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2. Recent advances in 3D bioprinted tumor models for personalized medicine

Author

Gnatowski, P. (Przemysław), Piłat, E. (Edyta), Kucińska-Lipka, J. (Justyna), Saeb, M. R. (Mohammad Reza), Hamblin, M. R. (Michael R), Mozafari, M. (Masoud), Gnatowski, P. (Przemysław), Piłat, E. (Edyta), Kucińska-Lipka, J. (Justyna), Saeb, M. R. (Mohammad Reza), Hamblin, M. R. (Michael R), and Mozafari, M. (Masoud)

Abstract

Cancerous tumors are among the most fatal diseases worldwide, claiming nearly 10 million lives in 2020. Due to their complex and dynamic nature, modeling tumors accurately is a challenging task. Current models suffer from inadequate translation between in vitro and in vivo results, primarily due to the isotropic nature of tumors and their microenvironment’s relationship. To address these limitations, hydrogel-based 3D bioprinting is emerging as a promising approach to mimic cancer development and behavior. It provides precise control over individual elements’ size and distribution within the cancer microenvironment and enables the use of patient-derived tumor cells, rather than commercial lines. Consequently, hydrogel bioprinting is expected to become a state-of-the-art technique for cancer research. This manuscript presents an overview of cancer statistics, current modeling methods, and their limitations. Additionally, we highlight the significance of bioprinting, its applications in cancer modeling, and the importance of hydrogel selection. We further explore the current state of creating models for the five deadliest cancers using 3D bioprinting. Finally, we discuss current trends and future perspectives on the clinical use of cancer modeling using hydrogel bioprinting.

Published
2023

3. Ziritaxestat, a novel autotaxin inhibitor, and lung function in idiopathic pulmonary fibrosis

Author

Maher, TM, Ford, P, Brown, KK, Costabel, U, Cottin, V, Danoff, SK, Groenveld, I, Helmer, E, Jenkins, RG, Milner, J, Molenberghs, G, Penninckx, B, Randall, MJ, Van Den Blink, B, Fieuw, A, Vandenrijn, C, Rocak, S, Seghers, I, Shao, L, Taneja, A, Jentsch, G, Watkins, TR, Wuyts, WA, Kreuter, M, Verbruggen, N, Prasad, N, Wijsenbeek, MS, Chambers, D, Chia, M, Corte, T, Glaspole, I, Goh, N, Holmes, M, Malouf, M, Thien, F, Veitch, E, Bondue, B, Dahlqvist, C, Froidure, A, Slabbynck, H, Wuyts, W, Cartagena Salinas, C, Feijoó Seoane, R, Martínez, V, Maturana, R, Pavie Gallegos, J, Rosenblut, A, Silva, R, Undurraga Pereira, A, Doubkova, M, Pauk, N, Plackova, M, Sterclova, M, Bendstrup, E, Shaker, SB, Titlestad, I, Budweiser, S, Grohé, C, Koschel, D, Prasse, A, Weber, M, Wirtz, H, Antoniou, K, Daniil, Z, Gaga, M, Papakosta, D, Izumi, S, Okamoto, M, Guerreros Benavides, A, Iberico Barrera, C, Peña Villalobos, AM, Campo Ezquibela, A, Cifrian Martinez, JM, Fernandez Fabrellas, E, Leiro, V, Molina-Molina, M, Nieto Barbero, A, Sellares Torres, J, Valenzuela, C, Cheng, S-L, Kuo, P-H, Lee, K-Y, Sheu, C-C, Gunen, H, Mogulkoc Bishop, N, Nayci, S, Adamali, H, Bianchi, S, Chaudhuri, N, Gibbons, M, Hart, S, Molyneaux, P, Parfrey, H, Saini, G, Spencer, LG, Wiscombe, S, Antin-Ozerkis, D, Bascom, R, Belperio, J, Britt, E, Fitzgerald, J, Gomez Manjarres, D, Gotfried, M, Gupta, N, Hotchkin, D, Kaye, M, Kreider, M, Kureishy, S, Lacamera, P, Lancaster, L, Lasky, J, Lorch, D, Mannem, H, Morrow, L, Moua, T, Nambiar, A, Raghu, G, Raj, R, Ramaswamy, M, Reddy, R, Russell, T, Scholand, MB, Shea, B, Suliman, S, Swigris, J, Thavarajah, K, Tolle, L, Tomic, R, Warshoff, N, Wesselius, L, Yung, G, Bergna, M, De Salvo, M, Fernandez Acquier, M, Rodriguez, A, Saez Scherbovsky, P, Assayag, D, Dhar, A, Khalil, N, Morisset, J, Provencher, S, Ryerson, C, Shapera, S, Bourdin, A, Crestani, B, Lebargy, F, Reynaud-Gaubert, M, Bonella, FT, Claussen, M, Hammerl, P, Karagiannidis, C, Keller, C, Randerath, W, Stubbe, B, Csánky, E, Medgyasszay, B, Muller, V, Adir, Y, Bar-Shai, A, Berkman, N, Fink, G, Kramer, M, Shitrit, D, Bargagli, E, Gasparini, S, Harari, S, Ravaglia, C, Richeldi, L, Vancheri, C, Ebina, M, Fujita, M, Ichikado, K, Inoue, Y, Ishikawa, N, Kato, M, Kawamura, T, Kondoh, Y, Nishioka, Y, Ogura, T, Owan, I, Saito, T, Sakamoto, N, Sakamoto, K, Shirai, M, Suda, T, Tomii, K, Chung, MP, Jeong, SH, Park, CS, Park, JS, Song, JW, Uh, S-T, Chavarria Martinez, U, Montano Gonzalez, E, Ramirez, A, Selman Lama, ME, Bresser, P, Kramer, H, Mostard, R, Nossent, E, Veltkamp, M, Wijsenbeek, M, Beckert, L, Chang, CL, Veale, A, Wilsher, M, Bednarek, M, Gasior, G, Jasieniak-Pinis, G, Jassem, E, Mroz, R, Piotrowski, W, Abdullah, I, Ambaram, A, Irusen, E, Van der Linden, M, Van Zyl-Smit, R, Williams, P, Allen, J, Averill, F, Belloli, E, Brown, A, Case, A, Chaudhary, S, Criner, G, DeBoer, K, Dilling, D, Dorf, J, Enelow, R, Ettinger, N, Feldman, J, Gibson, K, Golden, J, Hamblin, M, Hunninghake, G, Karunakara, R, Kim, H, Luckhardt, T, Menon, P, Morrison, L, Oldham, J, Patel, N, Schmidt, S, Strek, M, Summer, R, Sussman, R, Tita, J, Veeraraghavan, S, Whelan, T, and Zibrak, J

Abstract

Importance There is a major need for effective, well-tolerated treatments for idiopathic pulmonary fibrosis (IPF). Objective To assess the efficacy and safety of the autotaxin inhibitor ziritaxestat in patients with IPF. Design, Setting, and Participants The 2 identically designed, phase 3, randomized clinical trials, ISABELA 1 and ISABELA 2, were conducted in Africa, Asia-Pacific region, Europe, Latin America, the Middle East, and North America (26 countries). A total of 1306 patients with IPF were randomized (525 patients at 106 sites in ISABELA 1 and 781 patients at 121 sites in ISABELA 2). Enrollment began in November 2018 in both trials and follow-up was completed early due to study termination on April 12, 2021, for ISABELA 1 and on March 30, 2021, for ISABELA 2. Interventions Patients were randomized 1:1:1 to receive 600 mg of oral ziritaxestat, 200 mg of ziritaxestat, or placebo once daily in addition to local standard of care (pirfenidone, nintedanib, or neither) for at least 52 weeks. Main Outcomes and Measures The primary outcome was the annual rate of decline for forced vital capacity (FVC) at week 52. The key secondary outcomes were disease progression, time to first respiratory-related hospitalization, and change from baseline in St George’s Respiratory Questionnaire total score (range, 0 to 100; higher scores indicate poorer health-related quality of life). Results At the time of study termination, 525 patients were randomized in ISABELA 1 and 781 patients in ISABELA 2 (mean age: 70.0 [SD, 7.2] years in ISABELA 1 and 69.8 [SD, 7.1] years in ISABELA 2; male: 82.4% and 81.2%, respectively). The trials were terminated early after an independent data and safety monitoring committee concluded that the benefit to risk profile of ziritaxestat no longer supported their continuation. Ziritaxestat did not improve the annual rate of FVC decline vs placebo in either study. In ISABELA 1, the least-squares mean annual rate of FVC decline was –124.6 mL (95% CI, −178.0 to −71.2 mL) with 600 mg of ziritaxestat vs –147.3 mL (95% CI, −199.8 to −94.7 mL) with placebo (between-group difference, 22.7 mL [95% CI, −52.3 to 97.6 mL]), and –173.9 mL (95% CI, −225.7 to −122.2 mL) with 200 mg of ziritaxestat (between-group difference vs placebo, −26.7 mL [95% CI, −100.5 to 47.1 mL]). In ISABELA 2, the least-squares mean annual rate of FVC decline was –173.8 mL (95% CI, −209.2 to −138.4 mL) with 600 mg of ziritaxestat vs –176.6 mL (95% CI, −211.4 to −141.8 mL) with placebo (between-group difference, 2.8 mL [95% CI, −46.9 to 52.4 mL]) and –174.9 mL (95% CI, −209.5 to −140.2 mL) with 200 mg of ziritaxestat (between-group difference vs placebo, 1.7 mL [95% CI, −47.4 to 50.8 mL]). There was no benefit with ziritaxestat vs placebo for the key secondary outcomes. In ISABELA 1, all-cause mortality was 8.0% with 600 mg of ziritaxestat, 4.6% with 200 mg of ziritaxestat, and 6.3% with placebo; in ISABELA 2, it was 9.3% with 600 mg of ziritaxestat, 8.5% with 200 mg of ziritaxestat, and 4.7% with placebo. Conclusions and Relevance Ziritaxestat did not improve clinical outcomes compared with placebo in patients with IPF receiving standard of care treatment with pirfenidone or nintedanib or in those not receiving standard of care treatment. Trial Registration ClinicalTrials.gov Identifiers: NCT03711162 and NCT03733444

Published
2023

6. Plasma proteomic signature predicts who will get persistent symptoms following SARS-CoV-2 infection

Author

Captur, G, Moon, JC, Topriceanu, C-C, Joy, G, Swadling, L, Hallqvist, J, Doykov, I, Patel, N, Spiewak, J, Baldwin, T, Hamblin, M, Menacho, K, Fontana, M, Treibel, TA, Manisty, C, O'Brien, B, Gibbons, JM, Pade, C, Brooks, T, Altmann, DM, Boyton, RJ, McKnight, Á, Maini, MK, Noursadeghi, M, Mills, K, Heywood, WE, UK COVIDsortium Investigators, and Medical Research Council (MRC)

Subjects
Adult, Male, Proteomics, Proteome, SARS-CoV-2, COVID-19, 1103 Clinical Sciences, General Medicine, Middle Aged, General Biochemistry, Genetics and Molecular Biology, 1117 Public Health and Health Services, Pharmaceutical Preparations, Case-Control Studies, Post-acute sequelae of SARS-CoV-2 (PASC), Humans, Female, UK COVIDsortium Investigators
Abstract

BACKGROUND: The majority of those infected by ancestral Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) during the UK first wave (starting March 2020) did not require hospitalisation. Most had a short-lived mild or asymptomatic infection, while others had symptoms that persisted for weeks or months. We hypothesized that the plasma proteome at the time of first infection would reflect differences in the inflammatory response that linked to symptom severity and duration. METHODS: We performed a nested longitudinal case-control study and targeted analysis of the plasma proteome of 156 healthcare workers (HCW) with and without lab confirmed SARS-CoV-2 infection. Targeted proteomic multiple-reaction monitoring analysis of 91 pre-selected proteins was undertaken in uninfected healthcare workers at baseline, and in infected healthcare workers serially, from 1 week prior to 6 weeks after their first confirmed SARS-CoV-2 infection. Symptom severity and antibody responses were also tracked. Questionnaires at 6 and 12 months collected data on persistent symptoms. FINDINGS: Within this cohort (median age 39 years, interquartile range 30-47 years), 54 healthcare workers (44% male) had PCR or antibody confirmed infection, with the remaining 102 (38% male) serving as uninfected controls. Following the first confirmed SARS-CoV-2 infection, perturbation of the plasma proteome persisted for up to 6 weeks, tracking symptom severity and antibody responses. Differentially abundant proteins were mostly coordinated around lipid, atherosclerosis and cholesterol metabolism pathways, complement and coagulation cascades, autophagy, and lysosomal function. The proteomic profile at the time of seroconversion associated with persistent symptoms out to 12 months. Data are available via ProteomeXchange with identifier PXD036590. INTERPRETATION: Our findings show that non-severe SARS-CoV-2 infection perturbs the plasma proteome for at least 6 weeks. The plasma proteomic signature at the time of seroconversion has the potential to identify which individuals are more likely to suffer from persistent symptoms related to SARS-CoV-2 infection. FUNDING INFORMATION: The COVIDsortium is supported by funding donated by individuals, charitable Trusts, and corporations including Goldman Sachs, Citadel and Citadel Securities, The Guy Foundation, GW Pharmaceuticals, Kusuma Trust, and Jagclif Charitable Trust, and enabled by Barts Charity with support from University College London Hospitals (UCLH) Charity. This work was additionally supported by the Translational Mass Spectrometry Research Group and the Biomedical Research Center (BRC) at Great Ormond Street Hospital.

Published
2022

7. Macrophage Cell Membrane-Cloaked Nanoplatforms for Biomedical Applications

Author

Lopes, J, Lopes, D, Pereira-Silva, M, Peixoto, D, Veiga, F, Hamblin, M, Conde, J, Corbo, C, Zare, E, Ashrafizadeh, M, Tay, F, Chen, C, Donnelly, R, Wang, X, Makvandi, P, Paiva-Santos, A, Lopes, Joana, Lopes, Daniela, Pereira-Silva, Miguel, Peixoto, Diana, Veiga, Francisco, Hamblin, Michael R, Conde, João, Corbo, Claudia, Zare, Ehsan Nazarzadeh, Ashrafizadeh, Milad, Tay, Franklin R, Chen, Chengshui, Donnelly, Ryan F, Wang, Xiangdong, Makvandi, Pooyan, Paiva-Santos, Ana Cláudia, Lopes, J, Lopes, D, Pereira-Silva, M, Peixoto, D, Veiga, F, Hamblin, M, Conde, J, Corbo, C, Zare, E, Ashrafizadeh, M, Tay, F, Chen, C, Donnelly, R, Wang, X, Makvandi, P, Paiva-Santos, A, Lopes, Joana, Lopes, Daniela, Pereira-Silva, Miguel, Peixoto, Diana, Veiga, Francisco, Hamblin, Michael R, Conde, João, Corbo, Claudia, Zare, Ehsan Nazarzadeh, Ashrafizadeh, Milad, Tay, Franklin R, Chen, Chengshui, Donnelly, Ryan F, Wang, Xiangdong, Makvandi, Pooyan, and Paiva-Santos, Ana Cláudia

Abstract

Biomimetic approaches utilize natural cell membrane-derived nanovesicles to camouflage nanoparticles to circumvent some limitations of nanoscale materials. This emergent cell membrane-coating technology is inspired by naturally occurring intercellular interactions, to efficiently guide nanostructures to the desired locations, thereby increasing both therapeutic efficacy and safety. In addition, the intrinsic biocompatibility of cell membranes allows the crossing of biological barriers and avoids elimination by the immune system. This results in enhanced blood circulation time and lower toxicity in vivo. Macrophages are the major phagocytic cells of the innate immune system. They are equipped with a complex repertoire of surface receptors, enabling them to respond to biological signals, and to exhibit a natural tropism to inflammatory sites and tumorous tissues. Macrophage cell membrane-functionalized nanosystems are designed to combine the advantages of both macrophages and nanomaterials, improving the ability of those nanosystems to reach target sites. Recent studies have demonstrated the potential of these biomimetic nanosystems for targeted delivery of drugs and imaging agents to tumors, inflammatory, and infected sites. The present review covers the preparation and biomedical applications of macrophage cell membrane-coated nanosystems. Challenges and future perspectives in the development of these membrane-coated nanosystems are addressed.

Published
2022

10. Transcriptomic and proteomic profile approaches toward drought and salinity stresses.

Author

GOHARRIZI, K. JAMSHIDI, KARAMI, S., HAMBLIN, M. R., MOMENI, M. M., BASAKI, T., DEHNAVI, M. MOSTAFAEI, and NAZARI, M.

Subjects
DROUGHT tolerance, IONIC equilibrium, DROUGHT management, SALINITY, PLANT breeding, DROUGHTS, PROTEOMICS
Abstract

Drought and salinity, which can alter the water balance, disrupt the ionic equilibrium, and create reactive oxygen species (ROS), are capable of destroying plant tissues. In this study, transcriptomics, proteomics, and metabolomics have been used to elucidate various abiotic stress responses. In transcriptional signaling pathways, abscisic acid (ABA) is one of the plant phytohormones that regulate the stress response. On the other hand, several regulons and factors of transcription contributed in the reaction to osmotic stresses, as well as in ABA-dependent/independent signaling pathways. However, the findings display that intricate molecular reaction of plants under stress conditions may be controlled by complicated regulative networks of gene expression and signal transduction, as well as by the interaction between them. From the point of view of proteomics, protein modifications in response to stress can be considered as a molecular tool to improve the resistance of plants to environmental stresses. These studies have provided new information about the significance of several gene and protein networks involved in the response of plants to salinity and drought, and the induction of tolerance. Moreover, identifying the crucial pathways which are involved in salinity and drought resistance can open doors for the establishment of commercial-resistant crop cultivars, and might be very useful in the next-generation crop breeding strategies to produce plants with salinity and drought-resistant traits. [ABSTRACT FROM AUTHOR]

Published
2023
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16. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease

Author

Distler, O, Highland, Kb, Gahlemann, M, Azuma, A, Fischer, A, Mayes, Md, Raghu, G, Sauter, W, Girard, M, Alves, M, Clerisme-Beaty, E, Stowasser, S, Tetzlaff, K, Kuwana, M, Maher, Tm, Bergna, M, Casado, G, Mannucci Walter, P, Proudman, S, Stevens, W, Thakkar, V, Troy, L, Loeffler-Ragg, J, Olschewski, H, Bondue, B, Houssiau, F, Smith, V, Wuyts, W, Johnson, S, Keystone, E, Khalidi, N, Levesque, M, Maturana Rozas, R, Silva Orellana, A, Huang, C, Li, J, Jiang, Z, Liu, Y, Xiao, W, Xu, J, Zeng, X, Zheng, Y, Zou, H, Becvar, R, Madsen, H, Søndergaard, K, Kilpeläinen, M, Myllärniemi, M, Agard, C, Allanore, Y, Bourdin, A, Cottin, V, Crestani, B, Diot, E, Dominique, S, Hachulla, E, Jouneau, S, Leroy, S, Nunes, H, Prevot, G, Wallaert, B, Wemeau, L, Aringer, M, Bewig, B, Blaas, S, Distler, J, Ehrchen, J, Ewert, R, Gläser, S, Henes, J, Hunzelmann, N, König, R, Kötter, I, Kreuter, M, Prasse, A, Schulze-Koops, H, Sfikakis, P, Vlachoyiannopoulos, P, Losonczy, G, Behera, D, Gayathri Devi HJ, Kadel, J, Kawedia, M, Kumar, D, Kumar, U, Lokhande, R, Malpani, A, Mohan, M, Nalawade, A, Parakh, U, Swarnakar, R, Shobha, V, Thangakunam, B, Udwadia, Z, Henry, M, O'Reilly, K, Balbir-Gurman, A, Kramer, M, Litinsky, I, Rosner, I, Cutolo, M, Gabrielli, A, Iaccarino, L, Pesci, A, Riccieri, V, Vettori, S, Funakubo, Y, Inoue, Y, Kawakami, A, Kawaguchi, Y, Kawamura, T, Kondoh, Y, Nanki, T, Nishioka, Y, Nozawa, K, Oguragawa, T, Okamoto, M, Sano, H, Sasai, R, Sasaki, N, Suda, T, Takahashi, H, Takeuchi, T, Tanaka, S, Yamasaki, Y, Ch'Ng, Ss, Cheah, C, Kan, S, Raja Mohamed RB, Selman, M, de Vries-Bouwstra JK, van den Toorn, L, Vonken, M, Voskuyl, Ae, Hoffmann-Vold, Am, Seip, M, Dankiewicz-Fares, I, Olesiejuk, R, Pulka, G, Szepietowski, J, Alves, J, Bernardes, M, Cordeiro, A, Costa, J, Neves, S, Salvador, Mj, Alegre Sancho, J, Carreira Delgado, P, Castellví Barranco, I, Cifrián Martínez, J, Guillén Del Castillo, A, Ovalles, Jg, López-Longo, Fj, Rivera Gallego, A, Freire Dapena MC, Román Ivorra JA, Ekwall, Ah, Maurer, B, Mihai, Cm, Müller, R, Mahakkanukrauh, A, Nantiruj, K, Siripaitoon, B, Denton, Cp, Herrick, A, Madhok, R, West, A, Bascom, R, Criner, G, Csuka, Me, Dematte D'Amico, J, Ettinger, N, Gerbino, A, Gerke, A, Glassberg, M, Glazer, C, Golden, J, Gripaldo, R, Gupta, N, Hamblin, M, Highland, K, Ho, L, Huggins, Jt, Hummers, L, Jones, L, Kahaleh, M, Khanna, D, Kim, H, Lancaster, Lh, Luckhardt, T, Mayes, M, Mendoza Ballesteros, F, Mooney, J, Mohabir, P, Morrissey, B, Moua, T, Padilla, M, Patel, N, Perez, R, Roman, J, Rossman, M, Russell, T, Saketkoo, L, Shah, A, Shlobin, O, Scholand, Mb, Simmssetts, R, Spiera, R, Steen, V, Veeraraghavan, S, Weigt, S., Distler, O, Highland, Kb, Gahlemann, M, Azuma, A, Fischer, A, Mayes, Md, Raghu, G, Sauter, W, Girard, M, Alves, M, Clerisme-Beaty, E, Stowasser, S, Tetzlaff, K, Kuwana, M, Maher, Tm, SENSCIS Trial Investigators., Bergna M, Casado, G, Mannucci Walter, P, Proudman, S, Stevens, W, Thakkar, V, Troy, L, Loeffler-Ragg, J, Olschewski, H, Bondue, B, Houssiau, F, Smith, V, Wuyts, W, Johnson, S, Keystone, E, Khalidi, N, Levesque, M, Maturana Rozas, R, Silva Orellana, A, Huang, C, Li, J, Jiang, Z, Liu, Y, Xiao, W, Xu, J, Zeng, X, Zheng, Y, Zou, H, Becvar, R, Madsen, H, Søndergaard, K, Kilpeläinen, M, Myllärniemi, M, Agard, C, Allanore, Y, Bourdin, A, Cottin, V, Crestani, B, Diot, E, Dominique, S, Hachulla, E, Jouneau, S, Leroy, S, Nunes, H, Prevot, G, Wallaert, B, Wemeau, L, Aringer, M, Bewig, B, Blaas, S, Distler, J, Ehrchen, J, Ewert, R, Gläser, S, Henes, J, Hunzelmann, N, König, R, Kötter, I, Kreuter, M, Prasse, A, Schulze-Koops, H, Sfikakis, P, Vlachoyiannopoulos, P, Losonczy, G, Behera, D, Gayathri Devi, Hj, Kadel, J, Kawedia, M, Kumar, D, Kumar, U, Lokhande, R, Malpani, A, Mohan, M, Nalawade, A, Parakh, U, Swarnakar, R, Shobha, V, Thangakunam, B, Udwadia, Z, Henry, M, O'Reilly, K, Balbir-Gurman, A, Kramer, M, Litinsky, I, Rosner, I, Cutolo, M, Gabrielli, A, Iaccarino, Laura, Pesci, A, Riccieri, V, Vettori, S, Funakubo, Y, Inoue, Y, Kawakami, A, Kawaguchi, Y, Kawamura, T, Kondoh, Y, Nanki, T, Nishioka, Y, Nozawa, K, Oguragawa, T, Okamoto, M, Sano, H, Sasai, R, Sasaki, N, Suda, T, Takahashi, H, Takeuchi, T, Tanaka, S, Yamasaki, Y, Ch'Ng, S, Cheah, C, Kan, S, Raja Mohamed, Rb, Selman, M, de Vries-Bouwstra, Jk, van den Toorn, L, Vonken, M, Voskuyl, Ae, Hoffmann-Vold, Am, Seip, M, Dankiewicz-Fares, I, Olesiejuk, R, Pulka, G, Szepietowski, J, Alves, J, Bernardes, M, Cordeiro, A, Costa, J, Neves, S, Salvador, Mj, Alegre Sancho, J, Carreira Delgado, P, Castellví Barranco, I, Cifrián Martínez, J, Guillén Del Castillo, A, Ovalles, Jg, López-Longo, Fj, Rivera Gallego, A, Freire Dapena, Mc, Román Ivorra, Ja, Ekwall, Ah, Maurer, B, Mihai, Cm, Müller, R, Mahakkanukrauh, A, Nantiruj, K, Siripaitoon, B, Denton, Cp, Herrick, A, Madhok, R, West, A, Bascom, R, Criner, G, Csuka, Me, Dematte D'Amico, J, Ettinger, N, Gerbino, A, Gerke, A, Glassberg, M, Glazer, C, Golden, J, Gripaldo, R, Gupta, N, Hamblin, M, Highland, K, Ho, L, Huggins, Jt, Hummers, L, Jones, L, Kahaleh, M, Khanna, D, Kim, H, Lancaster, Lh, Luckhardt, T, Mayes, M, Mendoza Ballesteros, F, Mooney, J, Mohabir, P, Morrissey, B, Moua, T, Padilla, M, Patel, N, Perez, R, Roman, J, Rossman, M, Russell, T, Saketkoo, L, Shah, A, Shlobin, O, Scholand, Mb, Simmssetts, R, Spiera, R, Steen, V, Veeraraghavan, S, Weigt, S., National Institute for Health Research, British Lung Foundation, University of Zurich, and Distler, Oliver

Subjects
Male, Vital capacity, Indoles, Vital Capacity, Administration, Oral, 2700 General Medicine, 030204 cardiovascular system & hematology, Pulmonary function testing, law.invention, oral, Idiopathic pulmonary fibrosis, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, SENSCIS Trial Investigators, CYCLOPHOSPHAMIDE, Clinical endpoint, scleroderma, 030212 general & internal medicine, Enzyme Inhibitors, 11 Medical and Health Sciences, lung diseases, Lung Diseases, Interstitial -- drug therapy -- etiology -- physiopathology, 10051 Rheumatology Clinic and Institute of Physical Medicine, General Medicine, respiratory system, Sciences bio-médicales et agricoles, Middle Aged, Protein-Tyrosine Kinases, MANIFESTATIONS, Disease Progression, Nintedanib, Female, TYROSINE KINASE INHIBITOR, Life Sciences & Biomedicine, CLINICAL-TRIALS, Adult, Diarrhea, medicine.medical_specialty, FIBROBLASTS, 610 Medicine & health, Placebo, administration, behavioral disciplines and activities, 03 medical and health sciences, FEV1/FVC ratio, Medicine, General & Internal, Double-Blind Method, Internal medicine, General & Internal Medicine, Enzyme Inhibitors -- adverse effects -- therapeutic use, SCORE, medicine, Humans, Indoles -- adverse effects -- therapeutic use, Scleroderma, Systemic -- complications -- drug therapy, Science & Technology, Scleroderma, Systemic, Protein-Tyrosine Kinases -- antagonists & inhibitors, business.industry, MORTALITY, interstitial, PULMONARY-FUNCTION, systemic, STANDARDIZATION, medicine.disease, EFFICACY, respiratory tract diseases, body regions, chemistry, adult, diarrhea, disease progression, double-blind method, enzyme inhibitors, female, humans, indoles, lung diseases, interstitial, male, middle aged, protein-tyrosine kinases, scleroderma, systemic, vital capacity, business, Lung Diseases, Interstitial, Diarrhea -- chemically induced
Abstract

Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and a leading cause of systemic sclerosis-related death. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD., info:eu-repo/semantics/published

Published
2019

25. Beginner-Coaches and Connectivity of Knowledge: Real-World Coaching and Self-Reported Importance of Prior Playing Experience

Author

Crisp Philippe and Hamblin May

Subjects
coach development, beginner-coaches, scaffolding knowledge, Sports, GV557-1198.995
Abstract

In what amounts to essentially being a part two to our previous work with six beginner-coaches that found noticeable benefits to reflective practice, yet a number of possible drawbacks such as time constraints and at times over-focusing on negative emotions (Hamblin & Crisp, 2022), we build upon the aims of that study that related to what beginner-coaches (in recreational sport fields) considered ideal coach learning within in-situ, practice-based contexts. Through revisiting the data of the first study (Hamblin & Crisp, 2022) and exploring an additional theme related to how the beginner-coaches identified sporting experience as a beneficial prerequisite to their own coaching practice, the present study sought to further investigate, and build upon, the findings and aspects of the first study. Continuing to explore how beginner-coaches who operate more within recreational (although still competitive) sport fields perceive in-situ, ideal learning, and continuing the same methodological approach, the present study conducted semi-structured interviews with another five beginner-coaches, adding to the six in the first study for a total of 11 participants.

Published
2023
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26. Transcriptomic and proteomic profile approaches toward drought and salinity stresses.

Author

GOHARRIZI, K. JAMSHIDI, KARAMI, S., HAMBLIN, M. R., MOMENI, M. M., BASAKI, T., DEHNAVI, M. MOSTAFAEI, and NAZARI, M.

Subjects
ABSCISIC acid, DROUGHT tolerance, IONIC equilibrium, DROUGHT management, SALINITY, DROUGHTS, PROTEOMICS, PLANT breeding
Abstract

Drought and salinity, which can alter the water balance, disrupt the ionic equilibrium, and create reactive oxygen species (ROS), are capable of destroying plant tissues. In this study, transcriptomics, proteomics, and metabolomics have been used to elucidate various abiotic stress responses. In transcriptional signaling pathways, abscisic acid (ABA) is one of the plant phytohormones that regulate the stress response. On the other hand, several regulons and factors of transcription contributed in the reaction to osmotic stresses, as well as in ABA-dependent/independent signaling pathways. However, the findings display that intricate molecular reaction of plants under stress conditions may be controlled by complicated regulative networks of gene expression and signal transduction, as well as by the interaction between them. From the point of view of proteomics, protein modifications in response to stress can be considered as a molecular tool to improve the resistance of plants to environmental stresses. These studies have provided new information about the significance of several gene and protein networks involved in the response of plants to salinity and drought, and the induction of tolerance. Moreover, identifying the crucial pathways which are involved in salinity and drought resistance can open doors for the establishment of commercial-resistant crop cultivars, and might be very useful in the next-generation crop breeding strategies to produce plants with salinity and drought-resistant traits. [ABSTRACT FROM AUTHOR]

Published
2022
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29. Long-term treatment with recombinant human pentraxin 2 protein in patients with idiopathic pulmonary fibrosis: an open-label extension study

Author

Raghu, G, van den Blink, B, Hamblin, M, Brown, A, Golden, J, Ho, L, Wijsenbeek, M, Vasakova, M, Pesci, A, Antin-Ozerkis, D, Meyer, K, Kreuter, M, Moran, D, Santin-Janin, H, Aubin, F, Mulder, G, Gupta, R, Richeldi, L, Raghu, Ganesh, van den Blink, Bernt, Hamblin, Mark J, Brown, A Whitney, Golden, Jeffrey A, Ho, Lawrence A, Wijsenbeek, Marlies S, Vasakova, Martina, Pesci, Alberto, Antin-Ozerkis, Danielle E, Meyer, Keith C, Kreuter, Michael, Moran, Donna, Santin-Janin, Hugues, Aubin, Francois, Mulder, Geert-Jan, Gupta, Renu, Richeldi, Luca, Raghu, G, van den Blink, B, Hamblin, M, Brown, A, Golden, J, Ho, L, Wijsenbeek, M, Vasakova, M, Pesci, A, Antin-Ozerkis, D, Meyer, K, Kreuter, M, Moran, D, Santin-Janin, H, Aubin, F, Mulder, G, Gupta, R, Richeldi, L, Raghu, Ganesh, van den Blink, Bernt, Hamblin, Mark J, Brown, A Whitney, Golden, Jeffrey A, Ho, Lawrence A, Wijsenbeek, Marlies S, Vasakova, Martina, Pesci, Alberto, Antin-Ozerkis, Danielle E, Meyer, Keith C, Kreuter, Michael, Moran, Donna, Santin-Janin, Hugues, Aubin, Francois, Mulder, Geert-Jan, Gupta, Renu, and Richeldi, Luca

Abstract

Background: Patients with idiopathic pulmonary fibrosis (IPF) treated with PRM-151, a recombinant human pentraxin 2 protein, in a phase 2 double-blind, randomised controlled trial had significantly reduced decline in percentage of predicted forced vital capacity (FVC) and stabilised 6-min walking distance compared with placebo over a 28-week period. Here we report the 76-week results of an open-label extension study. Methods: Patients who completed the 28-week double-blind period of the PRM-151-202 trial were eligible to participate in the open-label extension study. Patients previously enrolled in the PRM-151 group continued this treatment and those previously in the placebo group crossed over to PRM-151. All patients received PRM-151 in 28-week cycles with loading doses of 10 mg/kg by 60 min intravenous infusions on days 1, 3, and 5 in the first week of each cycle followed by one infusion of 10 mg/kg every 4 weeks. The primary objective of the open-label extension study was to assess the long-term safety and tolerability of PRM-151, which were assessed by analysing adverse events (AEs) up to week 76 in all patients who received at least one dose of PRM-151 during the open-label extension study. Exploratory efficacy analyses were done by assessing changes from baseline in percentage of predicted FVC and 6-min walking distance, with descriptive statistics to week 76 and with random-intercept mixed models to week 52. This study is registered with ClinicalTrials.gov, number NCT02550873, and with EudraCT, number 2014-004782-24. Findings: Of 116 patients who completed the double-blind treatment period, 111 entered the open-label extension study (74 from the PRM-151 group and 37 from the placebo group). 84 (76%) of 111 patients received concomitant IPF therapy (pirfenidone n=55 or nintedanib n=29). AEs were consistent with long-term IPF sequelae. 31 (28%) patients had serious AEs. Those occurring in two or more patients were pneumonia (six [5%] of 111), IPF exacerbation

Published
2019

34. BRIEF CO-ADMINISTRATION OF IDELALISIB MAY IMPROVE THE LONG-TERM EFFICACY OF FRONTLINE CHEMOIMMUNOTHERAPY IN CHRONIC LYMPHOCYTIC LEUKAEMIA: 3-YEAR FOLLOW-UP FROM THE RIALTO TRIAL

Author

Pettitt, A., primary, Kalakonda, N., additional, Cicconi, S., additional, Murphy, C., additional, Menon, G., additional, Coupland, S.E., additional, Oates, M., additional, Lin, K., additional, Pocock, C., additional, Jenkins, S., additional, Schuh, A., additional, Wandroo, F., additional, Rassam, S., additional, Duncombe, A.S., additional, Cervi, P., additional, Paneesha, S., additional, Aldouri, M., additional, Fox, C., additional, Knechtli, C., additional, Hamblin, M., additional, Turner, D., additional, and Hillmen, P., additional

Published
2019
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36. Improvement in Parameters of Hematologic and Immunologic Function and Patient Well-being in the Phase III RESONATE Study of Ibrutinib Versus Ofatumumab in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Author

Barrientos, JC, O'Brien, S, Brown, JR, Kay, NE, Reddy, NM, Coutre, S, Tam, C, Mulligan, S, Jaeger, U, Devereux, S, Pocock, C, Robak, T, Schuster, SJ, Schuh, A, Gill, D, Bloor, A, Dearden, C, Moreno, C, Cull, G, Hamblin, M, Jones, JA, Eckert, K, Solman, IG, Suzuki, S, Hsu, E, James, DF, Byrd, JC, Hillmen, P, Barrientos, JC, O'Brien, S, Brown, JR, Kay, NE, Reddy, NM, Coutre, S, Tam, C, Mulligan, S, Jaeger, U, Devereux, S, Pocock, C, Robak, T, Schuster, SJ, Schuh, A, Gill, D, Bloor, A, Dearden, C, Moreno, C, Cull, G, Hamblin, M, Jones, JA, Eckert, K, Solman, IG, Suzuki, S, Hsu, E, James, DF, Byrd, JC, and Hillmen, P

Abstract

BACKGROUND: Ibrutinib compared with ofatumumab significantly improves progression-free and overall survival in patients with previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). PATIENTS AND METHODS: Measures of well-being were assessed in RESONATE, where previously treated patients with CLL/SLL were randomized to receive ibrutinib 420 mg/day (n = 195) or ofatumumab (n = 196) for up to 24 weeks. Endpoints included hematologic function, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), disease-related symptoms, European Organization for Research and Treatment of Cancer Quality of Life Questionnaires Core 30 (EORTC QLQ-C30), and medical resource utilization. RESULTS: With up to 24 months' follow-up (median, 16.4 months), 79% of cytopenic patients showed sustained hematologic improvement (82% with improved platelet count, 69% with improved hemoglobin) on ibrutinib versus 43% on ofatumumab (P < .0001). Higher rates of clinically meaningful improvement were demonstrated with ibrutinib versus ofatumumab for FACIT-F and EORTC global health. Greater improvement was observed in disease-related weight loss, fatigue, night sweats, and abdominal discomfort with ibrutinib versus ofatumumab. Hospitalizations in the first 30 days occurred less frequently with ibrutinib than ofatumumab (0.087 vs. 0.184 events/patient; P = .0198). New-onset diarrhea was infrequent with ibrutinib after the first 6 months (47% at ≤6 months vs. 5% at 12-18 months). With ibrutinib, grade ≥ 3 hypertension occurred in 6%, grade ≥ 3 atrial fibrillation in 4%, major hemorrhage in 2%, and tumor lysis syndrome in 1% of patients. CONCLUSION: Ibrutinib led to significant improvements in hematologic function and disease symptomatology versus ofatumumab, and can restore quality of life while prolonging survival in relapsed/refractory CLL/SLL.

Published
2018

37. Effect of recombinant human pentraxin 2 vs placebo on change in forced vital capacity in patients with idiopathic pulmonary fibrosis a randomized clinical trial

Author

Raghu, G, Van Den Blink, B, Hamblin, M, Whitney Brown, A, Golden, J, Ho, L, Wijsenbeek, M, Vasakova, M, Pesci, A, Antin-Ozerkis, D, Meyer, K, Kreuter, M, Santin-Janin, H, Mulder, G, Bartholmai, B, Gupta, R, Richeldi, L, Raghu, Ganesh, Van Den Blink, Bernt, Hamblin, Mark J., Whitney Brown, A., Golden, Jeffrey A., Ho, Lawrence A., Wijsenbeek, Marlies S., Vasakova, Martina, Pesci, Alberto, Antin-Ozerkis, Danielle E., Meyer, Keith C., Kreuter, Michael, Santin-Janin, Hugues, Mulder, Geert-Jan, Bartholmai, Brian, Gupta, Renu, Richeldi, Luca, Raghu, G, Van Den Blink, B, Hamblin, M, Whitney Brown, A, Golden, J, Ho, L, Wijsenbeek, M, Vasakova, M, Pesci, A, Antin-Ozerkis, D, Meyer, K, Kreuter, M, Santin-Janin, H, Mulder, G, Bartholmai, B, Gupta, R, Richeldi, L, Raghu, Ganesh, Van Den Blink, Bernt, Hamblin, Mark J., Whitney Brown, A., Golden, Jeffrey A., Ho, Lawrence A., Wijsenbeek, Marlies S., Vasakova, Martina, Pesci, Alberto, Antin-Ozerkis, Danielle E., Meyer, Keith C., Kreuter, Michael, Santin-Janin, Hugues, Mulder, Geert-Jan, Bartholmai, Brian, Gupta, Renu, and Richeldi, Luca

Abstract

IMPORTANCE Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis. Approved therapies do not halt disease progression. OBJECTIVE To determine the effect of recombinant human pentraxin 2 vs placebo on change from baseline to week 28 in mean forced vital capacity (FVC) percentage of predicted value. DESIGN, SETTING, AND PARTICIPANTS Phase 2, randomized, double-blind, placebo-controlled trial conducted at 18 sites in 7 countries of eligible patients with IPF (N = 117; aged 40-80 years; FVC 50% and 90% predicted; ratio of forced expiratory volume in the first second/FVC >0.70; diffusing capacity for carbon monoxide [DLCO] 25% and 90% predicted; and distance of 150 m on the 6-minute walk test). Study period was August 2015-May 2017. INTERVENTIONS Patients were randomized to receive either recombinant human pentraxin 2 (10 mg/kg intravenous every 4 weeks, n = 77) or placebo (n = 39) for 24 weeks, and stratified by concurrent IPF treatment status. MAIN OUTCOMES AND MEASURES The primary end point was the least-squares mean change in FVC percentage of predicted value from baseline to week 28 (minimal clinically important difference, decline of 2%-6%). Secondary end points included mean change in lung volumes (total, normal, and interstitial lung abnormalities) on high-resolution computed tomography (HRCT) and 6-minute walk distance (minimal clinically important difference, 24-45 m). RESULTS Of 117 randomized patients, 116 received at least 1 dose of study drug (mean age, 68.6 years; 81.0% men; mean time since IPF diagnosis, 3.8 years), and 111 (95.7%) completed the study. The least-squares mean change in FVC percentage of predicted value from baseline to week 28 in patients treated with recombinant human pentraxin 2 was -2.5 vs -4.8 for those in the placebo group (difference, +2.3 [90% CI, 1.1 to 3.5]; P = .001). No significant treatment differences were observed in total lung volume (difference, 93.5 mL [90% CI, -27.7 to 214.7]), quan

Published
2018

38. Zinc phthalocyanines attached to gold nanorods for simultaneous hyperthermic and photodynamic therapies against melanoma in vitro

Author

Freitas, L F, Hamblin, M R, Anzengruber, F, Perussi, J R, Ribeiro, A O, Martins, V C A, Plepis, A M G, University of Zurich, and Freitas, L F

Subjects
3108 Radiation, 10177 Dermatology Clinic, 2741 Radiology, Nuclear Medicine and Imaging, 610 Medicine & health, 3614 Radiological and Ultrasound Technology, 1304 Biophysics
Published
2017
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40. Ibrutinib for Relapsed / Refractory CLL: A UK and Ireland Analysis of Outcomes in 315 patients

Author

Jacob, A, Bloor, A, Whiteway, A, Milne, AE, Kirkwood, AA, Hodson, A, Duncombe, AS, Schuh, A, von Barsewisch, B, Fegan, C, Fox, CP, Pocock, C, William, C, Dearden, C, Hutchinson, C, Balotis, C, De Lord, C, Kennedy, DB, Tucker, D, Vendenberghe, E, Maughan, E, Kumar, E, McNichol, F, Scott, F, Forconi, F, Campbell, G, Follows, GA, Pratt, G, Knight, H, Parry, H, Ringshausen, I, Whalley, I, Nielson, J, Allen, J, Arnold, J, Gribbon, J, Wallis, J, Blundell, J, Cwynarski, K, Bowles, KM, Ewings, M, Karanth, M, Dyer, MJ, Hamblin, M, Leach, M, Badat, M, Mir, N, Morley, N, Bienz, N, and Philpott, N

Abstract

In 2014, ibrutinib was made available for relapsed/refractory chronic lymphocytic leukaemia (CLL) patients. The UK CLL Forum collected data from UK/Ireland patients with a minimum of 1 year follow-up with pre-planned primary endpoints; the number of patients still on therapy at 1 year (Discontinuation Free Survival; DFS) and 1 year overall survival (OS). With a median 16 months follow-up, data on 315 patients demonstrated 1 year DFS of 73.7% and 1 year OS of 83.8%. Patients with better pre-treatment performance status (PS 0/1 vs 2+) had superior DFS (77.5% vs 61.3%;p14 days and had OS of 89.7%, while 26% of patients had dose reductions and 13% had temporary treatment breaks >14 days. We could not demonstrate a detrimental effect of dose reductions alone (1 year OS: 91.7%), but patients who had first year treatment breaks > 14 days, particularly permanent cessation of ibrutinib had both reduced 1 year OS (68.5%) and also a statistically significant excess mortality rate beyond one year. Although outcomes appear inferior to the RESONATE trial (1 year OS;90%: PFS;84%), this may partly reflect the inclusion of PS 2+ patients and that 17.5% of patients permanently discontinued ibrutinib due to an event other than disease progression.

Published
2016

41. Atrial Thrombosis: A near Fatal Complication of a Portacath

Author

Hunter S, Campbell G, Jaggia A, Golding L, Tonkin Jl, and Hamblin M

Subjects
Male, Catheterization, Central Venous, medicine.medical_specialty, 030309 nutrition & dietetics, 030232 urology & nephrology, Radiography, Interventional, Atrial thrombosis, Right atrial, Peripheral veins, 03 medical and health sciences, 0302 clinical medicine, Coronary thrombosis, Internal medicine, medicine, Humans, In patient, Heart Atria, cardiovascular diseases, Aged, 0303 health sciences, business.industry, Coronary Thrombosis, medicine.disease, Thrombosis, Surgery, Pulmonary embolism, Nephrology, cardiovascular system, Cardiology, Pulmonary Embolism, Tomography, X-Ray Computed, business, Complication
Abstract

Portacaths™ (Bard Medical Division, Georgia, USA) are routinely used for central venous access in patients with poor peripheral veins who require regular long-term venous access. Complications associated with central venous access devices, including infection and thrombosis, are well described in the literature; however, to our knowledge there have been few case reports of right atrial thrombi and pulmonary emboli related to implanted ports. This paper discusses the case of a patient who developed an atrial thrombosis 4 months after port placement and subsequent pulmonary emboli.

Published
2008
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42. EFFECT OF ADDING IDELALISIB TO FRONTLINE OFATUMUMAB PLUS EITHER CHLORAMBUCIL OR BENDAMUSTINE IN LESS FIT PATIENTS WITH CLL: PRELIMINARY RESULTS FROM THE NCRI RIALTO TRIAL.

Author

Pettitt, A.R., primary, Kalakonda, N., additional, Polydoros, F., additional, Bickerstaff, M., additional, Menon, G., additional, Coupland, S.E., additional, Oates, M., additional, Lin, K., additional, Pocock, C., additional, Jenkins, S., additional, Schuh, A., additional, Wandroo, F., additional, Rassam, S., additional, Duncombe, A.S., additional, Jenner, M., additional, Cervi, P., additional, Paneesha, S., additional, Aldouri, M., additional, Fox, C.P., additional, Knechtli, C., additional, Hamblin, M., additional, Turner, D., additional, and Hillmen, P., additional

Published
2017
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46. Negative Focus, Self-Doubt, and Issues of ‘Tool Proficiency’: Beginner-Coaches’ Reflections on Reflective Practice

Author

Hamblin May and Crisp Philippe

Subjects
coach learning, coach education, emotional reflection, self-confidence, decision-making, Sports, GV557-1198.995
Abstract

In the field of sports coaching education and learning, reflective practice is considered central to transforming experience and knowledge into expertise, and many governing bodies execute this through professional development and specific guidelines (Vallance, 2019). However, whilst the general consensus within academia and the vocational sector of coaching continue to espouse this approach, there is a lack of evidence to suggest how this is useful for beginner-coaches (defined as emerging-new, with less than three years of experience) as studies generally focus on expert coaches and oftentimes sit within the context of performance and/or elite sport. This study, therefore, aimed to explore the benefits and limitations of reflective practice, and to identify aspects of ideal learning for in-situ, practice-based context as perceived by beginner-coaches who operate more within recreational (although still competitive) sport fields. Situated within the UK context, the methodology comprised of semi-structured interviews conducted with six beginner-coaches. The findings demonstrated that whilst there were tangible benefits to the use of reflective practice (such as perceived additional competency and critical thinking), there were also limitations centred on time constraints, and an over-focus on negative emotions with a subsequent adverse impact on self-confidence and anxiety. The implications, including recommendations and thoughts for the future, are outlined within the paper.

Published
2022
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49. Self-generated morphology in lagoon reefs

Author

Blakeway, David, Hamblin, M., Blakeway, David, and Hamblin, M.

Abstract

The three-dimensional form of a coral reef develops through interactions and feedbacks between its constituent organisms and their environment. Reef morphology therefore contains a potential wealth of ecological information, accessible if the relationships between morphology and ecology can be decoded. Traditionally, reef morphology has been attributed to external controls such as substrate topography or hydrodynamic influences. Little is known about inherent reef morphology in the absence of external control. Here we use reef growth simulations, based on observations in the cellular reefs ofWestern Australia's Houtman Abrolhos Islands, to show that reef morphology is fundamentally determined by the mechanical behaviour of the reef-building organisms themselves-specifically their tendency to either remain in place or to collapse. Reef-building organisms that tend to remain in place, such as massive and encrusting corals or coralline algae, produce nodular reefs, whereas those that tend to collapse, such as branching Acropora, produce cellular reefs. The purest reef growth forms arise in sheltered lagoons dominated by a single type of reef builder, as in the branching Acropora-dominated lagoons of the Abrolhos. In these situations reef morphology can be considered a phenotype of the predominant reef building organism. The capacity to infer coral type from reef morphology can potentially be used to identify and map specific coral habitat in remotely sensed images. More generally, identifying ecological mechanisms underlying other examples of self-generated reef morphology can potentially improve our understanding of present-day reef ecology, because any ecological process capable of shaping a reef will almost invariably be an important process in real time on the living reef.

Published
2015

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