evolutionary timeframe, exposure to the first environmental condition can become associated with, and prime a response to, the second anticipated condition, thereby providing a fitness advantage. The opportunistic fungal pathogen Candida albicans has evolved anticipatory adaptive behaviours that increase virulence, immune evasion, and survival in the host. These behaviours reflect the environments where C. albicans has recently evolved, and examination of the pathways which regulate these adaptive responses have the potential to inform therapeutic strategies. Therefore, to help with the dissection of anticipatory responses, a fluorescence reporter system called the 'Rainbow System' was constructed. This system is designed to verify the order in which environmental conditions are temporally encountered by C. albicans in vivo. However, as discussed, further improvements are required before the system can be implemented. This study also examined one specific example of adaptive prediction in C. albicans. When this pathogen transits from the colon into the bloodstream it moves from a glucosefree niche to a glucose-containing environment where is likely to be attacked by circulating host phagocytes. Physiological levels of glucose enhance the resistance of C. albicans to oxidative stress and phagocytic killing. This glucose-enhanced oxidative stress resistance (GEXSR) is a likely example of adaptive prediction. C. albicans was shown to achieve this by accumulating the disaccharide stress protectant, trehalose, in response to glucose. This increase in trehalose accumulation, which appears to be controlled by the protein kinase A and glucose repression (AMPK) pathways, provides a significant fitness advantage during exposure to hydrogen peroxide in vitro and human neutrophils ex vivo. GEXSR might also promote host colonisation during systemic infection.

Published
2021

28. A CO2 sensing module modulates β-1,3-glucan exposure in Candida albicans

Author

Gabriela M. Avelar, Arnab Pradhan, Qinxi Ma, Emer Hickey, Ian Leaves, Corin Liddle, Alejandra V. Rodriguez Rondon, Ann-Kristin Kaune, Sophie Shaw, Corinne Maufrais, Natacha Sertour, Judith M. Bain, Daniel E. Larcombe, Leandro J. de Assis, Mihai G. Netea, Carol A. Munro, Delma S. Childers, Lars P. Erwig, Gordon D. Brown, Neil A. R. Gow, Marie-Elisabeth Bougnoux, Christophe d'Enfert, and Alistair J. P. Brown

Subjects
Candida albicans, pathogen-associated molecular patterns, β-glucan masking, carbonic anhydrase, NCE103, immune evasion, Microbiology, QR1-502
Abstract

ABSTRACT Microbial species capable of co-existing with healthy individuals, such as the commensal fungus Candida albicans, exploit multifarious strategies to evade our immune defenses. These strategies include the masking of immunoinflammatory pathogen-associated molecular patterns (PAMPs) at their cell surface. We reported previously that C. albicans actively reduces the exposure of the proinflammatory PAMP, β-1,3-glucan, at its cell surface in response to host-related signals such as lactate and hypoxia. Here, we show that clinical isolates of C. albicans display phenotypic variability with respect to their lactate- and hypoxia-induced β-1,3-glucan masking. We have exploited this variability to identify responsive and non-responsive clinical isolates. We then performed RNA sequencing on these isolates to reveal genes whose expression patterns suggested potential association with lactate- or hypoxia-induced β-1,3-glucan masking. The deletion of two such genes attenuated masking: PHO84 and NCE103. We examined NCE103-related signaling further because NCE103 has been shown previously to encode carbonic anhydrase, which promotes adenylyl cyclase-protein kinase A (PKA) signaling at low CO2 levels. We show that while CO2 does not trigger β-1,3-glucan masking in C. albicans, the Sch9-Rca1-Nce103 signaling module strongly influences β-1,3-glucan exposure in response to hypoxia and lactate. In addition to identifying a new regulatory module that controls PAMP exposure in C. albicans, our data imply that this module is important for PKA signaling in response to environmental inputs other than CO2.IMPORTANCEOur innate immune defenses have evolved to protect us against microbial infection in part via receptor-mediated detection of “pathogen-associated molecular patterns” (PAMPs) expressed by invading microbes, which then triggers their immune clearance. Despite this surveillance, many microbial species are able to colonize healthy, immune-competent individuals, without causing infection. To do so, these microbes must evade immunity. The commensal fungus Candida albicans exploits a variety of strategies to evade immunity, one of which involves reducing the exposure of a proinflammatory PAMP (β-1,3-glucan) at its cell surface. Most of the β-1,3-glucan is located in the inner layer of the C. albicans cell wall, hidden by an outer layer of mannan fibrils. Nevertheless, some β-1,3-glucan can become exposed at the fungal cell surface. However, in response to certain specific host signals, such as lactate or hypoxia, C. albicans activates an anticipatory protective response that decreases β-1,3-glucan exposure, thereby reducing the susceptibility of the fungus to impending innate immune attack. Here, we exploited the natural phenotypic variability of C. albicans clinical isolates to identify strains that do not display the response to β-1,3-glucan masking signals observed for the reference isolate, SC5314. Then, using genome-wide transcriptional profiling, we compared these non-responsive isolates with responsive controls to identify genes potentially involved in β-1,3-glucan masking. Mutational analysis of these genes revealed that a sensing module that was previously associated with CO2 sensing also modulates β-1,3-glucan exposure in response to hypoxia and lactate in this major fungal pathogen of humans.

Published
2024
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29. Using Expert Elicitation to Adjust Published Intervention Effects to Reflect the Local Context

Author

Jodi Gray, Tilenka R. Thynne, Vaughn Eaton, Rebecca Larcombe, Mahsa Tantiongco, and Jonathan Karnon

Subjects
Medicine (General), R5-920
Abstract

Background. Local health services make limited use of economic evaluation to inform decisions to fund new health service interventions. One barrier is the relevance of published intervention effects to the local setting, given these effects can strongly reflect the original evaluation context. Expert elicitation methods provide a structured approach to explicitly and transparently adjust published effect estimates, which can then be used in local-level economic evaluations to increase their local relevance. Expert elicitation was used to adjust published effect estimates for 2 interventions targeting the prevention of inpatient hypoglycemia. Methods. Elicitation was undertaken with 6 clinical experts. They were systematically presented with information regarding potential differences in patient characteristics and quality of care between the published study and local contexts, and regarding the design and application of the published study. The experts then assessed the intervention effects and provided estimates of the most realistic, most pessimistic, and most optimistic intervention effect sizes in the local context. Results. The experts estimated both interventions would be less effective in the local setting compared with the published effect estimates. For one intervention, the experts expected the lower complexity of admitted patients in the local setting would reduce the intervention’s effectiveness. For the other intervention, the reduced effect was largely driven by differences in the scope of implementation (hospital-wide in the local setting compared with targeted implementation in the evaluation). Conclusions. The pragmatic elicitation methods reported in this article provide a feasible and acceptable approach to assess and adjust published intervention effects to better reflect expected effects in the local context. Further development and application of these methods is proposed to facilitate the use of local-level economic evaluation. Highlights Local health services make limited use of economic evaluation to inform their decisions on the funding of new health service interventions. One barrier to use is the relevance of published intervention evaluations to the local setting. Expert elicitation methods provide a structured way to consider differences between the evaluation and local settings and to explicitly and transparently adjust published effect estimates for use in local economic evaluations. The pragmatic elicitation methods reported in this article offer a feasible and acceptable approach to adjusting published intervention effects to better reflect the effects expected in the local context. This increases the relevance of economic evaluations for local decision makers.

Published
2024
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30. Addressing the gap for racially diverse research involvement: The King's Model for minority ethnic research participant recruitment

Author

K. Ray Chaudhuri, A. Podlewska, Yue Hui Lau, C. Gonde, A. McIntosh, M.A. Qamar, S. O'Donoghue, K. Larcombe, M. Adeeko, A. Gupta, S. Bajwah, S. Lafond, O. Awogbemila, R. van Coller, A.M. Murtagh, and J.E. Ocloo

Subjects
Research participation, Ethnic minorities, Diversity, Inclusion, Public aspects of medicine, RA1-1270
Abstract

Objectives: Ethnic minorities (EM) are still underrepresented in research recruitment. Despite wide literature outlining the barriers, enablers and recommendations for driving inclusion and diversity in research, there is still little evidence for successful diversity in research participation, which has a direct impact on the quality of care provided to ethnically diverse individuals. A new, comprehensive approach to recruitment strategies is therefore necessary. Study design: service improvement initiative. Methods: In the light of the Covid-19 pandemic and the key public health need to address the disparity in care provided to non-white populations, we used a novel, comprehensive approach (The King's Model) comprising of local and community actions to promote inclusive research recruitment. We then compared rates of diverse recruitment in studies where the novel approach, was applied to studies which had been closed to recruitment at the time of analysis and where ethnicity data was available. Results: Our results demonstrate that following the introduction of the King's Model for diverse recruitment, commercial interventional study diverse recruitment increased from 6.4% to 16.1%, and for non-commercial studies, from 30.2% to 41.0% and 59.2% in the selected studies. Conclusions: King's Model is potentially a useful tool in enhancing non-Caucasian recruitment to clinical research. Enriched by additional recommendations based on our experiences during the Covid-19 research recruitment drive, we propose the King's Model is used to support ethnically diverse research recruitment. Further evidence is needed to replicate our findings, although this preliminary evidence provides granular details necessary to address the key unmet need of validating clinical research outcomes in non-white populations.

Published
2023
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31. A genomic survey of Clostridioides difficile isolates from hospitalized patients in Melbourne, Australia

Author

Sarah Larcombe, Galain C. Williams, Jacob Amy, Su Chen Lim, Thomas V. Riley, Anthony Muleta, Adele A. Barugahare, David R. Powell, Priscilla A. Johanesen, Allen C. Cheng, Anton Y. Peleg, and Dena Lyras

Subjects
Clostridioides difficile, hospital-acquired infection, whole-genome sequencing, genetic epidemiology, Microbiology, QR1-502
Abstract

ABSTRACT There has been a decrease in healthcare-associated Clostridioides difficile infection (CDI) in Australia, coupled with an increase in the genetic diversity of strains isolated in these settings, and an increase in community-associated cases. To explore this changing epidemiology, we studied the genetic relatedness of C. difficile isolated from patients at a major hospital in Melbourne, Australia. Whole-genome sequencing of C. difficile isolates from symptomatic (n = 61) and asymptomatic (n = 10) hospital patients was performed. Genomic comparisons were made using single-nucleotide polymorphism (SNP) analysis, ribotyping, and toxin, resistome, and mobilome profiling. C. difficle clade 1 strains were found to be predominant (64/71), with most strains (63/71) encoding both toxins A and B (A+B+). Despite these similarities, only two isolates were genetically related (≤2 SNPs) and a diverse range of ribotypes was detected, with those predominating including ribotypes commonly found in community-associated cases. Five non-toxigenic (A−B−CDT−) clade 1 strains were identified, all in asymptomatic patients. Three clade 4 (A−B+CDT−) and four clade 5 (A+B+CDT+) strains were detected also, with these strains more likely to carry antimicrobial resistance determinants, many of which were associated with mobile genetic elements. Overall, within a single hospital, C. difficile-associated disease was caused by a diverse range of strains, including many strain types associated with community and environmental sources. While strains carried asymptomatically were more likely to be non-toxigenic, toxigenic strains were isolated also from asymptomatic patients, which together suggest the presence of diverse sources of transmission, potentially including asymptomatic patients. IMPORTANCE There has been a decrease in healthcare-associated Clostridioides difficile infection in Australia, but an increase in the genetic diversity of infecting strains, and an increase in community-associated cases. Here, we studied the genetic relatedness of C. difficile isolated from patients at a major hospital in Melbourne, Australia. Diverse ribotypes were detected, including those associated with community and environmental sources. Some types of isolates were more likely to carry antimicrobial resistance determinants, and many of these were associated with mobile genetic elements. These results correlate with those of other recent investigations, supporting the observed increase in genetic diversity and prevalence of community-associated C. difficile, and consequently the importance of sources of transmission other than symptomatic patients. Thus, they reinforce the importance of surveillance for in both hospital and community settings, including asymptomatic carriage, food, animals, and other environmental sources to identify and circumvent important sources of C. difficile transmission.

Published
2023
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33. The Medicine Wheel: informing the management of tuberculosis outbreaks in Indigenous communities

Author

Pamela H. Orr, Kathleen McMullin, and Linda Larcombe

Subjects
Tuberculosis, health, culture, First Nations, traditional knowledge, knowledge translation, Arctic medicine. Tropical medicine, RC955-962
Abstract

ABSTRACTMany Indigenous communities in Canada experience endemic tuberculosis with superimposed periodic epidemic outbreaks. Failures in outbreak management have resulted in the “seeding” of future infection and disease. In this paper we present a model that may be used in planning, implementation and review of tuberculosis outbreak management in Cree Indigenous communities in Canada, based on the Medicine Wheel, a paradigm for holistic living. In the context of tuberculosis management, the Medicine Wheel provides a path for the establishment of respectful cross-cultural relationships, the expression of values through action, true community engagement and partnership, and the establishment of culture-based processes of transparency, accountability and change.

Published
2023
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35. How Can Universities Better Support the Mental Wellbeing of Higher Degree Research Students? A Study of Students' Suggestions

Author

Ryan, Tracii, Baik, Chi, and Larcombe, Wendy

Abstract

Prevalence studies indicate that higher degree research (Master's and Doctoral) students experience high rates of psychological distress. As a result, universities are seeking evidence-based interventions to better support the mental wellbeing of this student cohort. The present study contributes to that evidence base by asking higher degree research students (HDRs) from a large Australian research-intensive university what they think should be done to improve their wellbeing. After inductively analysing 595 open-ended survey responses, nine themes emerged. The four most prominent themes were culture and community, support services, supervisors and supervision practices, and peer engagement and networking. These themes are interpreted by drawing on the Job Demands-Resources theory of occupational stress. We also compare our findings with typologies of 'doctoral challenges' developed in prior research to extend and refine the 'roadmap' for policy, action and research to better understand and address the high levels of psychological distress that HDRs experience. Overall, the findings of this study suggest that HDRs are likely to benefit from a whole-of-university approach to supporting their wellbeing, and from an academic research culture that values the wellbeing of all its members.

Published
2022
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36. What Makes PhD Researchers Think Seriously about Discontinuing? An Exploration of Risk Factors and Risk Profiles

Author

Larcombe, Wendy, Ryan, Tracii, and Baik, Chi

Abstract

Although high PhD attrition rates are a matter of international concern, the factors that lead doctoral researchers to leave their programmes are not well understood. The present study addresses that issue by exploring factors that prompted thoughts of discontinuing among 1017 PhD researchers (PhDRs) at a public, research-intensive Australian university. We analyse the prevalence, strength and clustering of the most frequently identified factors, including mental health difficulties, financial pressures, and problems with supervision. The investigated factors were all strongly associated with thoughts of discontinuing; mental health difficulties were among the strongest factors, and financial stress was the most prevalent. An exploratory cluster analysis revealed that the risk factors co-present in distinctive ways such that six discrete groups of PhDRs are identifiable with varying risk profiles and socio-demographic characteristics. We discuss the research, policy and practice implications of these findings.

Published
2022
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37. Exploring Course Experiences That Predict Psychological Distress and Mental Wellbeing in Australian Undergraduate and Graduate Coursework Students

Author

Larcombe, Wendy, Baik, Chi, and Finch, Sue

Abstract

University students are known to be at heightened risk among their peers for experiencing psychological distress and mental health difficulties. To date, there have been few interventions designed to reduce stressors in the educational environment. This may be due to limited research investigating course-related correlates of students' distress. The present study addresses that gap by identifying and exploring the extent to which six common elements of coursework programmes predict students' scores on measures of depression, anxiety, stress, wellbeing and satisfaction with life. It finds that the investigated coursework experiences account for more variance in students' wellbeing scores than factors such as financial strain, worry about future employment, English language difficulties and minority group status. It is hoped these findings assist university course coordinators and academic educators to design and develop curricula, teaching approaches and learning environments likely to mitigate students' high levels of distress and actively support positive mental wellbeing.

Published
2022
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39. Diet choices : psychological impacts and influences

Author

Larcombe, Sam J.

Subjects
613.2, BF Psychology, GT Manners and customs, RA Public aspects of medicine, TX Home economics
Abstract

This research thesis further contributes to the understanding of both psychological influences on dietary choices and bodyweight status, and the impacts of diet interventions on psychological wellbeing. This thesis is split across three chapters, each outlined below: Chapter One A systematic review of the impacts of Mediterranean diet interventions on psychological wellbeing. Narrative synthesis within indicated that Mediterranean diet interventions may lead to a range of improvements in psychological wellbeing across clinical and non-clinical populations. Particular benefits on hedonic and eudaimonic psychological wellbeing are discussed. Clinical implications and future research directions are outlined. Chapter Two A research study examining the influence of implicit (relative to explicit) attitudes toward 'junk food', on habitual consumption of junk food and subsequent risk of overweight/obesity. Results suggested that implicit attitudes are significant and more powerful predictors of habitual consumption of junk food than explicit attitudes, and might influence risk of overweight/obesity. It is concluded that related interventions to improve public health may benefit from targeting implicit attitudes potentially influencing eating behaviours and habits. Chapter Three A personal reflective account of the process of conducting the research outlined in chapter one and two. A 'pragmatist reflective position' is broadly taken in order to aid learning from the research experiences. Following reflection across a range of topics within, numerous benefits to the role of clinical psychologist are highlighted and discussed.

Published
2020

40. Learning through an autonomous experience of art as a social practice

Author

Larcombe, Gavin

Subjects
707.1
Abstract

This practice-based research project is designed for artists who also work as teachers within a formal educational setting. It provides a practical methodology for those who wish to make art with students and would like to establish an alternative approach to learning. As a teacher of art, I believe it is important to continue practising as an artist as this can motivate and sustain a personal desire for learning. Through this, it is possible to inspire and instil a similar passion in the students. However, sustaining one's art practice, whilst fulfilling the requirements and responsibilities associated with teaching is not without its difficulties. To overcome this problem, I believe it is possible for the art teacher to regard their situation as a unique opportunity and consider their social interactions with students as a stimulus for making art. When developing my own art practice with students, I realised I would need to address questions relating to both ethics and aesthetics. This decision was made in response to the theoretical arguments of critics including, Nicolas Bourriaud, Claire Bishop and Grant Kester who frame the broader situation of art as a social practice. As a result, several pertinent questions arose, which would later inform my own practical experiments. • The activity of conversation often plays a necessary and valuable role when artists work with others. However, how can this activity be experienced as art and differentiated from other forms of social interaction? In other words, how do I distinguish my practice as art from the activity of teaching? In order to answer this question, I referred to the theoretical ideas of Jacques Rancière and Theodor Adorno. These ideas enabled me to recognise how the materials, methods and forms used by artists permit a variety of interpretation, enabling their work to be understood as art. In response, I sought to ensure my experiments when working with students would result in a physical artwork. This enabled the work to be partially judged in terms of its formal qualities and, therefore, distinguished as art. Although making a physical artwork with students proved valuable, I also needed to resolve the other important outcomes and educational benefits my methodology offered. As my research project progressed, further questions emerged. • When artists seek to work with other people there is a danger that cultural and educational inequalities are reiterated. This can involve the artist failing to recognise their own privileged position or acknowledge the differences of those invited to participate. Therefore, how does the artist as teacher negotiate this fraught social and educational process? In other words, what is the nature of my relationship with students? How does learning take place and what is being learnt? With further reference to Rancière I recognised how an overemphasis on the artist (teacher) or critic could limit one's ability to learn through art and could signal wider, social, educational and cultural inequalities. Rancière's solution to this problem involved a relationship based on absolute parity between the student and teacher. However, this approach to learning proved unrealistic in practice. In order to formulate a more pragmatic account of my working relationship with students I referred to my own practical experiments and the psychoanalytical ideas of Jacques Lacan. From this I was able to develop an alternative approach to learning through art. In practice this involved students being invited to take an active role in developing a curriculum. This curriculum often concerned a social issue, relevant and educationally significant to the students. When investigating this issue, students were trained to analyse appropriate information and texts in order to form their own opinions or arguments. In order to express these opinions through art, students were initially required to examine the way other artists create meaning through various methods and techniques. Examining these methods and techniques not only encouraged students to form their own interpretation of art but also provided inspiration when making their own artworks. As a result, I believe this approach represents a new method of teaching and making art with students. Through this methodology students gain a degree of control over their learning, reinforce critical literacy skills and develop an ability to interpret art, independent to that of the teacher. Equally this methodology provides an opportunity for the artist as teacher to learn with and be challenged by the students. As a result, a more realistic examination into the artist-student relationship occurs, thus influencing the artwork produced. Within the conclusion of this thesis a more detailed practical guide is provided for those wishing to adopt this methodology in the classroom.

Published
2020

41. Retrotransposon instability dominates the acquired mutation landscape of mouse induced pluripotent stem cells

Author

Patricia Gerdes, Sue Mei Lim, Adam D. Ewing, Michael R. Larcombe, Dorothy Chan, Francisco J. Sanchez-Luque, Lucinda Walker, Alexander L. Carleton, Cini James, Anja S. Knaupp, Patricia E. Carreira, Christian M. Nefzger, Ryan Lister, Sandra R. Richardson, Jose M. Polo, and Geoffrey J. Faulkner

Subjects
Science
Abstract

Retrotransposons are mobile genetic elements normally repressed by DNA methylation in differentiated cells. Here, the authors show that DNA hypomethylation in mouse induced pluripotent stem cells allows retrotransposons to jump, but this can be blocked with a reverse transcriptase inhibitor.

Published
2022
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42. Engineering a Dual Specificity γδ T-Cell Receptor for Cancer Immunotherapy

Author

David M. Davies, Giuseppe Pugliese, Ana C. Parente Pereira, Lynsey M. Whilding, Daniel Larcombe-Young, and John Maher

Subjects
γδ T-cell, Vγ9Vδ2 receptor, αvβ6 integrin, cancer, A20 peptide, foot and mouth disease virus, Biology (General), QH301-705.5
Abstract

γδ T-cells provide immune surveillance against cancer, straddling both innate and adaptive immunity. G115 is a clonal γδ T-cell receptor (TCR) of the Vγ9Vδ2 subtype which can confer responsiveness to phosphoantigens (PAgs) when genetically introduced into conventional αβ T-cells. Cancer immunotherapy using γδ TCR-engineered T-cells is currently under clinical evaluation. In this study, we sought to broaden the cancer specificity of the G115 γδ TCR by insertion of a tumour-binding peptide into the complementarity-determining region (CDR) three regions of the TCR δ2 chain. Peptides were selected from the foot and mouth disease virus A20 peptide which binds with high affinity and selectivity to αvβ6, an epithelial-selective integrin that is expressed by a range of solid tumours. Insertion of an A20-derived 12mer peptide achieved the best results, enabling the resulting G115 + A12 T-cells to kill both PAg and αvβ6-expressing tumour cells. Cytolytic activity of G115 + A12 T-cells against PAg-presenting K562 target cells was enhanced compared to G115 control cells, in keeping with the critical role of CDR3 δ2 length for optimal PAg recognition. Activation was accompanied by interferon (IFN)-γ release in the presence of either target antigen, providing a novel dual-specificity approach for cancer immunotherapy.

Published
2024
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45. Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity

Author

Huyghe, A., Furlan, G., Schroeder, J., Cascales, E., Trajkova, A., Ruel, M., Stüder, F., Larcombe, M., Yang Sun, Y. Bo, Mugnier, F., De Matteo, L., Baygin, A., Wang, J., Yu, Y., Rama, N., Gibert, B., Kielbassa, J., Tonon, L., Wajda, P., Gadot, N., Brevet, M., Siouda, M., Mulligan, P., Dante, R., Liu, P., Gronemeyer, H., Mendoza-Parra, M., Polo, J. M., and Lavial, F.

Published
2022
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47. Social and structural barriers and facilitators to HIV healthcare and harm reduction services for people experiencing syndemics in Manitoba: study protocol

Author

Linda Larcombe, Laurie Ireland, Ken Kasper, Yoav Keynan, Neora Pick, Michael Payne, Jared Bullard, Kathleen Deering, Julianne Sanguins, Katharina Maier, Andrea Krüsi, Zulma Vanessa Rueda, Margaret Haworth-Brockman, Cheryl Sobie, Enrique Villacis, Kimberly Templeton, Lauren MacKenzie, Tara Myran, and Adrienne Meyers

Subjects
Medicine
Abstract

Introduction In Manitoba, Canada, there has been an increase in the number of people newly diagnosed with HIV and those not returning for regular HIV care. The COVID-19 pandemic resulted in increased sex and gender disparities in disease risk and mortalities, decreased harm reduction services and reduced access to healthcare. These health crises intersect with increased drug use and drug poisoning deaths, houselessness and other structural and social factors most acutely among historically underserved groups. We aim to explore the social and structural barriers and facilitators to HIV care and harm reduction services experienced by people living with HIV (PLHIV) in Manitoba.Methods and analysis Our study draws on participatory action research design. Guiding the methodological design are the lived experiences of PLHIV. In-depth semi-structured face-to-face interviews and quantitative questionnaires will be conducted with two groups: (1) persons aged ≥18 years living or newly diagnosed with HIV and (2) service providers who work with PLHIV. Data collection will include sex, gender, sociodemographic information, income and housing, experiences with the criminal justice system, sexual practices, substance use practices and harm reduction access, experiences with violence and support, HIV care journey (since diagnosis until present), childhood trauma and a decision-making questionnaire. Data will be analysed intersectionally, employing grounded theory for thematic analysis, sex-based and gender-based analysis and social determinants of health and syndemic framework to understand the experiences of PLHIV in Manitoba.Ethics and dissemination We received approval from the University of Manitoba Health Ethics Research Board (HS25572; H2022:218), First Nations Health and Social Secretariat of Manitoba, Nine Circles Community Health Centre, Shared Health Manitoba (SH2022:194) and 7th Street Health Access Centre. Findings will be disseminated using community-focused knowledge translation strategies identified by participants, peers, community members and organisations, and reported in conferences, peer-reviewed journals and a website (www.alltogether4ideas.org).

Published
2023
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49. Randomised controlled trial comparing the clinical and cost-effectiveness of various washout policies versus no washout policy in preventing catheter associated complications in adults living with long-term catheters: study protocol for the CATHETER II study

Author

Mohamed Abdel-fattah, Diana Johnson, Lynda Constable, Ruth Thomas, Seonaidh Cotton, Sheela Tripathee, David Cooper, Sue Boran, Konstantinos Dimitropoulos, Suzanne Evans, Paraskeve Granitsiotis, Hashim Hashim, Mary Kilonzo, James Larcombe, Paul Little, Sara MacLennan, Peter Murchie, Phyo Kyaw Myint, James N’Dow, John Norrie, Muhammad Imran Omar, Catherine Paterson, Graham Scotland, Nikesh Thiruchelvam, and Graeme MacLennan

Subjects
Catheter blockage, Catheter washout solutions, Catheter maintenance solutions, Indwelling catheter, Long-term catheter, Symptomatic catheter-associated urinary tract infection, Medicine (General), R5-920
Abstract

Abstract Background Various washout policies are widely used in adults living with long-term catheters (LTC). There is currently insufficient evidence on the benefits and potential harms of prophylactic LTC washout policies in the prevention of blockages and other LTC-related adverse events, such as urinary tract infections. CATHETER II tests the hypothesis that weekly prophylactic LTC washouts (normal saline or citric acid) in addition to standard LTC care reduce the incidence of catheter blockage requiring intervention compared to standard LTC care only in adults living with LTC. Methods CATHETER II is a pragmatic three-arm open multi-centre superiority randomised controlled trial with an internal pilot, economic analysis, and embedded qualitative study. Eligible participants are adults aged ≥ 18 years, who have had a LTC in use for ≥ 28 days, have no plans to discontinue the use of the catheter, are able to undertake the catheter washouts, and complete trial documentation or have a carer able to help them. Participants are identified from general practitioner practices, secondary/tertiary care, community healthcare, care homes, and via public advertising strategies. Participants are randomised 1:1:1 to receive a weekly saline (0.9%) washout in addition to standard LTC care, a weekly citric acid (3.23%) washout in addition to standard LTC care or standard LTC care only. Participants and/or carers will receive training to administer the washouts. Patient-reported outcomes are collected at baseline and for 24 months post-randomisation. The primary clinical outcome is catheter blockage requiring intervention up to 24 months post-randomisation expressed per 1000 catheter days. Secondary outcomes include symptomatic catheter-associated urinary tract infection requiring antibiotics, catheter change, adverse events, NHS/ healthcare use, and impact on quality of life. Discussion This study will guide treatment decision-making and clinical practice guidelines regarding the effectiveness of various prophylactic catheter washout policies in men and women living with LTC. This research has received ethical approval from Wales Research Ethics Committee 6 (19/WA/0015). Trial registration ISRCTN ISRCTN17116445 . Registered prospectively on 06 November 2019

Published
2022
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