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1. Classification of variants of reduced penetrance in high-penetrance cancer susceptibility genes: Framework for genetics clinicians and clinical scientists by CanVIG-UK (Cancer Variant Interpretation Group-UK)

Author

Turnbull, C., Garrett, A., Loong, L., Choi, S., Torr, B., Allen, S., Durkie, M., Callaway, A., Drummond, J., Burghel, G.J., Robinson, R., Berry, I.R., Wallace, A.J., Eccles, D.M., Tischkowitz, M., Ellard, S., Hanson, H., Baple, E., Evans, D.G., Woodward, E., Lalloo, F., Samant, S., Lucassen, A., Znaczko, A., Shaw, A., Ansari, A., Kumar, A., Donaldson, A., Murray, A., Ross, A., Taylor-Beadling, A., Taylor, A., Innes, A., Brady, A., Kulkarni, A., Hogg, A.C., Bowden, A. Ramsay, Hadonou, A., Coad, B., McIldowie, B., Speight, B., DeSouza, B., Mullaney, B., McKenna, C., Brewer, C., Olimpio, C., Clabby, C., Crosby, C., Jenkins, C., Armstrong, C., Bowles, C., Brooks, C., Byrne, C., Maurer, C., Baralle, D., Chubb, D., Stobo, D., Moore, D., O'Sullivan, D., Donnelly, D., Randhawa, D., Halliday, D., Atkinson, E., Rauter, E., Johnston, E., Maher, E., Sofianopoulou, E., Petrides, E., McRonald, F., Pelz, F., Frayling, I., Corbett, G., Rea, G., Clouston, H., Powell, H., Williamson, H., Carley, H., Thomas, H.J.W., Tomlinson, I., Cook, J., Hoyle, J., Tellez, J., Whitworth, J., Williams, J., Murray, J., Campbell, J., Tolmie, J., Field, J., Mason, J., Burn, J., Bruty, J., Callaway, J., Grant, J., Del Rey Jimenez, J., Pagan, J., VanCampen, J., Barwell, J., Monahan, K., Tatton-Brown, K., Ong, K.R., Murphy, K., Andrews, K., Mokretar, K., Cadoo, K., Smith, K., Baker, K., Brown, K., Reay, K., McKay Bounford, K., Bradshaw, K., Russell, K., Stone, K., Snape, K., Crookes, L., Reed, L., Taggart, L., Yarram, L., Cobbold, L., Walker, L., Hawkes, L., Busby, L., Izatt, L., Kiely, L., Hughes, L., Side, L., Sarkies, L., Greenhalgh, K.-L., Shanmugasundaram, M., Duff, M., Bartlett, M., Watson, M., Owens, M., Bradford, M., Huxley, M., Slean, M., Ryten, M., Smith, M., Ahmed, M., Roberts, N., O'Brien, C., Middleton, O., Tarpey, P., Logan, P., Dean, P., May, P., Brace, P., Tredwell, R., Harrison, R., Hart, R., Kirk, R., Martin, R., Nyanhete, R., Wright, R., Davidson, R., Cleaver, R., Talukdar, S., Butler, S., Sampson, J., Ribeiro, S., Dell, S., Mackenzie, S., Hegarty, S., Albaba, S., McKee, S., Palmer-Smith, S., Heggarty, S., MacParland, S., Greville-Heygate, S., Daniels, S., Prapa, S., Abbs, S., Tennant, S., Hardy, S., MacMahon, S., McVeigh, T., Foo, T., Bedenham, T., Cranston, T., McDevitt, T., Clowes, V., Tripathi, V., McConnell, V., Woodwaer, N., Wallis, Y., Kemp, Z., Mullan, G., Pierson, L., Rainey, L., Joyce, C., Timbs, A., Reuther, A.-M., Frugtniet, B., Husher, C., Lawn, C., Corbett, C., Nocera-Jijon, D., Reay, D., Cross, E., Ryan, F., Lindsay, H., Oliver, J., Dring, J., Spiers, J., Harper, J., Ciucias, K., Connolly, L., Tsang, M., Brown, R., Shepherd, S., Begum, S., Tadiso, T., Linton-Willoughby, T., Heppell, H., Sahan, K., Worrillow, L., Allen, Z., Watt, C., Hegarty, M., Mitchell, R., Coles, R., Nickless, G., Cojocaru, E., Doal, I., Sava, F., McCarthy, C., Jeeneea, R., Goudie, D., McConachie, M., Botosneanu, S., Kavanaugh, G., Sherlaw, C., Tsoulaki, O., Forde, C., Petley, E., Jones, A.-B., Oprych, K., Pryde, S., Hyder, Z., Elkhateeb, N., Braham, R., Hanington, L., Huntley, C., Irving, R., Sadan, A., Ramos, M., Elliot, C., Wren, D., Lobo, D., McLean, J., May, D., Kearney, L., Campbell, T., Asakura, K., Alwadi, L., O’Shea, R., Gabriel, J., Chiecchio, L., Bowman, P., Sutton, L.A., Walsh, C., Cloke, V., Ucanok, D., Davies, J., Pleasance, B., Maguire, E., Whaite, A., Best, S., Westbury, S., Logan, A., Navarajasegaran, D., Bench, A., Wightman, P., Cartwright, A., Higgs, E., J.Bott, Whitehouse, H., Stevens, J., Martin, D., Dunlop, J., Thomas, S., Sau, C., Farndon, S., Coleman, N., Angelini, P., Massey, H., Rowlands, C., Garcia-Petit, C., Gillespie, K., Alder, A., Middleton, E., Cassidy, C., Orfali, N., Webb, A., Luharia, A., Walker, N., Charlton, J., Andreou, A., Peddie, J., Khan, M., Wilkinson, L., Bezuidenhout, H., Edis, M., Callard, A., Ostrowski, P., Moverley, P., Bean, K., Dunne, A., Moleirinho, A., Waller, S., Cox, K., Greensmith, L., Brittle, A., Gossan, N., Freestone, L., Shak, C., Langford, T., Clinch, Y., Livesey, H., Borland, S., Joshi, A., Wall, K., Whitworth, A., Wilsdon, A., Edgerley, K., Pugh, S., Chrysochoidi, N., Mutch, S., McMullan, C., Johnston, Y., Muraru, M., May, A., Begum, R., Smith, C., Patel, R., Bhatnagar, I., Brown, D., Willan, J., Taylor, S., Jones, K., Ramsden, C., Taiwo, O., Jaudzemaite, J., Sharmin, R., Young, L., O’Dubhshlaine, C., McSorley, L., Rodriguez, I. Abreu, Lillis, S., Alexopoulos, P., Mortensson, E., Kingham, L., Moore, R., Kosicka-Slawinska, M., Aslam, S., Wells, R., Carter, A., Warren, H., Rolf, E., Reed, H., Pearce, L., Lock, D., Ali, F., Kolozi, A., White, N., Wood, D., Hayden, C., Garrett, Alice, Allen, Sophie, Durkie, Miranda, Burghel, George J., Robinson, Rachel, Callaway, Alison, Field, Joanne, Frugtniet, Bethan, Palmer-Smith, Sheila, Grant, Jonathan, Pagan, Judith, McDevitt, Trudi, Rowlands, Charlie F., McVeigh, Terri, Hanson, Helen, and Turnbull, Clare

Published
2025
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3. Quantifying prediction of pathogenicity for within-codon concordance (PM5) using 7541 functional classifications of BRCA1 and MSH2 missense variants

Author

Samant, S., Lucassen, A., Znaczko, A., Shaw, A., Ansari, A., Kumar, A., Donaldson, A., Murray, A., Ross, A., Taylor-Beadling, A., Taylor, A., Innes, A., Brady, A., Kulkarni, A., Hogg, A.-C., Bowden, A. Ramsay, Hadonou, A., Coad, B., McIldowie, B., Speight, B., DeSouza, B., Mullaney, B., McKenna, C., Brewer, C., Olimpio, C., Clabby, C., Crosby, C., Jenkins, C., Armstrong, C., Bowles, C., Brooks, C., Byrne, C., Maurer, C., Baralle, D., Chubb, D., Stobo, D., Moore, D., O'Sullivan, D., Donnelly, D., Randhawa, D., Halliday, D., Atkinson, E., Baple, E., Rauter, E., Johnston, E., Woodward, E., Maher, E., Sofianopoulou, E., Petrides, E., Lalloo, F., McRonald, F., Pelz, F., Frayling, I., Evans, G., Corbett, G., Rea, G., Clouston, H., Powell, H., Williamson, H., Carley, H., Thomas, H.J.W., Tomlinson, I., Cook, J., Hoyle, J., Tellez, J., Whitworth, J., Williams, J., Murray, J., Campbell, J., Tolmie, J., Field, J., Mason, J., Burn, J., Bruty, J., Callaway, J., Grant, J., Del Rey Jimenez, J., Pagan, J., VanCampen, J., Barwell, J., Monahan, K., Tatton-Brown, K., Ong, K.-R., Murphy, K., Andrews, K., Mokretar, K., Cadoo, K., Smith, K., Baker, K., Brown, K., Reay, K., McKay Bounford, K., Bradshaw, K., Russell, K., Stone, K., Snape, K., Crookes, L., Reed, L., Taggart, L., Yarram, L., Cobbold, L., Walker, L., Hawkes, L., Busby, L., Izatt, L., Kiely, L., Hughes, L., Side, L., Sarkies, L., Greenhalgh, K.-L., Shanmugasundaram, M., Duff, M., Bartlett, M., Watson, M., Owens, M., Bradford, M., Huxley, M., Slean, M., Ryten, M., Smith, M., Ahmed, M., Roberts, N., O'Brien, C., Middleton, O., Tarpey, P., Logan, P., Dean, P., May, P., Brace, P., Tredwell, R., Harrison, R., Hart, R., Kirk, R., Martin, R., Nyanhete, R., Wright, R., Davidson, R., Cleaver, R., Talukdar, S., Butler, S., Sampson, J., Ribeiro, S., Dell, S., Mackenzie, S., Hegarty, S., Albaba, S., McKee, S., Palmer-Smith, S., Heggarty, S., MacParland, S., Greville-Heygate, S., Daniels, S., Prapa, S., Abbs, S., Tennant, S., Hardy, S., MacMahon, S., McVeigh, T., Foo, T., Bedenham, T., Cranston, T., McDevitt, T., Clowes, V., Tripathi, V., McConnell, V., Woodwaer, N., Wallis, Y., Kemp, Z., Mullan, G., Pierson, L., Rainey, L., Joyce, C., Timbs, A., Reuther, A.-M., Frugtniet, B., Husher, C., Lawn, C., Corbett, C., Nocera-Jijon, D., Reay, D., Cross, E., Ryan, F., Lindsay, H., Oliver, J., Dring, J., Spiers, J., Harper, J., Ciucias, K., Connolly, L., Tsang, M., Brown, R., Shepherd, S., Begum, S., Tadiso, T., Linton-Willoughby, T., Heppell, H., Sahan, K., Worrillow, L., Allen, Z., Barlett, M., Watt, C., Hegarty, M., Loong, Lucy, Cubuk, Cankut, Choi, Subin, Allen, Sophie, Torr, Beth, Garrett, Alice, Loveday, Chey, Durkie, Miranda, Callaway, Alison, Burghel, George J., Drummond, James, Robinson, Rachel, Berry, Ian R., Wallace, Andrew, Eccles, Diana M., Tischkowitz, Marc, Ellard, Sian, Ware, James S., Hanson, Helen, and Turnbull, Clare

Published
2022
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17. The crows

Author

Middleton, O. E.

Published
1967

19. Beginnings

Author

Middleton, O. E.

Published
1967

21. Deportee

Author

Middleton, O. E.

Published
1949

22. Savviness of prey to introduced predators.

Author

Wallach, AD, Ramp, D, Benítez-López, A, Wooster, EIF, Carroll, S, Carthey, AJR, Rogers, EIE, Middleton, O, Zawada, KJA, Svenning, J-C, Avidor, E, Lundgren, E, Wallach, AD, Ramp, D, Benítez-López, A, Wooster, EIF, Carroll, S, Carthey, AJR, Rogers, EIE, Middleton, O, Zawada, KJA, Svenning, J-C, Avidor, E, and Lundgren, E

Abstract

The prey naivety hypothesis posits that prey are vulnerable to introduced predators because many generations in slow gradual coevolution are needed for appropriate avoidance responses to develop. It predicts that prey will be more responsive to native than introduced predators and less responsive to introduced predators that differ substantially from native predators and from those newly established. To test these predictions, we conducted a global meta-analysis of studies that measured the wariness responses of small mammals to the scent of sympatric mammalian mesopredators. We identified 26 studies that met our selection criteria. These studies comprised 134 experiments reporting on the responses of 36 small mammal species to the scent of six introduced mesopredators and 12 native mesopredators. For each introduced mesopredator, we measured their phylogenetic and functional distance to local native mesopredators and the number of years sympatric with their prey. We used predator and prey body mass as a measure of predation risk. Globally, small mammals were similarly wary of the scent of native and introduced mesopredators; phylogenetic and functional distance between introduced mesopredators and closest native mesopredators had no effect on wariness; and wariness was unrelated to the number of prey generations, or years, since first contact with introduced mesopredators. Small mammal wariness was associated with predator-prey body mass ratio, regardless of the nativity. The one thing animals do not seem to recognize is whether their predators are native.

Published
2023

24. Quantifying prediction of pathogenicity for within-codon concordance (PM5) using 7541 functional classifications of BRCA1 and MSH2 missense variants

Author

Loong, Lucy, primary, Cubuk, Cankut, additional, Choi, Subin, additional, Allen, Sophie, additional, Torr, Beth, additional, Garrett, Alice, additional, Loveday, Chey, additional, Durkie, Miranda, additional, Callaway, Alison, additional, Burghel, George J., additional, Drummond, James, additional, Robinson, Rachel, additional, Berry, Ian R., additional, Wallace, Andrew, additional, Eccles, Diana M., additional, Tischkowitz, Marc, additional, Ellard, Sian, additional, Ware, James S., additional, Hanson, Helen, additional, Turnbull, Clare, additional, Samant, S., additional, Lucassen, A., additional, Znaczko, A., additional, Shaw, A., additional, Ansari, A., additional, Kumar, A., additional, Donaldson, A., additional, Murray, A., additional, Ross, A., additional, Taylor-Beadling, A., additional, Taylor, A., additional, Innes, A., additional, Brady, A., additional, Kulkarni, A., additional, Hogg, A.-C., additional, Bowden, A. Ramsay, additional, Hadonou, A., additional, Coad, B., additional, McIldowie, B., additional, Speight, B., additional, DeSouza, B., additional, Mullaney, B., additional, McKenna, C., additional, Brewer, C., additional, Olimpio, C., additional, Clabby, C., additional, Crosby, C., additional, Jenkins, C., additional, Armstrong, C., additional, Bowles, C., additional, Brooks, C., additional, Byrne, C., additional, Maurer, C., additional, Baralle, D., additional, Chubb, D., additional, Stobo, D., additional, Moore, D., additional, O'Sullivan, D., additional, Donnelly, D., additional, Randhawa, D., additional, Halliday, D., additional, Atkinson, E., additional, Baple, E., additional, Rauter, E., additional, Johnston, E., additional, Woodward, E., additional, Maher, E., additional, Sofianopoulou, E., additional, Petrides, E., additional, Lalloo, F., additional, McRonald, F., additional, Pelz, F., additional, Frayling, I., additional, Evans, G., additional, Corbett, G., additional, Rea, G., additional, Clouston, H., additional, Powell, H., additional, Williamson, H., additional, Carley, H., additional, Thomas, H.J.W., additional, Tomlinson, I., additional, Cook, J., additional, Hoyle, J., additional, Tellez, J., additional, Whitworth, J., additional, Williams, J., additional, Murray, J., additional, Campbell, J., additional, Tolmie, J., additional, Field, J., additional, Mason, J., additional, Burn, J., additional, Bruty, J., additional, Callaway, J., additional, Grant, J., additional, Del Rey Jimenez, J., additional, Pagan, J., additional, VanCampen, J., additional, Barwell, J., additional, Monahan, K., additional, Tatton-Brown, K., additional, Ong, K.-R., additional, Murphy, K., additional, Andrews, K., additional, Mokretar, K., additional, Cadoo, K., additional, Smith, K., additional, Baker, K., additional, Brown, K., additional, Reay, K., additional, McKay Bounford, K., additional, Bradshaw, K., additional, Russell, K., additional, Stone, K., additional, Snape, K., additional, Crookes, L., additional, Reed, L., additional, Taggart, L., additional, Yarram, L., additional, Cobbold, L., additional, Walker, L., additional, Hawkes, L., additional, Busby, L., additional, Izatt, L., additional, Kiely, L., additional, Hughes, L., additional, Side, L., additional, Sarkies, L., additional, Greenhalgh, K.-L., additional, Shanmugasundaram, M., additional, Duff, M., additional, Bartlett, M., additional, Watson, M., additional, Owens, M., additional, Bradford, M., additional, Huxley, M., additional, Slean, M., additional, Ryten, M., additional, Smith, M., additional, Ahmed, M., additional, Roberts, N., additional, O'Brien, C., additional, Middleton, O., additional, Tarpey, P., additional, Logan, P., additional, Dean, P., additional, May, P., additional, Brace, P., additional, Tredwell, R., additional, Harrison, R., additional, Hart, R., additional, Kirk, R., additional, Martin, R., additional, Nyanhete, R., additional, Wright, R., additional, Davidson, R., additional, Cleaver, R., additional, Talukdar, S., additional, Butler, S., additional, Sampson, J., additional, Ribeiro, S., additional, Dell, S., additional, Mackenzie, S., additional, Hegarty, S., additional, Albaba, S., additional, McKee, S., additional, Palmer-Smith, S., additional, Heggarty, S., additional, MacParland, S., additional, Greville-Heygate, S., additional, Daniels, S., additional, Prapa, S., additional, Abbs, S., additional, Tennant, S., additional, Hardy, S., additional, MacMahon, S., additional, McVeigh, T., additional, Foo, T., additional, Bedenham, T., additional, Cranston, T., additional, McDevitt, T., additional, Clowes, V., additional, Tripathi, V., additional, McConnell, V., additional, Woodwaer, N., additional, Wallis, Y., additional, Kemp, Z., additional, Mullan, G., additional, Pierson, L., additional, Rainey, L., additional, Joyce, C., additional, Timbs, A., additional, Reuther, A.-M., additional, Frugtniet, B., additional, Husher, C., additional, Lawn, C., additional, Corbett, C., additional, Nocera-Jijon, D., additional, Reay, D., additional, Cross, E., additional, Ryan, F., additional, Lindsay, H., additional, Oliver, J., additional, Dring, J., additional, Spiers, J., additional, Harper, J., additional, Ciucias, K., additional, Connolly, L., additional, Tsang, M., additional, Brown, R., additional, Shepherd, S., additional, Begum, S., additional, Tadiso, T., additional, Linton-Willoughby, T., additional, Heppell, H., additional, Sahan, K., additional, Worrillow, L., additional, Allen, Z., additional, Barlett, M., additional, Watt, C., additional, and Hegarty, M., additional

Published
2022
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25. Classification of variants of reduced penetrance in high-penetrance cancer susceptibility genes: Framework for genetics clinicians and clinical scientists by CanVIG-UK (Cancer Variant Interpretation Group-UK)

Author

Garrett, Alice, Allen, Sophie, Durkie, Miranda, Burghel, George J., Robinson, Rachel, Callaway, Alison, Field, Joanne, Frugtniet, Bethan, Palmer-Smith, Sheila, Grant, Jonathan, Pagan, Judith, McDevitt, Trudi, Rowlands, Charlie F., McVeigh, Terri, Hanson, Helen, Turnbull, Clare, Turnbull, C., Garrett, A., Loong, L., Choi, S., Torr, B., Allen, S., Durkie, M., Callaway, A., Drummond, J., Burghel, G.J., Robinson, R., Berry, I.R., Wallace, A.J., Eccles, D.M., Tischkowitz, M., Ellard, S., Hanson, H., Baple, E., Evans, D.G., Woodward, E., Lalloo, F., Samant, S., Lucassen, A., Znaczko, A., Shaw, A., Ansari, A., Kumar, A., Donaldson, A., Murray, A., Ross, A., Taylor-Beadling, A., Taylor, A., Innes, A., Brady, A., Kulkarni, A., Hogg, A.C., Bowden, A. Ramsay, Hadonou, A., Coad, B., McIldowie, B., Speight, B., DeSouza, B., Mullaney, B., McKenna, C., Brewer, C., Olimpio, C., Clabby, C., Crosby, C., Jenkins, C., Armstrong, C., Bowles, C., Brooks, C., Byrne, C., Maurer, C., Baralle, D., Chubb, D., Stobo, D., Moore, D., O'Sullivan, D., Donnelly, D., Randhawa, D., Halliday, D., Atkinson, E., Rauter, E., Johnston, E., Maher, E., Sofianopoulou, E., Petrides, E., McRonald, F., Pelz, F., Frayling, I., Corbett, G., Rea, G., Clouston, H., Powell, H., Williamson, H., Carley, H., Thomas, H.J.W., Tomlinson, I., Cook, J., Hoyle, J., Tellez, J., Whitworth, J., Williams, J., Murray, J., Campbell, J., Tolmie, J., Field, J., Mason, J., Burn, J., Bruty, J., Callaway, J., Grant, J., Del Rey Jimenez, J., Pagan, J., VanCampen, J., Barwell, J., Monahan, K., Tatton-Brown, K., Ong, K.R., Murphy, K., Andrews, K., Mokretar, K., Cadoo, K., Smith, K., Baker, K., Brown, K., Reay, K., McKay Bounford, K., Bradshaw, K., Russell, K., Stone, K., Snape, K., Crookes, L., Reed, L., Taggart, L., Yarram, L., Cobbold, L., Walker, L., Walker, L., Hawkes, L., Busby, L., Izatt, L., Kiely, L., Hughes, L., Side, L., Sarkies, L., Greenhalgh, K.-L., Shanmugasundaram, M., Duff, M., Bartlett, M., Watson, M., Owens, M., Bradford, M., Huxley, M., Slean, M., Ryten, M., Smith, M., Ahmed, M., Roberts, N., O'Brien, C., Middleton, O., Tarpey, P., Logan, P., Dean, P., May, P., Brace, P., Tredwell, R., Harrison, R., Hart, R., Kirk, R., Martin, R., Nyanhete, R., Wright, R., Martin, R., Davidson, R., Cleaver, R., Talukdar, S., Butler, S., Sampson, J., Ribeiro, S., Dell, S., Mackenzie, S., Hegarty, S., Albaba, S., McKee, S., Palmer-Smith, S., Heggarty, S., MacParland, S., Greville-Heygate, S., Daniels, S., Prapa, S., Abbs, S., Tennant, S., Hardy, S., MacMahon, S., McVeigh, T., Foo, T., Bedenham, T., Cranston, T., McDevitt, T., Clowes, V., Tripathi, V., McConnell, V., Woodwaer, N., Wallis, Y., Kemp, Z., Mullan, G., Pierson, L., Rainey, L., Joyce, C., Timbs, A., Reuther, A.-M., Frugtniet, B., DeSouza, B., Husher, C., Lawn, C., Corbett, C., Nocera-Jijon, D., Reay, D., Cross, E., Ryan, F., Lindsay, H., Oliver, J., Dring, J., Spiers, J., Harper, J., Ciucias, K., Connolly, L., Tsang, M., Brown, R., Shepherd, S., Begum, S., Daniels, S., Tadiso, T., Linton-Willoughby, T., Heppell, H., Sahan, K., Worrillow, L., Allen, Z., Watt, C., Hegarty, M., Mitchell, R., Coles, R., Nickless, G., Cojocaru, E., Doal, I., Sava, F., McCarthy, C., Jeeneea, R., Goudie, D., McConachie, M., Botosneanu, S., Kavanaugh, G., Russell, K., Sherlaw, C., Tsoulaki, O., Forde, C., Petley, E., Jones, A.-B., Oprych, K., Pryde, S., Hyder, Z., Elkhateeb, N., Braham, R., Hanington, L., Huntley, C., Irving, R., Sadan, A., Ramos, M., Elliot, C., Wren, D., Lobo, D., McLean, J., May, D., Kearney, L., Campbell, T., Asakura, K., Alwadi, L., O’Shea, R., Gabriel, J., Chiecchio, L., Bowman, P., Sutton, L.A., Walsh, C., Cloke, V., Ucanok, D., Davies, J., Pleasance, B., Maguire, E., Whaite, A., Best, S., Westbury, S., Logan, A., Navarajasegaran, D., Bench, A., Wightman, P., Cartwright, A., Higgs, E., J.Bott, Whitehouse, H., Stevens, J., Martin, D., Dunlop, J., Thomas, S., Sau, C., Farndon, S., Coleman, N., Angelini, P., Duff, M., Massey, H., Rowlands, C., Garcia-Petit, C., Gillespie, K., Alder, A., Middleton, E., Cassidy, C., Orfali, N., Webb, A., Luharia, A., Walker, N., Charlton, J., Andreou, A., Peddie, J., Khan, M., Wilkinson, L., Bezuidenhout, H., Edis, M., Callard, A., Ostrowski, P., Moverley, P., Bean, K., Dunne, A., Moleirinho, A., Waller, S., Cox, K., Greensmith, L., Brittle, A., Gossan, N., Freestone, L., Shak, C., Langford, T., Clinch, Y., Livesey, H., Borland, S., Joshi, A., Wall, K., Whitworth, A., Wilsdon, A., Edgerley, K., Pugh, S., Chrysochoidi, N., Mutch, S., McMullan, C., Johnston, Y., Muraru, M., May, A., Begum, R., Smith, C., Patel, R., Bhatnagar, I., Taylor, A., Brown, D., Willan, J., Taylor, S., Jones, K., Cox, K., Ramsden, C., Taiwo, O., Jaudzemaite, J., Sharmin, R., Young, L., O’Dubhshlaine, C., McSorley, L., Rodriguez, I. Abreu, Lillis, S., Alexopoulos, P., Mortensson, E., Kingham, L., Moore, R., Kosicka-Slawinska, M., Aslam, S., Wells, R., Carter, A., Warren, H., Rolf, E., Reed, H., Pearce, L., Lock, D., Ali, F., Kolozi, A., White, N., Wood, D., and Hayden, C.

Abstract

Current practice is to report and manage likely pathogenic/pathogenic variants in a given cancer susceptibility gene as though having equivalent penetrance, despite increasing evidence of intervariant variability in risk associations. Using existing variant interpretation approaches, largely based on full-penetrance models, variants in which reduced penetrance is suspected may be classified inconsistently and/or as variants of uncertain significance. We aimed to develop a national consensus approach for such variants within the Cancer Variant Interpretation Group UK (CanVIG-UK) multidisciplinary network.

Published
2025
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26. Correction to Supporting Information for Lundgren et al., Introduced herbivores restore Late Pleistocene ecological functions

Author

Lundgren E, Ramp D, Rowan J, Middleton O, Schowanek SD, Sanisidro O, Carroll SP, Davis M, Sandom CJ, Svenning J-C, and Wallach A

Abstract

© 2020 National Academy of Sciences. All rights reserved. The authors note that Dataset S1 was published without complete presence/absence information per species. In addition, references 72, 73, 77, 85, 98, 100, 101, 103, 109, 112, 117, 119, 121, 122, 126, 129, 131, and 324 were inadvertently omitted from the SI Appendix references list. The SI Appendix and Dataset S1 have been corrected online.

Published
2020

27. Functional traits of the world’s late Quaternary large-bodied avian and mammalian herbivores

Author

Lundgren, EJ, Schowanek, SD, Rowan, J, Middleton, O, Pedersen, RØ, Wallach, AD, Ramp, D, Davis, M, Sandom, CJ, Svenning, J-C, Lundgren, EJ, Schowanek, SD, Rowan, J, Middleton, O, Pedersen, RØ, Wallach, AD, Ramp, D, Davis, M, Sandom, CJ, and Svenning, J-C

Abstract

Prehistoric and recent extinctions of large-bodied terrestrial herbivores had significant and lasting impacts on Earth’s ecosystems due to the loss of their distinct trait combinations. The world’s surviving large-bodied avian and mammalian herbivores remain among the most threatened taxa. As such, a greater understanding of the ecological impacts of large herbivore losses is increasingly important. However, comprehensive and ecologically-relevant trait datasets for extinct and extant herbivores are lacking. Here, we present HerbiTraits, a comprehensive functional trait dataset for all late Quaternary terrestrial avian and mammalian herbivores ≥10 kg (545 species). HerbiTraits includes key traits that influence how herbivores interact with ecosystems, namely body mass, diet, fermentation type, habitat use, and limb morphology. Trait data were compiled from 557 sources and comprise the best available knowledge on late Quaternary large-bodied herbivores. HerbiTraits provides a tool for the analysis of herbivore functional diversity both past and present and its effects on Earth’s ecosystems.

Published
2021

28. Reintroducing extirpated herbivores could partially reverse the late Quaternary decline of large and grazing species

Author

Schowanek, SD, Davis, M, Lundgren, EJ, Middleton, O, Rowan, J, Pedersen, R, Ramp, D, Sandom, CJ, Svenning, JC, Schowanek, SD, Davis, M, Lundgren, EJ, Middleton, O, Rowan, J, Pedersen, R, Ramp, D, Sandom, CJ, and Svenning, JC

Abstract

Aim: Reinstating large, native herbivores is an essential component of ecological restoration efforts, as these taxa can be important drivers of ecological processes. However, many herbivore species have gone globally or regionally extinct during the last 50,000 years, leaving simplified herbivore assemblages and trophically downgraded ecosystems. Here, we discuss to what extent trophic rewilding can undo these changes by reinstating native herbivores. Location: Global. Time period: We report functional trait changes from the Late Pleistocene to the present, and estimated trait changes under future scenarios. Major taxa studied: Wild, large (≥ 10 kg), terrestrial, mammalian herbivores. Methods: We use a functional trait dataset containing all late Quaternary large herbivores ≥ 10 kg to look at changes in the body mass and diet composition of herbivore assemblages, a proxy for species’ ecological effects. First, we assess how these traits have changed from the Late Pleistocene to the present. Next, we quantify how the current body mass and diet composition would change if all extant, wild herbivores were restored to their native ranges (and if no functional replacements were used), exploring scenarios with different baselines. Results: Defaunation has primarily removed large and grazing herbivores. Reinstating extant herbivores across their native ranges would reverse these changes, especially when reinstating them to their prehistoric distributions. It would partially restore herbivore body mass and diet composition to pre-anthropogenic conditions. However, in the absence of complementary interventions (e.g., introducing functional replacements), many herbivore assemblages would remain down-sized and browser dominated, relative to pre-anthropogenic conditions. Main conclusions: Many terrestrial herbivore assemblages—and hence ecosystems—would remain trophically downgraded, even after bringing back all extant, native herbivores. Therefore, complementary interventions

Published
2021

31. Introduced herbivores restore Late Pleistocene ecological functions

Author

Lundgren EJ, Ramp D, Rowan J, Middleton O, Schowanek SD, Sanisidro O, Carroll SP, Davis M, Sandom CJ, Svenning J-C, and Wallach AD

Subjects
Mammals, Animals, Humans, Biodiversity, Herbivory, Extinction, Biological, Introduced Species, Biological Evolution, Ecosystem
Abstract

Large-bodied mammalian herbivores dominated Earth’s terrestrial ecosystems for several million years before undergoing substantial extinctions and declines during the Late Pleistocene (LP) due to prehistoric human impacts. The decline of large herbivores led to widespread ecological changes due to the loss of their ecological functions, as driven by their unique combinations of traits. However, recently, humans have significantly increased herbivore species richness through introductions in many parts of the world, potentially counteracting LP losses. Here, we assessed the extent to which introduced herbivore species restore lost—or contribute novel—functions relative to preextinction LP assemblages. We constructed multidimensional trait spaces using a trait database for all extant and extinct mammalian herbivores ≥10 kg known from the earliest LP (∼130,000 ybp) to the present day. Extinction-driven contractions of LP trait space have been offset through introductions by ∼39% globally. Analysis of trait space overlap reveals that assemblages with introduced species are overall more similar to those of the LP than native-only assemblages. This is because 64% of introduced species are more similar to extinct rather than extant species within their respective continents. Many introduced herbivores restore trait combinations that have the capacity to influence ecosystem processes, such as wildfire and shrub expansion in drylands. Although introduced species have long been a source of contention, our findings indicate that they may, in part, restore ecological functions reflective of the past several million years before widespread human-driven extinctions.

Published
2020

32. Trophic rewilding presents regionally specific opportunities for mitigating climate change

Author

Sandom CJ, Middleton O, Lundgren E, Rowan J, Schowanek SD, Svenning J-C, and Faurby S

Subjects
Evolutionary Biology, 06 Biological Sciences, 11 Medical and Health Sciences
Abstract

Large-bodied mammalian herbivores can influence processes that exacerbate or mitigate climate change. Herbivore impacts are, in turn, influenced by predators that place top-down forcing on prey species within a given body size range. Here, we explore how the functional composition of terrestrial large-herbivore and -carnivore guilds varies between three mammal distribution scenarios: Present-Natural, Current-Day and Extant-Native Trophic (ENT) Rewilding. Considering the effects of herbivore species weakly influenced by top-down forcing, we quantify the relative influence keystone large-herbivore guilds have on methane emissions, woody vegetation expansion, fire dynamics, large-seed dispersal, and nitrogen and phosphorus transport potential. We find strong regional differences in the number of herbivores under weak top-down regulation between our three scenarios, with important implications for how they will influence climate change relevant processes. Under the Present-Natural non-ruminant, megaherbivore, browsers were a particularly important guild across much of the world. Megaherbivore extinction and range contraction and the arrival of livestock mean large, ruminant, grazers have become more dominant. ENT Rewilding can restore the Afrotropics and the Indo-Malay realm to the Present-Natural benchmark, but causes top-down forcing of the largest herbivores to become commonplace elsewhere. ENT Rewilding will reduce methane emissions, but does not maximize natural climate solution potential. This article is part of the theme issue 'Climate change and ecosystems: threats, opportunities and solutions'.

Published
2020

33. Quantifying prediction of pathogenicity for within-codon concordance (PM5) using 7541 functional classifications of BRCA1and MSH2missense variants

Author

Loong, Lucy, Cubuk, Cankut, Choi, Subin, Allen, Sophie, Torr, Beth, Garrett, Alice, Loveday, Chey, Durkie, Miranda, Callaway, Alison, Burghel, George J., Drummond, James, Robinson, Rachel, Berry, Ian R., Wallace, Andrew, Eccles, Diana M., Tischkowitz, Marc, Ellard, Sian, Ware, James S., Hanson, Helen, Turnbull, Clare, Samant, S., Lucassen, A., Znaczko, A., Shaw, A., Ansari, A., Kumar, A., Donaldson, A., Murray, A., Ross, A., Taylor-Beadling, A., Taylor, A., Innes, A., Brady, A., Kulkarni, A., Hogg, A.-C., Bowden, A. Ramsay, Hadonou, A., Coad, B., McIldowie, B., Speight, B., DeSouza, B., Mullaney, B., McKenna, C., Brewer, C., Olimpio, C., Clabby, C., Crosby, C., Jenkins, C., Armstrong, C., Bowles, C., Brooks, C., Byrne, C., Maurer, C., Baralle, D., Chubb, D., Stobo, D., Moore, D., O'Sullivan, D., Donnelly, D., Randhawa, D., Halliday, D., Atkinson, E., Baple, E., Rauter, E., Johnston, E., Woodward, E., Maher, E., Sofianopoulou, E., Petrides, E., Lalloo, F., McRonald, F., Pelz, F., Frayling, I., Evans, G., Corbett, G., Rea, G., Clouston, H., Powell, H., Williamson, H., Carley, H., Thomas, H.J.W., Tomlinson, I., Cook, J., Hoyle, J., Tellez, J., Whitworth, J., Williams, J., Murray, J., Campbell, J., Tolmie, J., Field, J., Mason, J., Burn, J., Bruty, J., Callaway, J., Grant, J., Del Rey Jimenez, J., Pagan, J., VanCampen, J., Barwell, J., Monahan, K., Tatton-Brown, K., Ong, K.-R., Murphy, K., Andrews, K., Mokretar, K., Cadoo, K., Smith, K., Baker, K., Brown, K., Reay, K., McKay Bounford, K., Bradshaw, K., Russell, K., Stone, K., Snape, K., Crookes, L., Reed, L., Taggart, L., Yarram, L., Cobbold, L., Walker, L., Walker, L., Hawkes, L., Busby, L., Izatt, L., Kiely, L., Hughes, L., Side, L., Sarkies, L., Greenhalgh, K.-L., Shanmugasundaram, M., Duff, M., Bartlett, M., Watson, M., Owens, M., Bradford, M., Huxley, M., Slean, M., Ryten, M., Smith, M., Ahmed, M., Roberts, N., O'Brien, C., Middleton, O., Tarpey, P., Logan, P., Dean, P., May, P., Brace, P., Tredwell, R., Harrison, R., Hart, R., Kirk, R., Martin, R., Nyanhete, R., Wright, R., Martin, R., Davidson, R., Cleaver, R., Talukdar, S., Butler, S., Sampson, J., Ribeiro, S., Dell, S., Mackenzie, S., Hegarty, S., Albaba, S., McKee, S., Palmer-Smith, S., Heggarty, S., MacParland, S., Greville-Heygate, S., Daniels, S., Prapa, S., Abbs, S., Tennant, S., Hardy, S., MacMahon, S., McVeigh, T., Foo, T., Bedenham, T., Cranston, T., McDevitt, T., Clowes, V., Tripathi, V., McConnell, V., Woodwaer, N., Wallis, Y., Kemp, Z., Mullan, G., Pierson, L., Rainey, L., Joyce, C., Timbs, A., Reuther, A.-M., Frugtniet, B., DeSouza, B., Husher, C., Lawn, C., Corbett, C., Nocera-Jijon, D., Reay, D., Cross, E., Ryan, F., Lindsay, H., Oliver, J., Dring, J., Spiers, J., Harper, J., Ciucias, K., Connolly, L., Tsang, M., Brown, R., Shepherd, S., Begum, S., Daniels, S., Tadiso, T., Linton-Willoughby, T., Heppell, H., Sahan, K., Worrillow, L., Allen, Z., Barlett, M., Watt, C., and Hegarty, M.

Abstract

Conditions and thresholds applied for evidence weighting of within-codon concordance (PM5) for pathogenicity vary widely between laboratories and expert groups. Because of the sparseness of available clinical classifications, there is little evidence for variation in practice.

Published
2022
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35. Bonding machine for forming a solar array strip

Author

Costogue, E. N, Downing, R. G, Middleton, O, Mueller, R. L, Yasui, R. K, Cairo, F. J, and Person, J. K

Subjects
Energy Production And Conversion
Abstract

A machine is described for attaching solar cells to a flexable substrate on which printed circuitry has been deposited. The strip is fed through: (1) a station in which solar cells are elevated into engagement with solder pads for the printed circuitry and thereafter heated by an infrared lamp; (2) a station at which flux and solder residue is removed; (3) a station at which electrical performance of the soldered cells is determined; (4) a station at which an encapsulating resin is deposited on the cells; (5) a station at which the encapsulated solar cells are examined for electrical performance; and (6) a final station at which the resulting array is wound on a takeup drum.

Published
1979

38. The Loners.

Author

MIDDLETON, O. E.

Subjects
WOMEN
Published
2008

39. Letters.

Author

Werry, John Scott, Riminton, John, Lee, Chris, Middleton, O. E., Morris, M., Young, Kevin, Dino, Bob, Morrison, Pat, Cave, Mervyn, Adams, David, Musker, D. M., and Hanna, Kate

Abstract

Several letters to the editor are presented in response to the articles in previous issues including "Save it for later," in the November 17, 2007 issue, plea for logical spelling by Allan Campbell in the November 10, 2007 issue and development proposal of the Central Plains Water irrigation by Dave Hansfold in the November 3, 2007 issue.

Published
2007

40. CÆSAR, KING EDWARD'S DOG.

Author

Middleton, O.

Subjects
CAESAR, King Edward's Dog (Poem), MIDDLETON, O.
Abstract

The poem "CÆsar, King Edward's Dog," by O. Middleton is presented. First Line: No deeper, truer love could spring; Last Line: To reach the spirit of the king.

Published
1916

41. Savviness of prey to introduced predators.

Author

Wallach AD, Ramp D, Benítez-López A, Wooster EIF, Carroll S, Carthey AJR, Rogers EIE, Middleton O, Zawada KJA, Svenning JC, Avidor E, and Lundgren E

Subjects
Animals, Phylogeny, Mammals, Predatory Behavior physiology, Introduced Species, Food Chain, Conservation of Natural Resources
Abstract

The prey naivety hypothesis posits that prey are vulnerable to introduced predators because many generations in slow gradual coevolution are needed for appropriate avoidance responses to develop. It predicts that prey will be more responsive to native than introduced predators and less responsive to introduced predators that differ substantially from native predators and from those newly established. To test these predictions, we conducted a global meta-analysis of studies that measured the wariness responses of small mammals to the scent of sympatric mammalian mesopredators. We identified 26 studies that met our selection criteria. These studies comprised 134 experiments reporting on the responses of 36 small mammal species to the scent of six introduced mesopredators and 12 native mesopredators. For each introduced mesopredator, we measured their phylogenetic and functional distance to local native mesopredators and the number of years sympatric with their prey. We used predator and prey body mass as a measure of predation risk. Globally, small mammals were similarly wary of the scent of native and introduced mesopredators; phylogenetic and functional distance between introduced mesopredators and closest native mesopredators had no effect on wariness; and wariness was unrelated to the number of prey generations, or years, since first contact with introduced mesopredators. Small mammal wariness was associated with predator-prey body mass ratio, regardless of the nativity. The one thing animals do not seem to recognize is whether their predators are native., (© 2022 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Published
2023
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42. Collapse of terrestrial mammal food webs since the Late Pleistocene.

Author

Fricke EC, Hsieh C, Middleton O, Gorczynski D, Cappello CD, Sanisidro O, Rowan J, Svenning JC, and Beaudrot L

Subjects
Animals, Deep Learning, Humans, Mammals, Predatory Behavior, Anthropogenic Effects, Extinction, Biological, Food Chain
Abstract

Food webs influence ecosystem diversity and functioning. Contemporary defaunation has reduced food web complexity, but simplification caused by past defaunation is difficult to reconstruct given the sparse paleorecord of predator-prey interactions. We identified changes to terrestrial mammal food webs globally over the past ~130,000 years using extinct and extant mammal traits, geographic ranges, observed predator-prey interactions, and deep learning models. Food webs underwent steep regional declines in complexity through loss of food web links after the arrival and expansion of human populations. We estimate that defaunation has caused a 53% decline in food web links globally. Although extinctions explain much of this effect, range losses for extant species degraded food webs to a similar extent, highlighting the potential for food web restoration via extant species recovery.

Published
2022
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43. Functional traits of the world's late Quaternary large-bodied avian and mammalian herbivores.

Author

Lundgren EJ, Schowanek SD, Rowan J, Middleton O, Pedersen RØ, Wallach AD, Ramp D, Davis M, Sandom CJ, and Svenning JC

Subjects
Animals, Ecosystem, Birds, Herbivory, Mammals
Abstract

Prehistoric and recent extinctions of large-bodied terrestrial herbivores had significant and lasting impacts on Earth's ecosystems due to the loss of their distinct trait combinations. The world's surviving large-bodied avian and mammalian herbivores remain among the most threatened taxa. As such, a greater understanding of the ecological impacts of large herbivore losses is increasingly important. However, comprehensive and ecologically-relevant trait datasets for extinct and extant herbivores are lacking. Here, we present HerbiTraits, a comprehensive functional trait dataset for all late Quaternary terrestrial avian and mammalian herbivores ≥10 kg (545 species). HerbiTraits includes key traits that influence how herbivores interact with ecosystems, namely body mass, diet, fermentation type, habitat use, and limb morphology. Trait data were compiled from 557 sources and comprise the best available knowledge on late Quaternary large-bodied herbivores. HerbiTraits provides a tool for the analysis of herbivore functional diversity both past and present and its effects on Earth's ecosystems.

Published
2021
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45. National Association of Medical Examiners position paper: Recommendations for the investigation and certification of deaths in people with epilepsy.

Author

Middleton O, Atherton D, Bundock E, Donner E, Friedman D, Hesdorffer D, Jarrell H, McCrillis A, Mena OJ, Morey M, Thurman D, Tian N, Tomson T, Tseng Z, White S, Wright C, and Devinsky O

Subjects
Epilepsy diagnosis, Humans, United States epidemiology, Coroners and Medical Examiners standards, Death Certificates, Death, Sudden epidemiology, Epilepsy mortality
Abstract

Sudden unexpected death of an individual with epilepsy can pose a challenge to death investigators, as most deaths are unwitnessed, and the individual is commonly found dead in bed. Anatomic findings (eg, tongue/lip bite) are commonly absent and of varying specificity, thereby limiting the evidence to implicate epilepsy as a cause of or contributor to death. Thus it is likely that death certificates significantly underrepresent the true number of deaths in which epilepsy was a factor. To address this, members of the National Association of Medical Examiners, North American SUDEP Registry, Epilepsy Foundation SUDEP Institute, American Epilepsy Society, and the Centers for Disease Control and Prevention constituted an expert panel to generate evidence-based recommendations for the practice of death investigation and autopsy, toxicological analysis, interpretation of autopsy and toxicology findings, and death certification to improve the precision of death certificate data available for public health surveillance of epilepsy-related deaths. The recommendations provided in this paper are intended to assist medical examiners, coroners, and death investigators when a sudden unexpected death in a person with epilepsy is encountered., (© 2018 National Association of Medical Examiners. This paper has been simultaneously published in Epilepsia. Volume 59, #3 and Academic Forensic Pathology: The Official Publication of the National Association of Medical Examiners, Volume 8, #1.)

Published
2018
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46. Heroin-related Deaths from the Hennepin County Medical Examiner's Office from 2004 Through 2015.

Author

Love SA, Lelinski J, Kloss J, Middleton O, and Apple FS

Subjects
Accidents statistics & numerical data, Adult, Coroners and Medical Examiners, Drug Overdose mortality, Female, Gas Chromatography-Mass Spectrometry, Heroin Dependence blood, Heroin Dependence urine, Homicide statistics & numerical data, Humans, Male, Middle Aged, Minnesota epidemiology, Morphine analysis, Morphine Derivatives analysis, Retrospective Studies, Sex Distribution, Suicide statistics & numerical data, Vitreous Body chemistry, Heroin Dependence mortality
Abstract

Over the past two decades, prescription and illicit opioid use has led to changes in public health policy to address the increasing number of opioid-related deaths. The purpose of this study was to review cases from Hennepin County Medical Examiner's Office between 2004 through 2015 where heroin was listed as a significant contributor or as the cause of death. We identified 322 heroin-related deaths, which were predominantly male (255; 79%). 6-Monoacetylmorphine (6-MAM) median (range) concentrations were as follows: blood (n = 7), 0.010 (0.006-0.078) mg/L; urine (n = 30), 0.359 (0.009-1.75) mg/L; and vitreous humor (n = 31), 0.034 (0.004-0.24) mg/L. Free morphine was measurable in 273 cases and the percent free morphine (range), when grouped by COD, was opioid (n = 124), 28% (2.2%-92%), and mixed drug toxicity (n = 135), 35.3% (1.5%-100%); (p < 0.01). Quantitation of 6-MAM in blood and vitreous humor, along with a free to total morphine ratio >26%, was useful in establishing heroin-related deaths., (© 2017 American Academy of Forensic Sciences.)

Published
2018
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47. Identification and pharmacological inactivation of the MYCN gene network as a therapeutic strategy for neuroblastic tumor cells.

Author

Chayka O, D'Acunto CW, Middleton O, Arab M, and Sala A

Subjects
Apoptosis, Cell Differentiation, Cell Line, Tumor, Cell Separation, Flow Cytometry, Genes, myc, Genome-Wide Association Study, HEK293 Cells, Humans, Lentivirus genetics, Membrane Proteins metabolism, N-Myc Proto-Oncogene Protein, Neuroblastoma drug therapy, Neuroblastoma metabolism, Prognosis, Protein Serine-Threonine Kinases metabolism, Protein-Tyrosine Kinases metabolism, Proto-Oncogene Proteins metabolism, RNA, Small Interfering metabolism, RecQ Helicases metabolism, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Nuclear Proteins metabolism, Oncogene Proteins metabolism
Abstract

The MYC family of transcription factors consists of three well characterized members, c-MYC, L-MYC, and MYCN, deregulated in the majority of human cancers. In neuronal tumors such as neuroblastoma, MYCN is frequently activated by gene amplification, and reducing its expression by RNA interference has been shown to promote growth arrest and apoptosis of tumor cells. From a clinical perspective, RNA interference is not yet a viable option, and small molecule inhibitors of transcription factors are difficult to develop. We therefore planned to identify, at the global level, the genes interacting functionally with MYCN required to promote fitness of tumor cells facing oncogenic stress. To find genes whose inactivation is synthetically lethal to MYCN, we implemented a genome-wide approach in which we carried out a drop-out shRNA screen using a whole genome library that was delivered into isogenic neuroblastoma cell lines expressing or not expressing MYCN. After the screen, we selected for in-depth analysis four shRNAs targeting AHCY, BLM, PKMYT1, and CKS1B. These genes were chosen because they are directly regulated by MYC proteins, associated with poor prognosis of neuroblastoma patients, and inhibited by small molecule compounds. Mechanistically, we found that BLM and PKMYT1 are required to limit oncogenic stress and promote stabilization of the MYCN protein. Cocktails of small molecule inhibitors of CKS1B, AHCY, BLM, and PKMYT1 profoundly affected the growth of all neuroblastoma cell lines but selectively caused death of MYCN-amplified cells. Our findings suggest that drugging the MYCN network is a promising avenue for the treatment of high risk, neuroblastic cancers., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Published
2015
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48. Superiority of postmortem liver fentanyl concentrations over peripheral blood influenced by postmortem interval for determination of fentanyl toxicity.

Author

Palamalai V, Olson KN, Kloss J, Middleton O, Mills K, Strobl AQ, Thomas LC, and Apple FS

Subjects
Fentanyl toxicity, Gas Chromatography-Mass Spectrometry, Humans, Time Factors, Fentanyl blood, Forensic Toxicology methods, Liver chemistry, Postmortem Changes
Abstract

Objective: The current study was undertaken to determine the relationship between postmortem (PM) peripheral blood (PB) and liver fentanyl concentrations and the role of measuring liver fentanyl concentrations in cause of death investigations in medical examiner cases in which fentanyl was identified., Design and Methods: FB and liver tissue were routinely collected at autopsy from 4 Minnesota medical examiners' offices in 2010-2011. Samples were analyzed by gas chromatography-mass spectrometry (GC-MS)., Results: PB fentanyl ranged from <2-15μg/L in non-drug related deaths (n=5), <2-22μg/L from mixed drug toxicity (n=26) and 3.7-56μg/L from fentanyl toxicity (n=33). Liver fentanyl ranged from 11 to 104μg/kg, 6 to 235μg/kg, and 18 to 365μg/kg, respectively. PB and liver fentanyl showed a modest correlation (r=0.67). PM interval to the liver/blood ratio showed a decreasing ratio over increasing PM interval in cases from fentanyl and mixed drug toxicity. Liver fentanyl concentrations best define therapeutic use at <23μg/kg and fatal toxicity at >56μg/kg, without substantial overlap as found in blood fentanyl concentrations., Conclusion: Discriminatory liver fentanyl concentrations suggestive of therapeutic or toxic drug levels may better assist cause of death determination in cases of suspected fentanyl toxicity than postmortem PB concentrations. Peripheral blood fentanyl concentrations appear to undergo postmortem redistribution, associated with an increasing PM interval., (Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Published
2013
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49. Suicide by gabapentin overdose.

Author

Middleton O

Subjects
Amines blood, Anticonvulsants blood, Cyclohexanecarboxylic Acids blood, Depressive Disorder, Major psychology, Drug Overdose, Female, Forensic Toxicology, Gabapentin, Humans, Middle Aged, gamma-Aminobutyric Acid blood, Amines poisoning, Anticonvulsants poisoning, Cyclohexanecarboxylic Acids poisoning, Suicide, gamma-Aminobutyric Acid poisoning
Abstract

Gabapentin is an antiepileptic drug that is prescribed for both FDA-approved and multiple off-label conditions, and has a relatively safe side-effect profile. Rare cases of overdose-related adverse effects have been reported in the literature. Described herein are the circumstances and autopsy findings of a 62-year-old woman with a history of depression, whose death was caused by intentional ingestion of excess gabapentin. The postmortem peripheral blood gabapentin concentration as determined by high-performance liquid chromatography/tandem mass spectroscopy was 88 μg/mL. Previously reported cases of individuals surviving gabapentin overdoses are discussed and compared with this case. Based on a review of the available literature, this appears to be the first published report of a death due solely to gabapentin toxicity., (© 2011 American Academy of Forensic Sciences.)

Published
2011
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50. Postmortem redistribution of fentanyl in blood.

Author

Olson KN, Luckenbill K, Thompson J, Middleton O, Geiselhart R, Mills KM, Kloss J, and Apple FS

Subjects
Fentanyl blood, Gas Chromatography-Mass Spectrometry, Humans, Liver metabolism, Muscle, Skeletal metabolism, Myocardium metabolism, Narcotics blood, Narcotics pharmacokinetics, Tissue Distribution, Autopsy, Fentanyl pharmacokinetics, Postmortem Changes
Abstract

Fentanyl concentrations were measured in postmortem specimens collected in 20 medical examiner cases from femoral blood (FB), heart blood (HB), heart tissue, liver tissue, and skeletal muscle. Unique was a subset of 7 cases in which FB was obtained at 2 postmortem intervals, shortly after death (FB1) and at autopsy (FB2). The mean collection times of FB1 and FB2 after death were 4.0 and 21.6 hours, respectively. Fentanyl concentrations for FB1 and FB2 ranged from undetectable to 14.6 microg/L (mean, 4.6 microg/L) and 2.0 to 52.5 microg/L (mean, 17.3 microg/L), respectively. Corresponding mean HB, liver tissue, and heart tissue fentanyl concentrations were 29.8 microg/L, 109.7 mg/kg, and 103.4 mg/kg, respectively. The fentanyl HB/FB1 ratio (mean, 8.39) was higher compared with the corresponding HB/FB2 ratio (mean, 3.48). These results suggest that postmortem redistribution of fentanyl can occur in FB.

Published
2010
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