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3. Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes

Author

McAllan, Liam, Baranasic, Damir, Villicaña, Sergio, Brown, Scarlett, Zhang, Weihua, Lehne, Benjamin, Adamo, Marco, Jenkinson, Andrew, Elkalaawy, Mohamed, Mohammadi, Borzoueh, Hashemi, Majid, Fernandes, Nadia, Lambie, Nathalie, Williams, Richard, Christiansen, Colette, Yang, Youwen, Zudina, Liudmila, Lagou, Vasiliki, Tan, Sili, Castillo-Fernandez, Juan, King, James W. D., Soong, Richie, Elliott, Paul, Scott, James, Prokopenko, Inga, Cebola, Inês, Loh, Marie, Lenhard, Boris, Batterham, Rachel L., Bell, Jordana T., Chambers, John C., Kooner, Jaspal S., and Scott, William R.

Published
2023
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4. K6-linked ubiquitylation marks formaldehyde-induced RNA-protein crosslinks for resolution

Author

Suryo Rahmanto, Aldwin, Blum, Christian J., Scalera, Claudia, Heidelberger, Jan B., Mesitov, Mikhail, Horn-Ghetko, Daniel, Gräf, Justus F., Mikicic, Ivan, Hobrecht, Rebecca, Orekhova, Anna, Ostermaier, Matthias, Ebersberger, Stefanie, Möckel, Martin M., Krapoth, Nils, Da Silva Fernandes, Nádia, Mizi, Athanasia, Zhu, Yajie, Chen, Jia-Xuan, Choudhary, Chunaram, Papantonis, Argyris, Ulrich, Helle D., Schulman, Brenda A., König, Julian, and Beli, Petra

Published
2023
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11. Mutation of p53 increases the competitive ability of pluripotent stem cells.

Author

Montero, Salvador Perez, Paul, Pranab K., di Gregorio, Aida, Bowling, Sarah, Shepherd, Solomon, Fernandes, Nadia J., Lima, Ana, Pérez-Carrasco, Rubén, and Rodriguez, Tristan A.

Subjects
PLURIPOTENT stem cells, CELL division, EMBRYOLOGY, CELL death, NEIGHBORHOODS
Abstract

During development, the rate of tissue growth is determined by the relative balance of cell division and cell death. Cell competition is a fitness quality-control mechanism that contributes to this balance by eliminating viable cells that are less fit than their neighbours. The mutations that confer cells with a competitive advantage and the dynamics of the interactions between winner and loser cells are not well understood. Here, we show that embryonic cells lacking the tumour suppressor p53 are 'super-competitors' that eliminate their wild-type neighbours through the direct induction of apoptosis. This elimination is context dependent, as it does not occur when cells are pluripotent and it is triggered by the onset of differentiation. Furthermore, by combining mathematical modelling and cell-based assays we show that the elimination of wild-type cells is not through competition for space or nutrients, but instead is mediated by short-range interactions that are dependent on the local cell neighbourhood. This highlights the importance of the local cell neighbourhood and the competitive interactions within this neighbourhood for the regulation of proliferation during early embryonic development. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Body composition and lung cancer-associated cachexia in TRACERx

Author

Al-Sawaf, Othman, Weiss, Jakob, Skrzypski, Marcin, Lam, Jie Min, Karasaki, Takahiro, Zambrana, Francisco, Kidd, Andrew C, Frankell, Alexander M, Watkins, Thomas BK, Martinez-Ruiz, Carlos, Puttick, Clare, Black, James RM, Huebner, Ariana, Al Bakir, Maise, Sokac, Mateo, Collins, Susie, Veeriah, Selvaraju, Magno, Neil, Naceur-Lombardelli, Cristina, Prymas, Paulina, Toncheva, Antonia, Ward, Sophia, Jayanth, Nick, Salgado, Roberto, Bridge, Christopher P, Christiani, David C, Mak, Raymond H, Bay, Camden, Rosenthal, Michael, Sattar, Naveed, Welsh, Paul, Liu, Ying, Perrimon, Norbert, Popuri, Karteek, Beg, Mirza Faisal, McGranahan, Nicholas, Hackshaw, Allan, Breen, Danna M, O'Rahilly, Stephen, Birkbak, Nicolai J, Aerts, Hugo JWL, Jamal-Hanjani, Mariam, Swanton, Charles, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Fennell, Dean A, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Price, Gillian, Kerr, Keith M, Benafif, Sarah, Gilbert, Kayleigh, Naidu, Babu, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Middleton, Gary, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Blackhall, Fiona H, Krebs, Matthew G, Summers, Yvonne, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Dive, Caroline, Schwarz, Roland F, Kaufmann, Tom L, Wilson, Gareth A, Rosenthal, Rachel, Van Loo, Peter, Szallasi, Zoltan, Kisistok, Judit, Diossy, Miklos, Demeulemeester, Jonas, Bunkum, Abigail, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Bailey, Chris, Abbosh, Christopher, Weeden, Clare E, Lee, Claudia, Richard, Corentin, Hiley, Crispin T, Moore, David A, Pearce, David R, Karagianni, Despoina, Biswas, Dhruva, Levi, Dina, Hoxha, Elena, Cadieux, Elizabeth Larose, Lim, Emilia L, Colliver, Emma, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran, Lowe, Helen L, Matos, Ignacio Garcia, Goldman, Jacki, Reading, James L, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Hartley, John A, Peggs, Karl S, Enfield, Katey SS, Selvaraju, Kayalvizhi, Thol, Kerstin, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Grigoriadis, Kristiana, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Duran, Marcos Vasquez, Litovchenko, Maria, Sunderland, Mariana Werner, Hill, Mark S, Dietzen, Michelle, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Pich, Oriol, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Quezada, Sergio A, Vanloo, Sharon, Zaccaria, Simone, Hessey, Sonya, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Marafioti, Teresa, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Forster, Martin D, Lee, Siow Ming, Borg, Elaine, Falzon, Mary, Papadatos-Pastos, Dionysis, Wilson, James, Ahmad, Tanya, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Lawrence, David, Patrini, Davide, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Hoogenboom, Emilie Martinoni, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Cave, Judith, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Nicholson, Andrew G, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Blyth, Kevin G, Dick, Craig, Le Quesne, John, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
Male, Proteomics, Cachexia, Lung Neoplasms, Antigens, Neoplasm, Carcinoma, Non-Small-Cell Lung, Body Weight, Body Composition, Humans, Neoplasm Recurrence, Local, Muscle, Skeletal, Neoplasm Proteins
Abstract

Cancer-associated cachexia (CAC) is a major contributor to morbidity and mortality in individuals with non-small cell lung cancer. Key features of CAC include alterations in body composition and body weight. Here, we explore the association between body composition and body weight with survival and delineate potential biological processes and mediators that contribute to the development of CAC. Computed tomography-based body composition analysis of 651 individuals in the TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study suggested that individuals in the bottom 20th percentile of the distribution of skeletal muscle or adipose tissue area at the time of lung cancer diagnosis, had significantly shorter lung cancer-specific survival and overall survival. This finding was validated in 420 individuals in the independent Boston Lung Cancer Study. Individuals classified as having developed CAC according to one or more features at relapse encompassing loss of adipose or muscle tissue, or body mass index-adjusted weight loss were found to have distinct tumor genomic and transcriptomic profiles compared with individuals who did not develop such features. Primary non-small cell lung cancers from individuals who developed CAC were characterized by enrichment of inflammatory signaling and epithelial-mesenchymal transitional pathways, and differentially expressed genes upregulated in these tumors included cancer-testis antigen MAGEA6 and matrix metalloproteinases, such as ADAMTS3. In an exploratory proteomic analysis of circulating putative mediators of cachexia performed in a subset of 110 individuals from TRACERx, a significant association between circulating GDF15 and loss of body weight, skeletal muscle and adipose tissue was identified at relapse, supporting the potential therapeutic relevance of targeting GDF15 in the management of CAC. ispartof: NATURE MEDICINE vol:29 issue:4 ispartof: location:United States status: Published online

Published
2023

14. The evolution of non-small cell lung cancer metastases in TRACERx

Author

Al Bakir, Maise, Huebner, Ariana, Martinez-Ruiz, Carlos, Grigoriadis, Kristiana, Watkins, Thomas BK, Pich, Oriol, Moore, David A, Veeriah, Selvaraju, Ward, Sophia, Laycock, Joanne, Johnson, Diana, Rowan, Andrew, Razaq, Maryam, Akther, Mita, Naceur-Lombardelli, Cristina, Prymas, Paulina, Toncheva, Antonia, Hessey, Sonya, Dietzen, Michelle, Colliver, Emma, Frankell, Alexander, Bunkum, Abigail, Lim, Emilia L, Karasaki, Takahiro, Abbosh, Christopher, Hiley, Crispin T, Hill, Mark S, Cook, Daniel E, Wilson, Gareth A, Salgado, Roberto, Nye, Emma, Stone, Richard Kevin, Fennell, Dean A, Price, Gillian, Kerr, Keith M, Naidu, Babu, Middleton, Gary, Summers, Yvonne, Lindsay, Colin R, Blackhall, Fiona H, Cave, Judith, Blyth, Kevin G, Nair, Arjun, Ahmed, Asia, Taylor, Magali N, Procter, Alexander James, Falzon, Mary, Lawrence, David, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Papadatos-Pastos, Dionysis, Forster, Martin D, Lee, Siow Ming, Ahmad, Tanya, Quezada, Sergio, Peggs, Karl S, Van Loo, Peter, Dive, Caroline, Hackshaw, Allan, Birkbak, Nicolai J, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, Swanton, Charles, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Benafif, Sarah, Gilbert, Kayleigh, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Krebs, Matthew G, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Aerts, Hugo JWL, Schwarz, Roland F, Kaufmann, Tom L, Rosenthal, Rachel, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Demeulemeester, Jonas, Stewart, Aengus, Magness, Alastair, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Bailey, Chris, Puttick, Clare, Weeden, Clare E, Lee, Claudia, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Biswas, Dhruva, Levi, Dina, Hoxha, Elena, Larose Cadieux, Elizabeth, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran, Lowe, Helen L, Matos, Ignacio, Goldman, Jacki, Reading, James L, Black, James RM, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Lam, Jie Min, Hartley, John A, Enfield, Katey SS, Selvaraju, Kayalvizhi, Thol, Kerstin, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Vasquez, Marcos, Litovchenko, Maria, Werner Sunderland, Mariana, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Hobson, Philip, Pawlik, Piotr, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Marafioti, Teresa, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Borg, Elaine, Wilson, James, Patrini, Davide, Martinoni Hoogenboom, Emilie, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Nicholson, Andrew G, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Dick, Craig, Le Quesne, John, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
Clonal Evolution, Cohort Studies, Evolution, Molecular, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Disease Progression, Humans, Neoplasm Metastasis, Neoplasm Recurrence, Local, Clone Cells
Abstract

Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse. ispartof: NATURE vol:616 issue:7957 ispartof: location:England status: Published online

Published
2023

15. The evolution of lung cancer and impact of subclonal selection in TRACERx

Author

Frankell, Alexander M, Dietzen, Michelle, Al Bakir, Maise, Lim, Emilia L, Karasaki, Takahiro, Ward, Sophia, Veeriah, Selvaraju, Colliver, Emma, Huebner, Ariana, Bunkum, Abigail, Hill, Mark S, Grigoriadis, Kristiana, Moore, David A, Black, James RM, Liu, Wing Kin, Thol, Kerstin, Pich, Oriol, Watkins, Thomas BK, Naceur-Lombardelli, Cristina, Cook, Daniel E, Salgado, Roberto, Wilson, Gareth A, Bailey, Chris, Angelova, Mihaela, Bentham, Robert, Martinez-Ruiz, Carlos, Abbosh, Christopher, Nicholson, Andrew G, Le Quesne, John, Biswas, Dhruva, Rosenthal, Rachel, Puttick, Clare, Hessey, Sonya, Lee, Claudia, Prymas, Paulina, Toncheva, Antonia, Smith, Jon, Xing, Wei, Nicod, Jerome, Price, Gillian, Kerr, Keith M, Naidu, Babu, Middleton, Gary, Blyth, Kevin G, Fennell, Dean A, Forster, Martin D, Lee, Siow Ming, Falzon, Mary, Hewish, Madeleine, Shackcloth, Michael J, Lim, Eric, Benafif, Sarah, Russell, Peter, Boleti, Ekaterini, Krebs, Matthew G, Lester, Jason F, Papadatos-Pastos, Dionysis, Ahmad, Tanya, Thakrar, Ricky M, Lawrence, David, Navani, Neal, Janes, Sam M, Dive, Caroline, Blackhall, Fiona H, Summers, Yvonne, Cave, Judith, Marafioti, Teresa, Herrero, Javier, Quezada, Sergio A, Peggs, Karl S, Schwarz, Roland F, Van Loo, Peter, Miedema, Daniel M, Birkbak, Nicolai J, Hiley, Crispin T, Hackshaw, Allan, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, Swanton, Charles, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joa, Primrose, Lindsay, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Gilbert, Kayleigh, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Aerts, Hugo JWL, Kaufmann, Tom L, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Demeulemeester, Jonas, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Weeden, Clare E, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Levi, Dina, Hoxha, Elena, Larose Cadieux, Elizabeth, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran L, Lowe, Helen L, Matos, Ignacio, Goldman, Jacki, Reading, James L, Rane, Jayant K, Lam, Jie Min, Hartley, John A, Enfield, Katey SS, Selvaraju, Kayalvizhi, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Vasquez, Marcos, Litovchenko, Maria, Werner Sunderland, Mariana, Leung, Michelle, Escudero, Mickael, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Borg, Elaine, Wilson, James, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Patrini, Davide, Martinoni Hoogenboom, Emilie, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Danson, Sarah, Robinson, Lily, Dick, Craig, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
Lung Neoplasms, Treatment Outcome, DNA Copy Number Variations, Mutagenesis, Carcinoma, Non-Small-Cell Lung, Mutation, Smoking, Humans, Adenocarcinoma of Lung, Neoplasm Recurrence, Local, Phylogeny
Abstract

Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource. ispartof: NATURE vol:616 issue:7957 ispartof: location:England status: Published online

Published
2023

16. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx

Author

Karasaki, Takahiro, Moore, David A, Veeriah, Selvaraju, Naceur-Lombardelli, Cristina, Toncheva, Antonia, Magno, Neil, Ward, Sophia, Al Bakir, Maise, Watkins, Thomas BK, Grigoriadis, Kristiana, Huebner, Ariana, Hill, Mark S, Frankell, Alexander M, Abbosh, Christopher, Puttick, Clare, Zhai, Haoran, Gimeno-Valiente, Francisco, Saghafinia, Sadegh, Kanu, Nnennaya, Dietzen, Michelle, Pich, Oriol, Lim, Emilia L, Martinez-Ruiz, Carlos, Black, James RM, Biswas, Dhruva, Campbell, Brittany B, Lee, Claudia, Colliver, Emma, Enfield, Katey SS, Hessey, Sonya, Hiley, Crispin T, Zaccaria, Simone, Litchfield, Kevin, Birkbak, Nicolai J, Cadieux, Elizabeth Larose, Demeulemeester, Jonas, Van Loo, Peter, Adusumilli, Prasad R, Tan, Kay See, Cheema, Waseem, Sanchez-Vega, Francisco, Jones, David R, Rekhtman, Natasha, Travis, William D, Hackshaw, Allan, Marafioti, Teresa, Salgado, Roberto, Le Quesne, John, Nicholson, Andrew G, McGranahan, Nicholas, Swanton, Charles, Jamal-Hanjani, Mariam, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Fennell, Dean A, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Price, Gillian, Kerr, Keith M, Benafif, Sarah, Gilbert, Kayleigh, Naidu, Babu, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Middleton, Gary, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Blackhall, Fiona H, Krebs, Matthew G, Summers, Yvonne, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Dive, Caroline, Aerts, Hugo JWL, Schwarz, Roland F, Kaufmann, Tom L, Wilson, Gareth A, Rosenthal, Rachel, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Bunkum, Abigail, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Castignani, Carla, Bailey, Chris, Weeden, Clare E, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Levi, Dina, Hoxha, Elena, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Lowe, Helen L, Matos, Ignacio Garcia, Goldman, Jacki, Reading, James L, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Lam, Jie Min, Hartley, John A, Peggs, Karl S, Selvaraju, Kayalvizhi, Thol, Kerstin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Duran, Marcos Vasquez, Litovchenko, Maria, Sunderland, Mariana Werner, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Prymas, Paulina, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Quezada, Sergio A, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Forster, Martin D, Lee, Siow Ming, Borg, Elaine, Falzon, Mary, Papadatos-Pastos, Dionysis, Wilson, James, Ahmad, Tanya, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Lawrence, David, Patrini, Davide, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Hoogenboom, Emilie Martinoni, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Cave, Judith, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Blyth, Kevin G, Dick, Craig, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
TRACERx Consortium
Abstract

Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions in predominantly high-grade pattern tumors exhibited higher proliferation and lower clonal diversity, potentially reflecting large recent subclonal expansions. Co-occurrence of truncal loss of chromosomes 3p and 3q was enriched in predominantly low-/mid-grade tumors, while purely undifferentiated solid-pattern tumors had a higher frequency of truncal arm or focal 3q gains and SMARCA4 gene alterations compared with mixed-pattern tumors with a solid component, suggesting distinct evolutionary trajectories. Clonal evolution analysis revealed that tumors tend to evolve toward higher-grade patterns. The presence of micropapillary pattern and 'tumor spread through air spaces' were associated with intrathoracic recurrence, in contrast to the presence of solid/cribriform patterns, necrosis and preoperative circulating tumor DNA detection, which were associated with extra-thoracic recurrence. These data provide insights into the relationship between LUAD morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk. ispartof: NATURE MEDICINE vol:29 issue:4 ispartof: location:United States status: Published online

Published
2023

17. Evaluating the Accessibility of Adaptive TV Based Web Applications

Author

Fernandes, Nádia, Costa, Daniel, Duarte, Carlos, Carriço, Luís, Tan, Desney, Editor-in-chief, Vanderdonckt, Jean, Editor-in-chief, Pribeanu, Costin, Series editor, Wesson, Janet, Series editor, Calvary, Gaëlle, Series editor, Cao, Xiang, Series editor, Gonzalez Calleros, Juan, Series editor, Biswas, Pradipta, editor, Duarte, Carlos, editor, Langdon, Patrick, editor, and Almeida, Luis, editor

Published
2015
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20. Web Accessibility in Africa: A Study of Three African Domains

Author

Costa, Daniel, Fernandes, Nádia, Neves, Sofia, Duarte, Carlos, Hijón-Neira, Raquel, Carriço, Luís, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Kotzé, Paula, editor, Marsden, Gary, editor, Lindgaard, Gitte, editor, Wesson, Janet, editor, and Winckler, Marco, editor

Published
2013
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21. Assessing the Effort of Repairing the Accessibility of Web Sites

Author

Fernandes, Nádia, Carriço, Luís, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Miesenberger, Klaus, editor, Karshmer, Arthur, editor, Penaz, Petr, editor, and Zagler, Wolfgang, editor

Published
2012
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22. Accessibility of Dynamic Adaptive Web TV Applications

Author

Costa, Daniel, Fernandes, Nádia, Duarte, Carlos, Carriço, Luís, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Miesenberger, Klaus, editor, Karshmer, Arthur, editor, Penaz, Petr, editor, and Zagler, Wolfgang, editor

Published
2012
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23. An Architecture for Multiple Web Accessibility Evaluation Environments

Author

Fernandes, Nádia, Lopes, Rui, Carriço, Luís, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Nierstrasz, Oscar, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Sudan, Madhu, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Vardi, Moshe Y., Series editor, Weikum, Gerhard, Series editor, and Stephanidis, Constantine, editor

Published
2011
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24. Global spatial dynamics and vaccine-induced fitness changes of Bordetella pertussis

Author

Lefrancq, Noémie, primary, Bouchez, Valérie, additional, Fernandes, Nadia, additional, Barkoff, Alex-Mikael, additional, Bosch, Thijs, additional, Dalby, Tine, additional, Åkerlund, Thomas, additional, Darenberg, Jessica, additional, Fabianova, Katerina, additional, Vestrheim, Didrik F., additional, Fry, Norman K., additional, González-López, Juan José, additional, Gullsby, Karolina, additional, Habington, Adele, additional, He, Qiushui, additional, Litt, David, additional, Martini, Helena, additional, Piérard, Denis, additional, Stefanelli, Paola, additional, Stegger, Marc, additional, Zavadilova, Jana, additional, Armatys, Nathalie, additional, Landier, Annie, additional, Guillot, Sophie, additional, Hong, Samuel L., additional, Lemey, Philippe, additional, Parkhill, Julian, additional, Toubiana, Julie, additional, Cauchemez, Simon, additional, Salje, Henrik, additional, and Brisse, Sylvain, additional

Published
2022
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26. Framework proposal based on absorptive capacity for agile transformation with a focus on overcoming barriers in information technology departments

Author

Fernandes, Nadia Pedrosa, Martens, Cristina Dai Prá, Silva, Luciano Ferreira da, Ruas, Roberto Lima, Penha, Renato, and Rossetto, Carlos Ricardo

Subjects
ADMINISTRACAO [CIENCIAS SOCIAIS APLICADAS], agile approach, barriers, absorptive capacity, transformação ágil, innovation, agile transformation, project management, agility, capacidade absortiva, inovação, gerenciamento de projetos, abordagem ágil, agilidade, barreiras
Abstract

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2022-08-01T21:33:59Z No. of bitstreams: 1 Nadia Pedrosa Fernandes.pdf: 2693520 bytes, checksum: d529a31f8980390172ee1524cfb9863c (MD5) Made available in DSpace on 2022-08-01T21:33:59Z (GMT). No. of bitstreams: 1 Nadia Pedrosa Fernandes.pdf: 2693520 bytes, checksum: d529a31f8980390172ee1524cfb9863c (MD5) Previous issue date: 2021-11-26 A traditional approach to project management or product development created in the 1970s began to prove outdated, with its first stages of planning and providing the requirements, with the necessary changes and aggressive in most markets. The agile approach thus emerges as a promise to improve companies' responsiveness and innovation and leverage the performance of their technology projects, which leads companies into an agile race in the early 2000s - a phenomenon known as agile transformation. After a few years of agile practices, the literature has scientifically proven its benefits, but it does not provide guidance on how to carry out an agile transformation and even less on how to face barriers that are so characteristic of this process. In this context, the main objective of this research was to propose a framework that presents actions to overcome barriers of agile transformation, from the perspective of absorptive resources (ACAP), in Information Technology (IT) departments. To this end, the theme of agile transformation was explored through in-depth research with agile transformation participants. The identified transcripts were analyzed using the Grounded Theory strategy in three iterative analysis cycles: open, axial and selective. Data analysis procedures were based on the technique of constant comparisons that support the analysis cycles of Grounded Theory with the support of the Atlas.ti tool. Data were collected and propagated until the results of the identifications were incorporated and triangulated with the support of documental research to result in the elaboration of the framework with actions to overcome barriers of agile transformation. Evidence of the use of ACAP was found to a greater or lesser degree in the overcoming of barriers in all the declared ones, however, the greatest focus of actions resides on potential ACAP, to the detriment of the ACAP performed. As a theoretical contribution, the research required the addition of two new dimensions: propagation and adaptation and a more iterative and recursive ACAP flow with knowledge propagation as an elementary condition for agile transformation success. Based on the literature review and the findings of this research, some prescriptions were developed for the practitioner community to facilitate agile transformation. A abordagem tradicional de gerenciamento de projetos ou de desenvolvimento de produtos, criada nos anos 1970, com suas longas etapas de planejamento e centenas de requisitos descritos, começou a se mostrar defasada, diante das mudanças frequentes e da competitividade agressiva na maioria dos mercados. A abordagem ágil surge, então, como promessa para melhorar a responsividade e inovação das empresas e alavancar o desempenho de seus projetos de tecnologia, o que leva as empresas à uma corrida agilista no início dos anos 2000 – fenômeno conhecido como transformação ágil. Após alguns anos de práticas ágeis, a literatura já comprova cientificamente seus benefícios, mas não orienta bem quanto à forma de realizar a transformação ágil e menos ainda sobre como enfrentar as barreiras tão características desse processo. Nesse contexto, o objetivo principal desta pesquisa foi propor um framework que apresente as ações de superação de barreiras da transformação ágil, sob a ótica das capacidades absortivas (ACAP), em departamentos de Tecnologia da Informação (TI). Para tanto, o tema da transformação ágil foi explorado por meio de entrevistas em profundidade com participantes da transformação ágil. As transcrições das entrevistas foram analisadas via estratégia da Grounded Theory, em três ciclos iterativos de análise: aberta, axial e seletiva. Os procedimentos de análise de dados foram embasados na técnica das comparações constantes, que suportam os ciclos de análise da Grounded Theory, com o apoio da ferramenta Atlas.ti. Os dados foram coletados e analisados até que os resultados das entrevistas fossem saturados e triangulados com o suporte da pesquisa documental, para resultar na elaboração do framework com as ações de superação de barreiras da transformação ágil. Evidências do uso da ACAP foram encontradas em maior ou menor grau na superação de barreiras em todas as entrevistas, entretanto, o foco maior das ações reside sobre ACAP potencial, em detrimento da ACAP realizada. Como contribuição teórica, a pesquisa sugere a adição de duas novas dimensões: propagação e adaptação e um fluxo de ACAP mais iterativo e recursivo tendo a propagação do conhecimento como condição elementar para o sucesso da transformação ágil. Com base na revisão da literatura e achados desta pesquisa, algumas prescrições foram desenvolvidas para a comunidade praticante a fim de uma condução facilitada da transformação ágil.

Published
2021

27. Spatial dynamics and vaccine-induced fitness changes of Bordetella pertussis

Author

Lefrancq, Noemie, primary, Bouchez, Valerie, additional, Fernandes, Nadia, additional, Barkoff, Alex-Mikael, additional, Bosch, Thijs, additional, Dalby, Tine, additional, Akerlund, Thomas, additional, Fabianova, Katerina, additional, Vestrheim, Didrik F, additional, Fry, Norman K., additional, Gonzalez-Lopez, Juan Jose, additional, Gullsby, Karolina, additional, Habington, Adele, additional, He, Qiushui, additional, Litt, David, additional, Martini, Helena, additional, Pierard, Denis, additional, Stefanelli, Paola, additional, Stegger, Marc K., additional, Zavadilov, Jana, additional, Armatys, Nathalie, additional, Landier, Annie, additional, Guillot, Sophie, additional, Hong, Samuel L, additional, Lemey, Philippe, additional, Parkhill, Julian, additional, Toubiana, Julie, additional, Cauchemez, Simon, additional, Salje, Henrik, additional, and Brisse, Sylvain, additional

Published
2021
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30. Acción civil pública: forma célere y efectiva de protección de los derechos fundamentales de los trabajadores

Author

Fernandes, Nadia Soraggi, Pimenta, José Roberto Freire Orientador, and Pontifícia Universidade Católica de Minas Gerais.Programa de Pós-Graduação em Direito Instituição

Subjects
Trabalhadores-Direitos fundamentais-Teses, Direito processual coletivo-Teses, Ação civil pública-Teses, Direito do trabalho-Aspectos sociais-Teses, 331.16
Abstract

Dissertação (mestrado) - Pontifícia Universidade Católica de Minas Gerais, Programa de Pós-Graduação em Direito. Bibliografia: f. 204-211 Resumo: Tem por objetivo a presente obra a demonstração da relevância da ação civil pública na defesa dos direitos fundamentais dos trabalhadores e na própria efetividade da Justiça Trabalhista. Para tanto, procurou este estudo destacar os benefícios dessa nova concepção processual de tutela coletiva para a proteção e efetivação não somente dos direitos metaindividuais, mas também dos tradicionais direitos individuais trabalhistas, salientando que, para a sua real implantação, devem os operadores do Direito adotá-la com uma nova mentalidade, na busca da superação dos obstáculos que a ela ainda se antepõem e, sobretudo, do aprimoramento do seu sistema. Assim, foram analisados os seus pontos sensíveis, principalmente no que se refere ao acesso à justiça, ao modo de ser do processo e à utilidade das decisões, na perspectiva de um processo de resultados capaz de tornar realidade os direitos dos trabalhadores, atendendo às promessas constitucionais e contribuindo para a afirmação do Estado Democrático de Direito. Abstract: Tiene como objetivo la presente obra la demostración de la relevancia de la acción civil pública en la defensa de los derechos fundamentales de los trabajadores y en la propia efectividad de la Justicia del Trabajo. Para tanto, buscó este estudio destacar los beneficios de esa nueva concepción procesal de tutela colectiva para la protección y efectuación no solamente de los derechos metaindividuales, pero también de los tradicionales derechos individuales laborales, resaltando que, para su real implantación, deben los operadores del Derecho adoptarla con una nueva mentalidad, en la búsqueda de la superación de los obstáculos que a ella aún se le anteponen y, sobretodo, del perfeccionamiento de su sistema. Así, fueron analizados sus puntos sensibles en lo que se refiere al acceso a la justicia, al modo de ser del proceso y a la utilidad de las decisiones, bajo la perspectiva de un proceso de resultados capaz de volver realidad los derechos de los trabajadores, atendiendo a las promesas constitucionales y contribuyendo para la afirmación del Estado Democrático de Derecho.

Published
2009

31. O processo de decisão de compra por meio da web: um estudo de campo aplicando o CHIC.

Author

DE OLIVEIRA NASCIMENTO, CAMILA, TURUO ONO, ARNALDO, NERGUISIAN, NATHÁLIA, CARVALHO ALVES, JÉSSICA, and MORO FERNANDES, NADIA

Subjects
ELECTRONIC commerce, ECONOMIC aspects of decision making, CONSUMER behavior research, INTERNET & economics, MARKETING research
Abstract

Copyright of Educação Matemática Pesquisa is the property of Pontificia Universidade Catolica de Sao Paulo, Programa de Estudos Pos-Grad. em Educacao Matematica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2014

32. Global spatial dynamics and vaccine-induced fitness changes of Bordetella pertussis

Author

Noémie Lefrancq, Valérie Bouchez, Nadia Fernandes, Alex-Mikael Barkoff, Thijs Bosch, Tine Dalby, Thomas Åkerlund, Jessica Darenberg, Katerina Fabianova, Didrik F. Vestrheim, Norman K. Fry, Juan José González-López, Karolina Gullsby, Adele Habington, Qiushui He, David Litt, Helena Martini, Denis Piérard, Paola Stefanelli, Marc Stegger, Jana Zavadilova, Nathalie Armatys, Annie Landier, Sophie Guillot, Samuel L. Hong, Philippe Lemey, Julian Parkhill, Julie Toubiana, Simon Cauchemez, Henrik Salje, Sylvain Brisse, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of Cambridge [UK] (CAM), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre national de Référence de la Coqueluche et autres Bordetelloses - National Reference Center for Whooping Cough and other Bordetella infections (CNR), University of Turku, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Statens Serum Institut [Copenhagen], The Public Health Agency of Sweden, National Institute of Public Health [Prague], Norwegian Institute of Public Health [Oslo] (NIPH), Public Health England [London], Vall d'Hebron University Hospital [Barcelona], Universitat Autònoma de Barcelona (UAB), Uppsala University, Children's Health Ireland [Crumlin, Dublin, Ireland] (CHI), Vrije Universiteit Brussel (VUB), Istituto Superiore di Sanità (ISS), Rega Institute, Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), The study was supported financially by the French Government Investissement d’Avenir grant ANR-16-CONV-0005 (INCEPTION project, to S.B. and H.S.). The National Reference Center for Whooping Cough and Other Bordetella Infections receives support from Institut Pasteur and Public Health France (Santé publique France, Saint Maurice, France). This work was also supported financially by the French Government’s Investissement d’Avenir program Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID) to S.B. and a European Research Council (no. 804744 to H.S.). P.L. acknowledges funding from the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 725422-ReservoirDOCS)., ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 804744,H2020-EU.1.1.,ARBODYNAMIC(2019), European Project: 725422,ERC-2016-COG,ReservoirDOCS(2017), Supporting clinical sciences, Microbiology and Infection Control, Clinical Biology, Lefrancq, Noémie [0000-0001-5991-6169], Bouchez, Valérie [0000-0002-5947-6383], Fernandes, Nadia [0000-0003-4595-9939], Dalby, Tine [0000-0003-4774-7091], Åkerlund, Thomas [0000-0001-7516-0218], Darenberg, Jessica [0000-0002-8528-8570], Fabianova, Katerina [0000-0001-8374-4395], Fry, Norman K [0000-0003-4862-6507], González-López, Juan José [0000-0003-2419-5909], Gullsby, Karolina [0000-0002-9673-0483], Habington, Adele [0000-0001-6997-3327], Litt, David [0000-0002-9215-0553], Martini, Helena [0000-0002-5877-9948], Piérard, Denis [0000-0002-7756-3691], Stefanelli, Paola [0000-0003-1620-4385], Stegger, Marc [0000-0003-0321-1180], Armatys, Nathalie [0000-0003-2042-4241], Landier, Annie [0000-0002-8278-4026], Hong, Samuel L [0000-0001-6354-4943], Lemey, Philippe [0000-0003-2826-5353], Parkhill, Julian [0000-0002-7069-5958], Cauchemez, Simon [0000-0001-9186-4549], Salje, Henrik [0000-0003-3626-4254], Brisse, Sylvain [0000-0002-2516-2108], and Apollo - University of Cambridge Repository

Subjects
Europe, Pertussis Vaccine, Genotype, Whooping Cough, [SDV]Life Sciences [q-bio], Humans, General Medicine, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bordetella pertussis
Abstract

As with other pathogens, competitive interactions between Bordetella pertussis strains drive infection risk. Vaccines are thought to perturb strain diversity through shifts in immune pressures; however, this has rarely been measured because of inadequate data and analytical tools. We used 3344 sequences from 23 countries to show that, on average, there are 28.1 transmission chains circulating within a subnational region, with the number of chains strongly associated with host population size. It took 5 to 10 years for B. pertussis to be homogeneously distributed throughout Europe, with the same time frame required for the United States. Increased fitness of pertactin-deficient strains after implementation of acellular vaccines, but reduced fitness otherwise, can explain long-term genotype dynamics. These findings highlight the role of vaccine policy in shifting local diversity of a pathogen that is responsible for 160,000 deaths annually.

Published
2022
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33. Mutation of p53 increases the competitive ability of pluripotent stem cells.

Author

Perez Montero S, Paul PK, di Gregorio A, Bowling S, Shepherd S, Fernandes NJ, Lima A, Pérez-Carrasco R, and Rodriguez TA

Subjects
Tumor Suppressor Protein p53 genetics, Mutation genetics, Apoptosis genetics, Cell Communication physiology, Pluripotent Stem Cells
Abstract

During development, the rate of tissue growth is determined by the relative balance of cell division and cell death. Cell competition is a fitness quality-control mechanism that contributes to this balance by eliminating viable cells that are less fit than their neighbours. The mutations that confer cells with a competitive advantage and the dynamics of the interactions between winner and loser cells are not well understood. Here, we show that embryonic cells lacking the tumour suppressor p53 are 'super-competitors' that eliminate their wild-type neighbours through the direct induction of apoptosis. This elimination is context dependent, as it does not occur when cells are pluripotent and it is triggered by the onset of differentiation. Furthermore, by combining mathematical modelling and cell-based assays we show that the elimination of wild-type cells is not through competition for space or nutrients, but instead is mediated by short-range interactions that are dependent on the local cell neighbourhood. This highlights the importance of the local cell neighbourhood and the competitive interactions within this neighbourhood for the regulation of proliferation during early embryonic development., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Published
2024
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