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19. Intradermal air pouch leukocytosis as an in vivo test for nanoparticles

Author

Vandooren J, Berghmans N, Dillen C, Van Aelst I, Ronsse I, Israel LL, Rosenberger I, Kreuter J, Lellouche JP, Michaeli S, Locatelli E, Comes Franchini M, Aiertza MK, Sánchez-Abella L, Loinaz I, Edwards DR, Shenkman L, and Opdenakker G

Subjects
Medicine (General), R5-920
Abstract

Jennifer Vandooren,1 Nele Berghmans,1 Chris Dillen,1 Ilse Van Aelst,1 Isabelle Ronsse,1 Liron Limor Israel,2 Ina Rosenberger,3 Jörg Kreuter,3 Jean-Paul Lellouche,2 Shulamit Michaeli,4 Erica Locatelli,5 Mauro Comes Franchini,5 Miren K Aiertza,6 Laura Sánchez-Abella,6 Iraida Loinaz,6 Dylan R Edwards,7 Louis Shenkman,8 Ghislain Opdenakker1 1Rega Institute for Medical Research, University of Leuven, Leuven, Belgium; 2Department of Chemistry and Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan, Tel Aviv, Israel; 3Institut für Pharmazeutische Technologie, Johann Wolfgang Goethe-Universität, Frankfurt, Germany; 4The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat Gan, Tel Aviv, Israel; 5Department of Industrial Chemistry Toso Montanari, University of Bologna, Bologna, Italy; 6New Materials Department, Fundación CIDETEC, San Sebastián, Spain; 7School of Biological Sciences, University of East Anglia, Norwich, UK; 8Tel Aviv University, Ramat Aviv, Tel Aviv, Israel Abstract: The need for test systems for nanoparticle biocompatibility, toxicity, and inflammatory or adaptive immunological responses is paramount. Nanoparticles should be free of microbiological and chemical contaminants, and devoid of toxicity. Nevertheless, in the absence of contamination, these particles may still induce undesired immunological effects in vivo, such as enhanced autoimmunity, hypersensitivity reactions, and fibrosis. Here we show that artificial particles of specific sizes affect immune cell recruitment as tested in a dermal air pouch model in mice. In addition, we demonstrate that the composition of nanoparticles may influence immune cell recruitment in vivo. Aside from biophysical characterizations in terms of hydrodynamic diameter, zeta potential, concentration, and atomic concentration of metals, we show that – after first-line in vitro assays – characterization of cellular and molecular effects by dermal air pouch analysis is straightforward and should be included in the quality control of nanoparticles. We demonstrate this for innate immunological effects such as neutrophil recruitment and the production of immune-modulating matrix metalloproteases such as MMP-9; we propose the use of air pouch leukocytosis analysis as a future standard assay. Keywords: nanoparticles, biocompatibility, toxicity, air pouch, immunologyA Letter to the Editor has been received and published for this article.

Published
2013

20. A National audit of the care of patients with acute kidney injury in England and Wales in 2019 and the association with patient outcomes

Author

Lee, Dr Keegan, Dan Cooper, Carr, Dr Edward, Marthi, Dr Amar, Swift, Dr Oscar, Hull, Dr Katherine, Nimmo, Dr Ailish, Liewm, Dr Hui, Tariq, Dr Behram, Whitehead, Dr Jenny, Edney, Dr Naomi, Whitbread, Dr Daniel, Mohamed, Dr Maha, Duffy, Dr Sam, Edwards, Dr Gwenno, Czajka, Dr Rachael, Ahmad, Dr Syed Hasan, Joslin, Dr Jennifer, Yong, Dr Esther Siaw Tsin, Chaudry, Dr Saurabh, McGuinness, Dr Daniel, Defreitas, Dr Sarah, Nosseir, Dr Heba, Seal, Dr Katherine, Amaran, Dr Mo, Gulati, Dr Kavita, Azam, Dr Muhammad J, Williams, Dr Jennifer, Smith-Jackson, Yin, Dr Bo-song, Shuaib, Dr Rishana, Akter, Dr Mosammat, Arimoto, Dr Ryoki, Oluyombo, Dr Rotimi, Davies, Dr Mark, Patel, Dr Purvi, Best-Trent, Tony, Handra, Dr Heidy, Mackie, Sarah, Wright, Kelly, Rahman, Dr Manzur, Cheema, Dr Hashem, Sardar, Dr Abbas, Harvard, Dr Lucy, Brook, Dr Matthew, Elphic, Dr Emma, Ahmed, Dr Mawahib, Ammar, Dr Kanbar, Harbe, Dr Madi, Corke, Dr Emma, Stacey, Dr Hannah, Yousif, Dr Mosab, Mohamed, Dr Dalal, Soe, Dr Lae Thandar, Sherna, Dr Adenwalla, Soutter, Dr Lauren, Davari, Dr Maria, Abburu, Dr Sneha, Wells, Dr James, Winterbottom, Dr Claire, Bottomley, Dr Matt, Morris, Dr Holly, Sadiq, Dr Anavami, Youssouf, Dr Sajeda, Graham-Brown, M.P.M., Casula, A., Savino, M., Humphrey, T., Pyart, R., Amaran, M., Williams, J., Crowe, K., and Medcalf, J.F.

Published
2024
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22. Correction: Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.

Author

Liang, J, Le, TH, Velez Edwards, DR, Tayo, BO, Gaulton, KJ, Smith, JA, Lu, Y, Jensen, RA, Chen, G, Yanek, LR, Schwander, K, Tajuddin, SM, Sofer, T, Kim, W, Kayima, J, McKenzie, CA, Fox, E, Nalls, MA, Young, JH, Sun, YV, Lane, JM, Cechova, S, Zhou, J, Tang, H, Fornage, M, Musani, SK, Wang, H, Lee, J, Adeyemo, A, Dreisbach, AW, Forrester, T, Chu, P-L, Cappola, A, Evans, MK, Morrison, AC, Martin, LW, Wiggins, KL, Hui, Q, Zhao, W, Jackson, RD, Ware, EB, Faul, JD, Reiner, AP, Bray, M, Denny, JC, Mosley, TH, Palmas, W, Guo, X, Papanicolaou, GJ, Penman, AD, Polak, JF, Rice, K, Taylor, KD, Boerwinkle, E, Bottinger, EP, Liu, K, Risch, N, Hunt, SC, Kooperberg, C, Zonderman, AB, Laurie, CC, Becker, DM, Cai, J, Loos, RJF, Psaty, BM, Weir, DR, Kardia, SLR, Arnett, DK, Won, S, Edwards, TL, Redline, S, Cooper, RS, Rao, DC, Rotter, JI, Rotimi, C, Levy, D, Chakravarti, A, Zhu, X, and Franceschini, N

Abstract

[This corrects the article DOI: 10.1371/journal.pgen.1006728.].

Published
2018

24. HEAD AND NECK LYMPHANGIOMAS.

Author

Sepúlveda A., Dr. Ilson, Edwards, Dr. Paul, Sauer, Dr. David, and Naief, Dr. Nasser Said Al

Abstract

Lymphatic malformations [LM] are benign hamartomatous growths that reflect abnormal development of lymphatic channels. They primarily affect children & young adults but may occur at any age and in any location. 75% of all LM are diagnosed in the H&N. This research was performed with multi-institutional collaboration when the demographics of 23 cases of H&N lymphangiomas/LM were retrospectively reviewed, including one case from the max. sinus which is considered rare. 9 [39.1%] and 14 [60.8%] occurred in males & females respectively, with an age range of "6-88" y.o. Lesions ranged from 1.5 mm to 40 mm in size. One LM involved each of the max. sinus, submand. space, neck, and cervicothoracic region. 19 [82.6%] cases occurred intraorally; tongue [8]: 4-R&L lateral, 3-dorsal, 1-base], followed by gingiva [6], buccal mucosa [2], soft palate [2], and labial mucosa [1 case]. All cases were surgically excised except one managed with IMRT. Post-management follow-up was documented in 9 [39.13%] showing no recurrence but was not available in [52.1%] of cases. Lesions were clinically interpreted as various entities. The diagnosis was histologically confirmed in all cases. As in hemangiomas, it is a dilemma to classify lymphangiomas as true neoplasms, hamartomas, or lymphangiectasias. For practical purposes, the distinction is of little value knowing all lesions are benign and management is related to location and clinical extent. The (ISSVA) in 2018, separated vascular anomalies into tumors and malformations, where the latter included lymphatic malformations (LM). LM may be divided into congenital and acquired, clinically separated into superficial and deeply seated, or macrocytic, microcystic, or an admixture of both types based on size, respectively. Little or no difference exists in the histomorphologic features between these categories. We present the demographics in a series of H&N LM, imaging characteristics, and updated review of the entity. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Publisher Correction:Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

Author

Surendran, P, Feofanova, EV, Lahrouchi, N, Ntalla, I, Karthikeyan, S, Cook, J, Chen, L, Mifsud, B, Yao, C, Kraja, AT, Cartwright, JH, Hellwege, JN, Giri, A, Tragante, V, Thorleifsson, G, Liu, DJ, Prins, BP, Stewart, ID, Cabrera, CP, Eales, JM, Akbarov, A, Auer, PL, Bielak, LF, Bis, JC, Braithwaite, VS, Brody, JA, Daw, EW, Warren, HR, Drenos, F, Nielsen, SF, Faul, JD, Fauman, EB, Fava, C, Ferreira, T, Foley, CN, Franceschini, N, Gao, H, Giannakopoulou, O, Giulianini, F, Gudbjartsson, DF, Guo, X, Harris, SE, Havulinna, AS, Helgadottir, A, Huffman, JE, Hwang, S-J, Kanoni, S, Kontto, J, Larson, MG, Li-Gao, R, Lindstrom, J, Lotta, LA, Lu, Y, Luan, J, Mahajan, A, Malerba, G, Masca, NGD, Mei, H, Menni, C, Mook-Kanamori, DO, Mosen-Ansorena, D, Muller-Nurasyid, M, Pare, G, Paul, DS, Perola, M, Poveda, A, Rauramaa, R, Richard, M, Richardson, TG, Sepulveda, N, Sim, X, Smith, AV, Smith, JA, Staley, JR, Stanakova, A, Sulem, P, Theriault, S, Thorsteinsdottir, U, Trompet, S, Varga, TV, Velez Edwards, DR, Veronesi, G, Weiss, S, Willems, SM, Yao, J, Young, R, Yu, B, Zhang, W, Zhao, J-H, Zhao, W, Evangelou, E, Aeschbacher, S, Asllanaj, E, Blankenberg, S, Bonnycastle, LL, Bork-Jensen, J, Brandslund, I, Braund, PS, Burgess, S, Cho, K, Christensen, C, Connell, J, De Mutsert, R, Dominiczak, AF, Dorr, M, Eiriksdottir, G, Farmaki, A-E, Gaziano, JM, Grarup, N, Grove, ML, Hallmans, G, Hansen, T, Have, CT, Heiss, G, Jorgensen, ME, Jousilahti, P, Kajantie, E, Kamat, M, Karajamaki, A, Karpe, F, Koistinen, HA, Kovesdy, CP, Kuulasmaa, K, Laatikainen, I, Lannfelt, L, Lee, I-T, Lee, W-J, Linneberg, A, Martin, LW, Moitry, M, Nadkarni, G, Neville, MJ, Palmer, CNA, Papanicolaou, GJ, Pedersen, O, Peters, J, Poulter, N, Rasheed, A, Rasmussen, KL, Rayner, NW, Magi, R, Renstrom, F, Rettig, R, Rossouw, J, Schreiner, PJ, Sever, PS, Sigurdsson, EL, Skaaby, T, Sun, YV, Sundstrom, J, Thorgeirsson, G, Esko, T, Trabetti, E, Tsao, PS, Tuomi, T, Turner, ST, Tzoulaki, I, Vaartjes, I, Vergnaud, A-C, Willer, CJ, Wilson, PWF, Witte, DR, Yonova-Doing, E, Zhang, H, Aliya, N, Almgren, P, Amouyel, P, Asselbergs, FW, Barnes, MR, Blakemore, AI, Boehnke, M, Bots, ML, Bottinger, EP, Buring, JE, Chambers, JC, Chen, Y-DI, Chowdhury, R, Conen, D, Correa, A, Davey Smith, G, Boer, RAD, Deary, IJ, Dedoussis, G, Deloukas, P, Di Angelantonio, E, Elliott, P, Felix, SB, Ferrieres, J, Ford, I, Fornage, M, Franks, PW, Franks, S, Frossard, P, Gambaro, G, Gaunt, TR, Groop, L, Gudnason, V, Harris, TB, Hayward, C, Hennig, BJ, Herzig, K-H, Ingelsson, E, Tuomilehto, J, Jarvelin, M-R, Jukema, JW, Kardia, SLR, Kee, F, Kooner, JS, Kooperberg, C, Launer, LJ, Lind, L, Loos, RJF, Majumder, AAS, Laakso, M, McCarthy, MI, Melander, O, Mohlke, KL, Murray, AD, Nordestgaard, BG, Orho-Melander, M, Packard, CJ, Padmanabhan, S, Palmas, W, Polasek, O, Porteous, DJ, Prentice, AM, Province, MA, Relton, CL, Rice, K, Ridker, PM, Rolandsson, O, Rosendaal, FR, Rotter, JI, Rudan, I, Salomaa, V, Samani, NJ, Sattar, N, Sheu, WH-H, Smith, BH, Soranzo, N, Spector, TD, Starr, JM, Sebert, S, Taylor, KD, Lakka, TA, Timpson, NJ, Tobin, MD, Van der Harst, P, Van der Meer, P, Ramachandran, VS, Verweij, N, Virtamo, J, Volker, U, Weir, DR, Zeggini, E, Charchar, FJ, Wareham, NJ, Langenberg, C, Tomaszewski, M, Butterworth, AS, Caulfield, MJ, Danesh, J, Edwards, TL, Holm, H, Hung, AM, Lindgren, CM, Liu, C, Manning, AK, Morris, AP, Morrison, AC, O'Donnell, CJ, Psaty, BM, Saleheen, D, Stefansson, K, Boerwinkle, E, Chasman, DI, Levy, D, Newton-Cheh, C, Munroe, PB, Howson, JMM, and United Kingdom Research and Innovation

Subjects
Genetics & Heredity, Understanding Society Scientific Group, Science & Technology, business.industry, Published Erratum, Million Veteran Program, MEDLINE, Computational biology, 06 Biological Sciences, Biology, Blood pressure, Text mining, Meta-analysis, EPIC-InterAct, Genetics, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, business, Life Sciences & Biomedicine, EPIC-CVD, 11 Medical and Health Sciences, LifeLines Cohort Study, Developmental Biology
Abstract

In the version of this article originally published, the e-mail address of corresponding author Patricia B. Munroe was incorrect. The error has been corrected in the HTML and PDF versions of the article.

Published
2021

34. FRI-057-A review of primary biliary cholangitis practice in Wales: Time for specialist care

Author

Haboubi, Hasan, primary, Shenbagaraj, Lavanya, additional, Abdul-Sattar, Asma, additional, Harborne, Philip, additional, Philips, Andrew, additional, Appanna, Gautham, additional, Yahya, Dr. Imran, additional, Navaratnam, Janardhan, additional, Edwards, Dr. Kate, additional, Alrubaiy, Laith, additional, Newbould, Dr. Rachel, additional, Vincent, Dr. Rebecca, additional, Mannem, Dr. Seetharam, additional, Gardezi, Dr. Syed Anjum, additional, Aslam, Dr. Usama, additional, Jennings, Dr. Victoria, additional, Samuel, David, additional, Pembroke, Tom, additional, Ch’ng, Chin Lye, additional, Srivastava, Dr. Brijesh, additional, Yousuf, Dr. Fidan, additional, and Yeoman, Andrew, additional

Published
2019
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35. USE OF PYTHAGOREAN THEOREM TO OPTIMISE NEEDLE LENGTH SELECTION FOR IN-PLANE ULTRASOUND GUIDED APPROACHES TO REGIONAL ANAESTHESIA.

Author

Edwards, Dr Charles

Abstract

Background and Aims:Selecting the ideal needle length is an important factor in successful ultrasound guided procedures: too long and the needle will be difficult to control, too short and there is a risk that the target cannot be reached. Educational materials often recommend needle lengths for procedures but obviously patients vary in size and shape. We describe a mathematical method for selecting the optimum needle length for any ultrasound transducer/target structure combination.Methods:Pythagorean Theorem states that for a right-angled triangle the square of the hypotenuse is equal to the sum of the squares of the other two sides. The needle length can be calculated from the target depth and width, measured from the centre of the ultrasound probe to needle entry point, see Figure1.ResultsIn general, it is best to use the shortest needle that will allow the furthest part of the target to be reached. Have in mind the maximum target depth that can be reached with a 50mm needle with the equipment you are using. You can easily calculate a table for your own equipment by measuring the distance from the centre of the probe to the edge of the probe plus 4mm working distance for needle insertion. Use this figure for value b in the formula, see Figure 2.Conclusions:The application of Pythagorean theorem and production of reference table allows quick and easy selection of optimum needle length. This is useful for new trainees and in departments where a range of makes/models of ultrasound machine are used.

Published
2017

36. 'The British School of Sculpture, C.1760-1832 '

Author

Burnage, Sarah, Edwards, Dr Jason, Burnage, Sarah, and Edwards, Dr Jason

Subjects
Sculpture--Great Britain--History--Congresses
Abstract

The British School of Sculpture, c. 1760?1832 represents the first edited collection exploring one of the most significant moments in British art history, returning to centre stage a wide range of sculpture considered for the first time by some of the most important scholars in the field. Following a historical and historiographical introduction by the editors, situating British sculpture in relation to key events and developments in the period, and the broader scholarship on British art more generally in the period and beyond, the book contains nine wide-ranging case studies that consider the place of antique and modern sculpture in British country houses in the period, monuments to heroes of commerce and the Napoleonic Wars, the key debates fought around ideal sculpture at the Royal Academy, the reception of British sculpture across Europe, the reception of Hindu sculpture deriving from India in Britain, and the relationship of sculpture to emerging industrial markets, both at home and abroad. Challenging characterisations of the period as'neoclassical', the volume reveals British sculpture to be a much more eclectic and various field of endeavour, both in service of the state and challenging it, and open to sources ranging from the newly arrived Parthenon Frieze to contemporary print culture.

Published
2016

37. Genomic analyses for age at menarche identify 389 independent signals and indicate BMI-independent effects of puberty timing on cancer susceptibility

Author

Nora Franceschini, Rico Rueedi, Gerardo Heiss, Behrooz Z. Alizadeh, Marike Gabrielson, Henry Völzke, Daniela Ruggiero, Judith S. Brand, Stig E. Bojesen, Iffat Rahman, Fergus J. Couch, Patrick Sulem, Harold Snieder, Jenny Chang-Claude, Caterina Barbieri, Ute Hamann, Hinds D, Pascal Guénel, Amanda B. Spurdle, Paul M. Ridker, Ulla Sovio, Roger L. Milne, Hamdi Mbarek, H Brenner, Hilary K. Finucane, Maristella Steri, Lude Franke, Emmi Tikkanen, Ivana Kolcic, Vitart, Ken K. Ong, Alison M. Dunning, Aarno Palotie, Caroline Hayward, Jouke J. Hottenga, Abhishek Sarkar, Stefania Lenarduzzi, Nicholas G. Martin, Katharina E. Schraut, Eva Albrecht, Hiltrud Brauch, Lisette Stolk, Joop S.E. Laven, Penelope A. Lind, Ilaria Gandin, Patrik K. E. Magnusson, Ellen A. Nohr, Tanguy Corre, Jing Hua Zhao, N J Timpson, Jenny A. Visser, Harald Grallert, P. A. Fasching, Susan M. Ring, Stöckl D, Grant W. Montgomery, Marzyeh Amini, Velez Edwards Dr, Thomas Meitinger, Qinghua Wang, David Karasik, Daniel I. Chasman, Nicholas J. Wareham, Alexander Teumer, Mellissa C. Southey, Kathryn L. Lunetta, S. E. Medland, Dieter Flesch-Janys, Maartje J. Hooning, Lili Milani, D Lambrechts, Ozren Polasek, Po-Ru Loh, James F. Wilson, Campbell A, Julian Peto, Ellen W. Demerath, Christian Gieger, de Geus Ej, Cox A, Javier Benítez, Mitul Shah, Eric Boerwinkle, Matthias W. Beckmann, Thorsteindottir U, Julie E. Buring, De Vivo I, Hannes Helgason, Paolo Radice, Tracy A. O'Mara, L. J. Launer, D. F. Gudbjartsson, Frits R. Rosendaal, C.A. Hartman, Stefania Bandinelli, Felix R. Day, Lynda M. Rose, van Dijk Kw, Natalia Perjakova, Anneli Pouta, Igor Rudan, Sven Bergmann, Kamila Czene, Georgia Chenevix-Trench, Pau Navarro, Sean Whalen, Heli Nevanlinna, Teresa Nutile, Diana L. Cousminer, Albert V. Smith, Massimo Mangino, Uwe Völker, Michela Traglia, Lindsay Fernández-Rhodes, Ayush Giri, Linda Broer, Albertine J. Oldehinkel, Isabel dos-Santos-Silva, Peter Vollenweider, Jian'an Luan, Nancy L. Pedersen, Irene L. Andrulis, Reedik Mägi, Robert Winqvist, Gonneke Willemsen, John L. Hopper, Gudnason, Marjanka K. Schmidt, David G. Hunter, Robert A. Scott, T.B. Harris, Joanne M. Murabito, David J. Porteous, Harry Campbell, Eleonora Porcu, D.I. Boomsma, Thibaud Boutin, M. A. Ikram, Doug Easton, Magdalena Zoledziewska, Meir J. Stampfer, Katherine S. Pollard, Eulalia Catamo, Tõnu Esko, M-R Jarvelin, Laura Crisponi, Claudia Langenberg, Marek Zygmunt, Antonietta Robino, Emily Hallberg, Manjeet K. Bolla, Ruth Ks, Bruce H W Wolffenbuttel, Lavinia Paternoster, Tyrer Jp, P. Kraft, George Davey-Smith, Robert Karlsson, Graham G. Giles, Jingmei Li, Pharoah Pd, Segrè Av, Marina Ciullo, Perry, Brumat Marco, Peter K. Joshi, Chunyan He, Sara Lindström, Joe Dennis, Thérèse Truong, Yongmei Liu, Anna Marie Mulligan, Mike A. Nalls, Cinzia Sala, K. Stefansson, Murray A, Debbie A Lawlor, Tung Jy, Deborah J. Thompson, Dennis O. Mook-Kanamori, Daniela Toniolo, Luigi Ferrucci, Peter Devilee, S. Chanock, Cristina Menni, George McMahon, Murielle Bochud, A. Metspalu, Tomohiro Tanaka, E. Widen, Hae Kyung Im, Dale R. Nyholt, Ilja M. Nolte, Thomas Brüning, Christina Meisinger, Annette Peters, Kyriaki Michailidou, Per Hall, Rossella Sorice, Genevieve Lachance, Johan G. Eriksson, Francesco Cucca, A.G. Uitterlinden, Z. Kutalik, Mark I. McCarthy, Frank B. Hu, Konstantin Strauch, Tim D. Spector, Elisabeth Altmaier, S. Ulivi, Alkes L. Price, Arto Mannermaa, Raymond Noordam, and de Mutsert R

Subjects
Genetics, 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Genotype, Menarche, Trait, Cancer susceptibility, Genomics, Biology, 030304 developmental biology
Abstract

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Here, we analyse 1000-Genome reference panel imputed genotype data on up to ~370,000 women and identify 389 independent signals (all P−8) for age at menarche, a notable milestone in female pubertal development. In Icelandic data from deCODE, these signals explain ~7.4% of the population variance in age at menarche, corresponding to one quarter of the estimated heritability. We implicate over 250 genes via coding variation or associated gene expression, and demonstrate enrichment across genes active in neural tissues. We identify multiple rare variants near the imprinted genes MKRN3 and DLK1 that exhibit large effects on menarche only when paternally inherited. Disproportionate effects of variants on early or late puberty timing are observed: single variant and heritability estimates are larger for early than late puberty timing in females. The opposite pattern is seen in males, with larger estimates for late than early puberty timing. Mendelian randomization analyses indicate causal inverse associations, independent of BMI, between puberty timing and risks for breast and endometrial cancers in women, and prostate cancer in men. In aggregate, our findings reveal new complexity in the genetic regulation of puberty timing and support new causal links with adult cancer risks.

Published
2016
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38. Genome-wide meta-analyses of breast, ovarian, and prostate cancer association studies identify multiple new susceptibility loci shared by at least two cancer types

Author

Kar, SP, Beesley, J, Al Olama, AA, Michailidou, K, Tyrer, J, Kote-Jarai, ZA, Lawrenson, K, Lindstrom, S, Ramus, SJ, Thompson, DJ, Kibel, AS, Dansonka-Mieszkowska, A, Michael, A, Dieffenbach, AK, Gentry-Maharaj, A, Whittemore, AS, Wolk, A, Monteiro, A, Peixoto, A, Kierzek, A, Cox, A, Rudolph, A, Gonzalez-Neira, A, Wu, AH, Lindblom, A, Swerdlow, A, Ziogas, A, Ekici, AB, Burwinkel, B, Karlan, BY, Nordestgaard, BG, Blomqvist, C, Phelan, C, McLean, C, Pearce, CL, Vachon, C, Cybulski, C, Slavov, C, Stegmaier, C, Maier, C, Ambrosone, CB, Hogdall, CK, Teerlink, CC, Kang, D, Tessier, DC, Schaid, DJ, Stram, DO, Cramer, DW, Neal, DE, Eccles, D, Flesch-Janys, D, Velez Edwards, DR, Wokozorczyk, D, Levine, DA, Yannoukakos, D, Sawyer, EJ, Bandera, EV, Poole, EM, Goode, EL, Khusnutdinova, E, Hogdall, E, Song, F, Bruinsma, F, Heitz, F, Modugno, F, Hamdy, FC, Wiklund, F, Giles, GG, Olsson, H, Wildiers, H, and Ulmer, HU

Abstract

© 2016 American Association for Cancer Research. Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10−8 seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/ BCL2L11; rs7937840/11q12/ INCENP; rs1469713/19p13/ GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/ SMC2; rs8037137/15q26/ RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/ NSUN4; rs9375701/6q23/ L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10−5 in the three-cancer meta-analysis. SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers.

Published
2016

39. Metalloproteinase-dependent and -independent processes contribute to inhibition of breast cancer cell migration, angiogenesis and liver metastasis by a disintegrin and metalloproteinase with thrombospondin motifs-15

Author

Kelwick, R, Wagstaff, L, Decock, J, Roghi, C, Cooley, LS, Robinson, SD, Arnold, H, Gavrilović, J, Jaworski, DM, Yamamoto, K, Nagase, H, Seubert, B, Krüger, A, and Edwards, DR

Abstract

The ADAMTS proteinases are a family of secreted, matrix-associated enzymes that have diverse roles in the regulation of tissue organization and vascular homeostasis. Several of the 19 human family members have been identified as having either tumor promoting or suppressing roles. We previously demonstrated that decreased ADAMTS15 expression correlated with a worse clinical outcome in mammary carcinoma (e.g., Porter et al., Int J Cancer 2006;118:1241-7). We have explored the effects of A Disintegrin and Metalloproteinase with Thrombospondin motifs-15 (ADAMTS-15) on the behavior of MDA-MB-231 and MCF-7 breast cancer cells by stable expression of either a wild-type (wt) or metalloproteinase-inactive (E362A) protein. No effects on mammary cancer cell proliferation or apoptosis were observed for either form of ADAMTS-15. However, both forms reduced cell migration on fibronectin or laminin matrices, though motility on a Type I collagen matrix was unimpaired. Knockdown of syndecan-4 attenuated the inhibitory effects of ADAMTS-15 on cell migration. In contrast to its effects on cell migration, wt ADAMTS-15 but not the E362A inactive mutant inhibited endothelial tubulogenesis in 3D collagen gels and angiogenesis in the aortic ring assay. In experimental metastasis assays in nude mice, MDA-MB-231 cells expressing either form of ADAMTS-15 showed reduced spread to the liver, though lung colonization was enhanced for cells expressing wt ADAMTS-15. These studies indicate that extracellular ADAMTS-15 has multiple actions on tumor pathophysiology. Via modulation of cell-ECM interactions, which likely involve syndecan-4, it attenuates mammary cancer cell migration independent of its metalloproteinase activity; however, its antiangiogenic action requires catalytic functionality, and its effects on metastasis in vivo are tissue niche-dependent.

Published
2016

40. British society for matrix biology autumn meeting

Author

Sudre, L, Cheung, F, Kevorkian, L, Young, D, Darrah, C, Donell, S, Shepstone, L, Porter, S, Brockbank, S, Edwards, DR, Parker, A, Clark, I, Boubriak, O, Urban, J, Cui, Z, Tew, SR, Li, Y, Tweats, L, Hawkins, R, Hardingham, T, Green, D, Partridge, K, Leveque, I, Mann, S, and Oreffo, R

Published
2016

41. Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

Author

Eccles, SA, Aboagye, EO, Ali, S, Anderson, AS, Armes, J, Berditchevski, F, Blaydes, JP, Brennan, K, Brown, NJ, Bryant, HE, Bundred, NJ, Burchell, JM, Campbell, AM, Carroll, JS, Clarke, RB, Coles, CE, Cook, GJR, Cox, A, Curtin, NJ, Dekker, LV, Silva, IS, Duffy, SW, Easton, DF, Eccles, DM, Edwards, DR, Edwards, J, Evans, DG, Fenlon, DF, Flanagan, JM, Foster, C, Gallagher, WM, Garcia-Closas, M, Gee, JMW, Gescher, AJ, Goh, V, Groves, AM, Harvey, AJ, Harvie, M, Hennessy, BT, Hiscox, S, Holen, I, Howell, SJ, Howell, A, Hubbard, G, Hulbert-Williams, N, Hunter, MS, Jasani, B, Jones, LJ, Key, TJ, Kirwan, CC, Kong, A, Kunkler, IH, Langdon, SP, Leach, MO, Mann, DJ, Marshall, JF, Martin, LA, Martin, SG, Macdougall, JE, Miles, DW, Miller, WR, Morris, JR, Moss, SM, Mullan, P, Natrajan, R, O’Connor, JPB, O’Connor, R, Palmieri, C, Pharoah, PDP, Rakha, EA, Reed, E, Robinson, SP, Sahai, E, Saxton, JM, Schmid, P, Smalley, MJ, Speirs, V, Stein, R, Stingl, J, Streuli, CH, Tutt, ANJ, Velikova, G, Walker, RA, Watson, CJ, Williams, KJ, Young, LS, Thompson, AM, Carroll, Jason [0000-0003-3643-0080], Coles, Charlotte [0000-0003-4473-8552], Easton, Douglas [0000-0003-2444-3247], Pharoah, Paul [0000-0001-8494-732X], Watson, Christine [0000-0002-8548-5902], Apollo - University of Cambridge Repository, and Cancer Research UK

Subjects
Cancer Research, medicine.medical_specialty, ONCOLOGY DRUG DEVELOPMENT, Breast Neoplasms, Translational research, ESTROGEN-RECEPTOR-BETA, MAMMARY-GLAND DEVELOPMENT, Metastasis, Translational Research, Biomedical, RC0254, chemistry.chemical_compound, Breast cancer, QUALITY-OF-LIFE, ADJUVANT MULTINATIONAL TRIAL, Epidemiology of cancer, Animals, Humans, Medicine, Oncology & Carcinogenesis, Intensive care medicine, Translational Medical Research, Medicine(all), Gynecology, Science & Technology, TRANSGENIC MOUSE MODELS, business.industry, Research, Cancer, RANDOMIZED CONTROLLED-TRIAL, Luminespib, A300, ONCOLOGY, medicine.disease, EPITHELIAL-MESENCHYMAL TRANSITION, CIRCULATING TUMOR-CELLS, B900, Oncology, RISK PREDICTION MODEL, chemistry, Hormonal therapy, Female, Personalized medicine, business, Life Sciences & Biomedicine, 1112 Oncology And Carcinogenesis
Abstract

IntroductionBreast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice.MethodsMore than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer ‘stem’ cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account.ResultsThe 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working.ConclusionsWith resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years.

Published
2016

42. Prolonged survival in resistant myeloma after treatment with interferon—a case report and review

Author

Edwards Dr

Subjects
Male, Cancer Research, Chemotherapy, business.industry, medicine.medical_treatment, Complete remission, Combination chemotherapy, Hematology, General Medicine, Immunotherapy, Middle Aged, Oncology, Interferon, Immunopathology, Antineoplastic Combined Chemotherapy Protocols, Immunology, medicine, Humans, Interferons, Multiple Myeloma, business, After treatment, medicine.drug
Abstract

We present a case of resistant, rapidly progressive myeloma where interferon was added to combination chemotherapy. The addition of interferon produced a complete remission, which has lasted almost 4 years to date

Published
2006

43. Reducing phosphorus runoff and improving poultry production with alum

Author

Philip A. Moore, Tommy C. Daniel, and Edwards Dr

Subjects
Alum, Phosphorus, Broiler, chemistry.chemical_element, Agriculture, General Medicine, Eutrophication, Ammonia volatilization from urea, Feed conversion ratio, Poultry, Feces, chemistry.chemical_compound, chemistry, Agronomy, Soil water, Litter, Alum Compounds, Animals, Environmental science, Animal Science and Zoology, Water Pollutants, Chemical, Poultry litter
Abstract

This is a review paper on the effects of aluminum sulfate (alum) on ammonia volatilization and P runoff from poultry litter. Initially, laboratory studies were conducted that showed P solubility could be reduced in poultry litter with Al, Ca, and Fe amendments, indicating that these amendments may reduce P runoff. These results were confirmed in small plot studies in which alum applications to litter were shown to decrease P concentrations in runoff by as much as 87%, while improving tall fescue yields. Leaf tissue analyses indicated that the yield improvements were due to increased N availability, which we hypothesized was due to reduced NH3 volatilization. This result was confirmed in laboratory studies that showed that alum was one of the most effective (and cost-effective) compounds for reducing NH3 volatilization. Field trials conducted at commercial broiler farms in conjunction with the Environmental Protection Agency showed that alum additions to poultry litter lowered litter pH, particularly during the first 3 to 4 wk of each growout, which resulted in less NH3 volatilization and lower atmospheric NH3. Ammonia volatilization rates were reduced by 97% for the first 4 wk of the growout. Broilers grown on alum-treated litter were heavier than the controls (1.73 vs 1.66 kg) and had lower mortality (3.9 vs 4.2%) and better feed efficiency (1.98 vs 2.04). Electricity and propane use were lower for alum-treated houses. As a result of these economic benefits to the integrator and grower, the benefit:cost ratio of alum addition was 1.96. Phosphorus concentrations in runoff from small watersheds were 75% lower from alum-treated litter than normal litter over a 3-yr period. Long-term small plot studies on alum use have shown that alum-treated litter results in lower soil test P levels than normal litter and does not increase Al availability in soils or uptake by plants.

Published
1999

45. British society for matrix biology autumn meeting

Author

Sudre, L, Cheung, F, Kevorkian, L, Young, DA, Darrah, C, Donell, ST, Shepstone, L, Porter, S, Brockbank, S, Edwards, DR, Parker, AE, Clark, IM, Boubriak, OA, Urban, JPG, Cui, Z, Tew, SR, Li, Y, Tweats, LM, Hawkins, RE, Hardingham, TE, Green, D, Partridge, KA, Leveque, I, Mann, S, Oreffo, ROC, Ball, SG, Kielty, CM, Qin, M, Tai, G, Polak, JM, Bishop, AE, Stolzing, A, Scutt, A, Screen, HRC, Shelton, JC, Bader, DL, Lee, DA, Hall, A, Hayes, A, Brown, L, Tubo, R, Caterson, B, Blain, EJ, Gilbert, SJ, Duance, VC, Davies, L, Blain, E, Duance, V, Shengda, Z, Wu, M-H, Xu, X, Heywood, HK, Sims, T, Miot, S, Martin, I, Roughley, PJ, Soranzo, C, Pavesio, A, Hollander, AP, Yang, X, Webb, D, Blaker, J, Maquet, V, Boccaccini, AR, Cooper, C, Eves, P, Beck, AJ, Shard, AG, Gawkrodger, DJ, Mac Neil, S, Rajpar, MH, Kadler, KE, Thornton, DJ, Briggs, MD, Boot-Handford, RP, Ellis, MJ, Tai, C-C, Perera, S, Chaudhuri, JB, Callender, P, Mason, DJ, Colley, H, Mc Arthur, S, Mirmalek-Sani, SH, Roach, HI, Hanley, NA, Wilson, DI, MacIntosh, AC, Crawford, A, Hatton, PV, Wallis, G, Shah, R, Knowles, JC, Hunt, NP, Lewis, MP, Rippon, HJ, Ali, BE, De Bank, PA, Kellam, B, Shakesheff, KM, Comerford, EJ, Tarlton, JF, Wales, A, Bailey, AJ, Innes, JF, Olivier, V, Xie, Y, Descamps, M, Hivart, P, Lu, J, Hardouin, P, Anderson, V, Spiller, DG, Vaughan-Thomas, A, Eissa, SZS, Faram, T, Birch, HL, Zeugolis, D, Paul, G, Attenburrow, G, Bhadal, N, Whawell, SA, Worrall, LK, Rose, FRAJ, Bradshaw, TD, Stevens, MFG, Chuo, CB, Wiseman, MA, Phillips, JB, Brown, RA, Harrison, CA, Gossiel, F, Bullock, AJ, Blumsohn, A, Li, Z, Derham, B, Gaissmaier, C, Fritz, J, Krackhardt, T, Flesch, I, Aicher, WK, Ashammakhi, N, Liu, K-K, Yang, Y, Ahearne, M, Then, K, El Haj, A, Cheung, I, Wright, TC, Kostyuk, O, Baria, KE, Chowdhury, TT, Sharma, AM, Bomzon, Z, Kimmel, E, Knight, MM, Dickinson, S, Pittarello, L, Fish, RS, Ralphs, JR, Farjanel, J, Sève, S, Borel, A, Sommer, P, Hulmes, DJS, Whiting, CV, Dalton, SJ, Mitchell, DC, Kafienah, W, Mistry, S, Hollander, A, Cartmell, S, Magnay, J, Dobson, J, Appleby, RN, Salter, DM, Scutt, N, Rolf, CG, Barry, JJA, Nazhat, SN, Scotchford, CA, Howdle, SM, Roberts, S, Gargiulo, B, Evans, EH, Menage, J, Johnson, WEB, Eisenstein, S, Richardson, JB, Stenfeldt, C, Avery, NC, Tidswell, H, Crabtree, J, Frazer, A, Fraser, S, Wong, M, Beckett, K, Grobbelaar, A, Mudera, V, Bax, DV, Cain, SA, Humphries, MJ, Lomas, A, Oldershaw, R, Murdoch, A, Brennan, K, Redman, S, Haughton, L, Dowthwaite, G, Williams, A, Archer, CW, Esfandiari, E, Stokes, CR, Cox, TM, Evans, MJ, Bailey, M, Hayman, AR, Day, MJ, Williams, R, Evans, D, Adesida, A, Millwards-Sadler, J, Salter, D, Smith, R, Korda, M, Porter, R, Kalia, P, Wiseman, M, Blunn, G, Goodship, A, McClumpha, A, Horrocks, M, Pabbruwe, MB, Du, X, Stewart, K, Suciati, T, Lakey, RL, Pennington, CJ, Cawston, TE, Palmer, L, Tasman, C, Clare, M, Gidley, J, Sandy, J, Mansell, J, Ellis, T, Burger, F, Lauder, R, Khan, I, and Smith, M

Published
2005

47. An automated electronic method for quantifying spinning (circling) in children with autistic disorder

Author

Bracha Hs, Livingston R, Edwards Dr, Dykman K, and Adam B

Subjects
Causes of autism, Male, medicine.medical_specialty, Rotation, media_common.quotation_subject, Pilot Projects, Audiology, Motor Activity, Social Environment, Neglect, Orientation, mental disorders, medicine, Humans, In patient, Autistic Disorder, Child, Dominance, Cerebral, Spinning, Normal control, media_common, Monitoring, Physiologic, Cerebral Cortex, Group membership, Control subjects, medicine.disease, Play and Playthings, Psychiatry and Mental health, Child, Preschool, Autism, Female, Neurology (clinical), Stereotyped Behavior, Psychology, Arousal
Abstract

This pilot study examined and quantified rotational asymmetry (the tendency to turn preferentially to the right or left side). An automated device was used to measure turning (circling) in 9 children with autism and 27 normal control subjects and confirmed clinical observations of stereotypical spinning behavior in patients with autism. This behavior was significantly preferential toward the left side relative to control subjects (P = 0.0009, two-tailed). Group membership accounted for approximately 40% of variance. Although the precise causes of autism are not known, these preliminary data suggest that the spinning behavior often seen in children with neurodevelopmental disorders can be reliably measured. Furthermore, spinning in autism may most often manifest as specific right-hemispace neglect.

Published
1995

49. Clinical phenotype and molecular analysis of a three-generation family with an interstitial deletion of the short arm of chromosome 5

Author

Susanne M. Gollin, W. Wilson, Laura D Keppen, Edwards Dr, Joan Overhauser, and Jeffrey R. Sawyer

Subjects
Male, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Microcephaly, Cri du Chat Syndrome, High resolution, Trisomy, Biology, Hybrid Cells, Intellectual Disability, Muscle Hypertonia, medicine, Humans, Abnormalities, Multiple, Genetics (clinical), Genetics, Cytogenetics, Chromosome, Chromosome Mapping, DNA, medicine.disease, Phenotype, Molecular biology, Blotting, Southern, Child, Preschool, Hypertonia, Chromosomes, Human, Pair 5, Female, medicine.symptom, Chromosome Deletion, Chromosomes, Human, Pair 18
Abstract

We report on a 3-generation family with an interstitial deletion of the short arm of chromosome 5. Varied manifestations were found among the affected individuals including microcephaly, hypertonia, and micrognathia; mental retardation was common to all affected individuals. High resolution chromosome analysis was interpreted as del(5) (pter- > p14.3::p13.3- > qter). Molecular comparison of the deletion in this family with individuals with other 5p deletions suggests that the clinical findings are due specifically to the chromosomal material deleted from 5p13.

Published
1992

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