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79 results on '"German, A. J."'

1. The Histopathological Characteristic of Gastric Carcinoma in the Belgian Tervueren and Groenendael Dog: A Comparison of Two Classification Methods

Author: Intensieve zorgafdeling, Pathobiologie, Interne geneeskunde GD, CS_Genetics, Kijan, Christina, Hugen, Sanne, Thomas, Rachel E., Oberbauer, Anita M., Leegwater, Peter A. J., Fieten, Hille, German, Alexander J., Mandigers, Paul J. J., Intensieve zorgafdeling, Pathobiologie, Interne geneeskunde GD, CS_Genetics, Kijan, Christina, Hugen, Sanne, Thomas, Rachel E., Oberbauer, Anita M., Leegwater, Peter A. J., Fieten, Hille, German, Alexander J., and Mandigers, Paul J. J.
Published: 2023

2. The Histopathological Characteristic of Gastric Carcinoma in the Belgian Tervueren and Groenendael Dog: A Comparison of Two Classification Methods.

Author: Kijan, Christina, Kijan, Christina, Hugen, Sanne, Thomas, Rachel E, Oberbauer, Anita M, Leegwater, Peter AJ, Fieten, Hille, German, Alexander J, Mandigers, Paul JJ, Kijan, Christina, Kijan, Christina, Hugen, Sanne, Thomas, Rachel E, Oberbauer, Anita M, Leegwater, Peter AJ, Fieten, Hille, German, Alexander J, and Mandigers, Paul JJ
Abstract: Gastric carcinoma is generally considered to be a rare disease in dogs, carrying a grave prognosis. However, in the Tervueren and Groenendael varieties of the Belgian Shepherd dog breed, the disease is highly prevalent. While histopathology is the gold standard for diagnosing gastric carcinoma, there is no general consensus on the methods for histological classification in these cases. Biopsies of a group of 61 dogs with confirmed gastric carcinoma (45 Tervueren and 16 Groenendael) were examined and classified according to World Health Organization (WHO) and Laurén classifications. Kaplan-Meier curves were used to compare survival between the different subtypes and simple and multiple linear regression were used to analyse the association between age of onset and breed variant, sex, neuter status, location of the tumour, inflammation score, and Laurén and WHO classifications. Mean age at diagnosis was significantly different in Groenendael (10.1 ± 2.01) and Tervueren dogs (8.5 ± 1.90). The Laurén classification resulted in 29 (48%) diffuse- and 32 (52%) intestinal-type tumours. Applying the WHO classification resulted in 30 (49%) tubular carcinoma growth patterns and 31 (51%) others. Median survival time was significantly reduced for the diffuse type as compared to the intestinal type according to the Laurén classification, with the same median survival time results for tubular compared to non-tubular subtypes according to the WHO classification (median survival time of 61 vs. 182 days, respectively). Using the WHO and Lauren classification on tumour biopsies may help the practising clinician in the prognostication of gastric carcinoma in Tervueren and Groenendael dogs.
Published: 2023

3. The Histopathological Characteristic of Gastric Carcinoma in the Belgian Tervueren and Groenendael Dog: A Comparison of Two Classification Methods

Author: Intensieve zorgafdeling, Pathobiologie, Interne geneeskunde GD, CS_Genetics, Genetics, Kijan, Christina, Hugen, Sanne, Thomas, Rachel E., Oberbauer, Anita M., Leegwater, Peter A. J., Fieten, Hille, German, Alexander J., Mandigers, Paul J. J., Intensieve zorgafdeling, Pathobiologie, Interne geneeskunde GD, CS_Genetics, Genetics, Kijan, Christina, Hugen, Sanne, Thomas, Rachel E., Oberbauer, Anita M., Leegwater, Peter A. J., Fieten, Hille, German, Alexander J., and Mandigers, Paul J. J.
Published: 2023

4. Drosophila functional screening of de novo variants in autism uncovers damaging variants and facilitates discovery of rare neurodevelopmental diseases

Author: Marcogliese, Paul C., Deal, Samantha L., Andrews, Jonathan, Harnish, J. Michael, Bhavana, V. Hemanjani, Graves, Hillary K., Jangam, Sharayu, Luo, Xi, Liu, Ning, Bei, Danqing, Hull, Brooke, Pan, Hongling, Bhadane, Pradnya, Longley, Colleen M., Haelterman, Nele A., Kanca, Oguz, Manivannan, Sathiya N., Rossetti, Linda Z., German, Ryan J., Gerard, Amanda, Schwaibold, Eva Maria Christina, Fehr, Sarah, Guerrini, Renzo, Vetro, Annalisa, England, Eleina, Murali, Chaya N., Barakat, Tahsin Stefan, van Dooren, Marieke F., Wilke, Martina, van Slegtenhorst, Marjon, Lesca, Gaetan, Sabatier, Isabelle, Chatron, Nicolas, Brownstein, Catherine A., Madden, Jill A., Agrawal, Pankaj B., Keren, Boris, Courtin, Thomas, Perrin, Laurence, Brugger, Melanie, Roser, Timo, Leiz, Steffen, Mau-Them, Frederic Tran, Delanne, Julian, Sukarova-Angelovska, Elena, Trajkova, Slavica, Rosenhahn, Erik, Strehlow, Vincent, Platzer, Konrad, Keller, Roberto, Pavinato, Lisa, Brusco, Alfredo, Rosenfeld, Jill A., Marom, Ronit, Wangler, Michael F., Yamamoto, Shinya, Marcogliese, Paul C., Deal, Samantha L., Andrews, Jonathan, Harnish, J. Michael, Bhavana, V. Hemanjani, Graves, Hillary K., Jangam, Sharayu, Luo, Xi, Liu, Ning, Bei, Danqing, Hull, Brooke, Pan, Hongling, Bhadane, Pradnya, Longley, Colleen M., Haelterman, Nele A., Kanca, Oguz, Manivannan, Sathiya N., Rossetti, Linda Z., German, Ryan J., Gerard, Amanda, Schwaibold, Eva Maria Christina, Fehr, Sarah, Guerrini, Renzo, Vetro, Annalisa, England, Eleina, Murali, Chaya N., Barakat, Tahsin Stefan, van Dooren, Marieke F., Wilke, Martina, van Slegtenhorst, Marjon, Lesca, Gaetan, Sabatier, Isabelle, Chatron, Nicolas, Brownstein, Catherine A., Madden, Jill A., Agrawal, Pankaj B., Keren, Boris, Courtin, Thomas, Perrin, Laurence, Brugger, Melanie, Roser, Timo, Leiz, Steffen, Mau-Them, Frederic Tran, Delanne, Julian, Sukarova-Angelovska, Elena, Trajkova, Slavica, Rosenhahn, Erik, Strehlow, Vincent, Platzer, Konrad, Keller, Roberto, Pavinato, Lisa, Brusco, Alfredo, Rosenfeld, Jill A., Marom, Ronit, Wangler, Michael F., and Yamamoto, Shinya
Abstract: Individuals with autism spectrum disorder (ASD) exhibit an increased burden of de novo mutations (DNMs) in a broadening range of genes. While these studies have implicated hundreds of genes in ASD pathogenesis, which DNMs cause functional consequences in vivo remains unclear. We functionally test the effects of ASD missense DNMs using Drosophila through humanizationrescue and overexpression-based strategies. We examine 79 ASD variants in 74 genes identified in the Simons Simplex Collection and find 38% of them to cause functional alterations. Moreover, we identify GLRA2 as the cause of a spectrum of neurodevelopmental phenotypes beyond ASD in 13 previously undiagnosed subjects. Functional characterization of variants in ASD candidate genes points to conserved neurobiological mechanisms and facilitates gene discovery for rare neurodevelopmental diseases.
Published: 2022

5. Drosophila functional screening of de novo variants in autism uncovers damaging variants and facilitates discovery of rare neurodevelopmental diseases

Author: Marcogliese, Paul C., Deal, Samantha L., Andrews, Jonathan, Harnish, J. Michael, Bhavana, V. Hemanjani, Graves, Hillary K., Jangam, Sharayu, Luo, Xi, Liu, Ning, Bei, Danqing, Chao, Yu Hsin, Hull, Brooke, Lee, Pei Tseng, Pan, Hongling, Bhadane, Pradnya, Huang, Mei Chu, Longley, Colleen M., Chao, Hsiao Tuan, Chung, Hyung lok, Haelterman, Nele A., Kanca, Oguz, Manivannan, Sathiya N., Rossetti, Linda Z., German, Ryan J., Gerard, Amanda, Schwaibold, Eva Maria Christina, Fehr, Sarah, Guerrini, Renzo, Vetro, Annalisa, England, Eleina, Murali, Chaya N., Barakat, Tahsin Stefan, van Dooren, Marieke F., Wilke, Martina, van Slegtenhorst, Marjon, Lesca, Gaetan, Sabatier, Isabelle, Chatron, Nicolas, Brownstein, Catherine A., Madden, Jill A., Agrawal, Pankaj B., Keren, Boris, Courtin, Thomas, Perrin, Laurence, Brugger, Melanie, Roser, Timo, Leiz, Steffen, Mau-Them, Frederic Tran, Delanne, Julian, Sukarova-Angelovska, Elena, Marcogliese, Paul C., Deal, Samantha L., Andrews, Jonathan, Harnish, J. Michael, Bhavana, V. Hemanjani, Graves, Hillary K., Jangam, Sharayu, Luo, Xi, Liu, Ning, Bei, Danqing, Chao, Yu Hsin, Hull, Brooke, Lee, Pei Tseng, Pan, Hongling, Bhadane, Pradnya, Huang, Mei Chu, Longley, Colleen M., Chao, Hsiao Tuan, Chung, Hyung lok, Haelterman, Nele A., Kanca, Oguz, Manivannan, Sathiya N., Rossetti, Linda Z., German, Ryan J., Gerard, Amanda, Schwaibold, Eva Maria Christina, Fehr, Sarah, Guerrini, Renzo, Vetro, Annalisa, England, Eleina, Murali, Chaya N., Barakat, Tahsin Stefan, van Dooren, Marieke F., Wilke, Martina, van Slegtenhorst, Marjon, Lesca, Gaetan, Sabatier, Isabelle, Chatron, Nicolas, Brownstein, Catherine A., Madden, Jill A., Agrawal, Pankaj B., Keren, Boris, Courtin, Thomas, Perrin, Laurence, Brugger, Melanie, Roser, Timo, Leiz, Steffen, Mau-Them, Frederic Tran, Delanne, Julian, and Sukarova-Angelovska, Elena
Abstract: Individuals with autism spectrum disorder (ASD) exhibit an increased burden of de novo mutations (DNMs) in a broadening range of genes. While these studies have implicated hundreds of genes in ASD pathogenesis, which DNMs cause functional consequences in vivo remains unclear. We functionally test the effects of ASD missense DNMs using Drosophila through “humanization” rescue and overexpression-based strategies. We examine 79 ASD variants in 74 genes identified in the Simons Simplex Collection and find 38% of them to cause functional alterations. Moreover, we identify GLRA2 as the cause of a spectrum of neurodevelopmental phenotypes beyond ASD in 13 previously undiagnosed subjects. Functional characterization of variants in ASD candidate genes points to conserved neurobiological mechanisms and facilitates gene discovery for rare neurodevelopmental diseases.
Published: 2022

6. Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials

Author: Axfors, Cathrine, Janiaud, Perrine, Schmitt, Andreas M., Van't Hooft, Janneke, Smith, Emily R., Haber, Noah A., Abayomi, Akin, Abduljalil, Manal, Abdulrahman, Abdulkarim, Acosta-Ampudia, Yeny, Aguilar-Guisado, Manuela, Al-Beidh, Farah, Alejandria, Marissa M., Alfonso, Rachelle N., Ali, Mohammad, AlQahtani, Manaf, AlZamrooni, Alaa, Anaya, Juan-Manuel, Ang, Mark Angelo C., Aomar, Ismael F., Argumanis, Luis E., Averyanov, Alexander, Baklaushev, Vladimir P., Balionis, Olga, Benfield, Thomas, Berry, Scott, Birocco, Nadia, Bonifacio, Lynn B., Bowen, Asha C., Bown, Abbie, Cabello-Gutierrez, Carlos, Camacho, Bernardo, Camacho-Ortiz, Adrian, Campbell-Lee, Sally, Cao, Damon H., Cardesa, Ana, Carnate, Jose M., Castillo, German Jr J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Neto, Abel Costa, D'Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, Diaz-Coronado, Juan C., Diaz Ponce-Medrano, Juan A., Donneau, Anne-Francoise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae S., Estcourt, Lise J., Evans, Amy, Evasan, Agnes L. M., Fareli, Christian J., Fernandez-Sanchez, Veronica, Galassi, Claudia, Gallo, Juan E., Garcia, Patricia J., Garcia, Patricia L., Garcia, Jesus A., Garigliany, Mutien, Garza-Gonzalez, Elvira, Gauiran, Deonne Thaddeus, V, Gaviria Garcia, Paula A., Giron-Gonzalez, Jose-Antonio, Gomez-Almaguer, David, Gordon, Anthony C., Gothot, Andre, Grass Guaqueta, Jeser Santiago, Green, Cameron, Grimaldi, David, Hammond, Naomi E., Harvala, Heli, Heralde, Francisco M., Herrick, Jesica, Higgins, Alisa M., Hills, Thomas E., Hines, Jennifer, Holm, Karin, Hoque, Ashraful, Hoste, Eric, Ignacio, Jose M., Ivanov, Alexander, V, Janssen, Maike, Jennings, Jeffrey H., Jha, Vivekanand, King, Ruby Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Francois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-Diaz, Jorge M., Lopez-Robles, Concepcion, Lopez-Cardenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Macias, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Ruben D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Javier Martinez-Marcos, Francisco, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma Angelina L., Misset, Benoit, Molton, James S., Mondragon, Alric, V, Monsalve, Diana M., Choghakabodi, Parastoo Moradi, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, Muller-Tidow, Carsten, Murphy, Erin, Najdovski, Tome, Nichol, Alistair D., Nielsen, Henrik, Novak, Richard M., O'Sullivan, Matthew V. N., Olalla, Julian, Osibogun, Akin, Osikomaiya, Bodunrin, Oyonarte, Salvador, Pardo-Oviedo, Juan M., Patel, Mahesh C., Paterson, David L., Pena-Perez, Carlos A., Perez-Calatayud, Angel A., Perez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md M., Rahman, Md S., Ramesh, Mayur, Ramirez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodriguez, Yhojan, Rodriguez-Bano, Jesus, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza M., Sasadeusz, Joe, Scozzari, Gitana, Shankar-Hari, Manu, Sharma, Gorav, Snelling, Thomas, Soto, Alonso, Tagayuna, Pedrito Y., Tang, Amy, Tatem, Geneva, Teofili, Luciana, Tong, Steven Y. C., Turgeon, Alexis F., Veloso, Januario D., Venkatesh, Balasubramanian, Ventura-Enriquez, Yanet, Webb, Steve A., Wiese, Lothar, Wiken, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., Hemkens, Lars G., Axfors, Cathrine, Janiaud, Perrine, Schmitt, Andreas M., Van't Hooft, Janneke, Smith, Emily R., Haber, Noah A., Abayomi, Akin, Abduljalil, Manal, Abdulrahman, Abdulkarim, Acosta-Ampudia, Yeny, Aguilar-Guisado, Manuela, Al-Beidh, Farah, Alejandria, Marissa M., Alfonso, Rachelle N., Ali, Mohammad, AlQahtani, Manaf, AlZamrooni, Alaa, Anaya, Juan-Manuel, Ang, Mark Angelo C., Aomar, Ismael F., Argumanis, Luis E., Averyanov, Alexander, Baklaushev, Vladimir P., Balionis, Olga, Benfield, Thomas, Berry, Scott, Birocco, Nadia, Bonifacio, Lynn B., Bowen, Asha C., Bown, Abbie, Cabello-Gutierrez, Carlos, Camacho, Bernardo, Camacho-Ortiz, Adrian, Campbell-Lee, Sally, Cao, Damon H., Cardesa, Ana, Carnate, Jose M., Castillo, German Jr J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Neto, Abel Costa, D'Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, Diaz-Coronado, Juan C., Diaz Ponce-Medrano, Juan A., Donneau, Anne-Francoise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae S., Estcourt, Lise J., Evans, Amy, Evasan, Agnes L. M., Fareli, Christian J., Fernandez-Sanchez, Veronica, Galassi, Claudia, Gallo, Juan E., Garcia, Patricia J., Garcia, Patricia L., Garcia, Jesus A., Garigliany, Mutien, Garza-Gonzalez, Elvira, Gauiran, Deonne Thaddeus, V, Gaviria Garcia, Paula A., Giron-Gonzalez, Jose-Antonio, Gomez-Almaguer, David, Gordon, Anthony C., Gothot, Andre, Grass Guaqueta, Jeser Santiago, Green, Cameron, Grimaldi, David, Hammond, Naomi E., Harvala, Heli, Heralde, Francisco M., Herrick, Jesica, Higgins, Alisa M., Hills, Thomas E., Hines, Jennifer, Holm, Karin, Hoque, Ashraful, Hoste, Eric, Ignacio, Jose M., Ivanov, Alexander, V, Janssen, Maike, Jennings, Jeffrey H., Jha, Vivekanand, King, Ruby Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Francois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-Diaz, Jorge M., Lopez-Robles, Concepcion, Lopez-Cardenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Macias, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Ruben D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Javier Martinez-Marcos, Francisco, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma Angelina L., Misset, Benoit, Molton, James S., Mondragon, Alric, V, Monsalve, Diana M., Choghakabodi, Parastoo Moradi, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, Muller-Tidow, Carsten, Murphy, Erin, Najdovski, Tome, Nichol, Alistair D., Nielsen, Henrik, Novak, Richard M., O'Sullivan, Matthew V. N., Olalla, Julian, Osibogun, Akin, Osikomaiya, Bodunrin, Oyonarte, Salvador, Pardo-Oviedo, Juan M., Patel, Mahesh C., Paterson, David L., Pena-Perez, Carlos A., Perez-Calatayud, Angel A., Perez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md M., Rahman, Md S., Ramesh, Mayur, Ramirez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodriguez, Yhojan, Rodriguez-Bano, Jesus, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza M., Sasadeusz, Joe, Scozzari, Gitana, Shankar-Hari, Manu, Sharma, Gorav, Snelling, Thomas, Soto, Alonso, Tagayuna, Pedrito Y., Tang, Amy, Tatem, Geneva, Teofili, Luciana, Tong, Steven Y. C., Turgeon, Alexis F., Veloso, Januario D., Venkatesh, Balasubramanian, Ventura-Enriquez, Yanet, Webb, Steve A., Wiese, Lothar, Wiken, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., and Hemkens, Lars G.
Abstract: Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Co
Published: 2021
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7. Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials

Author: Axfors, Cathrine, Janiaud, Perrine, Schmitt, Andreas M., Van't Hooft, Janneke, Smith, Emily R., Haber, Noah A., Abayomi, Akin, Abduljalil, Manal, Abdulrahman, Abdulkarim, Acosta-Ampudia, Yeny, Aguilar-Guisado, Manuela, Al-Beidh, Farah, Alejandria, Marissa M., Alfonso, Rachelle N., Ali, Mohammad, AlQahtani, Manaf, AlZamrooni, Alaa, Anaya, Juan-Manuel, Ang, Mark Angelo C., Aomar, Ismael F., Argumanis, Luis E., Averyanov, Alexander, Baklaushev, Vladimir P., Balionis, Olga, Benfield, Thomas, Berry, Scott, Birocco, Nadia, Bonifacio, Lynn B., Bowen, Asha C., Bown, Abbie, Cabello-Gutierrez, Carlos, Camacho, Bernardo, Camacho-Ortiz, Adrian, Campbell-Lee, Sally, Cao, Damon H., Cardesa, Ana, Carnate, Jose M., Castillo, German Jr J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Neto, Abel Costa, D'Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, Diaz-Coronado, Juan C., Diaz Ponce-Medrano, Juan A., Donneau, Anne-Francoise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae S., Estcourt, Lise J., Evans, Amy, Evasan, Agnes L. M., Fareli, Christian J., Fernandez-Sanchez, Veronica, Galassi, Claudia, Gallo, Juan E., Garcia, Patricia J., Garcia, Patricia L., Garcia, Jesus A., Garigliany, Mutien, Garza-Gonzalez, Elvira, Gauiran, Deonne Thaddeus, V, Gaviria Garcia, Paula A., Giron-Gonzalez, Jose-Antonio, Gomez-Almaguer, David, Gordon, Anthony C., Gothot, Andre, Grass Guaqueta, Jeser Santiago, Green, Cameron, Grimaldi, David, Hammond, Naomi E., Harvala, Heli, Heralde, Francisco M., Herrick, Jesica, Higgins, Alisa M., Hills, Thomas E., Hines, Jennifer, Holm, Karin, Hoque, Ashraful, Hoste, Eric, Ignacio, Jose M., Ivanov, Alexander, V, Janssen, Maike, Jennings, Jeffrey H., Jha, Vivekanand, King, Ruby Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Francois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-Diaz, Jorge M., Lopez-Robles, Concepcion, Lopez-Cardenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Macias, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Ruben D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Javier Martinez-Marcos, Francisco, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma Angelina L., Misset, Benoit, Molton, James S., Mondragon, Alric, V, Monsalve, Diana M., Choghakabodi, Parastoo Moradi, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, Muller-Tidow, Carsten, Murphy, Erin, Najdovski, Tome, Nichol, Alistair D., Nielsen, Henrik, Novak, Richard M., O'Sullivan, Matthew V. N., Olalla, Julian, Osibogun, Akin, Osikomaiya, Bodunrin, Oyonarte, Salvador, Pardo-Oviedo, Juan M., Patel, Mahesh C., Paterson, David L., Pena-Perez, Carlos A., Perez-Calatayud, Angel A., Perez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md M., Rahman, Md S., Ramesh, Mayur, Ramirez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodriguez, Yhojan, Rodriguez-Bano, Jesus, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza M., Sasadeusz, Joe, Scozzari, Gitana, Shankar-Hari, Manu, Sharma, Gorav, Snelling, Thomas, Soto, Alonso, Tagayuna, Pedrito Y., Tang, Amy, Tatem, Geneva, Teofili, Luciana, Tong, Steven Y. C., Turgeon, Alexis F., Veloso, Januario D., Venkatesh, Balasubramanian, Ventura-Enriquez, Yanet, Webb, Steve A., Wiese, Lothar, Wiken, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., Hemkens, Lars G., Axfors, Cathrine, Janiaud, Perrine, Schmitt, Andreas M., Van't Hooft, Janneke, Smith, Emily R., Haber, Noah A., Abayomi, Akin, Abduljalil, Manal, Abdulrahman, Abdulkarim, Acosta-Ampudia, Yeny, Aguilar-Guisado, Manuela, Al-Beidh, Farah, Alejandria, Marissa M., Alfonso, Rachelle N., Ali, Mohammad, AlQahtani, Manaf, AlZamrooni, Alaa, Anaya, Juan-Manuel, Ang, Mark Angelo C., Aomar, Ismael F., Argumanis, Luis E., Averyanov, Alexander, Baklaushev, Vladimir P., Balionis, Olga, Benfield, Thomas, Berry, Scott, Birocco, Nadia, Bonifacio, Lynn B., Bowen, Asha C., Bown, Abbie, Cabello-Gutierrez, Carlos, Camacho, Bernardo, Camacho-Ortiz, Adrian, Campbell-Lee, Sally, Cao, Damon H., Cardesa, Ana, Carnate, Jose M., Castillo, German Jr J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Neto, Abel Costa, D'Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, Diaz-Coronado, Juan C., Diaz Ponce-Medrano, Juan A., Donneau, Anne-Francoise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae S., Estcourt, Lise J., Evans, Amy, Evasan, Agnes L. M., Fareli, Christian J., Fernandez-Sanchez, Veronica, Galassi, Claudia, Gallo, Juan E., Garcia, Patricia J., Garcia, Patricia L., Garcia, Jesus A., Garigliany, Mutien, Garza-Gonzalez, Elvira, Gauiran, Deonne Thaddeus, V, Gaviria Garcia, Paula A., Giron-Gonzalez, Jose-Antonio, Gomez-Almaguer, David, Gordon, Anthony C., Gothot, Andre, Grass Guaqueta, Jeser Santiago, Green, Cameron, Grimaldi, David, Hammond, Naomi E., Harvala, Heli, Heralde, Francisco M., Herrick, Jesica, Higgins, Alisa M., Hills, Thomas E., Hines, Jennifer, Holm, Karin, Hoque, Ashraful, Hoste, Eric, Ignacio, Jose M., Ivanov, Alexander, V, Janssen, Maike, Jennings, Jeffrey H., Jha, Vivekanand, King, Ruby Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Francois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-Diaz, Jorge M., Lopez-Robles, Concepcion, Lopez-Cardenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Macias, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Ruben D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Javier Martinez-Marcos, Francisco, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma Angelina L., Misset, Benoit, Molton, James S., Mondragon, Alric, V, Monsalve, Diana M., Choghakabodi, Parastoo Moradi, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, Muller-Tidow, Carsten, Murphy, Erin, Najdovski, Tome, Nichol, Alistair D., Nielsen, Henrik, Novak, Richard M., O'Sullivan, Matthew V. N., Olalla, Julian, Osibogun, Akin, Osikomaiya, Bodunrin, Oyonarte, Salvador, Pardo-Oviedo, Juan M., Patel, Mahesh C., Paterson, David L., Pena-Perez, Carlos A., Perez-Calatayud, Angel A., Perez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md M., Rahman, Md S., Ramesh, Mayur, Ramirez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodriguez, Yhojan, Rodriguez-Bano, Jesus, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza M., Sasadeusz, Joe, Scozzari, Gitana, Shankar-Hari, Manu, Sharma, Gorav, Snelling, Thomas, Soto, Alonso, Tagayuna, Pedrito Y., Tang, Amy, Tatem, Geneva, Teofili, Luciana, Tong, Steven Y. C., Turgeon, Alexis F., Veloso, Januario D., Venkatesh, Balasubramanian, Ventura-Enriquez, Yanet, Webb, Steve A., Wiese, Lothar, Wiken, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., and Hemkens, Lars G.
Abstract: Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Co
Published: 2021
Full Text: View/download PDF

8. Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials

Author: Axfors, Cathrine, Janiaud, Perrine, Schmitt, Andreas M., Van't Hooft, Janneke, Smith, Emily R., Haber, Noah A., Abayomi, Akin, Abduljalil, Manal, Abdulrahman, Abdulkarim, Acosta-Ampudia, Yeny, Aguilar-Guisado, Manuela, Al-Beidh, Farah, Alejandria, Marissa M., Alfonso, Rachelle N., Ali, Mohammad, AlQahtani, Manaf, AlZamrooni, Alaa, Anaya, Juan-Manuel, Ang, Mark Angelo C., Aomar, Ismael F., Argumanis, Luis E., Averyanov, Alexander, Baklaushev, Vladimir P., Balionis, Olga, Benfield, Thomas, Berry, Scott, Birocco, Nadia, Bonifacio, Lynn B., Bowen, Asha C., Bown, Abbie, Cabello-Gutierrez, Carlos, Camacho, Bernardo, Camacho-Ortiz, Adrian, Campbell-Lee, Sally, Cao, Damon H., Cardesa, Ana, Carnate, Jose M., Castillo, German Jr J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Neto, Abel Costa, D'Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, Diaz-Coronado, Juan C., Diaz Ponce-Medrano, Juan A., Donneau, Anne-Francoise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae S., Estcourt, Lise J., Evans, Amy, Evasan, Agnes L. M., Fareli, Christian J., Fernandez-Sanchez, Veronica, Galassi, Claudia, Gallo, Juan E., Garcia, Patricia J., Garcia, Patricia L., Garcia, Jesus A., Garigliany, Mutien, Garza-Gonzalez, Elvira, Gauiran, Deonne Thaddeus, V, Gaviria Garcia, Paula A., Giron-Gonzalez, Jose-Antonio, Gomez-Almaguer, David, Gordon, Anthony C., Gothot, Andre, Grass Guaqueta, Jeser Santiago, Green, Cameron, Grimaldi, David, Hammond, Naomi E., Harvala, Heli, Heralde, Francisco M., Herrick, Jesica, Higgins, Alisa M., Hills, Thomas E., Hines, Jennifer, Holm, Karin, Hoque, Ashraful, Hoste, Eric, Ignacio, Jose M., Ivanov, Alexander, V, Janssen, Maike, Jennings, Jeffrey H., Jha, Vivekanand, King, Ruby Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Francois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-Diaz, Jorge M., Lopez-Robles, Concepcion, Lopez-Cardenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Macias, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Ruben D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Javier Martinez-Marcos, Francisco, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma Angelina L., Misset, Benoit, Molton, James S., Mondragon, Alric, V, Monsalve, Diana M., Choghakabodi, Parastoo Moradi, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, Muller-Tidow, Carsten, Murphy, Erin, Najdovski, Tome, Nichol, Alistair D., Nielsen, Henrik, Novak, Richard M., O'Sullivan, Matthew V. N., Olalla, Julian, Osibogun, Akin, Osikomaiya, Bodunrin, Oyonarte, Salvador, Pardo-Oviedo, Juan M., Patel, Mahesh C., Paterson, David L., Pena-Perez, Carlos A., Perez-Calatayud, Angel A., Perez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md M., Rahman, Md S., Ramesh, Mayur, Ramirez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodriguez, Yhojan, Rodriguez-Bano, Jesus, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza M., Sasadeusz, Joe, Scozzari, Gitana, Shankar-Hari, Manu, Sharma, Gorav, Snelling, Thomas, Soto, Alonso, Tagayuna, Pedrito Y., Tang, Amy, Tatem, Geneva, Teofili, Luciana, Tong, Steven Y. C., Turgeon, Alexis F., Veloso, Januario D., Venkatesh, Balasubramanian, Ventura-Enriquez, Yanet, Webb, Steve A., Wiese, Lothar, Wiken, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., Hemkens, Lars G., Axfors, Cathrine, Janiaud, Perrine, Schmitt, Andreas M., Van't Hooft, Janneke, Smith, Emily R., Haber, Noah A., Abayomi, Akin, Abduljalil, Manal, Abdulrahman, Abdulkarim, Acosta-Ampudia, Yeny, Aguilar-Guisado, Manuela, Al-Beidh, Farah, Alejandria, Marissa M., Alfonso, Rachelle N., Ali, Mohammad, AlQahtani, Manaf, AlZamrooni, Alaa, Anaya, Juan-Manuel, Ang, Mark Angelo C., Aomar, Ismael F., Argumanis, Luis E., Averyanov, Alexander, Baklaushev, Vladimir P., Balionis, Olga, Benfield, Thomas, Berry, Scott, Birocco, Nadia, Bonifacio, Lynn B., Bowen, Asha C., Bown, Abbie, Cabello-Gutierrez, Carlos, Camacho, Bernardo, Camacho-Ortiz, Adrian, Campbell-Lee, Sally, Cao, Damon H., Cardesa, Ana, Carnate, Jose M., Castillo, German Jr J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Neto, Abel Costa, D'Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, Diaz-Coronado, Juan C., Diaz Ponce-Medrano, Juan A., Donneau, Anne-Francoise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae S., Estcourt, Lise J., Evans, Amy, Evasan, Agnes L. M., Fareli, Christian J., Fernandez-Sanchez, Veronica, Galassi, Claudia, Gallo, Juan E., Garcia, Patricia J., Garcia, Patricia L., Garcia, Jesus A., Garigliany, Mutien, Garza-Gonzalez, Elvira, Gauiran, Deonne Thaddeus, V, Gaviria Garcia, Paula A., Giron-Gonzalez, Jose-Antonio, Gomez-Almaguer, David, Gordon, Anthony C., Gothot, Andre, Grass Guaqueta, Jeser Santiago, Green, Cameron, Grimaldi, David, Hammond, Naomi E., Harvala, Heli, Heralde, Francisco M., Herrick, Jesica, Higgins, Alisa M., Hills, Thomas E., Hines, Jennifer, Holm, Karin, Hoque, Ashraful, Hoste, Eric, Ignacio, Jose M., Ivanov, Alexander, V, Janssen, Maike, Jennings, Jeffrey H., Jha, Vivekanand, King, Ruby Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Francois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-Diaz, Jorge M., Lopez-Robles, Concepcion, Lopez-Cardenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Macias, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Ruben D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Javier Martinez-Marcos, Francisco, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma Angelina L., Misset, Benoit, Molton, James S., Mondragon, Alric, V, Monsalve, Diana M., Choghakabodi, Parastoo Moradi, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, Muller-Tidow, Carsten, Murphy, Erin, Najdovski, Tome, Nichol, Alistair D., Nielsen, Henrik, Novak, Richard M., O'Sullivan, Matthew V. N., Olalla, Julian, Osibogun, Akin, Osikomaiya, Bodunrin, Oyonarte, Salvador, Pardo-Oviedo, Juan M., Patel, Mahesh C., Paterson, David L., Pena-Perez, Carlos A., Perez-Calatayud, Angel A., Perez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md M., Rahman, Md S., Ramesh, Mayur, Ramirez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodriguez, Yhojan, Rodriguez-Bano, Jesus, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza M., Sasadeusz, Joe, Scozzari, Gitana, Shankar-Hari, Manu, Sharma, Gorav, Snelling, Thomas, Soto, Alonso, Tagayuna, Pedrito Y., Tang, Amy, Tatem, Geneva, Teofili, Luciana, Tong, Steven Y. C., Turgeon, Alexis F., Veloso, Januario D., Venkatesh, Balasubramanian, Ventura-Enriquez, Yanet, Webb, Steve A., Wiese, Lothar, Wiken, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., and Hemkens, Lars G.
Abstract: Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Co
Published: 2021
Full Text: View/download PDF

9. Association between convalescent plasma treatment and mortality in COVID-19:a collaborative systematic review and meta-analysis of randomized clinical trials

Author: Axfors, Cathrine, Janiaud, Perrine, Schmitt, Andreas M., van’t Hooft, Janneke, Smith, Emily R., Haber, Noah A., Abayomi, Akin, Abduljalil, Manal, Abdulrahman, Abdulkarim, Acosta-Ampudia, Yeny, Aguilar-Guisado, Manuela, Al-Beidh, Farah, Alejandria, Marissa M., Alfonso, Rachelle N., Ali, Mohammad, AlQahtani, Manaf, AlZamrooni, Alaa, Anaya, Juan Manuel, Ang, Mark Angelo C., Aomar, Ismael F., Argumanis, Luis E., Averyanov, Alexander, Baklaushev, Vladimir P., Balionis, Olga, Benfield, Thomas, Berry, Scott, Birocco, Nadia, Bonifacio, Lynn B., Bowen, Asha C., Bown, Abbie, Cabello-Gutierrez, Carlos, Camacho, Bernardo, Camacho-Ortiz, Adrian, Campbell-Lee, Sally, Cao, Damon H., Cardesa, Ana, Carnate, Jose M., Castillo, German Jr J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U.H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D’Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, Díaz-Coronado, Juan C., Díaz Ponce-Medrano, Juan A., Donneau, Anne Françoise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae S., Estcourt, Lise J., Evans, Amy, Evasan, Agnes L.M., Fareli, Christian J., Fernandez-Sanchez, Veronica, Galassi, Claudia, Gallo, Juan E., Garcia, Patricia J., Garcia, Patricia L., Garcia, Jesus A., Garigliany, Mutien, Garza-Gonzalez, Elvira, Gauiran, Deonne Thaddeus V., Gaviria García, Paula A., Giron-Gonzalez, Jose Antonio, Gómez-Almaguer, David, Gordon, Anthony C., Gothot, André, Grass Guaqueta, Jeser Santiago, Green, Cameron, Grimaldi, David, Hammond, Naomi E., Harvala, Heli, Heralde, Francisco M., Herrick, Jesica, Higgins, Alisa M., Hills, Thomas E., Hines, Jennifer, Holm, Karin, Hoque, Ashraful, Hoste, Eric, Ignacio, Jose M., Ivanov, Alexander V., Janssen, Maike, Jennings, Jeffrey H., Jha, Vivekanand, King, Ruby Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre François, Lim, Lyn Li, Lim, Jodor, Ljungquist, Oskar, Llaca-Díaz, Jorge M., López-Robles, Concepción, López-Cárdenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Macías, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rubén D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Martínez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma Angelina L., Misset, Benoît, Molton, James S., Mondragon, Alric V., Monsalve, Diana M., Moradi Choghakabodi, Parastoo, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, Müller-Tidow, Carsten, Murphy, Erin, Najdovski, Tome, Nichol, Alistair D., Nielsen, Henrik, Novak, Richard M., O’Sullivan, Matthew V.N., Olalla, Julian, Osibogun, Akin, Osikomaiya, Bodunrin, Oyonarte, Salvador, Pardo-Oviedo, Juan M., Patel, Mahesh C., Paterson, David L., Peña-Perez, Carlos A., Perez-Calatayud, Angel A., Pérez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md M., Rahman, Md S., Ramesh, Mayur, Ramírez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodríguez, Yhojan, Rodríguez-Baño, Jesús, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza M., Sasadeusz, Joe, Scozzari, Gitana, Shankar-Hari, Manu, Sharma, Gorav, Snelling, Thomas, Soto, Alonso, Tagayuna, Pedrito Y., Tang, Amy, Tatem, Geneva, Teofili, Luciana, Tong, Steven Y.C., Turgeon, Alexis F., Veloso, Januario D., Venkatesh, Balasubramanian, Ventura-Enriquez, Yanet, Webb, Steve A., Wiese, Lothar, Wikén, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P.A., Hemkens, Lars G., Axfors, Cathrine, Janiaud, Perrine, Schmitt, Andreas M., van’t Hooft, Janneke, Smith, Emily R., Haber, Noah A., Abayomi, Akin, Abduljalil, Manal, Abdulrahman, Abdulkarim, Acosta-Ampudia, Yeny, Aguilar-Guisado, Manuela, Al-Beidh, Farah, Alejandria, Marissa M., Alfonso, Rachelle N., Ali, Mohammad, AlQahtani, Manaf, AlZamrooni, Alaa, Anaya, Juan Manuel, Ang, Mark Angelo C., Aomar, Ismael F., Argumanis, Luis E., Averyanov, Alexander, Baklaushev, Vladimir P., Balionis, Olga, Benfield, Thomas, Berry, Scott, Birocco, Nadia, Bonifacio, Lynn B., Bowen, Asha C., Bown, Abbie, Cabello-Gutierrez, Carlos, Camacho, Bernardo, Camacho-Ortiz, Adrian, Campbell-Lee, Sally, Cao, Damon H., Cardesa, Ana, Carnate, Jose M., Castillo, German Jr J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U.H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D’Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, Díaz-Coronado, Juan C., Díaz Ponce-Medrano, Juan A., Donneau, Anne Françoise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae S., Estcourt, Lise J., Evans, Amy, Evasan, Agnes L.M., Fareli, Christian J., Fernandez-Sanchez, Veronica, Galassi, Claudia, Gallo, Juan E., Garcia, Patricia J., Garcia, Patricia L., Garcia, Jesus A., Garigliany, Mutien, Garza-Gonzalez, Elvira, Gauiran, Deonne Thaddeus V., Gaviria García, Paula A., Giron-Gonzalez, Jose Antonio, Gómez-Almaguer, David, Gordon, Anthony C., Gothot, André, Grass Guaqueta, Jeser Santiago, Green, Cameron, Grimaldi, David, Hammond, Naomi E., Harvala, Heli, Heralde, Francisco M., Herrick, Jesica, Higgins, Alisa M., Hills, Thomas E., Hines, Jennifer, Holm, Karin, Hoque, Ashraful, Hoste, Eric, Ignacio, Jose M., Ivanov, Alexander V., Janssen, Maike, Jennings, Jeffrey H., Jha, Vivekanand, King, Ruby Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre François, Lim, Lyn Li, Lim, Jodor, Ljungquist, Oskar, Llaca-Díaz, Jorge M., López-Robles, Concepción, López-Cárdenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Macías, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rubén D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Martínez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma Angelina L., Misset, Benoît, Molton, James S., Mondragon, Alric V., Monsalve, Diana M., Moradi Choghakabodi, Parastoo, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, Müller-Tidow, Carsten, Murphy, Erin, Najdovski, Tome, Nichol, Alistair D., Nielsen, Henrik, Novak, Richard M., O’Sullivan, Matthew V.N., Olalla, Julian, Osibogun, Akin, Osikomaiya, Bodunrin, Oyonarte, Salvador, Pardo-Oviedo, Juan M., Patel, Mahesh C., Paterson, David L., Peña-Perez, Carlos A., Perez-Calatayud, Angel A., Pérez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md M., Rahman, Md S., Ramesh, Mayur, Ramírez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodríguez, Yhojan, Rodríguez-Baño, Jesús, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza M., Sasadeusz, Joe, Scozzari, Gitana, Shankar-Hari, Manu, Sharma, Gorav, Snelling, Thomas, Soto, Alonso, Tagayuna, Pedrito Y., Tang, Amy, Tatem, Geneva, Teofili, Luciana, Tong, Steven Y.C., Turgeon, Alexis F., Veloso, Januario D., Venkatesh, Balasubramanian, Ventura-Enriquez, Yanet, Webb, Steve A., Wiese, Lothar, Wikén, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P.A., and Hemkens, Lars G.
Abstract: Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evi
Published: 2021

10. Association between convalescent plasma treatment and mortality in COVID-19:a collaborative systematic review and meta-analysis of randomized clinical trials

Author: Axfors, Cathrine, Janiaud, Perrine, Schmitt, Andreas M., van’t Hooft, Janneke, Smith, Emily R., Haber, Noah A., Abayomi, Akin, Abduljalil, Manal, Abdulrahman, Abdulkarim, Acosta-Ampudia, Yeny, Aguilar-Guisado, Manuela, Al-Beidh, Farah, Alejandria, Marissa M., Alfonso, Rachelle N., Ali, Mohammad, AlQahtani, Manaf, AlZamrooni, Alaa, Anaya, Juan Manuel, Ang, Mark Angelo C., Aomar, Ismael F., Argumanis, Luis E., Averyanov, Alexander, Baklaushev, Vladimir P., Balionis, Olga, Benfield, Thomas, Berry, Scott, Birocco, Nadia, Bonifacio, Lynn B., Bowen, Asha C., Bown, Abbie, Cabello-Gutierrez, Carlos, Camacho, Bernardo, Camacho-Ortiz, Adrian, Campbell-Lee, Sally, Cao, Damon H., Cardesa, Ana, Carnate, Jose M., Castillo, German Jr J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U.H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D’Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, Díaz-Coronado, Juan C., Díaz Ponce-Medrano, Juan A., Donneau, Anne Françoise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae S., Estcourt, Lise J., Evans, Amy, Evasan, Agnes L.M., Fareli, Christian J., Fernandez-Sanchez, Veronica, Galassi, Claudia, Gallo, Juan E., Garcia, Patricia J., Garcia, Patricia L., Garcia, Jesus A., Garigliany, Mutien, Garza-Gonzalez, Elvira, Gauiran, Deonne Thaddeus V., Gaviria García, Paula A., Giron-Gonzalez, Jose Antonio, Gómez-Almaguer, David, Gordon, Anthony C., Gothot, André, Grass Guaqueta, Jeser Santiago, Green, Cameron, Grimaldi, David, Hammond, Naomi E., Harvala, Heli, Heralde, Francisco M., Herrick, Jesica, Higgins, Alisa M., Hills, Thomas E., Hines, Jennifer, Holm, Karin, Hoque, Ashraful, Hoste, Eric, Ignacio, Jose M., Ivanov, Alexander V., Janssen, Maike, Jennings, Jeffrey H., Jha, Vivekanand, King, Ruby Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre François, Lim, Lyn Li, Lim, Jodor, Ljungquist, Oskar, Llaca-Díaz, Jorge M., López-Robles, Concepción, López-Cárdenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Macías, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rubén D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Martínez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma Angelina L., Misset, Benoît, Molton, James S., Mondragon, Alric V., Monsalve, Diana M., Moradi Choghakabodi, Parastoo, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, Müller-Tidow, Carsten, Murphy, Erin, Najdovski, Tome, Nichol, Alistair D., Nielsen, Henrik, Novak, Richard M., O’Sullivan, Matthew V.N., Olalla, Julian, Osibogun, Akin, Osikomaiya, Bodunrin, Oyonarte, Salvador, Pardo-Oviedo, Juan M., Patel, Mahesh C., Paterson, David L., Peña-Perez, Carlos A., Perez-Calatayud, Angel A., Pérez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md M., Rahman, Md S., Ramesh, Mayur, Ramírez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodríguez, Yhojan, Rodríguez-Baño, Jesús, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza M., Sasadeusz, Joe, Scozzari, Gitana, Shankar-Hari, Manu, Sharma, Gorav, Snelling, Thomas, Soto, Alonso, Tagayuna, Pedrito Y., Tang, Amy, Tatem, Geneva, Teofili, Luciana, Tong, Steven Y.C., Turgeon, Alexis F., Veloso, Januario D., Venkatesh, Balasubramanian, Ventura-Enriquez, Yanet, Webb, Steve A., Wiese, Lothar, Wikén, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P.A., Hemkens, Lars G., Axfors, Cathrine, Janiaud, Perrine, Schmitt, Andreas M., van’t Hooft, Janneke, Smith, Emily R., Haber, Noah A., Abayomi, Akin, Abduljalil, Manal, Abdulrahman, Abdulkarim, Acosta-Ampudia, Yeny, Aguilar-Guisado, Manuela, Al-Beidh, Farah, Alejandria, Marissa M., Alfonso, Rachelle N., Ali, Mohammad, AlQahtani, Manaf, AlZamrooni, Alaa, Anaya, Juan Manuel, Ang, Mark Angelo C., Aomar, Ismael F., Argumanis, Luis E., Averyanov, Alexander, Baklaushev, Vladimir P., Balionis, Olga, Benfield, Thomas, Berry, Scott, Birocco, Nadia, Bonifacio, Lynn B., Bowen, Asha C., Bown, Abbie, Cabello-Gutierrez, Carlos, Camacho, Bernardo, Camacho-Ortiz, Adrian, Campbell-Lee, Sally, Cao, Damon H., Cardesa, Ana, Carnate, Jose M., Castillo, German Jr J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U.H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Costa Neto, Abel, D’Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, Díaz-Coronado, Juan C., Díaz Ponce-Medrano, Juan A., Donneau, Anne Françoise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae S., Estcourt, Lise J., Evans, Amy, Evasan, Agnes L.M., Fareli, Christian J., Fernandez-Sanchez, Veronica, Galassi, Claudia, Gallo, Juan E., Garcia, Patricia J., Garcia, Patricia L., Garcia, Jesus A., Garigliany, Mutien, Garza-Gonzalez, Elvira, Gauiran, Deonne Thaddeus V., Gaviria García, Paula A., Giron-Gonzalez, Jose Antonio, Gómez-Almaguer, David, Gordon, Anthony C., Gothot, André, Grass Guaqueta, Jeser Santiago, Green, Cameron, Grimaldi, David, Hammond, Naomi E., Harvala, Heli, Heralde, Francisco M., Herrick, Jesica, Higgins, Alisa M., Hills, Thomas E., Hines, Jennifer, Holm, Karin, Hoque, Ashraful, Hoste, Eric, Ignacio, Jose M., Ivanov, Alexander V., Janssen, Maike, Jennings, Jeffrey H., Jha, Vivekanand, King, Ruby Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre François, Lim, Lyn Li, Lim, Jodor, Ljungquist, Oskar, Llaca-Díaz, Jorge M., López-Robles, Concepción, López-Cárdenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Macías, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Rubén D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Martínez-Marcos, Francisco Javier, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma Angelina L., Misset, Benoît, Molton, James S., Mondragon, Alric V., Monsalve, Diana M., Moradi Choghakabodi, Parastoo, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, Müller-Tidow, Carsten, Murphy, Erin, Najdovski, Tome, Nichol, Alistair D., Nielsen, Henrik, Novak, Richard M., O’Sullivan, Matthew V.N., Olalla, Julian, Osibogun, Akin, Osikomaiya, Bodunrin, Oyonarte, Salvador, Pardo-Oviedo, Juan M., Patel, Mahesh C., Paterson, David L., Peña-Perez, Carlos A., Perez-Calatayud, Angel A., Pérez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md M., Rahman, Md S., Ramesh, Mayur, Ramírez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodríguez, Yhojan, Rodríguez-Baño, Jesús, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza M., Sasadeusz, Joe, Scozzari, Gitana, Shankar-Hari, Manu, Sharma, Gorav, Snelling, Thomas, Soto, Alonso, Tagayuna, Pedrito Y., Tang, Amy, Tatem, Geneva, Teofili, Luciana, Tong, Steven Y.C., Turgeon, Alexis F., Veloso, Januario D., Venkatesh, Balasubramanian, Ventura-Enriquez, Yanet, Webb, Steve A., Wiese, Lothar, Wikén, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P.A., and Hemkens, Lars G.
Abstract: Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evi
Published: 2021

11. Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials

Author: Axfors, Cathrine, Janiaud, Perrine, Schmitt, Andreas M., Van't Hooft, Janneke, Smith, Emily R., Haber, Noah A., Abayomi, Akin, Abduljalil, Manal, Abdulrahman, Abdulkarim, Acosta-Ampudia, Yeny, Aguilar-Guisado, Manuela, Al-Beidh, Farah, Alejandria, Marissa M., Alfonso, Rachelle N., Ali, Mohammad, AlQahtani, Manaf, AlZamrooni, Alaa, Anaya, Juan-Manuel, Ang, Mark Angelo C., Aomar, Ismael F., Argumanis, Luis E., Averyanov, Alexander, Baklaushev, Vladimir P., Balionis, Olga, Benfield, Thomas, Berry, Scott, Birocco, Nadia, Bonifacio, Lynn B., Bowen, Asha C., Bown, Abbie, Cabello-Gutierrez, Carlos, Camacho, Bernardo, Camacho-Ortiz, Adrian, Campbell-Lee, Sally, Cao, Damon H., Cardesa, Ana, Carnate, Jose M., Castillo, German Jr J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Neto, Abel Costa, D'Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, Diaz-Coronado, Juan C., Diaz Ponce-Medrano, Juan A., Donneau, Anne-Francoise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae S., Estcourt, Lise J., Evans, Amy, Evasan, Agnes L. M., Fareli, Christian J., Fernandez-Sanchez, Veronica, Galassi, Claudia, Gallo, Juan E., Garcia, Patricia J., Garcia, Patricia L., Garcia, Jesus A., Garigliany, Mutien, Garza-Gonzalez, Elvira, Gauiran, Deonne Thaddeus, V, Gaviria Garcia, Paula A., Giron-Gonzalez, Jose-Antonio, Gomez-Almaguer, David, Gordon, Anthony C., Gothot, Andre, Grass Guaqueta, Jeser Santiago, Green, Cameron, Grimaldi, David, Hammond, Naomi E., Harvala, Heli, Heralde, Francisco M., Herrick, Jesica, Higgins, Alisa M., Hills, Thomas E., Hines, Jennifer, Holm, Karin, Hoque, Ashraful, Hoste, Eric, Ignacio, Jose M., Ivanov, Alexander, V, Janssen, Maike, Jennings, Jeffrey H., Jha, Vivekanand, King, Ruby Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Francois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-Diaz, Jorge M., Lopez-Robles, Concepcion, Lopez-Cardenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Macias, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Ruben D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Javier Martinez-Marcos, Francisco, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma Angelina L., Misset, Benoit, Molton, James S., Mondragon, Alric, V, Monsalve, Diana M., Choghakabodi, Parastoo Moradi, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, Muller-Tidow, Carsten, Murphy, Erin, Najdovski, Tome, Nichol, Alistair D., Nielsen, Henrik, Novak, Richard M., O'Sullivan, Matthew V. N., Olalla, Julian, Osibogun, Akin, Osikomaiya, Bodunrin, Oyonarte, Salvador, Pardo-Oviedo, Juan M., Patel, Mahesh C., Paterson, David L., Pena-Perez, Carlos A., Perez-Calatayud, Angel A., Perez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md M., Rahman, Md S., Ramesh, Mayur, Ramirez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodriguez, Yhojan, Rodriguez-Bano, Jesus, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza M., Sasadeusz, Joe, Scozzari, Gitana, Shankar-Hari, Manu, Sharma, Gorav, Snelling, Thomas, Soto, Alonso, Tagayuna, Pedrito Y., Tang, Amy, Tatem, Geneva, Teofili, Luciana, Tong, Steven Y. C., Turgeon, Alexis F., Veloso, Januario D., Venkatesh, Balasubramanian, Ventura-Enriquez, Yanet, Webb, Steve A., Wiese, Lothar, Wiken, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., Hemkens, Lars G., Axfors, Cathrine, Janiaud, Perrine, Schmitt, Andreas M., Van't Hooft, Janneke, Smith, Emily R., Haber, Noah A., Abayomi, Akin, Abduljalil, Manal, Abdulrahman, Abdulkarim, Acosta-Ampudia, Yeny, Aguilar-Guisado, Manuela, Al-Beidh, Farah, Alejandria, Marissa M., Alfonso, Rachelle N., Ali, Mohammad, AlQahtani, Manaf, AlZamrooni, Alaa, Anaya, Juan-Manuel, Ang, Mark Angelo C., Aomar, Ismael F., Argumanis, Luis E., Averyanov, Alexander, Baklaushev, Vladimir P., Balionis, Olga, Benfield, Thomas, Berry, Scott, Birocco, Nadia, Bonifacio, Lynn B., Bowen, Asha C., Bown, Abbie, Cabello-Gutierrez, Carlos, Camacho, Bernardo, Camacho-Ortiz, Adrian, Campbell-Lee, Sally, Cao, Damon H., Cardesa, Ana, Carnate, Jose M., Castillo, German Jr J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Neto, Abel Costa, D'Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, Diaz-Coronado, Juan C., Diaz Ponce-Medrano, Juan A., Donneau, Anne-Francoise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae S., Estcourt, Lise J., Evans, Amy, Evasan, Agnes L. M., Fareli, Christian J., Fernandez-Sanchez, Veronica, Galassi, Claudia, Gallo, Juan E., Garcia, Patricia J., Garcia, Patricia L., Garcia, Jesus A., Garigliany, Mutien, Garza-Gonzalez, Elvira, Gauiran, Deonne Thaddeus, V, Gaviria Garcia, Paula A., Giron-Gonzalez, Jose-Antonio, Gomez-Almaguer, David, Gordon, Anthony C., Gothot, Andre, Grass Guaqueta, Jeser Santiago, Green, Cameron, Grimaldi, David, Hammond, Naomi E., Harvala, Heli, Heralde, Francisco M., Herrick, Jesica, Higgins, Alisa M., Hills, Thomas E., Hines, Jennifer, Holm, Karin, Hoque, Ashraful, Hoste, Eric, Ignacio, Jose M., Ivanov, Alexander, V, Janssen, Maike, Jennings, Jeffrey H., Jha, Vivekanand, King, Ruby Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Francois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-Diaz, Jorge M., Lopez-Robles, Concepcion, Lopez-Cardenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Macias, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Ruben D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Javier Martinez-Marcos, Francisco, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma Angelina L., Misset, Benoit, Molton, James S., Mondragon, Alric, V, Monsalve, Diana M., Choghakabodi, Parastoo Moradi, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, Muller-Tidow, Carsten, Murphy, Erin, Najdovski, Tome, Nichol, Alistair D., Nielsen, Henrik, Novak, Richard M., O'Sullivan, Matthew V. N., Olalla, Julian, Osibogun, Akin, Osikomaiya, Bodunrin, Oyonarte, Salvador, Pardo-Oviedo, Juan M., Patel, Mahesh C., Paterson, David L., Pena-Perez, Carlos A., Perez-Calatayud, Angel A., Perez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md M., Rahman, Md S., Ramesh, Mayur, Ramirez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodriguez, Yhojan, Rodriguez-Bano, Jesus, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza M., Sasadeusz, Joe, Scozzari, Gitana, Shankar-Hari, Manu, Sharma, Gorav, Snelling, Thomas, Soto, Alonso, Tagayuna, Pedrito Y., Tang, Amy, Tatem, Geneva, Teofili, Luciana, Tong, Steven Y. C., Turgeon, Alexis F., Veloso, Januario D., Venkatesh, Balasubramanian, Ventura-Enriquez, Yanet, Webb, Steve A., Wiese, Lothar, Wiken, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., and Hemkens, Lars G.
Abstract: Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Co
Published: 2021
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12. Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials

Author: Axfors, Cathrine, Janiaud, Perrine, Schmitt, Andreas M., Van't Hooft, Janneke, Smith, Emily R., Haber, Noah A., Abayomi, Akin, Abduljalil, Manal, Abdulrahman, Abdulkarim, Acosta-Ampudia, Yeny, Aguilar-Guisado, Manuela, Al-Beidh, Farah, Alejandria, Marissa M., Alfonso, Rachelle N., Ali, Mohammad, AlQahtani, Manaf, AlZamrooni, Alaa, Anaya, Juan-Manuel, Ang, Mark Angelo C., Aomar, Ismael F., Argumanis, Luis E., Averyanov, Alexander, Baklaushev, Vladimir P., Balionis, Olga, Benfield, Thomas, Berry, Scott, Birocco, Nadia, Bonifacio, Lynn B., Bowen, Asha C., Bown, Abbie, Cabello-Gutierrez, Carlos, Camacho, Bernardo, Camacho-Ortiz, Adrian, Campbell-Lee, Sally, Cao, Damon H., Cardesa, Ana, Carnate, Jose M., Castillo, German Jr J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Neto, Abel Costa, D'Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, Diaz-Coronado, Juan C., Diaz Ponce-Medrano, Juan A., Donneau, Anne-Francoise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae S., Estcourt, Lise J., Evans, Amy, Evasan, Agnes L. M., Fareli, Christian J., Fernandez-Sanchez, Veronica, Galassi, Claudia, Gallo, Juan E., Garcia, Patricia J., Garcia, Patricia L., Garcia, Jesus A., Garigliany, Mutien, Garza-Gonzalez, Elvira, Gauiran, Deonne Thaddeus, V, Gaviria Garcia, Paula A., Giron-Gonzalez, Jose-Antonio, Gomez-Almaguer, David, Gordon, Anthony C., Gothot, Andre, Grass Guaqueta, Jeser Santiago, Green, Cameron, Grimaldi, David, Hammond, Naomi E., Harvala, Heli, Heralde, Francisco M., Herrick, Jesica, Higgins, Alisa M., Hills, Thomas E., Hines, Jennifer, Holm, Karin, Hoque, Ashraful, Hoste, Eric, Ignacio, Jose M., Ivanov, Alexander, V, Janssen, Maike, Jennings, Jeffrey H., Jha, Vivekanand, King, Ruby Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Francois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-Diaz, Jorge M., Lopez-Robles, Concepcion, Lopez-Cardenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Macias, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Ruben D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Javier Martinez-Marcos, Francisco, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma Angelina L., Misset, Benoit, Molton, James S., Mondragon, Alric, V, Monsalve, Diana M., Choghakabodi, Parastoo Moradi, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, Muller-Tidow, Carsten, Murphy, Erin, Najdovski, Tome, Nichol, Alistair D., Nielsen, Henrik, Novak, Richard M., O'Sullivan, Matthew V. N., Olalla, Julian, Osibogun, Akin, Osikomaiya, Bodunrin, Oyonarte, Salvador, Pardo-Oviedo, Juan M., Patel, Mahesh C., Paterson, David L., Pena-Perez, Carlos A., Perez-Calatayud, Angel A., Perez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md M., Rahman, Md S., Ramesh, Mayur, Ramirez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodriguez, Yhojan, Rodriguez-Bano, Jesus, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza M., Sasadeusz, Joe, Scozzari, Gitana, Shankar-Hari, Manu, Sharma, Gorav, Snelling, Thomas, Soto, Alonso, Tagayuna, Pedrito Y., Tang, Amy, Tatem, Geneva, Teofili, Luciana, Tong, Steven Y. C., Turgeon, Alexis F., Veloso, Januario D., Venkatesh, Balasubramanian, Ventura-Enriquez, Yanet, Webb, Steve A., Wiese, Lothar, Wiken, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., Hemkens, Lars G., Axfors, Cathrine, Janiaud, Perrine, Schmitt, Andreas M., Van't Hooft, Janneke, Smith, Emily R., Haber, Noah A., Abayomi, Akin, Abduljalil, Manal, Abdulrahman, Abdulkarim, Acosta-Ampudia, Yeny, Aguilar-Guisado, Manuela, Al-Beidh, Farah, Alejandria, Marissa M., Alfonso, Rachelle N., Ali, Mohammad, AlQahtani, Manaf, AlZamrooni, Alaa, Anaya, Juan-Manuel, Ang, Mark Angelo C., Aomar, Ismael F., Argumanis, Luis E., Averyanov, Alexander, Baklaushev, Vladimir P., Balionis, Olga, Benfield, Thomas, Berry, Scott, Birocco, Nadia, Bonifacio, Lynn B., Bowen, Asha C., Bown, Abbie, Cabello-Gutierrez, Carlos, Camacho, Bernardo, Camacho-Ortiz, Adrian, Campbell-Lee, Sally, Cao, Damon H., Cardesa, Ana, Carnate, Jose M., Castillo, German Jr J., Cavallo, Rossana, Chowdhury, Fazle R., Chowdhury, Forhad U. H., Ciccone, Giovannino, Cingolani, Antonella, Climacosa, Fresthel Monica M., Compernolle, Veerle, Cortez, Carlo Francisco N., Neto, Abel Costa, D'Antico, Sergio, Daly, James, Danielle, Franca, Davis, Joshua S., De Rosa, Francesco Giuseppe, Denholm, Justin T., Denkinger, Claudia M., Desmecht, Daniel, Diaz-Coronado, Juan C., Diaz Ponce-Medrano, Juan A., Donneau, Anne-Francoise, Dumagay, Teresita E., Dunachie, Susanna, Dungog, Cecile C., Erinoso, Olufemi, Escasa, Ivy Mae S., Estcourt, Lise J., Evans, Amy, Evasan, Agnes L. M., Fareli, Christian J., Fernandez-Sanchez, Veronica, Galassi, Claudia, Gallo, Juan E., Garcia, Patricia J., Garcia, Patricia L., Garcia, Jesus A., Garigliany, Mutien, Garza-Gonzalez, Elvira, Gauiran, Deonne Thaddeus, V, Gaviria Garcia, Paula A., Giron-Gonzalez, Jose-Antonio, Gomez-Almaguer, David, Gordon, Anthony C., Gothot, Andre, Grass Guaqueta, Jeser Santiago, Green, Cameron, Grimaldi, David, Hammond, Naomi E., Harvala, Heli, Heralde, Francisco M., Herrick, Jesica, Higgins, Alisa M., Hills, Thomas E., Hines, Jennifer, Holm, Karin, Hoque, Ashraful, Hoste, Eric, Ignacio, Jose M., Ivanov, Alexander, V, Janssen, Maike, Jennings, Jeffrey H., Jha, Vivekanand, King, Ruby Anne N., Kjeldsen-Kragh, Jens, Klenerman, Paul, Kotecha, Aditya, Krapp, Fiorella, Labanca, Luciana, Laing, Emma, Landin-Olsson, Mona, Laterre, Pierre-Francois, Lim, Lyn-Li, Lim, Jodor, Ljungquist, Oskar, Llaca-Diaz, Jorge M., Lopez-Robles, Concepcion, Lopez-Cardenas, Salvador, Lopez-Plaza, Ileana, Lucero, Josephine Anne C., Lundgren, Maria, Macias, Juan, Maganito, Sandy C., Malundo, Anna Flor G., Manrique, Ruben D., Manzini, Paola M., Marcos, Miguel, Marquez, Ignacio, Javier Martinez-Marcos, Francisco, Mata, Ana M., McArthur, Colin J., McQuilten, Zoe K., McVerry, Bryan J., Menon, David K., Meyfroidt, Geert, Mirasol, Ma Angelina L., Misset, Benoit, Molton, James S., Mondragon, Alric, V, Monsalve, Diana M., Choghakabodi, Parastoo Moradi, Morpeth, Susan C., Mouncey, Paul R., Moutschen, Michel, Muller-Tidow, Carsten, Murphy, Erin, Najdovski, Tome, Nichol, Alistair D., Nielsen, Henrik, Novak, Richard M., O'Sullivan, Matthew V. N., Olalla, Julian, Osibogun, Akin, Osikomaiya, Bodunrin, Oyonarte, Salvador, Pardo-Oviedo, Juan M., Patel, Mahesh C., Paterson, David L., Pena-Perez, Carlos A., Perez-Calatayud, Angel A., Perez-Alba, Eduardo, Perkina, Anastasia, Perry, Naomi, Pouladzadeh, Mandana, Poyato, Inmaculada, Price, David J., Quero, Anne Kristine H., Rahman, Md M., Rahman, Md S., Ramesh, Mayur, Ramirez-Santana, Carolina, Rasmussen, Magnus, Rees, Megan A., Rego, Eduardo, Roberts, Jason A., Roberts, David J., Rodriguez, Yhojan, Rodriguez-Bano, Jesus, Rogers, Benjamin A., Rojas, Manuel, Romero, Alberto, Rowan, Kathryn M., Saccona, Fabio, Safdarian, Mehdi, Santos, Maria Clariza M., Sasadeusz, Joe, Scozzari, Gitana, Shankar-Hari, Manu, Sharma, Gorav, Snelling, Thomas, Soto, Alonso, Tagayuna, Pedrito Y., Tang, Amy, Tatem, Geneva, Teofili, Luciana, Tong, Steven Y. C., Turgeon, Alexis F., Veloso, Januario D., Venkatesh, Balasubramanian, Ventura-Enriquez, Yanet, Webb, Steve A., Wiese, Lothar, Wiken, Christian, Wood, Erica M., Yusubalieva, Gaukhar M., Zacharowski, Kai, Zarychanski, Ryan, Khanna, Nina, Moher, David, Goodman, Steven N., Ioannidis, John P. A., and Hemkens, Lars G.
Abstract: Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Co
Published: 2021
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13. Immunoglobulin A N-glycosylation Presents Important Body Fluid-specific Variations in Lactating Mothers.

Author: Goonatilleke, Elisha, Goonatilleke, Elisha, Smilowitz, Jennifer T, Mariño, Karina V, German, Bruce J, Lebrilla, Carlito B, Barboza, Mariana, Goonatilleke, Elisha, Goonatilleke, Elisha, Smilowitz, Jennifer T, Mariño, Karina V, German, Bruce J, Lebrilla, Carlito B, and Barboza, Mariana
Abstract: Secretory Immunoglobulin A (SIgA) is central to mucosal immunity: represents one of the main immunological mechanisms of defense against the potential attack of pathogens. During lactation SIgA is produced by plasmablasts in the mammary gland and is present in breast milk, playing a vital role in the passive immunity of the newborn. Interestingly, the different components of SIgA are highly N-glycosylated, and these N-Glycans have an essential role in health maintenance. In this work, we performed a glycomic study to compare N-glycosylation of SIgA purified from mature breast milk and saliva, and plasma IgA from the same lactating participants. Our results revealed a greater diversity than previously reported, with 89 glycan compositions that may correspond to over 250 structures. Among these glycans, 54 glycan compositions were characterized as body-fluid specific. Most of these unique N-Glycan compositions identified in SIgA from mature milk and IgA from plasma were fucosylated and both fucosylated and sialylated species, whereas in salivary SIgA the unique structures were mainly undecorated complex N-Glycans. In addition, we evaluated the effect of delivery mode on (S)IgA glycosylation. Lactating participants who had given birth by vaginal delivery presented an increased proportion of high mannose and fucosylated glycans in salivary SIgA, and selected high mannose, fucosylated, sialylated, and both fucosylated and sialylated glycans in plasma IgA, indicating that the hormonal changes during vaginal delivery could affect plasma and saliva IgA. These results reveal the structural details that provide a new dimension to the roles of (S)IgA N-Glycans in different tissues, and especially in maternal and new-born protection and infant development. The design of optimal recombinant IgA molecules specifically targeted to protect mucosal surfaces will need to include this dimension of structural detail.
Published: 2019

14. A surrogate-based multi-disciplinary design optimization framework modeling wing–propeller interaction

Author: Alba, Christian (author), Elham, Ali (author), German, Brian J. (author), Veldhuis, L.L.M. (author), Alba, Christian (author), Elham, Ali (author), German, Brian J. (author), and Veldhuis, L.L.M. (author)
Abstract: This paper presents a multi-disciplinary design optimization (MDO) framework for design of a general aviation aircraft wing considering the effects of tractor propellers on the wing aerodynamic characteristics. In pursuit of this objective, a wing–propeller full-interaction aerodynamic routine was developed and integrated with structural and performance models. A substantive contribution of the work is the approach for effectively modeling wing effects on propeller slipstream development while still leveraging traditional propeller and wing analysis tools. Several optimizations were carried out, starting from an existing aircraft design, to test different local and global surrogate-based optimization frameworks and to allow for the assessment of the resulting solutions and corresponding computational performance metrics. Examination of the total function calls and run times showed that the use of surrogate models improves overall optimization performance, provided that suitable surrogate modeling techniques are chosen., Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., Flight Performance and Propulsion
Published: 2018
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15. A Deletion in the Canine POMC Gene Is Associated with Weight and Appetite in Obesity-Prone Labrador Retriever Dogs

Author: Raffan, Eleanor, Dennis, Rowena J., O'Donovan, Conor J., Becker, Julia M., Scott, Robert A., Smith, Stephen P., Withers, David J., Wood, Claire J., Conci, Elena, Clements, Dylan N., Summers, Kim M., German, Alexander J., Mellersh, Cathryn S., Arendt, Maja L., Iyemere, Valentine P., Withers, Elaine, Soder, Josefin, Wernersson, Sara, Andersson, Goran, Lindblad-Toh, Kerstin, Yeo, Giles S. H., O'Rahilly, Stephen, Raffan, Eleanor, Dennis, Rowena J., O'Donovan, Conor J., Becker, Julia M., Scott, Robert A., Smith, Stephen P., Withers, David J., Wood, Claire J., Conci, Elena, Clements, Dylan N., Summers, Kim M., German, Alexander J., Mellersh, Cathryn S., Arendt, Maja L., Iyemere, Valentine P., Withers, Elaine, Soder, Josefin, Wernersson, Sara, Andersson, Goran, Lindblad-Toh, Kerstin, Yeo, Giles S. H., and O'Rahilly, Stephen
Abstract: Sequencing of candidate genes for obesity in Labrador retriever dogs identified a 14 bp deletion in pro-opiomelanocortin (POMC) with an allele frequency of 12%. The deletion disrupts the b-MSH and beta-endorphin coding sequences and is associated with body weight (per allele effect of 0.33 SD), adiposity, and greater food motivation. Among other dog breeds, the deletion was only found in the closely related flat-coat retriever (FCR), where it is similarly associated with body weight and food motivation. The mutation is significantly more common in Labrador retrievers selected to become assistance dogs than pets. In conclusion, the deletion in POMC is a significant modifier of weight and appetite in Labrador retrievers and FCRs and may influence other behavioral traits.
Published: 2016
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16. A Deletion in the Canine POMC Gene Is Associated with Weight and Appetite in Obesity-Prone Labrador Retriever Dogs

Author: Raffan, Eleanor, Dennis, Rowena J., O'Donovan, Conor J., Becker, Julia M., Scott, Robert A., Smith, Stephen P., Withers, David J., Wood, Claire J., Conci, Elena, Clements, Dylan N., Summers, Kim M., German, Alexander J., Mellersh, Cathryn S., Arendt, Maja L., Iyemere, Valentine P., Withers, Elaine, Soder, Josefin, Wernersson, Sara, Andersson, Goran, Lindblad-Toh, Kerstin, Yeo, Giles S. H., O'Rahilly, Stephen, Raffan, Eleanor, Dennis, Rowena J., O'Donovan, Conor J., Becker, Julia M., Scott, Robert A., Smith, Stephen P., Withers, David J., Wood, Claire J., Conci, Elena, Clements, Dylan N., Summers, Kim M., German, Alexander J., Mellersh, Cathryn S., Arendt, Maja L., Iyemere, Valentine P., Withers, Elaine, Soder, Josefin, Wernersson, Sara, Andersson, Goran, Lindblad-Toh, Kerstin, Yeo, Giles S. H., and O'Rahilly, Stephen
Abstract: Sequencing of candidate genes for obesity in Labrador retriever dogs identified a 14 bp deletion in pro-opiomelanocortin (POMC) with an allele frequency of 12%. The deletion disrupts the b-MSH and beta-endorphin coding sequences and is associated with body weight (per allele effect of 0.33 SD), adiposity, and greater food motivation. Among other dog breeds, the deletion was only found in the closely related flat-coat retriever (FCR), where it is similarly associated with body weight and food motivation. The mutation is significantly more common in Labrador retrievers selected to become assistance dogs than pets. In conclusion, the deletion in POMC is a significant modifier of weight and appetite in Labrador retrievers and FCRs and may influence other behavioral traits.
Published: 2016
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17. A Deletion in the Canine POMC Gene Is Associated with Weight and Appetite in Obesity-Prone Labrador Retriever Dogs

Author: Raffan, Eleanor, Dennis, Rowena J., O'Donovan, Conor J., Becker, Julia M., Scott, Robert A., Smith, Stephen P., Withers, David J., Wood, Claire J., Conci, Elena, Clements, Dylan N., Summers, Kim M., German, Alexander J., Mellersh, Cathryn S., Arendt, Maja L., Iyemere, Valentine P., Withers, Elaine, Soder, Josefin, Wernersson, Sara, Andersson, Goran, Lindblad-Toh, Kerstin, Yeo, Giles S. H., O'Rahilly, Stephen, Raffan, Eleanor, Dennis, Rowena J., O'Donovan, Conor J., Becker, Julia M., Scott, Robert A., Smith, Stephen P., Withers, David J., Wood, Claire J., Conci, Elena, Clements, Dylan N., Summers, Kim M., German, Alexander J., Mellersh, Cathryn S., Arendt, Maja L., Iyemere, Valentine P., Withers, Elaine, Soder, Josefin, Wernersson, Sara, Andersson, Goran, Lindblad-Toh, Kerstin, Yeo, Giles S. H., and O'Rahilly, Stephen
Abstract: Sequencing of candidate genes for obesity in Labrador retriever dogs identified a 14 bp deletion in pro-opiomelanocortin (POMC) with an allele frequency of 12%. The deletion disrupts the b-MSH and beta-endorphin coding sequences and is associated with body weight (per allele effect of 0.33 SD), adiposity, and greater food motivation. Among other dog breeds, the deletion was only found in the closely related flat-coat retriever (FCR), where it is similarly associated with body weight and food motivation. The mutation is significantly more common in Labrador retrievers selected to become assistance dogs than pets. In conclusion, the deletion in POMC is a significant modifier of weight and appetite in Labrador retrievers and FCRs and may influence other behavioral traits.
Published: 2016
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18. A Deletion in the Canine POMC Gene Is Associated with Weight and Appetite in Obesity-Prone Labrador Retriever Dogs

Author: Raffan, Eleanor, Dennis, Rowena J., O'Donovan, Conor J., Becker, Julia M., Scott, Robert A., Smith, Stephen P., Withers, David J., Wood, Claire J., Conci, Elena, Clements, Dylan N., Summers, Kim M., German, Alexander J., Mellersh, Cathryn S., Arendt, Maja L., Iyemere, Valentine P., Withers, Elaine, Soder, Josefin, Wernersson, Sara, Andersson, Goran, Lindblad-Toh, Kerstin, Yeo, Giles S. H., O'Rahilly, Stephen, Raffan, Eleanor, Dennis, Rowena J., O'Donovan, Conor J., Becker, Julia M., Scott, Robert A., Smith, Stephen P., Withers, David J., Wood, Claire J., Conci, Elena, Clements, Dylan N., Summers, Kim M., German, Alexander J., Mellersh, Cathryn S., Arendt, Maja L., Iyemere, Valentine P., Withers, Elaine, Soder, Josefin, Wernersson, Sara, Andersson, Goran, Lindblad-Toh, Kerstin, Yeo, Giles S. H., and O'Rahilly, Stephen
Abstract: Sequencing of candidate genes for obesity in Labrador retriever dogs identified a 14 bp deletion in pro-opiomelanocortin (POMC) with an allele frequency of 12%. The deletion disrupts the b-MSH and beta-endorphin coding sequences and is associated with body weight (per allele effect of 0.33 SD), adiposity, and greater food motivation. Among other dog breeds, the deletion was only found in the closely related flat-coat retriever (FCR), where it is similarly associated with body weight and food motivation. The mutation is significantly more common in Labrador retrievers selected to become assistance dogs than pets. In conclusion, the deletion in POMC is a significant modifier of weight and appetite in Labrador retrievers and FCRs and may influence other behavioral traits.
Published: 2016
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19. A Deletion in the Canine POMC Gene Is Associated with Weight and Appetite in Obesity-Prone Labrador Retriever Dogs

Author: Raffan, Eleanor, Dennis, Rowena J., O'Donovan, Conor J., Becker, Julia M., Scott, Robert A., Smith, Stephen P., Withers, David J., Wood, Claire J., Conci, Elena, Clements, Dylan N., Summers, Kim M., German, Alexander J., Mellersh, Cathryn S., Arendt, Maja L., Iyemere, Valentine P., Withers, Elaine, Soder, Josefin, Wernersson, Sara, Andersson, Goran, Lindblad-Toh, Kerstin, Yeo, Giles S. H., O'Rahilly, Stephen, Raffan, Eleanor, Dennis, Rowena J., O'Donovan, Conor J., Becker, Julia M., Scott, Robert A., Smith, Stephen P., Withers, David J., Wood, Claire J., Conci, Elena, Clements, Dylan N., Summers, Kim M., German, Alexander J., Mellersh, Cathryn S., Arendt, Maja L., Iyemere, Valentine P., Withers, Elaine, Soder, Josefin, Wernersson, Sara, Andersson, Goran, Lindblad-Toh, Kerstin, Yeo, Giles S. H., and O'Rahilly, Stephen
Abstract: Sequencing of candidate genes for obesity in Labrador retriever dogs identified a 14 bp deletion in pro-opiomelanocortin (POMC) with an allele frequency of 12%. The deletion disrupts the b-MSH and beta-endorphin coding sequences and is associated with body weight (per allele effect of 0.33 SD), adiposity, and greater food motivation. Among other dog breeds, the deletion was only found in the closely related flat-coat retriever (FCR), where it is similarly associated with body weight and food motivation. The mutation is significantly more common in Labrador retrievers selected to become assistance dogs than pets. In conclusion, the deletion in POMC is a significant modifier of weight and appetite in Labrador retrievers and FCRs and may influence other behavioral traits.
Published: 2016
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20. Biochemicalparametersrelated to the metabolic syndrome in healthydogs and theirrelationshipswith body condition score

Author: Europeancollege of veterinaryinternalmedicine (2016), Gomez-Fernandez, C, Farnir, F., Höglund, Katja, Gouni, Vassiliki, Wiberg, Maria, Lundgren Willesen, J., Hanas, Sofia, McEntee, Kathleen, Mejer Sørensen, L., Tiret, Laurent, Häggström, Jens, Lohi, Hannes, Chetboul, Valérie, Fredholm, Merete, Lequarré, Anne Sophie, German, Alex J, Peeters, Dominique, Merveille, Anne-Christine, Europeancollege of veterinaryinternalmedicine (2016), Gomez-Fernandez, C, Farnir, F., Höglund, Katja, Gouni, Vassiliki, Wiberg, Maria, Lundgren Willesen, J., Hanas, Sofia, McEntee, Kathleen, Mejer Sørensen, L., Tiret, Laurent, Häggström, Jens, Lohi, Hannes, Chetboul, Valérie, Fredholm, Merete, Lequarré, Anne Sophie, German, Alex J, Peeters, Dominique, and Merveille, Anne-Christine
Abstract: info:eu-repo/semantics/nonPublished
Published: 2016

21. A Research Agenda for Tradespace Exploration and Analysis of Engineered Resilient Systems

Author: ARMY RESEARCH LAB ABERDEEN PROVING GROUND MD, Spero, Eric, Bloebaum, Christina L, German, Brian J, Pyster, Art, Ross, Adam M, ARMY RESEARCH LAB ABERDEEN PROVING GROUND MD, Spero, Eric, Bloebaum, Christina L, German, Brian J, Pyster, Art, and Ross, Adam M
Abstract: This paper describes the activity of a workshop on Data-Driven Tradespace Exploration and Analysis: A Key Technical Thrust of Engineered Resilient Systems (ERS). The workshop was attended by 40 academic, government, and industry researchers and practitioners involved in tradespace exploration for a variety of engineering domains. The one-and-one-half day workshop sought to develop near and far term tradespace technology research recommendations for the ERS Priority Steering Council (PSC) Lead. To determine promising research areas, workshop attendees were asked to describe desired tradespace capabilities, the associated current approach and its deficiencies, and gaps between the two states. These research areas were summarized in statements of need, supporting rationale, and investment timeframe. Resilience in the context of ERS is more than robustness; resilience implies that when the system is placed into an environment in which it was not originally intended to operate, after some degradation in performance, the system can be adapted or reconfigured to perform at its intended levels. To support design for resilience, more alternatives must be generated earlier, considered longer, explored over multiple, dynamic alternative futures, and searched exhaustively. The workshop described in this paper was organized to discuss current methods, process, and tools for performing these tradespace analysis related tasks and to better understand existing tradespace capabilities and their suitability for ERS., Presented at the Conference on Systems Engineering Research (CSER 2014), Redondo Beach, CA, March 21-22, 2014 and published in Procedia Computer Science v28, 2014. Prepared in collaborartion with Iowa State University, Ames, IA; Georgia Institute of Technology, Atlanta, GA; Stevens Institute of Technology, Washington, DC; and Massachusetts Institute of Technology, Cambridge, MA. The original document contains color images.
Published: 2014

22. IR microspectroscopy: potential applications in cervical cancer screening.

Author: Walsh, Michael J., German, Matthew J., Singh, Maneesh, Pollock, Hubert M., Hammiche, Azzedine, Kyrgiou, Maria, Stringfellow, Helen F., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., Martin, Francis L, Walsh, Michael J., German, Matthew J., Singh, Maneesh, Pollock, Hubert M., Hammiche, Azzedine, Kyrgiou, Maria, Stringfellow, Helen F., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., and Martin, Francis L
Abstract: Screening exfoliative cytology for early dysplastic cells reduces incidence and mortality from squamous carcinoma of the cervix. In the developed world, screening programmes have adopted a 3?5 years recall system. In its absence, cervical cancer would be the second most common female cancer in these regions; instead, it is currently eleventh. However, there exist a number of limitations to the smear test even given the removal of contaminants using liquid-based cytology. It is prohibitively expensive, labour-intensive and subject to inaccuracies that give rise to significant numbers of false negatives. There remains a need for novel approaches to allow efficient and objective interrogation of exfoliative cytology. Methods that variously exploit infrared (IR) microspectroscopy are one possibility. Using IR microspectroscopy, an integrated ?biochemical-cell fingerprint? of the lipid, protein and carbohydrate composition of a biomolecular entity may be derived in the form of a spectrum via vibrational transitions of individual chemical bonds. Powerful statistical approaches (e.g. principal component analysis) now facilitate the interrogation of large amounts of spectroscopic data to allow the extraction of what may be small but extremely significant biomarker differences between disease-free and pre-malignant or malignant samples. An increasing wealth of literature points to the ability of IR microspectroscopy to allow the segregation of cells based on their disease status. We review the current evidence supporting its diagnostic potential in cancer biology.
Published: 2007

23. ATR microspectroscopy with multivariate analysis segregates grades of exfoliative cervical cytology.

Author: Walsh, Michael J., Singh, Maneesh N., Pollock, Hubert M., Cooper, Leanne J., German, Matthew J., Stringfellow, Helen F., Fullwood, Nigel J., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., Martin, Francis L, Walsh, Michael J., Singh, Maneesh N., Pollock, Hubert M., Cooper, Leanne J., German, Matthew J., Stringfellow, Helen F., Fullwood, Nigel J., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., and Martin, Francis L
Abstract: Although cervical cancer screening in the UK has led to reductions in the incidence of invasive disease, this programme remains flawed. We set out to examine the potential of infrared (IR) microspectroscopy to allow the profiling of cellular biochemical constituents associated with disease progression. Attenuated total reflection-Fourier Transform IR (ATR) microspectroscopy was employed to interrogate spectral differences between samples of exfoliative cervical cytology collected into liquid based cytology (LBC). These were histologically characterised as normal (n = 5), low-grade (n = 5), high-grade (n = 5) or severe dyskaryosis (? carcinoma) (n = 5). Examination of resultant spectra was coupled with principal component analysis (PCA) and subsequent linear discriminant analysis (LDA). The interrogation of LBC samples using ATR microspectroscopy with PCA?LDA facilitated the discrimination of different categories of exfoliative cytology and allowed the identification of potential biomarkers of abnormality; these occurred prominently in the IR spectral region 1200 cm?1?950 cm?1 consisting of carbohydrates, phosphate, and glycogen. Shifts in the centroids of amide I (≈1650 cm?1) and II (≈1530 cm?1) absorbance bands, indicating conformational changes to the secondary structure of intracellular proteins and associated with increasing disease progression, were also noted. This work demonstrates the potential of ATR microspectroscopy coupled with multivariate analysis to be an objective alternative to routine cytology.
Published: 2007

24. ATR microspectroscopy with multivariate analysis segregates grades of exfoliative cervical cytology.

Author: Walsh, Michael J., Singh, Maneesh N., Pollock, Hubert M., Cooper, Leanne J., German, Matthew J., Stringfellow, Helen F., Fullwood, Nigel J., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., Martin, Francis L, Walsh, Michael J., Singh, Maneesh N., Pollock, Hubert M., Cooper, Leanne J., German, Matthew J., Stringfellow, Helen F., Fullwood, Nigel J., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., and Martin, Francis L
Abstract: Although cervical cancer screening in the UK has led to reductions in the incidence of invasive disease, this programme remains flawed. We set out to examine the potential of infrared (IR) microspectroscopy to allow the profiling of cellular biochemical constituents associated with disease progression. Attenuated total reflection-Fourier Transform IR (ATR) microspectroscopy was employed to interrogate spectral differences between samples of exfoliative cervical cytology collected into liquid based cytology (LBC). These were histologically characterised as normal (n = 5), low-grade (n = 5), high-grade (n = 5) or severe dyskaryosis (? carcinoma) (n = 5). Examination of resultant spectra was coupled with principal component analysis (PCA) and subsequent linear discriminant analysis (LDA). The interrogation of LBC samples using ATR microspectroscopy with PCA?LDA facilitated the discrimination of different categories of exfoliative cytology and allowed the identification of potential biomarkers of abnormality; these occurred prominently in the IR spectral region 1200 cm?1?950 cm?1 consisting of carbohydrates, phosphate, and glycogen. Shifts in the centroids of amide I (≈1650 cm?1) and II (≈1530 cm?1) absorbance bands, indicating conformational changes to the secondary structure of intracellular proteins and associated with increasing disease progression, were also noted. This work demonstrates the potential of ATR microspectroscopy coupled with multivariate analysis to be an objective alternative to routine cytology.
Published: 2007

25. IR microspectroscopy: potential applications in cervical cancer screening.

Author: Walsh, Michael J., German, Matthew J., Singh, Maneesh, Pollock, Hubert M., Hammiche, Azzedine, Kyrgiou, Maria, Stringfellow, Helen F., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., Martin, Francis L, Walsh, Michael J., German, Matthew J., Singh, Maneesh, Pollock, Hubert M., Hammiche, Azzedine, Kyrgiou, Maria, Stringfellow, Helen F., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., and Martin, Francis L
Abstract: Screening exfoliative cytology for early dysplastic cells reduces incidence and mortality from squamous carcinoma of the cervix. In the developed world, screening programmes have adopted a 3?5 years recall system. In its absence, cervical cancer would be the second most common female cancer in these regions; instead, it is currently eleventh. However, there exist a number of limitations to the smear test even given the removal of contaminants using liquid-based cytology. It is prohibitively expensive, labour-intensive and subject to inaccuracies that give rise to significant numbers of false negatives. There remains a need for novel approaches to allow efficient and objective interrogation of exfoliative cytology. Methods that variously exploit infrared (IR) microspectroscopy are one possibility. Using IR microspectroscopy, an integrated ?biochemical-cell fingerprint? of the lipid, protein and carbohydrate composition of a biomolecular entity may be derived in the form of a spectrum via vibrational transitions of individual chemical bonds. Powerful statistical approaches (e.g. principal component analysis) now facilitate the interrogation of large amounts of spectroscopic data to allow the extraction of what may be small but extremely significant biomarker differences between disease-free and pre-malignant or malignant samples. An increasing wealth of literature points to the ability of IR microspectroscopy to allow the segregation of cells based on their disease status. We review the current evidence supporting its diagnostic potential in cancer biology.
Published: 2007

26. Preliminary work on the development of a novel detection method for osteoporosis.

Author: Moran, P., Towler, M. R., Chowdhury, S., Saunders, J., German, Matthew J., Lawson, N. Stuart, Pollock, Hubert M., Pillay, I., Lyons, D., Moran, P., Towler, M. R., Chowdhury, S., Saunders, J., German, Matthew J., Lawson, N. Stuart, Pollock, Hubert M., Pillay, I., and Lyons, D.
Abstract: Osteoporosis affects both the organic and mineral phases of bone resulting in a decrease in resistance to fracture. Dual x-ray absorptiometry (DEXA) scans are used for diagnosing osteoporosis, which is conventionally characterised by a decrease in mineral density. Unfortunately, some patients who suffer osteoporotic fractures have normal bone density, because both the organic and the mineral phase are affected. However, there are currently no methods of evaluating the health of the organic phase. Patients undergoing treatment for osteoporosis have reported hardening of their fingernails. As the properties of nail and bone may be linked in a comparable, measurable way, this work used both mechanical (nano-indentation) and chemical (Raman spectroscopy) methods to evaluate differences between fingernails sourced from osteoporotic and non-osteoporotic patients. The difference in mean modulus between the nails sourced from the groups was 1.1 GPa. The disulphide bond content of fingernail samples from each group was measured by Raman spectroscopy and disulphide bond content of fingernail was found to be significantly lower in the osteoporotic group. It can be concluded that a relationship between the mechanical and chemical properties of nail and bone may exist in a measurable way. This work has suggested that changes in the organic phase of bone are reflected in similar proteins, such as keratin, from which fingernails are composed. Collagen and keratin are two distinct structural proteins, but they share the need for protein sulphation and disulphide bond formation, via cysteine, for their structural integrity. A disorder of either process should lead to disordered collagen and keratin synthesis.
Published: 2007

27. IR microspectroscopy: potential applications in cervical cancer screening.

Author: Walsh, Michael J., German, Matthew J., Singh, Maneesh, Pollock, Hubert M., Hammiche, Azzedine, Kyrgiou, Maria, Stringfellow, Helen F., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., Martin, Francis L., Walsh, Michael J., German, Matthew J., Singh, Maneesh, Pollock, Hubert M., Hammiche, Azzedine, Kyrgiou, Maria, Stringfellow, Helen F., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., and Martin, Francis L.
Abstract: Screening exfoliative cytology for early dysplastic cells reduces incidence and mortality from squamous carcinoma of the cervix. In the developed world, screening programmes have adopted a 3–5 years recall system. In its absence, cervical cancer would be the second most common female cancer in these regions; instead, it is currently eleventh. However, there exist a number of limitations to the smear test even given the removal of contaminants using liquid-based cytology. It is prohibitively expensive, labour-intensive and subject to inaccuracies that give rise to significant numbers of false negatives. There remains a need for novel approaches to allow efficient and objective interrogation of exfoliative cytology. Methods that variously exploit infrared (IR) microspectroscopy are one possibility. Using IR microspectroscopy, an integrated ‘biochemical-cell fingerprint’ of the lipid, protein and carbohydrate composition of a biomolecular entity may be derived in the form of a spectrum via vibrational transitions of individual chemical bonds. Powerful statistical approaches (e.g. principal component analysis) now facilitate the interrogation of large amounts of spectroscopic data to allow the extraction of what may be small but extremely significant biomarker differences between disease-free and pre-malignant or malignant samples. An increasing wealth of literature points to the ability of IR microspectroscopy to allow the segregation of cells based on their disease status. We review the current evidence supporting its diagnostic potential in cancer biology.
Published: 2007

28. ATR microspectroscopy with multivariate analysis segregates grades of exfoliative cervical cytology.

Author: Walsh, Michael J., Singh, Maneesh N., Pollock, Hubert M., Cooper, Leanne J., German, Matthew J., Stringfellow, Helen F., Fullwood, Nigel J., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., Martin, Francis L., Walsh, Michael J., Singh, Maneesh N., Pollock, Hubert M., Cooper, Leanne J., German, Matthew J., Stringfellow, Helen F., Fullwood, Nigel J., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., and Martin, Francis L.
Abstract: Although cervical cancer screening in the UK has led to reductions in the incidence of invasive disease, this programme remains flawed. We set out to examine the potential of infrared (IR) microspectroscopy to allow the profiling of cellular biochemical constituents associated with disease progression. Attenuated total reflection-Fourier Transform IR (ATR) microspectroscopy was employed to interrogate spectral differences between samples of exfoliative cervical cytology collected into liquid based cytology (LBC). These were histologically characterised as normal (n = 5), low-grade (n = 5), high-grade (n = 5) or severe dyskaryosis (? carcinoma) (n = 5). Examination of resultant spectra was coupled with principal component analysis (PCA) and subsequent linear discriminant analysis (LDA). The interrogation of LBC samples using ATR microspectroscopy with PCA–LDA facilitated the discrimination of different categories of exfoliative cytology and allowed the identification of potential biomarkers of abnormality; these occurred prominently in the IR spectral region 1200 cm−1–950 cm−1 consisting of carbohydrates, phosphate, and glycogen. Shifts in the centroids of amide I (≈1650 cm−1) and II (≈1530 cm−1) absorbance bands, indicating conformational changes to the secondary structure of intracellular proteins and associated with increasing disease progression, were also noted. This work demonstrates the potential of ATR microspectroscopy coupled with multivariate analysis to be an objective alternative to routine cytology.
Published: 2007

29. Preliminary work on the development of a novel detection method for osteoporosis.

Author: Moran, P., Towler, M. R., Chowdhury, S., Saunders, J., German, Matthew J., Lawson, N. Stuart, Pollock, Hubert M., Pillay, I., Lyons, D., Moran, P., Towler, M. R., Chowdhury, S., Saunders, J., German, Matthew J., Lawson, N. Stuart, Pollock, Hubert M., Pillay, I., and Lyons, D.
Abstract: Osteoporosis affects both the organic and mineral phases of bone resulting in a decrease in resistance to fracture. Dual x-ray absorptiometry (DEXA) scans are used for diagnosing osteoporosis, which is conventionally characterised by a decrease in mineral density. Unfortunately, some patients who suffer osteoporotic fractures have normal bone density, because both the organic and the mineral phase are affected. However, there are currently no methods of evaluating the health of the organic phase. Patients undergoing treatment for osteoporosis have reported hardening of their fingernails. As the properties of nail and bone may be linked in a comparable, measurable way, this work used both mechanical (nano-indentation) and chemical (Raman spectroscopy) methods to evaluate differences between fingernails sourced from osteoporotic and non-osteoporotic patients. The difference in mean modulus between the nails sourced from the groups was 1.1 GPa. The disulphide bond content of fingernail samples from each group was measured by Raman spectroscopy and disulphide bond content of fingernail was found to be significantly lower in the osteoporotic group. It can be concluded that a relationship between the mechanical and chemical properties of nail and bone may exist in a measurable way. This work has suggested that changes in the organic phase of bone are reflected in similar proteins, such as keratin, from which fingernails are composed. Collagen and keratin are two distinct structural proteins, but they share the need for protein sulphation and disulphide bond formation, via cysteine, for their structural integrity. A disorder of either process should lead to disordered collagen and keratin synthesis.
Published: 2007

30. ATR microspectroscopy with multivariate analysis segregates grades of exfoliative cervical cytology.

Author: Walsh, Michael J., Singh, Maneesh N., Pollock, Hubert M., Cooper, Leanne J., German, Matthew J., Stringfellow, Helen F., Fullwood, Nigel J., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., Martin, Francis L., Walsh, Michael J., Singh, Maneesh N., Pollock, Hubert M., Cooper, Leanne J., German, Matthew J., Stringfellow, Helen F., Fullwood, Nigel J., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., and Martin, Francis L.
Abstract: Although cervical cancer screening in the UK has led to reductions in the incidence of invasive disease, this programme remains flawed. We set out to examine the potential of infrared (IR) microspectroscopy to allow the profiling of cellular biochemical constituents associated with disease progression. Attenuated total reflection-Fourier Transform IR (ATR) microspectroscopy was employed to interrogate spectral differences between samples of exfoliative cervical cytology collected into liquid based cytology (LBC). These were histologically characterised as normal (n = 5), low-grade (n = 5), high-grade (n = 5) or severe dyskaryosis (? carcinoma) (n = 5). Examination of resultant spectra was coupled with principal component analysis (PCA) and subsequent linear discriminant analysis (LDA). The interrogation of LBC samples using ATR microspectroscopy with PCA–LDA facilitated the discrimination of different categories of exfoliative cytology and allowed the identification of potential biomarkers of abnormality; these occurred prominently in the IR spectral region 1200 cm−1–950 cm−1 consisting of carbohydrates, phosphate, and glycogen. Shifts in the centroids of amide I (≈1650 cm−1) and II (≈1530 cm−1) absorbance bands, indicating conformational changes to the secondary structure of intracellular proteins and associated with increasing disease progression, were also noted. This work demonstrates the potential of ATR microspectroscopy coupled with multivariate analysis to be an objective alternative to routine cytology.
Published: 2007

31. IR microspectroscopy: potential applications in cervical cancer screening.

Author: Walsh, Michael J., German, Matthew J., Singh, Maneesh, Pollock, Hubert M., Hammiche, Azzedine, Kyrgiou, Maria, Stringfellow, Helen F., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., Martin, Francis L., Walsh, Michael J., German, Matthew J., Singh, Maneesh, Pollock, Hubert M., Hammiche, Azzedine, Kyrgiou, Maria, Stringfellow, Helen F., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., and Martin, Francis L.
Abstract: Screening exfoliative cytology for early dysplastic cells reduces incidence and mortality from squamous carcinoma of the cervix. In the developed world, screening programmes have adopted a 3–5 years recall system. In its absence, cervical cancer would be the second most common female cancer in these regions; instead, it is currently eleventh. However, there exist a number of limitations to the smear test even given the removal of contaminants using liquid-based cytology. It is prohibitively expensive, labour-intensive and subject to inaccuracies that give rise to significant numbers of false negatives. There remains a need for novel approaches to allow efficient and objective interrogation of exfoliative cytology. Methods that variously exploit infrared (IR) microspectroscopy are one possibility. Using IR microspectroscopy, an integrated ‘biochemical-cell fingerprint’ of the lipid, protein and carbohydrate composition of a biomolecular entity may be derived in the form of a spectrum via vibrational transitions of individual chemical bonds. Powerful statistical approaches (e.g. principal component analysis) now facilitate the interrogation of large amounts of spectroscopic data to allow the extraction of what may be small but extremely significant biomarker differences between disease-free and pre-malignant or malignant samples. An increasing wealth of literature points to the ability of IR microspectroscopy to allow the segregation of cells based on their disease status. We review the current evidence supporting its diagnostic potential in cancer biology.
Published: 2007

32. ATR microspectroscopy with multivariate analysis segregates grades of exfoliative cervical cytology.

Author: Walsh, Michael J., Singh, Maneesh N., Pollock, Hubert M., Cooper, Leanne J., German, Matthew J., Stringfellow, Helen F., Fullwood, Nigel J., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., Martin, Francis L, Walsh, Michael J., Singh, Maneesh N., Pollock, Hubert M., Cooper, Leanne J., German, Matthew J., Stringfellow, Helen F., Fullwood, Nigel J., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., and Martin, Francis L
Abstract: Although cervical cancer screening in the UK has led to reductions in the incidence of invasive disease, this programme remains flawed. We set out to examine the potential of infrared (IR) microspectroscopy to allow the profiling of cellular biochemical constituents associated with disease progression. Attenuated total reflection-Fourier Transform IR (ATR) microspectroscopy was employed to interrogate spectral differences between samples of exfoliative cervical cytology collected into liquid based cytology (LBC). These were histologically characterised as normal (n = 5), low-grade (n = 5), high-grade (n = 5) or severe dyskaryosis (? carcinoma) (n = 5). Examination of resultant spectra was coupled with principal component analysis (PCA) and subsequent linear discriminant analysis (LDA). The interrogation of LBC samples using ATR microspectroscopy with PCA?LDA facilitated the discrimination of different categories of exfoliative cytology and allowed the identification of potential biomarkers of abnormality; these occurred prominently in the IR spectral region 1200 cm?1?950 cm?1 consisting of carbohydrates, phosphate, and glycogen. Shifts in the centroids of amide I (≈1650 cm?1) and II (≈1530 cm?1) absorbance bands, indicating conformational changes to the secondary structure of intracellular proteins and associated with increasing disease progression, were also noted. This work demonstrates the potential of ATR microspectroscopy coupled with multivariate analysis to be an objective alternative to routine cytology.
Published: 2007

33. IR microspectroscopy: potential applications in cervical cancer screening.

Author: Walsh, Michael J., German, Matthew J., Singh, Maneesh, Pollock, Hubert M., Hammiche, Azzedine, Kyrgiou, Maria, Stringfellow, Helen F., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., Martin, Francis L, Walsh, Michael J., German, Matthew J., Singh, Maneesh, Pollock, Hubert M., Hammiche, Azzedine, Kyrgiou, Maria, Stringfellow, Helen F., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., and Martin, Francis L
Abstract: Screening exfoliative cytology for early dysplastic cells reduces incidence and mortality from squamous carcinoma of the cervix. In the developed world, screening programmes have adopted a 3?5 years recall system. In its absence, cervical cancer would be the second most common female cancer in these regions; instead, it is currently eleventh. However, there exist a number of limitations to the smear test even given the removal of contaminants using liquid-based cytology. It is prohibitively expensive, labour-intensive and subject to inaccuracies that give rise to significant numbers of false negatives. There remains a need for novel approaches to allow efficient and objective interrogation of exfoliative cytology. Methods that variously exploit infrared (IR) microspectroscopy are one possibility. Using IR microspectroscopy, an integrated ?biochemical-cell fingerprint? of the lipid, protein and carbohydrate composition of a biomolecular entity may be derived in the form of a spectrum via vibrational transitions of individual chemical bonds. Powerful statistical approaches (e.g. principal component analysis) now facilitate the interrogation of large amounts of spectroscopic data to allow the extraction of what may be small but extremely significant biomarker differences between disease-free and pre-malignant or malignant samples. An increasing wealth of literature points to the ability of IR microspectroscopy to allow the segregation of cells based on their disease status. We review the current evidence supporting its diagnostic potential in cancer biology.
Published: 2007

34. IR microspectroscopy: potential applications in cervical cancer screening.

Author: Walsh, Michael J., German, Matthew J., Singh, Maneesh, Pollock, Hubert M., Hammiche, Azzedine, Kyrgiou, Maria, Stringfellow, Helen F., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., Martin, Francis L, Walsh, Michael J., German, Matthew J., Singh, Maneesh, Pollock, Hubert M., Hammiche, Azzedine, Kyrgiou, Maria, Stringfellow, Helen F., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., and Martin, Francis L
Abstract: Screening exfoliative cytology for early dysplastic cells reduces incidence and mortality from squamous carcinoma of the cervix. In the developed world, screening programmes have adopted a 3?5 years recall system. In its absence, cervical cancer would be the second most common female cancer in these regions; instead, it is currently eleventh. However, there exist a number of limitations to the smear test even given the removal of contaminants using liquid-based cytology. It is prohibitively expensive, labour-intensive and subject to inaccuracies that give rise to significant numbers of false negatives. There remains a need for novel approaches to allow efficient and objective interrogation of exfoliative cytology. Methods that variously exploit infrared (IR) microspectroscopy are one possibility. Using IR microspectroscopy, an integrated ?biochemical-cell fingerprint? of the lipid, protein and carbohydrate composition of a biomolecular entity may be derived in the form of a spectrum via vibrational transitions of individual chemical bonds. Powerful statistical approaches (e.g. principal component analysis) now facilitate the interrogation of large amounts of spectroscopic data to allow the extraction of what may be small but extremely significant biomarker differences between disease-free and pre-malignant or malignant samples. An increasing wealth of literature points to the ability of IR microspectroscopy to allow the segregation of cells based on their disease status. We review the current evidence supporting its diagnostic potential in cancer biology.
Published: 2007

35. ATR microspectroscopy with multivariate analysis segregates grades of exfoliative cervical cytology.

Author: Walsh, Michael J., Singh, Maneesh N., Pollock, Hubert M., Cooper, Leanne J., German, Matthew J., Stringfellow, Helen F., Fullwood, Nigel J., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., Martin, Francis L, Walsh, Michael J., Singh, Maneesh N., Pollock, Hubert M., Cooper, Leanne J., German, Matthew J., Stringfellow, Helen F., Fullwood, Nigel J., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., and Martin, Francis L
Abstract: Although cervical cancer screening in the UK has led to reductions in the incidence of invasive disease, this programme remains flawed. We set out to examine the potential of infrared (IR) microspectroscopy to allow the profiling of cellular biochemical constituents associated with disease progression. Attenuated total reflection-Fourier Transform IR (ATR) microspectroscopy was employed to interrogate spectral differences between samples of exfoliative cervical cytology collected into liquid based cytology (LBC). These were histologically characterised as normal (n = 5), low-grade (n = 5), high-grade (n = 5) or severe dyskaryosis (? carcinoma) (n = 5). Examination of resultant spectra was coupled with principal component analysis (PCA) and subsequent linear discriminant analysis (LDA). The interrogation of LBC samples using ATR microspectroscopy with PCA?LDA facilitated the discrimination of different categories of exfoliative cytology and allowed the identification of potential biomarkers of abnormality; these occurred prominently in the IR spectral region 1200 cm?1?950 cm?1 consisting of carbohydrates, phosphate, and glycogen. Shifts in the centroids of amide I (≈1650 cm?1) and II (≈1530 cm?1) absorbance bands, indicating conformational changes to the secondary structure of intracellular proteins and associated with increasing disease progression, were also noted. This work demonstrates the potential of ATR microspectroscopy coupled with multivariate analysis to be an objective alternative to routine cytology.
Published: 2007

36. Infrared spectroscopy with multivariate analysis potentially facilitates the segregation of different types of prostate cell

Author: German, M J, Hammiche, A, Ragavan, N, Tobin, M J, Fullwood, N J, Matanhelia, S S, Hindley, A C, Nicholson, C M, Pollock, H M, Martin, Francis L, German, M J, Hammiche, A, Ragavan, N, Tobin, M J, Fullwood, N J, Matanhelia, S S, Hindley, A C, Nicholson, C M, Pollock, H M, and Martin, Francis L
Abstract: The prostate gland is conventionally divided into zones or regions. This morphology is of clinical significance as prostate cancer (CaP) occurs mainly in the peripheral zone (PZ). We obtained tissue sets consisting of paraffin-embedded blocks of cancer-free transition zone (TZ) and PZ and adjacent CaP from patients (n = 6) who had undergone radical retropubic prostatectomy; a seventh tissue set of snap-frozen PZ and TZ was obtained from a CaP-free gland removed after radical cystoprostatectomy. Paraffin-embedded tissue slices were sectioned (10-μm thick) and mounted on suitable windows to facilitate infrared (IR) spectra acquisition before being dewaxed and air dried; cryosections were dessicated on BaF2 windows. Spectra were collected employing synchrotron Fourier-transform infrared (FTIR) microspectroscopy in transmission mode or attenuated total reflection-FTIR (ATR) spectroscopy. Epithelial cell and stromal IR spectra were subjected to principal component analysis to determine whether wavenumber-absorbance relationships expressed as single points in “hyperspace” might on the basis of multivariate distance reveal biophysical differences between cells in situ in different tissue regions. After spectroscopic analysis, plotted clusters and their loadings curves highlighted marked variation in the spectral region containing DNA/RNA bands (≈1490–1000 cm−1). By interrogating the intrinsic dimensionality of IR spectra in this small cohort sample, we found that TZ epithelial cells appeared to align more closely with those of CaP while exhibiting marked structural differences compared to PZ epithelium. IR spectra of PZ stroma also suggested that these cells are structurally more different to CaP than those located in the TZ. Because the PZ exhibits a higher occurrence of CaP, other factors (e.g., hormone exposure) may modulate the growth kinetics of initiated epithelial cells in this region. The results of this pilot study surprisingly indicate that TZ epithelial cells ar
Published: 2006

37. Infrared spectroscopy with multivariate analysis potentially facilitates the segregation of different types of prostate cell

Author: German, M J, Hammiche, A, Ragavan, N, Tobin, M J, Fullwood, N J, Matanhelia, S S, Hindley, A C, Nicholson, C M, Pollock, H M, Martin, Francis L, German, M J, Hammiche, A, Ragavan, N, Tobin, M J, Fullwood, N J, Matanhelia, S S, Hindley, A C, Nicholson, C M, Pollock, H M, and Martin, Francis L
Abstract: The prostate gland is conventionally divided into zones or regions. This morphology is of clinical significance as prostate cancer (CaP) occurs mainly in the peripheral zone (PZ). We obtained tissue sets consisting of paraffin-embedded blocks of cancer-free transition zone (TZ) and PZ and adjacent CaP from patients (n = 6) who had undergone radical retropubic prostatectomy; a seventh tissue set of snap-frozen PZ and TZ was obtained from a CaP-free gland removed after radical cystoprostatectomy. Paraffin-embedded tissue slices were sectioned (10-μm thick) and mounted on suitable windows to facilitate infrared (IR) spectra acquisition before being dewaxed and air dried; cryosections were dessicated on BaF2 windows. Spectra were collected employing synchrotron Fourier-transform infrared (FTIR) microspectroscopy in transmission mode or attenuated total reflection-FTIR (ATR) spectroscopy. Epithelial cell and stromal IR spectra were subjected to principal component analysis to determine whether wavenumber-absorbance relationships expressed as single points in “hyperspace” might on the basis of multivariate distance reveal biophysical differences between cells in situ in different tissue regions. After spectroscopic analysis, plotted clusters and their loadings curves highlighted marked variation in the spectral region containing DNA/RNA bands (≈1490–1000 cm−1). By interrogating the intrinsic dimensionality of IR spectra in this small cohort sample, we found that TZ epithelial cells appeared to align more closely with those of CaP while exhibiting marked structural differences compared to PZ epithelium. IR spectra of PZ stroma also suggested that these cells are structurally more different to CaP than those located in the TZ. Because the PZ exhibits a higher occurrence of CaP, other factors (e.g., hormone exposure) may modulate the growth kinetics of initiated epithelial cells in this region. The results of this pilot study surprisingly indicate that TZ epithelial cells ar
Published: 2006

38. Discrimination of exfoliative cytology samples employing ATR-FTIR microspectroscopy.

Author: Walsh, Michael J., German, Mathew J., Pollock, Hubert M., Hammiche, Azzadine, Singh, Maneesh, Kyrgiou, Maria, Stringfellow, Helen, Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., Martin, Francis L, Walsh, Michael J., German, Mathew J., Pollock, Hubert M., Hammiche, Azzadine, Singh, Maneesh, Kyrgiou, Maria, Stringfellow, Helen, Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., and Martin, Francis L
Abstract: The aetiology of cervical cancer is strongly associated with viral infection (i.e. human papillomavirus (HPV)); other risk factors include low socio-economic class, multiple sexual partners, smoking and poor diet. Cervical cancer screening employing smears of exfoliative cytology for the visual identification of atypical cells has successfully led to a fall in mortality from this disease. However, false negatives occur when a smear is determined normal although atypical cells (be they pre-malignant or malignant) are present. The use of attenuated total reflection (ATR)-FTIR microspectroscopy to interrogate samples of exfoliative cytology is a novel approach to screening that may allow the rapid profiling of a pathological status. Changes in derived vibrational spectra may be associated with a biochemical biomarker of dyskaryosis. To investigate this possibility, we interrogated eight cervical samples of exfoliative cytology using ATR-FTIR microspectroscopy. Two were normal, two were low-grade cervical intraepithelial neoplasia (CIN)1, two were high-grade (CIN2/3) and two were invasive carcinoma samples. Cellular material was applied to an ATR crystal and vibrational spectra were obtained using a Bruker Vector 22 FTIR spectrometer with Helios ATR attachment. At least 10 spectra per sample of exfoliative cytology were acquired in the ATR mode using Bruker OPUS software; these spectra were then individually baseline corrected. These derived spectra were subsequently analysed using principal component analysis (PCA). Cluster plots allowed the identification of any spatial separation (pointing to increasing dissimilarity) as a function of spectral differences between different samples in a 3-D ??hyperspace??. Apparently independent of oncogenic HPV genotype, successful discrimination between normal, CIN1, CIN2/3 and invasive carcinoma samples was obtained. Normal and invasive carcinoma samples exhibited 100% segregation in ??hyperspace?? and the samples classified as low
Published: 2006

39. Characterization of Putative Stem Cell Populations in the Cornea Using Synchrotron Infrared Microspectroscopy.

Author: German, Matthew J., Pollock, Hubert M., Zhao, Bojun, Tobin, Mark J., Hammiche, Azzedine, Bentley, Adam, Cooper, Leanne J., Martin, Francis L, Fullwood, Nigel J., German, Matthew J., Pollock, Hubert M., Zhao, Bojun, Tobin, Mark J., Hammiche, Azzedine, Bentley, Adam, Cooper, Leanne J., Martin, Francis L, and Fullwood, Nigel J.
Abstract: PURPOSE. High-resolution synchrotron radiation-based Fourier transform infrared (SR-FTIR) microspectroscopy coupled with multivariate analysis was used to investigate the characteristics of putative adult stem cell (SC), transiently amplified (TA) cell, and terminally differentiated (TD) cell populations of the corneal epithelium. METHODS. Spectra of individual cells in situ in cryosections of bovine cornea were collected by using a synchrotron microspectroscopy facility at Daresbury Laboratory (United Kingdom). The resultant spectra were analyzed by multivariate analysis. RESULTS. The median spectra of the three different cell populations showed marked differences, which correlated with their degree of differentiation and proliferative capacity. Multivariate (principal component) analysis (PCA) showed that the three cell populations could be segregated into discrete clusters, with only a slight overlap between the SC and TA cell populations. Further analysis (Mann-Whitney test) indicated that the most significant (P < 0.001) spectral differences between the SC and TA cell populations were chiefly associated with changes in nucleic acid conformation. CONCLUSIONS. SR-FTIR microspectroscopy coupled with PCA appears to enable the identification of SC, TA cell, and TD cell populations. The results also suggest that a small subpopulation of cells in the corneal epithelial SC niche possess TA cell-like characteristics. The most significant spectral characteristics associated with the SCs appear to relate to differences in nucleic acid conformation. This finding is consistent with recent theories suggesting that the control of differentiation is related to major changes in chromatin structure.
Published: 2006

40. Characterization of Putative Stem Cell Populations in the Cornea Using Synchrotron Infrared Microspectroscopy.

Author: German, Matthew J., Pollock, Hubert M., Zhao, Bojun, Tobin, Mark J., Hammiche, Azzedine, Bentley, Adam, Cooper, Leanne J., Martin, Francis L, Fullwood, Nigel J., German, Matthew J., Pollock, Hubert M., Zhao, Bojun, Tobin, Mark J., Hammiche, Azzedine, Bentley, Adam, Cooper, Leanne J., Martin, Francis L, and Fullwood, Nigel J.
Abstract: PURPOSE. High-resolution synchrotron radiation-based Fourier transform infrared (SR-FTIR) microspectroscopy coupled with multivariate analysis was used to investigate the characteristics of putative adult stem cell (SC), transiently amplified (TA) cell, and terminally differentiated (TD) cell populations of the corneal epithelium. METHODS. Spectra of individual cells in situ in cryosections of bovine cornea were collected by using a synchrotron microspectroscopy facility at Daresbury Laboratory (United Kingdom). The resultant spectra were analyzed by multivariate analysis. RESULTS. The median spectra of the three different cell populations showed marked differences, which correlated with their degree of differentiation and proliferative capacity. Multivariate (principal component) analysis (PCA) showed that the three cell populations could be segregated into discrete clusters, with only a slight overlap between the SC and TA cell populations. Further analysis (Mann-Whitney test) indicated that the most significant (P < 0.001) spectral differences between the SC and TA cell populations were chiefly associated with changes in nucleic acid conformation. CONCLUSIONS. SR-FTIR microspectroscopy coupled with PCA appears to enable the identification of SC, TA cell, and TD cell populations. The results also suggest that a small subpopulation of cells in the corneal epithelial SC niche possess TA cell-like characteristics. The most significant spectral characteristics associated with the SCs appear to relate to differences in nucleic acid conformation. This finding is consistent with recent theories suggesting that the control of differentiation is related to major changes in chromatin structure.
Published: 2006

41. Discrimination of exfoliative cytology samples employing ATR-FTIR microspectroscopy.

Author: Walsh, Michael J., German, Mathew J., Pollock, Hubert M., Hammiche, Azzadine, Singh, Maneesh, Kyrgiou, Maria, Stringfellow, Helen, Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., Martin, Francis L, Walsh, Michael J., German, Mathew J., Pollock, Hubert M., Hammiche, Azzadine, Singh, Maneesh, Kyrgiou, Maria, Stringfellow, Helen, Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., and Martin, Francis L
Abstract: The aetiology of cervical cancer is strongly associated with viral infection (i.e. human papillomavirus (HPV)); other risk factors include low socio-economic class, multiple sexual partners, smoking and poor diet. Cervical cancer screening employing smears of exfoliative cytology for the visual identification of atypical cells has successfully led to a fall in mortality from this disease. However, false negatives occur when a smear is determined normal although atypical cells (be they pre-malignant or malignant) are present. The use of attenuated total reflection (ATR)-FTIR microspectroscopy to interrogate samples of exfoliative cytology is a novel approach to screening that may allow the rapid profiling of a pathological status. Changes in derived vibrational spectra may be associated with a biochemical biomarker of dyskaryosis. To investigate this possibility, we interrogated eight cervical samples of exfoliative cytology using ATR-FTIR microspectroscopy. Two were normal, two were low-grade cervical intraepithelial neoplasia (CIN)1, two were high-grade (CIN2/3) and two were invasive carcinoma samples. Cellular material was applied to an ATR crystal and vibrational spectra were obtained using a Bruker Vector 22 FTIR spectrometer with Helios ATR attachment. At least 10 spectra per sample of exfoliative cytology were acquired in the ATR mode using Bruker OPUS software; these spectra were then individually baseline corrected. These derived spectra were subsequently analysed using principal component analysis (PCA). Cluster plots allowed the identification of any spatial separation (pointing to increasing dissimilarity) as a function of spectral differences between different samples in a 3-D ??hyperspace??. Apparently independent of oncogenic HPV genotype, successful discrimination between normal, CIN1, CIN2/3 and invasive carcinoma samples was obtained. Normal and invasive carcinoma samples exhibited 100% segregation in ??hyperspace?? and the samples classified as low
Published: 2006

42. Discrimination of exfoliative cytology samples employing ATR-FTIR microspectroscopy.

Author: Walsh, Michael J., German, Mathew J., Pollock, Hubert M., Hammiche, Azzadine, Singh, Maneesh, Kyrgiou, Maria, Stringfellow, Helen, Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., Martin, Francis L., Walsh, Michael J., German, Mathew J., Pollock, Hubert M., Hammiche, Azzadine, Singh, Maneesh, Kyrgiou, Maria, Stringfellow, Helen, Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., and Martin, Francis L.
Abstract: The aetiology of cervical cancer is strongly associated with viral infection (i.e. human papillomavirus (HPV)); other risk factors include low socio-economic class, multiple sexual partners, smoking and poor diet. Cervical cancer screening employing smears of exfoliative cytology for the visual identification of atypical cells has successfully led to a fall in mortality from this disease. However, false negatives occur when a smear is determined normal although atypical cells (be they pre-malignant or malignant) are present. The use of attenuated total reflection (ATR)-FTIR microspectroscopy to interrogate samples of exfoliative cytology is a novel approach to screening that may allow the rapid profiling of a pathological status. Changes in derived vibrational spectra may be associated with a biochemical biomarker of dyskaryosis. To investigate this possibility, we interrogated eight cervical samples of exfoliative cytology using ATR-FTIR microspectroscopy. Two were normal, two were low-grade cervical intraepithelial neoplasia (CIN)1, two were high-grade (CIN2/3) and two were invasive carcinoma samples. Cellular material was applied to an ATR crystal and vibrational spectra were obtained using a Bruker Vector 22 FTIR spectrometer with Helios ATR attachment. At least 10 spectra per sample of exfoliative cytology were acquired in the ATR mode using Bruker OPUS software; these spectra were then individually baseline corrected. These derived spectra were subsequently analysed using principal component analysis (PCA). Cluster plots allowed the identification of any spatial separation (pointing to increasing dissimilarity) as a function of spectral differences between different samples in a 3-D ‘‘hyperspace’’. Apparently independent of oncogenic HPV genotype, successful discrimination between normal, CIN1, CIN2/3 and invasive carcinoma samples was obtained. Normal and invasive carcinoma samples exhibited 100% segregation in ‘‘hyperspace’’ and the samples classified as low
Published: 2006

43. Characterization of Putative Stem Cell Populations in the Cornea Using Synchrotron Infrared Microspectroscopy.

Author: German, Matthew J., Pollock, Hubert M., Zhao, Bojun, Tobin, Mark J., Hammiche, Azzedine, Bentley, Adam, Cooper, Leanne J., Martin, Francis L., Fullwood, Nigel J., German, Matthew J., Pollock, Hubert M., Zhao, Bojun, Tobin, Mark J., Hammiche, Azzedine, Bentley, Adam, Cooper, Leanne J., Martin, Francis L., and Fullwood, Nigel J.
Abstract: PURPOSE. High-resolution synchrotron radiation-based Fourier transform infrared (SR-FTIR) microspectroscopy coupled with multivariate analysis was used to investigate the characteristics of putative adult stem cell (SC), transiently amplified (TA) cell, and terminally differentiated (TD) cell populations of the corneal epithelium. METHODS. Spectra of individual cells in situ in cryosections of bovine cornea were collected by using a synchrotron microspectroscopy facility at Daresbury Laboratory (United Kingdom). The resultant spectra were analyzed by multivariate analysis. RESULTS. The median spectra of the three different cell populations showed marked differences, which correlated with their degree of differentiation and proliferative capacity. Multivariate (principal component) analysis (PCA) showed that the three cell populations could be segregated into discrete clusters, with only a slight overlap between the SC and TA cell populations. Further analysis (Mann-Whitney test) indicated that the most significant (P < 0.001) spectral differences between the SC and TA cell populations were chiefly associated with changes in nucleic acid conformation. CONCLUSIONS. SR-FTIR microspectroscopy coupled with PCA appears to enable the identification of SC, TA cell, and TD cell populations. The results also suggest that a small subpopulation of cells in the corneal epithelial SC niche possess TA cell-like characteristics. The most significant spectral characteristics associated with the SCs appear to relate to differences in nucleic acid conformation. This finding is consistent with recent theories suggesting that the control of differentiation is related to major changes in chromatin structure.
Published: 2006

44. Infrared spectroscopy with multivariate analysis potentially facilitates the segregation of different types of prostate cell. (vol 90, pg 3738, 2006)

Author: German, M J, Hammiche, A, Ragavan, N, Tobin, M J, Fullwood, N J, Matanhelia, S S, Hindley, A C, Nicholson, C M, Pollock, H M, Martin, F L, German, M J, Hammiche, A, Ragavan, N, Tobin, M J, Fullwood, N J, Matanhelia, S S, Hindley, A C, Nicholson, C M, Pollock, H M, and Martin, F L
Published: 2006

45. Infrared Spectroscopy with Multivariate Analysis Potentially Facilitates the Segregation of Different Types of Prostate Cell.

Author: German, M. J., Hammiche, A., Ragavan, N., Tobin, M. J., Cooper, Leanne J., Matanhelia, S. S., Hindley, A. C., Nicholson, C. M., Fullwood, N. J., Pollock, H. M., Martin, F. L., German, M. J., Hammiche, A., Ragavan, N., Tobin, M. J., Cooper, Leanne J., Matanhelia, S. S., Hindley, A. C., Nicholson, C. M., Fullwood, N. J., Pollock, H. M., and Martin, F. L.
Abstract: The prostate gland is conventionally divided into zones or regions. This morphology is of clinical significance as prostate cancer (CaP) occurs mainly in the peripheral zone (PZ). We obtained tissue sets consisting of paraffin-embedded blocks of cancer-free transition zone (TZ) and PZ and adjacent CaP from patients (n = 6) who had undergone radical retropubic prostatectomy; a seventh tissue set of snap-frozen PZ and TZ was obtained from a CaP-free gland removed after radical cystoprostatectomy. Paraffin-embedded tissue slices were sectioned (10-µm thick) and mounted on suitable windows to facilitate infrared (IR) spectra acquisition before being dewaxed and air dried; cryosections were dessicated on BaF2 windows. Spectra were collected employing synchrotron Fourier-transform infrared (FTIR) microspectroscopy in transmission mode or attenuated total reflection-FTIR (ATR) spectroscopy. Epithelial cell and stromal IR spectra were subjected to principal component analysis to determine whether wavenumber-absorbance relationships expressed as single points in "hyperspace" might on the basis of multivariate distance reveal biophysical differences between cells in situ in different tissue regions. After spectroscopic analysis, plotted clusters and their loadings curves highlighted marked variation in the spectral region containing DNA/RNA bands (1490–1000 cm–1). By interrogating the intrinsic dimensionality of IR spectra in this small cohort sample, we found that TZ epithelial cells appeared to align more closely with those of CaP while exhibiting marked structural differences compared to PZ epithelium. IR spectra of PZ stroma also suggested that these cells are structurally more different to CaP than those located in the TZ. Because the PZ exhibits a higher occurrence of CaP, other factors (e.g., hormone exposure) may modulate the growth kinetics of initiated epithelial cells in this region. The results of this pilot study surprisingly indicate that TZ epithelial cells are
Published: 2006

46. Infrared Spectroscopy with Multivariate Analysis Potentially Facilitates the Segregation of Different Types of Prostate Cell.

Author: German, M. J., Hammiche, A., Ragavan, N., Tobin, M. J., Cooper, Leanne J., Matanhelia, S. S., Hindley, A. C., Nicholson, C. M., Fullwood, N. J., Pollock, H. M., Martin, F. L., German, M. J., Hammiche, A., Ragavan, N., Tobin, M. J., Cooper, Leanne J., Matanhelia, S. S., Hindley, A. C., Nicholson, C. M., Fullwood, N. J., Pollock, H. M., and Martin, F. L.
Abstract: The prostate gland is conventionally divided into zones or regions. This morphology is of clinical significance as prostate cancer (CaP) occurs mainly in the peripheral zone (PZ). We obtained tissue sets consisting of paraffin-embedded blocks of cancer-free transition zone (TZ) and PZ and adjacent CaP from patients (n = 6) who had undergone radical retropubic prostatectomy; a seventh tissue set of snap-frozen PZ and TZ was obtained from a CaP-free gland removed after radical cystoprostatectomy. Paraffin-embedded tissue slices were sectioned (10-µm thick) and mounted on suitable windows to facilitate infrared (IR) spectra acquisition before being dewaxed and air dried; cryosections were dessicated on BaF2 windows. Spectra were collected employing synchrotron Fourier-transform infrared (FTIR) microspectroscopy in transmission mode or attenuated total reflection-FTIR (ATR) spectroscopy. Epithelial cell and stromal IR spectra were subjected to principal component analysis to determine whether wavenumber-absorbance relationships expressed as single points in "hyperspace" might on the basis of multivariate distance reveal biophysical differences between cells in situ in different tissue regions. After spectroscopic analysis, plotted clusters and their loadings curves highlighted marked variation in the spectral region containing DNA/RNA bands (1490–1000 cm–1). By interrogating the intrinsic dimensionality of IR spectra in this small cohort sample, we found that TZ epithelial cells appeared to align more closely with those of CaP while exhibiting marked structural differences compared to PZ epithelium. IR spectra of PZ stroma also suggested that these cells are structurally more different to CaP than those located in the TZ. Because the PZ exhibits a higher occurrence of CaP, other factors (e.g., hormone exposure) may modulate the growth kinetics of initiated epithelial cells in this region. The results of this pilot study surprisingly indicate that TZ epithelial cells are
Published: 2006

47. Characterization of Putative Stem Cell Populations in the Cornea Using Synchrotron Infrared Microspectroscopy.

Author: German, Matthew J., Pollock, Hubert M., Zhao, Bojun, Tobin, Mark J., Hammiche, Azzedine, Bentley, Adam, Cooper, Leanne J., Martin, Francis L., Fullwood, Nigel J., German, Matthew J., Pollock, Hubert M., Zhao, Bojun, Tobin, Mark J., Hammiche, Azzedine, Bentley, Adam, Cooper, Leanne J., Martin, Francis L., and Fullwood, Nigel J.
Abstract: PURPOSE. High-resolution synchrotron radiation-based Fourier transform infrared (SR-FTIR) microspectroscopy coupled with multivariate analysis was used to investigate the characteristics of putative adult stem cell (SC), transiently amplified (TA) cell, and terminally differentiated (TD) cell populations of the corneal epithelium. METHODS. Spectra of individual cells in situ in cryosections of bovine cornea were collected by using a synchrotron microspectroscopy facility at Daresbury Laboratory (United Kingdom). The resultant spectra were analyzed by multivariate analysis. RESULTS. The median spectra of the three different cell populations showed marked differences, which correlated with their degree of differentiation and proliferative capacity. Multivariate (principal component) analysis (PCA) showed that the three cell populations could be segregated into discrete clusters, with only a slight overlap between the SC and TA cell populations. Further analysis (Mann-Whitney test) indicated that the most significant (P < 0.001) spectral differences between the SC and TA cell populations were chiefly associated with changes in nucleic acid conformation. CONCLUSIONS. SR-FTIR microspectroscopy coupled with PCA appears to enable the identification of SC, TA cell, and TD cell populations. The results also suggest that a small subpopulation of cells in the corneal epithelial SC niche possess TA cell-like characteristics. The most significant spectral characteristics associated with the SCs appear to relate to differences in nucleic acid conformation. This finding is consistent with recent theories suggesting that the control of differentiation is related to major changes in chromatin structure.
Published: 2006

48. Discrimination of exfoliative cytology samples employing ATR-FTIR microspectroscopy.

Author: Walsh, Michael J., German, Mathew J., Pollock, Hubert M., Hammiche, Azzadine, Singh, Maneesh, Kyrgiou, Maria, Stringfellow, Helen, Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., Martin, Francis L, Walsh, Michael J., German, Mathew J., Pollock, Hubert M., Hammiche, Azzadine, Singh, Maneesh, Kyrgiou, Maria, Stringfellow, Helen, Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., and Martin, Francis L
Abstract: The aetiology of cervical cancer is strongly associated with viral infection (i.e. human papillomavirus (HPV)); other risk factors include low socio-economic class, multiple sexual partners, smoking and poor diet. Cervical cancer screening employing smears of exfoliative cytology for the visual identification of atypical cells has successfully led to a fall in mortality from this disease. However, false negatives occur when a smear is determined normal although atypical cells (be they pre-malignant or malignant) are present. The use of attenuated total reflection (ATR)-FTIR microspectroscopy to interrogate samples of exfoliative cytology is a novel approach to screening that may allow the rapid profiling of a pathological status. Changes in derived vibrational spectra may be associated with a biochemical biomarker of dyskaryosis. To investigate this possibility, we interrogated eight cervical samples of exfoliative cytology using ATR-FTIR microspectroscopy. Two were normal, two were low-grade cervical intraepithelial neoplasia (CIN)1, two were high-grade (CIN2/3) and two were invasive carcinoma samples. Cellular material was applied to an ATR crystal and vibrational spectra were obtained using a Bruker Vector 22 FTIR spectrometer with Helios ATR attachment. At least 10 spectra per sample of exfoliative cytology were acquired in the ATR mode using Bruker OPUS software; these spectra were then individually baseline corrected. These derived spectra were subsequently analysed using principal component analysis (PCA). Cluster plots allowed the identification of any spatial separation (pointing to increasing dissimilarity) as a function of spectral differences between different samples in a 3-D ??hyperspace??. Apparently independent of oncogenic HPV genotype, successful discrimination between normal, CIN1, CIN2/3 and invasive carcinoma samples was obtained. Normal and invasive carcinoma samples exhibited 100% segregation in ??hyperspace?? and the samples classified as low
Published: 2006

49. Characterization of Putative Stem Cell Populations in the Cornea Using Synchrotron Infrared Microspectroscopy.

Author: German, Matthew J., Pollock, Hubert M., Zhao, Bojun, Tobin, Mark J., Hammiche, Azzedine, Bentley, Adam, Cooper, Leanne J., Martin, Francis L, Fullwood, Nigel J., German, Matthew J., Pollock, Hubert M., Zhao, Bojun, Tobin, Mark J., Hammiche, Azzedine, Bentley, Adam, Cooper, Leanne J., Martin, Francis L, and Fullwood, Nigel J.
Abstract: PURPOSE. High-resolution synchrotron radiation-based Fourier transform infrared (SR-FTIR) microspectroscopy coupled with multivariate analysis was used to investigate the characteristics of putative adult stem cell (SC), transiently amplified (TA) cell, and terminally differentiated (TD) cell populations of the corneal epithelium. METHODS. Spectra of individual cells in situ in cryosections of bovine cornea were collected by using a synchrotron microspectroscopy facility at Daresbury Laboratory (United Kingdom). The resultant spectra were analyzed by multivariate analysis. RESULTS. The median spectra of the three different cell populations showed marked differences, which correlated with their degree of differentiation and proliferative capacity. Multivariate (principal component) analysis (PCA) showed that the three cell populations could be segregated into discrete clusters, with only a slight overlap between the SC and TA cell populations. Further analysis (Mann-Whitney test) indicated that the most significant (P < 0.001) spectral differences between the SC and TA cell populations were chiefly associated with changes in nucleic acid conformation. CONCLUSIONS. SR-FTIR microspectroscopy coupled with PCA appears to enable the identification of SC, TA cell, and TD cell populations. The results also suggest that a small subpopulation of cells in the corneal epithelial SC niche possess TA cell-like characteristics. The most significant spectral characteristics associated with the SCs appear to relate to differences in nucleic acid conformation. This finding is consistent with recent theories suggesting that the control of differentiation is related to major changes in chromatin structure.
Published: 2006

50. Discrimination of exfoliative cytology samples employing ATR-FTIR microspectroscopy.

Author: Walsh, Michael J., German, Mathew J., Pollock, Hubert M., Hammiche, Azzadine, Singh, Maneesh, Kyrgiou, Maria, Stringfellow, Helen, Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., Martin, Francis L, Walsh, Michael J., German, Mathew J., Pollock, Hubert M., Hammiche, Azzadine, Singh, Maneesh, Kyrgiou, Maria, Stringfellow, Helen, Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., and Martin, Francis L
Abstract: The aetiology of cervical cancer is strongly associated with viral infection (i.e. human papillomavirus (HPV)); other risk factors include low socio-economic class, multiple sexual partners, smoking and poor diet. Cervical cancer screening employing smears of exfoliative cytology for the visual identification of atypical cells has successfully led to a fall in mortality from this disease. However, false negatives occur when a smear is determined normal although atypical cells (be they pre-malignant or malignant) are present. The use of attenuated total reflection (ATR)-FTIR microspectroscopy to interrogate samples of exfoliative cytology is a novel approach to screening that may allow the rapid profiling of a pathological status. Changes in derived vibrational spectra may be associated with a biochemical biomarker of dyskaryosis. To investigate this possibility, we interrogated eight cervical samples of exfoliative cytology using ATR-FTIR microspectroscopy. Two were normal, two were low-grade cervical intraepithelial neoplasia (CIN)1, two were high-grade (CIN2/3) and two were invasive carcinoma samples. Cellular material was applied to an ATR crystal and vibrational spectra were obtained using a Bruker Vector 22 FTIR spectrometer with Helios ATR attachment. At least 10 spectra per sample of exfoliative cytology were acquired in the ATR mode using Bruker OPUS software; these spectra were then individually baseline corrected. These derived spectra were subsequently analysed using principal component analysis (PCA). Cluster plots allowed the identification of any spatial separation (pointing to increasing dissimilarity) as a function of spectral differences between different samples in a 3-D ??hyperspace??. Apparently independent of oncogenic HPV genotype, successful discrimination between normal, CIN1, CIN2/3 and invasive carcinoma samples was obtained. Normal and invasive carcinoma samples exhibited 100% segregation in ??hyperspace?? and the samples classified as low
Published: 2006

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