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2. Copy number architectures define treatment-mediated selection of lethal prostate cancer clones

Author

Hasan, A, Cremaschi, P, Wetterskog, D, Jayaram, A, Wong, S, Williams, S, Pasam, A, Trigos, A, Trujillo, B, Grist, E, Friedrich, S, Vainauskas, O, Parry, M, Ismail, M, Devlies, W, Wingate, A, Linch, M, Naceur-Lombardelli, C, Zaccaria, S, Hessey, S, Shiu, K, Bridgewater, J, Hochhauser, D, Forster, M, Lee, S, Ahmad, T, Papadatos-Pastos, D, Janes, S, Van Loo, P, Enfield, K, Mcgranahan, N, Huebner, A, Quezada, S, Beck, S, Parker, P, Enver, T, Hynds, R, Pearce, D, Falzon, M, Proctor, I, Sinclair, R, Lok, C, Rhodes, Z, Moore, D, Marafioti, T, Mitchison, M, Ellery, P, Sivakumar, M, Brandner, S, Rowan, A, Hiley, C, Veeriah, S, Shaw, H, Toncheva, A, Prymas, P, Watkins, T, Bailey, C, Martinez Ruiz, C, Litchfield, K, Al-Bakir, M, Kanu, N, Ward, S, Lim, E, Reading, J, Chain, B, Akay, M, Flanagan, A, Biswas, D, Pich, O, Dietzen, M, Puttick, C, Colliver, E, Magness, A, Angelova, M, Black, J, Lucas, O, Hill, W, Liu, W, Frankell, A, Magno, N, Athanasopoulou, F, Salgado, R, Lee, C, Grigoriadis, K, Al-Sawaf, O, Karasaki, T, Bunkum, A, Noorani, I, Benafif, S, Barbe, V, Bola, S, Leone, G, Alifrangis, C, Mcgovern, U, Thol, K, Gamble, S, Ung, S, Sahwangarrom, T, Marin, C, Pawlik, P, Lam, J, Richard, C, Vendramin, R, Dijkstra, K, Rane, J, Nicod, J, Dwornik, A, Bowles, K, Zaidi, R, Gishen, F, Stone, P, Stirling, C, Turajlic, S, Larkin, J, Pickering, L, Furness, A, Young, K, Drake, W, Edmonds, K, Hunter, N, Mangwende, M, Pearce, K, Grostate, L, Au, L, Spain, L, Shepherd, S, Yan, H, Shum, B, Tippu, Z, Hanley, B, Spencer, C, Emmerich, M, Gerard, C, Schmitt, A, Del Rosario, L, Carlyle, E, Lewis, C, Holt, L, Lucanas, A, O'Flaherty, M, Hazell, S, Mudhar, H, Messiou, C, Latifoltojar, A, Fendler, A, Byrne, F, Pallikonda, H, Lobon, I, Coulton, A, Cattin, A, Deng, D, Feng, H, Yousaf, N, Popat, S, Curtis, O, Milner-Watts, C, Stamp, G, Nye, E, Murra, A, Korteweg, J, Kelly, D, Terry, L, Biano, J, Peat, K, Kelly, K, Grieco, C, Le, M, D'Arienzo, P, Turay, E, Hill, P, Josephs, D, Irshad, S, Spicer, J, Mahadeva, U, Green, A, Stewart, R, Wright, N, Pulman, G, Mitu, R, Phillips-Boyd, S, Enting, D, Rudman, S, Ghosh, S, Karapanagiotou, E, Pintus, E, Tutt, A, Howlett, S, Brenton, J, Caldas, C, Fitzgerald, R, Jimenez-Linan, M, Provenzano, E, Cluroe, A, Paterson, A, Aitken, S, Allinson, K, Stewart, G, Mcdermott, U, Beddowes, E, Maughan, T, Ansorge, O, Campbell, P, Roxburgh, P, Fraser, S, Blyth, K, Le Quesne, J, Krebs, M, Blackhall, F, Summers, Y, Oliveira, P, Ortega-Franco, A, Dive, C, Gomes, F, Carter, M, Dransfield, J, Thomas, A, Fennell, D, Shaw, J, Wilson, C, Marrone, D, Naidu, B, Baijal, S, Tanchel, B, Langman, G, Robinson, A, Collard, M, Cockcroft, P, Ferris, C, Bancroft, H, Kerr, A, Middleton, G, Webb, J, Kadiri, S, Colloby, P, Olisemeke, B, Wilson, R, Shackleford, H, Osman, A, Tomlinson, I, Jogai, S, Holden, S, Fernandes, T, Mcneish, I, Hampton, B, Mckenzie, M, Hackshaw, A, Sharp, A, Chan, K, Farrelly, L, Bridger, H, Leslie, R, Tookman, A, Swanton, C, Jamal-Hanjani, M, Lise, S, Sandhu, S, Attard, G, Hasan A. M. M., Cremaschi P., Wetterskog D., Jayaram A., Wong S. Q., Williams S., Pasam A., Trigos A., Trujillo B., Grist E., Friedrich S., Vainauskas O., Parry M., Ismail M., Devlies W., Wingate A., Linch M., Naceur-Lombardelli C., Zaccaria S., Hessey S., Shiu K. -K., Bridgewater J., Hochhauser D., Forster M., Lee S. -M., Ahmad T., Papadatos-Pastos D., Janes S., Van Loo P., Enfield K., McGranahan N., Huebner A., Quezada S., Beck S., Parker P., Enver T., Hynds R. E., Pearce D. R., Falzon M., Proctor I., Sinclair R., Lok C. -W., Rhodes Z., Moore D., Marafioti T., Mitchison M., Ellery P., Sivakumar M., Brandner S., Rowan A., Hiley C., Veeriah S., Shaw H., Toncheva A., Prymas P., Watkins T. B. K., Bailey C., Martinez Ruiz C., Litchfield K., Al-Bakir M., Kanu N., Ward S., Lim E., Reading J., Chain B., Watkins T., Akay M., Flanagan A., Biswas D., Pich O., Dietzen M., Puttick C., Colliver E., Magness A., Angelova M., Black J., Lucas O., Hill W., Liu W. -K., Frankell A., Magno N., Athanasopoulou F., Salgado R., Lee C., Grigoriadis K., Al-Sawaf O., Karasaki T., Bunkum A., Noorani I., Benafif S., Barbe V., Bola S. K., Leone G., Alifrangis C., McGovern U., Thol K., Gamble S., Ung S. K., Sahwangarrom T., Marin C. P., Wong S., Pawlik P., Lam J. M., Richard C., Vendramin R., Dijkstra K., Rane J., Nicod J., Dwornik A., Bowles K., Zaidi R., Gishen F., Stone P., Stirling C., Turajlic S., Larkin J., Pickering L., Furness A., Young K., Drake W., Edmonds K., Hunter N., Mangwende M., Pearce K., Grostate L., Au L., Spain L., Shepherd S., Yan H., Shum B., Tippu Z., Hanley B., Spencer C., Emmerich M., Gerard C., Schmitt A. M., Del Rosario L., Carlyle E., Lewis C., Holt L., Lucanas A., O'Flaherty M., Hazell S., Mudhar H., Messiou C., Latifoltojar A., Fendler A., Byrne F., Pallikonda H., Lobon I., Coulton A., Cattin A. -L., Deng D., Feng H., Yousaf N., Popat S., Curtis O., Milner-Watts C., Stamp G., Nye E., Murra A., Korteweg J., Kelly D., Terry L., Biano J., Peat K., Kelly K., Grieco C., Le M. L., D'Arienzo P. D., Turay E., Hill P., Josephs D., Irshad S., Spicer J., Mahadeva U., Green A., Stewart R., Wright N., Pulman G., Mitu R., Phillips-Boyd S., Enting D., Rudman S., Ghosh S., Karapanagiotou E., Pintus E., Tutt A., Howlett S., Brenton J., Caldas C., Fitzgerald R., Jimenez-Linan M., Provenzano E., Cluroe A., Paterson A., Aitken S., Allinson K., Stewart G., McDermott U., Beddowes E., Maughan T., Ansorge O., Campbell P., Roxburgh P., Fraser S., Blyth K., Le Quesne J., Krebs M., Blackhall F., Summers Y., Oliveira P., Ortega-Franco A., Dive C., Gomes F., Carter M., Dransfield J., Thomas A., Fennell D., Shaw J., Wilson C., Marrone D., Naidu B., Baijal S., Tanchel B., Langman G., Robinson A., Collard M., Cockcroft P., Ferris C., Bancroft H., Kerr A., Middleton G., Webb J., Kadiri S., Colloby P., Olisemeke B., Wilson R., Shackleford H., Osman A., Tomlinson I., Jogai S., Holden S., Fernandes T., McNeish I., Hampton B., McKenzie M., Hackshaw A., Sharp A., Chan K., Farrelly L., Bridger H., Leslie R., Tookman A., Swanton C., Jamal-Hanjani M., Lise S., Sandhu S., Attard G., Hasan, A, Cremaschi, P, Wetterskog, D, Jayaram, A, Wong, S, Williams, S, Pasam, A, Trigos, A, Trujillo, B, Grist, E, Friedrich, S, Vainauskas, O, Parry, M, Ismail, M, Devlies, W, Wingate, A, Linch, M, Naceur-Lombardelli, C, Zaccaria, S, Hessey, S, Shiu, K, Bridgewater, J, Hochhauser, D, Forster, M, Lee, S, Ahmad, T, Papadatos-Pastos, D, Janes, S, Van Loo, P, Enfield, K, Mcgranahan, N, Huebner, A, Quezada, S, Beck, S, Parker, P, Enver, T, Hynds, R, Pearce, D, Falzon, M, Proctor, I, Sinclair, R, Lok, C, Rhodes, Z, Moore, D, Marafioti, T, Mitchison, M, Ellery, P, Sivakumar, M, Brandner, S, Rowan, A, Hiley, C, Veeriah, S, Shaw, H, Toncheva, A, Prymas, P, Watkins, T, Bailey, C, Martinez Ruiz, C, Litchfield, K, Al-Bakir, M, Kanu, N, Ward, S, Lim, E, Reading, J, Chain, B, Akay, M, Flanagan, A, Biswas, D, Pich, O, Dietzen, M, Puttick, C, Colliver, E, Magness, A, Angelova, M, Black, J, Lucas, O, Hill, W, Liu, W, Frankell, A, Magno, N, Athanasopoulou, F, Salgado, R, Lee, C, Grigoriadis, K, Al-Sawaf, O, Karasaki, T, Bunkum, A, Noorani, I, Benafif, S, Barbe, V, Bola, S, Leone, G, Alifrangis, C, Mcgovern, U, Thol, K, Gamble, S, Ung, S, Sahwangarrom, T, Marin, C, Pawlik, P, Lam, J, Richard, C, Vendramin, R, Dijkstra, K, Rane, J, Nicod, J, Dwornik, A, Bowles, K, Zaidi, R, Gishen, F, Stone, P, Stirling, C, Turajlic, S, Larkin, J, Pickering, L, Furness, A, Young, K, Drake, W, Edmonds, K, Hunter, N, Mangwende, M, Pearce, K, Grostate, L, Au, L, Spain, L, Shepherd, S, Yan, H, Shum, B, Tippu, Z, Hanley, B, Spencer, C, Emmerich, M, Gerard, C, Schmitt, A, Del Rosario, L, Carlyle, E, Lewis, C, Holt, L, Lucanas, A, O'Flaherty, M, Hazell, S, Mudhar, H, Messiou, C, Latifoltojar, A, Fendler, A, Byrne, F, Pallikonda, H, Lobon, I, Coulton, A, Cattin, A, Deng, D, Feng, H, Yousaf, N, Popat, S, Curtis, O, Milner-Watts, C, Stamp, G, Nye, E, Murra, A, Korteweg, J, Kelly, D, Terry, L, Biano, J, Peat, K, Kelly, K, Grieco, C, Le, M, D'Arienzo, P, Turay, E, Hill, P, Josephs, D, Irshad, S, Spicer, J, Mahadeva, U, Green, A, Stewart, R, Wright, N, Pulman, G, Mitu, R, Phillips-Boyd, S, Enting, D, Rudman, S, Ghosh, S, Karapanagiotou, E, Pintus, E, Tutt, A, Howlett, S, Brenton, J, Caldas, C, Fitzgerald, R, Jimenez-Linan, M, Provenzano, E, Cluroe, A, Paterson, A, Aitken, S, Allinson, K, Stewart, G, Mcdermott, U, Beddowes, E, Maughan, T, Ansorge, O, Campbell, P, Roxburgh, P, Fraser, S, Blyth, K, Le Quesne, J, Krebs, M, Blackhall, F, Summers, Y, Oliveira, P, Ortega-Franco, A, Dive, C, Gomes, F, Carter, M, Dransfield, J, Thomas, A, Fennell, D, Shaw, J, Wilson, C, Marrone, D, Naidu, B, Baijal, S, Tanchel, B, Langman, G, Robinson, A, Collard, M, Cockcroft, P, Ferris, C, Bancroft, H, Kerr, A, Middleton, G, Webb, J, Kadiri, S, Colloby, P, Olisemeke, B, Wilson, R, Shackleford, H, Osman, A, Tomlinson, I, Jogai, S, Holden, S, Fernandes, T, Mcneish, I, Hampton, B, Mckenzie, M, Hackshaw, A, Sharp, A, Chan, K, Farrelly, L, Bridger, H, Leslie, R, Tookman, A, Swanton, C, Jamal-Hanjani, M, Lise, S, Sandhu, S, Attard, G, Hasan A. M. M., Cremaschi P., Wetterskog D., Jayaram A., Wong S. Q., Williams S., Pasam A., Trigos A., Trujillo B., Grist E., Friedrich S., Vainauskas O., Parry M., Ismail M., Devlies W., Wingate A., Linch M., Naceur-Lombardelli C., Zaccaria S., Hessey S., Shiu K. -K., Bridgewater J., Hochhauser D., Forster M., Lee S. -M., Ahmad T., Papadatos-Pastos D., Janes S., Van Loo P., Enfield K., McGranahan N., Huebner A., Quezada S., Beck S., Parker P., Enver T., Hynds R. E., Pearce D. R., Falzon M., Proctor I., Sinclair R., Lok C. -W., Rhodes Z., Moore D., Marafioti T., Mitchison M., Ellery P., Sivakumar M., Brandner S., Rowan A., Hiley C., Veeriah S., Shaw H., Toncheva A., Prymas P., Watkins T. B. K., Bailey C., Martinez Ruiz C., Litchfield K., Al-Bakir M., Kanu N., Ward S., Lim E., Reading J., Chain B., Watkins T., Akay M., Flanagan A., Biswas D., Pich O., Dietzen M., Puttick C., Colliver E., Magness A., Angelova M., Black J., Lucas O., Hill W., Liu W. -K., Frankell A., Magno N., Athanasopoulou F., Salgado R., Lee C., Grigoriadis K., Al-Sawaf O., Karasaki T., Bunkum A., Noorani I., Benafif S., Barbe V., Bola S. K., Leone G., Alifrangis C., McGovern U., Thol K., Gamble S., Ung S. K., Sahwangarrom T., Marin C. P., Wong S., Pawlik P., Lam J. M., Richard C., Vendramin R., Dijkstra K., Rane J., Nicod J., Dwornik A., Bowles K., Zaidi R., Gishen F., Stone P., Stirling C., Turajlic S., Larkin J., Pickering L., Furness A., Young K., Drake W., Edmonds K., Hunter N., Mangwende M., Pearce K., Grostate L., Au L., Spain L., Shepherd S., Yan H., Shum B., Tippu Z., Hanley B., Spencer C., Emmerich M., Gerard C., Schmitt A. M., Del Rosario L., Carlyle E., Lewis C., Holt L., Lucanas A., O'Flaherty M., Hazell S., Mudhar H., Messiou C., Latifoltojar A., Fendler A., Byrne F., Pallikonda H., Lobon I., Coulton A., Cattin A. -L., Deng D., Feng H., Yousaf N., Popat S., Curtis O., Milner-Watts C., Stamp G., Nye E., Murra A., Korteweg J., Kelly D., Terry L., Biano J., Peat K., Kelly K., Grieco C., Le M. L., D'Arienzo P. D., Turay E., Hill P., Josephs D., Irshad S., Spicer J., Mahadeva U., Green A., Stewart R., Wright N., Pulman G., Mitu R., Phillips-Boyd S., Enting D., Rudman S., Ghosh S., Karapanagiotou E., Pintus E., Tutt A., Howlett S., Brenton J., Caldas C., Fitzgerald R., Jimenez-Linan M., Provenzano E., Cluroe A., Paterson A., Aitken S., Allinson K., Stewart G., McDermott U., Beddowes E., Maughan T., Ansorge O., Campbell P., Roxburgh P., Fraser S., Blyth K., Le Quesne J., Krebs M., Blackhall F., Summers Y., Oliveira P., Ortega-Franco A., Dive C., Gomes F., Carter M., Dransfield J., Thomas A., Fennell D., Shaw J., Wilson C., Marrone D., Naidu B., Baijal S., Tanchel B., Langman G., Robinson A., Collard M., Cockcroft P., Ferris C., Bancroft H., Kerr A., Middleton G., Webb J., Kadiri S., Colloby P., Olisemeke B., Wilson R., Shackleford H., Osman A., Tomlinson I., Jogai S., Holden S., Fernandes T., McNeish I., Hampton B., McKenzie M., Hackshaw A., Sharp A., Chan K., Farrelly L., Bridger H., Leslie R., Tookman A., Swanton C., Jamal-Hanjani M., Lise S., Sandhu S., and Attard G.

Abstract

Despite initial responses to hormone treatment, metastatic prostate cancer invariably evolves to a lethal state. To characterize the intra-patient evolutionary relationships of metastases that evade treatment, we perform genome-wide copy number profiling and bespoke approaches targeting the androgen receptor (AR) on 167 metastatic regions from 11 organs harvested post-mortem from 10 men who died from prostate cancer. We identify diverse and patient-unique alterations clustering around the AR in metastases from every patient with evidence of independent acquisition of related genomic changes within an individual and, in some patients, the co-existence of AR-neutral clones. Using the genomic boundaries of pan-autosome copy number changes, we confirm a common clone of origin across metastases and diagnostic biopsies, and identified in individual patients, clusters of metastases occupied by dominant clones with diverged autosomal copy number alterations. These autosome-defined clusters are characterized by cluster-specific AR gene architectures, and in two index cases are topologically more congruent than by chance (p-values 3.07 × 10−8 and 6.4 × 10−4). Integration with anatomical sites suggests patterns of spread and points of genomic divergence. Here, we show that copy number boundaries identify treatment-selected clones with putatively distinct lethal trajectories.

Published
2023

3. Habilidades autorregulatorias e higiene bucal infantil con el apoyo de los padres

Author

Martha Leticia Gaeta, Judith Cavazos, and Ma. del Rosario L. Cabrera

Subjects
autogestión, comportamiento, desarrollo de habilidades, salud bucal, Social Sciences, Social sciences (General), H1-99
Abstract

En este artículo se analizan diferentes variables que inciden en la conducta de auto-cuidado de los pacientes pediátricos que asisten a consulta médica, así como en la de sus padres, para una buena salud oral como son: las creencias de autoeficacia, la intención y el control del comportamiento. En el contexto mexicano, participaron 43 pacientes pediátricos, entre 6 y 13 años de edad, y 36 padres de familia, entre 21 y 47 años de edad, que acompañaban a sus hijos a recibir tratamiento dental. Los resultados muestran que los pacientes pediátricos presentan mayor autoeficacia que su progenitor encuestado; en cambio, los padres presentan mejores respuestas en intención de comportamiento y hábitos de higiene bucal. El control de la acción no presenta diferencias significativas entre los pacientes pediátricos y sus padres.

Published
2017

7. Fatty Acid Composition and Nutritional Indices/Ratios of Colostrum and Milk from Crossbred Goats in the Philippines.

Author

Bondoc, O. L., Del Rosario, N. A., Del Rosario, L. L. G. M., and Ramirez, D. N.

Subjects
OMEGA-6 fatty acids, FATTY acids, GOAT milk, COLOSTRUM, UNSATURATED fatty acids, OLEIC acid, PALMITIC acid
Abstract

Fatty acid (FA) profiles are important measures of the nutritional quality of goat's milk that may impact human cardiovascular health and disease. This study is aimed to compare the FA composition and FA-based nutritional indices/ratios of goat colostrum and milk from crossbred goats in relation to published reports on milk FAs involving purebred goats from other countries. A total of 121 colostrum and milk samples collected on the 30th, 60th, and 90th day of lactation from 33 crossbred goats with Anglo Nubian or Boer sires were analyzed by gas chromatography. The major FAs with the highest proportion in both colostrum and milk were oleic acid (C18:1-n9c), palmitic acid (C16:0), myristic acid (C14:0), and stearic acid (C18:0). Oleic acid, palmitic acid, and myristic acid were significantly higher (p<0.05) in colostrum than in milk (i.e., 27.4% vs 16.8%-22.9%, 24.8% vs 17.8%-19.6%, and 9.6% vs 5.2%-7.4%, respectively). Stearic acid was comparable in colostrum (8.8%) and milk (7.6%-10.8%). Total SFA and MUFA were higher in colostrum than in milk. Colostrum and milk contained low levels (less than 1.5%) of polyunsaturated fatty acids (PUFAs) - omega-6 FAs [i.e., linoleic acid C18:2 n-6 and arachidonic acid C20:4 n-6] and omega-3 FAs [i.e., a-linolenic acid C18:3 n-3 and docosahexaenoic acid C22:6 n-3]. The SFAs (C12:0, C14:0, C16:0, and C18:0) in relation to total MUFAs and PUFAs are known to contribute to the increase in cardiovascular disease. Thus, milk from crossbred goats seems to be more beneficial for cardiovascular health because of its lower atherogenicity and thrombogenicity and higher hypocholesterolemic/hypercholesterolemic ratio than those reported for several transboundary and local breeds. [ABSTRACT FROM AUTHOR]

Published
2023
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8. Immune responses following third COVID-19 vaccination are reduced in patients with hematological malignancies compared to patients with solid

Author

Fendler, A, Shepherd, STC, Au, L, Wilkinson, KA, Wu, M, Schmitt, AM, Tippu, Z, Farag, S, Rogiers, A, Harvey, R, Carlyle, E, Edmonds, K, Del Rosario, L, Lingard, K, Mangwende, M, Holt, L, Ahmod, H, Korteweg, J, Foley, T, Barber, T, Emslie-Henry, A, Caulfield-Lynch, N, Byrne, F, Shum, B, Gerard, CL, Deng, D, Kjaer, S, Song, O-R, Queval, C, Kavanagh, C, Wall, EC, Carr, EJ, Namjou, S, Caidan, S, Gavrielides, M, MacRae, JI, Kelly, G, Peat, K, Kelly, D, Murra, A, Kelly, K, O'Flaherty, M, Shea, RL, Gardner, G, Murray, D, Popat, S, Yousaf, N, Jhanji, S, Van As, N, Young, K, Furness, AJS, Pickering, L, Beale, R, Swanton, C, Crick COVID19 consortium, Gandhi, S, Gamblin, S, Bauer, DLV, Kassiotis, G, Howell, M, Nicholson, E, Walker, S, Wilkinson, RJ, Larkin, J, Turajlic, S, CAPTURE consortium, and Wellcome Trust

Subjects
Cancer Research, Crick COVID19 consortium, Oncology, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, 1109 Neurosciences, CAPTURE consortium
Abstract

In this report from the CAPTURE study (NCT03226886), we demonstrate that a third dose of COVID-19 vaccine boosts neutralizing antibody (NAb) and cellular responses in patients with cancer, including those that had undetectable NAb titers (NAbT) following two vaccine doses or for whom NAbT waned. We have noted that one key member of the CAPTURE consortium—Sanjay Popat—was inadvertently not included in the author list. We now include him as a co-author. There are no additional changes to the declaration of interests statement, since Dr. Popat declares no competing conflict of interest. This author list change is now reflected in the online version of this letter.

Published
2022
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9. 1557O Adaptive immunity to SARS-CoV-2 infection and vaccination in cancer patients: The CAPTURE study

Author

Shepherd, S.T.C., primary, Fendler, A., additional, Au, L., additional, Byrne, F., additional, Wilkinson, K., additional, Wu, M., additional, Schmitt, A.M., additional, Joharatnam-Hogan, N., additional, Shum, B., additional, Del Rosario, L., additional, Edmonds, K., additional, Carlyle, E., additional, Nicholson, E., additional, Howell, M., additional, Swanton, C., additional, Walker, S., additional, Kassiotis, G., additional, Wilkinson, R., additional, Larkin, J., additional, and Turajlic, S., additional

Published
2021
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11. ADAPTeR: A phase II study of anti-PD1 (nivolumab) therapy as pre- and post-operative therapy in metastatic renal cell carcinoma

Author

Au, L., primary, Litchfield, K., additional, Rowan, A., additional, Horswell, S., additional, Byrne, F., additional, Nicol, D., additional, Fotiadis, N., additional, Salgado, R.F., additional, Hazell, S., additional, Lopez, J.I., additional, Hatipoglu, E., additional, Del Rosario, L., additional, Pickering, L., additional, Gore, M., additional, Chain, B., additional, Quezada, S., additional, Larkin, J.M.G., additional, Swanton, C., additional, and Turajlic, S., additional

Published
2019
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12. Habilidades de auto-regulação e higiene bucal das crianças com o apoio dos pais

Author

Gaeta, Martha Leticia, Cavazos, Judith, and Cabrera, Ma. del Rosario L.

Subjects
desarrollo de habilidades, autogestión, behavior, auto-gestão, skills development, comportamento, saúde oral, Self-management, oral health, salud bucal, desenvolvimento de habilidades, comportamiento
Abstract

En este artículo se analizan diferentes variables que inciden en la conducta de auto-cuidado de los pacientes pediátricos que asisten a consulta médica, así como en la de sus padres, para una buena salud oral como son: las creencias de autoeficacia, la intención y el control del comportamiento. En el contexto mexicano, participaron 43 pacientes pediátricos, entre 6 y 13 años de edad, y 36 padres de familia, entre 21 y 47 años de edad, que acompañaban a sus hijos a recibir tratamiento dental. Los resultados muestran que los pacientes pediátricos presentan mayor autoeficacia que su progenitor encuestado; en cambio, los padres presentan mejores respuestas en intención de comportamiento y hábitos de higiene bucal. El control de la acción no presenta diferencias significativas entre los pacientes pediátricos y sus padres. In this article the authors analyze different variables that influence the self-care behavior of pediatric patients attending medical consultations, as well as the behavior of their parents, in relation to achieving good oral health. These variables include: self-belief, behavioral intention and control. In this study conducted in Mexico, participants included 43 pediatric patients aged between 6 and 13 years old, and 36 parents aged between 21 and 47 years of age who accompanied their children to receive dental treatment. The results show that pediatric patients have higher self-belief than their parents. However, parents have better behavioral intentions and oral hygiene habits than their children. There were no significant differences between pediatric patients and their parents in action control. Neste artigo se analisam diferentes variáveis que influenciam o comportamento de auto-atendimento de pacientes pediátricos que frequentam consultas médicas, bem como seus pais, para uma boa saúde bucal como são: as crenças de autoeficácia, a intenção e o controle comportamental. No contexto mexicano, participaram 43 pacientes pediátricos entre 6 e 13 anos de idade, e 36 pais entre 21 e 47 anos de idade, que acompanharam seus filhos para receber tratamento. Os resultados mostram que os pacientes pediátricos tem maior autoeficácia do que seu progenitor correspondente. Os pais têm melhores respostas na intenção comportamental e hábitos de higiene bucal. O controle da ação não apresenta diferenças significativas entre pacientes pediátricos e seus pais.

Published
2017

15. A phase II trial of induction chemotherapy and chemo-IMRT for head and neck squamous cell cancers at risk of bilateral nodal spread: the application of a bilateral superficial lobe parotid-sparing IMRT technique and treatment outcomes

Author

Miah, A B, primary, Schick, U, additional, Bhide, S A, additional, Guerrero-Urbano, M-T, additional, Clark, C H, additional, Bidmead, A M, additional, Bodla, S, additional, Del Rosario, L, additional, Thway, K, additional, Wilson, P, additional, Newbold, K L, additional, Harrington, K J, additional, and Nutting, C M, additional

Published
2014
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16. Rendimiento en grano de cinco cultivares de “ñuña" Phaseolus vulgaris L. (Fabaceae) por la fijación biológica de nitrógeno atmosférico con Rhizobium phaseoli.

Author

Cuadros Negri, María del Rosario L. and Gómez Carrión, José

Abstract

The bean Phaseolus vulgaris L. (Fabaceae) is one of the most important species in Peru and the world for human nourishment. It also improves the ground because it fixes atmospheric nitrogen in symbiosis with Rhizobium phaseoli .It allows saving fertilizer, economical upside for farmers. This research has been carried out in a trial field located in Lima (Peru), from September 2012 to June 2013. The objectives were to evaluate the “ñuña" bean's cultivar performance (P. vulgaris L.) within the production of seeds in symbiosis with R. phaseoli and to select the cultivar the most high performing and which expresses the greatest compatibility in symbiosis. The experimental methodology was the Randomized Complete Block Design (RCB) in 15 treatments (with Rhizobium inoculation, the witnesses: without inoculation and with fertilizer N.P.K.), 05 “ñuña" bean's cultivars and three essays. The following factors have been evaluated: earliness, nodulation and nitrogen fixation (FBN) and performance; which were analyzed in the statistical software, SPSS. There are significant statistical differences between treatments. In the Tukey's average comparison test at 5 % turned out that treatments with inoculation and fertilized with urea do not differ. When evaluating the earliness factors in days, the cultivar N°1 “azulita" had the best performance (at flower's stems appearance, at blooming, at physiological maturity and harvest). What is more, cultivar N° 3 also had the lowest number of days and nodule appearance (74.78 days) in inoculated cultivars tests. The cultivar N°1 presented the best size, nodule number and weight performance. The inoculated cultivar showed the highest performance, especially the N°1 (5,148 kg/ht). As a conclusion, the “ñuña Azulita" had the best performance in grain and it had the greatest compatibility in symbiosis with R. phaseoli. Besides, the biological fixation of nitrogen (FBN) through symbiosis can replace the fertilization with urea, because it is less expensive and does not affect negatively the ecological system. [ABSTRACT FROM AUTHOR]

Published
2016

18. A phase II trial of induction chemotherapy and chemo-IMRT for head and neck squamous cell cancers at risk of bilateral nodal spread: the application of a bilateral superficial lobe parotid-sparing IMRT technique and treatment outcomes.

Author

Miah, A B, Schick, U, Bhide, S A, Guerrero-Urbano, M-T, Clark, C H, Bidmead, A M, Bodla, S, Del Rosario, L, Thway, K, Wilson, P, Newbold, K L, Harrington, K J, and Nutting, C M

Subjects
CANCER chemotherapy, INTENSITY modulated radiotherapy, CELLS, FLUOROURACIL, XEROSTOMIA, PAPILLOMAVIRUSES, DEGLUTITION disorders, CANCER
Abstract

Purpose:To determine the feasibility of induction chemotherapy and chemo-IMRT in head and neck squamous cell cancers at risk of bilateral nodal spread (midline tumours) and to evaluate whether bilateral superficial lobe parotid-sparing IMRT can reduce the incidence of ⩾G2 subjective xerostomia.Methods:Patients with midline tumours were enrolled to a phase II trial to receive induction platinum/5-fluorouracil and concomitant platinum with combined superficial lobe parotid-sparing IMRT. The primary site and involved nodal levels received 65 Gy in 30 fractions (f) and at risk nodal levels, 54 Gy/30f. Incidence of ⩾G2 subjective xerostomia was defined as the primary endpoint. Secondary endpoints included incidences of acute and late toxicities and survival outcomes dependent on human papilloma virus (HPV) status.Results:One hundred and twenty patients with midline cancers completed treatment between December 2005 and May 2010 with median follow-up of 50 months. Incidences of ⩾G2 acute toxicities were: dysphagia 75%; xerostomia 65%; mucositis 86%; pain 83%; and fatigue 64%. At 12 months, ⩾G2 subjective xerostomia was observed in 21% (17% in HPV +ve). Two-year loco-regional progression-free survival (PFS) was 90.7% (95% CI: 85.2-96.2). According to HPV status, there was a significant difference for 2-year loco-regional PFS, 76.8% (HPV-negative) vs 98.6% (HPV-positive), P=0.001. 2-year overall survival was 93% for HPV-positive compared with 52% for HPV-negative cases, P<0.001.Conclusions:Sequential chemotherapy/chemo-IMRT for midline tumours is feasible, with excellent survival outcomes. At 1 year, 21% experience ⩾G2 subjective xerostomia. Two-year survival outcomes differ significantly between HPV-positive and HPV-negative disease, suggesting development of different treatment schedules for the different disease entities. [ABSTRACT FROM AUTHOR]

Published
2015
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19. Emergence of a new Vibrio parahaemolyticus serotype in raw oysters: A prevention quandary.

Author

Daniels, Nicholas A., Ray, Beverly, Easton, Alyssa, Marano, Nina, Kahn, Emily, McShan, II, Andre L., Del Rosario, Lamuels, Baldwin, Tamara, Kingsley, Monica A., Puhr, Nancy D., Wells, Joy G., Angulo, Frederick J., Daniels, N A, Ray, B, Easton, A, Marano, N, Kahn, E, McShan, A L 2nd, Del Rosario, L, and Baldwin, T

Subjects
VIBRIO infections, OYSTERS, VIBRIO, FOOD, HEALTH, SAFETY regulations
Abstract

Context: In May and June 1998, reported Vibrio parahaemolyticus infections increased sharply in Texas.Objective: To determine factors that contributed to the increase in V parahaemolyticus infections.Design, Setting, and Participants: Cross-sectional survey of persons reporting gastroenteritis after eating seafood in Texas; survey of environmental conditions in Galveston Bay.Main Outcome Measures: Traceback of oysters, water quality measures in harvest areas, presence of V parahaemolyticus in stool cultures; comparison of median values for environmental conditions before and during the outbreak compared with during the previous 5 years.Results: Between May 31 and July 10, 1998, 416 persons in 13 states reported having gastroenteritis after eating oysters harvested from Galveston Bay. All 28 available stool specimens from affected persons yielded V parahaemolyticus serotype O3:K6 isolates. Oyster beds met current bacteriologic standards during harvest and fecal coliform counts in water samples were within acceptable limits. Median water temperature and salinity during May and June 1998 were 30.0 degrees C and 29.6 parts per thousand (ppt) compared with 28.9 degrees C and 15.6 ppt for the previous 5 years (P<.001).Conclusions: This is the first reported outbreak of V parahaemolyticus serotype O3:K6 infection in the United States. The emergence of a virulent serotype and elevated seawater temperatures and salinity levels may have contributed to this large multistate outbreak of V parahaemolyticus. Bacteriologic monitoring at harvest sites did not prevent this outbreak, suggesting that current policy and regulations regarding the safety of raw oysters require reevaluation. Consumers and physicians should understand that raw or undercooked oysters can cause illness even if harvested from monitored beds. In patients who develop acute gastroenteritis within 4 days of consuming raw or undercooked oysters, a stool specimen should be tested for Vibrio species using specific media. JAMA. 2000;284:1541-1545. [ABSTRACT FROM AUTHOR]

Published
2000
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20. What seafarers think of CBT

Author

Ellis, Neil, Sampson, Helen, Aguado, J. C., Baylon, A., Del Rosario, L., Lim, Y. F., Velga, J., Ellis, Neil, Sampson, Helen, Aguado, J. C., Baylon, A., Del Rosario, L., Lim, Y. F., and Velga, J.

24. Sotrovimab restores neutralization against current Omicron subvariants in patients with blood cancer.

Author

Wu MY, Shepherd STC, Fendler A, Carr EJ, Au L, Harvey R, Dowgier G, Hobbs A, Herman LS, Ragno M, Adams L, Schmitt AM, Tippu Z, Shum B, Farag S, Rogiers A, O'Reilly N, Bawumia P, Smith C, Carlyle E, Edmonds K, Del Rosario L, Lingard K, Mangwende M, Holt L, Ahmod H, Korteweg J, Foley T, Barber T, Hepworth S, Emslie-Henry A, Caulfield-Lynch N, Byrne F, Deng D, Williams B, Brown M, Caidan S, Gavrielides M, MacRae JI, Kelly G, Peat K, Kelly D, Murra A, Kelly K, O'Flaherty M, Popat S, Yousaf N, Jhanji S, Tatham K, Cunningham D, Van As N, Young K, Furness AJS, Pickering L, Beale R, Swanton C, Gandhi S, Gamblin S, Bauer DLV, Kassiotis G, Howell M, Walker S, Nicholson E, Larkin J, Wall EC, and Turajlic S

Subjects
Humans, SARS-CoV-2, COVID-19, Hematologic Neoplasms drug therapy, Neoplasms
Abstract

Wu et al. report that patients with hematologic malignancies have reduced immunity against SARS-CoV-2 Omicron subvariants and Sotrovimab retains neutralizing capacity against all tested Omicron subvariants., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Published
2023
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25. Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer.

Author

Fendler A, Shepherd STC, Au L, Wu M, Harvey R, Wilkinson KA, Schmitt AM, Tippu Z, Shum B, Farag S, Rogiers A, Carlyle E, Edmonds K, Del Rosario L, Lingard K, Mangwende M, Holt L, Ahmod H, Korteweg J, Foley T, Barber T, Emslie-Henry A, Caulfield-Lynch N, Byrne F, Deng D, Kjaer S, Song OR, Queval CJ, Kavanagh C, Wall EC, Carr EJ, Caidan S, Gavrielides M, MacRae JI, Kelly G, Peat K, Kelly D, Murra A, Kelly K, O'Flaherty M, Shea RL, Gardner G, Murray D, Popat S, Yousaf N, Jhanji S, Tatham K, Cunningham D, Van As N, Young K, Furness AJS, Pickering L, Beale R, Swanton C, Gandhi S, Gamblin S, Bauer DLV, Kassiotis G, Howell M, Nicholson E, Walker S, Wilkinson RJ, Larkin J, and Turajlic S

Subjects
Humans, Antibodies, Neutralizing, Antibodies, Viral, BNT162 Vaccine, Clinical Studies as Topic, Immunity, SARS-CoV-2, COVID-19 prevention & control, COVID-19 Vaccines immunology, Neoplasms
Abstract

Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886), we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralizing antibody titers (NAbTs) using a live virus microneutralization assay against wild-type (WT), Delta, and Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titers and T cell responses after the fourth vaccine dose increased compared with that after the third vaccine dose. Patients who received B cell-depleting therapies within the 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination., Competing Interests: Declaration of interests The authors declare no competing interest., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2022
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26. Omicron neutralising antibodies after third COVID-19 vaccine dose in patients with cancer.

Author

Fendler A, Shepherd STC, Au L, Wu M, Harvey R, Schmitt AM, Tippu Z, Shum B, Farag S, Rogiers A, Carlyle E, Edmonds K, Del Rosario L, Lingard K, Mangwende M, Holt L, Ahmod H, Korteweg J, Foley T, Barber T, Emslie-Henry A, Caulfield-Lynch N, Byrne F, Deng D, Kjaer S, Song OR, Queval C, Kavanagh C, Wall EC, Carr EJ, Caidan S, Gavrielides M, MacRae JI, Kelly G, Peat K, Kelly D, Murra A, Kelly K, O'Flaherty M, Shea RL, Gardner G, Murray D, Yousaf N, Jhanji S, Tatham K, Cunningham D, Van As N, Young K, Furness AJS, Pickering L, Beale R, Swanton C, Gandhi S, Gamblin S, Bauer DLV, Kassiotis G, Howell M, Nicholson E, Walker S, Larkin J, and Turajlic S

Subjects
Antibodies, Neutralizing immunology, Antibodies, Viral immunology, COVID-19 Vaccines, Humans, SARS-CoV-2, COVID-19 prevention & control, Neoplasms
Abstract

Competing Interests: DC has received institutional grant funding from MedImmune/AstraZeneca, Clovis, Eli Lilly, 4SC, Bayer, Celgene, Leap, Roche. DLVB has received grant funding from AstraZeneca. CS is funded by CRUK (TRACERx, PEACE and CRUK Cancer Immunotherapy Catalyst Network), the CRUK Lung Cancer Centre of Excellence (C11496/A30025), the Rosetrees Trust, Butterfield and Stoneygate Trusts, the Novo Nordisk Foundation (ID16584), a Royal Society Professorship Enhancement award (RP/EA/180007), the National Institute of Health Research (NIHR) Biomedical Research Centre at University College London Hospitals, the CRUK University College London Centre, the Experimental Cancer Medicine Centre and the Breast Cancer Research Foundation (BCRF 20-157). This work was supported by a Stand Up To Cancer‐LUNGevity-American Lung Association Lung Cancer Interception Dream Team Translational research grant (SU2C-AACR-DT23-17 to SMD and AES). Stand Up To Cancer is a division of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the scientific partner of SU2C. CS received an ERC Advanced Grant (PROTEUS) from the European Research Council under the European Union's Horizon 2020 research and innovation programme (835297). CS is a Royal Society Napier Research Professor (RP150154). ST is funded by Cancer Research UK (A29911); the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC10988), the UK Medical Research Council (FC10988), and the Wellcome Trust (FC10988); the NIHR Biomedical Research Centre at the Royal Marsden Hospital and Institute of Cancer Research (grant reference number A109), the Royal Marsden Cancer Charity, The Rosetrees Trust (A2204), Ventana Medical Systems (grant reference numbers 10467 and 10530), the National Institute of Health (U01 CA247439) and Melanoma Research Alliance (686061). ST has received speaking fees from Roche, Astra Zeneca, Novartis, and Ipsen. ST has the following patents filed: Indel mutations as a therapeutic target and predictive biomarker PCTGB2018/051892 PCTGB2018/051893 and Clear Cell Renal Cell Carcinoma Biomarkers P113326GB. All other authors declare no competing interests. AF, STCS, LA, MW, and RH contributed equally.

Published
2022
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27. Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: the CAPTURE study.

Author

Fendler A, Shepherd STC, Au L, Wilkinson KA, Wu M, Byrne F, Cerrone M, Schmitt AM, Joharatnam-Hogan N, Shum B, Tippu Z, Rzeniewicz K, Boos LA, Harvey R, Carlyle E, Edmonds K, Del Rosario L, Sarker S, Lingard K, Mangwende M, Holt L, Ahmod H, Korteweg J, Foley T, Bazin J, Gordon W, Barber T, Emslie-Henry A, Xie W, Gerard CL, Deng D, Wall EC, Agua-Doce A, Namjou S, Caidan S, Gavrielides M, MacRae JI, Kelly G, Peat K, Kelly D, Murra A, Kelly K, O'Flaherty M, Dowdie L, Ash N, Gronthoud F, Shea RL, Gardner G, Murray D, Kinnaird F, Cui W, Pascual J, Rodney S, Mencel J, Curtis O, Stephenson C, Robinson A, Oza B, Farag S, Leslie I, Rogiers A, Iyengar S, Ethell M, Messiou C, Cunningham D, Chau I, Starling N, Turner N, Welsh L, van As N, Jones RL, Droney J, Banerjee S, Tatham KC, O'Brien M, Harrington K, Bhide S, Okines A, Reid A, Young K, Furness AJS, Pickering L, Swanton C, Gandhi S, Gamblin S, Bauer DLV, Kassiotis G, Kumar S, Yousaf N, Jhanji S, Nicholson E, Howell M, Walker S, Wilkinson RJ, Larkin J, and Turajlic S

Subjects
Aged, Antibodies, Neutralizing blood, Antibodies, Neutralizing immunology, Antibodies, Viral blood, Antibodies, Viral immunology, BNT162 Vaccine administration & dosage, COVID-19 blood, COVID-19 immunology, ChAdOx1 nCoV-19 administration & dosage, Female, Humans, Immunity, Cellular, Immunogenicity, Vaccine, Male, Middle Aged, Neoplasms blood, Neoplasms complications, Prospective Studies, T-Lymphocytes immunology, BNT162 Vaccine immunology, COVID-19 prevention & control, ChAdOx1 nCoV-19 immunology, Neoplasms immunology, SARS-CoV-2 immunology
Abstract

Coronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) ( NCT03226886 ) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80% of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic., (© 2021. The Author(s).)

Published
2021
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28. Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma.

Author

Au L, Hatipoglu E, Robert de Massy M, Litchfield K, Beattie G, Rowan A, Schnidrig D, Thompson R, Byrne F, Horswell S, Fotiadis N, Hazell S, Nicol D, Shepherd STC, Fendler A, Mason R, Del Rosario L, Edmonds K, Lingard K, Sarker S, Mangwende M, Carlyle E, Attig J, Joshi K, Uddin I, Becker PD, Sunderland MW, Akarca A, Puccio I, Yang WW, Lund T, Dhillon K, Vasquez MD, Ghorani E, Xu H, Spencer C, López JI, Green A, Mahadeva U, Borg E, Mitchison M, Moore DA, Proctor I, Falzon M, Pickering L, Furness AJS, Reading JL, Salgado R, Marafioti T, Jamal-Hanjani M, Kassiotis G, Chain B, Larkin J, Swanton C, Quezada SA, and Turajlic S

Subjects
CD8-Positive T-Lymphocytes, Carcinoma, Renal Cell genetics, Clinical Trials, Phase II as Topic, Endogenous Retroviruses genetics, Gene Expression Profiling methods, Genomics methods, Humans, Immune Checkpoint Inhibitors pharmacology, Kidney Neoplasms genetics, Nivolumab pharmacology, Prospective Studies, Sequence Analysis, RNA, Single-Cell Analysis, Tumor Escape, Tumor Microenvironment, Exome Sequencing, Carcinoma, Renal Cell drug therapy, Drug Resistance, Neoplasm, Immune Checkpoint Inhibitors administration & dosage, Kidney Neoplasms drug therapy, Nivolumab administration & dosage, Receptors, Antigen, T-Cell genetics
Abstract

ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity. Maintenance of highly similar clusters of TCRs post-treatment predict response, suggesting ongoing antigen engagement and survival of families of T cells likely recognizing the same antigens. In responders, nivolumab-bound CD8 + T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action., Competing Interests: Declaration of interests L.A. is funded by the Royal Marsden Cancer Charity. E.H. and M.M. are funded by Cancer Research UK (CRUK). F.B. is funded by the Rosetrees Trust (M829). J.A. is a full-time employee of Hoffmann-La Roche AG (Basel, Switzerland). D.A.M has received consultancy fees from AstraZeneca, Thermo Fisher, and Eli Lilly. A.F. has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 892360. L.P. has received research funding from Pierre Fabre, and honoraria from Pfizer, Ipsen, Bristol-Myers Squibb, and EUSA Pharma. R.S. has received non-financial support from Merck and Bristol Myers Squibb; research support from Merck, Puma Biotechnology, and Roche; and advisory board fees for Bristol Myers Squibb; and personal fees from Roche for an advisory board related to a trial-research project; all related to breast cancer research projects. R.S. reports no conflict of interests related to this project. M.J.H. is a Cancer Research UK (CRUK) Clinician Scientist (RCCFEL\100099) and has received funding from CRUK, National Institute for Health Research, Rosetrees Trust, UKI NETs and NIHR University College London Hospitals Biomedical Research Center. M.J.H. is a member of the Scientific Advisory Board and Steering Committee for Achilles Therapeutics. G.K. is a scientific co-founder of and consulting for Enara Bio and a member of its scientific advisory board. G.K. receives core funding from the Francis Crick Institute (FC0010099). B.C. is supported by a CRUK Project Grant. J.L. has received research funding from Bristol-Myers Squibb, Merck, Novartis, Pfizer, Achilles Therapeutics, Roche, Nektar Therapeutics, Covance, Immunocore, Pharmacyclics, and Aveo, and served as a consultant to Achilles, AstraZeneca, Boston Biomedical, Bristol-Myers Squibb, Eisai, EUSA Pharma, GlaxoSmithKline, Ipsen, Imugene, Incyte, iOnctura, Kymab, Merck Serono, Nektar, Novartis, Pierre Fabre, Pfizer, Roche Genentech, Secarna, and Vitaccess. C.S. acknowledges grant support from Pfizer, AstraZeneca, Bristol-Myers Squibb, Roche-Ventana, Boehringer-Ingelheim, Archer Dx Inc (collaboration in minimal residual disease sequencing technologies), and Ono Pharmaceutical, is an AstraZeneca Advisory Board member and Chief Investigator for the MeRmaiD1 clinical trial, has consulted for Pfizer, Novartis, GlaxoSmithKline, MSD, Bristol-Myers Squibb, Celgene, AstraZeneca, Illumina, Genentech, Roche-Ventana, GRAIL, Medicxi, Bicycle Therapeutics, and the Sarah Cannon Research Institute, has stock options in Apogen Biotechnologies, Epic Bioscience, GRAIL, and has stock options and is co-founder of Achilles Therapeutics. Patents: C.S. holds European patents relating to assay technology to detect tumor recurrence (PCT/GB2017/053289); to targeting neoantigens (PCT/EP2016/059401), identifying patent response to immune checkpoint blockade (PCT/EP2016/071471), determining HLA LOH (PCT/GB2018/052004), predicting survival rates of patients with cancer (PCT/GB2020/050221), identifying patients who respond to cancer treatment (PCT/GB2018/051912), a US patent relating to detecting tumor mutations (PCT/US2017/28013) and both a European and US patent related to identifying insertion/deletion mutation targets (PCT/GB2018/051892). C.S. is Royal Society Napier Research Professor (RP150154). His work is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001169), the UK Medical Research Council (FC001169), and the Wellcome Trust (FC001169). C.S. is funded by Cancer Research UK (TRACERx, PEACE and CRUK Cancer Immunotherapy Catalyst Network), Cancer Research UK Lung Cancer Center of Excellence, the Rosetrees Trust, Butterfield and Stoneygate Trusts, NovoNordisk Foundation (ID16584), Royal Society Research Professorship Enhancement Award (RP/EA/180007), the NIHR BRC at University College London Hospitals, the CRUK-UCL Center, Experimental Cancer Medicine Center and the Breast Cancer Research Foundation, USA (BCRF). His research is supported by a Stand Up To Cancer-LUNGevity-American Lung Association Lung Cancer Interception Dream Team Translational Research Grant (SU2C-AACR-DT23-17). Stand Up To Cancer is a program of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the Scientific Partner of SU2C. C.S. also receives funding from the European Research Council (ERC) under the European Union’s Seventh Framework Program (FP7/2007-2013) Consolidator Grant (FP7-THESEUS-617844), European Commission ITN (FP7-PloidyNet 607722), an ERC Advanced Grant (PROTEUS) from the European Research Council under the European Union’s Horizon 2020 research and innovation program (835297), and Chromavision from the European Union’s Horizon 2020 research and innovation program (665233). S.A.Q. is a CRUK Senior Cancer Research Fellowship (C36463/A22246) and is funded by a CRUK Biotherapeutic Program Grant (C36463/A20764) and the Rosetrees and Stonygate Trusts (A1388) and a donation from the Khoo Teck Puat UK Foundation via the UCL Cancer Institute Research Trust (539288). S.T. is funded by Cancer Research UK (grant reference number C50947/A18176), the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC0010988), the UK Medical Research Council (FC0010988), and the Wellcome Trust (FC0010988), the National Institute for Health Research (NIHR) Biomedical Research Center at the Royal Marsden Hospital and Institute of Cancer Research (grant reference number A109), the Royal Marsden Cancer Charity, The Rosetrees Trust (grant reference number A2204), Ventana Medical Systems Inc (grant reference numbers 10467 and 10530), the National Institutes of Health (Bethesda, MD) and Melanoma Research Alliance. ST has received speaking fees from Roche, Astra Zeneca, Novartis, and Ipsen. S.T. has the following patents filed: Indel mutations as a therapeutic target and predictive biomarker PCTGB2018/051892 and PCTGB2018/051893 and Clear Cell Renal Cell Carcinoma Biomarkers P113326GB., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2021
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29. Functional antibody and T-cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study.

Author

Fendler A, Au L, Shepherd STC, Byrne F, Cerrone M, Boos LA, Rzeniewicz K, Gordon W, Shum B, Gerard CL, Ward B, Xie W, Schmitt AM, Joharatnam-Hogan N, Cornish GH, Pule M, Mekkaoui L, Ng KW, Carlyle E, Edmonds K, Del Rosario L, Sarker S, Lingard K, Mangwende M, Holt L, Ahmod H, Stone R, Gomes C, Flynn HR, Agua-Doce A, Hobson P, Caidan S, Howell M, Wu M, Goldstone R, Crawford M, Cubitt L, Patel H, Gavrielides M, Nye E, Snijders AP, MacRae JI, Nicod J, Gronthoud F, Shea RL, Messiou C, Cunningham D, Chau I, Starling N, Turner N, Welsh L, van As N, Jones RL, Droney J, Banerjee S, Tatham KC, Jhanji S, O'Brien M, Curtis O, Harrington K, Bhide S, Bazin J, Robinson A, Stephenson C, Slattery T, Khan Y, Tippu Z, Leslie I, Gennatas S, Okines A, Reid A, Young K, Furness AJS, Pickering L, Gandhi S, Gamblin S, Swanton C, Nicholson E, Kumar S, Yousaf N, Wilkinson KA, Swerdlow A, Harvey R, Kassiotis G, Larkin J, Wilkinson RJ, and Turajlic S

Abstract

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study (NCT03226886) integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2-positive, 94 were symptomatic and 2 patients died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies, 82% had neutralizing antibodies against WT, whereas neutralizing antibody titers (NAbT) against the Alpha, Beta, and Delta variants were substantially reduced. Whereas S1-reactive antibody levels decreased in 13% of patients, NAbT remained stable up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment-specific, but presented compensatory cellular responses, further supported by clinical. Overall, these findings advance the understanding of the nature and duration of immune response to SARS-CoV-2 in patients with cancer.

Published
2021
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30. Cytokine release syndrome in a patient with colorectal cancer after vaccination with BNT162b2.

Author

Au L, Fendler A, Shepherd STC, Rzeniewicz K, Cerrone M, Byrne F, Carlyle E, Edmonds K, Del Rosario L, Shon J, Haynes WA, Ward B, Shum B, Gordon W, Gerard CL, Xie W, Joharatnam-Hogan N, Young K, Pickering L, Furness AJS, Larkin J, Harvey R, Kassiotis G, Gandhi S, Swanton C, Fribbens C, Wilkinson KA, Wilkinson RJ, Lau DK, Banerjee S, Starling N, Chau I, and Turajlic S

Subjects
COVID-19 metabolism, COVID-19 prevention & control, Humans, Male, SARS-CoV-2 isolation & purification, COVID-19 Vaccines adverse effects, Colorectal Neoplasms metabolism, Cytokine Release Syndrome
Abstract

Patients with cancer are currently prioritized in coronavirus disease 2019 (COVID-19) vaccination programs globally, which includes administration of mRNA vaccines. Cytokine release syndrome (CRS) has not been reported with mRNA vaccines and is an extremely rare immune-related adverse event of immune checkpoint inhibitors. We present a case of CRS that occurred 5 d after vaccination with BTN162b2 (tozinameran)-the Pfizer-BioNTech mRNA COVID-19 vaccine-in a patient with colorectal cancer on long-standing anti-PD-1 monotherapy. The CRS was evidenced by raised inflammatory markers, thrombocytopenia, elevated cytokine levels (IFN-γ/IL-2R/IL-18/IL-16/IL-10) and steroid responsiveness. The close temporal association of vaccination and diagnosis of CRS in this case suggests that CRS was a vaccine-related adverse event; with anti-PD1 blockade as a potential contributor. Overall, further prospective pharmacovigillence data are needed in patients with cancer, but the benefit-risk profile remains strongly in favor of COVID-19 vaccination in this population., (© 2021. The Author(s).)

Published
2021
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31. Theory of mind, facial recognition and emotional processing in schizophrenia.

Author

Rodríguez Sosa JT, Acosta Ojeda M, and Rodríguez Del Rosario L

Abstract

Social cognition can be understood as "the mental operations underlying social interactions, which include the human ability to perceive the intentions and dispositions of others" (Brothers, 1990). Theory of mind, atributtional style, social perception are involved in social cognition. It is wellknown that social cognition is impaired in individuals with schizophrenia. Recent investigations for social cognition in schizophrenia has showed that there is a relationship among social cognition, neurocognition and psychosocial functioning. The purpose of this article is to provide a review of social cognition in schizophrenia focusing on the deficit in Theory of mind described by Frith and recent neuroimaging studies. In fact neuroimaging research has demonstrated specific brain regions consistently engaged during theory of mind tasks.We also present some of the instruments avalaible to evaluate social cognition and to review and improve the main intervention programs. Social cognition may be an important target for pharmacological and psychosocial treatments in the future., (Copyright © 2010 SEP y SEPB. Published by Elsevier Espana. All rights reserved.)

Published
2011
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32. 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and the risk of acute lymphoblastic leukemia (ALL) in Filipino children.

Author

Alcasabas P, Ravindranath Y, Goyette G, Haller A, Del Rosario L, Lesaca-Medina MY, Darga L, Ostrea EM Jr, Taub JW, and Everson RB

Subjects
Adolescent, Child, Child, Preschool, Female, Genotype, Humans, Infant, Male, Multivariate Analysis, Polymerase Chain Reaction, Risk Factors, Methylenetetrahydrofolate Reductase (NADPH2) genetics, Polymorphism, Genetic, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics
Abstract

Background: 5,10-Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism. Polymorphisms at the C677T and A1298C loci are associated with reduced activity; consequently more folate substrates are shunted toward thymidylate and DNA synthesis. Several studies have reported a reduced risk of developing ALL in children with MTHFR polymorphisms. The objective of this study was to determine the association between MTHFR polymorphisms and ALL in Filipino children., Procedure: We conducted a case control study in children diagnosed with ALL at the Philippine General Hospital from 1/2001 through 12/2005. Bone marrow aspirate slides were reviewed by two expert hematologists to verify the morphologic diagnosis of ALL. DNA was isolated from the slides and MTHFR polymorphisms, C677T and A1298C, were determined using Taqman real-time PCR. Cord blood of healthy Filipino newborns served as control., Results: There were a total of 191 ALL and 394 controls genotyped. The distribution of C677T polymorphisms was similar in the two groups (P = 1.0). However, for A1298C, there was significantly more AC and CC genotypes in the ALL compared to controls (P = 0.02; OR 1.57; CI: 1.08-2.28). The 1298C allele frequency for the control group was 36.8% and 677T allele frequency was 9.9%., Conclusion: A1298C polymorphisms is associated with an increased risk for ALL in Filipino children. This may be due to a difference in leukemia biology or to a high prevalence of folate deficiency in Filipinos. Our study reiterates the gene and environment interaction in leukemogenesis.

Published
2008
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33. Wireless pH testing as an adjunct to unsedated transnasal esophagoscopy: the safety and efficacy of transnasal telemetry capsule placement.

Author

Belafsky PC, Allen K, Castro-Del Rosario L, and Roseman D

Subjects
Chronic Disease, Female, Gastric Acidity Determination instrumentation, Humans, Hydrogen-Ion Concentration, Male, Middle Aged, Prospective Studies, Treatment Outcome, Capsules, Cough etiology, Esophagoscopy methods, Gastroesophageal Reflux etiology, Monitoring, Physiologic instrumentation
Abstract

Objectives: The introduction of 48-hour wireless pH testing offers clinicians a new alternative for the objective documentation of reflux. The success of transnasal wireless pH capsule placement has not been previously described. The purpose of this investigation was to describe our experience with transnasal wireless pH capsule placement., Methodology: All patients undergoing unsedated transnasal esophagoscopy and wireless pH capsule placement between January 1, 2003 and July 31, 2003 were prospectively evaluated. Data concerning patient tolerance, success of capsule placement and function, complications, and pH recordings were collected., Results: During this time, 46 persons were evaluated. The mean age of the cohort was 52 years. Of the patients, 50% were male. The indications for the procedure were chronic cough (18/46), gastroesophageal reflux disease (18/46), and larygopharyngeal reflux (10). Of the procedures performed, 85% (39/46) were successful. Complications included epistaxis (2/46), laryngospasm (2/46), and vasovagal reaction (1/46)., Conclusions: The transnasal placement of a wireless pH capsule is a safe and effective diagnostic adjunct to unsedated transnasal esophagoscopy.

Published
2004
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35. Prospective investigation of cryptic outbreaks of Salmonella agona salmonellosis.

Author

Taylor JP, Barnett BJ, del Rosario L, Williams K, and Barth SS

Subjects
Demography, Electrophoresis, Gel, Pulsed-Field methods, Food Microbiology, Humans, Incidence, Interviews as Topic, Salmonella classification, Seasons, Texas epidemiology, Urban Population, Disease Outbreaks, Salmonella isolation & purification, Salmonella Infections epidemiology
Abstract

The number of Salmonella agona isolates reported annually in Texas from 1992 through 1994 ranged from 14 to 21. An increase in incidence of S. agona infections was noted in the fall of 1995. Pulsed-field gel electrophoresis (PFGE) analysis identified prospectively two possible cryptic outbreaks caused by an indistinguishable strain which was isolated from 18 of 59 patients who were culture positive from March through December 1995. These 18 patients had onset of illness from 20 May through 3 October 1995. Eight individuals resided in the Austin area, eight resided in San Antonio, and two resided in Houston; none had attended a common social gathering or owned common pets. Six patients in San Antonio and one patient from Houston recalled eating food items from the same Mexican food restaurant in San Antonio. S. agona organisms with the same PFGE profile were isolated from machacado, an air-dried, raw beef product prepared at the restaurant. The machacado had been shredded in a kitchen blender which was the probable source for cross-contamination of other food items. Five patients in Austin reported eating at a popular Mexican food restaurant in Austin. Improperly prepared machacado also may have been served at the Austin restaurant; however, sufficient quantities of machacado were not available for analysis. PFGE was essential in determining whether the cases constituted outbreaks and was invaluable in guiding the epidemiological investigation.

Published
1998
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36. Fluothane (halothane) anesthesia and acute hepatic toxicity.

Author

Bhoopathi B, Ostapowicz F, and Del Rosario L

Subjects
Acute Disease, Female, Humans, Hysterectomy, Middle Aged, Postoperative Complications chemically induced, Anesthesia, Inhalation adverse effects, Chemical and Drug Induced Liver Injury etiology, Halothane adverse effects
Published
1974

37. Staffing for patient care.

Author

Castillo NK and Del Rosario L

Subjects
Nursing Service, Hospital, Nursing Staff, Hospital
Published
1970

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