290 results on '"Smith HG"'
Search Results
2. CropPol: A dynamic, open and global database on crop pollination
- Author
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Allen-Perkins, A, Magrach, A, Dainese, M, Garibaldi, LA, Kleijn, D, Rader, R, Reilly, JR, Winfree, R, Lundin, O, McGrady, CM, Brittain, C, Biddinger, DJ, Artz, DR, Elle, E, Hoffman, G, Ellis, JD, Daniels, J, Gibbs, J, Campbell, JW, Brokaw, J, Wilson, JK, Mason, K, Ward, KL, Gundersen, KB, Bobiwash, K, Gut, L, Rowe, LM, Boyle, NK, Williams, NM, Joshi, NK, Rothwell, N, Gillespie, RL, Isaacs, R, Fleischer, SJ, Peterson, SS, Rao, S, Pitts-Singer, TL, Fijen, T, Boreux, V, Rundlof, M, Viana, BF, Klein, A-M, Smith, HG, Bommarco, R, Carvalheiro, LG, Ricketts, TH, Ghazoul, J, Krishnan, S, Benjamin, FE, Loureiro, J, Castro, S, Raine, NE, de Groot, GA, Horgan, FG, Hipolito, J, Smagghe, G, Meeus, I, Eeraerts, M, Potts, SG, Kremen, C, Garcia, D, Minarro, M, Crowder, DW, Pisanty, G, Mandelik, Y, Vereecken, NJ, Leclercq, N, Weekers, T, Lindstrom, SAM, Stanley, DA, Zaragoza-Trello, C, Nicholson, CC, Scheper, J, Rad, C, Marks, EAN, Mota, L, Danforth, B, Park, M, Bezerra, ADM, Freitas, BM, Mallinger, RE, Oliveira da Silva, F, Willcox, B, Ramos, DL, da Silva e Silva, FD, Lazaro, A, Alomar, D, Gonzalez-Estevez, MA, Taki, H, Cariveau, DP, Garratt, MPD, Nabaes Jodar, DN, Stewart, RIA, Ariza, D, Pisman, M, Lichtenberg, EM, Schueepp, C, Herzog, F, Entling, MH, Dupont, YL, Michener, CD, Daily, GC, Ehrlich, PR, Burns, KLW, Vila, M, Robson, A, Howlett, B, Blechschmidt, L, Jauker, F, Schwarzbach, F, Nesper, M, Diekoetter, T, Wolters, V, Castro, H, Gaspar, H, Nault, BA, Badenhausser, I, Petersen, JD, Tscharntke, T, Bretagnolle, V, Willis Chan, DS, Chacoff, N, Andersson, GKS, Jha, S, Colville, JF, Veldtman, R, Coutinho, J, Bianchi, FJJA, Sutter, L, Albrecht, M, Jeanneret, P, Zou, Y, Averill, AL, Saez, A, Sciligo, AR, Vergara, CH, Bloom, EH, Oeller, E, Badano, EI, Loeb, GM, Grab, H, Ekroos, J, Gagic, V, Cunningham, SA, Astrom, J, Cavigliasso, P, Trillo, A, Classen, A, Mauchline, AL, Montero-Castano, A, Wilby, A, Woodcock, BA, Sidhu, CS, Steffan-Dewenter, I, Vogiatzakis, IN, Herrera, JM, Otieno, M, Gikungu, MW, Cusser, SJ, Nauss, T, Nilsson, L, Knapp, J, Ortega-Marcos, JJ, Gonzalez, JA, Osborne, JL, Blanche, R, Shaw, RF, Hevia, V, Stout, J, Arthur, AD, Blochtein, B, Szentgyorgyi, H, Li, J, Mayfield, MM, Woyciechowski, M, Nunes-Silva, P, Halinski de Oliveira, R, Henry, S, Simmons, BI, Dalsgaard, B, Hansen, K, Sritongchuay, T, O'Reilly, AD, Chamorro Garcia, FJ, Nates Parra, G, Magalhaes Pigozo, C, Bartomeus, I, Allen-Perkins, A, Magrach, A, Dainese, M, Garibaldi, LA, Kleijn, D, Rader, R, Reilly, JR, Winfree, R, Lundin, O, McGrady, CM, Brittain, C, Biddinger, DJ, Artz, DR, Elle, E, Hoffman, G, Ellis, JD, Daniels, J, Gibbs, J, Campbell, JW, Brokaw, J, Wilson, JK, Mason, K, Ward, KL, Gundersen, KB, Bobiwash, K, Gut, L, Rowe, LM, Boyle, NK, Williams, NM, Joshi, NK, Rothwell, N, Gillespie, RL, Isaacs, R, Fleischer, SJ, Peterson, SS, Rao, S, Pitts-Singer, TL, Fijen, T, Boreux, V, Rundlof, M, Viana, BF, Klein, A-M, Smith, HG, Bommarco, R, Carvalheiro, LG, Ricketts, TH, Ghazoul, J, Krishnan, S, Benjamin, FE, Loureiro, J, Castro, S, Raine, NE, de Groot, GA, Horgan, FG, Hipolito, J, Smagghe, G, Meeus, I, Eeraerts, M, Potts, SG, Kremen, C, Garcia, D, Minarro, M, Crowder, DW, Pisanty, G, Mandelik, Y, Vereecken, NJ, Leclercq, N, Weekers, T, Lindstrom, SAM, Stanley, DA, Zaragoza-Trello, C, Nicholson, CC, Scheper, J, Rad, C, Marks, EAN, Mota, L, Danforth, B, Park, M, Bezerra, ADM, Freitas, BM, Mallinger, RE, Oliveira da Silva, F, Willcox, B, Ramos, DL, da Silva e Silva, FD, Lazaro, A, Alomar, D, Gonzalez-Estevez, MA, Taki, H, Cariveau, DP, Garratt, MPD, Nabaes Jodar, DN, Stewart, RIA, Ariza, D, Pisman, M, Lichtenberg, EM, Schueepp, C, Herzog, F, Entling, MH, Dupont, YL, Michener, CD, Daily, GC, Ehrlich, PR, Burns, KLW, Vila, M, Robson, A, Howlett, B, Blechschmidt, L, Jauker, F, Schwarzbach, F, Nesper, M, Diekoetter, T, Wolters, V, Castro, H, Gaspar, H, Nault, BA, Badenhausser, I, Petersen, JD, Tscharntke, T, Bretagnolle, V, Willis Chan, DS, Chacoff, N, Andersson, GKS, Jha, S, Colville, JF, Veldtman, R, Coutinho, J, Bianchi, FJJA, Sutter, L, Albrecht, M, Jeanneret, P, Zou, Y, Averill, AL, Saez, A, Sciligo, AR, Vergara, CH, Bloom, EH, Oeller, E, Badano, EI, Loeb, GM, Grab, H, Ekroos, J, Gagic, V, Cunningham, SA, Astrom, J, Cavigliasso, P, Trillo, A, Classen, A, Mauchline, AL, Montero-Castano, A, Wilby, A, Woodcock, BA, Sidhu, CS, Steffan-Dewenter, I, Vogiatzakis, IN, Herrera, JM, Otieno, M, Gikungu, MW, Cusser, SJ, Nauss, T, Nilsson, L, Knapp, J, Ortega-Marcos, JJ, Gonzalez, JA, Osborne, JL, Blanche, R, Shaw, RF, Hevia, V, Stout, J, Arthur, AD, Blochtein, B, Szentgyorgyi, H, Li, J, Mayfield, MM, Woyciechowski, M, Nunes-Silva, P, Halinski de Oliveira, R, Henry, S, Simmons, BI, Dalsgaard, B, Hansen, K, Sritongchuay, T, O'Reilly, AD, Chamorro Garcia, FJ, Nates Parra, G, Magalhaes Pigozo, C, and Bartomeus, I
- Abstract
Seventy five percent of the world's food crops benefit from insect pollination. Hence, there has been increased interest in how global change drivers impact this critical ecosystem service. Because standardized data on crop pollination are rarely available, we are limited in our capacity to understand the variation in pollination benefits to crop yield, as well as to anticipate changes in this service, develop predictions, and inform management actions. Here, we present CropPol, a dynamic, open, and global database on crop pollination. It contains measurements recorded from 202 crop studies, covering 3,394 field observations, 2,552 yield measurements (i.e., berry mass, number of fruits, and fruit density [kg/ha], among others), and 47,752 insect records from 48 commercial crops distributed around the globe. CropPol comprises 32 of the 87 leading global crops and commodities that are pollinator dependent. Malus domestica is the most represented crop (32 studies), followed by Brassica napus (22 studies), Vaccinium corymbosum (13 studies), and Citrullus lanatus (12 studies). The most abundant pollinator guilds recorded are honey bees (34.22% counts), bumblebees (19.19%), flies other than Syrphidae and Bombyliidae (13.18%), other wild bees (13.13%), beetles (10.97%), Syrphidae (4.87%), and Bombyliidae (0.05%). Locations comprise 34 countries distributed among Europe (76 studies), North America (60), Latin America and the Caribbean (29), Asia (20), Oceania (10), and Africa (7). Sampling spans three decades and is concentrated on 2001-2005 (21 studies), 2006-2010 (40), 2011-2015 (88), and 2016-2020 (50). This is the most comprehensive open global data set on measurements of crop flower visitors, crop pollinators and pollination to date, and we encourage researchers to add more datasets to this database in the future. This data set is released for non-commercial use only. Credits should be given to this paper (i.e., proper citation), and the products generated with this da
- Published
- 2022
3. Backyard buzz: human population density modifies the value of vegetation cover for insect pollinators in a subtropical city
- Author
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Persson, AS, Westman, A, Smith, TJ, Mayfield, MM, Olsson, P, Smith, HG, Fuller, R, Persson, AS, Westman, A, Smith, TJ, Mayfield, MM, Olsson, P, Smith, HG, and Fuller, R
- Abstract
Urbanisation drives overall declines in insect pollinators. Although urban green spaces can provide suitable habitat for pollinators much remains to be learned about how urban landscapes either promote or negatively impact pollinators. We investigated how backyard design, local (100 m) and landscape (500 m) scale vegetation cover and human population density were associated with non-eusocial native bee species, eusocial bees (Apis melliferaandTetragonula spp.), and hoverflies, in residential green spaces of the subtropical city Brisbane, Australia. We found that associations between bee abundance and vegetation cover were moderated by human density, but the direction of this effect differed for non-eusocial and eusocial species. Non-eusocial bee abundance was positively associated with tree cover at local and landscape scales when human densities were low, but negatively so at high human population densities. We suggest this may be because the quality of vegetation for non-eusocial bees deteriorates as human density increases. In contrast, abundance of eusocial bees was negatively associated with increasing local cover of grass and shrubs at low levels of human density, but positively associated at high densities. This affinity to humans could partly be explained by domesticated “kept” hives. We found no effect of urban gradients on bee species richness. Hoverfly abundance was negatively related to human density and positively related to vegetation cover at local and landscape scales. At the backyard scale, both bee species richness and bee and hoverfly abundances were positively associated to flower abundance. Backyards with more vegetation cover had higher densities of non-eusocial bees. Our results thus support the idea that urban greening in densely populated areas at multiple spatial scales can benefit a range of insect pollinators.
- Published
- 2022
4. Improving body image at scale among Brazilian adolescents: study protocol for the co-creation and randomised trial evaluation of a chatbot intervention
- Author
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Matheson, EL, Smith, HG, Amaral, ACS, Meireles, JFF, Almeida, MC, Mora, G, Leon, C, Gertner, G, Ferrario, N, Suarez Battan, L, Linardon, Jake, Fuller-Tyszkiewicz, Matthew, Diedrichs, PC, Matheson, EL, Smith, HG, Amaral, ACS, Meireles, JFF, Almeida, MC, Mora, G, Leon, C, Gertner, G, Ferrario, N, Suarez Battan, L, Linardon, Jake, Fuller-Tyszkiewicz, Matthew, and Diedrichs, PC
- Published
- 2021
5. Reliably predicting pollinator abundance: Challenges of calibrating process‐based ecological models
- Author
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Gardner, E, Breeze, TD, Clough, Y, Smith, HG, Baldock, KCR, Campbell, A, Garratt, MPD, Gillespie, MAK, Kunin, WE, McKerchar, M, Memmott, J, Potts, SG, Senapathi, D, Stone, GN, Wäckers, F, Westbury, DB, Wilby, A, and Oliver, TH
- Abstract
1. Pollination is a key ecosystem service for global agriculture but evidence of pollinator population declines is growing. Reliable spatial modelling of pollinator abundance is essential if we are to identify areas at risk of pollination service deficit and effectively target resources to support pollinator populations. Many models exist which predict pollinator abundance but few have been calibrated against observational data from multiple habitats to ensure their predictions are accurate. 2. We selected the most advanced process‐based pollinator abundance model available and calibrated it for bumblebees and solitary bees using survey data collected at 239 sites across Great Britain. We compared three versions of the model: one parameterised using estimates based on expert opinion, one where the parameters are calibrated using a purely data‐driven approach and one where we allow the expert opinion estimates to inform the calibration process. 3. All three model versions showed significant agreement with the survey data, demonstrating this model's potential to reliably map pollinator abundance. However, there were significant differences between the nesting/floral attractiveness scores obtained by the two calibration methods and from the original expert opinion scores. 4. Our results highlight a key universal challenge of calibrating spatially explicit, process‐based ecological models. Notably, the desire to reliably represent complex ecological processes in finely mapped landscapes necessarily generates a large number of parameters, which are challenging to calibrate with ecological and geographical data that are often noisy, biased, asynchronous and sometimes inaccurate. Purely data‐driven calibration can therefore result in unrealistic parameter values, despite appearing to improve model‐data agreement over initial expert opinion estimates. We therefore advocate a combined approach where data‐driven calibration and expert opinion are integrated into an iterative Delphi‐like process, which simultaneously combines model calibration and credibility assessment. This may provide the best opportunity to obtain realistic parameter estimates and reliable model predictions for ecological systems with expert knowledge gaps and patchy ecological data.
- Published
- 2020
6. 4-1BB is a target for immunotherapy in patients with undifferentiated pleomorphic sarcoma
- Author
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Melake, MJ, primary, Smith, HG, additional, Mansfield, D, additional, Davies, E, additional, Dillon, MT, additional, Wilkins, AC, additional, Patin, EC, additional, Pedersen, M, additional, Buus, R, additional, Miah, AB, additional, Zaidi, SH, additional, Thway, K, additional, Melcher, AA, additional, Hayes, AJ, additional, Fenton, TR, additional, Harrington, KJ, additional, and McLaughlin, M, additional
- Published
- 2020
- Full Text
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7. Lattice dynamics of the A15 compound Nb3Sb
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Pintschovius, L, Smith, HG, Wakabayashi, N, Reichardt, W, Weber, W, Webb, GW, and Fisk, Z
- Subjects
Physical Sciences ,Chemical Sciences ,Engineering ,Fluids & Plasmas - Abstract
The phonon dispersion curves of Nb3Sb have been studied by inelastic neutron scattering. All the branches have been determined in the main symmetry directions and the results are analyzed with Born-von Kármán models of different complexity. A model with general forces up to the eighth-nearest neighbors gives excellent agreement with experiment. However, a rather good description of the dispersion curves is obtained with a model including axially symmetric forces up to the third-nearest neighbors, which indicates that these interactions are dominant. Temperature effects were found to be very small. Additional experiments were performed on polycrystalline samples to determine directly the phonon density of states. Our results obtained on Nb3Sb are compared with the available phonon data on Nb3Sn. © 1983 The American Physical Society.
- Published
- 1983
8. PHONON-SPECTRA IN A-15 SUPERCONDUCTING COMPOUNDS
- Author
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SMITH, HG, WAKABAYASHI, N, CHANG, YK, LOWNDES, D, WEBB, GW, FISK, Z, MUELLER, FM, and ARKO, A
- Published
- 1980
9. Crop pests and predators exhibit inconsistent responses to surrounding landscape composition
- Author
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Karp, DS, Chaplin-Kramer, R, Meehan, TD, Martin, EA, DeClerck, F, Grab, H, Gratton, C, Hunt, L, Larsen, AE, Martinez-Salinas, A, O'Rourke, ME, Rusch, A, Poveda, K, Jonsson, M, Rosenheim, JA, Schellhorn, NA, Tscharntke, T, Wratten, SD, Zhang, W, Iverson, AL, Adler, LS, Albrecht, M, Alignier, A, Angelella, GM, Anjum, MZ, Avelino, J, Batary, P, Baveco, JM, Bianchi, FJJA, Birkhofer, K, Bohnenblust, EW, Bommarco, R, Brewer, MJ, Caballero-Lopez, B, Carriere, Y, Carvalheiro, LG, Cayuela, L, Centrella, M, Cetkovic, A, Henri, DC, Chabert, A, Costamagna, AC, De la Mora, A, de Kraker, J, Desneux, N, Diehl, E, Diekoetter, T, Dormann, CF, Eckberg, JO, Entling, MH, Fiedler, D, Franck, P, van Veen, FJF, Frank, T, Gagic, V, Garratt, MPD, Getachew, A, Gonthier, DJ, Goodell, PB, Graziosi, I, Groves, RL, Gurr, GM, Hajian-Forooshani, Z, Heimpel, GE, Herrmann, JD, Huseth, AS, Inclan, DJ, Ingrao, AJ, Iv, P, Jacot, K, Johnson, GA, Jones, L, Kaiser, M, Kaser, JM, Keasar, T, Kim, TN, Kishinevsky, M, Landis, DA, Lavandero, B, Lavigne, C, Le Ralec, A, Lemessa, D, Letourneau, DK, Liere, H, Lu, Y, Lubin, Y, Luttermoser, T, Maas, B, Mace, K, Madeira, F, Mader, V, Cortesero, AM, Marini, L, Martinez, E, Martinson, HM, Menozzi, P, Mitchell, MGE, Miyashita, T, Molina, GAR, Molina-Montenegro, MA, O'Neal, ME, Opatovsky, I, Ortiz-Martinez, S, Nash, M, Ostman, O, Ouin, A, Pak, D, Paredes, D, Parsa, S, Parry, H, Perez-Alvarez, R, Perovic, DJ, Peterson, JA, Petit, S, Philpott, SM, Plantegenest, M, Plecas, M, Pluess, T, Pons, X, Potts, SG, Pywell, RF, Ragsdale, DW, Rand, TA, Raymond, L, Ricci, B, Sargent, C, Sarthou, J-P, Saulais, J, Schackermann, J, Schmidt, NP, Schneider, G, Schuepp, C, Sivakoff, FS, Smith, HG, Whitney, KS, Stutz, S, Szendrei, Z, Takada, MB, Taki, H, Tamburini, G, Thomson, LJ, Tricault, Y, Tsafack, N, Tschumi, M, Valantin-Morison, M, Mai, VT, van der Werf, W, Vierling, KT, Werling, BP, Wickens, JB, Wickens, VJ, Woodcock, BA, Wyckhuys, K, Xiao, H, Yasuda, M, Yoshioka, A, Zou, Y, Karp, DS, Chaplin-Kramer, R, Meehan, TD, Martin, EA, DeClerck, F, Grab, H, Gratton, C, Hunt, L, Larsen, AE, Martinez-Salinas, A, O'Rourke, ME, Rusch, A, Poveda, K, Jonsson, M, Rosenheim, JA, Schellhorn, NA, Tscharntke, T, Wratten, SD, Zhang, W, Iverson, AL, Adler, LS, Albrecht, M, Alignier, A, Angelella, GM, Anjum, MZ, Avelino, J, Batary, P, Baveco, JM, Bianchi, FJJA, Birkhofer, K, Bohnenblust, EW, Bommarco, R, Brewer, MJ, Caballero-Lopez, B, Carriere, Y, Carvalheiro, LG, Cayuela, L, Centrella, M, Cetkovic, A, Henri, DC, Chabert, A, Costamagna, AC, De la Mora, A, de Kraker, J, Desneux, N, Diehl, E, Diekoetter, T, Dormann, CF, Eckberg, JO, Entling, MH, Fiedler, D, Franck, P, van Veen, FJF, Frank, T, Gagic, V, Garratt, MPD, Getachew, A, Gonthier, DJ, Goodell, PB, Graziosi, I, Groves, RL, Gurr, GM, Hajian-Forooshani, Z, Heimpel, GE, Herrmann, JD, Huseth, AS, Inclan, DJ, Ingrao, AJ, Iv, P, Jacot, K, Johnson, GA, Jones, L, Kaiser, M, Kaser, JM, Keasar, T, Kim, TN, Kishinevsky, M, Landis, DA, Lavandero, B, Lavigne, C, Le Ralec, A, Lemessa, D, Letourneau, DK, Liere, H, Lu, Y, Lubin, Y, Luttermoser, T, Maas, B, Mace, K, Madeira, F, Mader, V, Cortesero, AM, Marini, L, Martinez, E, Martinson, HM, Menozzi, P, Mitchell, MGE, Miyashita, T, Molina, GAR, Molina-Montenegro, MA, O'Neal, ME, Opatovsky, I, Ortiz-Martinez, S, Nash, M, Ostman, O, Ouin, A, Pak, D, Paredes, D, Parsa, S, Parry, H, Perez-Alvarez, R, Perovic, DJ, Peterson, JA, Petit, S, Philpott, SM, Plantegenest, M, Plecas, M, Pluess, T, Pons, X, Potts, SG, Pywell, RF, Ragsdale, DW, Rand, TA, Raymond, L, Ricci, B, Sargent, C, Sarthou, J-P, Saulais, J, Schackermann, J, Schmidt, NP, Schneider, G, Schuepp, C, Sivakoff, FS, Smith, HG, Whitney, KS, Stutz, S, Szendrei, Z, Takada, MB, Taki, H, Tamburini, G, Thomson, LJ, Tricault, Y, Tsafack, N, Tschumi, M, Valantin-Morison, M, Mai, VT, van der Werf, W, Vierling, KT, Werling, BP, Wickens, JB, Wickens, VJ, Woodcock, BA, Wyckhuys, K, Xiao, H, Yasuda, M, Yoshioka, A, and Zou, Y
- Abstract
The idea that noncrop habitat enhances pest control and represents a win-win opportunity to conserve biodiversity and bolster yields has emerged as an agroecological paradigm. However, while noncrop habitat in landscapes surrounding farms sometimes benefits pest predators, natural enemy responses remain heterogeneous across studies and effects on pests are inconclusive. The observed heterogeneity in species responses to noncrop habitat may be biological in origin or could result from variation in how habitat and biocontrol are measured. Here, we use a pest-control database encompassing 132 studies and 6,759 sites worldwide to model natural enemy and pest abundances, predation rates, and crop damage as a function of landscape composition. Our results showed that although landscape composition explained significant variation within studies, pest and enemy abundances, predation rates, crop damage, and yields each exhibited different responses across studies, sometimes increasing and sometimes decreasing in landscapes with more noncrop habitat but overall showing no consistent trend. Thus, models that used landscape-composition variables to predict pest-control dynamics demonstrated little potential to explain variation across studies, though prediction did improve when comparing studies with similar crop and landscape features. Overall, our work shows that surrounding noncrop habitat does not consistently improve pest management, meaning habitat conservation may bolster production in some systems and depress yields in others. Future efforts to develop tools that inform farmers when habitat conservation truly represents a win-win would benefit from increased understanding of how landscape effects are modulated by local farm management and the biology of pests and their enemies.
- Published
- 2018
10. Combined ATR and DNA-PK Inhibition Radiosensitizes Tumor Cells Independently of Their p53 Status.
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Hafsi, H, Dillon, MT, Barker, HE, Kyula, JN, Schick, U, Paget, JT, Smith, HG, Pedersen, M, McLaughlin, M, Harrington, KJ, Hafsi, H, Dillon, MT, Barker, HE, Kyula, JN, Schick, U, Paget, JT, Smith, HG, Pedersen, M, McLaughlin, M, and Harrington, KJ
- Abstract
Head and neck squamous cell carcinoma (HNSCC) is a significant cause of cancer deaths. Cisplatin-based chemoradiotherapy is a standard of care for locally advanced disease. ATR and DNA-PK inhibition (DNA-PKi) are actively being investigated in clinical trials with preclinical data supporting clinical translation as radiosensitizers. Here, we hypothesized that targeting both ATR and DNA-PK with small molecule inhibitors would increase radiosensitization of HNSCC cell lines. Radiosensitization was assessed by Bliss independence analysis of colony survival data. Strong cell cycle perturbing effects were observed with ATR inhibition reversing the G2/M arrest observed for radiation-DNA-PKi. Increased apoptosis in combination groups was measured by Sub-G1 DNA populations. DNA-PKi increased radiation-induced RAD51 and gamma-H2Ax foci, with the addition of ATR inhibition reducing levels of both. A sharp increase in nuclear fragmentation after aberrant mitotic transit appears to be the main driver of decreased survival due to irradiation and dual ATR/DNA-PKi. Dual inhibition of DNA-PK and ATR represents a novel approach in combination with radiation, with efficacy appearing to be independent of p53 status. Due to toxicity concerns, careful assessment is necessary in any future translation of single or dual radiosensitization approaches. Ongoing clinical trials into the ATR inhibitor AZD6738 plus radiation, and the phenotypically similar combination of AZD6738 and the PARP inhibitor olaparib, are likely to be key in ascertaining the toxicity profile of such combinations.
- Published
- 2018
11. Non-bee insects are important contributors to global crop pollination
- Author
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De O Pereira, N, Lindström, SAM, Winfree, R, Garrat, MPD, Gross, SL, Bartomeus, I, Monteiro, VM, Howlett, BG, Herzog, F, Szentgyörgyi, H, Stanley, DA, Pattemore, DE, Cunningham, SA, Gemmill-Herren, B, Scheper, J, Freitas, BM, Foully, B, Vergara, CH, Krishnan, S, Klein, A-M, Ghazoul, J, Brittain, C, Potts, SG, Mandelik, Y, Smith, HG, Stout, JC, Jauker, F, Kleijn, D, Andersson, GKS, Viana, BF, Woyciechowski, M, Hipólito, J, Schüepp, Christof, Chacoff, NP, Reemer, M, Taki, H, Bommarco, R, Nilsson, L, Garibaldi, LA, Rader, R, Griffin, Carvalheiro, LG, Arthur, AD, Herbertsson, L, Lemos, CQ, Jaggar, S, Entling, MH, Sheffield, CS, Mayfield, MM, Pisanty, G, and Rundlöf, M
- Subjects
590 Animals (Zoology) ,570 Life sciences ,biology ,580 Plants (Botany) - Abstract
Many of the world’s crops are pollinated by insects, and bees are often assumed to be the most important pollinators. To our knowledge, our study is the first quantitative evaluation of the relative contribution of non-bee pollinators to global pollinator-dependent crops. Across 39 studies we show that insects other than bees are efficient pollinators providing 39% of visits to crop flowers. A shift in perspective from a bee-only focus is needed for assessmentsofcroppollinatorb iodiversity and the economic value of pollination. These studies should also consider the services provided by other types of insects, such as flies, wasps, beetles, and butterflies—important pollinators that a re currently overlooked.
- Published
- 2015
- Full Text
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12. Elastofibroma dorsi: The clunking tumour that need not cause alarm
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Smith, HG, primary, Hannay, JAF, additional, Thway, K, additional, Messiou, C, additional, Smith, MJF, additional, Strauss, DC, additional, and Hayes, AJ, additional
- Published
- 2016
- Full Text
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13. Regional variations in the referral criteria for the surgical treatment of varicose veins
- Author
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Smith, HG, primary, Khan, MEA, additional, Harrison, SL, additional, Abdul-Latiff, A, additional, Hamid, S, additional, Alchikhali, T, additional, Derodra, J, additional, and Vig, S, additional
- Published
- 2015
- Full Text
- View/download PDF
14. Initial flux of sediment-associated radiocesium to the ocean from the largest river impacted by Fukushima Daiichi Nuclear Power Plant
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Yamashiki, Y, Onda, Y, Smith, HG, Blake, WH, Wakahara, T, Igarashi, Y, Matsuura, Y, Yoshimura, K, Yamashiki, Y, Onda, Y, Smith, HG, Blake, WH, Wakahara, T, Igarashi, Y, Matsuura, Y, and Yoshimura, K
- Abstract
This study aimed to quantify the flux of radiocesium in the Abukuma Basin (5,172 km(2)), the largest river system affected by fallout from the Fukushima Daiichi Nuclear Power Plant (FDNPP) event. In the period from 10 August 2011 to 11 May 2012 an estimated 84 to 92% of the total radiocesium transported in the basin's fluvial system was carried in particulate form. During this monitoring period Typhoon Roke (September 2011) was observed to induce a significant and temporally punctuated redistribution of radiocesium. The storm-mobilised radiocesium was an estimated 6.18 Terabecquerels corresponding to 61.4% of the total load delivered to the coastal zone during the observation period. The total flux of radiocesium into the Pacific Ocean estimated at the outlet station (basin area 5,172 km(2)) was 5.34 TBq for (137)Cs, and 4.74 TBq for (134)Cs, corresponding to 1.13% of the total estimated radiocesium fallout over the basin catchment (890 TBq). This was equivalent to the estimated amount of direct leakage from FDNPP to the ocean during June 2011 to September 2012 of 17 TBq and the Level 3 Scale Leakage on 21 August 2013 (24 TBq).
- Published
- 2014
15. Search for a retroviral cause for sarcoidosis: no evidence from peripheral blood studies
- Author
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Lyons, DJ, primary, Sinclair, A, additional, Smith, HG, additional, Mitchell, DN, additional, and Dalgleish, AG, additional
- Published
- 1991
- Full Text
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16. Atypical antipsychotics in the treatment of schizophrenia during pregnancy and the postpartum.
- Author
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Yaeger D, Smith HG, and Altshuler LL
- Published
- 2006
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17. Light-activated calcium release from sonicated bovine retinal rod outer segment disks
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Fager Rs, Smith Hg, and Litman Rj
- Subjects
Light ,genetic structures ,Sonication ,Ionophore ,chemistry.chemical_element ,Calcium ,Biochemistry ,chemistry.chemical_compound ,Adsorption ,Animals ,Photoreceptor Cells ,Binding Sites ,biology ,Temperature ,Biological Transport ,Retinal ,Hydrogen-Ion Concentration ,Kinetics ,Membrane ,chemistry ,Rhodopsin ,biology.protein ,Biophysics ,Cattle ,Glass ,sense organs ,Stoichiometry - Abstract
Calcium trapped within sonicated and resealed bovine rod outer segment disks is released upon light exposure with a stoichiometry of 0.75 +/- 0.05 calcium for each rhodopsin bleached. The amount of calcium liberated is proportional to the amount of bleaching in the range of 20 to 100% bleaching and is relatively insensitive to the internal trapped calcium concentration. The results are obtained using a flow system in which the disk membrane vesicles are adsorbed on glass particle supported by a filter. The external calcium is washed away and subsequent calcium release is monitored by collecting fractions of the effluent before, during, and after light exposure. Disks that are sonicated and allowed to reseal prior to incubation with 45Ca show no change in calcium efflux upon bleaching. The light-activated calcium release is also eliminated if disks sonicated in the presence of 45Ca are treated with a calcium ionophore prior to bleaching. The results demonstrate that the light-released calcium comes from the disks and not from the external disk surface. Lowering temperature to 3--4 degrees C surpresses the light-stimulated release, implicating a transition after the formation of metarhodopsin I in the transport process. The resluts suggest a model for the disk in which each bleached rhodopsin functions as a "one-shot carrier" to transport a single calcium ion across the membrane.
- Published
- 1977
18. Alkyl glucosides as effective solubilizing agents for bovine rhodopsin. A comparison with several commonly used detergents
- Author
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Burton J. Litman, Smith Hg, and Gene W. Stubbs
- Subjects
Rhodopsin ,Circular dichroism ,Light ,Protein Conformation ,Detergents ,Biophysics ,Ferric Compounds ,Biochemistry ,chemistry.chemical_compound ,Glucosides ,Animals ,Organic chemistry ,Denaturation (biochemistry) ,Alkyl ,Octyl glucoside ,chemistry.chemical_classification ,Chromatography ,biology ,Myoglobin ,Circular Dichroism ,Cell Biology ,Membrane ,Digitonin ,Solubility ,chemistry ,Spectrophotometry ,biology.protein ,Cattle ,Spectrophotometry, Ultraviolet ,sense organs ,Decyl glucoside ,Retinal Pigments - Abstract
The suitability of octyl and decyl-beta-D-glucoside as solubilizing agents for the bovine retinal rod outer segment disc membrane was investigated and compared to that of hexadecyltrimethylammonium bromide, N,N-dimethyldodecylamine oxide, Emulphogene BC-720 and digitonin. The properties measured included the thermal stability of rhodopsin, regenerability of bleached rhodopsin by addition of 11-cis-retinal, and the rate of denaturation of bleached rhodopsin as measured by changes in the ultraviolet CD spectrum. Denaturing tendencies of the detergents were also evaluated by observing their effects on the absorption and CD spectra of sperm whale metmyoglobin. Our results demonstrate that octyl glucoside is superior to the other detergents, with the possible exception of digitonin, by the above criteria. Unlike digitonin, however, octyl glucoside affords rapid solubilization of the disc membrane and is itself highly soluble. Decyl glucoside has properties equivalent or superior to octyl glucoside, but salts and buffers interfere with its ability to solubilize the disc membrane. The well defined chemical composition, ease of removal by dialysis, and non-denaturing properties of the alkyl glucosides make them attractive detergents for membrane research.
- Published
- 1976
19. Forensic Archaeology
- Author
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Morse, D, Crusoe, D, and Smith, HG
- Abstract
Physical anthropology has long been a necessary part of criminal investigation. Archaeology, which is another branch of anthropology, has rarely, if ever, been used even when the investigations involved a buried body. The purpose of this presentation is to demonstrate the value of using modern archaeological techniques as an aid in investigations made necessary by the search for or the discovery of burials, either skeletonized or partly decomposed.
- Published
- 1976
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20. Clostridial myonecrosis: an unusual presentation
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Porter Rc, Smith Hg, Hutto Jo, and Stallworth
- Subjects
Microbiology (medical) ,Male ,medicine.medical_specialty ,Scalp ,business.industry ,Cellulitis ,Dermatology ,Diagnosis, Differential ,Infectious Diseases ,Child, Preschool ,Face ,Pediatrics, Perinatology and Child Health ,medicine ,Humans ,Presentation (obstetrics) ,business ,Gas Gangrene - Published
- 1984
21. [10] Preparation of osmotically intact rod outer segment disks by Ficoll flotation
- Author
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Smith Hg and Litman Bj
- Subjects
Aqueous solution ,Chromatography ,biology ,Chemistry ,Thin section ,Ficoll ,Permeation ,law.invention ,Retinal rods ,Membrane ,Rhodopsin ,law ,biology.protein ,sense organs ,Electron microscope - Abstract
Publisher Summary This chapter discusses the preparation of osmotically intact rod outer segment disks by ficoll flotation. Rhodopsin, in retinal rods, is located primarily in the membranes of flattened disks found stacked within the rod outer segments (ROS). This structural organization serves both to provide a long absorbing pathlength of rhodopsin molecules for incident photons and to orient rhodopsin molecules for maximal light absorption efficiency. Disks have been isolated from ROS that are obtained by flotation on either sucrose or metrizamide. The ROS are burst in an aqueous hypotonic solution of 5% Ficoll, under which conditions the disks swell but do not burst. The density of the swollen disks is determined by the weighted contributions of the membranes and intradiskal trapped volume. The fact that the disks float in 5% Ficoll implies that they are osmotically active. This is confirmed by thin section electron microscopy and by the contrast in refraction between the disks and the Ficoll solution as seen with a phase contrast microscope. Disks prepared by Ficoll flotation have been shown to be intact with respect to permeation by concanavalin A, 2.6 and at 0°, by lipid labeling reagents.
- Published
- 1982
22. External calcium inhibits the efflux of calcium from isolated retinal rod outer segment disks
- Author
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Smith Hg and Capalbo Pm
- Subjects
Cell Membrane Permeability ,Light ,Chemistry ,chemistry.chemical_element ,Calcium ,Buffers ,Inhibitory postsynaptic potential ,Rod Cell Outer Segment ,Biochemistry ,Kinetics ,Membrane ,Permeability (electromagnetism) ,Lanthanum ,Biophysics ,Animals ,Cattle ,Photoreceptor Cells ,Efflux ,Binding site ,Ion transporter - Abstract
Increasing the concentration of calcium in the external buffer flowing past isolated, intact bovine retinal rod outer segment disks immobilized in a flow system reduced the rate of radioactive calcium efflux from within the disks in the dark. We interpret these results as extradiskal calcium acting at an inhibitory binding site to block the calcium efflux. A Scatchard analysis of the external calcium dependence of the efflux yields an apparent dissociation constant of 50 microM, which further suggests that the inhibition is mediated by a specific membrane binding site. The observed inhibition of calcium efflux may represent a functional role for the high-affinity calcium binding site which has been identified by others in previous physical studies of the disk membrane. This external calcium inhibited permeability may explain some of the discrepancies in the reported calcium transport properties of disks. Variations in the external calcium concentration may alter the calcium content of isolated disks, thereby indirectly affecting other transport functions including the measured light-induced release of calcium. No evidence was found for either Na/Ca or Ca/Ca exchange processes across the disk membrane. Lanthanum was even more effective than calcium in inhibiting calcium efflux in the dark. Neither lanthanum nor calcium inhibited the light-induced efflux of calcium from disks, which implies either that light and extradiskal calcium regulate separate permeability processes in the disk membrane or that light greatly reduces the affinity of the inhibitory site for calcium and lanthanum.
- Published
- 1985
23. Light-induced permeability changes in sonicated bovine disks: arsenazo III and flow system measurements
- Author
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Smith Hg and Bauer Pj
- Subjects
Rhodopsin ,Sucrose ,Light ,Chemistry ,Sonication ,Arsenazo III ,Inulin ,Temperature ,Biological Transport ,Hydrogen-Ion Concentration ,Biochemistry ,Permeability ,Phosphates ,Flow system ,Permeability (earth sciences) ,Kinetics ,Glucose ,Light induced ,Biophysics ,Animals ,Calcium ,Cattle ,Photoreceptor Cells ,Azo Compounds - Published
- 1979
24. Delivery of crop pollination services is an insufficient argument for wild pollinator conservation
- Author
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Kleijn, D, Winfree, R, Bartomeus, I, Carvalheiro, LG, Henry, M, Rufus Isaacs, R, Klein, AM, Kremen, C, Rader, R, Ricketts, TH, Williams, NM, Adamson, NL, Ascher, JS, Báldi, A, Batáry, P, Benjamin, F, Biesmeijer, JC, Blitzer, EJ, Bommarco, R, Brand, MR, Bretagnolle, V, Button, L, Cariveau, DP, Chifflet, R, Colville, JF, Danforth, BN, Elle, E, Garratt, MPD, Herzog, F, Holzschuh, A, Howlett, BG, Jauker, F, Jha, S, Knop, Eva, Krewenka, KM, Le Féon, V, Mandelik, Y, May, EA, Park, MG, Pisanty, G, Reemer, M, Riedinger, V, Rollin, O, Rundlöf, M, Sardiñas, HS, Scheper, J, Sciligo, AR, Smith, HG, Steffan-Dewenter, I, Thorp, T, Tscharntke, T, Verhulst, J, Viana, BF, Vaissière, BE, Veldtman, R, Westphal, C, Potts, SG, and M'Gonigle, Leithen K
- Subjects
2. Zero hunger ,fungi ,food and beverages ,570 Life sciences ,biology ,15. Life on land - Abstract
There is compelling evidence that more diverse ecosystems deliver greater benefits to people, and these ecosystem services have become a key argument for biodiversity conservation. However, it is unclear how much biodiversity is needed to deliver ecosystem services in a cost-effective way. Here we show that, while the contribution of wild bees to crop production is significant, service delivery is restricted to a limited subset of all known bee species. Across crops, years and biogeographical regions, crop-visiting wild bee communities are dominated by a small number of common species, and threatened species are rarely observed on crops. Dominant crop pollinators persist under agricultural expansion and many are easily enhanced by simple conservation measures, suggesting that cost-effective management strategies to promote crop pollination should target a different set of species than management strategies to promote threatened bees. Conserving the biological diversity of bees therefore requires more than just ecosystem-service-based arguments.
25. Dermatomyositis
- Author
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Smith Hg
- Subjects
World Wide Web ,medicine.medical_specialty ,business.industry ,General surgery ,General Engineering ,medicine ,General Earth and Planetary Sciences ,General Medicine ,Dermatomyositis ,medicine.disease ,business ,General Environmental Science - Published
- 1955
26. Corrections - Light-Induced Permeability Changes in Sonicated Bovine Disks: Arsenazo III and Flow System Measurements
- Author
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Paul Bauer and Smith Hg
- Subjects
Permeability (earth sciences) ,Flow system ,Chemistry ,Sonication ,Light induced ,Biophysics ,Mineralogy ,Arsenazo III ,Biochemistry - Published
- 1980
27. Dye pack injury causing third-degree burns.
- Author
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Wroblewski RL, Smith HG, Wroblewski, Robert L, and Smith, Howard G
- Published
- 2008
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28. Vitamin C infusion decreases fluid requirements.
- Author
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Graham DA, Bhullar I, and Smith HG
- Published
- 2007
29. A global synthesis reveals biodiversity-mediated benefits for crop production
- Author
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Dainese, M, Martin, EA, Aizen, MA, Albrecht, M, Bartomeus, I, Bommarco, R, Carvalheiro, LG, Chaplin-Kramer, R, Gagic, V, Garibaldi, LA, Ghazoul, J, Grab, H, Jonsson, M, Karp, DS, Kennedy, CM, Kleijn, D, Kremen, C, Landis, DA, Letourneau, DK, Marini, L, Poveda, K, Rader, R, Smith, HG, Tscharntke, T, Andersson, GKS, Badenhausser, I, Baensch, S, Bezerra, ADM, Bianchi, FJJA, Boreux, V, Bretagnolle, V, Caballero-Lopez, B, Cavigliasso, P, Ćetković, A, Chacoff, NP, Classen, A, Cusser, S, Da Silva E Silva, FD, de Groot, GA, Dudenhöffer, JH, Ekroos, J, Fijen, T, Franck, P, Freitas, BM, Garratt, MPD, Gratton, C, Hipólito, J, Holzschuh, A, Hunt, L, Iverson, AL, Jha, S, Keasar, T, Kim, TN, Kishinevsky, M, Klatt, BK, Klein, AM, Krewenka, KM, Krishnan, Smitha, Larsen, AE, Lavigne, C, Liere, H, Maas, B, Mallinger, RE, Pachon, EM, Martínez-Salinas, A, Meehan, TD, Mitchell, MGE, Molina, GAR, Nesper, M, Nilsson, L, O'Rourke, ME, Peters, MK, Plećaš, M, Potts, SG, Ramos, DDL, Rosenheim, JA, Rundlöf, M, Rusch, A, Sáez, A, Scheper, J, Schleuning, M, Schmack, JM, Sciligo, AR, Seymour, Colleen, Stanley, DA, Stewart, R, Stout, JC, Sutter, L, Takada, MB, Taki, H, Tamburini, G, Tschumi, M, Viana, BF, Westphal, C, Willcox, BK, Wratten, SD, Yoshioka, A, Zaragoza-Trello, C, Zhang, Wei, Zou, Yi, and Steffan-Dewenter, I
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30. Crop pests and predators exhibit inconsistent responses to surrounding landscape composition
- Author
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Karp, DS, Chaplin-Kramer, R, Meehan, TD, Martin, EA, DeClerck, F, Grab, H, Gratton, C, Hunt, L, Larsen, AE, Martínez-Salinas, A, O Rourke, ME, Rusch, A, Poveda, K, Jonsson, M, Rosenheim, JA, Schellhorn, NA, Tscharntke, T, Wratten, SD, Zhang, Wei, Iverson, AL, Adler, LS, Albrecht, M, Alignier, A, Angelella, GM, Anjum, MZ, Avelino, J, Batáry, P, Baveco, JM, Bianchi, FJJA, Birkhofer, K, Bohnenblust, EW, Bommarco, R, Brewer, MJ, Caballero-López, B, Carrière, Y, Carvalheiro, LG, Cayuela, L, Centrella, M, Ćetković, A, Henri, DC, Chabert, A, Costamagna, AC, De la Mora, A, de Kraker, J, Desneux, N, Diehl, E, Diekötter, T, Dormann, CF, Eckberg, JO, Entling, MH, Fiedler, D, Franck, P, van Veen, FJF, Frank, T, Gagic, V, Garratt, MPD, Getachew, A, Gonthier, DJ, Goodell, PB, Graziosi, I, Groves, RL, Gurr, GM, Hajian-Forooshani, Z, Heimpel, GE, Herrmann, JD, Huseth, AS, Inclán, DJ, Ingrao, AJ, Iv, P, Jacot, K, Johnson, GA, Jones, L, Kaiser, M, Kaser, JM, Keasar, T, Kim, TN, Kishinevsky, M, Landis, DA, Lavandero, B, Lavigne, C, Le Ralec, A, Lemessa, D, Letourneau, DK, Liere, H, Lu, Yanhui, Lubin, Y, Luttermoser, T, Maas, B, Mace, K, Madeira, F, Mader, V, Cortesero, AM, Marini, L, Martinez, E, Martinson, HM, Menozzi, P, Mitchell, MGE, Miyashita, T, Molina, GAR, Molina-Montenegro, MA, O'Neal, ME, Opatovsky, I, Ortiz-Martinez, S, Nash, M, Östman, Ö, Ouin, A, Pak, D, Paredes, D, Parsa, S, Parry, H, Perez-Alvarez, R, Perović, DJ, Peterson, JA, Petit, S, Philpott, SM, Plantegenest, M, Plećas, M, Pluess, T, Pons, X, Potts, SG, Pywell, RF, Ragsdale, DW, Rand, TA, Raymond, L, Ricci, B, Sargent, C, Sarthou, J-P, Saulais, J, Schäckermann, J, Schmitt, NP, Schneider, G, Schüepp, C, Sivakoff, FS, Smith, HG, Stack Whitney, K, Stutz, S, Szendrei, Z, Takada, MB, Taki, H, Tamburini, G, Thomson, LJ, Tricault, Y, Tsafack, N, Tschumi, M, Valantin-Morison, M, Van Trinh, M, van der Werf, W, Vierling, KT, Werling, BP, Wickens, JB, Wickens, VJ, Woodcock, BA, Wyckhuys, KAG, Xiao, Haijun, Yasuda, M, Yoshioka, A, and Zou Yi
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31. The Association of Mismatch Repair Status with Microscopically Positive (R1) Margins in Stage III Colorectal Cancer: A Retrospective Cohort Study.
- Author
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Smith HG, Schlesinger NH, Chiranth D, and Qvortrup C
- Subjects
- Humans, Female, Male, Retrospective Studies, Aged, Survival Rate, Middle Aged, Follow-Up Studies, Prognosis, Aged, 80 and over, Colorectal Neoplasms pathology, Colorectal Neoplasms surgery, DNA Mismatch Repair, Neoplasm Staging, Margins of Excision
- Abstract
Background: There is mounting evidence that microscopically positive (R1) margins in patients with colorectal cancer (CRC) may represent a surrogate for aggressive cancer biology rather than technical failure during surgery. However, whether detectable biological differences exist between CRC with R0 and R1 margins is unknown. We sought to investigate whether mismatch repair (MMR) status differs between Stage III CRC with R0 or R1 margins., Methods: Patients treated for Stage III CRC from January 1, 2016 to December 31, 2019 were identified by using the Danish Colorectal Cancer Group database. Patients were stratified according to MMR status (proficient [pMMR] vs. deficient [dMMR]) and margin status. Outcomes of interest included the R1 rate according to MMR and overall survival., Results: A total of 3636 patients were included, of whom 473 (13.0%) had dMMR colorectal cancers. Patients with dMMR cancers were more likely to be elderly, female, and have right-sided cancers. R1 margins were significantly more common in patients with dMMR cancers (20.5% vs. 15.2%, p < 0.001), with the greatest difference seen in the rate of R1 margins related to the primary tumour (8.9% vs. 4.7%) rather than to lymph node metastases (11.6% vs. 10.5%). This association was seen in both right- and left-sided cancers. On multivariable analyses, R1 margins, but not MMR status, were associated with poorer survival, alongside age, pN stage, perineural invasion, and extramural venous invasion., Conclusions: In patients with Stage III CRC, dMMR status is associated with increased risks of R1 margins following potentially curative surgery, supporting the use of neoadjuvant immunotherapy in this patient group., (© 2024. The Author(s).)
- Published
- 2024
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32. Structural basis of Pseudomonas aeruginosa penicillin binding protein 3 inhibition by the siderophore-antibiotic cefiderocol.
- Author
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Smith HG, Basak S, Aniebok V, Beech MJ, Alshref FM, Allen MD, Farley AJM, and Schofield CJ
- Abstract
The breakthrough cephalosporin cefiderocol, approved for clinical use in 2019, has activity against many Gram-negative bacteria. The catechol group of cefiderocol enables it to efficiently enter bacterial cells via the iron/siderophore transport system thereby reducing resistance due to porin channel mutations and efflux pump upregulation. Limited information is reported regarding the binding of cefiderocol to its key proposed target, the transpeptidase penicillin binding protein 3 (PBP3). We report studies on the reaction of cefiderocol and the related cephalosporins ceftazidime and cefepime with Pseudomonas aeruginosa PBP3, including inhibition measurements, protein observed mass spectrometry, and X-ray crystallography. The three cephalosporins form analogous 3-exomethylene products with P. aeruginosa PBP3 following elimination of the C3' side chain. pIC
50 and kinact / Ki measurements with isolated PBP3 imply ceftazidime and cefiderocol react less efficiently than cefepime and, in particular, meropenem with P. aeruginosa PBP3. Crystal structures inform on conserved and different interactions involved in binding of the three cephalosporins and meropenem to P. aeruginosa PBP3. The results will aid development of cephalosporins with improved PBP3 inhibition properties., Competing Interests: The authors have no conflicts to declare., (This journal is © The Royal Society of Chemistry.)- Published
- 2024
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33. Outcomes of patients admitted with malignant small bowel obstruction: a subgroup multicentre observational cohort analysis.
- Author
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Hupfeld NB, Burcharth J, Jensen TK, Lolle I, Nielsen LBJ, Tolver MA, Skovsen AP, and Smith HG
- Subjects
- Humans, Male, Female, Aged, Middle Aged, Aged, 80 and over, Treatment Outcome, Adult, Cohort Studies, Survival Rate, Intestinal Neoplasms mortality, Intestinal Neoplasms complications, Intestinal Neoplasms pathology, Intestinal Neoplasms surgery, Intestinal Obstruction etiology, Intestinal Obstruction mortality, Intestinal Obstruction surgery, Intestine, Small pathology, Palliative Care
- Abstract
Introduction and Purpose of the Study: Small bowel obstruction (SBO) accounts for a substantial proportion of emergency surgical admissions. Malignancy is a common cause of obstruction, either due to a primary tumour or intra-abdominal metastases. However, little is known regarding the current treatment or outcomes of patients with malignant SBO. This study aimed to characterise the treatment of malignant SBO and identify areas for potential improvement and compare overall survival of patients with malignant SBO to patients with non-malignant SBO., Materials and Methods: This was a subgroup analysis of a multicentre observational study of patients admitted with SBO. Details regarding these patients' diagnoses, treatments, and outcomes up to 1-year after admission were recorded. The primary outcome was overall survival in patients with malignant SBO., Results: A total of 316 patients with small bowel obstruction were included, of whom 33 (10.4%) had malignant SBO. Out of the 33 patients with malignant SBO, 20 patients (60.6%) were treated with palliative intent although only 7 patients were seen by a palliative team during admission. Nutritional assessments were performed on 12 patients, and 11 of these patients received parenteral nutrition. 23 patients underwent surgery, with the most common surgical interventions being loop ileostomies (9 patients) and gastrointestinal bypasses (9 patients). 4 patients underwent right hemicolectomies, with a primary anastomosis formed and 1 patient had a right hemicolectomy with a terminal ileostomy. Median survival was 114 days, and no difference was seen in survival between patients treated with or without palliative intent., Conclusion: Malignant SBO is associated with significant risks of short-term complications and a poor prognosis. Consideration should be given to the early involvement of senior decision-makers upon patient admission is essential for optimal management and setting expectation for a realistic outcome., (© 2024. The Author(s).)
- Published
- 2024
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34. Leiomyosarcoma of the abdomen and retroperitoneum; a systematic review.
- Author
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Øines MN, Smith HG, Preisler L, and Penninga L
- Abstract
Background: Intraabdominal and retroperitoneal leiomyosarcomas are rare cancers, which cause significant morbidity and mortality. Symptoms, treatment and follow up differs from other cancers, and proper diagnosis and treatment of intraabdominal and retroperitoneal leiomyosarcomas is of utmost importance. We performed a systematic review to collect and summarize available evidence for diagnosis and treatment for these tumours., Methods: We performed a systematic literature search of Pubmed from the earliest entry possible, until January 2021. Our search phrase was (((((colon) OR (rectum)) OR (intestine)) OR (abdomen)) OR (retroperitoneum)) AND (leiomyosarcoma). All hits were evaluated by two of the authors., Results: Our predefined search identified 1983 hits, we selected 218 hits and retrieved full-text copies of these. 144 studies were included in the review., Discussion: This review summarizes the current knowledge and evidence on non-uterine abdominal and retroperitoneal leiomyosarcomas. The review has revealed a lack of high-quality evidence, and randomized clinical trials. There is a great need for more substantial and high-quality research in the area of leiomyosarcomas of the abdomen and retroperitoneum., Systematic Review Registration: PROSPERO, identifier, CRD42023480527., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Øines, Smith, Preisler and Penninga.)
- Published
- 2024
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35. Small bowel obstruction.
- Author
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Walshaw J, Smith HG, and Lee MJ
- Subjects
- Humans, Intestinal Obstruction surgery, Intestinal Obstruction etiology, Intestine, Small
- Published
- 2024
- Full Text
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36. Optimizing Nutritional Needs of Burn Patients: An Evaluation of Nutritional Assessment Tools, Feeding Strategies, and Their Impact on Patient Outcomes.
- Author
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Zagales R, Watts E, Awan MU, Hernandez N, Haddadi M, Smith HG, and Elkbuli A
- Abstract
Background: Optimal nutritional support is essential to the recovery and improved outcomes of burn patients. This review aims to explore existing literature to evaluate nutrition assessment tools, feeding formulations' caloric predictive ability, timing of initiation of feeding, optimal nutritional composition, and caloric intake in burn patients., Methods: Three databases were searched to glean studies investigating nutrition in acute severe adult burn patient populations in four areas: outcomes based on feeding type and timing, the caloric predictability of nutritional assessment tools, outcomes associated with the composition of feeding formulas, and considerations related to caloric intake. Outcomes of interest included the effects of nutritional assessments using feeding type, nutritional administration timing, formula composition, and caloric intake on mortality rate, length of stay, and infection., Results: A total of 19 studies were included. Nutritional assessment tools were determined to over- or underestimate resting energy expenditure (REE). Milner was the most accurate alternative to indirect calorimetry. Early enteral nutrition in burn patients within 24 hours of admission was preferred. 5 studies evaluated micronutrients and yielded variable results. Low-fat high-carbohydrate diets were the ideal macronutrient composition. Burn patients were shown to receive lower caloric intake than recommended., Conclusions: Findings showed that while nutritional assessment tools tend to inaccurately estimate REE in burn patients, the ideal alternative to indirect calorimetry is the Milner equation. Several new equations may be worthy alternatives but require further validation. Enteral feeding should be initiated within the first 24 hours of burn injury whenever possible and should contain a high-carbohydrate/low-fat composition., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
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37. Current treatment of pT1 rectal cancers in Denmark: A retrospective national cohort study.
- Author
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Smith HG, Schlesinger NH, Krarup PM, and Nordholm-Carstensen A
- Subjects
- Humans, Denmark epidemiology, Male, Retrospective Studies, Female, Aged, Middle Aged, Treatment Outcome, Lymphatic Metastasis, Organ Sparing Treatments statistics & numerical data, Organ Sparing Treatments methods, Databases, Factual, Rectum surgery, Rectum pathology, Aged, 80 and over, Rectal Neoplasms therapy, Rectal Neoplasms pathology, Rectal Neoplasms surgery, Proctectomy methods, Neoplasm Staging
- Abstract
Aim: Organ preservation strategies for patients with rectal cancer are increasingly common. In appropriately selected patients, local excision (LE) of pT1 cancers can reduce morbidity without compromising cancer-related outcomes. However, determining the need for completion surgery after LE can be challenging, and it is unknown if prior LE compromises subsequent total mesorectal excision (TME). The aim of this study is to describe the current management of patients with pT1 rectal cancers., Method: This is a retrospective national cohort study of the Danish Colorectal Cancer Group database, including patients with newly diagnosed pT1 cancers between 2016 and 2020. Patients were stratified according to treatment into LE alone, completion TME after LE or upfront TME. The treatment and outcomes of these groups were compared., Results: A total of 1056 patients were included. Initial LE was performed in 715 patients (67.7%), of whom 194 underwent completion TME (27.1%). The remaining 341 patients underwent upfront TME (32.3%). Patients undergoing LE alone were more likely to be male with low rectal cancers and greater comorbidity. No differences in specimen quality or perioperative outcomes were noted between patients undergoing completion or upfront TME. Eighty-five patients (15.9%) had lymph node metastases (LNM). Pathological risk factors poorly discriminated between patients with and without LNM, with similar rates seen in patients with zero (14.1%), one (12.0%) or two (14.4%) risk factors., Conclusion: LE is a key component of the treatment of pT1 rectal cancer and does not appear to affect the outcomes of completion TME. Patient selection for completion TME remains a major challenge, with current stratification methods appearing to be inadequate., (© 2024 The Author(s). Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)
- Published
- 2024
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38. Pollinator-mediated effects of landscape-scale land use on grassland plant community composition and ecosystem functioning - seven hypotheses.
- Author
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Hederström V, Ekroos J, Friberg M, Krausl T, Opedal ØH, Persson AS, Petrén H, Quan Y, Smith HG, and Clough Y
- Subjects
- Animals, Plants classification, Ecosystem, Biodiversity, Pollination physiology, Grassland, Insecta physiology
- Abstract
Environmental change is disrupting mutualisms between organisms worldwide. Reported declines in insect populations and changes in pollinator community compositions in response to land use and other environmental drivers have put the spotlight on the need to conserve pollinators. While this is often motivated by their role in supporting crop yields, the role of pollinators for reproduction and resulting taxonomic and functional assembly in wild plant communities has received less attention. Recent findings suggest that observed and experimental gradients in pollinator availability can affect plant community composition, but we know little about when such shifts are to be expected, or the impact they have on ecosystem functioning. Correlations between plant traits related to pollination and plant traits related to other important ecosystem functions, such as productivity, nitrogen uptake or palatability to herbivores, lead us to expect non-random shifts in ecosystem functioning in response to changes in pollinator communities. At the same time, ecological and evolutionary processes may counteract these effects of pollinator declines, limiting changes in plant community composition, and in ecosystem functioning. Despite calls to investigate community- and ecosystem-level impacts of reduced pollination, the study of pollinator effects on plants has largely been confined to impacts on plant individuals or single-species populations. With this review we aim to break new ground by bringing together aspects of landscape ecology, ecological and evolutionary plant-insect interactions, and biodiversity-ecosystem functioning research, to generate new ideas and hypotheses about the ecosystem-level consequences of pollinator declines in response to land-use change, using grasslands as a focal system. Based on an integrated set of seven hypotheses, we call for more research investigating the putative pollinator-mediated links between landscape-scale land use and ecosystem functioning. In particular, future research should use combinations of experimental and observational approaches to assess the effects of changes in pollinator communities over multiple years and across species on plant communities and on trait distributions both within and among species., (© 2023 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)
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- 2024
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39. Current Management of T1 Colon Cancer in Denmark: A Nationwide Cohort Study.
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Ebbehøj AL, Jørgensen LN, Smith HG, and Krarup PM
- Abstract
Objective: To describe the management of T1 colon cancer in a retrospective study of a national cancer registry., Background: There is increasing interest in the potential of local excision (LE) as an organ-preserving treatment for early colon cancer. However, accurate identification of patients who may have lymph node metastases (LNM) and require further surgery is a major challenge., Methods: Patients diagnosed with T1 colon cancer in Denmark from 2016 to 2020 were included and divided according to treatment: polypectomy (referred to as LE), upfront colectomy and completion colectomy. Primary outcome was the proportion of patients diagnosed by LE. Secondary outcomes included the rate of LNM, the association of histopathological risk factors with LNM, and overall survival., Results: 1,749 patients were included, and 1,022 patients (58.4%) underwent initial LE. The rate of R1 margins after initial LE was 31.0%. Colectomy was performed in 1,160 patients (upfront in 727, completion in 433), of whom 58.3% had pT1 cancer. The rate of LNM was 11.5%. Rates of LNM were similar in patients undergoing upfront or completion colectomy (10.2% vs 12.4%, P=0.392), and in patients with any single histopathological risk factor compared to those with none (8.9% vs 10.6%, P=0.565). Although overall survival was significantly shorter in patients undergoing LE alone, no association between survival and treatment strategy was found on multivariable analysis., Conclusions: LE is the most common mode of diagnosis in patients with T1 colon cancer and does not negatively impact survival and postoperative outcomes. Current strategies to stratify patients to completion surgery appear insufficient, and more robust predictors are needed., Competing Interests: Conflicts of Interest and Sources of Funding: Dr. Krarup has received personal fees and served as proctor and speaker for Intuitive Surgical, and received a research grant from Pharmacosmos A/S. The remaining authors declare no conflicts of interest. The current study was supported by the Arvid Nilsson’s Foundation, Bispebjerg and Frederiksberg Hospitals’ Internal Research Grants, the Else and Mogens Wedell-Wedellsborg’s Foundation, the Inge and Jørgen Larsen’s Memorial Foundation, and the NEYE Foundation., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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40. Neoadjuvant treatment of colorectal cancer: comprehensive review.
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Smith HG, Nilsson PJ, Shogan BD, Harji D, Gambacorta MA, Romano A, Brandl A, and Qvortrup C
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- Humans, Immunotherapy methods, Rectal Neoplasms therapy, Rectal Neoplasms pathology, Chemoradiotherapy methods, Neoadjuvant Therapy, Colorectal Neoplasms therapy
- Abstract
Background: Neoadjuvant therapy has an established role in the treatment of patients with colorectal cancer. However, its role continues to evolve due to both advances in the available treatment modalities, and refinements in the indications for neoadjuvant treatment and subsequent surgery., Methods: A narrative review of the most recent relevant literature was conducted., Results: Short-course radiotherapy and long-course chemoradiotherapy have an established role in improving local but not systemic disease control in patients with rectal cancer. Total neoadjuvant therapy offers advantages over short-course radiotherapy and long-course chemoradiotherapy, not only in terms of increased local response but also in reducing the risk of systemic relapses. Non-operative management is increasingly preferred to surgery in patients with rectal cancer and clinical complete responses but is still associated with some negative impacts on functional outcomes. Neoadjuvant chemotherapy may be of some benefit in patients with locally advanced colon cancer with proficient mismatch repair, although patient selection is a major challenge. Neoadjuvant immunotherapy in patients with deficient mismatch repair cancers in the colon or rectum is altering the treatment paradigm for these patients., Conclusion: Neoadjuvant treatments for patients with colon or rectal cancers continue to evolve, increasing the complexity of decision-making for patients and clinicians alike. This review describes the current guidance and most recent developments., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)
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- 2024
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41. Evolutionary plant-pollinator responses to anthropogenic land-use change: impacts on ecosystem services.
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Pontarp M, Runemark A, Friberg M, Opedal ØH, Persson AS, Wang L, and Smith HG
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- Animals, Plants genetics, Insecta genetics, Agriculture, Ecosystem, Pollination
- Abstract
Agricultural intensification at field and landscape scales, including increased use of agrochemicals and loss of semi-natural habitats, is a major driver of insect declines and other community changes. Efforts to understand and mitigate these effects have traditionally focused on ecological responses. At the same time, adaptations to pesticide use and habitat fragmentation in both insects and flowering plants show the potential for rapid evolution. Yet we lack an understanding of how such evolutionary responses may propagate within and between trophic levels with ensuing consequences for conservation of species and ecological functions in agroecosystems. Here, we review the literature on the consequences of agricultural intensification on plant and animal evolutionary responses and interactions. We present a novel conceptualization of evolutionary change induced by agricultural intensification at field and landscape scales and emphasize direct and indirect effects of rapid evolution on ecosystem services. We exemplify by focusing on economically and ecologically important interactions between plants and pollinators. We showcase available eco-evolutionary theory and plant-pollinator modelling that can improve predictions of how agricultural intensification affects interaction networks, and highlight available genetic and trait-focused methodological approaches. Specifically, we focus on how spatial genetic structure affects the probability of propagated responses, and how the structure of interaction networks modulates effects of evolutionary change in individual species. Thereby, we highlight how combined trait-based eco-evolutionary modelling, functionally explicit quantitative genetics, and genomic analyses may shed light on conditions where evolutionary responses impact important ecosystem services., (© 2023 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)
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- 2024
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42. Selection despite low genetic diversity and high gene flow in a rapid island invasion of the bumblebee, Bombus terrestris.
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Kardum Hjort C, Paris JR, Smith HG, and Dudaniec RY
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- Animals, Australia, Bees genetics, Genetic Variation genetics, Tasmania, Gene Flow, Introduced Species
- Abstract
Invasive species are predicted to adjust their morphological, physiological and life-history traits to adapt to their non-native environments. Although a loss of genetic variation during invasion may restrict local adaptation, introduced species often thrive in novel environments. Despite being founded by just a few individuals, Bombus terrestris (Hymenoptera: Apidae) has in less than 30 years successfully spread across the island of Tasmania (Australia), becoming abundant and competitive with native pollinators. We use RADseq to investigate what neutral and adaptive genetic processes associated with environmental and morphological variation allow B. terrestris to thrive as an invasive species in Tasmania. Given the widespread abundance of B. terrestris, we expected little genetic structure across Tasmania and weak signatures of environmental and morphological selection. We found high gene flow with low genetic diversity, although with significant isolation-by-distance and spatial variation in effective migration rates. Restricted migration was evident across the mid-central region of Tasmania, corresponding to higher elevations, pastural land, low wind speeds and low precipitation seasonality. Tajima's D indicated a recent population expansion extending from the south to the north of the island. Selection signatures were found for loci in relation to precipitation, wind speed and wing loading. Candidate loci were annotated to genes with functions related to cuticle water retention and insect flight muscle stability. Understanding how a genetically impoverished invasive bumblebee has rapidly adapted to a novel island environment provides further understanding about the evolutionary processes that determine successful insect invasions, and the potential for invasive hymenopteran pollinators to spread globally., (© 2023 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)
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- 2024
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43. Seed treatment with clothianidin induces changes in plant metabolism and alters pollinator foraging preferences.
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Klatt BK, Wurz A, Herbertsson L, Rundlöf M, Svensson GP, Kuhn J, Vessling S, de La Vega B, Tscharntke T, Clough Y, and Smith HG
- Subjects
- Bees, Animals, Glucosinolates, Neonicotinoids toxicity, Plant Nectar, Seeds chemistry, Pollination, Insecticides toxicity, Insecticides analysis
- Abstract
Neonicotinoids, systemic insecticides that are distributed into all plant tissues and protect against pests, have become a common part of crop production, but can unintentionally also affect non-target organisms, including pollinators. Such effects can be direct effects from insecticide exposure, but neonicotinoids can affect plant physiology, and effects could therefore also be indirectly mediated by changes in plant phenology, attractiveness and nutritional value. Under controlled greenhouse conditions, we tested if seed treatment with the neonicotinoid clothianidin affected oilseed rape's production of flower resources for bees and the content of the secondary plant products glucosinolates that provide defense against herbivores. Additionally, we tested if seed treatment affected the attractiveness of oilseed rape to flower visiting bumblebees, using outdoor mesocosms. Flowers and leaves of clothianidin-treated plants had different profiles of glucosinolates compared with untreated plants. Bumblebees in mesocosms foraged slightly more on untreated plants. Neither flower timing, flower size nor the production of pollen and nectar differed between treatments, and therefore cannot explain any preference for untreated oilseed rape. We instead propose that this small but significant preference for untreated plants was related to the altered glucosinolate profile caused by clothianidin. Thereby, this study contributes to the understanding of the complex relationships between neonicotinoid-treated crops and pollinator foraging choices, by suggesting a potential mechanistic link by which insecticide treatment can affect insect behavior., (© 2023. The Author(s).)
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- 2023
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44. Variations in the definition and perceived importance of positive resection margins in patients with colorectal cancer - an EYSAC international survey.
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Smith HG, Schlesinger NH, Qvortrup C, Chiranth D, Lundon D, Ben-Yaacov A, Caballero C, Suppan I, Kok JH, Holmberg CJ, Mohan H, Montagna G, Santrac N, Sayyed R, Schrage Y, Sgarbura O, Ceelen W, Lorenzon L, and Brandl A
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- Humans, Margins of Excision, Surveys and Questionnaires, Europe, Retrospective Studies, Surgical Oncology, Colonic Neoplasms
- Abstract
Introduction: Microscopically positive resection margins (R1) are associated with poorer outcomes in patients with colorectal cancer. However, different definitions of R1 margins exist. It is unclear to what extent the definitions used in everyday clinical practice differ within and between nations. This study sought to investigate variations in the definition of R1 margins in colorectal cancer and the importance of margin status in clinical decision-making., Materials and Methods: A 14-point survey was developed by members of The European Society of Surgical Oncology (ESSO) Youngs Surgeons and Alumni Club (EYSAC) Research Academy targeting all members of the multidisciplinary team (MDT) treating patients with colorectal cancer. The survey was distributed on social media, in ESSO's monthly newsletter and via national societies., Results: In total, 137 responses were received. Most respondents were from Europe (89.7%), with the majority from Denmark (56.9%). Less than 2/3 of respondents defined R1 margins as the presence of viable cancer cells ≤1 mm of the margin. Only 60% reported that subdivisions of R1 margins (primary tumour vs tumour deposit vs metastatic lymph node) are routinely available. More than 20% of respondents reported that pathology reports are not routinely reviewed at MDT meetings. Less than half of respondents considered margin status in decision-making for type and duration of adjuvant chemotherapy in Stage III colon cancer., Conclusion: The definitions and perceived clinical importance of microscopically positive margins in patients with colorectal cancer appear to vary. Adoption of an international dataset for pathology reporting may help to standardise current practices., Competing Interests: Declarations of competing interest The authors have no declarations of interest, (© 2023 Published by Elsevier Ltd.)
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- 2023
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45. One-year outcomes following operative or non-operative management of adhesional small bowel obstruction.
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Mortensen MR, Alouda M, Bond Z, Burcharth J, Finne KF, Jensen TK, Lolle I, Malik T, Ngo-Stuyt L, Nielsen LBJ, Olausson M, Skovsen AP, Tolver MA, and Smith HG
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- Humans, Hospitalization, Length of Stay, Prospective Studies, Retrospective Studies, Intestinal Obstruction etiology, Intestinal Obstruction surgery
- Abstract
Background: A trial of initial non-operative management is recommended in stable patients with adhesional small bowel obstruction. However, recent retrospective studies have suggested that early operative management may be of benefit in reducing subsequent recurrences. This study aimed to compare recurrence rates and survival in patients with adhesional small bowel obstruction treated operatively or non-operatively., Methods: This was a prospective cohort study conducted at six acute hospitals in Denmark, including consecutive patients admitted with adhesional small bowel obstruction over a 4-month interval. Patients were stratified into two groups according to their treatment (operative versus non-operative) and followed up for 1 year after their index admission. Primary outcomes were recurrence of small bowel obstruction and overall survival within 1 year of index admission., Results: A total of 201 patients were included, 118 (58.7 per cent) of whom were treated operatively during their index admission. Patients undergoing operative treatment had significantly better 1-year recurrence-free survival compared with patients managed non-operatively (operative 92.5 per cent versus non-operative 66.6 per cent, P <0.001). However, when the length of index admission was taken into account, patients treated non-operatively spent significantly less time admitted to hospital in the first year (median 3 days non-operative versus 6 days operative, P <0.001). On multivariable analysis, operative treatment was associated with decreased risks of recurrence (HR 0.22 (95 per cent c.i. 0.10-0.48), P <0.001) but an increased all-cause mortality rate (HR 2.48 (95 per cent c.i. 1.13-5.46), P = 0.024)., Conclusion: Operative treatment of adhesional small bowel obstruction is associated with reduced risks of recurrence but increased risk of death in the first year after admission., Registration Number: NCT04750811 (http://www.clinicaltrials.gov).prior (registration date: 11 February 2021)., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)
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- 2023
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46. Impact of adjuvant chemotherapy on long-term overall survival in patients with high-risk stage II colon cancer: a nationwide cohort study.
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Rosberg V, Jessen M, Qvortrup C, Smith HG, and Krarup PM
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- Humans, Aged, Cohort Studies, Chemotherapy, Adjuvant, Risk Factors, Anastomotic Leak, Neoplasm Staging, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Retrospective Studies, Colonic Neoplasms surgery
- Abstract
Background: This study aimed to investigate the impact of adjuvant chemotherapy on long-term survival in unselected patients with high-risk stage II colon cancer including an analysis of each high-risk feature., Materials and Methods: Data from the Danish Colorectal Cancer Group, the National Patient Registry and the Danish Pathology Registry from 2014 to 2018 were merged. Patients surviving > 90 days were included. High-risk features were defined as emergency presentation, including self-expanding metal stents (SEMS)/loop-ostomy as a bridge to resection, grade B or C anastomotic leakage, pT4 tumors, lymph node yield < 12 or signet cell carcinoma. Eligibility criteria for chemotherapy were age < 75 years, proficient MMR gene expression, and performance status ≤ 2. The primary outcome was 5-year overall survival. Secondary outcomes included the proportion of eligible patients allocated for adjuvant chemotherapy and the time to first administration., Results: In total 939 of 3937 patients with stage II colon cancer had high-risk features, of whom 408 were eligible for chemotherapy. 201 (49.3%) patients received adjuvant chemotherapy, with a median time to first administration of 35 days after surgery. The crude 5-year overall survival was 84.9% in patients receiving adjuvant chemotherapy compared with 66.3% in patients not receiving chemotherapy, p < 0.001. This association corresponded to an absolute risk difference of 14%., Conclusion: 5-year overall survival was significantly higher in patients with high-risk stage II colon cancer treated with adjuvant chemotherapy compared with no chemotherapy. Adjuvant treatment was given to less than half of the patients who were eligible for it.
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- 2023
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47. Real-world accuracy of computed tomography in patients admitted with small bowel obstruction: a multicentre prospective cohort study.
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Nielsen LBJ, Ærenlund MP, Alouda M, Azzam M, Bjerke T, Burcharth J, Dibbern CB, Jensen TK, Jordhøj JQ, Lolle I, Malik T, Ngo-Stuyt L, Nielsen EØ, Olausson M, Skovsen AP, Tolver MA, and Smith HG
- Subjects
- Humans, Prospective Studies, Retrospective Studies, Hospitalization, Tomography, X-Ray Computed, Intestinal Obstruction diagnostic imaging, Intestinal Obstruction surgery
- Abstract
Purpose: Small bowel obstruction (SBO) is a common surgical emergency. Previous studies have shown the value computed tomography (CT) scanning in both confirming this diagnosis and identifying indications for urgent surgical intervention, such as strangulated bowel or closed loop obstructions. However, most of the literature is based on retrospective expert review of previous imaging and little data regarding the real-time accuracy of CT reporting is available. Here, we investigated the real-world accuracy of CT reporting in patients admitted with SBO., Methods: This was a multicentre prospective study including consecutive patients admitted with SBO. The primary outcomes were the sensitivity and specificity of CT scanning for bowel obstruction with ischaemia and closed loop obstruction. Data were retrieved from the original CT reports written by on-call radiologists and compared with operative findings., Results: One hundred seventy-six patients were included, all of whom underwent CT scanning with intravenous contrast followed by operative management of SBO. Bowel obstruction with ischaemia was noted in 20 patients, with a sensitivity and specificity of CT scanning of 40.0% and 85.5%, respectively. Closed loop obstructions were noted in 26 patients, with a sensitivity and specificity of CT scanning of 23.1% and 98.0%, respectively., Conclusions: The real-world accuracy of CT scanning appears to be lower than previously reported in the literature. Strategies to address this could include the development of standardised reporting schemas and to increase the surgeon's own familiarity with relevant CT features in patients admitted with SBO., (© 2023. The Author(s).)
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- 2023
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48. Inter-hospital variation in management of patients with small bowel obstruction in Denmark.
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Tolver MA, Ærenlund MP, Azzam M, Bjerke T, Burcharth J, Dibbern CB, Jensen TK, Jordhøj JQ, Lolle I, Ngo-Stuyt L, Nielsen EØ, Nielsen LBJ, Olausson M, Skovsen AP, and Smith HG
- Subjects
- Humans, Prospective Studies, Hospitals, Length of Stay, Denmark, Intestinal Obstruction etiology, Intestinal Obstruction surgery
- Abstract
Introduction: Inter-hospital variation in the management of small bowel obstruction (SBO) has been described in other countries, but the extent to which similar variations exist in Denmark remains unknown. This study aimed to compare the management of SBO between hospitals in Denmark and identify potential areas for improvement METHODS. This was a multicentre prospective study performed at six emergency hospitals. Patients aged ≥ 18 years with a diagnosis of SBO were eligible for inclusion. The primary study endpoints were the proportion of patients undergoing operative versus non-operative management, laparoscopic surgery versus open surgery and the success rate of non-operative management., Results: A total of 316 patients were included. No differences were noted in diagnostic pathways or operative versus non-operative management. However, variations were noted in compliance with peri-operative care bundles, ranging from 63.2% to 95.8%. The surgical approach also varied, with the use of laparoscopic surgery ranging from 20.7% to 71.0% (p less-than 0.001). Variations were also noted in duration of surgery (63-124 minutes, p less-than 0.001), time to re-introduction of normal diet and length of hospital stay (3-8.5 days, p less-than 0.001). No differences were observed in 30-day or 90-day mortality rates., Conclusion: The management of SBO in Denmark is relatively standardised. Future efforts should focus on improving adherence to multidisciplinary peri-operative protocols, optimising patient selection for laparoscopic surgery and standardising nutritional therapy., Funding: None., Trial Registration: NCT04750811., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)
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- 2023
49. Molecular basis for short-chain thioester hydrolysis by acyl hydrolase domains in trans -acyltransferase polyketide synthases.
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Fage CD, Passmore M, Tatman BP, Smith HG, Jian X, Dissanayake UC, Andrés Cisneros G, Challis GL, Lewandowski JR, and Jenner M
- Abstract
Polyketide synthases (PKSs) are multi-domain enzymatic assembly lines that biosynthesise a wide selection of bioactive natural products from simple building blocks. In contrast to their cis -acyltransferase (AT) counterparts, trans -AT PKSs rely on stand-alone AT domains to load extender units onto acyl carrier protein (ACP) domains embedded in the core PKS machinery. Trans -AT PKS gene clusters also encode acyl hydrolase (AH) domains, which are predicted to share the overall fold of AT domains, but hydrolyse aberrant acyl chains from ACP domains, thus ensuring efficient polyketide biosynthesis. How such domains specifically target short acyl chains, in particular acetyl groups, tethered as thioesters to the substrate-shuttling ACP domains, with hydrolytic rather than acyl transfer activity, has remained unclear. To answer these questions, we solved the first structure of an AH domain and performed structure-guided activity assays on active site variants. Our results offer key insights into chain length control and selection against coenzyme A-tethered substrates, and clarify how the interaction interface between AH and ACP domains contributes to recognition of cognate and non-cognate ACP domains. Combining our experimental findings with molecular dynamics simulations allowed for the production of a data-driven model of an AH:ACP domain complex. Our results advance the currently incomplete understanding of polyketide biosynthesis by trans -AT PKSs, and provide foundations for future bioengineering efforts.
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- 2023
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50. Transvaginal resection of gastrointestinal stromal tumor in the rectum.
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Penninga L, Smith HG, Brinch CM, Krarup-Hansen A, and Preisler L
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- Female, Humans, Aged, Imatinib Mesylate therapeutic use, Pelvis, Rectum, Gastrointestinal Stromal Tumors diagnosis, Gastrointestinal Stromal Tumors drug therapy, Gastrointestinal Stromal Tumors surgery
- Abstract
A gastrointestinal stromal tumour (GIST) can occur anywhere in the gastrointestinal tract, though rectal GIST is rare. The primary treatment of GIST is surgical resection. Neoadjuvant imatinib treatment may cause tumor reduction and allow local resection. This is a case report of a 70-year-old woman with a high level of comorbidity who was diagnosed with a low rectal GIST. She was successfully treated with imatinib followed by complete GIST resection using a transvaginal technique.
- Published
- 2023
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