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2. Lineage switching of the cellular distribution of BRAFV600E in multisystem Langerhans cell histiocytosis

Author

Milne, Paul, Bomken, Simon, Slater, Olga, Kumar, Ashish, Nelson, Adam, Roy, Somak, Velazquez, Jessica, Mankad, Kshitij, Nicholson, James, Yeomanson, Dan, Grundy, Richard, Kamal, Ahmed, Penn, Anthony, Pears, Jane, Millen, Gerard, Morland, Bruce, Hayden, James, Lam, Jason, Madkhali, Maymoon, MacDonald, Jamie, Singh, Preeti, Pagan, Sarah, Rodriguez-Galindo, Carlos, Minkov, Milen, Donadieu, Jean, Picarsic, Jennifer, Allen, Carl, Bigley, Venetia, and Collin, Matthew

Published
2023
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3. Epigenetic regulator genes direct lineage switching in MLL/AF4 leukemia

Author

Tirtakusuma, Ricky, Szoltysek, Katarzyna, Milne, Paul, Grinev, Vasily V., Ptasinska, Anetta, Chin, Paulynn S., Meyer, Claus, Nakjang, Sirintra, Hehir-Kwa, Jayne Y., Williamson, Daniel, Cauchy, Pierre, Keane, Peter, Assi, Salam A., Ashtiani, Minoo, Kellaway, Sophie G., Imperato, Maria R., Vogiatzi, Fotini, Schweighart, Elizabeth K., Lin, Shan, Wunderlich, Mark, Stutterheim, Janine, Komkov, Alexander, Zerkalenkova, Elena, Evans, Paul, McNeill, Hesta, Elder, Alex, Martinez-Soria, Natalia, Fordham, Sarah E., Shi, Yuzhe, Russell, Lisa J., Pal, Deepali, Smith, Alex, Kingsbury, Zoya, Becq, Jennifer, Eckert, Cornelia, Haas, Oskar A., Carey, Peter, Bailey, Simon, Skinner, Roderick, Miakova, Natalia, Collin, Matthew, Bigley, Venetia, Haniffa, Muzlifah, Marschalek, Rolf, Harrison, Christine J., Cargo, Catherine A., Schewe, Denis, Olshanskaya, Yulia, Thirman, Michael J., Cockerill, Peter N., Mulloy, James C., Blair, Helen J., Vormoor, Josef, Allan, James M., Bonifer, Constanze, Heidenreich, Olaf, and Bomken, Simon

Published
2022
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9. Dendritic cell development in haematological malignancies and neoplasia

Author

Milne, Paul

Subjects
616.99
Abstract

Dendritic cells (DC) play a major role in the detection of antigens, initiation of immunity and induction and regulation of tolerance. DCs are Bone Marrow (BM) derived and their development may be influenced by haematological malignancy in several ways. Firstly, myelodysplastic, myeloproliferative or leukaemic transformation of bone marrow progenitors may involve DC precursors directly, when they become part of a malignant clone, or indirectly when neoplastic expansion of other lineages compromises the development of DCs. Secondly, neoplasia of the dendritic cell lineage itself may occur in a heterogeneous group of histiocytic disorders including Langerhans cell histiocytosis (LCH) and Erdheim Chester disease (ECD). The first part of this thesis concerns the effect of haematological malignancies on the generation of DCs; in particular the relationship between DC, monocyte, B and NK lymphoid cell (DCML) deficiency, caused by GATA2 gene mutations, sporadic myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). Comprehensive flow cytometric methods for profiling of the DCs and monocytes in the peripheral blood (PB) and peripheral tissues, and the CD34+ progenitors of the BM have been developed. Using these methods, it was possible to see that patients with the three diseases differed on several grounds. DCML deficiencies associated with a younger age of presentation, better preserved haemoglobin, neutrophils and platelets and much more severe defects of DCs, monocytes, and lymphoid cells. In patients with MDS, deficiencies are more moderate and mononuclear cell generation in AML patients is surprisingly preserved. Serum levels of Fms-like tyrosine kinase 3 ligand (FLT3L) also differed, with massively increased levels in DCML deficiency, stable levels in MDS and deficiencies in AML. Finally, strategies of grouping of AML patients have proven to be possible by using progenitor cell or DC related phenotypic markers which may correlate to known cytogenetic abnormalities. The second part of this thesis explores the origin of the cells of LCH and ECD, both neoplasia involving DC-like cells. RT-PCR assays were developed to detect the BRAFV600E mutation, which is present in ~60% of LCH and ECD viii cases. Surprisingly, it was seen that LCH and ECD express BRAFV600E in differing peripheral blood fractions. In LCH, 78-94% of all BRAFV600E alleles were found in HLA-DR+Lineage- cells, localised to the monocytes and CD1c+ myeloid DCs (mDCs). However in ECD, 80-82% of mutated alleles were recovered from the HLA-DR-Lineage- quadrant, localised to CD33+ early myeloid cells, and no mutation was found in the monocytes or mDCs. The final part of the thesis examines whether the circulating cells which carry the BRAFV600E mutation in LCH and ECD can actually develop into LCH-like cells. In order to do this, culture systems were developed with a variety of cytokines and conditions. These experiments showed that CD14+ and CD16+ monocytes and CD1c+ mDCs could all induce the Langerhans Cell (LC) markers CD1a and Langerin in response to GM-CSF, TGFβ and BMP7, however only the CD1c+ mDCs could express Langerin at the high levels seen in LCs, along with EpCam and Birbeck granules. Several techniques have been developed to study DCs in haematological malignancies. Throughout this thesis, these techniques have provided valuable data on the development and homeostasis of human DCs.

Published
2015

13. Genome‐wide association study identifies the first germline genetic variant associated with Erdheim Chester disease

Author

Martínez‐López, Javier, primary, Márquez, Ana, additional, Pegoraro, Francesco, additional, Ortiz‐Fernández, Lourdes, additional, Acosta‐Herrera, Marialbert, additional, Kerick, Martin, additional, Gelain, Elena, additional, Diamond, Eli L., additional, Durham, Benjamin H., additional, Abdel‐Wahab, Omar, additional, Go, Ronald S., additional, Koster, Matthew J., additional, Dagna, Lorenzo, additional, Campochiaro, Corrado, additional, Collin, Matthew, additional, Milne, Paul, additional, Estrada‐Veras, Juvianee I., additional, O'Brien, Kevin, additional, Papo, Matthias, additional, Cohen‐Aubar, Fleur, additional, Amoura, Zahir, additional, Haroche, Julien, additional, Martín, Javier, additional, and Vaglio, Augusto, additional

Published
2023
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14. PB2208: CLUSTER ANALYSIS UNVEILS THE CLINICAL SPECTRUM OF ERDHEIM-CHESTER DISEASE

Author

Tesi, Michelangelo, primary, Pegoraro, Francesco, additional, Peyronel, Francesco, additional, Mazzariol, Martina, additional, Gelain, Elena, additional, Koster, Matthew, additional, Go, Ronald, additional, Goyal, Gaurav, additional, Collin, Matthew, additional, Milne, Paul, additional, Pagan, Sarah, additional, Cohen-Aubart, Fleur, additional, Papo, Matthias, additional, Estrada-Veras, Juvianee, additional, Mazor, Roei, additional, Dagna, Lorenzo, additional, Diamond, Eli, additional, Vaglio, Augusto, additional, and Haroche, Julien, additional

Published
2023
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16. Genome‐Wide Association Study Identifies the First Germline Genetic Variant Associated With Erdheim‐Chester Disease.

Author

Martínez‐López, Javier, Márquez, Ana, Pegoraro, Francesco, Ortiz‐Fernández, Lourdes, Acosta‐Herrera, Marialbert, Kerick, Martin, Gelain, Elena, Diamond, Eli L., Durham, Benjamin H., Abdel‐Wahab, Omar, Go, Ronald S., Koster, Matthew J., Dagna, Lorenzo, Campochiaro, Corrado, Collin, Matthew, Milne, Paul, Estrada‐Veras, Juvianee I., O'Brien, Kevin, Papo, Matthias, and Cohen‐Aubar, Fleur

Subjects
GENETIC mutation, CONFIDENCE intervals, GENOME-wide association studies, CELLULAR signal transduction, GENE expression, DESCRIPTIVE statistics, DATA analysis software, ODDS ratio, HEMATOPOIESIS, LOGISTIC regression analysis, ERDHEIM-Chester disease
Abstract

Objective: Erdheim‐Chester disease (ECD) is rare histiocytosis with a wide range of clinical manifestations. Somatic mutations are key to the pathogenesis of the disease; however, the relationship between germline genetic variants and ECD has not been examined so far. The present study aims to explore the inherited genetic component of ECD by performing the first genome‐wide association study. Methods: After quality controls, a cohort of 255 patients with ECD and 7,471 healthy donors was included in this study. Afterward, a logistic regression followed by in silico functional annotation was performed. Results: A signal at the 18q12.3 genomic region was identified as a new susceptibility locus for ECD (P = 2.75 × 10−11; Odds Ratio = 2.09). This association was annotated to the SETBP1 gene, which is involved in clonal haematopoiesis. Functional annotation of this region and of the identified suggestive signals revealed additional genes that could be potentially involved in the pathogenesis of the disease. Conclusion: Overall, this work demonstrates that germline genetic variants can impact on the development of ECD and suggests new pathways with a potential pathogenic role. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Genome-wide association study identifies the first germline genetic variant associated with Erdheim Chester disease

Author

Histio UK, National Human Genome Research Institute (US), Redes de Investigación Cooperativa Orientadas a Resultados en Salud (España), Instituto de Salud Carlos III, Agencia Estatal de Investigación (España), Ministerio de Ciencia e Innovación (España), Martínez López, Javier, Márquez, Ana, Pegoraro, Francesco, Ortiz-Fernández, Lourdes, Acosta-Herrera, Marialbert, Kerick, Martin, Gelain, Elena, Diamond, Eli L., Durham, Benjamin H., Abdel-Wahab, Omar, Go, Ronald S., Koster, Matthew J., Dagna, Lorenzo, Campochiaro, Corrado, Collin, Matthew, Milne, Paul, Estrada-Veras, Juvianee I., O'Brien, Kevin, Papo, Matthias, Cohen-Aubar, Fleur, Amoura, Zahir, Haroche, Julien, Martín, Javier, Vaglio, Augusto, Histio UK, National Human Genome Research Institute (US), Redes de Investigación Cooperativa Orientadas a Resultados en Salud (España), Instituto de Salud Carlos III, Agencia Estatal de Investigación (España), Ministerio de Ciencia e Innovación (España), Martínez López, Javier, Márquez, Ana, Pegoraro, Francesco, Ortiz-Fernández, Lourdes, Acosta-Herrera, Marialbert, Kerick, Martin, Gelain, Elena, Diamond, Eli L., Durham, Benjamin H., Abdel-Wahab, Omar, Go, Ronald S., Koster, Matthew J., Dagna, Lorenzo, Campochiaro, Corrado, Collin, Matthew, Milne, Paul, Estrada-Veras, Juvianee I., O'Brien, Kevin, Papo, Matthias, Cohen-Aubar, Fleur, Amoura, Zahir, Haroche, Julien, Martín, Javier, and Vaglio, Augusto

Abstract

[Objective] Erdheim-Chester disease (ECD) is rare histiocytosis with a wide range of clinical manifestations. Somatic mutations are key to the pathogenesis of the disease; however, the relationship between germline genetic variants and ECD has not been examined so far. The present study aims to explore the inherited genetic component of ECD by performing the first genome-wide association study., [Methods] After quality controls, a cohort of 255 ECD patients and 7,471 healthy donors was included in this study. Afterwards, a logistic regression followed by in silico functional annotation was performed., [Results] A signal at the 18q12.3 genomic region was identified as a new susceptibility locus for ECD (p-value=2.75x10-11; OR=2.09). This association was annotated to the SETBP1 gene, which is involved in clonal haematopoiesis. Functional annotation of this region and of the identified suggestive signals revealed additional genes that could be potentially involved in the pathogenesis of the disease., [Conclusion] Overall, this work demonstrates that germline genetic variants can impact on the development of ECD and suggests new pathways with a potential pathogenic role.

Published
2023

19. Polynuclear copper-lanthanoid complexes of pyridone ligands

Author

Milne, Paul Edward Young

Subjects
546.3
Abstract

The crystal structures of several copper and mixed copper-lanthanoid complexes are reported, using the 6-chloro and 6-methyl derivatives of 2-pyridone as a ligand. With 6-chloro-2-pyridone, a novel dimeric copper complex results, which has been structually and physically studied. This species, under certain conditions, exhibits a dissociation reaction which has been examined using U.V.-vis. and E.P.R. spectroscopy and by cyclic voltammetry. Reaction of this dimeric copper compound with methanol and ethylene glycol results in the formation of tetranuclear and polymeric copper complexes respectively, which have both been structurally characterised. The reaction of this copper dimer with various lanthanoids results in the formation of a series of mixed copper-lanthanoid species based on four structural types. Reactions in methanol dichloromethane result in three structural configurations depending on size of the lanthanoid used (with La and Ce, LnCu3 with five ligands; with Gd, Dy and Er LnCu3 with eight ligands and for Yb Ln2Cu2 with four ligands). The reaction of lanthanum with the dimeric copper species in a variety of solvents gave a further two structures, one of which (in ethanol) has a similar structure to those observed with Gd, Dy and Er in methanol, while in acetonitrile a fourth structural type occurs, based on La2Cu2 with six ligands. With the 6-methyl-2-pyridone an unusual hexanuclear 'metallocrown' results, which has been characterised structually and by proton and sodium-23 NMR. The reaction of this species with lanthanoids in methanol yields a range of closely related mixed copper-lanthanoid compounds all based on Ln2Cu2 (as seen for the product of Yb with the copper dimer in methanol). The only difference between the structures is a change in the coordination number of the lanthanoid between Sm and Gd to accommodate the contraction in lanthanoid size. The mixed phase reaction of this 'metallocrown' with lanthanum nitrate yields an extremely remarkable structure based on a La8Cu12 core.

Published
1993

20. Notch-dependent cooperativity between myeloid lineages promotes Langerhans cell histiocytosis pathology

Author

Kvedaraite, Egle, primary, Milne, Paul, additional, Khalilnezhad, Ahad, additional, Chevrier, Marion, additional, Sethi, Raman, additional, Lee, Hong Kai, additional, Hagey, Daniel W., additional, von Bahr Greenwood, Tatiana, additional, Mouratidou, Natalia, additional, Jädersten, Martin, additional, Lee, Nicole Yee Shin, additional, Minnerup, Lara, additional, Tan, Yingrou, additional, Dutertre, Charles-Antoine, additional, Benac, Nathan, additional, Hwang, You Yi, additional, Lum, Josephine, additional, Loh, Amos Hong Pheng, additional, Jansson, Jessica, additional, Teng, Karen Wei Weng, additional, Khalilnezhad, Shabnam, additional, Xu, Weili, additional, Resteu, Anastasia, additional, Tey, Hong Liang, additional, Guan, Ng Lai, additional, Larbi, Anis, additional, Howland, Shanshan Wu, additional, Arnell, Henrik, additional, Andaloussi, Samir E. L., additional, Braier, Jorge, additional, Rassidakis, Georgios, additional, Galluzzo, Laura, additional, Dzionek, Andrzej, additional, Henter, Jan-Inge, additional, Chen, Jinmiao, additional, Collin, Matthew, additional, and Ginhoux, Florent, additional

Published
2022
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22. The evolution of cellular deficiency in GATA2 mutation

Author

Dickinson, Rachel E., Milne, Paul, Jardine, Laura, Zandi, Sasan, Swierczek, Sabina I., McGovern, Naomi, Cookson, Sharon, Ferozepurwalla, Zaveyna, Langridge, Alexander, Pagan, Sarah, Gennery, Andrew, Heiskanen-Kosma, Tarja, Hämäläinen, Sari, Seppänen, Mikko, Helbert, Matthew, Tholouli, Eleni, Gambineri, Eleonora, Reykdal, Sigrún, Gottfreðsson, Magnús, Thaventhiran, James E., Morris, Emma, Hirschfield, Gideon, Richter, Alex G., Jolles, Stephen, Bacon, Chris M., Hambleton, Sophie, Haniffa, Muzlifah, Bryceson, Yenan, Allen, Carl, Prchal, Josef T., Dick, John E., Bigley, Venetia, and Collin, Matthew

Published
2014
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24. Lineage-switching of the cellular distribution of BRAFV600E in multisystem Langerhans cell histiocytosis

Author

Milne, Paul, primary, Bomken, Simon, additional, Slater, Olga, additional, Kumar, Ashish R., additional, Nelson, Adam S, additional, Roy, Somak, additional, Velazquez, Jessica, additional, Mankad, Kshitij, additional, Nicholson, James, additional, Yeomanson, Dan, additional, Grundy, Richard, additional, Kamal, Ahmed, additional, Penn, Anthony, additional, Pears, Jane, additional, Millen, Gerard, additional, Morland, Bruce, additional, Hayden, James Timothy, additional, Lam, Jason, additional, Madkhali, Maymoon, additional, Macdonald, Jamie Liam, additional, Singh, Preeti, additional, Pagan, Sarah, additional, Rodriguez-Galindo, Carlos, additional, Minkov, Milen, additional, Donadieu, Jean, additional, Picarsic, Jennifer, additional, Allen, Carl E, additional, Bigley, Venetia, additional, and Collin, Matthew, additional

Published
2022
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26. Epigenetic regulator genes direct lineage switching in MLL/AF4 leukemia

Author

Onderzoek Beeld, Cancer, Tirtakusuma, Ricky, Szoltysek, Katarzyna, Milne, Paul, Grinev, Vasily V, Ptasinska, Anetta, Chin, Paulynn S, Meyer, Claus, Nakjang, Sirintra, Hehir-Kwa, Jayne Y, Williamson, Daniel, Cauchy, Pierre, Keane, Peter, Assi, Salam A, Ashtiani, Minoo, Kellaway, Sophie G, Imperato, Maria R, Vogiatzi, Fotini, Schweighart, Elizabeth K, Lin, Shan, Wunderlich, Mark, Stutterheim, Janine, Komkov, Alexander, Zerkalenkova, Elena, Evans, Paul, McNeill, Hesta, Elder, Alex, Martinez-Soria, Natalia, Fordham, Sarah E, Shi, Yuzhe, Russell, Lisa J, Pal, Deepali, Smith, Alex, Kingsbury, Zoya, Becq, Jennifer, Eckert, Cornelia, Haas, Oskar A, Carey, Peter, Bailey, Simon, Skinner, Roderick, Miakova, Natalia, Collin, Matthew, Bigley, Venetia, Haniffa, Muzlifah, Marschalek, Rolf, Harrison, Christine J, Cargo, Catherine A, Schewe, Denis, Olshanskaya, Yulia, Thirman, Michael J, Cockerill, Peter N, Mulloy, James C, Blair, Helen J, Vormoor, Josef, Allan, James M, Bonifer, Constanze, Heidenreich, Olaf, Bomken, Simon, Onderzoek Beeld, Cancer, Tirtakusuma, Ricky, Szoltysek, Katarzyna, Milne, Paul, Grinev, Vasily V, Ptasinska, Anetta, Chin, Paulynn S, Meyer, Claus, Nakjang, Sirintra, Hehir-Kwa, Jayne Y, Williamson, Daniel, Cauchy, Pierre, Keane, Peter, Assi, Salam A, Ashtiani, Minoo, Kellaway, Sophie G, Imperato, Maria R, Vogiatzi, Fotini, Schweighart, Elizabeth K, Lin, Shan, Wunderlich, Mark, Stutterheim, Janine, Komkov, Alexander, Zerkalenkova, Elena, Evans, Paul, McNeill, Hesta, Elder, Alex, Martinez-Soria, Natalia, Fordham, Sarah E, Shi, Yuzhe, Russell, Lisa J, Pal, Deepali, Smith, Alex, Kingsbury, Zoya, Becq, Jennifer, Eckert, Cornelia, Haas, Oskar A, Carey, Peter, Bailey, Simon, Skinner, Roderick, Miakova, Natalia, Collin, Matthew, Bigley, Venetia, Haniffa, Muzlifah, Marschalek, Rolf, Harrison, Christine J, Cargo, Catherine A, Schewe, Denis, Olshanskaya, Yulia, Thirman, Michael J, Cockerill, Peter N, Mulloy, James C, Blair, Helen J, Vormoor, Josef, Allan, James M, Bonifer, Constanze, Heidenreich, Olaf, and Bomken, Simon

Published
2022

27. Lineage switching of the cellular distribution of BRAFV600Ein multisystem Langerhans cell histiocytosis

Author

Milne, Paul, Bomken, Simon, Slater, Olga, Kumar, Ashish, Nelson, Adam, Roy, Somak, Velazquez, Jessica, Mankad, Kshitij, Nicholson, James, Yeomanson, Dan, Grundy, Richard, Kamal, Ahmed, Penn, Anthony, Pears, Jane, Millen, Gerard, Morland, Bruce, Hayden, James, Lam, Jason, Madkhali, Maymoon, MacDonald, Jamie, Singh, Preeti, Pagan, Sarah, Rodriguez-Galindo, Carlos, Minkov, Milen, Donadieu, Jean, Picarsic, Jennifer, Allen, Carl, Bigley, Venetia, and Collin, Matthew

Abstract

•BRAFV600Ealleles are mainly found in myeloid cells at diagnosis of multisystem LCH.•After more than 2 years, T cells account for 85% of persistent BRAFV600Emutation detected in peripheral blood mononuclear cells.

Published
2023
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29. Epigenetic regulator genes direct lineage switching in MLL-AF4 leukaemia

Author

Tirtakusuma, Ricky, primary, Szoltysek, Katarzyna, additional, Milne, Paul, additional, Grinev, Vasily V, additional, Ptasinska, Anetta, additional, Meyer, Claus, additional, Nakjang, Sirintra, additional, Hehir-Kwa, Jayne Y, additional, Williamson, Daniel, additional, Cauchy, Pierre, additional, Assi, Salam A, additional, Imperato, Maria R, additional, Vogiatzi, Fotini, additional, Lin, Shan, additional, Wunderlich, Mark, additional, Stutterheim, Janine, additional, Komkov, Alexander, additional, Zerkalenkova, Elena, additional, Evans, Paul, additional, McNeill, Hesta, additional, Elder, Alex, additional, Martinez-Soria, Natalia, additional, Fordham, Sarah E, additional, Shi, Yuzhe, additional, Russell, Lisa J, additional, Pal, Deepali, additional, Smith, Alex, additional, Kingsbury, Zoya, additional, Becq, Jennifer, additional, Eckert, Cornelia, additional, Haas, Oskar A, additional, Carey, Peter, additional, Bailey, Simon, additional, Skinner, Roderick, additional, Miakova, Natalia, additional, Collin, Matthew, additional, Bigley, Venetia, additional, Haniffa, Muzlifah, additional, Marschalek, Rolf, additional, Harrison, Christine J, additional, Cargo, Catherine A, additional, Schewe, Denis, additional, Olshanskaya, Yulia, additional, Thirman, Michael J, additional, Cockerill, Peter N, additional, Mulloy, James C, additional, Blair, Helen J, additional, Vormoor, Josef, additional, Allan, James M, additional, Bonifer, Constanze, additional, Heidenreich, Olaf, additional, and Bomken, Simon, additional

Published
2021
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30. Human Dermal CD14+ Cells Are a Transient Population of Monocyte-Derived Macrophages

Author

McGovern, Naomi, Schlitzer, Andreas, Gunawan, Merry, Jardine, Laura, Shin, Amanda, Poyner, Elizabeth, Green, Kile, Dickinson, Rachel, Wang, Xiao-nong, Low, Donovan, Best, Katie, Covins, Samuel, Milne, Paul, Pagan, Sarah, Aljefri, Khadija, Windebank, Martin, Saavedra, Diego Miranda, Larbi, Anis, Wasan, Pavandip Singh, Duan, Kaibo, Poidinger, Michael, Bigley, Venetia, Ginhoux, Florent, Collin, Matthew, and Haniffa, Muzlifah

Published
2014
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37. VEMURAFENIB IN CHILDREN WITH REFRACTORY LCH: 53 PATIENTS TREATED IN EU AND LEBANON

Author

Donadieu, Jean, Larabi, Islam Amine, Tardieu, Mathilde, Visser, Johannes, Hutter, Caroline, Sieni, Elena, Kabbara, Nabil, Barkaoui, Mohamed, Milne, Paul, Haroche, Julien, Taly, Valérie, Collinson, Matthew, Alvarez, Jean-Claude, J.F., Emile, Heritier, Sébastien, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Service de Dermatologie [CHU de Grenoble site Nord], CHU de Grenoble site Nord, Department of Paediatric Oncology and Haematology [Cambridge, UK], University of Cambridge [UK] (CAM), St Anna Kinderspital [Vienna Austria], Dipartimento di Oncoematologia Pediatrica [Firenze, Italy], Azienda Ospedaliero Universitaria A. Meyer [Firenze, Italy], Division Pediatric Hematology Oncology [Beirut, Lebanon], Université Saint-Joseph de Beyrouth (USJ), Pediatric Hematology Oncology [Beirut, Lebanon], Rafic Hariri University Hospital [Beirut, Lebanon], Institute of Cellular Medicine [Newcastle], Newcastle University [Newcastle], Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Saint Anna Children's Hospital [Vienne] = St Anna Kinderspital (St. Anna Children's Hospital), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and TALY, Valerie

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019
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41. Effective gas-phase diffusion coefficients in soils at varying water content measured using a one-flow sorbent-based technique

Author

Batterman, Stuart, Padmanabham, Iyer, and Milne, Paul

Subjects
Diffusion -- Research, Soil research -- Analysis, Environmental issues, Science and technology
Abstract

A study was conducted on gas-phase diffusion coefficients in unsaturated soils. Steady-state and unsteady-state methods and a new one-flow sorbent-based technique were used at various water contents. Results showed a curvilinear relationship between the effective diffusion coefficient and air-filled porosity. The one-flow sorbent-based technique was found to provide improved characterization of diffusive processes in soils due to its convenience and flexibility.

Published
1996

42. Transformational learning: Integrated Education for Integrated Care and Services

Author

Gurbutt, Dawne, Milne, Paul, Gurbutt, Dawne, and Milne, Paul

Abstract

The National Health Service in the UK is placing increased emphasis on Integrated Care and closer working relationships between services and professions. This provides both a challenge and an opportunity for universities preparing students for clinical roles as it represents a shift, supported by technology, away from traditional modes of learning and, ultimately, of practice. The creation of new medical school at the University of Central Lancashire UK facilitated an increased emphasis on Inter-professional education (IPE), driven in part by the requirements of the professional bodies. Utilising a strong activity theory pedagogy resulted in the development of a forum theatre approach to case studies using interactive learning elements and small group work across professions, the programme involved nine professional groups from four schools across the university. Sessions involved service users and actors as well as the student participants and staff from all courses. The data from evaluations from across the 7 session programme (N= 1742) indicated that students appreciated the importance of IPE whilst some found it challenging. Issues identified as challenging included lack of confidence, IPE not being examinable resulting in some students devaluing the experience, and timetable issues. However, students gained insights into the roles and skills of others, viewed health services more holistically and agreed that IPE was a useful preparation for practice. Some students developed inter-cohort relationships which extended beyond the classroom into informal learning settings. The commitment of staff to integrated learning and collaborative practice was central to the transformative elements of learning experience, leading to discussion of values and a clear patient focus. Initially arising from the development of the medical curriculum, staff ownership of IPE has resulted in a wide level of engagement across the university incorporating interdisciplinary as well as int

Published
2019

43. New high-spin clusters featuring transition metals

Author

Day, P., primary, Underhill, A. E., additional, Brechin, Euan K., additional, Graham, Alasdair, additional, Milne, Paul E. Y., additional, Murrie, Mark, additional, Parsons, Simon, additional, and Winpenny, Richard E. P., additional

Published
1999
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44. Cation control on the crystal organization of hexanuclear carbonyl cluster anions

Author

Braga, Dario, Grepioni, Fabrizia, Milne, Paul, and Parisini, Emilio

Subjects
Anions -- Research, Chemistry
Abstract

Researchers used empirical packing potential energy measurements, van der Waals volume investigation and computer graphics to study the crystal structures of 28 hexanuclear carbonyl cluster anions, and to study the association between shape, size and charge of the component ions and the development of selective agregates (piles, 'snakes', layers) in the crystal lattice. In the case of large organic cations, the packing type is basically that of molecular mixed crystals, but small cations move toward monodimensional aggregation of the anions.

Published
1993

45. LLT1 and CD161 Expression in Human Germinal Centers Promotes B Cell Activation and CXCR4 Downregulation

Author

Llibre, Alba, López-Macías, Constantino, Marafioti, Teresa, Mehta, Hema, Partridge, Amy, Kanzig, Carina, Rivellese, Felice, Galson, Jacob D., Walker, Lucy J., Milne, Paul, Phillips, Rodney E., Kelly, Dominic F., Freeman, Gordon J., El Shikh, Mohey Eldin, Klenerman, Paul, and Willberg, Christian B.

Subjects
B-Lymphocytes, Receptors, CXCR4, Down-Regulation, Receptors, Cell Surface, Cell Separation, Flow Cytometry, Germinal Center, Lymphocyte Activation, Real-Time Polymerase Chain Reaction, Immunohistochemistry, Humans, Clinical and Human Immunology, Lectins, C-Type, NK Cell Lectin-Like Receptor Subfamily B
Abstract

Germinal centers (GCs) are microanatomical structures critical for the development of high-affinity Abs and B cell memory. They are organized into two zones, light and dark, with coordinated roles, controlled by local signaling. The innate lectin-like transcript 1 (LLT1) is known to be expressed on B cells, but its functional role in the GC reaction has not been explored. In this study, we report high expression of LLT1 on GC-associated B cells, early plasmablasts, and GC-derived lymphomas. LLT1 expression was readily induced via BCR, CD40, and CpG stimulation on B cells. Unexpectedly, we found high expression of the LLT1 ligand, CD161, on follicular dendritic cells. Triggering of LLT1 supported B cell activation, CD83 upregulation, and CXCR4 downregulation. Overall, these data suggest that LLT1–CD161 interactions play a novel and important role in B cell maturation within the GC in humans., The Journal of Immunology, 196 (5), ISSN:0022-1767, ISSN:1048-3233, ISSN:1047-7381, ISSN:1550-6606

Published
2016

47. The path to transformation, navigating the barriers to forming the transient and the transitional learning groups in interprofessional education

Author

Gurbutt, Dawne and Milne, Paul

Subjects
X342
Abstract

The creation of a new medical school provided new opportunities to develop interprofessional education (IPE) with a pedagogic basis in transformational learning. The programme involved some transient groups – medical students working with different professional groups throughout the year and some learning interventions which proved to be transitional for students in intended and sometimes unintended ways. The path to transformational learning in interprofessional education requires the navigation of different perspectives and beliefs about learning, an element of tenacity and bravery in relation to holding to core pedagogic beliefs and an openness to co-production and evolution of learning elements. \ud Some learning episodes formed a transformative space within a particular time bounded location whilst others led to ongoing relationships and social connections beyond the classroom. Feedback indicated that transformation is not always comfortable or linear for students and the programme identified areas of challenge for both learners and staff as well as opportunities for development and co-creation. \ud This was a large IPE initiative involving staff and students from 9 disciplines across 7 schools and 3 faculties with involvement from service users and stakeholders. The programme incorporated almost 2000 separate student learning episodes. This paper will consider the programme from the perspective of students, creators of the learning elements and participatory staff from different disciplines, exploring the challenges, gains and learning from the initiative. \ud In considering these we suggest that social learning paradigms can help to give insight into their solution. For example, the intended and unintended outcomes could be considered through the perspectives of an integrated social learning paradigm. From the empirical data it is suggested that the paradigms of Activity theory and Complex adaptive systems theory give insight to how intended and unintended transformative learning takes place. These are inter-related as shown in the diagram.\ud Using complex adaptive system theory as part of the activity system theory paradigm, the inter-relationship between the components of the suggested social learning paradigm may be viewed as complex with any one component able to take precedent over the other. \ud It is suggested that the unintended transformative learning and the social connections established outside the classroom arose as a result of the mixed student professionals’ classroom moving through a process of having become a ‘self-organising system’. The students have spontaneously produced a system that could not have been predicted from ‘a knowledge of the previous state’ (i.e. the facilitated teaching session).\ud Analysis of the empirical data through the lens of social learning theories gives insight into the ‘how and why’ transformative learning takes place and might help to plan IPE sessions with greater confidence.

Published
2018

48. Vemurafenib for Refractory Multisystem Langerhans Cell Histiocytosis in Children: An International Observational Study

Author

Donadieu, Jean, primary, Larabi, Islam Amine, additional, Tardieu, Mathilde, additional, Visser, Johannes, additional, Hutter, Caroline, additional, Sieni, Elena, additional, Kabbara, Nabil, additional, Barkaoui, Mohamed, additional, Miron, Jean, additional, Chalard, François, additional, Milne, Paul, additional, Haroche, Julien, additional, Cohen, Fleur, additional, Hélias-Rodzewicz, Zofia, additional, Simon, Nicolas, additional, Jehanne, Mathilde, additional, Kolenova, Alexandra, additional, Pagnier, Anne, additional, Aladjidi, Nathalie, additional, Schneider, Pascale, additional, Plat, Geneviève, additional, Lutun, Anne, additional, Sonntagbauer, Anne, additional, Lehrnbecher, Thomas, additional, Ferster, Alina, additional, Efremova, Viktoria, additional, Ahlmann, Martina, additional, Blanc, Laurence, additional, Nicholson, James, additional, Lambilliote, Anne, additional, Boudiaf, Houda, additional, Lissat, Andrej, additional, Svojgr, Karel, additional, Bernard, Fanette, additional, Elitzur, Sarah, additional, Golan, Michal, additional, Evseev, Dmitriy, additional, Maschan, Michael, additional, Idbaih, Ahmed, additional, Slater, Olga, additional, Minkov, Milen, additional, Taly, Valerie, additional, Collin, Matthew, additional, Alvarez, Jean-Claude, additional, Emile, Jean-François, additional, and Héritier, Sébastien, additional

Published
2019
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49. OP0202 EFFECT OF RSLV-132 ON FATIGUE IN PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME – RESULTS OF A PHASE II RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PROOF OF CONCEPT STUDY

Author

Fisher, Benjamin, primary, Barone, Francesca, additional, Jobling, Kerry, additional, Gallagher, Peter, additional, Macrae, Victoria, additional, Filby, Andrew, additional, Hulmes, Gillian, additional, Milne, Paul, additional, Traianos, Emmanuella, additional, Iannizzotto, Valentina, additional, Dumusc, Alexandre, additional, Bowman, Simon J., additional, Tarn, Jessica, additional, Lendrem, Dennis, additional, Burge, Daniel, additional, Posada, James, additional, and Ng, Wan-fai, additional

Published
2019
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