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6. 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

7. 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

8. 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

9. 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

11. JUVENILE LIFE WITH (OUT) PAROLE.

Author

LESLIE, RACHEL E.

Subjects
*JUVENILE parole, *PUNISHMENT, *PAROLE
Abstract

Beginning in the late twentieth century, the Supreme Court gradually restricted the range of punishments that could be imposed on children convicted of crimes. The seminal cases Graham v. Florida, Miller v. Alabama, and Montgomery v. Louisiana banned the imposition of mandatory life without parole sentences on children who were under eighteen at the time of an offense and held that those juveniles must be given a “meaningful opportunity to obtain release based on demonstrated maturity and rehabilitation.” Some courts have extended the logic of these cases to invalidate life with parole sentences based on extremely long parole ineligibility periods, but no court has held that the practical unavailability of release within the current parole system makes any life sentence—regardless of its parole ineligibility period—functionally equivalent to life without parole. Building on recent scholarship about the constitutional role of parole release in juvenile sentencing, this Note points out that the Graham trilogy creates a substantive Eighth Amendment right for juveniles to be released upon a showing of maturity and rehabilitation, not merely a right to be considered for release. This Note exposes the failure of state parole systems to vindicate this right by systematically refusing to grant parole to juveniles. Because release on parole is a statistical improbability for juveniles sentenced to life with parole, this Note concludes that those sentences are actually unconstitutional sentences of de facto juvenile life without parole. [ABSTRACT FROM AUTHOR]

Published
2023

14. Allele-informed copy number evaluation of plasma DNA samples from metastatic prostate cancer patients: the PCF_SELECT consortium assay

Author

Orlando, Francesco, Romanel, Alessandro, Trujillo, Blanca, Sigouros, Michael, Wetterskog, Daniel, Quaini, Orsetta, Leone, Gianmarco, Xiang, Jenny Z, Wingate, Anna, Tagawa, Scott, Jayaram, Anuradha, Linch, Mark, Swanton, Charles, Jamal-Hanjani, Mariam, Abbosh, Chris, Zaccaria, Simone, Hessey, Sonya, Shiu, Kai-Keen, Bridgewater, John, Hochhauser, Daniel, Forster, Martin, Lee, Siow-Ming, Ahmad, Tanya, Papadatos-Pastos, Dionysis, Janes, Sam, Van Loo, Peter, Enfield, Katey, McGranahan, Nicholas, Huebner, Ariana, Quezada, Sergio, Beck, Stephan, Parker, Peter, Enver, Tariq, Hynds, Robert E, Dijkstra, Krijn, Pearce, David R, Falzon, Mary, Proctor, Ian, Sinclair, Ron, Lok, Chi-wah, Rhodes, Zoe, Moore, David, Marafioti, Teresa, Mitchison, Miriam, Ellery, Peter, Sivakumar, Monica, Brandner, Sebastian, Rowan, Andrew, Hiley, Crispin, Veeriah, Selvaraju, Shaw, Heather, Attard, Gert, Naceur-Lombardelli, Cristina, Toncheva, Antonia, Prymas, Paulina, Watkins, Tom, Bailey, Chris, Ruiz, Carlos Martinez, Litchfield, Kevin, Al-Bakir, Maise, Kanu, Nnenna, Ward, Sophie, Lim, Emilia, Reading, James, Chain, Benny, Alba, Blanca Trujillo, Akay, Melek, Flanagan, Adrienne, Biswas, Dhruva, Pich, Oriol, Dietzen, Michelle, Puttick, Clare, Colliver, Emma, Magness, Alistair, Angelova, Mihaela, Black, James, Lucas, Olivia, Hill, William, Liu, Wing-Kin, Frankell, Alexander, Magno, Neil, Athanasopoulou, Foteini, Wilson, Gareth, Rosenthal, Rachel, Salgado, Roberto, Lee, Claudia, Grigoriadis, Kristiana, Al-Sawaf, Othman, Karasaki, Takahiro, Bunkum, Abigail, Noorani, Imran, Benafif, Sarah, Barbe, Vittorio, Bola, Supreet, Vainauskas, Osvaldas, Hasan, Mahedi, Lise, Stefano, Leone, GianMarco, Alifrangis, Constantine, McGovern, Ursula, Thol, Kerstin, Gamble, Samuel, Ung, Seng Kuong, Sahwangarrom, Teerapon, Marin, Claudia Peinador, Wong, Sophia, Pawlik, Piotr, Gishen, Faye, Tookman, Adrian, Stone, Paddy, Stirling, Caroline, Turajlic, Samra, Larkin, James, Pickering, Lisa, Furness, Andrew, Young, Kate, Drake, Will, Edmonds, Kim, Hunter, Nikki, Mangwende, Mary, Pearce, Karla, Grostate, Lauren, Au, Lewis, Spain, Lavinia, Shepherd, Scott, Yan, Haixi, Shum, Ben, Tippu, Zayd, Hanley, Brian, Spencer, Charlotte, Emmerich, Max, Gerard, Camille, Schmitt, Andreas Michael, Del Rosario, Lyra, Carlyle, Eleanor, Lewis, Charlotte, Holt, Lucy, Lucanas, Analyn, O'Flaherty, Molly, Hazell, Steve, Mudhar, Hardeep, Messiou, Christina, Latifoltojar, Arash, Fendler, Annika, Byrne, Fiona, Pallinkonda, Husayn, Lobon, Irene, Coulton, Alex, Cattin, Anne Laure, Deng, Daqi, Feng, Geoffrey Hugang, Rowan, Andew, Yousaf, Nadia, Popat, Sanjay, Curtis, Olivia, Milner-Watts, Charlotte, Stamp, Gordon, Nye, Emma, Murra, Aida, Korteweg, Justine, Kelly, Denise, Terry, Lauren, Biano, Jennifer, Peat, Kema, Kelly, Kayleigh, Hill, Peter, Josephs, Debra, Irshad, Sheeba, Chandra, Ashish, Spicer, James, Mahadeva, Ula, Green, Anna, Stewart, Ruby, Iredale, Lara-Rose, Mackay, Tina, Deakin, Ben, Enting, Debra, Rudman, Sarah, Ghosh, Sharmistha, Karapagniotou, Lena, Pintus, Elias, Tutt, Andrew, Howlett, Sarah, Michalarea, Vasiliki, Brenton, James, Caldas, Carlos, Fitzgerald, Rebecca, Jimenez-Linan, Merche, Provenzano, Elena, Cluroe, Alison, Paterson, Anna, Aitken, Sarah, Allinson, Kieren, Stewart, Grant, McDermott, Ultan, Beddowes, Emma, Maughan, Tim, Ansorge, Olaf, Campbell, Peter, Roxburgh, Patricia, Fraser, Sioban, Kidd, Andrew, Blyth, Kevin, Le Quesne, John, Krebs, Matthew, Blackhall, Fiona, Summers, Yvonne, Oliveira, Pedro, Ortega-Franco, Ana, Dive, Caroline, Gomes, Fabio, Carter, Mat, Dransfield, Jo, Thomas, Anne, Fennell, Dean, Shaw, Jacqui, Naidu, Babu, Baijal, Shobhit, Tanchel, Bruce, Langman, Gerald, Robinson, Andrew, Collard, Martin, Cockcroft, Peter, Ferris, Charlotte, Bancroft, Hollie, Kerr, Amy, Middleton, Gary, Webb, Joanne, Kadiri, Salma, Colloby, Peter, Olisemeke, Bernard, Wilson, Rodelaine, Tomlinson, Ian, McNeish, Iain, Jogai, Sanjay, Holden, Samantha, Fernandes, Tania, Hampton, Blanche, McKenzie, Mairead, Hackshaw, Allan, Sharp, Abby, Chan, Kitty, Farrelly, Laura, Bridger, Hayley, Leslie, Rachel, Consortium, PEACE, Rubin, Mark A, Wyatt, Alexander W, Beltran, Himisha, Attard, Gerhardt, and Demichelis, Francesca

Subjects
Chemical Biology & High Throughput, Signalling & Oncogenes, Human Biology & Physiology, Ecology,Evolution & Ethology, Genome Integrity & Repair, Tumour Biology, Genetics & Genomics, Computational & Systems Biology
Abstract

Sequencing of cell-free DNA (cfDNA) in cancer patients’ plasma offers a minimally-invasive solution to detect tumor cell genomic alterations to aid real-time clinical decision-making. The reliability of copy number detection decreases at lower cfDNA tumor fractions, limiting utility at earlier stages of the disease. To test a novel strategy for detection of allelic imbalance, we developed a prostate cancer bespoke assay, PCF_SELECT, that includes an innovative sequencing panel covering ∼25 000 high minor allele frequency SNPs and tailored analytical solutions to enable allele-informed evaluation. First, we assessed it on plasma samples from 50 advanced prostate cancer patients. We then confirmed improved detection of genomic alterations in samples with

Published
2022
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18. Parental Allyship for Children With Dyslexia: A Conceptual Lens on Disability Experience.

Author

Leslie, Rachel, Brown, Alice, and Larsen, Ellen

Abstract

Current understandings of disability experience are centered around individuals who hold the disability identity and membership in the marginalized group. This perspective does not include the experiences of disability allies, such as parents, who act alongside their children to support their access and engagement in the education setting. This partial perspective is of concern because it does not reflect the depth and complexity of disability experience for those in allyship roles. This paper builds on current understandings of disability experience by introducing an emerging conceptual lens that defines and describes the nature of disability experience for those acting in allyship roles. Attention is focused on children with dyslexia and their parents to illustrate this conceptual lens. Extending on ecological models of interactions and understandings of subjective experience, the authors highlight how the proximity of the parental experience to the child’s dyslexic identity shapes parental allyship and present a lens of disability experience that includes primary, vicarious, and primary adjacent experience. The proposed conceptual lens offers researchers and educators an opportunity to view disability experience and allyship from an alternative perspective, and in doing so, consider a broader understanding of disability experience and allyship that would potentially provide insights into parent–school partnerships. [ABSTRACT FROM AUTHOR]

Published
2024
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23. NAPLAN testing is about to start. How can you support an anxious child?

Author

Leslie, Rachel

Subjects
MINDFULNESS, CHILD support, YOUNG adults, EDUCATIONAL finance
Abstract

Australian schools will soon begin NAPLAN tests for students in years 3, 5, 7, and 9. The tests will assess literacy and numeracy skills and the results will be made public. While some experts argue that NAPLAN is counterproductive and causes anxiety, others believe that the data collected is valuable for informing teaching practices and school funding. To support anxious students, parents and teachers can talk about the purpose of the test, emphasize that it is a learning experience, and teach children mindfulness techniques to manage anxiety. [Extracted from the article]

Published
2024

27. Cooperative and market-based solutions to pollution abatement problems

Author

Fine, Leslie Rachel

Subjects
Social Science, pollution abatement market solutions, Social Sciences
Abstract

This work concerns itself with the possibility of solutions, both cooperative and market based, to pollution abatement problems. In particular, we are interested in pollutant emissions in Southern California and possible solutions to the abatement problems enumerated in the 1990 Clean Air Act. A tradable pollution permit program has been implemented to reduce emissions, creating property rights associated with various pollutants. Before we discuss the performance of market-based solutions to LA's pollution woes, we consider the existence of cooperative solutions. In Chapter 2, we examine pollutant emissions as a trans boundary public bad. We show that for a class of environments in which pollution moves in a bi-directional, acyclic manner, there exists a sustainable coalition structure and associated levels of emissions. We do so via a new core concept, one more appropriate to modeling cooperative emissions agreements (and potential defection from them) than the standard definitions. However, this leaves the question of implementing pollution abatement programs unanswered. While the existence of a cost-effective permit market equilibrium has long been understood, the implementation of such programs has been difficult. The design of Los Angeles' REgional CLean Air Incentives Market (RECLAIM) alleviated some of the implementation problems, and in part exacerbated them. For example, it created two overlapping cycles of permits and two zones of permits for different geographic regions. While these design features create a market that allows some measure of regulatory control, they establish a very difficult trading environment with the potential for inefficiency arising from the transactions costs enumerated above and the illiquidity induced by the myriad assets and relatively few participants in this market. It was with these concerns in mind that the ACE market (Automated Credit Exchange) was designed. The ACE market utilizes an iterated combined-value call market (CV Market). Before discussing the performance of the RECLAIM program in general and the ACE mechanism in particular, we test experimentally whether a portfolio trading mechanism can overcome market illiquidity. Chapter 3 experimentally demonstrates the ability of a portfolio trading mechanism to overcome portfolio rebalancing problems, thereby inducing sufficient liquidity for markets to fully equilibrate. With experimental evidence in hand, we consider the CV Market's performance in the real world. We find that as the allocation of permits reduces to the level of historical emissions, prices are increasing. As of April of this year, prices are roughly equal to the cost of the Best Available Control Technology (BACT). This took longer than expected, due both to tendencies to mis-report emissions under the old regime, and abatement technology advances encouraged by the program. Vve also find that the ACE market provides liquidity where needed to encourage long-term planning on behalf of polluting facilities.

Published
2001
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30. Increasing Patient Accessibility and Use of Hand Sanitizer Through Introduction of a Single-Dose Packet.

Author

Douglass, Jillian, O'Donnell, Owen, Leslie, Rachel, Nienstadt, Linus, and DiGiorgio, Megan J.

Abstract

Preventing pathogen transmission via healthcare worker (HCW) hand hygiene (HH) is well-established. Emerging evidence suggests patients contaminate their environment with their flora and acquire pathogens on their hands through HCW and environment contact; therefore, there has been increasing interest in patient HH despite lack of guidance. Single-dose hand sanitizer packets (SDP) were evaluated as a solution for accessible patient HH. In a 270-bed hospital, Infection Preventionist randomly solicited patient participation in a study during daily rounds. Patients between September 4–17, 2018 were assigned to the control group (n=32), patients between September 18–November 28, 2018 were assigned to the intervention (n=35). A 7-question baseline survey assessing sanitizer accessibility and HH practices was distributed to the control group. The intervention group received a 24-count SDP via admission kit. Participants were not instructed how/when to use the SDP. A 9-question survey was distributed to the intervention group, including questions on hand cleaning practices, sanitizer accessibility, and evaluation of SDP. Results were analyzed with an independent samples t-test (α=0.05). The intervention group reported higher access to hand sanitizer than the control (mean of 5-point scale, 4.8 and 3.5, respectively; p˂0.001). Patients in the intervention group had higher sanitizer usage (mean of 4-point scale, 3.8 and 2.7, respectively; p˂0.001) and rated higher that they were able to keep their hands germ-free (mean of 5-point scale, intervention 4.7 and control 3.7; p˂0.001). Soap and water usage was higher in the control group (mean of 4-point scale, control 3.2 and intervention 2.4; p=0.003). Patients reported that SDP increased sanitizer accessibility, helped keep their hands germ-free, and increased their hand sanitizer usage. Considering limitations around sink and wall dispenser accessibility and cost constraints with providing patients individual sanitizer bottles, SDP could be a promising solution for admission kits. [ABSTRACT FROM AUTHOR]

Published
2019
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31. Abstracts from the 8th International Congress of the Asia Pacific Society of Infection Control (APSIC)

Author

Sutthiruk, Nantanit, Botti, Mari, Considine, Julie, Driscoll, Andrea, Hutchinson, Ana, Malathum, Kumthorn, Cucunawangsih, Cucunawangsih, Wiwing, Veronica, Puspitasari, Vivien, Shanmugakani, Rathina Kumar, Akeda, Yukihiro, Kodera, Takuya, Santanirand, Pitak, Tomono, Kazunori, Yamanaka, Takayuki, Moriuchi, Hiroyuki, Kitajima, Hiroyuki, Horikoshi, Yuho, Lavrinenko, Alyona, Azizov, Ilya, Tabriz, Nurlan, Kozhamuratov, Margulan, Serbo, Yekatherine, Yang, Dahae, Lee, Woonhyoung, Bae, Il Kwon, Lee, Jae Hyun, Lee, Hyukmin, Kim, Jung Ok, Jeong, Seok Hoon, Lee, Kyungwon, Peremalo, Thiba, Madhavan, Priya, Hamzah, Sharina, Than, Leslie, Wong, Eng Hwa, Desa, Mohd Nasir Mohd, Ng, Kee Peng, Geronimo, Marionne, Tayzon, Maria Fe, Maño, Maria Jesusa, Chow, Angela, Hon, Pei-Yun, Win, Mar-Kyaw, Ang, Brenda, Leo, Yee-Sin, See, Tina, Marin, Rocio Alvarez, de Sousa, Marta Aires, Kieffer, Nicolas, Nordmann, Patrice, Poirel, Laurent, Laochareonsuk, Wison, Petyu, Sireekul, Wanasitchaiwat, Pawin, Thana, Sutasinee, Bunyaphongphan, Chollathip, Boonsomsuk, Woranan, Maneepongpermpoon, Pakpoom, Jamulitrat, Silom, Sureshkumar, Dorairajan, Supraja, Kalyanaraman, Sharmila, Soundararajan, Setiawan, Benny, Lumbuun, Nicolaski, Nakayama, Haruo, Ota, Toshiko, Shirane, Naoko, Matuoka, Chikako, Kodama, Kentaro, Ohtsuka, Masanobu, Bacolcol, Silverose Ann Andales, Velmonte, Melecia, Alde, Allan, Chavez, Keithleen, Esteban, Arlene Joy, Lee, Aisa Jensen, Hsieh, Tai-Chin, Shio-ShinJean, Huang, Huey-Jen, Huang, Shu-Ju, Huang, Yu-Huan, Cheng, Pei-Chen, Yu, Su-Fang, Tsao, Shih-Ming, Lee, Yuan-Ti, Li, Chien-Feng, Lu, Min-Chi, Pruetpongpun, Nattapol, Khawcharoenporn, Thana, Damronglerd, Pansachee, Suwantarat, Nuntra, Apisarnthanarak, Anucha, Rutjanawech, Sasinuch, Cushinotto, Lisa, McBride, Patty, Williams, Harding, Liu, Hans, Hang, Phan Thi, Anh, Dinh Pham Phuong, Le, Ngai, Khu, Dung, Nguyen, Lam, Castillo, Roel Beltran, Gopalakrishnan, Ram, Ramasubramanian, Venkatasubramanian, Sreevidya, Subramanian, Jayapradha, Ranganathan, Umetsu, Atsushi, Noda, Tetsuhiro, Hashimoto, Kenyuu, Hayashi, Akihiro, Kabashima, Mikie, Jadczak, Ursula, Elvelund, Knut, Johnsen, Marit, Borgen, Bente, Lingaas, Egil, Mao, Chia-Hua, Chang, Fu-Chieh, Liu, Chang-Pan, Chao, Ru-Hui, Chang, Fu-chieh, Liu, Chang-pan, Pawapotako, Junpen, Prasertpan, Chadanan, Malaihuan, Wantanee, Uirungroj, Phisit, Saenjum, Chalermpong, Ouirungrog, Teerapat, Borrell, Sue, Bass, Pauline, Worth, Leon, Xian-li, Zhao, Xiao-long, Li, Xue-hua, Yao, Wei, Ren, Zeng, Zhang Xia, Kong, Man Ying, Lai, Christopher Koon Chi, Lee, Suet Yi, Tsang, Ngai Chong, O’Donoghue, M. M., Boost, M. V., Suen, L. K. P., Siu, G. K., Mui, K. W., Lai, C. K. C., Tsang, D. N. C., Sato, Yuka, Tateishi, Mariko, Mihashi, Mutsuko, Flor, Jose Paulo, Bautista, Marko, De Roxas, V. Jay, Vergara, Justine, Añonuevo, Nicolo Andrei, Kwek, Marion, Acuin, Jose, Sanchez, Anna Josea, Bathan, Avel, Jantan, Jamilah Binte, Guek, Chua Chor, Kian, Eu Chiow, Pirido, Pampe Anak, Aron, Nur Fadilah Binte Mohd, Estacio, Leah May, Palana, Francis Alvarez, Gracia, Michelle, Shamsuddin, Nur Syafiqah Binte, Castro, Kersten Timbad, Baloria, Madonna, Adam, Faezah Binte, Wei, Zhang, Fong, Poh Bee, Kalisvar, Marimuthu, Chuang, I-Ju, Yi-ChunCho, Chiu, Yu-Fen, Chen, Lung-Chih, Lin, Yi-Chun, Dong, Shao-Xing, Lee, Yi-Chieh, Kuan, Hui-Chen, Lin, Hsin-Hua, Chi, Chia-Chun, Lu, Chin-Te, Ya-Fen, Tang, Li-Hsiang, Su, Jien-Wei, Liu, Chao, Hsuehlan, ChangChien, PinRu, Chen, WeiFang, Lai, ChungHsu, Ara, Lutfe, Mowla, Syed Mohammad Niaz, Vashkar, Shaikh Mahmud Kamal, Chan, Wai Fong, ChunYau, Mabel Yin, LingChong, Karen Kam, OnLi, Tze, Kaur, Rajwinder, Yan, Ng Po, Chiu, Gloria Chor Shan, Cheung, Christina W. Y., Ching, Patricia T. Y., Ching, Radley H. C., Lam, Conita H. S., Kan, C. H., Lee, Shirley S. Y., Chen, C. P., Chan, Regina F. Y., Leung, Annie F. Y., Wong, Isadora L. C., Lam, S. S., Chan, Queenie W. L., Chan, Cecilia, Nematian, Seyed Sadeq Seyed, Palenik, Charles John, Askarian, Mehrdad, Hatam, Nahid, Nakamura, Itaru, Fujita, Hiroaki, Tsukimori, Ayaka, Kobayashi, Takehito, Sato, Akihiro, Fukushima, Shinji, Matsumoto, Tetsuya, De Roxas, V. James, De Roxas, V James, AndreiAñonuevo, Nicolo, Ho, Yeng May, Kum, Jia Qi, Poh, Bee Fong, Marimuthu, Kalisvar, Liu, Tzu-Yin, Chu, Sin-Man, Chen, Hui-Zhu, Chen, Tun-chieh, Chen, Yichun, Tsao, Ya-Ching, Skuntaniyom, Sumawadee, Tipluy, Pirawadee, Paengta, Sangwan, wongsaen, Ratchanee, thanomphan, Sutthiphun, Tariyo, Samettanet, Thongchuea, Buachan, Khamfu, Pattama, Thanomphan, Sutthiphan, Songtaweesin, Wipaporn Natalie, Anugulruengkit, Suvaporn, Samransamruajkit, Rujipat, Sosothikul, Darintr, Tansrijitdee, Ornanong, Nakphunsung, Anry, Srimuan, Patchareeyawan, Sophonphan, Jirachaya, ThanyaweePuthanakit, Payuk, Kunyanut, Picheansathian, Wilawan, Viseskul, Nongkran, DeNardo, Elizabeth, Leslie, Rachel, Cartner, Todd, Barbosa, Luciana, Werner, Heinz-Peter, Brill, Florian H. H., Kawagoe, Julia Yaeko, De Nardo, Elizabeth, Wilson, Sarah Edmonds, Macinga, David, Mays-Suko, Patricia, Duley, Collette, Hang, Tran Thi Thuy, Hanh, Tran Thi My, Gordon, Christopher, Durairaj, Roopa, Rohit, Anusha, Saravanakumar, Saujanya, Hemalatha, Jothymani, Hirano, Ryuichi, Sakamoto, Yuichi, Yamamoto, Shoji, Tachibana, Naoki, Miura, Miho, Hieda, Fumiyo, Sakai, Yoshiro, Watanabe, Hiroshi, Bacolcol, Silverose Ann, Chavez, Keitleen, Lim, Jia-Wei, Hein, Aung-Aung, Tin, Grace, Lim, Vanessa, Chao, Huwi-chun, Yeh, Chiu-Yin, Lo, Mei-feng, Piwpong, Chonlada, Rajborirug, Songyos, Preechawetchakul, Ploypailin, Pruekrattananapa, Yada, Sangsuwan, Tharntip, Wongsaen, Ratchanee, Paengta, Sungwan, Nilchon, Napatnun, Thanompan, Sutthipun, Tariyo, Samattanet, Kolesnichenko, Svetlana, Tishkambayev, Yerbol, Alibecov, Asylkhan, Serbo, Yekaterina, Nam, Youngwon, Park, Jae Hyeon, Hong, Yun Ji, Kim, Taek Soo, Park, Jeong Su, Park, Kyoung Un, Kim, Eui-Chong, Aziegbemhin, Samuel Abumhere, Enabulele, Onaiwu, Tung, Yao-Shen, Chen, An-Chi, Huang, Shen-Min, Yang, Yui-Yein, Wu, Li-Hung, Lin, Chin-cheng, Lien, Tzu Hao, Chang, Jia Hao, Huang, Yu Shan, Chen, Yi Shun, Sirilun, Sasithorn, Ouirungroj, Phisit, Trakulsomboon, Suwanna, Prasajak, Patcharee, Kwok, Maryanne W. N., Ng, Lady S. H., Wong, Lindy M. T., Poon, Lenina S. L., Lai, Mary K. L., Cheng, Holly H. S., Fong, S. K., Leung, Cindy F. Y., Hasegawa, Jumpei, Shirakawa, Hiroki, Wakai, Sachiko, Mieno, Makiko, Hatakeyama, Shuji, Deeudom, Manu, Tharavichitkul, Prasit, Chinniah, Terrence, Tan, Jackson, Prabu, Kavitha, Alam, Sartaj, Wynn, Aung Kyaw, Ahmad, Rashidah, Sidek, Amalina, Samsuddin, Dg Azizah, Ajis, Noraini, Ahmad, Aliyah, Magon, Susylawathi, Chu, Boon, Kuang, Jiqiu, Gao, Yan, Wang, Shoujun, Hao, Yunxiao, Liu, Rong, Li, Dongmei, Wang, Hui, Nishio, Hisanori, Mori, Hitomi, Morokuma, Yoshiko, Yamada, Takaaki, Kiyosuke, Makiko, Yasunaga, Sachie, Toyoda, Kazuhiro, Shimono, Nobuyuki, Babenko, Dmitriy, Turmuhambetova, Anar, Cheşcă, Antonella, Toleman, Mark A., Akhmaltdinova, Lyudmila L., Magsakay, Mark Albert, Macatibag, Angelo, Lerios, Jeannica Kriselle, Lavrineko, Alyona, Babenko, Dmitry, Sheck, Eugene, Edelstein, Mikhail, Li, Lih-Yue, Chan, Chiung-Wen, Pan, Hui-Chuan, Vanishakije, Wipa, Jaikampun, Warisra, Li, Su-Yin, Li, Jian-Feng, Wu, Yu-Ping, Lin, Chiao-Hui, Chang, Ping-Chin, Tariyo, Samatanet, Thanompan, Suttsiphan, Sukkra, Suchada, Zaman, Khalequ, Zaman, Sheikh Farzana, Zaman, Farzana, Aziz, Asma, Faisal, Sayeed-Bin, Traskine, Magali, Ruiz-Guiñazú, Javier, Borys, Dorota, Lam, Wendy Wai Yee, Chow, May, Choy, Lucy, Kam, Joseph, Salleh, Sharifah Azura, Yacob, Razila, Yusof, Siti Rokiah, Jalil, Nordiah Awang, Millan, Maria Lourdes, Acuin, Jose Lito, Velmonte, Melecia A., Bacolcol, Silverose Ann A., Ting, Ching-I, Dissayasriroj, Sunisa, Chinniah, Terrence Rohan, DiniSuhaimi, Jauharatud, Mirasin, Aizzuddin, Morni, Nurul, Samsuddin, Azizah, AbuBakar, Amalina, Shafiee, Amanie, Safar, Julaini, Annie, Leung, Ling, Fung Yuk, Edna, Lau, Kristine, Luk, Shinomiya, Satoshi, Yamamoto, Kumiko, Kjiwara, Kayoko, Yamaguchi, Mitsuhiro, Zhang, Wei, Poh, Bee-Fong, Chan, Ming-Chin, Wang, Chih-Chien, Huang, Huan-Yu, Lai, Chiung-Ling, Kosol, Sajeerat, Sakolwirat, Wantana, Paepong, Patchanee, Jansanga, Sawalee, Jaisamoot, Pattarin, Thongnuanual, Nuttha, Srithong, Chittima, Somsakul, Somporn, Plongpunth, Sutima, Punpop, Mukkapon, Malathum, Porntip, Peautiwat, Kulada, boon kirdram, Nattawipa, Klunklin, Pimpaporn, Samethadka, Geetha, Suzuki, Naoko, Asada, Hitomi, Katayama, Masao, Komano, Atsushi, Watanabe, Hidehiro, Seo, Hye Kyung, Hwang, Joo-Hee, Shin, Myoung Jin, Kim, Su Young, Kim, Eu Suk, Song, Kyoung-Ho, Kim, Hong Bin, Un, Lai-Si, Vong, Choi-Ian, Koh, Jocelyn, Agustinus, Sherly, Hassan, Rozita Bte Abu, Thinn, Yin Phyu, Ng, Benjamin, Tun, Soe Pyae, Ha, Su Mon Thi, Xiaoting, Xue, Li, Lin, Chuang, Leyland, Niroshika, Attanayaka Mudiyanselage Chulani, Perera, Kaluarachchige Anoma Kaluarachchi, Fernando, Dimingo Kankanamalage Diana Grace, Hemamala, Bodhipakshage Rohini, Yeh, Chiu-yin, Yang, Hui-Chun, Chiu, Hsiang-Ju, Shih, Ya-Ling, Chien, Yu-Shan, Lin, Wan-Yi, Pan, Chia-Yun, Chang, Ying-Yun, Yea, Chiu-Yuch, Chu, Ming-Hsien, Lee, Li-Chu, Yu-Hsiu, Lin, Siao-Pei, Guo, Pak-On, Leung, Mei-Fe, Sie, Jyh-Jou, Chen, Yong-Yuan, Chang, Kuo, Shu-Yuan, Lin, Yu-Hsiu, Zhang, Ji-Sheng, Leung, Pak-On, Sie, Mei-Fe, Chen, Jyh-Jou, Chen, Yan-Ru, Chen, Ying-Ling, Taou, Chi-Fen, Chen, Hsiao-Shan, Tang, Hung-Jen, Chen, Shin Yu, Chen, Yin Yin, Der Wang, Fu, Shih, Tzu-Ping, Chen, Chin-Yu, Chen, Su-Jung, Wu, Mei-chi, Yang, Wan-ju, Chou, Mei-ling, Yu, Man-Ling, Li, Li-Chu, Chu, Cheng-Wei, Tsou, Wen-Hao, Wu, Wen-Chih, Cheng, Wen-Chi, Sun, Cho-Ching, Lu, Shu-Hua, Yang, Hsin-Ling, Lu, Cheng-Yu, Hirunprapakorn, Nitchawan, Apivanich, Sirilux, Pornmee, Ttipakorn, Beowsomboon, Chonnikarnt, Kumkoom, Itthaporn, Kasatpibal, Nongyao, Chitreecheur, Jittaporn, Whitney, JoAnne D., Saokaew, Surasak, Kengkla, Kirati, Heitkemper, Margaret M., Muntajit, Thanomvong, Apivanich, Siriluk, Phan, Hang Thi, Dinh, Anh Pham Phuong, and Nguyen, Tuyet Thi Kim

Subjects
lcsh:RC109-216, Meeting Abstracts, lcsh:Infectious and parasitic diseases
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33. Relative Contributions of Cystathionine β-Synthase and γ-Cystathionase to H2S Biogenesis via Alternative Trans-sulfuration Reactions.

Author

Singh, Sangita, Padovani, Dominique, Leslie, Rachel A., Chiku, Taural, and Banerjee, Ruma

Subjects
*HYDROGEN sulfide, *CYSTATHIONINE gamma-lyase, *ADENOSYLMETHIONINE, *CHEMICAL kinetics, *PHYSIOLOGICAL effects of homocysteine, *SULFURATION
Abstract

In mammals, the two enzymes in the trans-sulfuration pathway, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), are believed to be chiefly responsible for hydrogen sulfide (H2S) biogenesis. In this study, we report a detailed kinetic analysis of the human and yeast CBS-catalyzed reactions that result in H2S generation. CBS from both organisms shows a marked preference for H2S generation by 13-replacement of cysteine by homocysteine. The alternative H2S-generating reactions, i.e. β-elimination of cysteine to generate serine or condensation of 2 mol of cysteine to generate lanthionine, are quantitatively less significant. The kinetic data were employed to simulate the turnover numbers of the various CBS-catalyzed reactions at physiologically relevant substrate concentrations. At equimolar concentrations of CBS and CSE, the simulations predict that H2S production by CBS would account for ∼25-70% of the total H2S generated via the trans-sulfuration pathway depending on the extent of allosteric activation of CBS by S-adenosylmethionine. The relative contribution of CBS to H2S genesis is expected to decrease under hyperhomocysteinemic conditions. CBS is predicted to be virtually the sole source of lanthionine, and CSE, but not CBS, efficiently cleaves lanthionine. The insensitivity of the CBS-catalyzed H2S-generating reactions to the grade of hyperhomocysteinemia is in stark contrast to the responsiveness of CSE and suggests a previously unrecognized role for CSE in intracellular homocysteine management. Finally, our studies reveal that the profligacy of the trans-sulfuration pathway results not only in a multiplicity of H2S-yielding reactions but also yields novel thioether metabolites, thus increasing the complexity of the sulfur metabolome. [ABSTRACT FROM AUTHOR]

Published
2009
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34. Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions.

Author

Singh S, Padovani D, Leslie RA, Chiku T, and Banerjee R

Subjects
Alanine analogs & derivatives, Alanine chemistry, Chromatography, High Pressure Liquid, Computer Simulation, Cysteine chemistry, Humans, Kinetics, Mass Spectrometry methods, Models, Biological, Models, Chemical, Molecular Conformation, Serine chemistry, Sulfides chemistry, Sulfur chemistry, Cystathionine beta-Synthase chemistry, Cystathionine gamma-Lyase chemistry, Hydrogen Sulfide chemistry
Abstract

In mammals, the two enzymes in the trans-sulfuration pathway, cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE), are believed to be chiefly responsible for hydrogen sulfide (H2S) biogenesis. In this study, we report a detailed kinetic analysis of the human and yeast CBS-catalyzed reactions that result in H2S generation. CBS from both organisms shows a marked preference for H2S generation by beta-replacement of cysteine by homocysteine. The alternative H2S-generating reactions, i.e. beta-elimination of cysteine to generate serine or condensation of 2 mol of cysteine to generate lanthionine, are quantitatively less significant. The kinetic data were employed to simulate the turnover numbers of the various CBS-catalyzed reactions at physiologically relevant substrate concentrations. At equimolar concentrations of CBS and CSE, the simulations predict that H2S production by CBS would account for approximately 25-70% of the total H2S generated via the trans-sulfuration pathway depending on the extent of allosteric activation of CBS by S-adenosylmethionine. The relative contribution of CBS to H2S genesis is expected to decrease under hyperhomocysteinemic conditions. CBS is predicted to be virtually the sole source of lanthionine, and CSE, but not CBS, efficiently cleaves lanthionine. The insensitivity of the CBS-catalyzed H2S-generating reactions to the grade of hyperhomocysteinemia is in stark contrast to the responsiveness of CSE and suggests a previously unrecognized role for CSE in intracellular homocysteine management. Finally, our studies reveal that the profligacy of the trans-sulfuration pathway results not only in a multiplicity of H2S-yielding reactions but also yields novel thioether metabolites, thus increasing the complexity of the sulfur metabolome.

Published
2009
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