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43 results on '"Tickle, S."'

1. Assessing Risk in the Retail Environment during the COVID-19 Pandemic

Author

Budd, C., Calvert, K., Johnson, S., and Tickle, S. O.

Subjects
Physics - Physics and Society, Quantitative Biology - Populations and Evolution
Abstract

The COVID-19 pandemic has caused unprecedented disruption, particularly in retail. Where essential demand cannot be fulfilled online, or where more stringent measures have been relaxed, customers must visit shop premises in person. This naturally gives rise to some risk of susceptible individuals (customers or staff) becoming infected. It is essential to minimise this risk as far as possible while retaining economic viability of the shop. We therefore explore and compare the spread of COVID-19 in different shopping situations involving person-to-person interactions: (i) free-flowing, unstructured shopping; (ii) structured shopping (e.g. a queue). We examine which of (i) or (ii) may be preferable for minimising the spread of COVID-19 in a given shop, subject to constraints such as the geometry of the shop; compliance of the population to local guidelines; and additional safety measures which may be available to the organisers of the shop. We derive a series of conclusions, such as unidirectional free movement being preferable to bidirectional shopping, and that the number of servers should be maximised as long as they can be well protected from infection.

Published
2020

2. A computationally efficient, high-dimensional multiple changepoint procedure with application to global terrorism incidence

Author

Tickle, S. O., Eckley, I. A., and Fearnhead, P.

Subjects
Statistics - Methodology, Statistics - Applications
Abstract

Detecting changepoints in datasets with many variates is a data science challenge of increasing importance. Motivated by the problem of detecting changes in the incidence of terrorism from a global terrorism database, we propose a novel approach to multiple changepoint detection in multivariate time series. Our method, which we call SUBSET, is a model-based approach which uses a penalised likelihood to detect changes for a wide class of parametric settings. We provide theory that guides the choice of penalties to use for SUBSET, and that shows it has high power to detect changes regardless of whether only a few variates or many variates change. Empirical results show that SUBSET out-performs many existing approaches for detecting changes in mean in Gaussian data; additionally, unlike these alternative methods, it can be easily extended to non-Gaussian settings such as are appropriate for modelling counts of terrorist events.

Published
2020

3. Parallelisation of a Common Changepoint Detection Method

Author

Tickle, S. O., Eckley, I. A., Fearnhead, P., and Haynes, K.

Subjects
Statistics - Methodology
Abstract

In recent years, various means of efficiently detecting changepoints in the univariate setting have been proposed, with one popular approach involving minimising a penalised cost function using dynamic programming. In some situations, these algorithms can have an expected computational cost that is linear in the number of data points; however, the worst case cost remains quadratic. We introduce two means of improving the computational performance of these methods, both based on parallelising the dynamic programming approach. We establish that parallelisation can give substantial computational improvements: in some situations the computational cost decreases roughly quadratically in the number of cores used. These parallel implementations are no longer guaranteed to find the true minimum of the penalised cost; however, we show that they retain the same asymptotic guarantees in terms of their accuracy in estimating the number and location of the changes.

Published
2018

4. The relationship between uremic toxins and symptoms in older men and women with advanced chronic kidney disease

Author

Massy Z. A., Chesnaye N. C., Larabi I. A., Dekker F. W., Evans M., Caskey F. J., Torino C., Porto G., Szymczak M., Drechsler C., Wanner C., Jager K. J., Alvarez J. C., Schneider A., Torp A., Iwig B., Perras B., Marx C., Blaser C., Emde C., Krieter D., Fuchs D., Irmler E., Platen E., Schmidt-Gurtler H., Schlee H., Naujoks H., Schlee I., Casar S., Beige J., Rothele J., Mazur J., Hahn K., Blouin K., Neumeier K., Anding-Rost K., Schramm L., Hopf M., Wuttke N., Frischmuth N., Ichtiaris P., Kirste P., Schulz P., Aign S., Biribauer S., Manan S., Roser S., Heidenreich S., Palm S., Schwedler S., Delrieux S., Renker S., Schattel S., Stephan T., Schmiedeke T., Weinreich T., Leimbach T., Stovesand T., Bahner U., Seeger W., Cupisti A., Sagliocca A., Ferraro A., Mele A., Naticchia A., Cosaro A., Ranghino A., Stucchi A., Pignataro A., De Blasio A., Pani A., Tsalouichos A., Bellasi A., Raffaele Di Iorio B., Butti A., Abaterusso C., Somma C., D'Alessandro C., Zullo C., Pozzi C., Bergamo D., Ciurlino D., Motta D., Russo D., Favaro E., Vigotti F., Ansali F., Conte F., Cianciotta F., Giacchino F., Cappellaio F., Pizzarelli F., Greco G., Bigatti G., Marinangeli G., Cabiddu G., Fumagalli G., Caloro G., Piccoli G., Capasso G., Gambaro G., Tognarelli G., Bonforte G., Conte G., Toscano G., Del Rosso G., Capizzi I., Baragetti I., Oldrizzi L., Gesualdo L., Biancone L., Magnano M., Ricardi M., Di Bari M., Laudato M., Luisa Sirico M., Ferraresi M., Provenzano M., Malaguti M., Palmieri N., Murrone P., Cirillo P., Dattolo P., Acampora P., Nigro R., Boero R., Scarpioni R., Sicoli R., Malandra R., Savoldi S., Bertoli S., Borrelli S., Maxia S., Maffei S., Mangano S., Cicchetti T., Rappa T., Palazzo V., De Simone W., Schrander A., Van Dam B., Siegert C., Gaillard C., Beerenhout C., Verburgh C., Janmaat C., Hoogeveen E., Hoorn E., Boots J., Boom H., Eijgenraam J. -W., Kooman J., Rotmans J., Vogt L., Raasveld M., Vervloet M., Van Buren M., Van Diepen M., Leurs P., Voskamp P., Blankestijn P., Van Esch S., Boorsma S., Berger S., Konings C., Aydin Z., Musiala A., Szymczak A., Olczyk E., Augustyniak-Bartosik H., Miskowiec-Wisniewska I., Manitius J., Pondel J., Jedrzejak K., Nowanska K., Nowak L., Durlik M., Dorota S., Nieszporek T., Heleniak Z., Jonsson A., Blom A. -L., Rogland B., Wallquist C., Vargas D., Dimeny E., Sundelin F., Uhlin F., Welander G., Bascaran Hernandez I., Grontoft K. -C., Stendahl M., Svensson M., Heimburger O., Kashioulis P., Melander S., Almquist T., Jensen U., Woodman A., McKeever A., Ullah A., McLaren B., Harron C., Barrett C., O'Toole C., Summersgill C., Geddes C., Glowski D., McGlynn D., Sands D., Roy G., Hirst G., King H., McNally H., Masri-Senghor H., Murtagh H., Rayner H., Turner J., Wilcox J., Berdeprado J., Wong J., Banda J., Jones K., Haydock L., Wilkinson L., Carmody M., Weetman M., Joinson M., Dutton M., Matthews M., Morgan N., Bleakley N., Cockwell P., Roderick P., Mason P., Kalra P., Sajith R., Chapman S., Navjee S., Crosbie S., Brown S., Tickle S., Mathavakkannan S., Kuan Y., Massy, Z. A., Chesnaye, N. C., Larabi, I. A., Dekker, F. W., Evans, M., Caskey, F. J., Torino, C., Porto, G., Szymczak, M., Drechsler, C., Wanner, C., Jager, K. J., Alvarez, J. C., Schneider, A., Torp, A., Iwig, B., Perras, B., Marx, C., Blaser, C., Emde, C., Krieter, D., Fuchs, D., Irmler, E., Platen, E., Schmidt-Gurtler, H., Schlee, H., Naujoks, H., Schlee, I., Casar, S., Beige, J., Rothele, J., Mazur, J., Hahn, K., Blouin, K., Neumeier, K., Anding-Rost, K., Schramm, L., Hopf, M., Wuttke, N., Frischmuth, N., Ichtiaris, P., Kirste, P., Schulz, P., Aign, S., Biribauer, S., Manan, S., Roser, S., Heidenreich, S., Palm, S., Schwedler, S., Delrieux, S., Renker, S., Schattel, S., Stephan, T., Schmiedeke, T., Weinreich, T., Leimbach, T., Stovesand, T., Bahner, U., Seeger, W., Cupisti, A., Sagliocca, A., Ferraro, A., Mele, A., Naticchia, A., Cosaro, A., Ranghino, A., Stucchi, A., Pignataro, A., De Blasio, A., Pani, A., Tsalouichos, A., Bellasi, A., Raffaele Di Iorio, B., Butti, A., Abaterusso, C., Somma, C., D'Alessandro, C., Zullo, C., Pozzi, C., Bergamo, D., Ciurlino, D., Motta, D., Russo, D., Favaro, E., Vigotti, F., Ansali, F., Conte, F., Cianciotta, F., Giacchino, F., Cappellaio, F., Pizzarelli, F., Greco, G., Bigatti, G., Marinangeli, G., Cabiddu, G., Fumagalli, G., Caloro, G., Piccoli, G., Capasso, G., Gambaro, G., Tognarelli, G., Bonforte, G., Conte, G., Toscano, G., Del Rosso, G., Capizzi, I., Baragetti, I., Oldrizzi, L., Gesualdo, L., Biancone, L., Magnano, M., Ricardi, M., Di Bari, M., Laudato, M., Luisa Sirico, M., Ferraresi, M., Provenzano, M., Malaguti, M., Palmieri, N., Murrone, P., Cirillo, P., Dattolo, P., Acampora, P., Nigro, R., Boero, R., Scarpioni, R., Sicoli, R., Malandra, R., Savoldi, S., Bertoli, S., Borrelli, S., Maxia, S., Maffei, S., Mangano, S., Cicchetti, T., Rappa, T., Palazzo, V., De Simone, W., Schrander, A., Van Dam, B., Siegert, C., Gaillard, C., Beerenhout, C., Verburgh, C., Janmaat, C., Hoogeveen, E., Hoorn, E., Boots, J., Boom, H., Eijgenraam, J. -W., Kooman, J., Rotmans, J., Vogt, L., Raasveld, M., Vervloet, M., Van Buren, M., Van Diepen, M., Leurs, P., Voskamp, P., Blankestijn, P., Van Esch, S., Boorsma, S., Berger, S., Konings, C., Aydin, Z., Musiala, A., Szymczak, A., Olczyk, E., Augustyniak-Bartosik, H., Miskowiec-Wisniewska, I., Manitius, J., Pondel, J., Jedrzejak, K., Nowanska, K., Nowak, L., Durlik, M., Dorota, S., Nieszporek, T., Heleniak, Z., Jonsson, A., Blom, A. -L., Rogland, B., Wallquist, C., Vargas, D., Dimeny, E., Sundelin, F., Uhlin, F., Welander, G., Bascaran Hernandez, I., Grontoft, K. -C., Stendahl, M., Svensson, M., Heimburger, O., Kashioulis, P., Melander, S., Almquist, T., Jensen, U., Woodman, A., Mckeever, A., Ullah, A., Mclaren, B., Harron, C., Barrett, C., O'Toole, C., Summersgill, C., Geddes, C., Glowski, D., Mcglynn, D., Sands, D., Roy, G., Hirst, G., King, H., Mcnally, H., Masri-Senghor, H., Murtagh, H., Rayner, H., Turner, J., Wilcox, J., Berdeprado, J., Wong, J., Banda, J., Jones, K., Haydock, L., Wilkinson, L., Carmody, M., Weetman, M., Joinson, M., Dutton, M., Matthews, M., Morgan, N., Bleakley, N., Cockwell, P., Roderick, P., Mason, P., Kalra, P., Sajith, R., Chapman, S., Navjee, S., Crosbie, S., Brown, S., Tickle, S., Mathavakkannan, S., Kuan, Y., Nephrology, ACS - Diabetes & metabolism, Medical Informatics, APH - Methodology, APH - Aging & Later Life, APH - Quality of Care, APH - Global Health, APH - Health Behaviors & Chronic Diseases, and ACS - Pulmonary hypertension & thrombosis

Subjects
Transplantation, Nephrology, uremic toxins, CKD, symptoms, symptom, elderly
Abstract

Background Patients with stage 4/5 chronic kidney disease (CKD) suffer from various symptoms. The retention of uremic solutes is thought to be associated with those symptoms. However, there are relatively few rigorous studies on the potential links between uremic toxins and symptoms in patients with CKD. Methods The EQUAL study is an ongoing observational cohort study of non-dialyzed patients with stage 4/5 CKD. EQUAL patients from Germany, Poland, Sweden and the UK were included in the present study (n = 795). Data and symptom self-report questionnaires were collected between April 2012 and September 2020. Baseline uric acid and parathyroid hormone and 10 uremic toxins were quantified. We tested the association between uremic toxins and symptoms and adjusted P-values for multiple testing. Results Symptoms were more frequent in women than in men with stage 4/5 CKD, while levels of various uremic toxins were higher in men. Only trimethylamine N-oxide (TMAO; positive association with fatigue), p-cresyl sulfate (PCS) with constipation and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (negative association with shortness of breath) demonstrated moderately strong associations with symptoms in adjusted analyses. The association of phenylacetylglutamine with shortness of breath was consistent in both sexes, although it only reached statistical significance in the full population. In contrast, TMAO (fatigue) and PCS and phenylacetylglutamine (constipation) were only associated with symptoms in men, who presented higher serum levels than women. Conclusion Only a limited number of toxins were associated with symptoms in persons with stage 4/5 CKD. Other uremic toxins, uremia-related factors or psychosocial factors not yet explored might contribute to symptom burden.

Published
2022
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5. Test of the detector system for the Stopping Target Monitor of the Mu2e experiment in the presence of a high flux gamma background

Author

Price, J., (0000-0001-6273-7102) Müller, S., (0000-0002-6486-353X) Ferrari, A., (0000-0001-8174-7795) Knodel, O., (0000-0001-5556-838X) Voigt, M., Keshavarzi, A., Motuk, E., Judson, D., Koltick, D., Miller, J., Plesniak, P., Edmonds, A., (0000-0003-4317-138X) Ufer, R., Huang, S., Chen, J., Chislett, R., Lancaster, M., (0000-0002-9260-5052) Rachamin, R., Tickle, S., Alvarez, C., Ginther, G., Harkness-Brennan, L., Price, J., (0000-0001-6273-7102) Müller, S., (0000-0002-6486-353X) Ferrari, A., (0000-0001-8174-7795) Knodel, O., (0000-0001-5556-838X) Voigt, M., Keshavarzi, A., Motuk, E., Judson, D., Koltick, D., Miller, J., Plesniak, P., Edmonds, A., (0000-0003-4317-138X) Ufer, R., Huang, S., Chen, J., Chislett, R., Lancaster, M., (0000-0002-9260-5052) Rachamin, R., Tickle, S., Alvarez, C., Ginther, G., and Harkness-Brennan, L.

Abstract

These data were taken to characterize the performance and test the data acquisition system of two detectors to be used to monitor the stopping target for the forth-coming Mu2e experiment at Fermilab; the High Purity Germanium (HPGe) and Lanthanum Bromide (LaBr) Detectors, in the presence of the pulsed gamma beam at ELBE. This measurement is crucial for the normalisation of the Mu2e experiment. The corresponding beamtime was carried out at the gELBE bremsstrahlung beamline of HZDR's ELBE radiation facility from April 21 to April 25, 2022 (GATE ID: 21202619-ST). The data sets represent the data taken with the LaBr detector by means of an ORTEC DSPEC 50 and a Lecroy/Teledyne HDO4104 oscilloscope.

Published
2022

8. Tests of the detector system for the Stopping Target Monitor of the MU2E experiment in a high flux pulsed gamma beam

Author

Alvarez, C., Chen, J., Edmonds, A., Ferrari, A., Huang, S., Keshavarzi, A., Knodel, O., Koltick, D., Lancaster, M., Miller, J. P., Müller, S., Popp, J. L., Rachamin, R., Simic, M., Tickle, S., Ufer, R., and Voigt, M.

Subjects
MU2E, gELBE, detector, dataset, muon conversion, Stopping Target Monitor (STM), Data Management, DAQ
Abstract

This dataset contains data generated with LaBr and Nal detector (DSPEC and oszilloscope data) at the gELBE beam. ThegELBE pulsed gamma beam to test the detector system for the Stopping Target Monitor of the MU2E experiment.ThegELBE pulsed gamma beam with narrow pulses set to about 600 kHz repetition rate - the choice of the ELBE CW mode with micropulses at 406 kHz or 812.5 kHz is ideal in our case- is the unique facility in the world suited to study the performance of the Stopping Target Monitor detector of the Mu2e Experiment. The STM monitor has the crucial role to normalize the charged lepton flavor muon conversion rate in the Mu2e experiment. The ability to operate at high rate in presence of background is crucial. We have at ELBE the unique possibility to validate the final methodology that will be employed by the STM detector.

Published
2021
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10. A computationally efficient, high-dimensional multiple changepoint procedure with application to global terrorism incidence

Author

Tickle, S. O., Eckley, I. A., Fearnhead, P., Tickle, S. O., Eckley, I. A., and Fearnhead, P.

Abstract

Detecting changepoints in datasets with many variates is a data science challenge of increasing importance. Motivated by the problem of detecting changes in the incidence of terrorism from a global terrorism database, we propose a novel approach to multiple changepoint detection in multivariate time series. Our method, which we call SUBSET, is a model-based approach which uses a penalised likelihood to detect changes for a wide class of parametric settings. We provide theory that guides the choice of penalties to use for SUBSET, and that shows it has high power to detect changes regardless of whether only a few variates or many variates change. Empirical results show that SUBSET out-performs many existing approaches for detecting changes in mean in Gaussian data; additionally, unlike these alternative methods, it can be easily extended to non-Gaussian settings such as are appropriate for modelling counts of terrorist events.

Published
2021

11. Assessing risk in the retail environment during the COVID-19 pandemic

Author

Budd, C., Calvert, K., Johnson, S., Tickle, S. O., Budd, C., Calvert, K., Johnson, S., and Tickle, S. O.

Abstract

The COVID-19 pandemic has caused unprecedented disruption, particularly in retail. Where essential demand cannot be fulfilled online, or where more stringent measures have been relaxed, customers must visit shop premises in person. This naturally gives rise to some risk of susceptible individuals (customers or staff) becoming infected. It is essential to minimize this risk as far as possible while retaining economic viability of the shop. We therefore explore and compare the spread of COVID-19 in different shopping situations involving person-to-person interactions: (i) free-flowing, unstructured shopping; (ii) structured shopping (e.g. a queue). We examine which of (i) or (ii) may be preferable for minimizing the spread of COVID-19 in a given shop, subject to constraints such as the geometry of the shop; compliance of the population to local guidelines; and additional safety measures which may be available to the organizers of the shop. We derive a series of conclusions, such as unidirectional free movement being preferable to bidirectional shopping, and that the number of servers should be maximized as long as they can be well protected from infection.

Published
2021

12. Gelatinase inhibitors and tumour metastasis

Author

Millican, A., primary, Baker, T. S., additional, Beeley, N. R. A., additional, Birch, M., additional, Boyce, B. A., additional, Chander, S., additional, Cockett, M., additional, Crabbe, T., additional, Docherty, A. J. P., additional, Eaton, D., additional, Hart, I., additional, Hynds, P., additional, Leonard, J., additional, Mason, B., additional, Millar, K., additional, Morphy, J. R., additional, Mountain, A., additional, O’Connell, J., additional, Porter, J., additional, Tickle, S., additional, Willenbrock, F. W., additional, and Willmott, N., additional

Published
1995
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13. Potent, selective inhibitors of human gelatinase and their potential in the treatment of tumour metastases

Author

Morphy, J. R., primary, Baker, T. S., additional, Beeley, N. R. A., additional, Birch, M., additional, Boyce, B. A., additional, Chander, S., additional, Cockett, M., additional, Crabbe, T., additional, Docherty, A. J. P., additional, Eaton, D., additional, Hart, I., additional, Hynds, P., additional, Leonard, J., additional, Mason, B., additional, Mountain, A., additional, Millican, T. A., additional, O’Connell, J., additional, Porter, J., additional, Tickle, S., additional, Willenbrock, F. W., additional, and Willmott, N., additional

Published
1994
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15. Parallelization of a Common Changepoint Detection Method.

Author

Tickle, S. O., Eckley, I. A., Fearnhead, P., and Haynes, K.

Subjects
*DYNAMIC programming
Abstract

In recent years, various means of efficiently detecting changepoints have been proposed, with one popular approach involving minimizing a penalized cost function using dynamic programming. In some situations, these algorithms can have an expected computational cost that is linear in the number of data points; however, the worst case cost remains quadratic. We introduce two means of improving the computational performance of these methods, both based on parallelizing the dynamic programming approach. We establish that parallelization can give substantial computational improvements: in some situations the computational cost decreases roughly quadratically in the number of cores used. These parallel implementations are no longer guaranteed to find the true minimum of the penalized cost; however, we show that they retain the same asymptotic guarantees in terms of their accuracy in estimating the number and location of the changes. for this article are available online. [ABSTRACT FROM AUTHOR]

Published
2020
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19. Innovation brief. High-throughput screening for high affinity antibodies.

Author

Tickle S, Adams R, Brown D, Griffiths M, Lightwood D, and Lawson A

Abstract

UCB Selected Lymphocyte Antibody Method (SLAM) is a rapid and efficient process for the generation of high-quality monoclonal antibodies, in which variable region gene sequences are recovered directly from specific, single B cells. Monoclonal antibody generation has been limited in the past by the relatively low efficiency of the hybridoma process. UCB SLAM process is well suited to high-throughput screening and has been extensively automated at UCB. If necessary, in excess of 1×109 B cells can be screened in a campaign, to discover a rare therapeutic antibody candidate, which meets the stringent selection criteria. Primary screening for antigen binders, on purified or cell expressed antigen, is performed using a homogeneous fluorescence assay format. Supernatants from positive wells are consolidated to allow further secondary screening and selection of antibodies with desired characteristics. Individual, specific B cells are identified using a fluorescence based method and isolated using a micromanipulator. The antibody variable region genes are cloned from DNA extracted from the single B cell. The genes are sequenced then prepared for transient expression to confirm activity. Antibodies with affinities (KD) in the sub 10 pM range against a range of therapeutic targets are routinely recovered using this process. [ABSTRACT FROM AUTHOR]

Published
2009
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22. Matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 expression and synthetic matrix metalloproteinase-2 inhibitor binding in ovarian carcinomas and tumor cell lines

Author

Afzal S, Lalani el-N, William Foulkes, Boyce B, Tickle S, Cardillo MR, Baker T, Pignatelli M, and Gw, Stamp

Subjects
Ovarian Neoplasms, Tissue Inhibitor of Metalloproteinase-2, Carcinoma, Antibodies, Monoclonal, Biotin, Metalloendopeptidases, Proteins, Amides, Immunohistochemistry, Mice, Gelatinases, Tumor Cells, Cultured, Animals, Humans, Matrix Metalloproteinase 2, Female, Protease Inhibitors, Tissue Distribution
Abstract

Enhanced matrix metalloproteinase-2 (MMP-2/72-kd type IV collagenase) action correlates with invasion in neoplasia. MMP-2 is inhibited in vivo by tissue inhibitors of metalloproteinases (TIMPs)-TIMP-1 and, especially, TIMP-2. A synthetic, biotinylated inhibitor specific for activated MMP-2 in solution phase, and immunohistochemistry were used to detect MMP-2 and TIMP-2 expression in cell lines and ovarian tumors and to analyze the surface-binding capacity of the inhibitors, which are potential therapeutic agents. Characterization of novel monoclonal antibodies to MMP-2 and TIMP-2 is described together with immunocytochemical staining of 83 paraffin-embedded ovarian tumors (67 malignant, 7 borderline, 9 benign) and 9 cell lines. Synthetic MMP-2 inhibitor binding under controlled conditions was visualized by immunofluorescence and avidin-biotin complex immunoperoxidase methods in cell lines and cryostat sections of ovarian tumors. MMP-2 and TIMP-2 showed heterogenous immunoreactivity, with enhanced staining on high-grade tumors, specifically at the invasive front and in vascular invasion. TIMP-2 immunoreactivity was maximal in malignant cell cytoplasm and less intense in desmoplastic fibroblasts. One monoclonal antibody to MMP-2 showed membrane immunoreactivity, apically polarized in benign and low-grade tumors but depolarized and strong in 37 of 44 cases of high-grade invasive tumors. Eleven of eighteen ovarian carcinomas and six of nine cell lines showed membrane localization of the synthetic inhibitor. Maximal binding occurred in the ovarian cell line OVCA 432 and the breast cell lines MCF 7 and MDA MB 435, all of which were immunoreactive for MMP-2. Cell lines propagated on type I collagen showed no enhancement in inhibitor binding. This study demonstrates cell surface binding of a synthetic MMP-2 inhibitor and provides new evidence of MMP-2 and TIMP-2 immunoreactivity in ovarian carcinomas and cell lines.

23. Mu2e Run I Sensitivity Projections for the Neutrinoless $\mu^- \to e^-$ Conversion Search in Aluminum

Author

Abdi, F., Abrams, R., Adentunji, J., Ahmed, W., Alber, R., Alexander, D., Allen, D., Allspach, D., Alvarez-Garcia, C., Ambrose, D., Ambrosio, G., Amirkhanov, A., Andreev, N., Ankenbrandt, C. M., Appleby, R., Arnold, D., Artikov, A., Atanov, N., Badgley, K., Ball, M., Baranov, V., Barker, J., Barnes, E., Barton, B., Bartoszek, L., Bellettini, G., Bernstein, R. H., Bersani, A., Bianchi, I., Biery, K., Bini, S., Blazey, G., Bloise, C., Boedigheimer, K., Boi, S., Bolton, T., Bono, J., Bonventre, R., Borghi, S., Borrel, L., Bossert, R., Bowcock, T., Bowden, M., Brandt, J., Breach, M., Brown, D., Brown, D. N., Brown, G., Brown, H., Budagov, I., Buelher, M., Bulugean, G. -M, Byrum, K., Campbell, M., Cao, H., Carey, R. M., Caron, J. F., Casey, B., Casler, H., Cervelli, F., Cheban, S., Chen, J., Chen, M., Cheng, C. -H, Chislett, R., Chitirasreemadam, N., Chokheli, D., Ciampa, K., Ciolini, R., Coghill, J., Colao, F., Coleman, R. N., Corrodi, S., Crescimbeni, L., Crowley, C., Culbertson, R., Cummings, M. A. C., Daniel, A., Davydov, Y., Demers, S., Deshpande, A., Devilbiss, M., Dey, J., Felice, G., Gouvea, A., Dhanraj, J., Ding, D., Dinnon, M., Diociaiuti, E., Dixon, S., Di Falco, S., Djilkibaev, R., Donati, S., Drake, G., Drendel, B., Duerling, G., Dukes, E. C., Dychkant, A., Echenard, B., Eddy, N., Edmonds, A., Ehrlich, R., Ekka, U., Evans, R., Evbota, D., Fabbricatore, P., Fagan, J., Farinon, S., Farrell, W., Farris, P., Feher, S., Fellenz, B., Fernandez, E., Ferrari, A., Ferrari, C., Finley, J., Flood, K., Flumerfelt, E., Fontana, F., Francis, K., Frand, M., Frank, M., Friedsam, H., Gallo, G., Gandrajula, R. P., Gaponenko, A., Gardner, M., Gargiulo, R., Gaugel, S., Genser, K. L., Gersabeck, M., Ginther, G., Gioiosa, A., Giovannella, S., Giusti, V., Glagolev, V., Glass, H., Glenzinski, D. A., Goadhouse, S., Goodenough, L., Grancagnolo, F., Gray, P., Group, C., Hahn, A., Hampai, D., Hansen, S., Happacher, F., Harkness-Brennan, L., Harrig, K., Hartsell, B., Hays, S., Hedges, M., Hedin, D., Heller, K., Herman, A., Hirsh, S., Hitlin, D. G., Hocker, A., Hooper, R., Horton-Smith, G., Huang, S., Huedem, E., Huffman, D., Hung, P. Q., Hungerford, E., Ibrahim, A., Israel, S., Jenkins, M., Johnstone, C., Jones, M., Jorjadze, V., Judson, D., Kampa, C., Kargiantoulakis, M., Kashikhin, V., Kasper, P., Keshavarzi, A., Khalatian, V., Kim, J. -H, Kiper, T., Knapp, D., Knodel, O., Knoepfel, K., Kokosa, L., Kolomensky, Yu G., Koltick, D., Kozlovsky, M., Kozminski, J., Kracczyk, G., Kramp, M., Krave, S., Krempetz, K., Kutschke, R. K., Kwarciany, R., Lackowski, T., Lamm, M. J., Lancaster, M., Larwill, M., Leavell, F., Lee, M. J., Leeb, D., Lema-Sinchi, J., Leveling, T., Lewis, R., Ley, A., Li, B., Li, Y., Lin, D., Lincoln, D., Logashenko, I., Lombardo, V., Lopes, M. L., Luca, A., Lynch, K. R., Mackenzie, M., Makulski, A., Manolis, J., Maravin, Yu, Marciano, W. J., Marini, A., Martin, E., Martinez, A., Martini, M., Mcarthur, D., Mcconologue, F., Mesmer, N., Messerly, B., Michelotti, L., Middleton, S., Miles, C., Miller, J. P., Nguyen, T. M., Miscetti, S., Mitchell, D., Miyashita, T., Mokhov, N., Molenaar, D., Molzon, W., Moore, J., Morescalchi, L., Morgan, J., Mott, J., Motuk, E., Mueller, S., Mukherjee, A., Murat, P., Musenich, R., Nagaslaev, V., Narayanan, A., Neely, R., Neuffer, D. V., Nguyen, M. T., Nicol, T., Niehoff, J., Nogiec, J., Norman, A., Northrup, K., O, V., Oh, S., Oksuzian, Yu, Olderr, P., Olson, M., Orris, D., Oshinowo, B., Ostojic, R., Oyang, J., Paesani, D., Pagan, S., Page, T., Palladino, A., Park, C., Pasciuto, D., Pedreschi, E., Peterson, T., Pezzullo, G., Pilipenko, R., Pla-Dalmau, A., Plesniak, P., Pohlman, N., Pollack, B., Poloubotko, V., Popovic, M., Popp, J. L., Frank C. Porter, Prebys, E. J., Price, J., Prieto, P., Pronskikh, V., Pushka, D., Quirk, J., Rabehl, R., Rachamin, R., Raffaelli, F., Ragheb, A., Rakness, G., Ray, R. E., Rechenmacher, R., Rivera, R., Rizzo, G., Roberts, B. L., Roberts, S., Roberts, T. J., Robotham, W., Roehrken, M., Rubinov, P., Rucinski, R., Rusu, V. L., Samavat, M. F., Sanzani, E., Saputi, A., Sarra, I., Sarychev, M., Scarpine, V., Schappert, W., Schmitt, M., Schmitter, P., Schoo, D., Schumacher, K., Shi, X., Singh, V., Sobering, T., Soleti, R., Solt, M., Song, H., Song, E., Spinella, F., Srivastav, M., Stefanik, A., Stetzler, S., Still, D., Stortini, M., Stratakis, D., Strauss, T., Sun, Y., Suslov, I., Syphers, M. J., Szemraj, L., Ta, J., Taffara, A., Tang, Z., Tanovic, N., Tartaglia, M., Tassielli, G., Taylor, R., Tecchio, M., Tickle, S., Tinsley, D., Tope, T., Torkelson, A., Tran, N., Trevor, J., Tschirhart, R. S., Turnberg, S., Uzunyan, S., Varier, D., Velasco, M., Vinas, L., Vitali, B., Vogel, G., Wagner, R., Wands, R., Wang, Y., Wang, C., Wang, M., Wardlaw, I., Warren, M., Werkema, S., White, Jr H. B., 11, J., Whitmore, J., Wielgos, R., Wildberger, R., Wills, L., Winter, P., Woods, R., Worel, C., Wu, Y., Xia, L., You, Z., Yucel, M., Zadeh, P., Zanetti, A. M., Zhadan, D., Zhu, R. -Y, Zifko, R., and Zutshi, V.

26. Serum metalloproteinases in prostate cancer

Author

Baker, T., Tickle, S., Wasan, H., Docherty, A., Flanders, J., and Waxman, J.

Subjects
Prostate cancer -- Physiological aspects, Metalloenzymes -- Physiological aspects, Business, Health care industry
Abstract

AUTHORS: T. Baker 1, S. Tickle 1, H. Wasan 2, A. Docherty 1, J. Flanders 2 and J. Waxman 2. 1Celltech Ltd., Slough, United Kingdom; 2Oncology Department, Hammersmith Hospital, London, [...]

Published
1993

27. Predicting Kidney Failure, Cardiovascular Disease and Death in Advanced CKD Patients

Author

Chava L. Ramspek, Rosemarijn Boekee, Marie Evans, Olof Heimburger, Charlotte M. Snead, Fergus J. Caskey, Claudia Torino, Gaetana Porto, Maciej Szymczak, Magdalena Krajewska, Christiane Drechsler, Christoph Wanner, Nicholas C. Chesnaye, Kitty J. Jager, Friedo W. Dekker, Maarten G.J. Snoeijs, Joris I. Rotmans, Merel van Diepen, Adamasco Cupisti, Adelia Sagliocca, Alberto Ferraro, Aleksandra Musiała, Alessandra Mele, Alessandro Naticchia, Alex Còsaro, Alistair Woodman, Andrea Ranghino, Andrea Stucchi, Andreas Jonsson, Andreas Schneider, Angelo Pignataro, Anita Schrander, Anke Torp, Anna McKeever, Anna Szymczak, Anna-Lena Blom, Antonella De Blasio, Antonello Pani, Aris Tsalouichos, Asad Ullah, Barbara McLaren, Bastiaan van Dam, Beate Iwig, Bellasi Antonio, Biagio Raffaele Di Iorio, Björn Rogland, Boris Perras, Butti Alessandra, Camille Harron, Carin Wallquist, Carl Siegert, Carla Barrett, Carlo Gaillard, Carlo Garofalo, Cataldo Abaterusso, Charles Beerenhout, Charlotte O'Toole, Chiara Somma, Christian Marx, Christina Summersgill, Christof Blaser, Claudia D'alessandro, Claudia Emde, Claudia Zullo, Claudio Pozzi, Colin Geddes, Cornelis Verburgh, Daniela Bergamo, Daniele Ciurlino, Daria Motta, Deborah Glowski, Deborah McGlynn, Denes Vargas, Detlef Krieter, Domenico Russo, Dunja Fuchs, Dympna Sands, Ellen Hoogeveen, Ellen Irmler, Emöke Dimény, Enrico Favaro, Eva Platen, Ewelina Olczyk, Ewout Hoorn, Federica Vigotti, Ferruccio Ansali, Ferruccio Conte, Francesca Cianciotta, Francesca Giacchino, Francesco Cappellaio, Francesco Pizzarelli, Fredrik Sundelin, Fredrik Uhlin, Gaetano Greco, Geena Roy, Giada Bigatti, Giancarlo Marinangeli, Gianfranca Cabiddu, Gillian Hirst, Giordano Fumagalli, Giorgia Caloro, Giorgina Piccoli, Giovanbattista Capasso, Giovanni Gambaro, Giuliana Tognarelli, Giuseppe Bonforte, Giuseppe Conte, Giuseppe Toscano, Goffredo Del Rosso, Gunilla Welander, Hanna Augustyniak-Bartosik, Hans Boots, Hans Schmidt-Gürtler, Hayley King, Helen McNally, Hendrik Schlee, Henk Boom, Holger Naujoks, Houda Masri-Senghor, Hugh Murtagh, Hugh Rayner, Ilona Miśkowiec-Wiśniewska, Ines Schlee, Irene Capizzi, Isabel Bascaran Hernandez, Ivano Baragetti, Jacek Manitius, Jane Turner, Jan-Willem Eijgenraam, Jeroen Kooman, Joachim Beige, Joanna Pondel, Joanne Wilcox, Jocelyn Berdeprado, Jochen Röthele, Jonathan Wong, Joris Rotmans, Joyce Banda, Justyna Mazur, Kai Hahn, Kamila Jędrzejak, Katarzyna Nowańska, Katja Blouin, Katrin Neumeier, Kirsteen Jones, Kirsten Anding-Rost, Knut-Christian Gröntoft, Lamberto Oldrizzi, Lesley Haydock, Liffert Vogt, Lily Wilkinson, Loreto Gesualdo, Lothar Schramm, Luigi Biancone, Łukasz Nowak, Maarten Raasveld, Magdalena Durlik, Manuela Magnano, Marc Vervloet, Marco Ricardi, Margaret Carmody, Maria Di Bari, Maria Laudato, Maria Luisa Sirico, Maria Stendahl, Maria Svensson, Maria Weetman, Marjolijn van Buren, Martin Joinson, Martina Ferraresi, Mary Dutton, Michael Matthews, Michele Provenzano, Monika Hopf, Moreno Malaguti, Nadja Wuttke, Neal Morgan, Nicola Palmieri, Nikolaus Frischmuth, Nina Bleakley, Paola Murrone, Paul Cockwell, Paul Leurs, Paul Roderick, Pauline Voskamp, Pavlos Kashioulis, Pawlos Ichtiaris, Peter Blankestijn, Petra Kirste, Petra Schulz, Phil Mason, Philip Kalra, Pietro Cirillo, Pietro Dattolo, Pina Acampora, Rincy Sajith, Rita Nigro, Roberto Boero, Roberto Scarpioni, Rosa Sicoli, Rosella Malandra, Sabine Aign, Sabine Cäsar, Sadie van Esch, Sally Chapman, Sandra Biribauer, Santee Navjee, Sarah Crosbie, Sharon Brown, Sheila Tickle, Sherin Manan, Silke Röser, Silvana Savoldi, Silvio Bertoli, Silvio Borrelli, Siska Boorsma, Stefan Heidenreich, Stefan Melander, Stefania Maxia, Stefano Maffei, Stefano Mangano, Stephanie Palm, Stijn Konings, Suresh Mathavakkannan, Susanne Schwedler, Sylke Delrieux, Sylvia Renker, Sylvia Schättel, Szyszkowska Dorota, Teresa Cicchetti, Teresa Nieszporek, Theresa Stephan, Thomas Schmiedeke, Thomas Weinreich, Til Leimbach, Tiziana Rappa, Tora Almquist, Torsten Stövesand, Udo Bahner, Ulrika Jensen, Valentina Palazzo, Walter De Simone, Wolfgang Seeger, Ying Kuan, Zbigniew Heleniak, Zeynep Aydin, Vascular Surgery, MUMC+: MA Med Staf Spec Vaatchirurgie (9), RS: Carim - V03 Regenerative and reconstructive medicine vascular disease, Ramspek, C. L., Boekee, R., Evans, M., Heimburger, O., Snead, C. M., Caskey, F. J., Torino, C., Porto, G., Szymczak, M., Krajewska, M., Drechsler, C., Wanner, C., Chesnaye, N. C., Jager, K. J., Dekker, F. W., Snoeijs, M. G. J., Rotmans, J. I., van Diepen, M., Cupisti, A., Sagliocca, A., Ferraro, A., Musiala, A., Mele, A., Naticchia, A., Cosaro, A., Woodman, A., Ranghino, A., Stucchi, A., Jonsson, A., Schneider, A., Pignataro, A., Schrander, A., Torp, A., Mckeever, A., Szymczak, A., Blom, A. -L., De Blasio, A., Pani, A., Tsalouichos, A., Ullah, A., Mclaren, B., van Dam, B., Iwig, B., Antonio, B., Di Iorio, B. R., Rogland, B., Perras, B., Alessandra, B., Harron, C., Wallquist, C., Siegert, C., Barrett, C., Gaillard, C., Garofalo, C., Abaterusso, C., Beerenhout, C., O'Toole, C., Somma, C., Marx, C., Summersgill, C., Blaser, C., D'Alessandro, C., Emde, C., Zullo, C., Pozzi, C., Geddes, C., Verburgh, C., Bergamo, D., Ciurlino, D., Motta, D., Glowski, D., Mcglynn, D., Vargas, D., Krieter, D., Russo, D., Fuchs, D., Sands, D., Hoogeveen, E., Irmler, E., Dimeny, E., Favaro, E., Platen, E., Olczyk, E., Hoorn, E., Vigotti, F., Ansali, F., Conte, F., Cianciotta, F., Giacchino, F., Cappellaio, F., Pizzarelli, F., Sundelin, F., Uhlin, F., Greco, G., Roy, G., Bigatti, G., Marinangeli, G., Cabiddu, G., Hirst, G., Fumagalli, G., Caloro, G., Piccoli, G., Capasso, G., Gambaro, G., Tognarelli, G., Bonforte, G., Conte, G., Toscano, G., Del Rosso, G., Welander, G., Augustyniak-Bartosik, H., Boots, H., Schmidt-Gurtler, H., King, H., Mcnally, H., Schlee, H., Boom, H., Naujoks, H., Masri-Senghor, H., Murtagh, H., Rayner, H., Miskowiec-Wisniewska, I., Schlee, I., Capizzi, I., Hernandez, I. B., Baragetti, I., Manitius, J., Turner, J., Eijgenraam, J. -W., Kooman, J., Beige, J., Pondel, J., Wilcox, J., Berdeprado, J., Rothele, J., Wong, J., Rotmans, J., Banda, J., Mazur, J., Hahn, K., Jedrzejak, K., Nowanska, K., Blouin, K., Neumeier, K., Jones, K., Anding-Rost, K., Grontoft, K. -C., Oldrizzi, L., Haydock, L., Vogt, L., Wilkinson, L., Gesualdo, L., Schramm, L., Biancone, L., Nowak, L., Raasveld, M., Durlik, M., Magnano, M., Vervloet, M., Ricardi, M., Carmody, M., Di Bari, M., Laudato, M., Sirico, M. L., Stendahl, M., Svensson, M., Weetman, M., van Buren, M., Joinson, M., Ferraresi, M., Dutton, M., Matthews, M., Provenzano, M., Hopf, M., Malaguti, M., Wuttke, N., Morgan, N., Palmieri, N., Frischmuth, N., Bleakley, N., Murrone, P., Cockwell, P., Leurs, P., Roderick, P., Voskamp, P., Kashioulis, P., Ichtiaris, P., Blankestijn, P., Kirste, P., Schulz, P., Mason, P., Kalra, P., Cirillo, P., Dattolo, P., Acampora, P., Sajith, R., Nigro, R., Boero, R., Scarpioni, R., Sicoli, R., Malandra, R., Aign, S., Casar, S., van Esch, S., Chapman, S., Biribauer, S., Navjee, S., Crosbie, S., Brown, S., Tickle, S., Manan, S., Roser, S., Savoldi, S., Bertoli, S., Borrelli, S., Boorsma, S., Heidenreich, S., Melander, S., Maxia, S., Maffei, S., Mangano, S., Palm, S., Konings, S., Mathavakkannan, S., Schwedler, S., Delrieux, S., Renker, S., Schattel, S., Dorota, S., Cicchetti, T., Nieszporek, T., Stephan, T., Schmiedeke, T., Weinreich, T., Leimbach, T., Rappa, T., Almquist, T., Stovesand, T., Bahner, U., Jensen, U., Palazzo, V., De Simone, W., Seeger, W., Kuan, Y., Heleniak, Z., Aydin, Z., Medical Informatics, APH - Aging & Later Life, APH - Methodology, APH - Quality of Care, Nephrology, ACS - Microcirculation, APH - Health Behaviors & Chronic Diseases, APH - Global Health, ACS - Pulmonary hypertension & thrombosis, ACS - Diabetes & metabolism, and Internal Medicine

Subjects
SDG 3 - Good Health and Well-being, external validation, Nephrology, cardiovascular disease, death, CKD, kidney failure, prognostic model
Abstract

Introduction: Predicting the timing and occurrence of kidney replacement therapy (KRT), cardiovascular events, and death among patients with advanced chronic kidney disease (CKD) is clinically useful and relevant. We aimed to externally validate a recently developed CKD G4+ risk calculator for these outcomes and to assess its potential clinical impact in guiding vascular access placement. Methods: We included 1517 patients from the European Quality (EQUAL) study, a European multicentre prospective cohort study of nephrology-referred advanced CKD patients aged ≥65 years. Model performance was assessed based on discrimination and calibration. Potential clinical utility for timing of referral for vascular access placement was studied with diagnostic measures and decision curve analysis (DCA). Results: The model showed a good discrimination for KRT and “death after KRT,” with 2-year concordance (C) statistics of 0.74 and 0.76, respectively. Discrimination for cardiovascular events (2-year C-statistic: 0.70) and overall death (2-year C-statistic: 0.61) was poorer. Calibration was fairly accurate. Decision curves illustrated that using the model to guide vascular access referral would generally lead to less unused arteriovenous fistulas (AVFs) than following estimated glomerular filtration rate (eGFR) thresholds. Conclusion: This study shows moderate to good predictive performance of the model in an older cohort of nephrology-referred patients with advanced CKD. Using the model to guide referral for vascular access placement has potential in combating unnecessary vascular surgeries.

Published
2022
Full Text
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28. Associations between depressive symptoms and disease progression in older patients with chronic kidney disease

Author

Eveleens Maarse, Boukje C., Chesnaye, Nicholas C., Robbert, Schouten, Michels, Wieneke M., Bos, Willem Jan W., Maciej, Szymczak, Magdalena, Krajewska, Marie Evans, Olof Heimburger, Caskey, Fergus J., Christoph, Wanner, Jager, Kitty J., Dekker, Friedo W., Yvette, Meuleman, Andreas, Schneider, Anke, Torp, Beate, Iwig, Boris, Perras, Christian, Marx, Christiane, Drechsler, Christof, Blaser, Claudia, Emde, Detlef, Krieter, Dunja, Fuchs, Ellen, Irmler, Eva, Platen, Hans, Schmidt-Gürtler, Hendrik, Schlee, Holger, Naujoks, Ines, Schlee, Sabine, Cäsar, Joachim, Beige, Jochen, Röthele, Justyna, Mazur, Kai, Hahn, Katja, Blouin, Katrin, Neumeier, Kirsten, Anding-Rost, Lothar, Schramm, Monika, Hopf, Nadja, Wuttke, Nikolaus, Frischmuth, Pawlos, Ichtiaris, Petra, Kirste, Petra, Schulz, Sabine, Aign, Sandra, Biribauer, Sherin, Manan, Silke, Röser, Stefan, Heidenreich, Stephanie, Palm, Susanne, Schwedler, Sylke, Delrieux, Sylvia, Renker, Sylvia, Schättel, Theresa, Stephan, Thomas, Schmiedeke, Thomas, Weinreich, Til, Leimbach, Torsten, Stövesand, Udo, Bahner, Wolfgang, Seeger, Cupisti, Adamasco, Adelia, Sagliocca, Alberto, Ferraro, Alessandra, Mele, Alessandro, Naticchia, Alex, Còsaro, Andrea, Ranghino, Andrea, Stucchi, Angelo, Pignataro, Antonella De Blasio, Antonello, Pani, Aris, Tsalouichos, Bellasi, Antonio, Biagio Raffaele Di Iorio, Butti, Alessandra, Cataldo, Abaterusso, Chiara, Somma, Claudia, D'Alessandro, Claudia, Torino, Claudia, Zullo, Claudio, Pozzi, Daniela, Bergamo, Daniele, Ciurlino, Daria, Motta, Domenico, Russo, Enrico, Favaro, Federica, Vigotti, Ferruccio, Ansali, Ferruccio, Conte, Francesca, Cianciotta, Francesca, Giacchino, Francesco, Cappellaio, Francesco, Pizzarelli, Gaetano, Greco, Gaetana, Porto, Giada, Bigatti, Giancarlo, Marinangeli, Gianfranca, Cabiddu, Giordano, Fumagalli, Giorgia, Caloro, Giorgina, Piccoli, Giovanbattista, Capasso, Giovanni, Gambaro, Giuliana, Tognarelli, Giuseppe, Bonforte, Giuseppe, Conte, Giuseppe, Toscano, Goffredo Del Rosso, Irene, Capizzi, Ivano, Baragetti, Lamberto, Oldrizzi, Loreto, Gesualdo, Luigi, Biancone, Manuela, Magnano, Marco, Ricardi, Maria Di Bari, Maria, Laudato, Maria Luisa Sirico, Martina, Ferraresi, Maurizio, Postorino, Michele, Provenzano, Moreno, Malaguti, Nicola, Palmieri, Paola, Murrone, Pietro, Cirillo, Pietro, Dattolo, Pina, Acampora, Rita, Nigro, Roberto, Boero, Roberto, Scarpioni, Rosa, Sicoli, Rosella, Malandra, Silvana, Savoldi, Silvio, Bertoli, Silvio, Borrelli, Stefania, Maxia, Stefano, Maffei, Stefano, Mangano, Teresa, Cicchetti, Tiziana, Rappa, Valentina, Palazzo, Walter De Simone, Anita, Schrander, Bastiaan van Dam, Carl, Siegert, Carlo, Gaillard, Charles, Beerenhout, Cornelis, Verburgh, Cynthia, Janmaat, Ellen, Hoogeveen, Ewout, Hoorn, Friedo, Dekker, Johannes, Boots, Henk, Boom, Jan-Willem, Eijgenraam, Jeroen, Kooman, Joris, Rotmans, Kitty, Jager, Liffert, Vogt, Maarten, Raasveld, Marc, Vervloet, Marjolijn van Buren, Merel van Diepen, Nicholas, Chesnaye, Paul, Leurs, Pauline, Voskamp, Peter, Blankestijn, Sadie van Esch, Siska, Boorsma, Stefan, Berger, Constantijn, Konings, Zeynep, Aydin, Aleksandra, Musiała, Anna, Szymczak, Ewelina, Olczyk, Hanna, Augustyniak-Bartosik, Ilona, Miśkowiec-Wiśniewska, Jacek, Manitius, Joanna, Pondel, Kamila, Jędrzejak, Katarzyna, Nowańska, Łukasz, Nowak, Magdalena, Durlik, Szyszkowska, Dorota, Teresa, Nieszporek, Zbigniew, Heleniak, Andreas, Jonsson, Anna-Lena, Blom, Björn, Rogland, Carin, Wallquist, Denes, Vargas, Emöke, Dimény, Fredrik, Sundelin, Fredrik, Uhlin, Gunilla, Welander, Isabel Bascaran Hernandez, Knut-Christian, Gröntoft, Maria, Stendahl, Maria, Svensson, Marie, Evans, Olof, Heimburger, Pavlos, Kashioulis, Stefan, Melander, Tora, Almquist, Ulrika, Jensen, Alistair, Woodman, Anna, Mckeever, Asad, Ullah, Barbara, Mclaren, Camille, Harron, Carla, Barrett, Charlotte, O'Toole, Christina, Summersgill, Colin, Geddes, Deborah, Glowski, Deborah, Mcglynn, Dympna, Sands, Fergus, Caskey, Geena, Roy, Gillian, Hirst, Hayley, King, Helen, Mcnally, Houda, Masri-Senghor, Hugh, Murtagh, Hugh, Rayner, Jane, Turner, Joanne, Wilcox, Jocelyn, Berdeprado, Jonathan, Wong, Joyce, Banda, Kirsteen, Jones, Lesley, Haydock, Lily, Wilkinson, Margaret, Carmody, Maria, Weetman, Martin, Joinson, Mary, Dutton, Michael, Matthews, Neal, Morgan, Nina, Bleakley, Paul, Cockwell, Paul, Roderick, Phil, Mason, Philip, Kalra, Rincy, Sajith, Sally, Chapman, Santee, Navjee, Sarah, Crosbie, Sharon, Brown, Sheila, Tickle, Suresh, Mathavakkannan, Ying, Kuan, Internal medicine, Nephrology, ACS - Diabetes & metabolism, Medical Informatics, APH - Methodology, APH - Aging & Later Life, Graduate School, APH - Quality of Care, ACS - Microcirculation, APH - Health Behaviors & Chronic Diseases, APH - Global Health, ACS - Pulmonary hypertension & thrombosis, Eveleens Maarse, B. C., Chesnaye, N. C., Schouten, R., Michels, W. M., Bos, W. J. W., Szymczak, M., Krajewska, M., Evans, M., Heimburger, O., Caskey, F. J., Wanner, C., Jager, K. J., Dekker, F. W., Meuleman, Y., Schneider, A., Torp, A., Iwig, B., Perras, B., Marx, C., Drechsler, C., Blaser, C., Emde, C., Krieter, D., Fuchs, D., Irmler, E., Platen, E., Schmidt-Gurtler, H., Schlee, H., Naujoks, H., Schlee, I., Casar, S., Beige, J., Rothele, J., Mazur, J., Hahn, K., Blouin, K., Neumeier, K., Anding-Rost, K., Schramm, L., Hopf, M., Wuttke, N., Frischmuth, N., Ichtiaris, P., Kirste, P., Schulz, P., Aign, S., Biribauer, S., Manan, S., Roser, S., Heidenreich, S., Palm, S., Schwedler, S., Delrieux, S., Renker, S., Schattel, S., Stephan, T., Schmiedeke, T., Weinreich, T., Leimbach, T., Stovesand, T., Bahner, U., Seeger, W., Cupisti, A., Sagliocca, A., Ferraro, A., Mele, A., Naticchia, A., Cosaro, A., Ranghino, A., Stucchi, A., Pignataro, A., De Blasio, A., Pani, A., Tsalouichos, A., Antonio, B., Raffaele Di Iorio, B., Alessandra, B., Abaterusso, C., Somma, C., D'Alessandro, C., Torino, C., Zullo, C., Pozzi, C., Bergamo, D., Ciurlino, D., Motta, D., Russo, D., Favaro, E., Vigotti, F., Ansali, F., Conte, F., Cianciotta, F., Giacchino, F., Cappellaio, F., Pizzarelli, F., Greco, G., Porto, G., Bigatti, G., Marinangeli, G., Cabiddu, G., Fumagalli, G., Caloro, G., Piccoli, G., Capasso, G., Gambaro, G., Tognarelli, G., Bonforte, G., Conte, G., Toscano, G., Del Rosso, G., Capizzi, I., Baragetti, I., Oldrizzi, L., Gesualdo, L., Biancone, L., Magnano, M., Ricardi, M., Di Bari, M., Laudato, M., Luisa Sirico, M., Ferraresi, M., Postorino, M., Provenzano, M., Malaguti, M., Palmieri, N., Murrone, P., Cirillo, P., Dattolo, P., Acampora, P., Nigro, R., Boero, R., Scarpioni, R., Sicoli, R., Malandra, R., Savoldi, S., Bertoli, S., Borrelli, S., Maxia, S., Maffei, S., Mangano, S., Cicchetti, T., Rappa, T., Palazzo, V., De Simone, W., Schrander, A., Van Dam, B., Siegert, C., Gaillard, C., Beerenhout, C., Verburgh, C., Janmaat, C., Hoogeveen, E., Hoorn, E., Boots, J., Boom, H., Eijgenraam, J. -W., Kooman, J., Rotmans, J., Vogt, L., Raasveld, M., Vervloet, M., Van Buren, M., Van Diepen, M., Leurs, P., Voskamp, P., Blankestijn, P., Van Esch, S., Boorsma, S., Berger, S., Konings, C., Aydin, Z., Musiala, A., Szymczak, A., Olczyk, E., Augustyniak-Bartosik, H., Miskowiec-Wisniewska, I., Manitius, J., Pondel, J., Jedrzejak, K., Nowanska, K., Nowak, L., Durlik, M., Dorota, S., Nieszporek, T., Heleniak, Z., Jonsson, A., Blom, A. -L., Rogland, B., Wallquist, C., Vargas, D., Dimeny, E., Sundelin, F., Uhlin, F., Welander, G., Bascaran Hernandez, I., Grontoft, K. -C., Stendahl, M., Svensson, M., Kashioulis, P., Melander, S., Almquist, T., Jensen, U., Woodman, A., Mckeever, A., Ullah, A., Mclaren, B., Harron, C., Barrett, C., O'Toole, C., Summersgill, C., Geddes, C., Glowski, D., Mcglynn, D., Sands, D., Roy, G., Hirst, G., King, H., Mcnally, H., Masri-Senghor, H., Murtagh, H., Rayner, H., Turner, J., Wilcox, J., Berdeprado, J., Wong, J., Banda, J., Jones, K., Haydock, L., Wilkinson, L., Carmody, M., Weetman, M., Joinson, M., Dutton, M., Matthews, M., Morgan, N., Bleakley, N., Cockwell, P., Roderick, P., Mason, P., Kalra, P., Sajith, R., Chapman, S., Navjee, S., Crosbie, S., Brown, S., Tickle, S., Mathavakkannan, S., and Kuan, Y.

Subjects
Transplantation, prospective cohort study, depressive symptoms, nephrology care, Nephrology, clinical outcome, chronic kidney disease, clinical trial, epidemiology, joint model, survival analysis, depressive symptom
Abstract

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (≥65 years; estimated glomerular filtration rate ≤20 mL/min/1.73 m2) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off ≤70; 0–100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was –0.12 mL/min/1.73 m2/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03–1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men.

Published
2022
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29. 'Are we all playing an elaborate game?' A Bourdieusian analysis of children’s participation in decision making in youth justice

Author

Creaney, S, Jamieson, J, Tickle, S, and Yates, J

Subjects
HV, K1
Abstract

There has been a lack of empirical research on children’s involvement in the design and delivery of youth offending services. This PhD investigates the extent and nature of children’s participation in planning, decision making and assessment in youth justice. It seeks to reveal the ‘logic’ and unmask the ‘hidden workings’ of participatory youth justice practice. The PhD involved 15 months of fieldwork, undertaken between 2016-2017 at a youth offending service in England. This involved participant observations and semi-structured interviews with children and young people (n=20) and professionals (n=20). Pierre Bourdieu’s analytical tools: habitus, capital, field and symbolic violence, were utilised to investigate the attitudes and behaviours of practitioners and those under supervision. This original and distinctive study produced new knowledge, uncovering both inclusive and exclusive aspects of practice that either facilitated or foreclosed children’s participation. Opportunities provided to young people to have a say and influence practice were strikingly unequal at the practice level. Involvement in shaping decision making and influencing processes was ostensibly reserved for the non-high risk, especially the ready to conform or those with seemingly malleable personality types. The study found that several young people were seeking to exert minimal energy in order to achieve a type of passive compliance with court order requirements. Professionals were concerned that they were also participating in this type of ‘game playing’. The PhD reveals insight into why agents may not contest the status quo despite experiencing hardship. The PhD presents cogent arguments for involving children more centrally in decision making, unlocking their potential and reversing a system that has traditionally ‘designed out’ opportunities for them to provide a perspective on their care/supervision or devalued the credibility/validity of their experiential knowledge. Peer mentoring was found to be a liberating and enlightening type of practice. Whilst not necessarily denouncing the adult professional voice and perspective, children and young people can be ‘experts by experience’.

30. Cyto-Mine: An Integrated, Picodroplet System for High-Throughput Single-Cell Analysis, Sorting, Dispensing, and Monoclonality Assurance.

Author

Josephides D, Davoli S, Whitley W, Ruis R, Salter R, Gokkaya S, Vallet M, Matthews D, Benazzi G, Shvets E, Gesellchen F, Geere D, Liu X, Li X, Mackworth B, Young W, Owen Z, Smith C, Starkie D, White J, Sweeney B, Hinchliffe M, Tickle S, Lightwood DJ, Rehak M, Craig FF, and Holmes D

Subjects
Animals, Antigens metabolism, CHO Cells, Cells, Immobilized cytology, Cricetulus, Flow Cytometry, Fluorescence Resonance Energy Transfer, Humans, Image Processing, Computer-Assisted, Immunoglobulin G metabolism, Mice, Clone Cells cytology, High-Throughput Screening Assays methods, Single-Cell Analysis methods, Software
Abstract

The primary goal of bioprocess cell line development is to obtain high product yields from robustly growing and well-defined clonal cell lines in timelines measured in weeks rather than months. Likewise, high-throughput screening of B cells and hybridomas is required for most cell line engineering workflows. A substantial bottleneck in these processes is detecting and isolating rare clonal cells with the required characteristics. Traditionally, this was achieved by the resource-intensive method of limiting dilution cloning, and more recently aided by semiautomated technologies such as cell sorting (e.g., fluorescence-activated cell sorting) and colony picking. In this paper we report on our novel Cyto-Mine Single Cell Analysis and Monoclonality Assurance System, which overcomes the limitations of current technologies by screening hundreds of thousands of individual cells for secreted target proteins, and then isolating and dispensing the highest producers into microtiter plate wells (MTP). The Cyto-Mine system performs this workflow using a fully integrated, microfluidic Cyto-Cartridge. Critically, all reagents and Cyto-Cartridges used are animal component-free (ACF) and sterile, thus allowing fast, robust, and safe isolation of desired cells.

Published
2020
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31. A fully automated primary screening system for the discovery of therapeutic antibodies directly from B cells.

Author

Tickle S, Howells L, O'Dowd V, Starkie D, Whale K, Saunders M, Lee D, and Lightwood D

Subjects
Animals, Antibodies isolation & purification, Rabbits, Rats, Antibodies therapeutic use, Automation, B-Lymphocytes immunology
Abstract

For a therapeutic antibody to succeed, it must meet a range of potency, stability, and specificity criteria. Many of these characteristics are conferred by the amino acid sequence of the heavy and light chain variable regions and, for this reason, can be screened for during antibody selection. However, it is important to consider that antibodies satisfying all these criteria may be of low frequency in an immunized animal; for this reason, it is essential to have a mechanism that allows for efficient sampling of the immune repertoire. UCB's core antibody discovery platform combines high-throughput B cell culture screening and the identification and isolation of single, antigen-specific IgG-secreting B cells through a proprietary technique called the "fluorescent foci" method. Using state-of-the-art automation to facilitate primary screening, extremely efficient interrogation of the natural antibody repertoire is made possible; more than 1 billion immune B cells can now be screened to provide a useful starting point from which to identify the rare therapeutic antibody. This article will describe the design, construction, and commissioning of a bespoke automated screening platform and two examples of how it was used to screen for antibodies against two targets., (© 2014 Society for Laboratory Automation and Screening.)

Published
2015
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32. Antibody-targeted chemotherapy of B-cell lymphoma using calicheamicin conjugated to murine or humanized antibody against CD22.

Author

DiJoseph JF, Popplewell A, Tickle S, Ladyman H, Lawson A, Kunz A, Khandke K, Armellino DC, Boghaert ER, Hamann P, Zinkewich-Peotti K, Stephens S, Weir N, and Damle NK

Subjects
Amino Acid Sequence, Aminoglycosides chemistry, Aminoglycosides immunology, Animals, Antibodies, Monoclonal genetics, Antibodies, Monoclonal immunology, Antineoplastic Agents immunology, Binding, Competitive, Cell Line, Tumor, Epitopes immunology, Female, Humans, Immunoconjugates immunology, Lymphoma, B-Cell immunology, Mice, Mice, Inbred BALB C, Mice, Nude, Molecular Sequence Data, Sialic Acid Binding Ig-like Lectin 2, Xenograft Model Antitumor Assays methods, Aminoglycosides therapeutic use, Antibodies, Monoclonal therapeutic use, Antigens, CD immunology, Antigens, Differentiation, B-Lymphocyte immunology, Antineoplastic Agents therapeutic use, Cell Adhesion Molecules immunology, Immunoconjugates therapeutic use, Lectins immunology, Lymphoma, B-Cell therapy
Abstract

Antibody-targeted chemotherapy with immunoconjugates of calicheamicin is a clinically validated strategy in cancer therapy. This study describes the selection of a murine anti-CD22 mAb, m5/44, as a targeting agent, its conjugation to a derivative of calicheamicin (CalichDM) via either acid-labile or acid-stable linkers, the antitumor activity of CalichDM conjugated to m5/44, and its subsequent humanization by CDR grafting. Murine IgG1 mAb m5/44 was selected based on its subnanomolar affinity for CD22 and ability to be internalized into B cells. CalichDM conjugated to m5/44 caused potent growth inhibition of CD22+ human B-cell lymphomas (BCLs) in vitro. The conjugate of m5/44 with an acid-labile linker was more potent than an acid-stable conjugate, a nonbinding conjugate with a similar acid-labile linker, or unconjugated CalichDMH in inhibiting BCL growth. CalichDM conjugated to m5/44 caused regression of established BCL xenografts in nude mice. In contrast, both unconjugated m5/44 and a nonbinding conjugate were ineffective against these xenografts. Based on the potent antitumor activity of m5/44-CalichDM conjugates, m5/44 was humanized by CDR grafting to create g5/44, an IgG4 anti-CD22 antibody. Both m5/44 and g5/44 bound CD22 with subnanomolar affinity. Competitive blocking with previously characterized murine anti-CD22 mAbs suggested that g5/44 recognizes epitope A located within the first N-terminal Ig-like domain of human CD22. Antitumor efficacy of CalichDM conjugated to g5/44 against BCL xenografts was more potent than its murine counterpart. Based on these results, a calicheamicin conjugate of g5/44, CMC-544, was selected for further development as a targeted chemotherapeutic agent for the treatment of B-cell malignancies.

Published
2005
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33. Homelessness and health: Leeds conference.

Author

Tickle S

Subjects
Health Services Needs and Demand, Humans, Needs Assessment, Community Health Services organization & administration, Ill-Housed Persons psychology
Published
2002

34. Pressure sores in children--the acute hospital perspective.

Author

Willock J, Hughes J, Tickle S, Rossiter G, Johnson C, and Pye H

Subjects
Acute Disease, Child, Child, Preschool, Humans, Incidence, Infant, Prevalence, United Kingdom, Child, Hospitalized statistics & numerical data, Pressure Ulcer epidemiology
Abstract

There is very little published literature on pressure sores in children and most of the existing literature is qualitative. Using literature from paediatric and adult studies, a schedule was designed to collect quantitative data on aspects that may predispose children to pressure injury. The schedule was piloted in an incidence and a prevalence study at the Royal Liverpool Children's NHS Trust. The sample size was 82 children for the incidence study and 183 children for the prevalence study. Six children in the incidence study and 12 children in the prevalence study sustained pressure injury. Data indicated that factors most strongly associated with pressure injury were nutritional status, mobility and consciousness level. Other factors that were implicated in increasing susceptibility to pressure injury were skin condition, body weight, haemodynamic status and hydration. Infants and young children most frequently sustained pressure injury on the occipital scalp area and heels. Although this was a small study, it produced some useful preliminary data, and was a valuable exercise to develop a tool for data collection on a larger scale.

Published
2000
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35. PDGFbeta receptor blockade inhibits intimal hyperplasia in the baboon.

Author

Hart CE, Kraiss LW, Vergel S, Gilbertson D, Kenagy R, Kirkman T, Crandall DL, Tickle S, Finney H, Yarranton G, and Clowes AW

Subjects
Animals, Catheterization adverse effects, Cell Division, Enzyme-Linked Immunosorbent Assay, Hyperplasia etiology, Hyperplasia prevention & control, Papio, Partial Thromboplastin Time, Time Factors, Tunica Intima metabolism, Antibodies, Monoclonal pharmacology, Heparin pharmacology, Receptors, Platelet-Derived Growth Factor antagonists & inhibitors, Receptors, Platelet-Derived Growth Factor immunology, Tunica Intima drug effects, Tunica Intima pathology
Abstract

Background: We have evaluated the use of a mouse/human chimeric anti-platelet-derived growth factor-beta receptor antibody in combination with heparin to inhibit intimal hyperplasia in the saphenous artery of the baboon after balloon angioplasty., Methods and Results: The study evaluated lesion development in sequential injuries made 28 days apart. Each animal received control treatment after the first injury and antibody/heparin therapy after the second injury to the contralateral artery. The antibody was administered by bolus intravenous injections (10 mg/kg) on study days 1, 4, 8, 15, and 22 and heparin coadministered by continuous intravenous infusion at a dose of 0.13 mg/kg per hour. Morphometric analysis of tissue sections showed a 53% decrease in intimal area after antibody/heparin treatment (P=0.005), corresponding to a 40% decrease in the intima-to-media ratio (P=0.005). Smooth muscle cell proliferation in the injured wall, measured at both 4 and 29 days after balloon injury, were similar in the control and antibody/heparin-treated animals., Conclusions: These data suggest that platelet-derived growth factor plays a key role in the development of intimal lesions at sites of acute vascular injury in the nonhuman primate.

Published
1999
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36. Conversion of highly malignant colon cancer from an aggressive to a controlled disease by oral administration of a metalloproteinase inhibitor.

Author

An Z, Wang X, Willmott N, Chander SK, Tickle S, Docherty AJ, Mountain A, Millican AT, Morphy R, Porter JR, Epemolu RO, Kubota T, Moossa AR, and Hoffman RM

Subjects
Animals, Colonic Neoplasms enzymology, Colonic Neoplasms pathology, Drug Screening Assays, Antitumor, Humans, Male, Mice, Mice, Nude, Transplantation, Heterologous, Amides therapeutic use, Antineoplastic Agents therapeutic use, Colonic Neoplasms drug therapy, Metalloendopeptidases antagonists & inhibitors, Neoplasm Proteins antagonists & inhibitors
Abstract

In this study, we describe the activity of CT1746, an orally-active synthetic MMP inhibitor that has a greater specificity for gelatinase A, gelatinase B and stromelysin than for interstitial collagenase and matrilysin, in a nude mouse model that better mimics the clinical development of human colon cancer. The model is constructed by surgical orthotopic implantation (SOI) of histologically-intact tissue of the metastatic human colon tumor cell line Co-3. Animals were gavaged with CT1746 twice a day at 100 mg/kg for 5 days after the SOI of Co-3 for 43 days. In this model CT1746 significantly prolonged the median survival time of the tumor-bearing animals from 51 to 78 days. Significant efficacy of CT1746 was observed on primary tumor growth (32% reduction in mean tumor area at day 36), total spread and metastasis (6/20 treated animals had no detectable spread and metastasis at autopsy compared to 100% incidence of secondaries in control groups). Efficacy of CT1746 could also be seen on reducing tumor spread and metastasis to individual organ sites such as the abdominal wall, cecum and lymph nodes compared to vehicle and untreated controls. We conclude that chronic administration of a peptidomimetic MMP inhibitor via the oral route is feasible and results in inhibition of solid tumor growth, spread and metastasis with increase in survival in this model of human cancer, thus converting aggressive cancer to a more controlled indolent disease.

Published
1997
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37. Matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 expression and synthetic matrix metalloproteinase-2 inhibitor binding in ovarian carcinomas and tumor cell lines.

Author

Afzal S, Lalani el-N, Foulkes WD, Boyce B, Tickle S, Cardillo MR, Baker T, Pignatelli M, and Stamp GW

Subjects
Amides metabolism, Animals, Antibodies, Monoclonal, Biotin analogs & derivatives, Biotin metabolism, Carcinoma pathology, Female, Humans, Immunohistochemistry, Matrix Metalloproteinase 2, Mice, Ovarian Neoplasms pathology, Protease Inhibitors metabolism, Tissue Distribution, Tissue Inhibitor of Metalloproteinase-2, Tumor Cells, Cultured metabolism, Carcinoma metabolism, Gelatinases antagonists & inhibitors, Gelatinases metabolism, Metalloendopeptidases antagonists & inhibitors, Metalloendopeptidases metabolism, Ovarian Neoplasms metabolism, Proteins metabolism
Abstract

Enhanced matrix metalloproteinase-2 (MMP-2/72-kd type IV collagenase) action correlates with invasion in neoplasia. MMP-2 is inhibited in vivo by tissue inhibitors of metalloproteinases (TIMPs)-TIMP-1 and, especially, TIMP-2. A synthetic, biotinylated inhibitor specific for activated MMP-2 in solution phase, and immunohistochemistry were used to detect MMP-2 and TIMP-2 expression in cell lines and ovarian tumors and to analyze the surface-binding capacity of the inhibitors, which are potential therapeutic agents. Characterization of novel monoclonal antibodies to MMP-2 and TIMP-2 is described together with immunocytochemical staining of 83 paraffin-embedded ovarian tumors (67 malignant, 7 borderline, 9 benign) and 9 cell lines. Synthetic MMP-2 inhibitor binding under controlled conditions was visualized by immunofluorescence and avidin-biotin complex immunoperoxidase methods in cell lines and cryostat sections of ovarian tumors. MMP-2 and TIMP-2 showed heterogenous immunoreactivity, with enhanced staining on high-grade tumors, specifically at the invasive front and in vascular invasion. TIMP-2 immunoreactivity was maximal in malignant cell cytoplasm and less intense in desmoplastic fibroblasts. One monoclonal antibody to MMP-2 showed membrane immunoreactivity, apically polarized in benign and low-grade tumors but depolarized and strong in 37 of 44 cases of high-grade invasive tumors. Eleven of eighteen ovarian carcinomas and six of nine cell lines showed membrane localization of the synthetic inhibitor. Maximal binding occurred in the ovarian cell line OVCA 432 and the breast cell lines MCF 7 and MDA MB 435, all of which were immunoreactive for MMP-2. Cell lines propagated on type I collagen showed no enhancement in inhibitor binding. This study demonstrates cell surface binding of a synthetic MMP-2 inhibitor and provides new evidence of MMP-2 and TIMP-2 immunoreactivity in ovarian carcinomas and cell lines.

Published
1996

38. Elevated plasma stromelysin levels in arthritis.

Author

Zucker S, Lysik RM, Zarrabi MH, Greenwald RA, Gruber B, Tickle SP, Baker TS, and Docherty AJ

Subjects
Adult, Aged, Analysis of Variance, Animals, Antibodies, Monoclonal, Enzyme-Linked Immunosorbent Assay, Female, Gelatinases blood, Gout enzymology, Humans, Male, Matrix Metalloproteinase 2, Matrix Metalloproteinase 3, Mice, Middle Aged, Osteoarthritis enzymology, Rabbits, Arthritis enzymology, Arthritis, Rheumatoid enzymology, Lupus Erythematosus, Systemic enzymology, Metalloendopeptidases blood
Abstract

Objective: To determine whether plasma concentrations of stromelysin-1 and gelatinase A are increased in patients with various forms of arthritis., Methods: A sensitive and specific sandwich enzyme linked immunosorbent assay (ELISA), which employs a murine monoclonal antibody and a rabbit polyclonal antibody to human stromelysin-1, was used to measure plasma stromelysin-1 in 53 healthy subjects, 113 patients with various forms of arthritis and connective tissue diseases, and 65 patients with cancer. Gelatinase A was also measured in these patients using specific polyclonal and monoclonal antibodies to gelatinase A in an ELISA:, Results: The plasma concentration of stromelysin-1 (X +/- SEM) was significantly increased (p < 0.001) in patients with rheumatoid arthritis (RA) (187 +/- 14 ng/ml) and systemic lupus erythematosus (SLE) (258 +/- 35 ng/ml) as compared to both healthy control subjects (50 +/- 4 ng/ml) or patients with cancer (61 +/- 20 ng/ml). Plasma stromelysin-1 was also significantly increased in smaller groups of men with osteoarthritis (OA) and gout. In contrast, plasma concentrations of gelatinase A were not significantly increased in patients with RA, OA or gout. In healthy subjects, the concentration of stromelysin-1 was significantly higher in men than women. No correlation was noted between plasma stromelysin-1 levels and age., Conclusion: The detection of elevated plasma levels of stromelysin-1 in patients with RA is consistent with increased stromelysin-1 concentrations in inflamed synovial tissues in this disease. The origin of increased plasma stromelysin-1 in SLE is speculative. Measurement of plasma stromelysin-1 may be useful in the diagnosis and management of patients with various forms of arthritis.

Published
1994

39. Plasma assay of matrix metalloproteinases (MMPs) and MMP-inhibitor complexes in cancer. Potential use in predicting metastasis and monitoring treatment.

Author

Zucker S, Lysik RM, Zarrabi HM, Moll U, Tickle SP, Stetler-Stevenson W, Baker TS, and Docherty AJ

Subjects
Female, Humans, Metalloendopeptidases antagonists & inhibitors, Monitoring, Physiologic, Neoplasm Proteins blood, Neoplasms pathology, Neoplasms therapy, Predictive Value of Tests, Pregnancy, Tissue Inhibitor of Metalloproteinase-2, Tissue Inhibitor of Metalloproteinases, Biomarkers, Tumor blood, Glycoproteins blood, Metalloendopeptidases blood, Neoplasm Metastasis, Neoplasms blood, Proteins analysis
Published
1994
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40. Mutation of the active site glutamic acid of human gelatinase A: effects on latency, catalysis, and the binding of tissue inhibitor of metalloproteinases-1.

Author

Crabbe T, Zucker S, Cockett MI, Willenbrock F, Tickle S, O'Connell JP, Scothern JM, Murphy G, and Docherty AJ

Subjects
Amino Acid Sequence, Base Sequence, Binding Sites genetics, Catalysis, DNA Primers, Electrophoresis, Polyacrylamide Gel, Enzyme Activation, Enzyme Precursors chemistry, Enzyme Precursors isolation & purification, Enzyme Precursors metabolism, Gelatinases chemistry, Gelatinases genetics, Glutamates genetics, Glutamic Acid, Humans, Matrix Metalloproteinase 2, Metalloendopeptidases chemistry, Metalloendopeptidases genetics, Molecular Sequence Data, Mutation, Tissue Inhibitor of Metalloproteinases, Gelatinases metabolism, Glutamates metabolism, Glycoproteins metabolism, Metalloendopeptidases metabolism
Abstract

Human gelatinase A, a member of the matrix metalloproteinase family, is secreted from cells as the M(r) 72,000 latent precursor, progelatinase A. The autolytic removal of an N-terminal propeptide generates the M(r) 66,000 active form. Mutants of recombinant progelatinase A, altered such that the proposed active site glutamic acid residue (E375) was replaced by either an aspartic acid (proE375-->D), an alanine (proE375-->A) or a glutamine (proE375-->Q), were purified from medium conditioned by transfected NS0 mouse myeloma cells. Like wild-type progelatinase A, the mutant proenzymes were inactive and could bind tissue inhibitor of metalloproteinases (TIMP)-2 but not TIMP-1 to their C-terminal domains. Their rates of autolytic processing induced by the organomercurial (4-aminophenyl) mercuric acetate, however, were markedly slower and, of the three M(r) 66,000 forms so produced, only E375-->D displayed any proteolytic activity against either a synthetic substrate (kcat/Km = 10% that of the wild-type enzyme) or denatured type I collagen (specific activity = 0.9% that of the wild-type enzyme). ProE375-->A and proE375-->Q could be more rapidly processed to their M(r) 66,000 forms by incubation with a deletion mutant of gelatinase A that has full catalytic activity but lacks the C-terminal domain [delta (418-631) gelatinase A]. These two M(r) 66,000 forms displayed low activity on a gelatin zymogram (approximately 0.01% that of the wild-type enzyme) but, like E375-->D were able to bind TIMP-1 with an affinity equal to that of the activated wild-type enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Published
1994
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41. Immunoassays for the detection of human collagenase, stromelysin, tissue inhibitor of metalloproteinases (TIMP) and enzyme-inhibitor complexes.

Author

Cooksley S, Hipkiss JB, Tickle SP, Holmes-Ievers E, Docherty AJ, Murphy G, and Lawson AD

Subjects
Antibodies, Monoclonal immunology, Antibody Specificity, DNA genetics, Enzyme Activation, Glycoproteins immunology, Glycoproteins pharmacology, Humans, Matrix Metalloproteinase 3, Metalloendopeptidases antagonists & inhibitors, Metalloendopeptidases immunology, Microbial Collagenase antagonists & inhibitors, Microbial Collagenase immunology, Recombinant Proteins analysis, Recombinant Proteins immunology, Tissue Inhibitor of Metalloproteinases, Enzyme-Linked Immunosorbent Assay, Glycoproteins analysis, Metalloendopeptidases analysis, Microbial Collagenase analysis
Abstract

Immunoassays have been developed for human collagenase, stromelysin, tissue inhibitor of metalloproteinases (TIMP) and TIMP complexed with both of the active enzymes. Selection of antibodies of defined specificity enabled measurement of both the pro and active forms of the metalloproteinase. Free TIMP was quantified by the selection of a monoclonal antibody which did not recognise TIMP when complexed with metalloproteinases. Detection of enzyme-inhibitor complexes was achieved by capturing the TIMP component of the complex and revealing the metalloenzyme using specific antibodies.

Published
1990
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42. Cell kinetic studies in the epidermis of mouse. III. The percent labelled mitosis (PLM) technique.

Author

Potten CS, Wichmann HE, Dobek K, Birch J, Codd TM, Horrocks L, Pedrick M, and Tickle SP

Subjects
Animals, Computers, Epidermal Cells, Humans, Male, Mathematics, Methods, Mice, Mice, Inbred DBA, Cell Cycle, Mitosis, Skin cytology
Abstract

Full PLM curves have been obtained for four sites in the mouse. The first peaks have been analysed by computer and the duration of the G2 + M and S phases determined together with their standard deviations. The full curves showed a general similarity for all four sites with no clear second peak. The data are compared with the published data for mouse and human epidermis using the in vivo PLM technique. The timing and shape of the first peak can vary considerably even for one site in mice. Hence, both G2 + M and S can vary in their durations. Cells labelled at one time of day exhibit different kinetic properties to those labelled at another time of day. The duration of G2 + M is shortest in dorsum labelled at 03.00 hours (3 X 2 hr) and longest in tail (up to 7 X 5 hr). The S-phase is shortest in dorsum (6 X 3-7 X 2 hr) and longest in tail or ear (13 X 3-14 X 1 hr). There is also a very large standard deviation in tail and foot. There is little general variability when the psoriatic human data are considered, which is surprising. The general variability amongst the data from experimental mice might also be expected amongst humans which might make comparisons between the cell kinetics of normal and diseased skin difficult.

Published
1985
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43. Use of extra-thoracic assisted breathing in the management of chronic obstructive lung diseases.

Author

Fountain FF Jr, Reynolds LB Jr, and Tickle SM

Subjects
Adolescent, Adult, Aged, Breathing Exercises, Chronic Disease, Emphysema therapy, Female, Humans, Male, Middle Aged, Nitrogen metabolism, Physical and Rehabilitation Medicine instrumentation, Positive-Pressure Respiration, Respiratory Function Tests, Spirometry, Vital Capacity, Lung Diseases, Obstructive therapy, Respiration, Artificial
Published
1973

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