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1. A new scoring system in Cystic Fibrosis: statistical tools for database analysis – a preliminary report

Author

Yearwood J, Hurst C, Hafen GM, Smith J, Dzalilov Z, and Robinson PJ

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Abstract Background Cystic fibrosis is the most common fatal genetic disorder in the Caucasian population. Scoring systems for assessment of Cystic fibrosis disease severity have been used for almost 50 years, without being adapted to the milder phenotype of the disease in the 21st century. The aim of this current project is to develop a new scoring system using a database and employing various statistical tools. This study protocol reports the development of the statistical tools in order to create such a scoring system. Methods The evaluation is based on the Cystic Fibrosis database from the cohort at the Royal Children's Hospital in Melbourne. Initially, unsupervised clustering of the all data records was performed using a range of clustering algorithms. In particular incremental clustering algorithms were used. The clusters obtained were characterised using rules from decision trees and the results examined by clinicians. In order to obtain a clearer definition of classes expert opinion of each individual's clinical severity was sought. After data preparation including expert-opinion of an individual's clinical severity on a 3 point-scale (mild, moderate and severe disease), two multivariate techniques were used throughout the analysis to establish a method that would have a better success in feature selection and model derivation: 'Canonical Analysis of Principal Coordinates' and 'Linear Discriminant Analysis'. A 3-step procedure was performed with (1) selection of features, (2) extracting 5 severity classes out of a 3 severity class as defined per expert-opinion and (3) establishment of calibration datasets. Results (1) Feature selection: CAP has a more effective "modelling" focus than DA. (2) Extraction of 5 severity classes: after variables were identified as important in discriminating contiguous CF severity groups on the 3-point scale as mild/moderate and moderate/severe, Discriminant Function (DF) was used to determine the new groups mild, intermediate moderate, moderate, intermediate severe and severe disease. (3) Generated confusion tables showed a misclassification rate of 19.1% for males and 16.5% for females, with a majority of misallocations into adjacent severity classes particularly for males. Conclusion Our preliminary data show that using CAP for detection of selection features and Linear DA to derive the actual model in a CF database might be helpful in developing a scoring system. However, there are several limitations, particularly more data entry points are needed to finalize a score and the statistical tools have further to be refined and validated, with re-running the statistical methods in the larger dataset.

Published
2008
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2. Reducing exacerbations in children and adults with primary ciliary dyskinesia using erdosteine and/or azithromycin therapy (REPEAT trial): study protocol for a multicentre, double-blind, double-dummy, 2x2 partial factorial, randomised controlled trial

Author

Chang, AB, Morgan, LC, Duncan, EL, Chatfield, MD, Schultz, A, Leo, PJ, McCallum, GB, McInerney-Leo, AM, McPhail, SM, Zhao, Y, Kruljac, C, Smith-Vaughan, HC, Morris, PS, Marchant, JM, Yerkovich, ST, Cook, AL, Wurzel, D, Versteegh, L, O'Farrell, H, McElrea, MS, Fletcher, S, D'Antoine, H, Stroil-Salama, E, Robinson, PJ, Grimwood, K, Chang, AB, Morgan, LC, Duncan, EL, Chatfield, MD, Schultz, A, Leo, PJ, McCallum, GB, McInerney-Leo, AM, McPhail, SM, Zhao, Y, Kruljac, C, Smith-Vaughan, HC, Morris, PS, Marchant, JM, Yerkovich, ST, Cook, AL, Wurzel, D, Versteegh, L, O'Farrell, H, McElrea, MS, Fletcher, S, D'Antoine, H, Stroil-Salama, E, Robinson, PJ, and Grimwood, K

Abstract

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare, progressive, inherited ciliopathic disorder, which is incurable and frequently complicated by the development of bronchiectasis. There are few randomised controlled trials (RCTs) involving children and adults with PCD and thus evidence of efficacy for interventions are usually extrapolated from people with cystic fibrosis. Our planned RCT seeks to address some of these unmet needs by employing a currently prescribed (but unapproved for long-term use in PCD) macrolide antibiotic (azithromycin) and a novel mucolytic agent (erdosteine). The primary aim of our RCT is to determine whether regular oral azithromycin and erdosteine over a 12-month period reduces acute respiratory exacerbations among children and adults with PCD. Our primary hypothesis is that: people with PCD who regularly use oral azithromycin and/or erdosteine will have fewer exacerbations than those receiving the corresponding placebo medications. Our secondary aims are to determine the effect of the trial medications on PCD-specific quality-of-life (QoL) and other clinical outcomes (lung function, time-to-next exacerbation, hospitalisations) and nasopharyngeal bacterial carriage and antimicrobial resistance. METHODS AND ANALYSIS: We are currently undertaking a multicentre, double-blind, double-dummy RCT to evaluate whether 12 months of azithromycin and/or erdosteine is beneficial for children and adults with PCD. We plan to recruit 104 children and adults with PCD to a parallel, 2×2 partial factorial superiority RCT at five sites across Australia. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, lung function and nasopharyngeal carriage by respiratory bacterial pathogens and their associated azithromycin resistance. ETHICS AND DISSEMINATION: Our RCT is conducted in accordance with Good Clinical Practice and the Australian legislation and National Health and Medical Research Council guidelines

Published
2022

4. Author Correction: Small molecule inhibition of Dynamin-dependent endocytosis targets multiple niche signals and impairs leukemia stem cells (Nature Communications, (2020), 11, 1, (6211), 10.1038/s41467-020-20091-6)

Author

Tremblay, CS, Chiu, SK, Saw, J, McCalmont, H, Litalien, V, Boyle, J, Sonderegger, SE, Chau, N, Evans, K, Cerruti, L, Salmon, JM, McCluskey, A, Lock, RB, Robinson, PJ, Jane, SM, Curtis, DJ, Tremblay, CS, Chiu, SK, Saw, J, McCalmont, H, Litalien, V, Boyle, J, Sonderegger, SE, Chau, N, Evans, K, Cerruti, L, Salmon, JM, McCluskey, A, Lock, RB, Robinson, PJ, Jane, SM, and Curtis, DJ

Abstract

In the original version of this Article, contributions from Jennifer R. Baker and Cecilia C. Russell from the University of Newcastle for synthesizing batches of Dynole 34-2 were not acknowledged. This error has now been corrected in both the PDF and HTML versions of the Article.

Published
2021

5. Author Correction: Small molecule inhibition of Dynamin-dependent endocytosis targets multiple niche signals and impairs leukemia stem cells.

Author

Tremblay, CS, Chiu, SK, Saw, J, McCalmont, H, Litalien, V, Boyle, J, Sonderegger, SE, Chau, N, Evans, K, Cerruti, L, Salmon, JM, McCluskey, A, Lock, RB, Robinson, PJ, Jane, SM, Curtis, DJ, Tremblay, CS, Chiu, SK, Saw, J, McCalmont, H, Litalien, V, Boyle, J, Sonderegger, SE, Chau, N, Evans, K, Cerruti, L, Salmon, JM, McCluskey, A, Lock, RB, Robinson, PJ, Jane, SM, and Curtis, DJ

Abstract

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21688-1

Published
2021

7. Small molecule inhibition of Dynamin-dependent endocytosis targets multiple niche signals and impairs leukemia stem cells

Author

Tremblay, CS, Chiu, SK, Saw, J, McCalmont, H, Litalien, V, Boyle, J, Sonderegger, SE, Chau, N, Evans, K, Cerruti, L, Salmon, JM, McCluskey, A, Lock, RB, Robinson, PJ, Jane, SM, Curtis, DJ, Tremblay, CS, Chiu, SK, Saw, J, McCalmont, H, Litalien, V, Boyle, J, Sonderegger, SE, Chau, N, Evans, K, Cerruti, L, Salmon, JM, McCluskey, A, Lock, RB, Robinson, PJ, Jane, SM, and Curtis, DJ

Abstract

Intensive chemotherapy for acute leukemia can usually induce complete remission, but fails in many patients to eradicate the leukemia stem cells responsible for relapse. There is accumulating evidence that these relapse-inducing cells are maintained and protected by signals provided by the microenvironment. Thus, inhibition of niche signals is a proposed strategy to target leukemia stem cells but this requires knowledge of the critical signals and may be subject to compensatory mechanisms. Signals from the niche require receptor-mediated endocytosis, a generic process dependent on the Dynamin family of large GTPases. Here, we show that Dynole 34-2, a potent inhibitor of Dynamin GTPase activity, can block transduction of key signalling pathways and overcome chemoresistance of leukemia stem cells. Our results provide a significant conceptual advance in therapeutic strategies for acute leukemia that may be applicable to other malignancies in which signals from the niche are involved in disease progression and chemoresistance.

Published
2020

8. Reply to Turnbull et al. And to Hulme et al.

Author

Breuer, O, Schultz, A, Turkovic, L, De Klerk, N, Keil, AD, Brennan, S, Harrison, J, Robertson, C, Robinson, PJ, Sly, Peter, Ranganathan, S, Stick, SM, Caudri, D, Breuer, O, Schultz, A, Turkovic, L, De Klerk, N, Keil, AD, Brennan, S, Harrison, J, Robertson, C, Robinson, PJ, Sly, Peter, Ranganathan, S, Stick, SM, and Caudri, D

Published
2020

9. Strategies to enable large-scale proteomics for reproducible research

Author

Poulos, RC, Hains, PG, Shah, R, Lucas, N, Xavier, D, Manda, SS, Anees, A, Koh, JMS, Mahboob, S, Wittman, M, Williams, SG, Sykes, EK, Hecker, M, Dausmann, M, Wouters, MA, Ashman, K, Yang, J, Wild, PJ, deFazio, A, Balleine, RL, Tully, B, Aebersold, R, Speed, TP, Liu, Y, Reddel, RR, Robinson, PJ, Zhong, Q, Poulos, RC, Hains, PG, Shah, R, Lucas, N, Xavier, D, Manda, SS, Anees, A, Koh, JMS, Mahboob, S, Wittman, M, Williams, SG, Sykes, EK, Hecker, M, Dausmann, M, Wouters, MA, Ashman, K, Yang, J, Wild, PJ, deFazio, A, Balleine, RL, Tully, B, Aebersold, R, Speed, TP, Liu, Y, Reddel, RR, Robinson, PJ, and Zhong, Q

Abstract

Reproducible research is the bedrock of experimental science. To enable the deployment of large-scale proteomics, we assess the reproducibility of mass spectrometry (MS) over time and across instruments and develop computational methods for improving quantitative accuracy. We perform 1560 data independent acquisition (DIA)-MS runs of eight samples containing known proportions of ovarian and prostate cancer tissue and yeast, or control HEK293T cells. Replicates are run on six mass spectrometers operating continuously with varying maintenance schedules over four months, interspersed with ~5000 other runs. We utilise negative controls and replicates to remove unwanted variation and enhance biological signal, outperforming existing methods. We also design a method for reducing missing values. Integrating these computational modules into a pipeline (ProNorM), we mitigate variation among instruments over time and accurately predict tissue proportions. We demonstrate how to improve the quantitative analysis of large-scale DIA-MS data, providing a pathway toward clinical proteomics.

Published
2020

11. Abstracts from the sixth meeting of the international association of pancreatology, November 2–4, 1994, Chicago, IL

Author

Burdick, Michael, Hollingsworth, Tony, Gansauge, S., Gansauge, F., Link, K. H., Schoenberg, M. H., Poch, B., Beger, H. G., Wagner, A. C. C., Steffen, H., Göke, B., Gaisano, H. Y., Sheu, L., Foskett, J. K., Trimble, W. S., Lee, Y. L., Kwon, H. Y., Park, H. S., Lee, S. M., Park, H. J., aguchi, S., Green, G. M., Mitamura, K., Komatsu, Y., Arai, I., Yamaura, H., Wang, OJ, Adrian, TE, Teyssen, S., Niebel, W., Niebergall, E., Singer, M. V., Umehara, K, Ohara, T, Kataoka, K, Okamura, H, Kato, M, Sakagami, J, Ohta, A, Murase, M, Hosoda, M, Yamane, Y, Kashima, K, Ibata, Y, Balthazar, Emil J., Banks, P. A., Garzof, S. G., Langevin, R. E., Silverman, S. G., Sica, G. T., Bassi, C., Benini, A., Muner, A., Falconi, M., Abbas, H., Pederzoli, P., Salvia, R., Minelli, E. Bertazzoni, Shaskar, S. Shanmuga, Shearer, M. G., Imrie, C. W., Brodmerkel, G. J., Reed, P. A., Carr-Locke, DL, Musa, A, Lichtenstein, DR, Dam, J Van, Banks, PA, Eisele, S., Schoenberg, M. H., Böchjer, M., Beger, H. G., Foitzik, Th., Fern’andez-del Castillo, C., Rattner, D. W., Ferraro, M. J., Warshaw, A. L., Foitzik, Th., Schmidt, J., Hotz, H., Warshaw, A. L., Buhr, H. J., Klar, E., Heinisch, A., Kadow, R., Bioss, U., Schölmerich, J., Zimgibl, H., Leser, H. -G., Manes, G., Rabitti, P. G., Laccetti, M., Cavallera, A., Paceili, L., Gagiione, G., Uomo, G., Marinqhini, A., Zinsmeister, A. R., Melton, L. J., DiMagno, E. P., Marotta, F., Chui, D. H., Barbi, G., Zhong, G. G., Marotta, F., Chui, D. H., Tajiri, H., Bellini, O., Zhong, G. G., Barbi, G., McKay, C, Baxter, J. N., Imrie, C. W., Mithöfer, K., Fern’andez-delCastillo, C., Frick, T. W., Lewandrowski, K., Rattner, D. W., Warshaw, A. L., Pezzilli, R., Billi, P., Miniero, R., Gullo, L., Barakat, B., Migliuli, M., Rau, B., Schad, M., Schoenberg, M., Beger, H. G., Richter, F., Matthias, R., Sakagami, J, Kataoka, K, Ohta, A, Umehara, K, Imoto, M, Murase, M, Hosoda, M, Yamane, Y, Kato, M, Kashima, K, Ashihara, T, Schofield, D, Sharer, NM, Heywood, KM, Waters, HM, Braganza, JM, Scott, P, Sharer, NM, Bilton, D, Deardon, D, Lee, S, Taylor, PM, McCloy, RF, Braganza, JM, Shen, J., Shao, H., Wu, Z. P., Jin, J. J., Shiel, N, Cassidy, O, Sharma, H, Braganza, J. M., Soöckmann, F., Ahrens, J., Leonhardt, U., Otto, J., Ritzel, U., Ramadori, G., Tian, Fuzhou, Hu, JZ, Huang, DR, Wang, XH, Lian, HW, Zhang, BY, Miao, JG, Li, Xu, Zhou, HT, Uomo, G., Rabitti, P. G., Laccetti, M., Manes, G., Esposico, P., Perrocti, F., Visconci, M., Vaccaro, M. I., Dagrosa, M. A., Mora, M. I., Sordelli, D. O., Vogt, W., MeOmann, H., Heinisch, A., Linseis, A., Holstege, A., Schölmerich, J., Leser, H. -G., Weiser, M. R., Gibbs, S. A. L., Hechcman, H. B., Moore, F. D., Worthington, H. V., Runt, L. P., HcCloy, R. F., KacLennan, I. A., Braqanza, J. M., Heath, D, Alexander, D, Wilson, C, Larvin, M, Imrie, CW, McMahon, MJ, Larvin, M, Ward, J, Robinson, PJ, Chalmers, AG, McMahon, MJ, Apte, M, Wilson, J, McCaughan, G, Korsten, M, Norton, I, Piroia, R, Bimmler, D., Frick, T. W., Scheele, G. A., Bockman, Dale E., Büchler, Markus, Beger, Hans G., Cavallini, G., Brunori, M. P., Rigo, L., Bovo, P., Filippini, M., Vaona, B., Di Francesco, V., Frulloni, L., Marcori, M., Farri, P. C., Laardini, M. T., Pederzoli, P., Chowdhury, Riaz, Ochi, Koji, Mizushima, Takaaki, Tsurumi, Tetsuya, Harada, Hideo, Laver, P., Hoist, J. J., Ohe, M. v. d., Goebell, H., Mi Zumoto, A., Sarr, M. G., DiMagno, E. P., Moore, R., Frey, C. F., Debas, H. T., Mulvihill, S. J., Onizuka, S., Kuroda, H., Kuroda, Y., Hongo, H., Matsuzaki, S., Ito, M., Sekine, L., Tsunoda, T., Pap, ’A., Hrisztov, V., Pap, ’A., Marosi, E., Simon, K., Tak’acs, T., Pederzoli, P., Falconi, M., Bassi, C., Bonora, A., Talamini, G., Saivia, R., Benini, L., Caldiron, E., Vesentini, S., Cavallini, G., Raijman, Isaac, Kortan, Paul, Haber, Gregory B., Ramesh, H, Varghese, CJ, Schofield, D, Kay, PM, Bottiglieri, T, Uden, S, Bilton, D, Braganza, JM, Gut, A, Segal, I, Snehalatha, C, Mohan, V, Braganza, JM, Silva, E., Ceneviva, R., Velludo, M. A. L., Silvan, E., Ruebner, B., Ceneviva, R., Velludo, M. A. L., Roselino, J. E. S., Foss, M. C., Talaraini, G., Falcaoi, M., Frmlltai, L, K Fraacesca, V., Maxwi, M., Vaosa, B., Baro, P., Baxu, C., Pedercoli, P., Cavalliai, G., Taiamini, G., Iacano, C., Faicsai, M., Frulloni, L., Rige, L., Castagnisi, A., Marcori, M., Angelini, G., Bassi, C., Bom, P., Vaoss, B., Vantini, I., Sen, G., Pederzali, P., Cavallini, G., Štimee, B, Bulajič, M, Milosavljevi’c, T, Krsti’c, R, Markovi’c, M, Korneti, V, Ugljcš’c, M, Abruzzesse, IL, Evans, DB, Larry, L, King, T, Raijman, I, Roubein, L, Frazier, M, lacono, C., Faca, E., Falezza, G., Bonora, E., Aurola PP, Serio, G., lacono, C., Nicoli, N., Mansueto, G. C., Zicari, M., Marchiori, L., Mangiante, G., Seno, G., Imarnura, M., Yamauchi, H., Inoue, M., Onda, M., UchlDa, E., Almqtq, T., Yamanaka, Y., Kqbayashi, T., Yokqyama, T., Aida, K., Sasajima, K., Tajiri, T., Egami, K., Yamashita, K., Naitq, Z., Asano, G., Lewandrowski, K. B., Kirby, R. E., Southern, J. F., Compton, C. C., Warshaw, A. L., Lip, J, Strömmer, L, Permert, J, Larsson, J, Adrian, TE, Loftus, E. V., Adkins, M. C., Olivares-Pakzad, B., Batts, K. P., Stephens, D. H., Farnell, M. B., Sarr, H. G., Thompson, G. B., van Heerden, J. A., Kelly, D. G., Miller, L. J., Pearson, R. K., Clain, J. E., Petersen, B. T., DiMagno, E. P., Matsumoto, Cancer S., Chowdhury, R., Mizushima, T., Ochi, K., Harada, H., Miki, H., Ozkan, Hnsan, Saisho, Hiromitsu, Yarnaguchi, Taketo, Ishihara, Takeshi, Kikuchi, Yasuharu, Tsuyuguchi, Toshio, Ohto, Masao, Pasqual, C., Sperti, C., Liesai, G., Guido, M., Pedrazzoli, S., Sperti, C., Pasquali, C., Khajeturian, E., Guolo, P., Pedrazzoli, S., Tadokoro, H., Watanabe, S., Moriyoshi, Y., Yoshida, K., Shiratori, K., Takeuchi, T., Uchida, E., Onda, M., Tajiri, T., Egami, K., Yamashita, K., Aida, K., Yamanaka, Y., Kobayashi, T., Aimoto, T., Yokoyama, T., Inoue, M., Naito, Z., Asano, G., Valentich, M. A., Monis, B., Barotto, N. N., and Herrera, P.

Published
1994
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12. The benefits of adding metformin to tamoxifen to protect the endometrium-A randomized placebo-controlled trial

Author

Davis, SR, Robinson, PJ, Jane, F, White, S, Brown, KA, Piessens, S, Edwards, A, McNeilage, J, Woinarski, J, Chipman, M, Bell, RJ, Davis, SR, Robinson, PJ, Jane, F, White, S, Brown, KA, Piessens, S, Edwards, A, McNeilage, J, Woinarski, J, Chipman, M, and Bell, RJ

Abstract

BACKGROUND: We investigated whether metformin prevents tamoxifen-induced endometrial changes and insulin resistance (IR) after a diagnosis of breast cancer. METHODS: This was a single-centre, randomized, double-blind, placebo-controlled, parallel group trial. Postmenopausal women with hormone receptor-positive breast cancer taking tamoxifen were randomly allocated to metformin 850 mg or identical placebo, twice daily, for 52 weeks. Outcome measures included double endometrial thickness (ET) measured by transvaginal ultrasound, fasting insulin, glucose and IR estimated by the homeostasis model of assessment (HOMA-IR). RESULTS: A total of 112 women were screened and 102 randomized. Results are presented as median (range). The 101 women who took at least one dose of medication were aged 56 (43-72) years, with 5(0.5-28) years postmenopause, and had taken tamoxifen for 28.9 (0-367.4) weeks. The baseline ET was 2.9 mm (1.4-21.9) for the placebo group (n = 52) and 2.5 mm (1.3-14.8) for the metformin group (n = 50). At 52 weeks, the median ET was statistically significantly lower for the metformin (n = 36) than for the placebo group (n = 45) (2.3 mm (1.4-7.8) vs 3.0 (1.2-11.3); P = 0.05). 13.3% allocated to placebo had an ET greater than 4 mm vs 5.7% for metformin (P = 0.26). There was no endometrial atypia or cancer. Compared with placebo, metformin resulted in significantly greater baseline-adjusted reductions in weight (P < 0.001), waist circumference (0.03) and HOMA-IR (P < 0.001). CONCLUSIONS: Metformin appears to inhibit tamoxifen-induced endometrial changes and has favourable metabolic effects. Further research into the adjuvant use of metformin after breast cancer and to prevent EH and cancer is warranted.

Published
2018

13. Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone

Author

Stempel, Da, Raphiou, Ih, Kral, Km, Yeakey, Am, Emmett, Ah, Prazma, Cm, Buaron, Ks, Pascoe, Sj, Austri, Investigators, Altieri, Hh, Antuni, Jd, Bergna, Ma, Cuadrado, Ja, De Gennaro MS, Fazio Lizandrelo CL, Gattolin, G, Gosn, Am, Larrateguy, Ld, Marcipar, Am, Maspero, Jf, Medina, Iv, Perez Chada RD, Silva, D, Victorio, Cf, Bardin, Pg, Carroll, Pa, Clements, Bs, Dore, Nd, Robinson, Pd, Fitzgerald, Da, Robinson, Pj, Russo, Ma, Sajkov, D, Thomas, Ps, Upham, Jw, Forstner, B, Kaik, G, Koeberl, Gh, Studnicka, M, Wallner, G, Balthazar, Y, Bauler, A, Dupont, Lj, Martinot, Jb, Ninane, V, Peché, R, Pilette, C, Dimitrova, R, Dimova, D, Kissyova Ibrishimova, G, Loboshka Becheva, M, Machkovska, M, Madjarov, S, Mandazhieva Pepelanova, M, Naidenova, I, Noleva, K, Takovska, N, Terziev, C, Aggarwal, Nk, Chapman, Kr, Csanadi, Ma, Dhillon, R, Henein, S, Kelly, Aj, Lam, As, Liem, Jj, Lougheed, Md, Lowe, Dw, Rizvi, Q, van den Berg, L, Zidel, B, Barros Monge MJ, Calvo Gil MA, Castillo Hofer CR, Diaz Amor PV, Lezana Soya, V, Quilodran Silva CN, Bolivar Grimaldos, F, Solarte-Rodriguez, I, Butkovic-Tomljanovic, R, Hegedus-Jungvirth, M, Ivkovic-Jurekovic, I, Simunov-Karuza, G, Buresova, M, Bursova, J, Fratrik, J, Guttlerova, E, Hartman, P, Jirmanova, I, Kalina, P, Kolman, P, Kucera, M, Povysilova, L, Pravda, P, Svabkova, A, Zakova, L, Backer, V, Maltbaek, N, Johnsen, Cr, Aries, Sp, Babyesiza, A, Barth, D, Benedix, A, Berg, P, Bergtholdt, B, Bettig, U, Bindig, Hw, Botzen, U, Brehler, R, Breyer, Go, Bruckhaus-Walter, M, Dapper, T, Eckhard, Jg, Engelhard, R, Feldmeyer, F, Fissan, H, Franz, Kh, Frick, Bs, Funck, J, Gessner, Cm, Ginko, T, Grigat, Ce, Grimm-Sachs, V, Groth, G, Hampf, J, Hanf, G, Havasi-Jost, G, Heinz, Gu, Helm, K, Hoeltz, S, Hofmann, S, Jander, R, Jandl, M, Jasch-Hoppe, B, Jung, T, Junggeburth, Jj, Kardos, P, Knueppel, W, Koch, T, Kolorz, C, Korduan, M, Korth-Wiemann, B, Krezdorn, Hg, Kroker, A, Kruell, M, Kuehne, P, Lenk, U, Liefring, E, Merke, J, Micke, L, Mitlehner, W, Mueller, H, Naudts, If, Neumann, G, Oldenburg, W, Overlack, A, Panzer, F, Reinholz, N, Remppis, R, Riegel, P, Rueckert, P, Schaetzl, Rj, Schauer, U, Hamelmann, E, Schenkenberger, I, Schlegel, V, Scholz, G, Schroers, M, Schwittay, A, Sebert, M, Tyler, K, Soemantri, Pa, Stock, P, Stuchlik, G, Unland, M, von Mallinckrodt, C, Wachter, J, Weber, U, Weberling, F, Wehgartner-Winkler, S, Weimer, J, Wiemer, S, Winkelmann, Ej, Zeisler, Kh, Ziegner, A, Zimny, Hh, Andrasofszky, Z, Bartha, A, Farkas, M, Gömöri, K, Kis, S, Major, K, Mészáros, I, Mezei, M, Rakvacs, M, Szalai, Z, Szántó, J, Szentesi, M, Szolnoki, E, Valyon, E, Zibotics, H, Anwar, J, Arimah, C, Djajalaksana, S, Rai, Ib, Setijadi, Ar, Setyanto, Db, Susanti, F, Syafiuddin, T, Syamsi, Ln, Wijanarko, P, Yunus, F, Bonavia, M, Braga, M, Chetta, Aa, Cerveri, I, Luisetti, M, Crimi, N, Cutrera, R, De Rosa, M, Esposito, S, Foresi, A, Gammeri, E, Iemoli, E, Legnani, Dl, Michetti, G, Pastorello, Ea, Pesci, A, Pistolesi, M, Riva, E, Romano, A, Scichilone, N, Terracciano, L, Tripodi, S, Choi, I, Kim, C, Kim, Js, Kim, Wj, Koh, Yy, Kwon, Ss, Lee, Sh, Lee, S, Lee, Sk, Park, Cs, Cirule, I, Eglite, R, Petrova, I, Poga, M, Smiltena, I, Chomiciene, A, Davoliene, I, Griskeviciene, V, Naudziunas, A, Naudziunas, S, Rudzeviciene, O, Sitkauskiene, B, Urbonas, G, Vaicius, D, Valavicius, A, Valiulis, A, Vebriene, J, bin Abdul Aziz FA, Daud, M, Ismail, Ai, Tengku Saifudin TI, Md Kassim RM, Mohd Fadzli FB, Wan Mohamad WH, Aguilar Dominguez PE, Aguilar-Orozco, Ra, Garza-Salinas, S, Ramirez-Diaz, Sp, Sánchez Llamas, F, Soto-Ramos, M, Velarde-Mora, Hj, Aguirre Sosa, I, Cisneros, Am, Estrella Viladegut RA, Matsuno Fuchigami, A, Adiaz-Baui, Tt, Bernan, Ap, Onia, Af, Sandagon, Mj, S-Naval, S, Yu, Cy, Bartuzi, Z, Bielous-Wilk, A, Błażowski, Ł, Bożek, A, Brzostek, J, Chorostowska-Wynimko, J, Ciekalska, K, Ziora, D, Cieslicki, J, Emeryk, A, Folcik, K, Gałuszka-Bilińska, A, Gawlik, R, Giejlo, M, Harat, R, Hofman, T, Jahnz-Różyk, K, Jedrzejczak, M, Kachel, T, Kamiński, D, Kelm Warchol, A, Konieczny, Z, Kwasniewski, A, Leszczyński, W, Mincewicz, G, Niezgoda, K, Olszewska-Ziąber, A, Onasz-Manitius, M, Pawlukiewicz, M, Piotrowicz, P, Piotrowski, W, Pisarczyk-Bogacka, E, Piskorz, P, Prokop-Staszecka, A, Roslan, A, Słomka, A, Smalera, E, Stelmach, I, Swierczynska-Krepa, M, Szmidt, M, Tarnowska-Matusiak, M, Tłuczykont, B, Tyminska, K, Waszkuc-Golonko, J, Wojciechowska, I, Alexandrescu, Ds, Neamtu, Ml, Todea, D, Alekseeva, E, Aleksandrova, E, Asherova, I, Barbarash, Ol, Bugrova, O, Bukreeva, Eb, Chermenskiy, A, Chizhova, O, Demko, I, Evdokimova, A, Giorgadze, Ml, Grigoryev, S, Irkhina, I, Khurkhurova, Nv, Kondyurina, Eg, Kostin, Vi, Kudelya, L, Laleko, Sl, Lenskaya, L, Levashov, S, Logvinenko, N, Martynov, A, Mizernitski, Y, Nemtsov, B, Novozhenov, Vg, Pavlishchuk, S, Popova, Vv, Reshetko, Ov, Sherenkov, A, Shirinsky, Vs, Shpagina, L, Soloviev, Ki, Tkachev, A, Trofimov, Vi, Vertkin, Al, Vorobeva, E, Idrisova, E, Yakushin, S, Zadionchenko, V, Zhiglinskaya, O, Zykov, K, Dopudja Pantic, V, Nadaskic, R, Nestorovic, B, Skodric Trifunovic, V, Stojanovic, A, Vukcevic, M, Vujic, T, Mitic Milikic, M, Banovcin, P, Horvathova, H, Karako, P Sr, Plutinsky, J, Pribulova, E, Szarazova, M, Zlatos, A, Adams, L, Badat, A, Bassa, A, Breedt, J, Bruning, A, Ellis, Gc, Emanuel, S, Fouche, Lf, Fulat, Ma, Gani, M, Ismail, Ms, Jurgens, Jc, Nell, H, Nieuwoudt, G, Noor, F, Bolliger, Ct, Puterman, As, Siddique, N, Trokis, Js, Vahed, Ya, Van Der Berg BJ, Van der Linden, M, Van Zyl, L, Visser, Ss, Antépara Ercoreca, I, Arnedillo Muñoz, A, Barbe Illa, F, Barreiro López, B, Blanco Aparicio, M, Boada Valmaseda, A, Bosque García, M, Bustamante Ruiz, A, Carretero Anibarro, P, Del Campo Matias, F, Echave-Sustaet, Jm, Espinosa de los Monteros Garde MJ, Garcia Hernandez GM, López Viña, A, Lores Obradors, L, Luengo Planas MT, Monsó Molas, E, Navarro Dourdil, A, Nieto García AJ, Perpina Tordera, M, Picado Valles, C, Rodriguez Alvarez Mdel, M, Saura Vinuesa, A, Serra Batlles, J, Soler Sempere MJ, Toran Montserrat, P, Valdés Cuadrado LG, Villasante Fernandez-Montes, C, Cheng, Sl, Chern, Jh, Chiu, Mh, Chung, Cl, Lai, Rs, Lin, Ck, Liu, Yc, Wang, Cc, Wei, Yf, Amer, L, Berenfus, Vi, Besh, L, Duka, Kd, Fushtey, Im, Garmash, N, Dudnyk, O, Godlevska, O, Vlasenko, Ma, Hospodarskyy, I, Iashyna, L, Kaladze, M, Khvelos, Si, Kostromina, Vp, Krakhmalova, O, Kryuchko, T, Kulynych, Ov, Krasko, Mp, Levchenko, O, Litvinova, T, Panina, Ss, Pasiyeshvili, Lm, Prystupa, Ln, Romaniuk, Li, Sirenko, I, Synenko, Vi, Vynnychenko, Lb, Yatsyshyn, Ri, Zaitsev, I, Zhebel, V, Zubarenko, O, Arthur, Cp, Brown, V, Burhan, H, Chaudhuri, R, Collier, D, Barnes, Nc, Davies, Ej, Ellery, A, Kwok, S, Lenney, W, Nordstrom, M, Pandya, Hc, Parker, Iw, Rajakulasingam, K, Seddon, P, Sharma, R, Thomas, Ec, Wakeling, Ja, Abalos-Galito, M, Abboy, C, Abreu, E, Ackerman, If, Acosta, Ia, Adaoag, Aa, Ahmed, M, Ali, Mi, Allen, Dr, Allen GG Jr, Diogo, Jj, Allison, Dc, Alwine, Lk, Apaliski, Sj, Arastu, Rs, Arora, Cm, Auerbach, D, Azzam, Sj, Badar FL 3rd, Baker, Jw, Barasch, Jp, Barber, Ma, Bardinas-Rodriguez, R, Barreiro, Tj, Baumbach, Rr, Baur, Ce, Baxter, Bs, Beach, Jl, Beasley, Rl, Beavins, Je, Beliveau, Wj, Benbow, Mj, Bennett, Nl, Bennett, Rl, Bernal, H, Bernstein, Di, Blaiss, Ms, Blumenthal, Kw, Boas, Sr, Borders, Jl, Boscia, Ja, Boulware, Wn, Bowling, Bt, Brabec, Ba, Bramlet, Dg, Figueroa, Dp, Brautigam, Df, Brownell, Jm, Bruce, Tr, Call, Rs, Campbell, Ca, Canaan, Ya, Cannon, Df, Carpio, Jm, Cathcart, Ws, Cevallos, Jp, Chauhan, Av, Chuang, Rb, Chevalier, D, Christensen, J, Christensen, Ta, Christina, Mo, Chrzanowski, Rr, Civitarese, Fa, Clark, Jp, Clifford, Dp, Lapidus, Rj, Coggi, Ja, Lenz, Jj, Cohen, Kr, Collins, Bg, Collins, H, Comellas, A, Condit, J, Cordasco EM Jr, Corder, Cn, Covar, Ra, Coverston, Kd, Croce, Sa, Cruz, H, Curtis, Ct, Daftary, Pk, Dalan, D, Dalawari, Sp, Daly, Wc, Davis, Kc, Dawes, Kw, Decotiis, Ba, Deluca, Rf, Desantis, Dm, De Valle OL, Diaz, Jl, Diaz, Jd, Dice, Jp, Elizalde, A, Hosler, Mr, Dixon, C, Dobkin, La, Dobrusin, Rs, Dransfield, Mt, Ebbeling, Wl, Edwards, Jd, Elacion, Jm, Elkayam, D, Ellison, Wt, Elsen, Jr, Engel, Lr, Ensz, Dj, Ericksen, Cl, Ervin, Je, Fang, C, Abrahamian, F, Farrah, Vb, Field, Jd, Fishman, Hj, Florea, R, Nayyar, S, Focil, A, Focauld, F, Franco MA Jr, Frandsen, Br, Ganti, K, Garcia, Fl, Lee, Wm, Garscadden, Ag, Gatti, Ea, Gellady, Am, George, Ar, Gibbon, Gw, Gleason, Gp, Goldberg, P, Goldstein, Mf, Gonzalez, Ge, Gower, Rg, Grande, Ja, Gregory, D, Grubb, Sd, Guthrie, Rp, Haas, Ta, Haft, Ks, Hajal, R, Hammond, Gd, Hansel, Nn, Hansen, Vr, Harris, Af, Hartman, An, Harvey, Rr, Hazan-Steinberg, S, Headley, Dm, Heigerick, Gc, Heller, Bn, Hendrix, El, Herrod, Jn, Hewitt, Mj, Hines, Rl, Hirdt, Ap, Hirschfield, Ja, Hoffman, Ks, Hogan, Ad, Howland, Wc, Hsu, Cc, Hsu, Fj, Hubbard, Wm, Hudson, Jd, Huffman, C, Hussain, M, Ioachimescu, Oc, Ismail, Ym, Jaffrani, Na, Jiang, N, Jones, Sw, Jordan, Rs, Joshi, Ke, Kaashmiri, Mw, Kalafer, M, Kamdar, Ba, Kanuga, Jg, Kao, Nl, Karetzky, M, Katsetos, Jc, Kay, Js, Kimmel, Ma, Kimura, Sh, Kingsley, Jk, Mahmood, Sm, Subich, Dc, Kirstein, Jl, Kleerup, Ec, Klein, Rm, Koh, Dw, Kohli, N, Koura, Fa, Kovacs, Sp, Kratzer, J, Kreit, Ci, Kreutter, Fm, Kubicki, Tm, Labuda, Jm, Latorre, Aj, Lara, Mm, Lechin, Ae, Lee, Jj, Lee, Md, Lentnek, Al, Lesh, Kw, Levins, Pf, Anspach, Rb, Levinsky, Dm, Lillestol, Mj, Lim, H, Livezey, Md, Lloyd-Turney, Cw, Lockey, Rf, Long, Ra, Lynch, Mj, Macgillivray, Bk, Mahadevan, Kp, Makam, Sk, Maloney, Mj, Mapel, D, Margolis, Bd, Margulies, J, Martin, Ef, Martin, Ee, Mascolo, M, Mataria, H, Sunbuli, M, Mathur, Rn, Mattar, Pn, Maynard, Km, Maynard, N, Mccormick, B, Mcelya, M, Mcevoy, Ce, Mckenzie, Wc, Medwedeff, Le, Mehta, Kd, Melamed, Ir, Meli, Jv, Merrick, Bh, Meyers, Pj, Miller, Bt, Minton, Sm, Miranda, Fg, Mohar, De, Montenegro, Ch, Morris, Fa, Morrison, Bs, Moss, Mh, Munoz, F, Naini, Gr, Nakamura, Ct, Naseeruddin, S, Nassim, C, Navazo, Lj, Nissim, Je, Norman, D, Oberoi, Ms, O'Connor, Tm, Offenberger, J, Orr, Rr, Osea, Ea, Paine, Wj, Rasmussen, Nl, Palatnik, M, Pangtay, D, Panuto, Ja, Patel, M, Perera, Ms, Perez, A, Peters PH Jr, Pimentel SM Jr, Pluto, Tm, Pollock, Mt, Posner, Ls, Pritchard, Jc, Pudi, Kk, Puig, Cm, Qaqundah, Py, Radbill, Mk, Rahman, St, Raikhel, M, Raissy, Hh, Ramstad, Ds, Ranasinghe, Es, Rangel, Os, Rapo, Se, Raschal, Sp, Reddy, Dg, Rehman, Sm, Reyes, Sr, Rhodes, Rb, Riffer, E, Rihal, Ps, Riley ED 4th, Rodriguez, Dh, Rogers, Cm, Rohlf, Jl, Romeu, H, Roney, Cw, Ronsick, So, Rosen, Jb, Rowe, Ms, Ruoff, Ge, Ryan, Eh, Saff, Rh, Saini, N, Anand, S, Balakrishnan, K, Samuels, Bs, Samuelson, Rj, Saniuk, Rj, Sargeant, Wo, Saunders, Mk, Saway, W, Scarupa, Md, White, Mv, Schear, Mj, Schwarz, Cm, Scott, Rb, Segall, N, Seibert, Af, Seidmeyer, V, Seidner, Mr, Seifer, Fd, Serje, J, Shah, Ms, Shah, Sb, Shapero, Pa, Shearer, Sd, Sheikh, Sq, Shepherd, Ts, Sher, Er, Sher, Ld, Short, Bh, Silas, Pe, Alvey, Jc, Silverfield, Jc, Simon, Sj, Sitar, S, Skoner, Dp, Smallow, Sa, Smart, Ba, Smith, Ca, Smith, Ke, Smith, Sk, Snyders, Gc, Soong, W, Soufer, J, Spangenthal, S, Stahlman, Je, Steele, Lg, Stegemoller, Rk, Stocks, J, Storms, Ww, Suen, J, Surowitz, Rz, Swauger, Jr, Taber, La, Tan, Ae, Pratt, Se, Tanus, T, Tarpay, Mm, Tarshis, Ga, Tenney, Jw, Tilghman, Kg, Trevino, Me, Troyan, Be, Twiddy, Sk, Updegrove, Jd, Urval, Kr, Uusinarkaus, Kt, Vaela, R, Van Cleeff, M, Varano, S, Vo, Qd, Wainz, Rj, Wald, Ja, Wall, Sj, Wasserman, Rl, Weinstein, Dl, Welker, Ja, Wellmon, B 2nd, Wells, T, Wenocur, Hs, Williams, Dl, Williams, Sl, Win, Ph, Wingo, Td, Wisman PP Jr, Wyszomierski, Da, Yamada, Hm, Yarows, S, Yunger TM Jr, Ziering, Rw., the AUSTRI Investigators, Stempel, D., Raphiou, I., Kral, K., Yeakey, A., Emmett, A., Prazma, C., Buaron, K., and Pascoe, S. Scichilone N tra i collaboratori

Subjects
Male, asthma, serious events, fluticasone, salmeterol, AUSTRI, Exacerbation, Intention to Treat Analysi, INHALED CORTICOSTEROIDS, Severity of Illness Index, law.invention, 0302 clinical medicine, Randomized controlled trial, law, immune system diseases, Ús terapèutic, Broncodilatadors, 030212 general & internal medicine, Child, Fluticasone, RISK, ACTING BETA-AGONISTS, EXACERBATIONS, METAANALYSIS, MORTALITY, SAFETY, DEATH, FDA, Medicine (all), Hazard ratio, General Medicine, Bronchodilator agents, Middle Aged, Fluticasone-Salmeterol Drug Combination, Bronchodilator Agents, Intention to Treat Analysis, Anesthesia, Female, Salmeterol, medicine.drug, Human, Adult, medicine.medical_specialty, Adolescent, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Fluticasone propionate, 03 medical and health sciences, Double-Blind Method, Internal medicine, Administration, Inhalation, medicine, Humans, Asma, Bronchodilator Agent, Asthma, Aged, Proportional Hazards Models, business.industry, Therapeutic use, medicine.disease, respiratory tract diseases, 030228 respiratory system, Fluticasone Propionate, Salmeterol Xinafoate Drug Combination, Proportional Hazards Model, business
Abstract

BACKGROUND The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate. METHODS In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, ≥12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of lifethreatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone–salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation. RESULTS Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone–salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthmarelated event in the fluticasone–salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P = 0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthmarelated intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone–salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone–salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P

Published
2016

14. The story of cystic fibrosis 1965-2015

Author

Massie, J, Robinson, PJ, Cooper, PJ, Massie, J, Robinson, PJ, and Cooper, PJ

Abstract

There have been dramatic changes in the care of children with cystic fibrosis (CF) from 1965 to 2015. The initial improvements were the result of incremental gains in medical knowledge and better use of available therapies. Some CF-specific drugs were developed (recombinant human DNase and purified tobramycin for inhalation), but these simply delayed the progression of the lung damage. The discovery of the CF transmembrane conductance regulator gene in 1989 created an explosion of knowledge of airway biology and CF pathophysiology. Now mutation-specific therapy to potentiate mutated CF transmembrane conductance regulator is available for some patients with CF and is transforming their lives. Further advances are eagerly anticipated to benefit all patients with CF.

Published
2016

15. The use of perioperative SofradexR eardrops in preventing tympanostomy tube blockage: a prospective double-blinded randomized-controlled trial

Author

Rea Pa, Arya Ak, and Robinson Pj

Subjects
Male, medicine.medical_specialty, Administration, Topical, medicine.medical_treatment, Dexamethasone, law.invention, Postoperative Complications, Anti-Infective Agents, Double-Blind Method, Randomized controlled trial, law, medicine, Humans, Prospective Studies, Tympanostomy tube, Grommet, Prospective cohort study, Intraoperative Care, business.industry, Gramicidin, Perioperative, Middle Ear Ventilation, Surgery, Clinical trial, Drug Combinations, medicine.anatomical_structure, Otorhinolaryngology, Child, Preschool, Anesthesia, Middle ear, Female, Complication, business, Follow-Up Studies, Framycetin
Abstract

Around 11-12% of tympanostomy tubes are reported to become blocked by middle ear secretions or blood immediately following surgery, and so no longer function. Many otologists routinely instil an antibiotic and steroid-containing solution at the time of surgery in the belief that this may reduce this complication. The aim of the study was to investigate the efficacy of instilling the antibiotic and steroid-containing solution Sofradex at the time of grommet insertion in preventing grommet blockage. Double-blind randomized-controlled trial, comparing rates of grommet blockage in ears treated with Sofradex drops against control (no drops) in patients undergoing bilateral grommet insertion. Sixty-one pairs of results were obtained. There was a significant difference between the rates of grommet blockage in the two groups. Grommets with Sofradex drops instilled perioperatively were nine times less likely to be blocked than controls [1.6%versus 13.1%, odds ratio (Sofradex/control) = 9.06, 95% confidence interval (CI): 1.04-78.82, P = 0.05]. There was no association between grommet blockage and perioperative bleeding or the nature and presence of middle ear secretions. Sofradex eardrops are effective in reducing the rate of grommet blockage when instilled perioperatively.

Published
2004

16. Diagnostic efficacy of gadoxetic acid (Primovist)-enhanced MRI and spiral CT for a therapeutic strategy: comparison with intraoperative and histopathologic findings in focal liver lesions

Author

Hammerstingl, R, Huppertz, A, Breuer, J, Balzer, T, Blakeborough, A, Carter, R, Fusté, Lc, Heinz Peer, G, Judmaier, W, Laniado, M, Manfredi, Riccardo, Mathieu, Dg, Müller, D, Mortelè, K, Reimer, P, Reiser, Mf, Robinson, Pj, Shamsi, K, Strotzer, M, Taupitz, M, Tombach, B, Valeri, G, van Beers BE, Vogl, Tj, and For the European EOB study group

Subjects
Adult, Gadolinium DTPA, Male, Magnetic resonance imaging, Computed tomography, Focal liver lesions, Liver-specific, Hepatobiliary, Gadoxetic acid-enhanced MRI, Therapeutic strategy, medicine.medical_specialty, Gadoxetic acid, Contrast Media, Sensitivity and Specificity, Gadoxetate Disodium, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Neuroradiology, Aged, Aged, 80 and over, medicine.diagnostic_test, business.industry, Ultrasound, Liver Neoplasms, Interventional radiology, General Medicine, Middle Aged, Spiral computed tomography, Female, Radiology, Differential diagnosis, business, Tomography, Spiral Computed, medicine.drug
Abstract

A multicenter study has been employed to evaluate the diagnostic efficacy of magnetic resonance imaging (MRI) using the new liver-specific contrast agent gadoxetic acid (Gd-EOB-DTPA, Primovist), as opposed to contrast-enhanced biphasic spiral computed tomography (CT), in the diagnosis of focal liver lesions, compared with a standard of reference (SOR). One hundred and sixty-nine patients with hepatic lesions eligible for surgery underwent Gd-EOB-DTPA-enhanced MRI as well as CT within 6 weeks. Pathologic evaluation of the liver specimen combined with intraoperative ultrasound established the SOR. Data sets were evaluated on-site (14 investigators) and off-site (three independent blinded readers). Gd-EOB-DTPA was well tolerated. Three hundred and two lesions were detected in 131 patients valid for analysis by SOR. The frequency of correctly detected lesions was significantly higher on Gd-EOB-DTPA-enhanced MRI compared with CT in the clinical evaluation [10.44%; 95% confidence interval (CI): 4.88, 16.0]. In the blinded reading there was a trend towards Gd-EOB-DTPA-enhanced MRI, not reaching statistical significance (2.14%; 95% CI: -4.32, 8.6). However, the highest rate of correctly detected lesions with a diameter below 1 cm was achieved by Gd-EOB-DTPA-enhanced MRI. Differential diagnosis was superior for Gd-EOB-DTPA-enhanced MRI (82.1%) versus CT (71.0%). A change in surgical therapy was documented in 19 of 131 patients (14.5%) post Gd-EOB-DTPA-enhanced MRI. Gd-EOB-DTPA-enhanced MRI was superior in the diagnosis and therapeutic management of focal liver lesions compared with CT.

Published
2008

18. Glucose Tolerance during Pulmonary Exacerbations in Children with Cystic Fibrosis

Author

Vij, N, Widger, J, Oliver, MR, O'Connell, M, Cameron, FJ, Ranganathan, S, Robinson, PJ, Vij, N, Widger, J, Oliver, MR, O'Connell, M, Cameron, FJ, Ranganathan, S, and Robinson, PJ

Abstract

BACKGROUND: Patients with Cystic Fibrosis (CF) are relatively insulinopenic and are at risk of diabetes, especially during times of stress. There is a paucity of data in the literature describing glucose tolerance during CF pulmonary exacerbations. We hypothesised that glucose tolerance would be worse during pulmonary exacerbations in children with CF than during clinical stability. METHODS: Patients with CF, 10 years or older, admitted with a pulmonary exacerbation underwent an OGTT within 48 hours of admission. A repeat OGTT was performed 4 to 6 weeks post discharge when the patients were well. RESULTS: Nine patients completed the study. Four patients were found to have normal glucose tolerance, 3 with impaired and 2 with CF related diabetes during the exacerbation. Mean change in 2-hour glucose was 1.1 mmol (SD = 0.77). At the follow up OGTT, 8 of 9 (89%) remained within their respective glucose tolerance status groupings. CONCLUSION: The findings of this study show that there is little difference in glucose tolerance during CF exacerbations compared to clinical stability in the majority of patients.

Published
2012

19. Identification of TPIT and other novel autoantigens in lymphocytic hypophysitis: immunoscreening of a pituitary cDNA library and development of immunoprecipitation assays.

Author

Smith, CJA, Bensing, S, Burns, C, Robinson, PJ, Kasperlik-Zaluska, AA, Scott, RJ, Kämpe, O, Crock, PA, Smith, CJA, Bensing, S, Burns, C, Robinson, PJ, Kasperlik-Zaluska, AA, Scott, RJ, Kämpe, O, and Crock, PA

Abstract

BACKGROUND: Lymphocytic hypophysitis is an organ-specific autoimmune disease of the pituitary gland. A specific and sensitive serological test currently does not exist to aid in the diagnosis. OBJECTIVE: To identify target autoantigens in lymphocytic hypophysitis and develop a diagnostic assay for these proteins. DESIGN/METHODS: A pituitary cDNA expression library was immunoscreened using sera from four patients with lymphocytic hypophysitis. Relevant cDNA clones from screening, along with previously identified autoantigens pituitary gland-specific factor 1a and 2 (PGSF1a and PGSF2) and neuron-specific enolase (NSE) were tested in an in vitro transcription and translation immunoprecipitation assay. The corticotroph-specific transcription factor, TPIT, was investigated separately as a candidate autoantigen. RESULTS: Significantly positive autoantibody reactivity against TPIT was found in 9/86 hypophysitis patients vs 1/90 controls (P = 0.018). The reactivity against TPIT was not specific for lymphocytic hypophysitis with autoantibodies detectable in the sera from patients with other autoimmune endocrine diseases. Autoantibodies were also detected against chromodomain-helicase-DNA binding protein 8, presynaptic cytomatrix protein (piccolo), Ca(2+)-dependent secretion activator, PGSF2 and NSE in serum samples from patients with lymphocytic hypophysitis, but at a frequency that did not differ from healthy controls. Importantly, 8/86 patients with lymphocytic hypophysitis had autoantibodies against any two autoantigens in comparison with 0/90 controls (P = 0.0093). CONCLUSIONS: TPIT, a corticotroph-specific transcription factor, was identified as a target autoantigen in 10.5% of patients with lymphocytic hypophysitis. Further autoantigens related to vesicle processing were also identified as potential autoantigens with different immunoreactivity patterns in patients and controls.

Published
2012

20. Identification and Characterisation of the RalA-ERp57 Interaction: Evidence for GDI Activity of ERp57

Author

Brymora, A, Duggin, IG, Berven, LA, van Dam, EM, Roufogalis, BD, Robinson, PJ, Brymora, A, Duggin, IG, Berven, LA, van Dam, EM, Roufogalis, BD, and Robinson, PJ

Abstract

RalA is a membrane-associated small GTPase that regulates vesicle trafficking. Here we identify a specific interaction between RalA and ERp57, an oxidoreductase and signalling protein. ERp57 bound specifically to the GDP-bound form of RalA, but not the GTP-bound form, and inhibited the dissociation of GDP from RalA in vitro. These activities were inhibited by reducing agents, but no disulphide bonds were detected between RalA and ERp57. Mutation of all four of ERp57's active site cysteine residues blocked sensitivity to reducing agents, suggesting that redox-dependent conformational changes in ERp57 affect binding to RalA. Mutations in the switch II region of the GTPase domain of RalA specifically reduced or abolished binding to ERp57, but did not block GTP-specific binding to known RalA effectors, the exocyst and RalBP1. Oxidative treatment of A431 cells with H2O2 inhibited cellular RalA activity, and the effect was exacerbated by expression of recombinant ERp57. The oxidative treatment significantly increased the amount of RalA localised to the cytosol. These findings suggest that ERp57 regulates RalA signalling by acting as a redox-sensitive guanine-nucleotide dissociation inhibitor (RalGDI). © 2012 Brymora et al.

Published
2012

21. A new scoring system in Cystic Fibrosis: statistical tools for database analysis - a preliminary report

Author

Hafen, GM, Hurst, C, Yearwood, J, Smith, J, Dzalilov, Z, Robinson, PJ, Hafen, GM, Hurst, C, Yearwood, J, Smith, J, Dzalilov, Z, and Robinson, PJ

Abstract

Background Cystic fibrosis is the most common fatal genetic disorder in the Caucasian population. Scoring systems for assessment of Cystic fibrosis disease severity have been used for almost 50 years, without being adapted to the milder phenotype of the disease in the 21st century. The aim of this current project is to develop a new scoring system using a database and employing various statistical tools. This study protocol reports the development of the statistical tools in order to create such a scoring system. Methods The evaluation is based on the Cystic Fibrosis database from the cohort at the Royal Children's Hospital in Melbourne. Initially, unsupervised clustering of the all data records was performed using a range of clustering algorithms. In particular incremental clustering algorithms were used. The clusters obtained were characterised using rules from decision trees and the results examined by clinicians. In order to obtain a clearer definition of classes expert opinion of each individual's clinical severity was sought. After data preparation including expert-opinion of an individual's clinical severity on a 3 point-scale (mild, moderate and severe disease), two multivariate techniques were used throughout the analysis to establish a method that would have a better success in feature selection and model derivation: 'Canonical Analysis of Principal Coordinates' and 'Linear Discriminant Analysis'. A 3-step procedure was performed with (1) selection of features, (2) extracting 5 severity classes out of a 3 severity class as defined per expert-opinion and (3) establishment of calibration datasets. Results (1) Feature selection: CAP has a more effective "modelling" focus than DA. (2) Extraction of 5 severity classes: after variables were identified as important in discriminating contiguous CF severity groups on the 3-point scale as mild/moderate and moderate/severe, Discriminant Fu

Published
2008

22. Autoimmune Hypophysitis

Author

Crock, PA, Bensing, Sophie, Smith, CJA, Burns, C, Robinson, PJ, Crock, PA, Bensing, Sophie, Smith, CJA, Burns, C, and Robinson, PJ

Published
2007

23. The small GTPases Rab5 and RalA regulate intracellular traffic of P-glycoprotein

Author

Fu, D, van Dam, EM, Brymora, A, Duggin, IG, Robinson, PJ, Roufogalis, BD, Fu, D, van Dam, EM, Brymora, A, Duggin, IG, Robinson, PJ, and Roufogalis, BD

Abstract

P-glycoprotein (P-gp) is a plasma membrane glycoprotein that can cause multidrug resistance (MDR) of cancer cells by acting as an ATP-dependent drug efflux pump. The regulatory effects of the small GTPases Rab5 and RalA on the intracellular trafficking of P-gp were investigated in HeLa cells. As expected, overexpressed enhanced green fluorescent protein (EGFP)-tagged P-gp (P-gp-EGFP) is mainly localised to the plasma membrane. However, upon cotransfection of either dominant negative Rab5 (Rab5-S34N) or constitutively active RalA (RalA-G23V) the intracellular P-gp-EGFP levels increased approximately 9 and 13 fold, respectively, compared to control P-gp-EGFP cells. These results suggest that Rab5 and RalA regulate P-gp trafficking between the plasma membrane and an intracellular compartment. In contrast, coexpression of constitutively active Rab5 (Rab5-Q79L) or dominant negative RalA (RalA-S28N) had no effect on the localisation of P-gp-EGFP. Furthermore, the intracellular accumulation of daunorubicin, a substrate for P-gp, increased significantly with an increased intracellular localisation of P-gp-EGFP. These results imply that it may be possible to overcome MDR by controlling the plasma membrane localisation of P-gp. © 2007 Elsevier B.V. All rights reserved.

Published
2007

30. Version 3 of the Read Codes

Author

Robinson Pj

Subjects
education.field_of_study, Information retrieval, Medical Records Systems, Computerized, Computer science, Terminology as Topic, Read codes, Humans, Radiology, Nuclear Medicine and imaging, General Medicine, Classification, Family Practice, education, United Kingdom
Published
1996

33. Urinary Incontinence in Young Nulligravid Women: A Cross-sectional Analysis.

Author

O'Halloran T, Bell RJ, Robinson PJ, and Davis SR

Abstract

BACKGROUND: Although pregnancy is a risk factor for urinary incontinence (UI), the extent of UI in nulligravid women has not been reported. OBJECTIVE: To investigate the rate of UI in a sample of young nulligravid women and its potential risk factors and effect on quality of life. DESIGN: Cross-sectional, self-administered questionnaire-based study. SETTING: University campuses and medical and allied health clinics. PARTICIPANTS: Nulligravid Australian women aged 16 to 30 years. MEASUREMENTS: The Questionnaire for Urinary Incontinence Diagnosis, the Psychological General Well-Being Index (PGWBI), the King's Health Questionnaire, and the International Physical Activity Questionnaire-Short Form. Demographic variables and potential risk factors were also documented. RESULTS: 1018 of 1620 questionnaires (63%) were returned, and 1002 provided analyzable data. The mean age of participants was 22.5 years (SD, 3.2). The rate of any UI was 12.6% (95% CI, 10.5% to 14.7%). Incontinence was slightly more common in students than in nonstudents (13.2% [CI, 11.0% to 15.8%] vs. 10.6% [CI, 6.7% to 14.6%]). Rates of UI varied according to sexual activity and use of combined oral contraceptives (COCs), with highest rates reported by students who were ever sexually active and not using COCs (21.5% [CI, 16.7% to 27.3%]). Women with UI reported significantly lower overall well-being than women without UI and had worse PGWBI scores related to anxiety, depression, positive well-being, and self-control. LIMITATION: A convenience sample of healthy, well-educated women was recruited, and response rates and participant characteristics varied by setting. CONCLUSION: In a sample of young nulligravid women, UI was associated with ever being sexually active and no COC use, as well as lower psychological well-being. Further research is needed to assess the prevalence and risk factors for UI in nulligravid women. PRIMARY FUNDING SOURCE: None. [ABSTRACT FROM AUTHOR]

Published
2012

34. Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening.

Author

Sly PD, Brennan S, Gangell C, de Klerk N, Murray C, Mott L, Stick SM, Robinson PJ, Robertson CF, Ranganathan SC, and Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST-CF)

Abstract

RATIONALE: The promise of newborn screening (NBS) for cystic fibrosis (CF) has not been fully realized, and the extent of improvement in respiratory outcomes is unclear. We hypothesized that significant lung disease was present at diagnosis. OBJECTIVES: To determine the extent of lung disease in a geographically defined population of infants with CF diagnosed after detection by NBS. METHODS: Fifty-seven infants (median age, 3.6 mo) with CF underwent bronchoalveolar lavage and chest computed tomography (CT) using a three-slice inspiratory and expiratory protocol. MEASUREMENTS AND MAIN RESULTS: Despite the absence of respiratory symptoms in 48 (84.2%) of infants, a substantial proportion had lung disease with bacterial infection detected in 12 (21.1%), including Staphylococcus aureus (n = 4) and Pseudomonas aeruginosa (n = 3); neutrophilic inflammation (41. 4 x 10(3) cells/ml representing 18.7% of total cell count); proinflammatory cytokines, with 44 (77.2%) having detectable IL-8; and 17 (29.8%) having detectable free neutrophil elastase activity. Inflammation was increased in those with infection and respiratory symptoms; however, the majority of those infected were asymptomatic. Radiologic evidence of structural lung disease was common, with 46 (80.7%) having an abnormal CT; 11 (18.6%) had bronchial dilatation, 27 (45.0%) had bronchial wall thickening, and 40 (66.7%) had gas trapping. On multivariate analysis, free neutrophil elastase activity was associated with structural lung disease. Most children with structural lung disease had no clinically apparent lung disease. CONCLUSIONS: These data support the need for full evaluation in infancy and argue for new treatment strategies, especially those targeting neutrophilic inflammation, if the promise of NBS for CF is to be realized. [ABSTRACT FROM AUTHOR]

Published
2009
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35. The effects of cancer chemotherapy on liver imaging.

Author

Robinson PJ and Robinson, Philip J A

Abstract

Chemotherapy changes the appearance of liver tumours and may also affect the liver parenchyma. Tumours respond with changes in size, outline, and internal architecture. The accuracy of liver CT for detecting metastases is reduced after chemotherapy. Histologic studies have shown that some metastases which become invisible on follow-up CT are completely sterile at later resection, but most 'disappearing' lesions still contain active tumour. Hepatic steatosis becomes much more common after chemotherapy. Diffuse fatty change may conceal metastases on US and CT, whilst focal steatosis may mimic tumour. Chemical-shift MRI will distinguish fat from tumour. Fatty change is usually reversible, unless the liver receives a 'second hit' of damage from other causes. Sinusoidal obstructive syndrome (SOS), nodular regenerative hyperplasia, veno-occlusive disease and peliosis are manifestations of microvascular injury which can result from chemotherapy. SOS, the most common of these, is undetectable on US and CT, but can be shown on SPIO-enhanced MRI. Although SOS causes no symptoms in most patients, it may cause increased bleeding from the friable liver at surgery, and greater risk of peri-operative adverse events. Rarer complications of chemotherapy include pseudo-cirrhosis and sclerosing cholangitis. [ABSTRACT FROM AUTHOR]

Published
2009
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37. The pathogenesis of ACTA1-related congenital fiber type disproportion.

Author

Clarke NF, Ilkovski B, Cooper S, Valova VA, Robinson PJ, Nonaka I, Feng J, Marston S, and North K

Abstract

OBJECTIVE: Mutations in ACTA1 have been associated with a variety of changes in muscle histology that likely result from fundamental differences in the way that ACTA1 mutations disrupt muscle function. Recently, we reported three patients with congenital fiber type disproportion (CFTD) caused by novel heterozygous missense mutations in ACTA1 (D292V, L221P, P332S) with marked type 1 fiber hypotrophy as the only pathological finding on muscle biopsy. We have investigated the basis for the histological differences between these CFTD patients and patients with ACTA1 nemaline myopathy (NM). METHODS AND RESULTS: Mass spectrometry and two-dimensional gel electrophoresis demonstrate that mutant actin accounts for 25 and 50% of alpha-skeletal actin in the skeletal muscle of patients with the P332S and D292V mutations, respectively, consistent with a dominant-negative disease mechanism. In vitro motility studies indicate that abnormal interactions between actin and tropomyosin are the likely principal cause of muscle weakness for D292V, with tropomyosin stabilized in the 'switched off' position. Both the D292V and P322S CFTD mutations are associated with normal sarcomeric structure on electron microscopy, which is atypical for severe NM. In contrast, we found no clear difference between ACTA1 mutations associated with NM and CFTD in tendency to polymerize or aggregate in C2C12 expression models. INTERPRETATION: These data suggest that ACTA1 CFTD mutations cause weakness by disrupting sarcomere function rather than structure. We raise the possibility that the presence or absence of structural disorganization when mutant actin incorporates into sarcomeres may be an important determinant of whether the histological patterns of CFTD or NM develop in ACTA1 myopathy. [ABSTRACT FROM AUTHOR]

Published
2007
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38. A multivariate analysis of the factors predicting hearing outcome after surgery for cholesteatoma in children.

Author

Chadha NK, Jardine A, Owens D, Gillett S, Robinson PJ, and Maw AR

Abstract

OBJECTIVE: To explore factors influencing hearing outcomes in children treated by canal wall up (CWU) and canal wall down (CWD) mastoid surgery. METHODS: Retrospective cohort study including three units in Bristol and Bath, UK. Ninety consecutive children underwent cholesteatoma mastoid surgery, with the first procedure between 1998 and 2001; minimum follow up was three disease-free years. RESULTS: The CWU and CWD cohorts significantly differed in pre-operative stage and hearing. After disease eradication, air conduction (AC) thresholds changed by +4.0 dB (95 per cent confidence intervals (95% CI) -2.0, 10.1) in the CWD group and -5.3 dB (95% CI -9.3, 1.3) in the CWU group (p=0.029). Using multiple linear regression to account for cohort differences, AC thresholds were increased by: pre-operative AC threshold (p<0.0001), initial ossicular stage (p=0.013), and CWD-surgery (p=0.005). CONCLUSION: Disease-free hearing was better with CWU-surgery, less initial ossicular damage, and better pre-operative hearing. Worse initial disease increased the likelihood of CWD surgery. Wider use of ossiculoplasty in the CWU cohort (51 per cent vs 5 per cent) may partially explain the superior results. [ABSTRACT FROM AUTHOR]

Published
2006
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40. Effects of segregation on an epidemic Pseudomonas aeruginosa strain in a cystic fibrosis clinic.

Author

Griffiths AL, Jamsen K, Carlin JB, Grimwood K, Carzino R, Robinson PJ, Massie J, and Armstrong DS

Abstract

The detection of a clonal Pseudomonas aeruginosa strain in 21% of children attending a cystic fibrosis clinic during 1999, which may have led to a worse prognosis, prompted strict infection control measures, including cohort segregation. We determined whether these strategies interrupted cross-infection within the clinic. Patients from 1999 were observed and a cross-sectional study of the 2002 clinic was performed. By 2002, the epidemic strain prevalence had decreased from 21 to 14% (p = 0.03), whereas the proportion of patients with nonepidemic P. aeruginosa strains was unchanged. The age- and sex-adjusted relative risk for epidemic strains among sputum producers in 2002 compared with 1999 was 0.64 (95% confidence interval, 0.47, 0.87; p = 0.004). Increased mortality or transfer to another clinic did not explain this reduction. Although children with epidemic strains may have had increased mortality (adjusted odds ratio, 2.0; 95% confidence interval, 0.6-6.8), they did not demonstrate greater morbidity than those with other P. aeruginosa isolates. Successful infection control measures provided additional indirect evidence for person-to-person transmission of an epidemic strain within the clinic. Further studies are needed to resolve whether cohort segregation completely eliminates cross-infection and if acquisition of epidemic isolates is associated with worse outcomes. [ABSTRACT FROM AUTHOR]

Published
2005
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41. Clinical assessment alone will not benefit patients with coronary heart disease: failure to achieve cholesterol targets in 12,045 patients -- the Healthwise II study.

Author

Brady AJB, Pittard JB, Grace JF, and Robinson PJ

Abstract

Healthwise II, a nurse-led audit programme in primary care during 1999-2002, assessed the uptake of secondary preventative measures for coronary heart disease (CHD). Risk factors, cardiovascular medications and blood cholesterol were recorded; 'at risk' patients were invited for a review after 6 months. Of 17,570 patients assessed, CHD was clinically present in 12,045 (69%); in these, aspirin usage was high (78%) but fewer patients were on a beta-blocker (40%), angiotensin-converting enzyme inhibitor (27%) or statin (49%). Blood pressure (BP) was controlled (<140/90) in only 41% of patients. Total cholesterol was >5 mmol/l in 49% of all CHD patients, half of whom were taking a statin. In the statin users, total cholesterol was uncontrolled (>5 mmol/l) in 38%. At follow-up, BP control remained at 42%, statin use increased to 57% and cholesterol remained elevated in 46%. Simple assessment in an audit programme fails to trigger change, and risk-factor modification for CHD remains inadequate. [ABSTRACT FROM AUTHOR]

Published
2005
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42. Implementation of evidence-based management of acute bronchiolitis.

Author

Robinson, Pj, Barben, Ju, and Robertson, Cf

Subjects
*RESPIRATORY infections in children, *DISEASE management, *PEDIATRICIANS
Abstract

Objective: Implementation of clinical guidelines is frequently delayed well beyond their dissemination and the publication of clinical evidence. The recently published Australian guidelines for the management of acute viral bronchiolitis (AVB) have been evaluated by assessing the current practice of Australian paediatricians. Methods: Questionnaire survey of all Australian paediatricians and a review of the literature. Results: Of a total of 891 questionnaires, 555 (62%) were returned. Of the respondents, 373 (67%) treated children with AVB and, of these, 232 (67%) treated 10–50 children per year. A wide variation in management practice for both outpatient and inpatient treatment of AVB was identified. Up to 70% of paediatricians who treated AVB indicated using pharmaceutical agents in their outpatient management (88% in inpatient management), most using these agents ‘sometimes’ or in high-risk children. Paediatric respiratory physicians tended to use bronchodilators less frequently than general paediatricians. Compared with many countries in Europe, few Australian paediatricians routinely use supplementary drugs in the inpatient management of AVB; in particular, bronchodilators (61 vs 7%) and corticosteroids (11 vs 1%) are used far less often. A review of the literature demonstrated that pharmaceutical agents do not influence the course of AVB. Conclusions: Despite a lack of evidence for their efficacy and the recommendation of the Australian guidelines, pharmaceutical agents are frequently used in the management of AVB by paediatricians in Australia, although far less than reported in a recently published European survey. Guidelines alone are not sufficient to implement change and there is a need for more specific strategies to ensure that children receive appropriate management for this common condition. [ABSTRACT FROM AUTHOR]

Published
2000

43. Staging of reflex sympathetic dystrophy with 99Tcm-HSA

Author

Parkin A and Robinson Pj

Subjects
Reflex Sympathetic Dystrophy, Pathology, medicine.medical_specialty, business.industry, medicine, Reflex, Humans, Dystrophy, Radiology, Nuclear Medicine and imaging, General Medicine, Radionuclide Imaging, business, Technetium Tc 99m Aggregated Albumin
Published
1992

45. The effect of dietary changes on the fatty acid composition of normal human depot fat

Author

Heyes Td, D.M. Morgan, Kingsbury Kj, Aylot C, Burton Pa, Emmerson R, and Robinson Pj

Subjects
Nutritional Sciences, Chemistry, Cholesterol, Depot, Applied Mathematics, General Mathematics, Fatty Acids, Adipose tissue, Blood lipids, Articles, Cod liver oil, chemistry.chemical_compound, Adipose Tissue, Blood chemistry, Blood plasma, Humans, Nutritional Physiological Phenomena, Food science, Fatty acid composition
Published
1962

46. Characterization of Stylosanthes introductions by using seed protein patterns

Author

Robinson, PJ and Megarrity, RG

Abstract

Seed protein patterns of 182 Stylosanthes accessions, representing 16 species and two hybrids, were obtained by polyacrylamide gel electrophoresis of crude extracts. All species could be recognized by examination of photographs and densitometer traces of the gels. Within the species capitata, guyanensis, hamata and viscosa considerable variation occurred, whilst the variation in humilis, scabra and fruticosa was not as great. Data from the densitometer traces were analysed by various methods of pattern analysis and the resulting classifications compared. A variance-standardized Euclidean distance coefficient was found to be the similarity measure of choice, whilst selection of fusion strategy was not as critical. Species relationships obtained by using the chemical data were not in agreement with the accepted taxonomic division of the genus into the sections Styposanthes and Stylosanthes. A classification based on the complete data set was compared with a working classification based on morphological and agronomic data, which is used in the agronomic assessment of the genus. Only within S. scabra did the two classifications conform. Morphological-agronomic (M-A) types within the species hamata and subsericea could be distinguished by the examination of the fine structure of the densitometer traces, whilst groups based on protein data in the species humilis, guyanensis, fruticosa and viscosa did not correspond with M-A groups. The application of seed protein patterns as a rapid and inexpensive means of identifying introductions of the genus at the species level, as well as characterizing types within certain species, is proposed.

Published
1975
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47. The effect of phosphorus and sulphur fertilization on the growth and distribution of dry matter, nitrogen, phosphorus, and sulphur in Townsville stylo (Stylosanthes humilis)

Author

Robinson, PJ and Jones, RK

Abstract

The effects of phosphorus and sulphur applications on the growth of Townsville slylo (Stylosanthes lzutnilis) and the redistribution of dry matter, nitrogen, phosphorus, and sulphur in various parts of the plant were examined in a glasshouse experiment. Large yield responses lo phosphorus and sulphur, and a highly significant interaction were obtained. Phosphorus and sulphur deficiency caused a 3-week delay in flowering. The rapid decline in nutrient concentrations both before and after flowering is discussed in relation to the use of critical values. Townsville stylo shows a very marked ability to translocate nutrients to the seed. Adequately fertilized plants contained only 0.02% phosphorus and 0.10% sulphur in the mature leaf, while the seeds contained 0.36% phosphorus and 0.36% sulphur. This is discussed in relation to animal nutrition during the dry season.

Published
1972
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48. Botanical and chemcial composition of a Townsville stylo-spear grass pasture in relation to conception rate of cows

Author

Ritson, JB, Edye, LA, and Robinson, PJ

Abstract

A previously described experiment designed to study the effect of stocking rate, superphosphate, and conservation of hay on the fertility of cows had shown that only superphosphate significantly increased the conception rate. The present paper discusses the nutritional adequacy of the pastures for breeding cows. All experimental factors significantly influenced yield and botanical composition. Pastures at the lower of two stocking rates remained dominated by perennial grasses while those at the higher rate became dominated by Townsville stylo and annual grasses. Conservation of hay increased annual species, and superphosphate increased Townsville stylo in lightly grazed pastures. Pasture yield was adequate at the lower stocking rate but became limiting at the higher rate. Superphosphate increased pasture yields during the third and fourth year. Superphosphate increased the phosphorus and sulphur contents of the three major components - Townsville stylo, perennial grasses, and annual grasses, the nitrogen content of Townsville stylo, and the sodium content of perennial and annual grasses. Stocking rate affected chemical composition in the third and fourth year: the high stocking rate increased the nitrogen contents of the three major components, the phosphorus and sulphur contents of Townsville stylo and perennial grasses, and the sodium contents of perennial and annual grasses. Cow conception rate was significantly and positively correlated with the phosphorus contents of the three major components, the sulphur content of Townsville stylo, and three yield attributes of annual grasses (dry matter, phosphorus, and nitrogen yield). The phosphorus content of all three components was less than 0.15 % for much of the year at the two lower rates of superphosphate; only at the highest rate did the pastures approach an adequate phosphorus content for pregnant and lactating cows. Phosphorus and sulphur deficiency could have limited the utilization of Townsville stylo protein by cattle on unfertilized pastures. Superphosphate at a rate of 126 kg/ha a year was adequate for maintaining Townsville stylo above the critical plant value for phosphorus, but inadequate to satisfy the phosphorus requirements of pregnant and lactating cows.

Published
1971
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49. Sulphur-nitrogen relationships in the tropical legume Stylosanthes humilis

Author

Jones, RK, Robinson, PJ, Haydock, KP, and Megarrity, RG

Abstract

The effects of age and sulphur fertilization on various sulphur fractions in the legume Stylosanthes humilis were examined. Plant material was obtained in two consecutive seasons from nodulated plants growing in the field and from a glasshouse experiment. A very close relationship between the concentration of total nitrogen (Nt), that of total sulphur (St), and age was found. In young material Nt increased at first then reached a plateau with increases in St (brought about by additions of sulphur). As the plants aged, however, both Nt and St declined and the relation between them became more nearly linear. Nt and St were also closely related in seed from these plants but the StlNt ratio was much lower than in the vegetative material. A moderate deficiency of sulphur had little effect on the ratio of alcohol-insoluble to total nitrogen. In contrast with published work on other species it was found that sulphur applications increased the ratio of sulphur to nitrogen in the alcohol-insoluble (protein) fraction.

Published
1971
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