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1. Short-Term Pediatric Acclimatization to Adaptive Hearing Aid Technology

Author: Pinkl, J, Cash, EK, Evans, TC, Neijman, T, Hamilton, JW, Ferguson, SD, Martinez, JL, Rumley, J, Hunter, LL, Moore, DR, Stewart, HJ, Pinkl, J, Cash, EK, Evans, TC, Neijman, T, Hamilton, JW, Ferguson, SD, Martinez, JL, Rumley, J, Hunter, LL, Moore, DR, and Stewart, HJ
Abstract: Purpose This exploratory study assessed the perceptual, cognitive, and academic learning effects of an adaptive, integrated, directionality, and noise reduction hearing aid program in pediatric users. Method Fifteen pediatric hearing aid users (6–12 years old) received new bilateral, individually fitted Oticon Opn hearing aids programmed with OpenSound Navigator (OSN) processing. Word recognition in noise, sentence repetition in quiet, nonword repetition, vocabulary learning, selective attention, executive function, memory, and reading and mathematical abilities were measured within 1 week of the initial hearing aid fitting and 2 months post fit. Caregivers completed questionnaires assessing their child's listening and communication abilities prior to study enrollment and after 2 months of using the study hearing aids. Results Caregiver reporting indicated significant improvements in speech and sound perception, spatial sound awareness, and the ability to participate in conversations. However, there was no positive change in performance in any of the measured skills. Mathematical scores significantly declined after 2 months. Conclusions OSN provided a perceived improvement in functional benefit, compared to their previous hearing aids, as reported by caregivers. However, there was no positive change in listening skills, cognition, and academic success after 2 months of using OSN. Findings may have been impacted by reporter bias, limited sample size, and a relatively short trial period. This study took place during the summer when participants were out of school, which may have influenced the decline in mathematical scores. The results support further exploration with age- and audiogram-matched controls, larger sample sizes, and longer test–retest intervals that correspond to the academic school year.
Published: 2021

2. Listening Difficulties in Children:Behavior and Brain Activation Produced by Dichotic Listening of CV Syllables

Author: Moore, DR, Hugdahl, K, Stewart, HJ, Vannest, J, Perdew, AJ, Sloat, NT, Cash, EK, Hunter, LL, Moore, DR, Hugdahl, K, Stewart, HJ, Vannest, J, Perdew, AJ, Sloat, NT, Cash, EK, and Hunter, LL
Abstract: Listening difficulties (LiD) are common in children with and without hearing loss. Impaired interactions between the two ears have been proposed as an important component of LiD when there is no hearing loss, also known as auditory processing disorder (APD). We examined the ability of 6–13 year old (y.o.) children with normal audiometric thresholds to identify and selectively attend to dichotically presented CV syllables using the Bergen Dichotic Listening Test (BDLT; www.dichoticlistening.com). Children were recruited as typically developing (TD; n = 39) or having LiD (n = 35) based primarily on composite score of the ECLiPS caregiver report. Different single syllables (ba, da, ga, pa, ta, ka) were presented simultaneously to each ear (6 × 36 trials). Children reported the syllable heard most clearly (non-forced, NF) or the syllable presented to the right [forced right (FR)] or left [forced left (FL)] ear. Interaural level differences (ILDs) manipulated bottom-up perceptual salience. Dichotic listening (DL) data [correct responses, laterality index (LI)] were analyzed initially by group (LiD, TD), age, report method (NF, FR, FL), and ILD (0, ± 15 dB) and compared with speech-in-noise thresholds (LiSN-S) and cognitive performance (NIH Toolbox). fMRI measured brain activation produced by a receptive speech task that segregated speech, phonetic, and intelligibility components. Some activated areas [planum temporale (PT), inferior frontal gyrus (IFG), and orbitofrontal cortex (OFC)] were correlated with dichotic results in TD children only. Neither group, age, nor report method affected the LI of right/left recall. However, a significant interaction was found between ear, group, and ILD. Laterality indices were small and tended to increase with age, as previously reported. Children with LiD had significantly larger mean LIs than TD children for stimuli with ILDs, especially those favoring the left ear. Neural activity associated with Speech, Phonetic, and Intelligibili
Published: 2020

3. Involuntary Orienting and Conflict Resolution during Auditory Attention:The Role of Ventral and Dorsal Streams

Author: Stewart, HJ, Shen, D, Sham, N, Alain, C, Stewart, HJ, Shen, D, Sham, N, and Alain, C
Abstract: Selective attention to sound object features such as pitch and location is associated with enhanced brain activity in ventral and dorsal streams, respectively. We examined the role of these pathways in involuntary orienting and conflict resolution using fMRI. Participants were presented with two tones that may, or may not, share the same nonspatial (frequency) or spatial (location) auditory features. In separate blocks of trials, participants were asked to attend to sound frequency or sound location and ignore the change in the task-irrelevant feature. In both attend-frequency and attend-location tasks, RTs were slower when the task-irrelevant feature changed than when it stayed the same (involuntary orienting). This behavioral cost coincided with enhanced activity in the pFC and superior temporal gyrus. Conflict resolution was examined by comparing situations where the change in stimulus features was congruent (both features changed) and incongruent (only one feature changed). Participants were slower and less accurate for incongruent than congruent sound features. This congruency effect was associated with enhanced activity in the pFC and was greater in the right superior temporal gyrus and medial frontal cortex during the attend-location task than during the attend-frequency task. Together, these findings do not support a strict division of “labor” into ventral and dorsal streams but rather suggest interactions between these pathways in situations involving changes in task-irrelevant sound feature and conflict resolution. These findings also validate the Test of Attention in Listening task by revealing distinct neural correlates for involuntary orienting and conflict resolution.
Published: 2020

4. Auditory cognition and perception of action video game players

Author: Stewart, HJ, Martinez, JL, Perdew, A, Green, CS, Moore, DR, Stewart, HJ, Martinez, JL, Perdew, A, Green, CS, and Moore, DR
Abstract: A training method to improve speech hearing in noise has proven elusive, with most methods failing to transfer to untrained tasks. One common approach to identify potentially viable training paradigms is to make use of cross-sectional designs. For instance, the consistent finding that people who chose to avidly engage with action video games as part of their normal life also show enhanced performance on non-game visual tasks has been used as a foundation to test the causal impact of such game play via true experiments (e.g., in more translational designs). However, little work has examined the association between action video game play and untrained auditory tasks, which would speak to the possible utility of using such games to improve speech hearing in noise. To examine this possibility, 80 participants with mixed action video game experience were tested on a visual reaction time task that has reliably shown superior performance in action video game players (AVGPs) compared to non-players (≤ 5 h/week across game categories) and multi-genre video game players (> 5 h/week across game categories). Auditory cognition and perception were tested using auditory reaction time and two speech-in-noise tasks. Performance of AVGPs on the visual task replicated previous positive findings. However, no significant benefit of action video game play was found on the auditory tasks. We suggest that, while AVGPs interact meaningfully with a rich visual environment during play, they may not interact with the games’ auditory environment. These results suggest that far transfer learning during action video game play is modality-specific and that an acoustically relevant auditory environment may be needed to improve auditory probabilistic thinking.
Published: 2020

5. Molecular biology of trophoblast interferons and studies of their effects in vivo

Author: Flint, APF, primary, Parkinson, TJ, additional, Stewart, HJ, additional, Vallet, JL, additional, and Lamming, GE, additional
Published: 2019
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6. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years

Author: Pan, H, Gray, R, Braybrooke, J, Davies, C, Taylor, C, Mcgale, P, Peto, R, Pritchard, Ki, Bergh, J, Dowsett, M, Hayes, Df, Albain, K, Anderson, S, Arriagada, R, Barlow, W, Bartlett, J, Bergsten‐nordström, E, Bliss, J, Boccardo, F, Bradley, R, Brain, E, Cameron, D, Clarke, M, Coates, A, Coleman, R, Correa, C, Costantino, J, Cuzick, J, Davidson, N, Dodwell, D, Di Leo, A, Ewertz, M, Forbes, J, Gelber, R, Gnant, M, Goldhirsch, A, Goodwin, P, Hill, C, Ingle, J, Jagsi, R, Janni, W, Loibl, S, Mackinnon, E, Martin, M, Mukai, H, Norton, L, Ohashi, Y, Paik, S, Perez, E, Piccart, M, Pierce, L, Poortmans, P, Raina, V, Ravdin, P, Regan, M, Robertson, J, Rutgers, E, Slamon, D, Sparano, J, Swain, S, Tutt, A, Viale, G, Von Minckwitz, G, Wang, X, Whelan, T, Wilcken, N, Winer, E, Wolmark, N, Wood, W, Zambetti, M, Alberro, Ja, Ballester, B, Deulofeu, P, Fábregas, R, Fraile, M, Gubern, Jm, Janer, J, Moral, A, De Pablo Jl, Peñalva, G, Puig, P, Ramos, M, Rojo, R, Santesteban, P, Serra, C, Solà, M, Solarnau, L, Solsona, J, Veloso, E, Vidal, S, Abe, O, Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Sakai, K, Sugimachi, K, Toi, M, Tominaga, T, Uchino, J, Yoshida, M, Haybittle, Jl, Leonard, Cf, Calais, G, Garaud, P, Collett, V, Delmestri, A, Sayer, J, Harvey, Vj, Holdaway, Im, Kay, Rg, Mason, Bh, Forbes, Jf, Balic, M, Bartsch, R, Fesl, C, Fitzal, F, Fohler, H, Greil, R, Jakesz, R, Marth, C, Mlineritsch, B, Pfeiler, G, Singer, Cf, Steger, Gg, Stöger, H, Canney, P, Yosef, Hma, Focan, C, Peek, U, Oates, Gd, Powell, J, Durand, M, Mauriac, L, Dolci, S, Larsimont, D, Nogaret, Jm, Philippson, C, Piccart, Mj, Masood, Mb, Parker, D, Price, Jj, Lindsay, Ma, Mackey, J, Hupperets, Psgj, Bates, T, Blamey, Rw, Chetty, U, Ellis, Io, Mallon, E, Morgan, Dal, Patnick, J, Pinder, S, Lohrisch, C, Nichol, A, Bramwell, Vh, Chen, Be, Gelmon, K, Goss, Pe, Levine, Mn, Parulekar, W, Pater, Jl, Shepherd, Le, Tu, D, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Weiss, Rb, Abu‐zahra, Ht, Portnoj, Sm, Bowden, S, Brookes, C, Dunn, J, Fernando, I, Lee, M, Poole, C, Rea, D, Spooner, D, Barrett‐lee, Pj, Mansel, Re, Monypenny, Ij, Gordon, Nh, Davis, Hl, Sestak, I, Lehingue, Y, Romestaing, P, Dubois, Jb, Delozier, T, Griffon, B, Mace Lesec’h, J, De La Lande, B, Mouret‐fourme, E, Mustacchi, G, Petruzelka, L, Pribylova, O, Owen, Jr, Harbeck, N, Jänicke, F, Meisner, C, Schmitt, M, Thomssen, C, Meier, P, Shan, Y, Shao, Yf, Zhao, Db, Chen, Zm, Howell, A, Swindell, R, Boddington, C, Burrett, Ja, Cutter, D, Duane, F, Evans, V, Gettins, L, Godwin, J, James, S, Kerr, A, Liu, H, Mannu, G, Mchugh, T, Morris, P, Read, S, Wang, Y, Wang, Z, Albano, J, De Oliveira Cf, Gervásio, H, Gordilho, J, Ejlertsen, B, Jensen, Mb, Johansen, H, Mouridsen, H, Palshof, T, Gelman, Rs, Harris, Jr, Henderson, C, Shapiro, Cl, Christiansen, P, Mouridsen, Ht, Fehm, T, Trampisch, Hj, Dalesio, O, De Vries Ege, Rodenhuis, S, Van Tinteren, H, Comis, Rl, Davidson, Ne, Robert, N, Sledge, G, Solin, Lj, Sparano, Ja, Tormey, Dc, Dixon, Jm, Forrest, P, Jack, W, Kunkler, I, Rossbach, J, Klijn, Jgm, Treurniet‐donker, Ad, Van Putten Wlj, Rotmensz, N, Veronesi, U, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, Jp, Van De Velde Cjh, Cunningham, Mp, Brufsky, Am, Coleman, Re, Llombart, Ha, Huovinen, R, Joensuu, H, Costa, A, Bonadonna, G, Gianni, L, Valagussa, P, Goldstein, Lj, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Luporsi, E, Namer, M, Carrasco, E, Segui, Ma, Eiermann, W, Hilfrich, J, Jonat, W, Kaufmann, M, Kreienberg, R, Schumacher, M, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Blohmer, Ju, Costa, Sd, Eidtmann, H, Gerber, B, Jackisch, C, De Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Pirozzoli, Mc, Sacco, M, Valentini, M, Mcardle, Cs, Smith, Dc, Stallard, S, Dent, Dm, Gudgeon, Ca, Hacking, A, Murray, E, Panieri, E, Werner, Id, Galligioni, E, Leone, B, Vallejo, Ct, Zwenger, A, Lopez, M, Erazo, A, Medina, Jy, Horiguchi, J, Takei, H, Fentiman, Is, Hayward, Jl, Rubens, Rd, Skilton, D, Scheurlen, H, Sohn, Hc, Untch, M, Dafni, U, Markopoulos, C, Fountzilas, G, Mavroudis, D, Klefstrom, P, Blomqvist, C, Saarto, T, Gallen, M, Tinterri, C, Margreiter, R, De Lafontan, B, Mihura, J, Roché, H, Asselain, B, Salmon, Rj, Vilcoq, Jr, André, F, Delaloge, S, Koscielny, S, Michiels, S, Rubino, C, A'Hern, R, Ellis, P, Kilburn, L, Yarnold, Jr, Benraadt, J, Kooi, M, Van De Velde Ao, Van Dongen Ja, Vermorken, Jb, Castiglione, M, Colleoni, M, Collins, J, Gelber, Rd, Lindtner, J, Price, Kn, Regan, Mm, Rudenstam, Cm, Senn, Hj, Thuerlimann, B, Bliss, Jm, Chilvers, Ced, Coombes, Rc, Hall, E, Marty, M, Buyse, M, Possinger, K, Schmid, P, Wallwiener, D, Bighin, C, Bruzzi, P, Del Mastro, L, Dozin, B, Pastorino, S, Pronzato, P, Sertoli, Mr, Foster, L, George, Wd, Stewart, Hj, Stroner, P, Borovik, R, Hayat, H, Inbar, Mj, Peretz, T, Robinson, E, Camerini, T, Formelli, F, Martelli, G, Di Mauro Mg, Perrone, F, Amadori, D, Martoni, A, Pannuti, F, Camisa, R, Musolino, A, Passalacqua, R, Iwata, H, Shien, T, Ikeda, T, Inokuchi, K, Sawa, K, Sonoo, H, Sadoon, M, Tulusan, Ah, Kohno, N, Miyashita, M, Takao, S, Ahn, Jh, Jung, Kh, Korzeniowski, S, Skolyszewski, J, Ogawa, M, Yamashita, J, Bastiaannet, E, Liefers, Gj, Christiaens, R, Neven, P, Paridaens, R, Van Den Bogaert, W, Braun, S, Martin, P, Romain, S, Janauer, M, Seifert, M, Sevelda, P, Zielinski, Cc, Hakes, T, Hudis, Ca, Wittes, R, Giokas, G, Kondylis, D, Lissaios, B, De La Huerta, R, Sainz, Mg, Ro, J, Camphausen, K, Danforth, D, Lichter, A, Lippman, M, Smart, D, Steinberg, S, D’Amico, C, Lioce, M, Paradiso, A, Ohno, S, Bass, G, Brown, A, Bryant, J, Dignam, J, Fisher, B, Geyer, C, Mamounas, Ep, Redmond, C, Wickerham, L, Aihara, T, Hozumi, Y, Baum, M, Jackson, Im, Palmer, Mk, Ingle, Jn, Suman, Vj, Bengtsson, No, Emdin, S, Jonsson, H, Venturini, M, Lythgoe, Jp, Kissin, M, Erikstein, B, Hannisdal, E, Jacobsen, Ab, Reinertsen, Kv, Varhaug, Je, Gundersen, S, Hauer‐jensen, M, Høst, H, Nissen‐meyer, R, Mitchell, Ak, Robertson, Jfr, Ueo, H, Di Palma, M, Mathé, G, Misset, Jl, Levine, M, Morimoto, K, Takatsuka, Y, Crossley, E, Harris, A, Talbot, D, Taylor, M, Cocconi, G, Di Blasio, B, Ivanov, V, Paltuev, R, Semiglazov, V, Brockschmidt, J, Cooper, Mr, Falkson, Ci, Hadji, P, A’Hern, R, Makris, A, Parton, M, Pennert, K, Powles, Tj, Smith, Ie, Gazet, Jc, Browne, L, Graham, P, Corcoran, N, Clack, G, Van Poznak, C, Deshpande, N, Di Martino, L, Douglas, P, Lindtner, A, Notter, G, Bryant, Ajs, Ewing, Gh, Firth, La, Krushen‐kosloski, Jl, Anderson, H, Killander, F, Malmström, P, Rydén, L, Arnesson, Lg, Carstensen, J, Dufmats, M, Fohlin, H, Nordenskjöld, B, Söderberg, M, Carpenter, Jt, Murray, N, Royle, Gt, Simmonds, Pd, Crowley, J, Gralow, J, Hortobagyi, G, Livingston, R, Martino, S, Osborne, Ck, Ravdin, Pm, Bondesson, T, Celebioglu, F, Dahlberg, K, Fornander, T, Fredriksson, I, Frisell, J, Göransson, E, Iiristo, M, Johansson, U, Lenner, E, Löfgren, L, Nikolaidis, P, Perbeck, L, Rotstein, S, Sandelin, K, Skoog, L, Svane, G, Af Trampe, E, Wadström, C, Maibach, R, Thürlimann, B, Holli, K, Rouhento, K, Safra, T, Brenner, H, Hercbergs, A, Yoshimoto, M, Paterson, Ahg, Fyles, A, Meakin, Jw, Panzarella, T, Bahi, J, Lemonnier, J, Martin, Al, Reid, M, Spittle, M, Bishop, H, Bundred, Nj, Forsyth, S, Pinder, Se, Deutsch, Gp, Kwong, Dlw, Pai, Vr, Senanayake, F, Rubagotti, A, Hackshaw, A, Houghton, J, Ledermann, J, Monson, K, Tobias, Js, Carlomagno, C, De Laurentiis, M, De Placido, S, Williams, L, Bell, R, Hinsley, S, Marshall, Hc, Pierce, Lj, Solomayer, E, Horsman, Jm, Lester, J, Winter, Mc, Buzdar, Au, Hsu, L, Love, Rr, Ahlgren, J, Garmo, H, Holmberg, L, Liljegren, G, Lindman, H, Wärnberg, F, Asmar, L, Jones, Se, Aft, R, Gluz, O, Liedtke, C, Nitz, U, Litton, A, Wallgren, A, Karlsson, P, Linderholm, Bk, Chlebowski, Rt, Caffier, H., Guided Treatment in Optimal Selected Cancer Patients (GUTS), Other departments, CCA - Cancer Treatment and Quality of Life, Radiotherapy, Pan, Hongchao, Gray, Richard, Braybrooke, Jeremy, Davies, Christina, Taylor, Carolyn, Mcgale, Paul, Peto, Richard, Pritchard, Kathleen I, Bergh, Jona, Dowsett, Mitch, Hayes, Daniel F, De Laurentiis, Michelino, MUMC+: MA Medische Oncologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and Interne Geneeskunde
Subjects: 0301 basic medicine, Oncology, medicine.medical_treatment, Kaplan-Meier Estimate, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Recurrence, Receptors, Neoplasm Metastasis, AMERICAN SOCIETY, Adjuvant, CLINICAL-PRACTICE GUIDELINE, Absolute risk reduction, Estrogen Antagonists, General Medicine, Estrogen Antagonist, CHEMOTHERAPY, Middle Aged, Prognosis, Neoplasm Metastasi, Local, POSTMENOPAUSAL WOMEN, Receptors, Estrogen, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Meta-analysis, Lymphatic Metastasis, Female, Human, Estrogen Antagonists/therapeutic use, Adult, Risk, medicine.medical_specialty, Prognosi, medicine.drug_class, DISCONTINUATION, Breast Neoplasms, Article, Drug Administration Schedule, LATE DISTANT RECURRENCE, 03 medical and health sciences, Breast cancer, Breast Neoplasms/drug therapy, Internal medicine, SCORE, medicine, Humans, SURGICAL ADJUVANT BREAST, Aged, Proportional Hazards Models, Chemotherapy, business.industry, Proportional hazards model, Lymphatic Metastasi, TAMOXIFEN THERAPY, ta3122, medicine.disease, Estrogen, RANDOMIZED-TRIALS, Discontinuation, Surgery, Neoplasm Recurrence, 030104 developmental biology, Proportional Hazards Model, Neoplasm Grading, Neoplasm Recurrence, Local, business
Abstract: Background The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)–positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment. Methods In this meta-analysis of the results of 88 trials involving 62,923 women with ER-positive breast cancer who were disease-free after 5 years of scheduled endocrine therapy, we used Kaplan–Meier and Cox regression analyses, stratified according to trial and treatment, to assess the associations of tumor diameter and nodal status (TN), tumor grade, and other factors with patients’ outcomes during the period from 5 to 20 years. Results Breast-cancer recurrences occurred at a steady rate throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status. Among the patients with stage T1 disease, the risk of distant recurrence was 13% with no nodal involvement (T1N0), 20% with one to three nodes involved (T1N1–3), and 34% with four to nine nodes involved (T1N4–9); among those with stage T2 disease, the risks were 19% with T2N0, 26% with T2N1–3, and 41% with T2N4–9. The risk of death from breast cancer was similarly dependent on TN status, but the risk of contralateral breast cancer was not. Given the TN status, the factors of tumor grade (available in 43,590 patients) and Ki-67 status (available in 7692 patients), which are strongly correlated with each other, were of only moderate independent predictive value for distant recurrence, but the status regarding the progesterone receptor (in 54,115 patients) and human epidermal growth factor receptor type 2 (HER2) (in 15,418 patients in trials with no use of trastuzumab) was not predictive. During the study period from 5 to 20 years, the absolute risk of distant recurrence among patients with T1N0 breast cancer was 10% for low-grade disease, 13% for moderate-grade disease, and 17% for high-grade disease; the corresponding risks of any recurrence or a contralateral breast cancer were 17%, 22%, and 26%, respectively. Conclusions After 5 years of adjuvant endocrine therapy, breast-cancer recurrences continued to occur steadily throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status, with risks ranging from 10 to 41%, depending on TN status and tumor grade. (Funded by Cancer Research UK and others.)
Published: 2017

7. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Author: Alberro, JA, Ballester, B, Deulofeu, P, Fabregas, R, Fraile, M, Gubern, JM, Janer, J, Moral, A, de Pablo, JL, Penalva, G, Puig, P, Ramos, M, Rojo, R, Santesteban, P, Serra, C, Sola, M, Solarnau, L, Solsona, J, Veloso, E, Vidal, S, Abe, O, Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Ohashi, Y, Sakai, K, Sugimachi, K, Toi, M, Tominaga, T, Uchino, J, Yoshida, M, Coles, CE, Haybittle, JL, Moebus, V, Leonard, CF, Calais, G, Garaud, P, Collett, V, Davies, C, Delmestri, A, Sayer, J, Harvey, VJ, Holdaway, IM, Kay, RG, Mason, BH, Forbe, JF, Franci, PA, Wilcken, N, Balic, M, Bartsch, R, Fesl, C, Fitzal, F, Fohler, H, Gnant, M, Greil, R, Jakesz, R, Marth, C, Mlineritsch, B, Pfeiler, G, Singer, CF, Steger, GG, Stoeger, H, Canney, P, Yosef, HMA, Focan, C, Peek, U, Oates, GD, Powell, J, Durand, M, Mauriac, L, Di Leo, A, Dolci, S, Larsimont, D, Nogaret, JM, Philippson, C, Piccart, MJ, Masood, MB, Parker, D, Price, JJ, Lindsay, MA, Mackey, J, Martin, M, Hupperets, PSGJ, Bates, T, Blamey, RW, Chetty, U, Ellis, IO, Mallon, E, Morgan, DAL, Patnick, J, Pinder, S, Lohrisch, C, Nichol, A, Bartlett, JMS, Bramwell, VH, Chen, BE, Chia, SKL, Gelmon, K, Goss, PE, Levine, MN, Parulekar, W, Pater, JL, Pritchard, KI, Shepherd, LE, Tu, D, Whelan, T, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Norton, L, Weiss, RB, Abu-Zahara, HT, Karpov, A, Portnoj, SL, Bowden, S, Brookes, C, Dunn, J, Fernando, I, Lee, M, Poole, C, Rea, D, Spooner, D, Barrett-Lee, PJ, Manse, RE, Monypenny, IJ, Gordon, NH, Davis, HL, Cuzick, J, Sestak, I, Lehingue, Y, Romestaing, P, Dubois, JB, Delozier, T, Griffon, B, Lesec'h, J Mace, Mustacchi, G, Petruzelka, L, Pribylova, O, Owen, JR, Meier, P, Shan, Y, Shao, YF, Wang, X, Zhao, DB, Howell, A, Swindell, R, Albano, J, de Oliveira, CF, Gervasio, H, Gordilho, J, Ejlertsen, B, Jensen, M-B, Mouridsen, H, Gelman, RS, Harris, JR, Hayes, D, Henderson, C, Shapiro, CL, Christiansen, P, Ewertz, M, Jensen, MB, Mouridsen, HT, Fehm, T, Trampisch, HJ, Dalesio, O, de Vries, EGE, Rodenhuis, S, van Tinteren, H, Comis, RL, Davidson, NE, Gray, R, Robert, N, Sledge, G, Solin, LJ, Sparano, JA, Tormey, DC, Wood, W, Cameron, D, Dixon, JM, Forrest, P, Jack, W, Kunkler, I, Rossbach, J, Klijn, JGM, Treurniet-Donker, AD, van Putten, WLJ, Rotmensz, N, Veronesi, U, Viale, G, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, JP, Poortmans, PM, Rutgers, E, van de Velde, CJH, Cunningham, MP, Huovinen, R, Joensuu, H, Costa, A, Bonadonna, G, Gianni, L, Valagussa, P, Goldstein, LJ, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Lupors, E, Namer, M, Carrasco, E, Segui, MA, Eierman, W, Hilfrich, J, Jonat, W, Kaufmann, M, Kreienberg, R, Schumacher, M, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Blohmer, JU, Costa, SD, Eidtmann, H, Gerber, B, Jackisch, C, Loib, S, von Minckwitz, G, de Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Pirozzoli, MC, Sacco, M, Valentini, M, McArdle, CS, Smith, DC, Stallard, S, Dent, DM, Gudgeon, CA, Hacking, A, Murray, E, Panieri, E, Werner, ID, De Salvo, GL, Del Bianco, P, Zavagno, G, Leone, B, Vallejo, CT, Zwenger, A, Galligioni, E, Lopez, M, Erazo, A, Medina, JY, Horiguchi, J, Takei, H, Fentiman, IS, Hayward, JL, Rubens, RD, Skilton, D, Scheurlen, H, Sohn, HC, Untch, M, Dafni, U, Markopoulos, C, Bamia, C, Fountzilas, G, Koliou, G-A, Manousou, K, Mavroudis, D, Klefstrom, P, Blomqvist, C, Saarto, T, Gallen, M, Canavese, G, Tinterri, C, Margreiter, R, de Lafontan, B, Mihura, J, Roche, H, Asselain, B, Salmon, RJ, Vilcoq, JR, Brain, E, de La Lande, B, Mouret-Fourme, E, Andre, F, Arriagada, R, Delaloge, S, Hill, C, Koscienly, S, Michiels, S, Rubino, C, A'Hern, R, Bliss, J, Ellis, P, Kilburn, L, Yarnold, JR, Benraadt, J, Kooi, M, van de Velde, AO, van Dongen, JA, Vermorken, JB, Castiglione, M, Coates, A, Colleoni, M, Collins, J, Forbes, J, Gelbe, RD, Goldhirsch, A, Lindtner, J, Price, KN, Regan, MM, Rudenstam, CM, Senn, HJ, Thuerlimann, B, Bliss, JM, Chilvers, CED, Coombes, RC, Hall, E, Marty, M, Buyse, M, Possinger, K, Schmid, P, Wallwiener, D, Foster, L, George, WD, Stewart, HJ, Stroner, P, Borovik, R, Hayat, H, Inbar, MJ, Peretz, T, Robinson, E, Camerini, T, Formelli, F, Martelli, G, Di Mauro, MG, Perrone, F, Amadori, D, Martoni, A, Pannuti, F, Camisa, R, Musolino, A, Passalacqua, R, Iwata, H, Shien, T, Ikeda, T, Inokuchi, K, Sawa, K, Sonoo, H, Sadoon, M, Tulusan, AH, Kohno, N, Miyashita, M, Takao, S, Ahn, J-H, Jung, KH, Korzeniowski, S, Skolyszewski, J, Ogawa, M, Yamashita, J, Bastiaannet, E, Liefers, GJ, Christiaens, R, Neven, P, Paridaens, R, Van den Bogaert, W, Gazet, JC, Corcoran, N, Deshpande, N, di Martino, L, Douglas, P, Host, H, Lindtner, A, Notter, G, Bryant, AJS, Ewing, GH, Firth, LA, Krushen-Kosloski, JL, Nissen-Meyer, R, Anderson, H, Killander, F, Malmstrom, P, Ryden, L, Arnesson, L-G, Carstense, J, Dufmats, M, Fohlin, H, Nordenskjold, B, Soderberg, M, Sundqvist, M, Carpenter, TJ, Murray, N, Royle, GT, Simmonds, PD, Albain, K, Barlow, W, Crowley, J, Gralow, J, Hortobagyi, G, Livingston, R, Martino, S, Osborne, CK, Ravdin, PM, Bergh, J, Bondesso, T, Celebiogl, F, Dahlberg, K, Fornander, T, Fredriksson, I, Frisell, J, Goransson, E, Iiristo, M, Johansson, U, Lenner, E, Lofgren, L, Nikolaidis, P, Perbeck, L, Rotstein, S, Sandelin, K, Skoog, L, Svane, G, af Trampe, E, Wadstrom, C, Janni, W, Maibach, R, Thurlimann, B, Hadji, P, Hozumi, J, Holli, K, Rouhento, K, Safra, T, Brenner, H, Hercbergs, A, Yoshimoto, M, Paterson, AHG, Fyles, A, Meakin, JW, Panzarella, T, Bahi, J, Lemonnier, J, Martin, AL, Reid, M, Spittle, M, Bishop, H, Bundred, NJ, Forbes, JF, Forsyth, S, George, WS, Pinder, SE, Deutsch, GP, Kwong, DLW, Pai, VR, Peto, R, Senanayake, F, Boccardo, F, Rubagotti, A, Baum, M, Hackshaw, A, Houghton, J, Ledermann, J, Monson, K, Tobias, JS, Carlomagno, C, De Laurentiis, M, De Placido, S, Schem, C, Williams, L, Bell, R, Coleman, RE, Dodwell, D, Hinsley, S, Marshall, HC, Pierce, LJ, Basso, SMM, Lumachi, F, Solomayer, E, Horsman, JM, Lester, J, Winter, MC, Buzdar, AU, Hsu, L, Love, RR, Ahlgren, J, Garmo, H, Holmberg, L, Lindman, H, Warnberg, F, Asmar, L, Jones, SE, Aft, R, Gluz, O, Harbeck, N, Liedtke, C, Nitz, U, Litton, A, Wallgren, A, Karlsson, P, Linderholm, BK, Chlebowski, RT, Caffier, H, Brufsky, AM, Llombart, HA, Asselain, B, Barlow, W, Bartlett, J, Bradley, R, Braybrooke, J, Davies, C, Dodwell, D, Gray, R, Mannu, G, Taylor, C, Peto, R, McGale, P, Pan, H, Wang, Y, Wang, Z, Department of Oncology, Clinicum, HUS Comprehensive Cancer Center, Medical Oncology, Cancer Research UK, and Pfizer Limited
Subjects: 0301 basic medicine, Oncology, Time Factors, SURGERY, medicine.medical_treatment, menopause, chemotherapy, Mastectomy, Segmental, Rate ratio, THERAPY, aromatase inhibitors, CEA, 0302 clinical medicine, Risk Factors, Medicine and Health Sciences, Breast, Neoplasm Metastasis, Randomized Controlled Trials as Topic, RISK, tamoxifen, breast tumor, CA15-3, axillary dissection, mastectomy, Middle Aged, Neoadjuvant Therapy, METHOTREXATE, 3. Good health, trastuzumab, Treatment Outcome, quadrantectomy, Chemotherapy, Adjuvant, axillary lymphnodes, 030220 oncology & carcinogenesis, Meta-analysis, SURVIVAL, Disease Progression, Female, Life Sciences & Biomedicine, axillary clearance, RADIOTHERAPY, medicine.drug, Adult, medicine.medical_specialty, Anthracycline, 3122 Cancers, Antineoplastic Agents, Breast Neoplasms, axillary nodes, sentinel node biopsy, 03 medical and health sciences, breast cancer, Breast cancer, SDG 3 - Good Health and Well-being, HER2, Internal medicine, Journal Article, medicine, cancer, Humans, Breast, breast cancer, breast diseases, cancer, malignancy, menopause, surgery, mastectomy, quadrantectomy, lumpectomy, axillary nodes, axillary lymphnodes, axillary dissection, axillary clearance, sentinel node biopsy, sentinel node, BRCA1, BRCA2, tamoxifen, aromatase inhibitors, breast tumor, osteoporosis, bisphosphonates, denosumab, trastuzumab, HER2, CEA, CA15-3, tumor marker, chemotherapy, endocrine therapy, Oncology & Carcinogenesis, RECURRENCE, bisphosphonates, Pathological, Neoplasm Staging, lumpectomy, Chemotherapy, Science & Technology, breast diseases, endocrine therapy, business.industry, denosumab, BRCA1, medicine.disease, BRCA2, osteoporosis, Radiation therapy, STIMULATING FACTOR, 030104 developmental biology, sentinel node, tumor marker, Methotrexate, Neoplasm Recurrence, Local, business, 1112 Oncology And Carcinogenesis, malignancy
Abstract: BACKGROUND: Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. METHODS: We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). FINDINGS: Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5-14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4-8·6]; rate ratio 1·37 [95% CI 1·17-1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92-1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95-1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94-1·15]; p=0·45). INTERPRETATION: Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered-eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy. FUNDING: Cancer Research UK, British Heart Foundation, UK Medical Research Council, and UK Department of Health. ispartof: LANCET ONCOLOGY vol:19 issue:1 pages:27-39 ispartof: location:England status: published
Published: 2017
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8. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials

Author: Mcgale, P., Taylor, C., Correa, C., Cutter, D., Duane, F., Ewertz, M., Gray, R., Mannu, G., Peto, R., Whelan, T., Wang, Y., Wang, Z., Darby, S., Albain, K., Anderson, S., Arriagada, R., Barlow, W., Bergh, J., Bergsten Nordström, E., Bliss, J., Burrett, J. A., Buyse, M., Cameron, D., Carrasco, E., Clarke, M., Coleman, R., Coates, A., Collins, R., Costantino, J., Cuzick, J., Davidson, N., Davies, C., Davies, K., Delmestri, A., Di Leo, A., Dowsett, M., Elphinstone, P., Evans, V., Forbes, J., Gelber, R., Gettins, L., Geyer, C., Gianni, L., Gnant, M., Goldhirsch, A., Godwin, J., Gregory, C., Hayes, D., Hill, C., Ingle, J., Jakesz, R., James, S., Janni, W., Kaufmann, M., Kerr, A., Liu, H., Mackinnon, E., Martín, M., Mchugh, T., Morris, P., Norton, L., Ohashi, Y., Paik, S., Pan, H. C., Perez, E., Piccart, M., Pierce, L., Pritchard, K., Pruneri, G., Raina, V., Ravdin, P., Robertson, J., Rutgers, E., Shao, Y. F., Sparano, J., Swain, S., Valagussa, P., Viale, G., Von Minckwitz, G., Winer, E., Wiang, X., Wood, Abe O, W., Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Ohashi, Y, Sakai, K, Sugimachi, K, Toi, M, Tominaga, T, Uchino, J, Yoshida, M, Haybittle, Jl, Leonard, Cf, Calais, G, Geraud, P, Collett, V, Davies, C, Delmestri, A, Sayer, J, Harvey, Vj, Holdaway, Im, Kay, Rg, Mason, Bh, Forbes, Jf, Wilcken, N, Bartsch, R, Dubsky, P, Fesl, C, Fohler, H, Gnant, M, Greil, R, Jakesz, R, Lang, A, Luschin-Ebengreuth, G, Marth, C, Mlineritsch, B, Samonigg, H, Singer, Cf, Steger, Gg, Stöger, H, Canney, P, Yosef, Hm, Focan, C, Peek, U, Oates, Gd, Powell, J, Durand, M, Mauriac, L, Di Leo, A, Dolci, S, Larsimont, D, Nogaret, Jm, Philippson, C, Piccart, Mj, Masood, Mb, Parker, D, Price, Jj, Lindsay, Ma, Mackey, J, Martin, M, Hupperets, Ps, Bates, T, Blamey, Rw, Chetty, U, Ellis, Io, Mallon, E, Morgan, Da, Patnick, J, Pinder, S, Olivotto, I, Ragaz, J, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Norton, L, Weiss, Rb, Abu-Zahra, Ht, Portnoj, Sm, Bowden, S, Brookes, C, Dunn, J, Fernando, I, Lee, M, Poole, C, Rea, D, Spooner, D, Barrett-Lee, Pj, Mansel, Re, Monypenny, Ij, Gordon, Nh, Davis, Hl, Cuzick, J, Lehingue, Y, Romestaing, P, Dubois, Jb, Delozier, T, Griffon, B, Mace Lesech, J, Brain, E, de La Lande, B, Mouret-Fourme, E, Mustacchi, G, Petruzelka, L, Pribylova, O, Owen, Jr, Harbeck, N, Jänicke, F, Meisner, C, Schmitt, M, Thomssen, C, Meier, P, Shan, Y, Shao, Yf, Wang, X, Zhao, Db, Chen, Zm, Pan, Hc, Howell, A, Swindell, R, Burrett, Ja, Clarke, M, Collins, R, Correa, C, Cutter, D, Darby, S, Davies, K, Elphinstone, P, Evans, V, Gettins, L, Godwin, J, Gray, R, Gregory, C, Hermans, D, Hicks, C, James, S, Kerr, A, Liu, H, Mackinnon, E, Lay, M, Mcgale, P, Mchugh, T, Morris, P, Peto, R, Taylor, C, Wang, Y, Albano, J, de Oliveira CF, Gervásio, H, Gordilho, J, Ejlertsen, B, Jensen, Mb, Johansen, H, Mouridsen, H, Palshof, T, Gelman, Rs, Harris, Jr, Hayes, D, Henderson, C, Shapiro, Cl, Winer, E, Christiansen, P, Ewertz, M, Møller, S, Mouridsen, Ht, Trampisch, Hj, Dalesio, O, de Vries EG, Rodenhuis, S, van Tinteren, H, Comis, Rl, Davidson, Ne, Robert, N, Sledge, G, Solin, Lj, Sparano, Ja, Tormey, Dc, Wood, W, Cameron, D, Dixon, Jm, Forrest, P, Jack, W, Kunkler, I, Rossbach, J, Klijn, Jg, Treurniet-Donker, Ad, van Putten WL, Rotmensz, N, Veronesi, U, Viale, G, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, Jp, Rutgers, E, van de Velde CJ, Cunningham, Mp, Huovinen, R, Joensuu, H, Costa, A, Bonadonna, G, Gianni, L, Valagussa, P, Goldstein, Lj, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Luporsi, E, Namer, M, Eiermann, W, Hilfrich, J, Jonat, W, Kaufmann, M, Kreienberg, R, Schumacher, M, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Blohmer, Ju, Costa, Sd, Eidtmann, H, Gerber, B, Jackisch, C, Loibl, S, von Minckwitz, G, de Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Pirozzoli, Mc, Sacco, M, Valentini, M, Mcardle, Cs, Smith, Dc, Stallard, S, Dent, Dm, Gudgeon, Ca, Hacking, A, Murray, E, Panieri, E, Werner, Id, Carrasco, E, Segui, Ma, Galligioni, E, Lopez, M, Erazo, A, Medina, Jy, Horiguchi, J, Takei, H, Fentiman, Is, Hayward, Jl, Rubens, Rd, Skilton, D, Scheurlen, H, Sohn, Hc, Untch, M, Dafni, U, Markopoulos, C, Fountzilas, G, Mavroudis, D, Klefstrom, P, Blomqvist, C, Saarto, T, Gallen, M, Tinterri, C, Margreiter, R, de Lafontan, B, Mihura, J, Roché, H, Asselain, B, Salmon, Rj, Vilcoq, Jr, André, F, Arriagada, R, Delaloge, S, Hill, C, Koscielny, S, Michiels, S, Rubino, C, A'Hern, R, Bliss, J, Ellis, P, Kilburn, L, Yarnold, Jr, Benraadt, J, Kooi, M, van de Velde AO, van Dongen JA, Vermorken, Jb, Castiglione, M, Coates, A, Colleoni, M, Collins, J, Forbes, J, Gelber, Rd, Goldhirsch, A, Lindtner, J, Price, Kn, Regan, Mm, Rudenstam, Cm, Senn, Hj, Thuerlimann, B, Bliss, Jm, Chilvers, Ce, Coombes, Rc, Hall, E, Marty, M, Buyse, M, Possinger, K, Schmid, P, Wallwiener, D, Foster, L, George, Wd, Stewart, Hj, Stroner, P, Borovik, R, Hayat, H, Inbar, Mj, Peretz, T, Robinson, E, Bruzzi, P, Del Mastro, L, Pronzato, P, Sertoli, Mr, Venturini, M, Camerini, T, De Palo, G, Di Mauro MG, Formelli, F, Amadori, D, Martoni, A, Pannuti, F, Camisa, R, Cocconi, G, Colozza, A, Passalacqua, R, Aogi, K, Takashima, S, Abe, O, Ikeda, T, Inokuchi, K, Sawa, K, Sonoo, H, Korzeniowski, S, Skolyszewski, J, Ogawa, M, Yamashita, J, Bastiaannet, E, van de Water, W, van Nes JG, Christiaens, R, Neven, P, Paridaens, R, Van den Bogaert, W, Braun, S, Martin, P, Romain, S, Janauer, M, Seifert, M, Sevelda, P, Zielinski, Cc, Hakes, T, Hudis, Ca, Wittes, R, Giokas, G, Kondylis, D, Lissaios, B, de la Huerta, R, Sainz, Mg, Altemus, R, Camphausen, K, Cowan, K, Danforth, D, Lichter, A, Lippman, M, O'Shaughnessy, J, Pierce, Lj, Steinberg, S, Venzon, D, Zujewski, Ja, D'Amico, C, Lioce, M, Paradiso, A, Chapman, Ja, Gelmon, K, Goss, Pe, Levine, Mn, Meyer, R, Parulekar, W, Pater, Jl, Pritchard, Ki, Shepherd, Le, Tu, D, Whelan, T, Ohno, S, Anderson, S, Bass, G, Brown, A, Bryant, J, Costantino, J, Dignam, J, Fisher, B, Geyer, C, Mamounas, Ep, Paik, S, Redmond, C, Swain, S, Wickerham, L, Wolmark, N, Baum, M, Jackson, Im, Palmer, Mk, Perez, E, Ingle, Jn, Suman, Vj, Bengtsson, No, Emdin, S, Jonsson, H, Lythgoe, Jp, Kissin, M, Erikstein, B, Hannisdal, E, Jacobsen, Ab, Varhaug, Je, Gundersen, S, Hauer-Jensen, M, Høst, H, Nissen-Meyer, R, Reinertsen, K, Mitchell, Ak, Robertson, Jf, Ueo, H, Di Palma, M, Mathé, G, Misset, Jl, Levine, M, Morimoto, K, Takatsuka, Y, Crossley, E, Harris, A, Talbot, D, Taylor, M, di Blasio, B, Ivanov, V, Paltuev, R, Semiglazov, V, Brockschmidt, J, Cooper, Mr, Falkson, Ci, Dowsett, M, Makris, A, Parton, M, Pennert, K, Powles, Tj, Smith, Ie, Gazet, Jc, Browne, L, Graham, P, Corcoran, N, Businico, A, Deshpande, N, di Martino, L, Douglas, P, Lindtner, A, Notter, G, Bryant, Aj, Ewing, Gh, Firth, La, Krushen-Kosloski, Jl, Anderson, H, Killander, F, Malmström, P, Rydén, L, Arnesson, Lg, Carstensen, J, Dufmats, M, Fohlin, H, Nordenskjöld, B, Söderberg, M, Carpenter, Jt, Murray, N, Royle, Gt, Simmonds, Pd, Albain, K, Barlow, W, Crowley, J, Gralow, J, Hortobagyi, G, Livingston, R, Martino, S, Osborne, Ck, Ravdin, Pm, Adolfsson, J, Bergh, J, Bondesson, T, Celebioglu, F, Dahlberg, K, Fornander, T, Fredriksson, I, Frisell, J, Göransson, E, Iiristo, M, Johansson, U, Lenner, E, Löfgren, L, Nikolaidis, P, Perbeck, L, Rotstein, S, Sandelin, K, Skoog, L, Svane, G, af Trampe, E, Wadström, C, Janni, W, Maibach, R, Thürlimann, B, Hakama, M, Holli, K, Isola, J, Rouhento, K, Saaristo, R, Brenner, H, Hercbergs, A, Yoshimoto, M, Paterson, Ah, Fyles, A, Meakin, Jw, Panzarella, T, Bahi, J, Reid, M, Spittle, M, Bishop, H, Bundred, Nj, Forsyth, S, Pinder, Se, Sestak, I, Deutsch, Gp, Kwong, Dl, Pai, Vr, Senanayake, F, Martin, Al, Boccardo, F, Rubagotti, A, Hackshaw, A, Houghton, J, Ledermann, J, Monson, K, Tobias, Js, Carlomagno, C, De Laurentiis, M, De Placido, S, Williams, L, Broglio, K, Buzdar, Au, Hsu, L, Love, Rr, Ahlgren, J, Garmo, H, Holmberg, L, Liljegren, G, Lindman, H, Wärnberg, F, Asmar, L, Jones, Se, Gluz, O, Liedtke, C, Nitz, U, Litton, A, Wallgren, A, Karlsson, P, Linderholm, Bk, Chlebowski, Rt, Caffier, H., McGale, P, Taylor, C, Correa, C, Cutter, D, Duane, F, Ewertz, M, Gray, R, Mannu, G, Peto, R, Whelan, T, Wang, Y, Wang, Z, Darby, S, Biomedische Technologie, RS: GROW - Oncology, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Mcgale, P, DE LAURENTIIS, Michelino, Other departments, CCA -Cancer Center Amsterdam, and Radiotherapy
Subjects: medicine.medical_specialty, medicine.medical_treatment, Breast Neoplasms, Rate ratio, Lower risk, Systemic therapy, Statistical significance, Medicine, Humans, Mastectomy, Randomized Controlled Trials as Topic, business.industry, Articles, General Medicine, Surgery, Radiation therapy, Axilla, Neoplasm Recurrence, medicine.anatomical_structure, Local, Meta-analysis, Lymphatic Metastasis, Lymph Node Excision, Female, Neoplasm Recurrence, Local, business, Breast Neoplasm, Human
Abstract: BACKGROUND: Postmastectomy radiotherapy was shown in previous meta-analyses to reduce the risks of both recurrence and breast cancer mortality in all women with node-positive disease considered together. However, the benefit in women with only one to three positive lymph nodes is uncertain. We aimed to assess the effect of radiotherapy in these women after mastectomy and axillary dissection.METHODS: We did a meta-analysis of individual data for 8135 women randomly assigned to treatment groups during 1964-86 in 22 trials of radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery versus the same surgery but no radiotherapy. Follow-up lasted 10 years for recurrence and to Jan 1, 2009, for mortality. Analyses were stratified by trial, individual follow-up year, age at entry, and pathological nodal status.FINDINGS: 3786 women had axillary dissection to at least level II and had zero, one to three, or four or more positive nodes. All were in trials in which radiotherapy included the chest wall, supraclavicular or axillary fossa (or both), and internal mammary chain. For 700 women with axillary dissection and no positive nodes, radiotherapy had no significant effect on locoregional recurrence (two-sided significance level [2p]>0·1), overall recurrence (rate ratio [RR], irradiated vs not, 1·06, 95% CI 0·76-1·48, 2p>0·1), or breast cancer mortality (RR 1·18, 95% CI 0·89-1·55, 2p>0·1). For 1314 women with axillary dissection and one to three positive nodes, radiotherapy reduced locoregional recurrence (2pINTERPRETATION: After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given. For today's women, who in many countries are at lower risk of recurrence, absolute gains might be smaller but proportional gains might be larger because of more effective radiotherapy.FUNDING: Cancer Research UK, British Heart Foundation, UK Medical Research Council.
Published: 2016
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9. Neural correlates of distraction and conflict resolution for nonverbal auditory events.

Author: Stewart, HJ, Amitay, S, Alain, C, Stewart, HJ, Amitay, S, and Alain, C
Abstract: In everyday situations auditory selective attention requires listeners to suppress task-irrelevant stimuli and to resolve conflicting information in order to make appropriate goal-directed decisions. Traditionally, these two processes (i.e. distractor suppression and conflict resolution) have been studied separately. In the present study we measured neuroelectric activity while participants performed a new paradigm in which both processes are quantified. In separate block of trials, participants indicate whether two sequential tones share the same pitch or location depending on the block’s instruction. For the distraction measure, a positive component peaking at ~250 ms was found – a distraction positivity. Brain electrical source analysis of this component suggests different generators when listeners attended to frequency and location, with the distraction by location more posterior than the distraction by frequency, providing support for the dual-pathway theory. For the conflict resolution measure, a negative frontocentral component (270–450 ms) was found, which showed similarities with that of prior studies on auditory and visual conflict resolution tasks. The timing and distribution are consistent with two distinct neural processes with suppression of task-irrelevant information occurring before conflict resolution. This new paradigm may prove useful in clinical populations to assess impairments in filtering out task-irrelevant information and/or resolving conflicting information.
Published: 2017

10. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials

Author: EARLY BREAST CANCER TRIALISTS' COLLABORATIVE GROUP (EBCTCG), Darby, S., Mcgale, P., Correa, C., Taylor, C., Arriagada, R., Clarke, M., Cutter, D., Davies, C., Ewertz, M., Godwin, J., Gray, R., Pierce, L., Whelan, T., Wang, Y., Peto, R., Albain, K, Anderson, S, Arriagada, R, Barlow, W, Bergh, J, Bliss, J, Buyse, M, Cameron, D, Carrasco, E, Clarke, M, Correa, C, Coates, A, Collins, R, Costantino, J, Cutter, D, Cuzick, J, Darby, S, Davidson, N, Davies, C, Davies, K, Delmestri, A, Di Leo, A, Dowsett, M, Elphinstone, P, Evans, V, Ewertz, M, Gelber, R, Gettins, L, Geyer, C, Goldhirsch, A, Godwin, J, Gray, R, Gregory, C, Hayes, D, Hill, C, Ingle, J, Jakesz, R, James, S, Kaufmann, M, Kerr, A, Mackinnon, E, Mcgale, P, Mchugh, T, Norton, L, Ohashi, Y, Paik, S, Pan, Hc, Perez, E, Peto, R, Piccart, M, Pierce, L, Pritchard, K, Pruneri, G, Raina, V, Ravdin, P, Robertson, J, Rutgers, E, Shao, Yf, Swain, S, Taylor, C, Valagussa, P, Viale, G, Whelan, T, Winer, E, Wang, Y, Wood, W, Abe, O, Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Sakai, K, Sugimachi, K, Toi, M, Tominaga, T, Uchino, J, Yoshida, M, Haybittle, Jl, Leonard, Cf, Calais, G, Geraud, P, Collett, V, Sayer, J, Harvey, Vj, Holdaway, Im, Kay, Rg, Mason, Bh, Forbes, Jf, Wilcken, N, Bartsch, R, Dubsky, P, Fesl, C, Fohler, H, Gnant, M, Greil, R, Lang, A, Luschin-Ebengreuth, G, Marth, C, Mlineritsch, B, Samonigg, H, Singer, Cf, Steger, Gg, Stöger, H, Canney, P, Yosef, Hm, Focan, C, Peek, U, Oates, Gd, Powell, J, Durand, M, Mauriac, L, Dolci, S, Larsimont, D, Nogaret, Jm, Philippson, C, Piccart, Mj, Masood, Mb, Parker, D, Price, Jj, Lindsay, Ma, Mackey, J, Martin, M, Hupperets, Ps, Bates, T, Blamey, Rw, Chetty, U, Ellis, Io, Mallon, E, Morgan, Da, Patnick, J, Pinder, S, Olivotto, I, Ragaz, J, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Weiss, Rb, Abu-Zahra, Ht, Portnoj, Sm, Bowden, S, Brookes, C, Dunn, J, Fernando, I, Lee, M, Poole, C, Rea, D, Spooner, D, Barrett-Lee, Pj, Mansel, Re, Monypenny, Ij, Gordon, Nh, Davis, Hl, Lehingue, Y, Romestaing, P, Dubois, Jb, Delozier, T, Griffon, B, Mace Lesec'h, J, Rambert, P, Mustacchi, G, Petruzelka, Pribylova, O, Owen, Jr, Harbeck, N, Jänicke, F, Meisner, C, Schmitt, M, Thomssen, C, Meier, P, Shan, Y, Wang, X, Zhao, Db, Chen, Zm, Howell, A, Swindell, R, Burrett, Ja, Hermans, D, Hicks, C, Lay, M, Albano, J, de Oliveira CF, Gervásio, H, Gordilho, J, Johansen, H, Mouridsen, Ht, Gelman, Rs, Harris, Jr, Henderson, C, Shapiro, Cl, Christiansen, P, Ejlertsen, B, Jensen, Mb, Møller, S, Carstensen, B, Palshof, T, Trampisch, Hj, Dalesio, O, de Vries EG, Rodenhuis, S, van Tinteren, H, Comis, Rl, Davidson, Ne, Robert, N, Sledge, G, Solin, Lj, Sparano, Ja, Tormey, Dc, Dixon, Jm, Forrest, P, Jack, W, Kunkler, I, Rossbach, J, Klijn, Jg, Treurniet-Donker, Ad, van Putten WL, Rotmensz, N, Veronesi, U, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, Jp, van de Velde CJ, Cunningham, Mp, Huovinen, R, Joensuu, H, Costa, A, Tinterri, C, Bonadonna, G, Gianni, L, Goldstein, Lj, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Luporsi, E, Namer, M, Eiermann, W, Hilfrich, J, Jonat, W, Kreienberg, R, Schumacher, M, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Blohmer, Ju, Costa, Sd, Eidtmann, H, Gerber, G, Jackisch, C, Loibl, S, von Minckwitz, G, de Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Pirozzoli, Mc, Sacco, M, Valentini, M, Mcardle, Cs, Smith, Dc, Stallard, S, Dent, Dm, Gudgeon, Ca, Hacking, A, Murray, E, Panieri, E, Werner, Id, Segui, Ma, Galligioni, E, Lopez, M, Erazo, A, Medina, Jy, Horiguchi, J, Takei, H, Fentiman, Is, Hayward, Jl, Rubens, Rd, Skilton, D, Scheurlen, H, Sohn, Hc, Untch, M, Dafni, U, Markopoulos, C, Dafni, D, Fountzilas, G, Mavroudis, D, Klefstrom, P, Saarto, T, Gallen, M, Margreiter, R, de Lafontan, B, Mihura, J, Roché, H, Asselain, B, Salmon, Rj, Vilcoq, Jr, Bourgier, C, Koscielny, S, Laplanche, A, Lê, Mg, Spielmann, M, A'Hern, R, Ellis, P, Kilburn, L, Yarnold, Jr, Benraadt, J, Kooi, M, van de Velde AO, van Dongen JA, Vermorken, Jb, Castiglione, M, Colleoni, M, Collins, J, Forbes, J, Gelber, Rd, Lindtner, J, Price, Kn, Regan, Mm, Rudenstam, Cm, Senn, Hj, Thuerlimann, B, Bliss, Jm, Chilvers, Ce, Coombes, Rc, Hall, E, Marty, M, Possinger, K, Schmid, P, Wallwiener, D, Foster, L, George, Wd, Stewart, Hj, Stroner, P, Borovik, R, Hayat, H, Inbar, Mj, Robinson, E, Bruzzi, P, Del Mastro, L, Pronzato, P, Sertoli, Mr, Venturini, M, Camerini, T, De Palo, G, Di Mauro MG, Formelli, F, Amadori, D, Martoni, A, Pannuti, F, Camisa, R, Cocconi, G, Colozza, A, Passalacqua, R, Aogi, K, Takashima, S, Ikeda, T, Inokuchi, K, Sawa, K, Sonoo, H, Korzeniowski, S, Skolyszewski, J, Ogawa, M, Yamashita, J, Bastiaannet, E, van de Water, W, van Nes JG, Christiaens, R, Neven, P, Paridaens, R, Van den Bogaert, W, Braun, S, Janni, W, Martin, P, Romain, S, Janauer, M, Seifert, M, Sevelda, P, Zielinski, Cc, Hakes, T, Hudis, Ca, Wittes, R, Giokas, G, Kondylis, D, Lissaios, B, de la Huerta, R, Sainz, Mg, Altemus, R, Camphausen, K, Cowan, K, Danforth, D, Lichter, A, Lippman, M, O'Shaughnessy, J, Pierce, Lj, Steinberg, S, Venzon, D, Zujewski, Ja, D'Amico, C, Lioce, M, Paradiso, A, Chapman, Ja, Gelmon, K, Goss, Pe, Levine, Mn, Meyer, R, Parulekar, W, Pater, Jl, Pritchard, Ki, Shepherd, Le, Tu, D, Ohno, S, Anderson, A, Bass, G, Brown, A, Bryant, J, Dignam, J, Fisher, B, Mamounas, Ep, Redmond, C, Wickerham, L, Wolmark, N, Baum, M, Jackson, Im, Palmer, Mk, Ingle, Jn, Suman, Vj, Bengtsson, No, Emdin, S, Jonsson, H, Lythgoe, Jp, Kissin, M, Erikstein, B, Hannisdal, E, Jacobsen, Ab, Varhaug, Je, Gundersen, S, Hauer-Jensen, M, Høst, H, Nissen-Meyer, R, Mitchell, Ak, Robertson, Jf, Ueo, H, Di Palma, M, Mathé, G, Misset, Jl, Levine, M, Morimoto, K, Takatsuka, Y, Crossley, E, Harris, A, Talbot, D, Taylor, M, Martin, Al, di Blasio, B, Ivanov, V, Paltuev, R, Semiglazov, V, Brockschmidt, J, Cooper, Mr, Falkson, Ci, Ashley, S, Makris, A, Powles, Tj, Smith, Ie, Gazet, Jc, Browne, L, Graham, P, Corcoran, N, Deshpande, N, di Martino, L, Douglas, P, Lindtner, A, Notter, G, Bryant, Aj, Ewing, Gh, Firth, La, Krushen-Kosloski, Jl, Anderson, H, Killander, F, Malmström, P, Rydén, L, Arnesson, Lg, Carstensen, J, Dufmats, M, Fohlin, H, Nordenskjöld, B, Söderberg, M, Carpenter, Jt, Murray, N, Royle, Gt, Simmonds, Pd, Crowley, J, Gralow, J, Green, S, Hortobagyi, G, Livingston, R, Martino, S, Osborne, Ck, Adolfsson, J, Bondesson, T, Celebioglu, F, Dahlberg, K, Fornander, T, Fredriksson, I, Frisell, J, Göransson, E, Iiristo, M, Johansson, U, Lenner, E, Löfgren, L, Nikolaidis, P, Perbeck, L, Rotstein, S, Sandelin, K, Skoog, L, Svane, G, af Trampe, E, Wadström, C, Maibach, R, Thürlimann, B, Hakama, M, Holli, K, Isola, J, Rouhento, K, Saaristo, R, Brenner, H, Hercbergs, A, Yoshimoto, M, Paterson, Ah, Fyles, A, Meakin, Jw, Panzarella, T, Bahi, J, Reid, M, Spittle, M, Bishop, H, Bundred, Nj, Forsyth, S, Pinder, Se, Sestak, I, Deutsch, Gp, Kwong, Dl, Pai, Vr, Senanayake, F, Boccardo, F, Rubagotti, A, Hackshaw, A, Houghton, J, Ledermann, J, Monson, K, Tobias, Js, Carlomagno, C, De Laurentiis, M, De Placido, S, Williams, L, Broglio, K, Buzdar, Au, Love, Rr, Ahlgren, J, Garmo, H, Holmberg, L, Liljegren, G, Lindman, H, Wärnberg, F, Asmar, L, Jones, Se, Gluz, O, Liedtke, C, Nitz, U, Litton, A, Wallgren, A, Karlsson, P, Linderholm, Bk, Chlebowski, Rt, Caffier, H, Mcgale, P, Correa, C, Taylor, C, Arriagada, R, Clarke, M, Cutter, D, Davies, C, Ewertz, M, Godwin, J, Gray, R, Pierce, L, Whelan, T, Wang, Y, Peto, R, Early Breast Cancer Trialists' Collaborative, Group, DE LAURENTIIS, Michelino, DE PLACIDO, Sabino, Carlomagno, Chiara, Darby, S, McGale, P, Interne Geneeskunde, RS: GROW - School for Oncology and Reproduction, Other departments, CCA -Cancer Center Amsterdam, and Radiotherapy
Subjects: Oncology, medicine.medical_specialty, Neoplasm Recurrence, Local - epidemiology, medicine.medical_treatment, Population, Breast Neoplasms, Mastectomy, Segmental, Breast cancer, breast cancer, Internal medicine, medicine, Breast-conserving surgery, Humans, education, skin and connective tissue diseases, radiotherapy, Randomized Controlled Trials as Topic, education.field_of_study, business.industry, Estrogen Antagonists - therapeutic use, Mortality rate, Age Factors, Estrogen Antagonists, General Medicine, Breast Neoplasms - mortality - therapy, medicine.disease, Surgery, Unilateral Breast Neoplasms, Radiation therapy, Clinical trial, meta-analysis, Tamoxifen, Receptors, Estrogen, Lymphatic Metastasis, Female, Radiotherapy, Adjuvant, Neoplasm Grading, Neoplasm Recurrence, Local, business, Mastectomy
Abstract: BACKGROUND: After breast-conserving surgery, radiotherapy reduces recurrence and breast cancer death, but it may do so more for some groups of women than for others. We describe the absolute magnitude of these reductions according to various prognostic and other patient characteristics, and relate the absolute reduction in 15-year risk of breast cancer death to the absolute reduction in 10-year recurrence risk. METHODS: We undertook a meta-analysis of individual patient data for 10,801 women in 17 randomised trials of radiotherapy versus no radiotherapy after breast-conserving surgery, 8337 of whom had pathologically confirmed node-negative (pN0) or node-positive (pN+) disease. FINDINGS: Overall, radiotherapy reduced the 10-year risk of any (ie, locoregional or distant) first recurrence from 35.0% to 19.3% (absolute reduction 15.7%, 95% CI 13.7-17.7, 2p/=20%), intermediate (10-19%), or lower (, link_to_OA_fulltext
Published: 2011
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11. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials

Author: EBCTCG, Abe, O., Abe, R., Enomoto, K., Kikuchi, K., Koyama, H., Masuda, H., Nomura, Y., Sakai, K., Sugimachi, K., Tominaga, T., Uchino, J., Yoshida, M., Haybittle, Jl, Davies, C., Harvey, Vj, Holdaway, Tm, Kay, Rg, Mason, Bh, Forbes, Jf, Wilcken, N., Gnant, M., Jakesz, R., Ploner, M., Yosef, Hma, Focan, C., Lobelle, Jp, Peek, U., Oates, Gd, Powell, J., Durand, M., Mauriac, L., Di Leo, A., Dolci, S., Piccart, Mj, Masood, Mb, Parker, D., Price, Jj, Hupperets, Psgj, Jackson, S., Ragaz, J., Berry, D., Broadwater, G., Cirrincione, C., Muss, H., Norton, L., Weiss, Rb, Abu-Zahra, Ht, Portnoj, Sm, Baum, M., Cuzick, J., Houghton, J., Riley, D., Gordon, Nh, Davis, Hl, Beatrice, A., Mihura, J., Naja, A., Lehingue, Y., Romestaing, P., Dubois, Jb, Delozier, T., Mace-Lesec H, J., Rambert, P., Andrysek, O., Barkmanova, J., Owen, Jr, Meier, P., Howell, A., Ribeiro, Gc, Swindell, R., Alison, R., Boreham, J., Clarke, M., Collins, R., Darby, S., Elphinstone, P., Evans, V., Godwin, J., Gray, R., Harwood, C., Hicks, C., James, S., Mackinnon, E., Mcgale, P., Mchugh, T., Mead, G., Peto, R., Wang, Y., Albano, J., Oliveira, Cf, Gervasio, H., Gordilho, J., Johansen, H., Mouridsen, Ht, Gelman, Rs, Harris, Jr, Henderson, Ic, Shapiro, Cl, Andersen, Kw, Axelsson, Ck, Blichert-Toft, M., Moller, S., Overgaard, J., Overgaard, M., Rose, C., Cartensen, B., Palshof, T., Trampisch, Hj, Dalesio, O., Vries, Ege, Rodenhuis, S., Tinteren, H., Comis, Rl, Davidson, Ne, Robert, N., Sledge, G., Tormey, Dc, Wood, W., Cameron, D., Chetty, U., Forrest, P., Jack, W., Rossbach, J., Klijn, Jgm, Treurniet-Donker, Ad, Putten, Wlj, Costa, A., Veronesi, U., Bartelink, H., Duchateau, L., Legrand, C., Sylvester, R., Hage, Ja, Velde, Cjh, Cunningham, Mp, Catalano, R., Creech, Rh, Bonneterre, J., Fargeot, P., Fumoleau, P., Kerbrat, P., Namer, M., Jonat, W., Kaufmann, M., Schumacher, M., Minckwitz, G., Bastert, G., Rauschecker, H., Sauer, R., Sauerbrei, W., Schauer, A., Schryver, A., Vakaet, L., Belfiglio, M., Nicolucci, A., Pellegrini, F., Sacco, M., Valentini, M., Mcardle, Cs, Smith, Dc, Galligioni, E., Boccardo, F., Rubagotti, A., Dent, Dm, Gudgeon, Ca, Hacking, A., Erazo, A., Medina, Jy, Izuo, M., Morishita, Y., Takei, H., Fentiman, Is, Hayward, Jl, Rubens, Rd, Skilton, D., Graeff, H., Janicke, F., Meisner, C., Scheurlen, H., Fournier, D., Dafni, U., Fountzilas, G., Klefstrom, P., Blomqvist, C., Saarto, T., Margreiter, R., Asselain, B., Salmon, Rj, Vilcoq, Jr, Rodrigo Arriagada, Hill, C., Laplanche, A., Le, Mg, Spielmann, M., Bruzzi, P., Montanaro, E., Rosso, R., Sertoli, MR, Venturini, M., Amadori, D., Benraadt, J., Kooi, M., Velde, Ao, Dongen, Ja, Vermorken, Jb, Castiglione, M., Cavalli, F., Coates, A., Collins, J., Forbes, J., Gelber, Rd, Goldhirsch, A., Lindtner, J., Price, Kn, Rudenstam, Cm, Senn, Hj, Bliss, Jm, Chilvers, Ced, Coombes, Rc, Hall, E., Marty, M., Borovik, R., Brufman, G., Hayat, H., Robinson, E., Wigler, N., Bonadonna, G., Camerini, T., Palo, G., Del Vecchio, M., Formelli, F., Valagussa, P., Martoni, A., Pannuti, F., Cocconi, G., Colozza, A., Camisa, R., Aogi, K., Takashima, S., Ikeda, T., Inokuchi, K., Sawa, K., Sonoo, H., Korzeniowski, S., Skolyszewski, J., Ogawa, M., Yamashita, J., Bonte, J., Christiaens, R., Paridaens, R., Den Boegart, W., Martin, P., Romain, S., Hakes, T., Hudis, Ca, Wittes, R., Giokas, G., Kondylis, D., Lissaios, B., La Huerta, R., Sainz, Mg, Altemus, R., Cowan, K., Danforth, D., Lichter, A., Lippman, M., O Shaughnessy, J., Pierce, Lj, Steinberg, S., Venzon, D., Zujewski, J., Paradiso, A., Lena, M., Schittulli, F., Myles, Jd, Pater, Jl, Pritchard, Ki, Anderson, S., Bass, G., Brown, A., Bryant, J., Costantino, J., Dignam, J., Fisher, B., Redmond, C., Wieand, S., Wolmark, N., Jackson, Im, Palmer, Mk, Ingle, Jn, Suman, Vj, Bengtsson, No, Jonsson, H., Larsson, Lg, Lythgoe, Jp, Kissin, M., Erikstein, B., Hannisdal, E., Jacobsen, Ab, Varhaug, Je, Gundersen, S., Hauer-Jensen, M., Host, H., Nissen-Meyer, R., Blamey, Rw, Mitchell, Ak, Morgan, Dal, Robertson, Jfr, Di Palma, M., Mathe, G., Misset, Jl, Clark, Rm, Levine, M., Morimoto, K., Takatsuka, Y., Crossley, E., Harris, A., Talbot, D., Taylor, M., Di Blasio, B., Ivanov, V., Semiglazov, V., Brockschmidt, J., Cooper, MR, Ueo, H., Falkson, Ci, A Hern, R., Ashley, S., Powles, Tj, Smith, Ie, Yarnold, Jr, Gazet, Jc, Cocoran, N., Deshpande, N., Di Martino, L., Douglas, P., Lindtner, A., Notter, G., Bryant, Ajs, Ewing, Gh, Firth, La, Krushen-Kosloski, Jl, Foster, L., George, Wd, Stewart, Hj, Stroner, P., Malmstrom, P., Moller, Tr, Ryden, S., Tengrup, I., Tennvall-Nittby, L., Carstenssen, J., Dufmats, M., Hatschek, T., Nordenskjold, B., Soderberg, M., Carpenter, Jt, Albain, K., Crowley, J., Green, S., Martino, S., Osborne, Ck, Ravdin, Pm, Glas, U., Johansson, U., Rutqvist, Le, Singnomklao, T., Wallgren, A., Maibach, R., Thurlimann, B., Brenner, H., Hercbergs, A., Yoshimoto, M., Deboer, G., Paterson, Ahg, Meakin, Jw, Panzarella, T., Shan, Y., Shao, Yf, Wang, X., Zhao, Db, Chen, Zm, Pan, Hc, Bahi, J., Reid, M., Spittle, M., Deutsch, Gp, Senanayake, F., Kwong, Dlw, Bianco, Ar, Carlomagno, C., Laurentiis, M., Placido, S., Buzdar, Au, Smith, T., Bergh, J., Holmberg, L., Liljegren, G., Nilsson, J., Seifert, M., Sevelda, P., Zielinsky, Cc, Buchanan, Rb, Cross, M., Royle, Gt, Dunn, Ja, Hills, Rk, Lee, M., Morrison, Jm, Spooner, D., Litton, A., Chlebowski, Rt, Caffier, H., Faculteit Medische Wetenschappen/UMCG, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Early Breast Cancer Trialists' Collaborative, Group, DE LAURENTIIS, Michelino, and DE PLACIDO, Sabino
Subjects: Oncology, medicine.medical_specialty, Antineoplastic Agents, Hormonal, DEATHS, Ovariectomy, Antineoplastic Agents, Breast Neoplasms, Aged, Anthracyclines, Antineoplastic Combined Chemotherapy Protocols, Cause of Death, Chemotherapy, Adjuvant, Female, Humans, Middle Aged, Neoplasm Metastasis, Neoplasm Recurrence, Local, Ovary, Randomized Controlled Trials as Topic, Receptors, Estrogen, Survival Rate, Tamoxifen, Medicine (all), Breast cancer, MammaPrint, Internal medicine, Receptors, medicine, Chemotherapy, TAMOXIFEN, skin and connective tissue diseases, Survival rate, Adjuvant, Gynecology, Hormonal, medicine.diagnostic_test, Oncotype DX Breast Cancer Assay, business.industry, General Medicine, medicine.disease, Estrogen, Neoplasm Recurrence, Local, Hormonal therapy, Oncotype DX, business, medicine.drug, Epirubicin
Abstract: Background Quinquennial overviews (1985–2000) of the randomised trials in early breast cancer have assessed the 5 year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxorubicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modern aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50–69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0·0001 for recurrence, 2p For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age ( These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1–2 years of tamoxifen versus none (33 000); and about 5 years versus 1–2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
Published: 2005

12. CMF versus oophorectomy in premenopausal (preMP) stage II breast cancer (BC)

Author: Everington, D, primary, Stewart, HJ, additional, and Leonard, RCF, additional
Published: 1993
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13. Is apocrine differentiation in breast carcinoma of prognostic significance?

Author: Bundred, NJ, primary, Walker, RA, additional, Everington, D, additional, White, GK, additional, Stewart, HJ, additional, and Miller, WR, additional
Published: 1990
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14. Randomised controlled trial of conservation therapy for breast cancer: 6-year analysis of the Scottish trial. Scottish Cancer Trials Breast Group.

Author: Forrest AP, Stewart HJ, Everington D, Prescott RJ, McArdle CS, Harnett AN, Smith DC, George WD, Scottish Cancer Trials Breast Group, Forrest, A P, Stewart, H J, Everington, D, Prescott, R J, McArdle, C S, Harnett, A N, Smith, D C, and George, W D
Abstract: Background: To determine whether, when primary breast cancer is treated by local excision supported by systemic therapy appropriate to the oestrogen receptor status (ER) of the tumour, local radiotherapy can be avoided.Methods: We carried out a randomised controlled trial in 585 patients aged less than 70 years with primary breast cancers of 4 cm or less in size in four specialist units and seven other hospitals in Scotland. After local excision of the tumour (1 cm margin) and an axillary lymph-node clearance or sample, all patients received systemic therapy with oral tamoxifen 20 mg daily or six 3-weekly intravenous bolus injections of cyclophosphamide 600 mg, methotrexate 50 mg, and fluorouracil 600 mg per m2, depending upon the ER concentration in the primary tumour. Patients were then randomly allocated to postoperative radical radiotherapy (50 Gy to breast with boost to the tumour bed) or to no further local treatment. The median follow-up of living patients was 5.7 years. The primary analysis was by intention to treat but since some patients did not receive systemic therapy appropriate to their ER status, a subsidiary analysis was restricted to 464 patients in whom all details of the protocol had been observed.Findings: In the primary analysis survival was equal in the radiotherapy and non-radiotherapy groups (hazard ratio [HR] 0.98, 95% CI 0.67-1.44). Event-free survival showed an advantage in the irradiated patients (HR 0.54, 95% CI 0.39-0.74), largely due to fewer loco-regional relapses (HR 0.20, 95% CI 0.12-0.33). The relapse rate in the ipsilateral breast was 24.5% in the non-irradiated group and 5.8% following breast irradiation. The subsidiary analysis confirmed these findings and indicated the advantage of radiotherapy irrespective of ER concentration. There was a non-significant trend towards fewer distant metastases in the irradiated group.Interpretation: After local excision of a primary breast cancer, we conclude that radiotherapy to the residual breast tissue is advisable even when selective adjuvant systemic therapy is given. [ABSTRACT FROM AUTHOR]
Published: 1996
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15. Randomised comparison of 5 years of adjuvant tamoxifen with continuous therapy for operable breast cancer. The Scottish Cancer Trials Breast Group.

Author: Stewart, HJ, Forrest, AP, Everington, D, McDonald, CC, Dewar, JA, Hawkins, RA, Prescott, RJ, George, WD, Stewart, H J, Forrest, A P, McDonald, C C, Dewar, J A, Hawkins, R A, Prescott, R J, and George, W D
Published: 1996
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16. EFFECTS OF RADIOTHERAPY AND SURGERY IN EARLY BREAST-CANCER - AN OVERVIEW OF THE RANDOMIZED TRIALS

Author: Abe, O., Abe, R., Asaishi, K., Enomoto, K., Hattori, T., Iino, Y., Kikuchi, K., Koyama, H., Sawa, K., Uchino, J., Yoshida, M., Vandevelde, Ao, Vermorken, Jb, Foroglou, P., Giokas, G., Lissaios, B., Harvey, Vj, Holdaway, Tm, Kay, Rg, Mason, Bh, Forbes, Jf, Focan, C., Lobelle, Jp, Peek, U., Oates, Gd, Powell, J., Bastert, G., Rauschecker, H., Sauer, R., Sauerbrei, W., Schauer, A., Schumacher, M., Gelman, Rs, Henderson, Ic, Shapiro, Cl, Hancock, Ak, Jackson, S., Ragaz, J., Delozier, T., Macelesech, J., Haybittle, Jl, Cirrincione, C., Korzun, A., Weiss, Rb, Wood, Wc, Baum, M., Houghton, J., Riley, D., Dent, Dm, Gudgeon, Ca, Hacking, A., Horgan, K., Hughes, L., Stewart, Hj, Gordon, Nh, Davis, Hl, Owen, Jr, Meier, P., Howell, A., Ribeiro, Gc, Swindell, R., Albano, J., Deoliveira, Cf, Gervasio, H., Gordilho, J., Carstensen, B., Palshof, T., Johansen, H., Korzeniowski, S., Skolyszewski, J., Andersen, Kw, Axelsson, Ck, Blicherttoft, M., Mouridsen, Ht, Overgaard, M., Rose, C., Corcoran, N., Trampisch, Hj, Abeloff, Md, Carbone, Pc, Glick, J., Gray, R., Tormey, Dc, Bartelink, H., Fentiman, Is, Paridaens, R., Vandriel, Ojr, Sylvester, Rj, Vandevelde, Cjh, Vanderschueren, E., Vandongen, Ja, Welvaart, K., Scanlon, Ef, Schurman, S., Deschryver, A., Yosef, Hma, Mcardle, Cs, Smith, Dc, Lara, Pc, Boccardo, F., Izuo, M., Morishita, Y., Bentley, A., Doran, Z., Hayward, Jl, Rubens, Rd, Kaufmann, M., Jonat, W., Scheurlen, H., Vonfournier, D., Klefstrom, P., Cuzick, J., Margreiter, R., Cavalli, F., Collins, J., Gelber, Rd, Goldhirsch, A., ISLEY, MR, Lindtner, J., Price, Kn, Rudenstam, Cm, Bliss, Jm, Chilvers, Ced, Coombes, Rc, Marty, M., Brufman, G., Hayat, H., Borovik, R., Robinson, E., Pannuti, F., Takashima, S., Yasutomi, T., Sonoo, H., Yamashita, J., Ogawa, M., Nomura, Y., Bonte, J., Tengrup, I., Tennvallnittby, L., Martin, P., Romain, S., Ahmann, D., Schaid, Dj, Buzdar, Au, Smith, T., Hakes, T., Norton, L., Wittes, R., Delahuerta, R., Sainz, Mg, Bonadonna, G., Delvecchio, M., Valagussa, P., Veronesi, U., Dubois, Jb, Bianco, Ar, Lippman, Me, Pierce, Lj, Simon, R., Steinberg, Sm, Brown, A., Fisher, B., Redmond, C., Wolmark, N., Jackson, Im, Palmer, Mk, Ingle, Jn, Bengtsson, No, Larsson, Lg, Lythgoe, Jp, Kissin, M., Hannisdal, E., Varhaug, Je, Blamey, Rw, Mitchell, Ak, Robertson, Jfr, Nakamura, Y., Mathe, G., Misset, Jl, Clarke, Ea, Mclaughlin, Jr, Clark, Rm, Levine, M., Morimoto, K., Gundersen, S., Hauerjensen, M., Host, H., Crossley, E., Durrant, K., Harris, A., Beighton, A., Chadbon, D., Clarke, M., Collins, R., Davies, C., Evans, V., Godwin, J., Greaves, E., Harwood, C., James, S., Mead, G., Muldahl, A., Peto, R., Tooth, A., Wheatley, K., Rambert, P., Asselain, B., Salmon, Rj, Vilcoq, Jr, Arriagada, R., Hill, C., Laplanche, A., Le, Mg, Spielmann, M., Cocconi, G., Diblasio, B., Catalano, R., Creech, Rh, Brockschmidt, J., COOPER, MR, Andrysek, O., Barkmanova, J., Treurnietdonker, Ad, Vanputten, Wlj, Easton, D., Powles, Tj, Gazet, Jc, Semiglazov, V., Deshpande, N., Dimartino, L., Douglas, P., Lindtner, A., Notter, G., Nissenmeyer, R., Forrest, Apm, Jack, W., Mcdonald, C., Moller, Tr, Ryden, S., Carstensen, J., Hatschek, T., Soderberg, M., Carpenter, Jt, Albain, K., Crowley, J., Green, S., Osborne, Ck, Rutquist, Le, Wallgren, A., Holm, Le, Castiglione, M., Fluckiger, H., Thurlimann, B., Hermann Brenner, Hercbergs, A., Yoshimoto, M., Deboer, G., Paterson, Ahg, Pritchard, Ki, Meakin, Jw, Panzarella, T., Naja, A., Bahi, J., Reid, M., Spittler, M., Senanayake, F., Holmberg, L., Sevelda, P., Zielinsky, Cc, Jakesz, R., Buchanan, Rb, Cross, M., Dunn, Ja, Gillespie, Wm, Kelly, K., Morrison, Jm, Litton, A., Chlebowski, Rt, Bezwoda, Wr, and Caffier, H.

17. Ovarian ablation in early breast cancer: Overview of the randomised trials

Author: Clarke, M., Collins, R., Davies, C., Godwin, J., Gray, R., Peto, R., Abe, O., Abe, R., Enomoto, K., Kikuchi, K., Koyama, H., Nomura, Y., Sakai, K., Sugimachi, K., Tominaga, T., Uchino, J., Yoshida, M., Vandevelde, Ao, Vandongen, Ja, Vermorken, Jb, Arvelakis, A., Giokas, G., Lissaios, B., Harvey, Vj, Holdaway, Tm, Kay, Rg, Mason, Bh, Coates, A., Forbes, Jf, Focan, C., Lobelle, Jp, Peek, U., Oates, Gd, Powell, J., Bastert, G., Rauschecker, H., Sauer, R., Sauerbrei, W., Schauer, A., Schumacher, M., Durand, M., Mauriac, L., Bartholomeus, S., Piccart, Mj, Gelman, Rs, Henderson, Ic, Shapiro, Cl, Hancock, Ak, Masood, Mb, Parker, D., Price, Jj, Jackson, S., Ragaz, J., Delozier, T., Macelesech, J., Haybittle, Jl, Cirrincione, C., Korzun, A., Weiss, Rb, Wood, Wc, Baum, M., Houghton, J., Riley, D., Dent, Dm, Gudgeon, Ca, Hacking, A., Horgan, K., Hughes, L., Stewart, Hj, Gordon, Nh, Davis, Hl, Lehingue, Y., Owen, Jr, Meier, P., Howell, A., Ribeiro, Gc, Swindell, R., Albano, J., Deoliveira, Cf, Gervasio, H., Gordilho, J., Carstensen, B., Palshof, T., Johansen, H., Korzeniowski, S., Skolyszewski, J., Andersen, Kw, Axelsson, Ck, Blicherttoft, M., Mouridsen, Ht, Overgaard, M., Rose, C., Corcoran, N., Trampisch, Hj, Abeloff, Md, Carbone, Pc, Glick, J., Tormey, Dc, Rossbach, J., Scanlon, Ef, Schurman, S., Deschryver, A., Yosef, Hma, Mcardle, Cs, Smith, Dc, Lara, Pc, Boccardo, F., Erazo, A., Medina, Jy, Izuo, M., Morishita, Y., Bentley, A., Doran, Z., Fentiman, Is, Hayward, Jl, Rubens, Rd, Kaufmann, M., Jonat, W., Scheurlen, H., Vonfournier, D., Fountzilas, G., Klefstrom, P., Blomqvist, C., Cuzick, J., Margreiter, R., Castiglione, M., Cavalli, F., Collins, J., Forbes, J., Gelber, Rd, Goldhirsch, A., Lindtner, J., Price, Kn, Rudenstam, Cm, Senn, Hj, Bliss, Jm, Chilvers, Ced, Coombes, Rc, Marty, M., Borovik, R., Brufman, G., Hayat, H., Robinson, E., Wigler, N., Pannuti, F., Takashima, S., Tasutomi, T., Sonoo, H., Yamashita, J., Ogawa, M., Hupperets, Psgj, Bonte, J., Tengrup, I., Tennvallnittby, L., Martin, P., Romain, S., Ahmann, D., Schaid, Dj, Buzdar, Au, Smith, T., Hakes, T., Norton, L., Wittes, R., Delahuerta, R., Sainz, Mg, Bonadonna, G., Delvecchio, M., Valagussa, P., Veronesi, U., Dubois, Jb, Bianco, Ar, Lippman, Me, Pierce, Lj, Simon, R., Steinberg, Sm, Brown, A., Fisher, B., Redmond, C., Wolmark, N., Jackson, Im, Palmer, Mk, Ingle, Jn, Suman, Vj, Bengtsson, No, Larsson, Lg, Lythgoe, Jp, Kissin, M., Hannisdal, E., Varhaug, Je, Nissenmeyer, R., Blamey, Rw, Mitchell, Ak, Robertson, Jfr, Nakamura, Y., Mathe, G., Misset, Jl, Abuzahra, Ht, Clarke, Ea, Mclaughlin, Jr, Clark, Rm, Levine, M., Myles, Jd, Pater, Jl, Pritchard, Ki, Morimoto, K., Sawa, K., Takatsuka, Y., Gundersen, S., Hauerjensen, M., Host, A., Crossley, E., Durrant, K., Harris, A., Beighton, A., Evans, V., Greaves, E., Harwood, C., James, S., Lau, E., Mead, G., Muldal, A., Naughton, A., Tooth, A., Wheatley, K., Rambert, P., Asselain, B., Salmon, Rj, Vilcoq, Jr, Rodrigo Arriagada, Hill, C., Laplanche, A., Le, Mg, Speilmann, M., Cocconi, G., Diblasio, B., Catalano, R., Creech, Rh, Brockschmidt, J., Cooper, MR, Andrysek, O., Barkmanova, J., Falkson, Cj, Abraham, M., Klijn, Jgm, Treurnietdonker, Ad, Vanputten, Wlj, Easton, D., Powles, Tj, Gazet, Jc, Semiglazov, V., Deshpande, N., Dimartino, L., Douglas, P., Host, H., Bryant, Ajs, Ewing, Gh, Krushenkosloski, Jl, Forrest, Apm, Jack, W., Mcdonald, C., Moller, Tr, Ryden, S., Carstensen, J., Hatschek, T., Soderberg, M., Carpenter, Jt, Albain, K., Crowley, J., Green, S., Martino, S., Osborne, Ck, Ravdin, Pm, Rutqvist, Le, Wallgren, A., Holm, Le, Yoshimoto, M., Deboer, G., Paterson, Ahg, Meakin, Jw, Panzarella, T., Naja, A., Bahi, J., Reid, M., Spittle, M., Senanayake, F., Bergh, J., Holmberg, L., Sevelda, P., Zielinsky, Cc, Jakesz, R., Gnant, M., Buchanan, Rb, Cross, M., Dunn, Ja, Gillespie, Wm, Kelly, K., Morrison, Jm, Litton, A., Chlebowski, Rt, Bezwoda, Wr, Caffier, H., Clarke, M, Collins, R, Davies, C, Godwin, J, Gray, R, Peto, R, Abe, O, Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Nomura, Y, Sakai, K, Sugimachi, K, Tominaga, T, Uchino, J, Yoshida, M, vandeVelde, A, vanDongen, J, Vermorken, J, Arvelakis, A, Giokas, G, Lissaios, B, Harvey, V, and Holdaway, T
Subjects: Oncology, medicine.medical_specialty, Breast cancer, business.industry, Internal medicine, medicine, Ovarian Ablation, General Medicine, business, medicine.disease, Early breast cancer
Abstract: Background Among women with early breast cancer, the effects of ovarian ablation on recurrence and death have been assessed by several randomised trials that now have long follow-up. In this report, the Early Breast Cancer Trialists' Collaborative Group present their third 5-yearly systematic overview (meta-analysis), now with 15 years' follow-up. Methods In 1995, information was sought on each patient in any randomised trial of ovarian ablation or suppression versus control that began before 1990. Data were obtained for 12 of the 13 studies that assessed ovarian ablation by irradiation or surgery, all of which began before 1980, but not for the four studies that assessed ovarian suppression by drugs, all of which began after 1985. Menopausal status was not consistently defined across trials; therefore, the main analyses are limited to women aged under 50 (rather than “premenopausal”) when randomised. Oestrogen receptors were measured only in the trials of ablation plus cytotoxic chemotherapy versus the same chemotherapy alone. Findings Among 2102 women aged under 50 when randomised, most of whom would have been premenopausal at diagnosis, 1130 deaths and an additional 153 recurrences were reported. 15-year survival was highly significantly improved among those allocated ovarian ablation (52·4 vs46·1%, 6·3 [SD 2·3] fewer deaths per 100 women, logrank 2p=0·001), as was recurrence-free survival (45·0 vs 39·0%, 2p=0·0007). The numbers of events were too small for any subgroup analyses to be reliable. The benefit was, however, significant both for those with (“node positive”) and for those without (“node negative”) axillary spread when diagnosed. In the trials of ablation plus cytotoxic chemotherapy versus the same chemotherapy alone, the benefit appeared smaller (even for women with oestrogen receptors detected on the primary tumour) than in the trials of ablation in the absence of chemotherapy (where the observed survival improvements were about six per 100 node-negative women and 12 per 100 node-positive women). Among 1354 women aged 50 or over when randomised, most of whom would have been perimenopausal or postmenopausal, there was only a nonsignificant improvement in survival and recurrence-free survival. improves long-term survival, at least in the absence of chemotherapy. Further randomised evidence is needed on the additional effects of ovarian ablation in the presence of other adjuvant treatments, and to assess the relevance of hormone-receptor measurements. Interpretation In women aged under 50 with early breast cancer, ablation of functioning ovaries significantly.

18. 'Like Poor Galley Slaves ....': Slavery and Convict Transportation

Author: Fernandes Dias, MS, Maxwell-Stewart, HJ, Fernandes Dias, MS, and Maxwell-Stewart, HJ
Abstract: Slavery was just one of a number of fonns of unfree labour associated with European overseas expansion. Indeed, of an estimated 5,300,000 unfree migrants carried on British vessels in the period 1519-1920, only about 58 percent were slaves. Of the remainder, 36 percent were indentured servants (predominantly drawn from the Indian subcontinent) and 6 percent (or approximately 310,000) were transported convicts. Although as a mechanism of enforced migration, it accounted for a minority of unfree voyages, convict transportation was a particularly long-lived practice. Introduced in 1615 by James 1 who gave the courts the discretion to reprieve felons on condition of enforced removal and labour "in foreign discoveries or other services beyond the seas", transportation was not abolished until 1920 when the last Indian convicts arrived at Port Blair in the Andaman Islands. Convict labour predated the use of slaves in many important British overseas possessions, including Barbados where they were used to cultivate tobacco. It also proved to be much' more durable than slavery. The convict establishment at Port Blair was not closed until 1939, over one hundred years after the ending of the apprenticeship system marked the fonnal demise of slavery as a legal institution within the British Empire.

19. A Spanish Convict, her clergyman biographer, and the amanuensis of her bastard son

Author: Frost, Lucy, Maxwell-Stewart, HJ, Frost, L, Ballyn, S, Frost, Lucy, Maxwell-Stewart, HJ, Frost, L, and Ballyn, S
Abstract: In 1829 Adelaide de la Thoreza, a twenty-three-year-old woman born in Madrid, was tried at London's Old Bailey and sentenced to seven years' transportation to Australia. Half a century later a Presbyterian clergyman in the New South Wales town of Richmond wrote a biography of this Spanish convict, who had recently died. In this book chapter we interrogate his romantic account of how the daughter of Spanish aristocrats became first a convict and then a pioneer mother, whose oldest son Alf was born in the Parramatta Female Factory and given the surname "Smith" to cover his illegitimacy. Alf's reminiscences of life as a drover were published in 1909.

20. 'Like Poor Galley Slaves ....': Slavery and Convict Transportation

Author: Fernandes Dias, MS, Maxwell-Stewart, HJ, Fernandes Dias, MS, and Maxwell-Stewart, HJ
Abstract: Slavery was just one of a number of fonns of unfree labour associated with European overseas expansion. Indeed, of an estimated 5,300,000 unfree migrants carried on British vessels in the period 1519-1920, only about 58 percent were slaves. Of the remainder, 36 percent were indentured servants (predominantly drawn from the Indian subcontinent) and 6 percent (or approximately 310,000) were transported convicts. Although as a mechanism of enforced migration, it accounted for a minority of unfree voyages, convict transportation was a particularly long-lived practice. Introduced in 1615 by James 1 who gave the courts the discretion to reprieve felons on condition of enforced removal and labour "in foreign discoveries or other services beyond the seas", transportation was not abolished until 1920 when the last Indian convicts arrived at Port Blair in the Andaman Islands. Convict labour predated the use of slaves in many important British overseas possessions, including Barbados where they were used to cultivate tobacco. It also proved to be much' more durable than slavery. The convict establishment at Port Blair was not closed until 1939, over one hundred years after the ending of the apprenticeship system marked the fonnal demise of slavery as a legal institution within the British Empire.

21. Slipping the shackles: escape from convict Australia

Author: Sandra Murray, Maxwell-Stewart, HJ, Sandra Murray, and Maxwell-Stewart, HJ

22. 'Like Poor Galley Slaves ....': Slavery and Convict Transportation

Author: Fernandes Dias, MS, Maxwell-Stewart, HJ, Fernandes Dias, MS, and Maxwell-Stewart, HJ
Abstract: Slavery was just one of a number of fonns of unfree labour associated with European overseas expansion. Indeed, of an estimated 5,300,000 unfree migrants carried on British vessels in the period 1519-1920, only about 58 percent were slaves. Of the remainder, 36 percent were indentured servants (predominantly drawn from the Indian subcontinent) and 6 percent (or approximately 310,000) were transported convicts. Although as a mechanism of enforced migration, it accounted for a minority of unfree voyages, convict transportation was a particularly long-lived practice. Introduced in 1615 by James 1 who gave the courts the discretion to reprieve felons on condition of enforced removal and labour "in foreign discoveries or other services beyond the seas", transportation was not abolished until 1920 when the last Indian convicts arrived at Port Blair in the Andaman Islands. Convict labour predated the use of slaves in many important British overseas possessions, including Barbados where they were used to cultivate tobacco. It also proved to be much' more durable than slavery. The convict establishment at Port Blair was not closed until 1939, over one hundred years after the ending of the apprenticeship system marked the fonnal demise of slavery as a legal institution within the British Empire.

23. Slipping the shackles: escape from convict Australia

Author: Sandra Murray, Maxwell-Stewart, HJ, Sandra Murray, and Maxwell-Stewart, HJ

24. Slipping the shackles: escape from convict Australia

Author: Sandra Murray, Maxwell-Stewart, HJ, Sandra Murray, and Maxwell-Stewart, HJ

25. A Spanish Convict, her clergyman biographer, and the amanuensis of her bastard son

Author: Frost, Lucy, Maxwell-Stewart, HJ, Frost, L, Ballyn, S, Frost, Lucy, Maxwell-Stewart, HJ, Frost, L, and Ballyn, S
Abstract: In 1829 Adelaide de la Thoreza, a twenty-three-year-old woman born in Madrid, was tried at London's Old Bailey and sentenced to seven years' transportation to Australia. Half a century later a Presbyterian clergyman in the New South Wales town of Richmond wrote a biography of this Spanish convict, who had recently died. In this book chapter we interrogate his romantic account of how the daughter of Spanish aristocrats became first a convict and then a pioneer mother, whose oldest son Alf was born in the Parramatta Female Factory and given the surname "Smith" to cover his illegitimacy. Alf's reminiscences of life as a drover were published in 1909.

26. A Spanish Convict, her clergyman biographer, and the amanuensis of her bastard son

Author: Frost, Lucy, Maxwell-Stewart, HJ, Frost, L, Ballyn, S, Frost, Lucy, Maxwell-Stewart, HJ, Frost, L, and Ballyn, S
Abstract: In 1829 Adelaide de la Thoreza, a twenty-three-year-old woman born in Madrid, was tried at London's Old Bailey and sentenced to seven years' transportation to Australia. Half a century later a Presbyterian clergyman in the New South Wales town of Richmond wrote a biography of this Spanish convict, who had recently died. In this book chapter we interrogate his romantic account of how the daughter of Spanish aristocrats became first a convict and then a pioneer mother, whose oldest son Alf was born in the Parramatta Female Factory and given the surname "Smith" to cover his illegitimacy. Alf's reminiscences of life as a drover were published in 1909.

27. Tumour cyclic AMP binding proteins and endocrine responsiveness in patients with inoperable breast cancer

Author: Watson, DMA, primary, Hawkins, RA, additional, Bundred, NJ, additional, Stewart, HJ, additional, and Miller, WR, additional
Published: 1987
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28. Breast Cancer – Which Patients?

Author: Stewart Hj
Subjects: Oncology, medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, education, Endocrine therapy, Cancer, medicine.disease, humanities, Endocrinology, Breast cancer, Internal medicine, medicine, Tamoxifen therapy, skin and connective tissue diseases, business, health care economics and organizations, Tamoxifen, medicine.drug
Abstract: The question of which breast cancer patients to treat has been addressed by reviewing posters presented at the International Symposium on Endocrine Therapy. To date, tamoxifen therapy is the dominant
Published: 1989
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29. Conservation Therapy for Breast Cancer

Author: Forrest, AP, Stewart, HJ, Everington, D, Prescott, RJ, McArdle, CS, and Harnett, AN
Published: 1997
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30. A maturational frequency discrimination deficit may explain developmental language disorder.

Author: Jones SD, Stewart HJ, and Westermann G
Subjects: Child, Humans, Auditory Perception physiology, Language Development, Language, Speech Perception physiology, Language Development Disorders
Abstract: Auditory perceptual deficits are widely observed among children with developmental language disorder (DLD). Yet, the nature of these deficits and the extent to which they explain speech and language problems remain controversial. In this study, we hypothesize that disruption to the maturation of the basilar membrane may impede the optimization of the auditory pathway from brainstem to cortex, curtailing high-resolution frequency sensitivity and the efficient spectral decomposition and encoding of natural speech. A series of computational simulations involving deep convolutional neural networks that were trained to encode, recognize, and retrieve naturalistic speech are presented to demonstrate the strength of this account. These neural networks were built on top of biologically truthful inner ear models developed to model human cochlea function, which-in the key innovation of the present study-were scheduled to mature at different rates over time. Delaying cochlea maturation qualitatively replicated the linguistic behavior and neurophysiology of individuals with language learning difficulties in a number of ways, resulting in (a) delayed language acquisition profiles, (b) lower spoken word recognition accuracy, (c) word finding and retrieval difficulties, (d) "fuzzy" and intersecting speech encodings and signatures of immature neural optimization, and (e) emergent working memory and attentional deficits. These simulations illustrate many negative cascading effects that a primary maturational frequency discrimination deficit may have on early language development and generate precise and testable hypotheses for future research into the nature and cost of auditory processing deficits in children with language learning difficulties. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Published: 2024
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31. Amplitude Modulation Perception and Cortical Evoked Potentials in Children With Listening Difficulties and Their Typically Developing Peers.

Author: Petley L, Blankenship C, Hunter LL, Stewart HJ, Lin L, and Moore DR
Subjects: Child, Humans, Cues, Evoked Potentials, Reaction Time, Perception, Evoked Potentials, Auditory, Noise, Speech Perception physiology
Abstract: Purpose: Amplitude modulations (AMs) are important for speech intelligibility, and deficits in speech intelligibility are a leading source of impairment in childhood listening difficulties (LiD). The present study aimed to explore the relationships between AM perception and speech-in-noise (SiN) comprehension in children and to determine whether deficits in AM processing contribute to childhood LiD. Evoked responses were used to parse the neural origins of AM processing., Method: Forty-one children with LiD and 44 typically developing children, ages 8-16 years, participated in the study. Behavioral AM depth thresholds were measured at 4 and 40 Hz. SiN tasks included the Listening in Spatialized Noise-Sentences Test (LiSN-S) and a coordinate response measure (CRM)-based task. Evoked responses were obtained during an AM change detection task using alternations between 4 and 40 Hz, including the N1 of the acoustic change complex, auditory steady-state response (ASSR), P300, and a late positive response (late potential [LP]). Maturational effects were explored via age correlations., Results: Age correlated with 4-Hz AM thresholds, CRM separated talker scores, and N1 amplitude. Age-normed LiSN-S scores obtained without spatial or talker cues correlated with age-corrected 4-Hz AM thresholds and area under the LP curve. CRM separated talker scores correlated with AM thresholds and area under the LP curve. Most behavioral measures of AM perception correlated with the signal-to-noise ratio and phase coherence of the 40-Hz ASSR. AM change response time also correlated with area under the LP curve. Children with LiD exhibited deficits with respect to 4-Hz thresholds, AM change accuracy, and area under the LP curve., Conclusions: The observed relationships between AM perception and SiN performance extend the evidence that modulation perception is important for understanding SiN in childhood. In line with this finding, children with LiD demonstrated poorer performance on some measures of AM perception, but their evoked responses implicated a primarily cognitive deficit., Supplemental Material: https://doi.org/10.23641/asha.25009103.
Published: 2024
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32. Amplitude modulation perception and cortical evoked potentials in children with listening difficulties and their typically-developing peers.

Author: Petley L, Blankenship C, Hunter LL, Stewart HJ, Lin L, and Moore DR
Abstract: Purpose: Amplitude modulations (AM) are important for speech intelligibility, and deficits in speech intelligibility are a leading source of impairment in childhood listening difficulties (LiD). The present study aimed to explore the relationships between AM perception and speech-in-noise (SiN) comprehension in children and to determine whether deficits in AM processing contribute to childhood LiD. Evoked responses were used to parse the neural origin of AM processing., Method: Forty-one children with LiD and forty-four typically-developing children, ages 8-16 y.o., participated in the study. Behavioral AM depth thresholds were measured at 4 and 40 Hz. SiN tasks included the LiSN-S and a Coordinate Response Measure (CRM)-based task. Evoked responses were obtained during an AM Change detection task using alternations between 4 and 40 Hz, including the N1 of the acoustic change complex, auditory steady-state response (ASSR), P300, and a late positive response (LP). Maturational effects were explored via age correlations., Results: Age correlated with 4 Hz AM thresholds, CRM Separated Talker scores, and N1 amplitude. Age-normed LiSN-S scores obtained without spatial or talker cues correlated with age-corrected 4 Hz AM thresholds and area under the LP curve. CRM Separated Talker scores correlated with AM thresholds and area under the LP curve. Most behavioral measures of AM perception correlated with the SNR and phase coherence of the 40 Hz ASSR. AM Change RT also correlated with area under the LP curve. Children with LiD exhibited deficits with respect to 4 Hz thresholds, AM Change accuracy, and area under the LP curve., Conclusions: The observed relationships between AM perception and SiN performance extend the evidence that modulation perception is important for understanding SiN in childhood. In line with this finding, children with LiD demonstrated poorer performance on some measures of AM perception, but their evoked responses implicated a primarily cognitive deficit.
Published: 2023
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33. Encouraging the use of the Veterans Crisis Line among high-risk Veterans: A randomized trial of a Crisis Line Facilitation intervention.

Author: Ilgen MA, Price AM, Coughlin LN, Pfeiffer PN, Stewart HJ, Pope E, and Britton PC
Subjects: Behavior Therapy, Crisis Intervention, Humans, Suicidal Ideation, Suicide, Attempted prevention & control, Veterans
Abstract: The Veterans Crisis Line (VCL) is a core component of VA's suicide prevention strategy. Despite the availability and utility of the VCL, many Veterans do not utilize this resource during times of crisis. A brief, psychoeducational behavioral intervention (termed Crisis Line Facilitation [CLF]) was developed to increase utilization of the VCL and reduce suicidal behaviors in high-risk Veterans. The therapist-led session includes educational information regarding the VCL, as well as a chance to discuss the participant's perceptions of contacting the VCL during periods of crisis. The final component of the session is a practice call placed to the VCL by both the therapist and the participant. The CLF intervention was compared to Enhanced Usual Care (EUC) during a multi-site randomized clinical trial for 307 Veteran participants recently hospitalized for a suicidal crisis who reported no contact with the VCL in the prior 12 months. Initial analyses indicated that participants randomized to the CLF intervention were less likely to report suicidal behaviors, including suicide attempts compared to participants randomized to receive EUC over 12-months of follow-up (χ 2 = 18.48/p < 0.0001), however this effect was not sustained when analyses were conducted on an individual level. No significant differences were found between conditions on VCL utilization. Initial evidence suggests a brief CLF intervention has an impact on preventing suicidal behaviors in Veterans treated in inpatient mental health programs; however, it may not change use of the VCL. This brief intervention could be easily adapted into clinical settings to be delivered by standard clinical staff., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
Published: 2022
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34. Adaptive Hearing Aid Benefit in Children With Mild/Moderate Hearing Loss: A Registered, Double-Blind, Randomized Clinical Trial.

Author: Stewart HJ, Cash EK, Pinkl J, Nakeva von Mentzer C, Lin L, Hunter LL, and Moore DR
Subjects: Child, Hearing Tests, Humans, Noise, Hearing Aids, Hearing Loss, Hearing Loss, Sensorineural rehabilitation, Speech Perception
Abstract: Objectives: We completed a registered double-blind randomized control trial to compare acclimatization to two hearing aid fitting algorithms by experienced pediatric hearing aid users with mild to moderate hearing loss. We hypothesized that extended use (up to 13 months) of an adaptive algorithm with integrated directionality and noise reduction, OpenSound Navigator (OSN), would result in improved performance on auditory, cognitive, academic, and caregiver- or self-report measures compared with a control, omnidirectional algorithm (OMNI)., Design: Forty children aged 6 to 13 years with mild to moderate/severe symmetric sensorineural hearing loss completed this study. They were all experienced hearing aid users and were recruited through the Cincinnati Children's Hospital Medical Center Division of Audiology. The children were divided into 20 pairs based on similarity of age (within 1 year) and hearing loss (level and configuration). Individuals from each pair were randomly assigned to either an OSN (experimental) or OMNI (control) fitting algorithm group. Each child completed an audiology evaluation, hearing aid fitting using physically identical Oticon OPN hearing aids, follow-up audiological appointment, and 2 research visits up to 13 months apart. Research visit outcome measures covered speech perception (in quiet and in noise), novel grammar and word learning, cognition, academic ability, and caregiver report of listening behaviors. Analysis of outcome differences between visits, groups, ages, conditions and their interactions used linear mixed models. Between 22 and 39 children provided useable data for each task., Results: Children using the experimental (OSN) algorithm did not show any significant performance differences on the outcome measures compared with those using the control (OMNI) algorithm. Overall performance of all children in the study increased across the duration of the trial on word repetition in noise, sentence repetition in quiet, and caregivers' assessment of hearing ability. There was a significant negative relationship between age at first hearing aid use, final Reading and Mathematical ability, and caregiver rated speech hearing. A significant positive relationship was found between daily hearing aid use and study-long change in performance on the Flanker test of inhibitory control and attention. Logged daily use of hearing aids related to caregiver rated spatial hearing. All results controlled for age at testing/evaluation and false discovery rate., Conclusions: Use of the experimental (OSN) algorithm neither enhanced nor reduced performance on auditory, cognitive, academic or caregiver report measures compared with the control (OMNI) algorithm. However, prolonged hearing aid use led to benefits in hearing, academic skills, attention, and caregiver evaluation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
Published: 2022
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35. Speech cortical activation and connectivity in typically developing children and those with listening difficulties.

Author: Stewart HJ, Cash EK, Hunter LL, Maloney T, Vannest J, and Moore DR
Subjects: Child, Humans, Adolescent, Auditory Perception, Noise, Vocabulary, Speech, Speech Perception physiology
Abstract: Listening difficulties (LiD) in people who have normal audiometry are a widespread but poorly understood form of hearing impairment. Recent research suggests that childhood LiD are cognitive rather than auditory in origin. We examined decoding of sentences using a novel combination of behavioral testing and fMRI with 43 typically developing children and 42 age matched (6-13 years old) children with LiD, categorized by caregiver report (ECLiPS). Both groups had clinically normal hearing. For sentence listening tasks, we found no group differences in fMRI brain cortical activation by increasingly complex speech stimuli that progressed in emphasis from phonology to intelligibility to semantics. Using resting state fMRI, we examined the temporal connectivity of cortical auditory and related speech perception networks. We found significant group differences only in cortical connections engaged when processing more complex speech stimuli. The strength of the affected connections was related to the children's performance on tests of dichotic listening, speech-in-noise, attention, memory and verbal vocabulary. Together, these results support the novel hypothesis that childhood LiD reflects difficulties in language rather than in auditory or phonological processing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2022
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36. Listening Difficulties in Children With Normal Audiograms: Relation to Hearing and Cognition.

Author: Petley L, Hunter LL, Motlagh Zadeh L, Stewart HJ, Sloat NT, Perdew A, Lin L, and Moore DR
Subjects: Adolescent, Auditory Perception, Child, Cognition, Cross-Sectional Studies, Hearing, Humans, Hearing Tests, Speech Perception
Abstract: Objectives: Children presenting at audiology services with caregiver-reported listening difficulties often have normal audiograms. The appropriate approach for the further assessment and clinical management of these children is currently unclear. In this Sensitive Indicators of Childhood Listening Difficulties (SICLiD) study, we assessed listening ability using a reliable and validated caregiver questionnaire (the Evaluation of Children's Listening and Processing Skills [ECLiPS]) in a large (n = 146) and heterogeneous sample of 6- to 13-year-old children with normal audiograms. Scores on the ECLiPS were related to a multifaceted laboratory assessment of the children's audiological, psycho- and physiological-acoustic, and cognitive abilities. This report is an overview of the SICLiD study and focuses on the children's behavioral performance. The overall goals of SICLiD were to understand the auditory and other neural mechanisms underlying childhood listening difficulties and translate that understanding into clinical assessment and, ultimately, intervention., Design: Cross-sectional behavioral assessment of children with "listening difficulties" and an age-matched "typically developing" control group. Caregivers completed the ECLiPS, and the resulting total standardized composite score formed the basis of further descriptive statistics, univariate, and multivariate modeling of experimental data., Results: All scores of the ECLiPS, the SCAN-3:C, a standardized clinical test suite for auditory processing, and the National Institutes of Health (NIH) Cognition Toolbox were significantly lower for children with listening difficulties than for their typically developing peers using group comparisons via t-tests and Wilcoxon Rank-Sum tests. A similar effect was observed on the Listening in Spatialized Noise-Sentences (LiSN-S) test for speech sentence-in-noise intelligibility but only reached significance for the Low Cue and High Cue conditions and the Talker Advantage derived score. Stepwise regression to examine the factors contributing to the ECLiPS Total scaled score (pooled across groups) yielded a model that explained 42% of its variance based on the SCAN-3:C composite, LiSN-S Talker Advantage, and the NIH Toolbox Picture Vocabulary, and Dimensional Change Card Sorting scores (F[4, 95] = 17.35, p < 0.001). High correlations were observed between many test scores including the ECLiPS, SCAN-3:C, and NIH Toolbox composite measures. LiSN-S Advantage measures generally correlated weakly and nonsignificantly with non-LiSN-S measures. However, a significant interaction was found between extended high-frequency threshold and LiSN-S Talker Advantage., Conclusions: Children with listening difficulties but normal audiograms have problems with the cognitive processing of auditory and nonauditory stimuli that include both fluid and crystallized reasoning. Analysis of poor performance on the LiSN-S Talker Advantage measure identified subclinical hearing loss as a minor contributing factor to talker segregation. Beyond auditory tests, evaluations of children with complaints of listening difficulties should include standardized caregiver observations and consideration of broad cognitive abilities., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
Published: 2021
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37. Short-Term Pediatric Acclimatization to Adaptive Hearing Aid Technology.

Author: Pinkl J, Cash EK, Evans TC, Neijman T, Hamilton JW, Ferguson SD, Martinez JL, Rumley J, Hunter LL, Moore DR, and Stewart HJ
Subjects: Acclimatization, Child, Humans, Noise, Hearing Aids, Hearing Loss, Sensorineural, Speech Perception
Abstract: Purpose This exploratory study assessed the perceptual, cognitive, and academic learning effects of an adaptive, integrated, directionality, and noise reduction hearing aid program in pediatric users. Method Fifteen pediatric hearing aid users (6-12 years old) received new bilateral, individually fitted Oticon Opn hearing aids programmed with OpenSound Navigator (OSN) processing. Word recognition in noise, sentence repetition in quiet, nonword repetition, vocabulary learning, selective attention, executive function, memory, and reading and mathematical abilities were measured within 1 week of the initial hearing aid fitting and 2 months post fit. Caregivers completed questionnaires assessing their child's listening and communication abilities prior to study enrollment and after 2 months of using the study hearing aids. Results Caregiver reporting indicated significant improvements in speech and sound perception, spatial sound awareness, and the ability to participate in conversations. However, there was no positive change in performance in any of the measured skills. Mathematical scores significantly declined after 2 months. Conclusions OSN provided a perceived improvement in functional benefit, compared to their previous hearing aids, as reported by caregivers. However, there was no positive change in listening skills, cognition, and academic success after 2 months of using OSN. Findings may have been impacted by reporter bias, limited sample size, and a relatively short trial period. This study took place during the summer when participants were out of school, which may have influenced the decline in mathematical scores. The results support further exploration with age- and audiogram-matched controls, larger sample sizes, and longer test-retest intervals that correspond to the academic school year.
Published: 2021
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38. Developing and testing Crisis Line Facilitation (CLF) to encourage help-seeking in adults receiving inpatient treatment for a suicidal crisis.

Author: Ilgen MA, Stewart HJ, Lhermitte SL, Pfeiffer PN, Britton PC, and Pope EB
Abstract: Military Veterans are at overall greater risk of suicide than non-Veterans and have experienced increases in rates of suicide that are on par with or exceed those of the general population. The Department of Veterans Affairs has undertaken several initiatives to reduce suicide among Veterans, including the development and expansion of the Veterans Crisis Line (VCL). The VCL has the potential to reduce suicidal behaviors, but it is likely underutilized by high-risk Veterans. This paper describes the development of Crisis Line Facilitation (CLF) a brief intervention, designed to increase use of the VCL in this high-risk population. In a single session, CLF presents psychoeducational information about the VCL, discusses the participant's perceived barriers and facilitators to future use of the VCL, and culminates in the Veteran calling the VCL with the therapist to provide firsthand experiences that may counter negative impressions of the line. The intervention development process, intervention and control condition, and self-reported change indices are presented. Preliminary results (N = 301) suggest Veterans receiving CLF may experience a significant increase in comfort with, and confidence in, using the VCL during future crises compared to those in the control condition.
Published: 2021
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39. Involuntary Orienting and Conflict Resolution during Auditory Attention: The Role of Ventral and Dorsal Streams.

Author: Stewart HJ, Shen D, Sham N, and Alain C
Subjects: Auditory Perception, Humans, Magnetic Resonance Imaging, Reaction Time, Brain Mapping, Negotiating
Abstract: Selective attention to sound object features such as pitch and location is associated with enhanced brain activity in ventral and dorsal streams, respectively. We examined the role of these pathways in involuntary orienting and conflict resolution using fMRI. Participants were presented with two tones that may, or may not, share the same nonspatial (frequency) or spatial (location) auditory features. In separate blocks of trials, participants were asked to attend to sound frequency or sound location and ignore the change in the task-irrelevant feature. In both attend-frequency and attend-location tasks, RTs were slower when the task-irrelevant feature changed than when it stayed the same (involuntary orienting). This behavioral cost coincided with enhanced activity in the pFC and superior temporal gyrus. Conflict resolution was examined by comparing situations where the change in stimulus features was congruent (both features changed) and incongruent (only one feature changed). Participants were slower and less accurate for incongruent than congruent sound features. This congruency effect was associated with enhanced activity in the pFC and was greater in the right superior temporal gyrus and medial frontal cortex during the attend-location task than during the attend-frequency task. Together, these findings do not support a strict division of "labor" into ventral and dorsal streams but rather suggest interactions between these pathways in situations involving changes in task-irrelevant sound feature and conflict resolution. These findings also validate the Test of Attention in Listening task by revealing distinct neural correlates for involuntary orienting and conflict resolution.
Published: 2020
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40. Auditory cognition and perception of action video game players.

Author: Stewart HJ, Martinez JL, Perdew A, Green CS, and Moore DR
Subjects: Adolescent, Adult, Attention, Case-Control Studies, Cross-Sectional Studies, Female, Hearing, Humans, Male, Reaction Time, Retrospective Studies, Speech Acoustics, Young Adult, Auditory Perception, Cognition, Learning, Video Games psychology
Abstract: A training method to improve speech hearing in noise has proven elusive, with most methods failing to transfer to untrained tasks. One common approach to identify potentially viable training paradigms is to make use of cross-sectional designs. For instance, the consistent finding that people who chose to avidly engage with action video games as part of their normal life also show enhanced performance on non-game visual tasks has been used as a foundation to test the causal impact of such game play via true experiments (e.g., in more translational designs). However, little work has examined the association between action video game play and untrained auditory tasks, which would speak to the possible utility of using such games to improve speech hearing in noise. To examine this possibility, 80 participants with mixed action video game experience were tested on a visual reaction time task that has reliably shown superior performance in action video game players (AVGPs) compared to non-players (≤ 5 h/week across game categories) and multi-genre video game players (> 5 h/week across game categories). Auditory cognition and perception were tested using auditory reaction time and two speech-in-noise tasks. Performance of AVGPs on the visual task replicated previous positive findings. However, no significant benefit of action video game play was found on the auditory tasks. We suggest that, while AVGPs interact meaningfully with a rich visual environment during play, they may not interact with the games' auditory environment. These results suggest that far transfer learning during action video game play is modality-specific and that an acoustically relevant auditory environment may be needed to improve auditory probabilistic thinking.
Published: 2020
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41. Listening Difficulties in Children: Behavior and Brain Activation Produced by Dichotic Listening of CV Syllables.

Author: Moore DR, Hugdahl K, Stewart HJ, Vannest J, Perdew AJ, Sloat NT, Cash EK, and Hunter LL
Abstract: Listening difficulties (LiD) are common in children with and without hearing loss. Impaired interactions between the two ears have been proposed as an important component of LiD when there is no hearing loss, also known as auditory processing disorder (APD). We examined the ability of 6-13 year old (y.o.) children with normal audiometric thresholds to identify and selectively attend to dichotically presented CV syllables using the Bergen Dichotic Listening Test (BDLT; www.dichoticlistening.com). Children were recruited as typically developing (TD; n = 39) or having LiD ( n = 35) based primarily on composite score of the ECLiPS caregiver report. Different single syllables (ba, da, ga, pa, ta, ka) were presented simultaneously to each ear (6 × 36 trials). Children reported the syllable heard most clearly (non-forced, NF) or the syllable presented to the right [forced right (FR)] or left [forced left (FL)] ear. Interaural level differences (ILDs) manipulated bottom-up perceptual salience. Dichotic listening (DL) data [correct responses, laterality index (LI)] were analyzed initially by group (LiD, TD), age, report method (NF, FR, FL), and ILD (0, ± 15 dB) and compared with speech-in-noise thresholds (LiSN-S) and cognitive performance (NIH Toolbox). fMRI measured brain activation produced by a receptive speech task that segregated speech, phonetic, and intelligibility components. Some activated areas [planum temporale (PT), inferior frontal gyrus (IFG), and orbitofrontal cortex (OFC)] were correlated with dichotic results in TD children only. Neither group, age, nor report method affected the LI of right/left recall. However, a significant interaction was found between ear, group, and ILD. Laterality indices were small and tended to increase with age, as previously reported. Children with LiD had significantly larger mean LIs than TD children for stimuli with ILDs, especially those favoring the left ear. Neural activity associated with Speech, Phonetic, and Intelligibility sentence cues did not differ significantly between groups. Significant correlations between brain activity level and BDLT were found in several frontal and temporal locations for the TD but not for the LiD group. Overall, the children with LiD had only subtle differences from TD children in the BDLT, and correspondingly minor changes in brain activation., (Copyright © 2020 Moore, Hugdahl, Stewart, Vannest, Perdew, Sloat, Cash and Hunter.)
Published: 2020
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42. The Relationship Between Hearing Loss and Substance Use Disorders Among Adults in the U.S.

Author: McKee MM, Meade MA, Zazove P, Stewart HJ, Jannausch ML, and Ilgen MA
Subjects: Adolescent, Adult, Age Factors, Alcoholism psychology, Cross-Sectional Studies, Female, Health Surveys statistics & numerical data, Hearing Loss psychology, Humans, Male, Middle Aged, Opioid-Related Disorders prevention & control, Opioid-Related Disorders psychology, Pain Management methods, Prescription Drug Misuse prevention & control, Prescription Drug Misuse psychology, Prevalence, Self Report statistics & numerical data, United States epidemiology, Young Adult, Alcoholism epidemiology, Hearing Loss epidemiology, Opioid-Related Disorders epidemiology, Prescription Drug Misuse statistics & numerical data
Abstract: Introduction: Hearing loss is common and associated with poorer health and impeded communication. Little is known about the association between hearing loss and substance use disorders in the general population. The objective of this study was to assess substance use disorder prevalence among individuals with hearing loss, versus those without hearing loss, in a nationally representative sample of adults., Methods: Two years (2015 and 2016) of National Survey on Drug Use and Health (unweighted N=86,186) were combined to compare substance use disorders among adults with and without self-reported hearing loss. Statistical analysis included descriptive frequencies, chi-square tests, and multiple logistic regressions. Analyses were performed in 2018., Results: Hearing loss prevalence across all age groups was 5.2%. Among younger age groups, after adjusting for sociodemographics, hearing loss was independently associated with an increased likelihood of experiencing a substance use disorder (ages 18-34 years, AOR=1.34, 95% CI=1.10, 1.64 vs 35-49 years, AOR=1.87, 95% CI=1.39, 2.53). Hearing loss was also associated with a greater likelihood of a prescription opioid use disorder (AOR=2.85, 95% CI=1.86, 4.39) in the group aged 18-34 years and, for the group aged 35-49 years, hearing loss increased the likelihood of both an alcohol use disorder (AOR=1.87, 95% CI=1.39, 2.53) and a prescription opioid use disorder (AOR=1.99, 95% CI=1.01, 3.91)., Conclusions: Hearing loss is independently associated with substance use disorders among those aged 49 years and younger; these associations are particularly pronounced for prescription opioid use disorders in the group aged 18-34 years. Given the concern of inappropriate use of prescription opioids, this information may have implications for healthcare providers' pain management for patients with hearing loss., (Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)
Published: 2019
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43. Optogenetic Tractography for anatomo-functional characterization of cortico-subcortical neural circuits in non-human primates.

Author: Senova S, Poupon C, Dauguet J, Stewart HJ, Dugué GP, Jan C, Hosomi K, Ralph GS, Barnes L, Drouot X, Pouzat C, Mangin JF, Pain F, Doignon I, Aron-Badin R, Brouillet E, Boyden ES, Mitrophanous KA, Hantraye P, and Palfi S
Subjects: Action Potentials, Animals, Genes, Reporter, Genetic Vectors, Lentivirus genetics, Macaca mulatta, Magnetic Resonance Imaging, Male, Motor Cortex anatomy & histology, Motor Cortex physiology, Opsins analysis, Opsins genetics, Subthalamic Nucleus anatomy & histology, Subthalamic Nucleus physiology, Transduction, Genetic, Connectome, Nerve Net anatomy & histology, Nerve Net physiology, Optogenetics methods
Abstract: Dissecting neural circuitry in non-human primates (NHP) is crucial to identify potential neuromodulation anatomical targets for the treatment of pharmacoresistant neuropsychiatric diseases by electrical neuromodulation. How targets of deep brain stimulation (DBS) and cortical targets of transcranial magnetic stimulation (TMS) compare and might complement one another is an important question. Combining optogenetics and tractography may enable anatomo-functional characterization of large brain cortico-subcortical neural pathways. For the proof-of-concept this approach was used in the NHP brain to characterize the motor cortico-subthalamic pathway (m_CSP) which might be involved in DBS action mechanism in Parkinson's disease (PD). Rabies-G-pseudotyped and Rabies-G-VSVg-pseudotyped EIAV lentiviral vectors encoding the opsin ChR2 gene were stereotaxically injected into the subthalamic nucleus (STN) and were retrogradely transported to the layer of the motor cortex projecting to STN. A precise anatomical mapping of this pathway was then performed using histology-guided high angular resolution MRI tractography guiding accurately cortical photostimulation of m_CSP origins. Photoexcitation of m_CSP axon terminals or m_CSP cortical origins modified the spikes distribution for photosensitive STN neurons firing rate in non-equivalent ways. Optogenetic tractography might help design preclinical neuromodulation studies in NHP models of neuropsychiatric disease choosing the most appropriate target for the tested hypothesis.
Published: 2018
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44. Neural correlates of distraction and conflict resolution for nonverbal auditory events.

Author: Stewart HJ, Amitay S, and Alain C
Subjects: Adolescent, Adult, Behavior, Electrophysiological Phenomena, Female, Humans, Male, Reaction Time, Task Performance and Analysis, Young Adult, Acoustic Stimulation, Attention physiology, Brain physiology, Conflict, Psychological, Negotiating
Abstract: In everyday situations auditory selective attention requires listeners to suppress task-irrelevant stimuli and to resolve conflicting information in order to make appropriate goal-directed decisions. Traditionally, these two processes (i.e. distractor suppression and conflict resolution) have been studied separately. In the present study we measured neuroelectric activity while participants performed a new paradigm in which both processes are quantified. In separate block of trials, participants indicate whether two sequential tones share the same pitch or location depending on the block's instruction. For the distraction measure, a positive component peaking at ~250 ms was found - a distraction positivity. Brain electrical source analysis of this component suggests different generators when listeners attended to frequency and location, with the distraction by location more posterior than the distraction by frequency, providing support for the dual-pathway theory. For the conflict resolution measure, a negative frontocentral component (270-450 ms) was found, which showed similarities with that of prior studies on auditory and visual conflict resolution tasks. The timing and distribution are consistent with two distinct neural processes with suppression of task-irrelevant information occurring before conflict resolution. This new paradigm may prove useful in clinical populations to assess impairments in filtering out task-irrelevant information and/or resolving conflicting information.
Published: 2017
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45. Optimizing Transgene Configuration and Protein Fusions to Maximize Dopamine Production for the Gene Therapy of Parkinson's Disease.

Author: Stewart HJ, Ralph GS, Fong-Wong L, Strickland I, McCloskey L, Barnes L, Blount I, Wells O, Truran CJ, Kingsman AJ, Palfi S, and Mitrophanous KA
Subjects: Animals, Cells, Cultured, Gene Transfer Techniques, Genetic Vectors, Humans, Male, Neurons cytology, Neurons metabolism, Parkinson Disease genetics, Rats, Rats, Wistar, Recombinant Fusion Proteins metabolism, Dopamine biosynthesis, Genetic Therapy, Parkinson Disease therapy, Recombinant Fusion Proteins genetics, Transgenes genetics
Abstract: Pharmacological dopamine replacement therapies provide the most well-established treatments for Parkinson's disease (PD). However, these long-term treatments can lead to motor complications and off-target effects. ProSavin(®), a lentiviral vector (LV)-based gene therapy approach aimed at restoring local and continuous dopamine production, through delivery of three enzymes in the dopamine biosynthesis pathway, was demonstrated to be safe and well-tolerated in a phase I/II clinical study of patients with advanced PD. Although improvements in motor behaviour were observed, the data indicated that higher levels of dopamine replacement might be required to maximize benefit. We attempted to increase production of dopamine, and its precursor L-Dopa in LV-transduced cells, by optimizing the gene order in the ProSavin expression cassette, and by creating fusions of two or three of the transgenes, using linker sequences. In vitro analysis showed that several gene arrangements provided significantly increased dopamine and/or L-Dopa production compared with ProSavin, and that LV titers and transgene expression were not affected by introducing gene fusions. One vector, equine infectious anemia virus (EIAV)-TCiA, was selected for further characterization and showed significant improvements in dopamine and L-Dopa production compared with ProSavin, in human neuronal cells. Further characterization of EIAV-TCiA demonstrated expression of all three dopamine enzymes in vivo and faithful delivery and integration of the expected gene expression cassette within the genome of target cells, as assessed by Northern and Southern blotting. In conclusion, we have developed a novel LV vector with an increased capacity for L-Dopa and dopamine production compared with the current ProSavin vector. Clinical evaluation of this vector will be performed to assess the benefits in patients with PD.
Published: 2016
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46. Modality-specificity of Selective Attention Networks.

Author: Stewart HJ and Amitay S
Abstract: Objective: To establish the modality specificity and generality of selective attention networks., Method: Forty-eight young adults completed a battery of four auditory and visual selective attention tests based upon the Attention Network framework: the visual and auditory Attention Network Tests (vANT, aANT), the Test of Everyday Attention (TEA), and the Test of Attention in Listening (TAiL). These provided independent measures for auditory and visual alerting, orienting, and conflict resolution networks. The measures were subjected to an exploratory factor analysis to assess underlying attention constructs., Results: The analysis yielded a four-component solution. The first component comprised of a range of measures from the TEA and was labeled "general attention." The third component was labeled "auditory attention," as it only contained measures from the TAiL using pitch as the attended stimulus feature. The second and fourth components were labeled as "spatial orienting" and "spatial conflict," respectively-they were comprised of orienting and conflict resolution measures from the vANT, aANT, and TAiL attend-location task-all tasks based upon spatial judgments (e.g., the direction of a target arrow or sound location)., Conclusions: These results do not support our a-priori hypothesis that attention networks are either modality specific or supramodal. Auditory attention separated into selectively attending to spatial and non-spatial features, with the auditory spatial attention loading onto the same factor as visual spatial attention, suggesting spatial attention is supramodal. However, since our study did not include a non-spatial measure of visual attention, further research will be required to ascertain whether non-spatial attention is modality-specific.
Published: 2015
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47. Development of a replication-competent lentivirus assay for dendritic cell-targeting lentiviral vectors.

Author: Farley DC, McCloskey L, Thorne BA, Tareen SU, Nicolai CJ, Campbell DJ, Bannister R, Stewart HJ, Pearson LJ, Moyer BJ, Robbins SH, Zielinski L, Kim T, Radcliffe PA, Mitrophanous KA, Gombotz WR, Miskin JE, and Kelley-Clarke B
Abstract: It is a current regulatory requirement to demonstrate absence of detectable replication-competent lentivirus (RCL) in lentiviral vector products prior to use in clinical trials. Immune Design previously described an HIV-1-based integration-deficient lentiviral vector for use in cancer immunotherapy (VP02). VP02 is enveloped with E1001, a modified Sindbis virus glycoprotein which targets dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) expressed on dendritic cells in vivo. Vector enveloped with E1001 does not transduce T-cell lines used in standard HIV-1-based RCL assays, making current RCL testing formats unsuitable for testing VP02. We therefore developed a novel assay to test for RCL in clinical lots of VP02. This assay, which utilizes a murine leukemia positive control virus and a 293F cell line expressing the E1001 receptor DC-SIGN, meets a series of evaluation criteria defined in collaboration with US regulatory authorities and demonstrates the ability of the assay format to amplify and detect a hypothetical RCL derived from VP02 vector components. This assay was qualified and used to test six independent GMP production lots of VP02, in which no RCL was detected. We propose that the evaluation criteria used to rationally design this novel method should be considered when developing an RCL assay for any lentiviral vector.
Published: 2015
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48. Nanog requires BRD4 to maintain murine embryonic stem cell pluripotency and is suppressed by bromodomain inhibitor JQ1 together with Lefty1.

Author: Horne GA, Stewart HJ, Dickson J, Knapp S, Ramsahoye B, and Chevassut T
Subjects: Animals, Cells, Cultured, Embryonic Stem Cells drug effects, Embryonic Stem Cells metabolism, Homeodomain Proteins genetics, Left-Right Determination Factors genetics, Mice, Nanog Homeobox Protein, Nuclear Proteins antagonists & inhibitors, Nuclear Proteins genetics, Pluripotent Stem Cells drug effects, Pluripotent Stem Cells metabolism, Transcription Factors antagonists & inhibitors, Transcription Factors genetics, Azepines pharmacology, Embryonic Stem Cells cytology, Homeodomain Proteins metabolism, Left-Right Determination Factors metabolism, Nuclear Proteins metabolism, Pluripotent Stem Cells cytology, Transcription Factors metabolism, Triazoles pharmacology
Abstract: Embryonic stem cells (ESCs) are maintained in an undifferentiated state through expression of the core transcriptional factors Nanog, Oct4, and Sox2. However, the epigenetic regulation of pluripotency is poorly understood. Differentiation of ESCs is accompanied by a global reduction of panacetylation of histones H3 and H4 suggesting that histone acetylation plays an important role in maintenance of ESC pluripotency. Acetylated lysine residues on histones are read by members of the bromodomain family that includes BET (bromodomain and extraterminal domain) proteins for which highly potent and selective inhibitors have been developed. In this study we demonstrate that the pan-BET bromodomain inhibitor JQ1 induces rapid spontaneous differentiation of murine ESCs by inducing marked transcriptional downregulation of Nanog as well as the stemness markers Lefty1 and Lefty2, but not Myc, often used as a marker of BET inhibitor activity in cancer. We show that the effects of JQ1 are recapitulated by knockdown of the BET family member BRD4 implicating this protein in Nanog regulation. These data are also supported by chromatin immunoprecipitation experiments which confirm BRD4 binding at the Nanog promoter that is known to require acetylation by the histone acetyltransferase MOF for transcriptional activity. In further support of our findings, we show that JQ1 antagonizes the stem cell-promoting effects of the histone deacetylase inhibitors sodium butyrate and valproic acid. Our data suggest that BRD4 is critical for the maintenance of ESC pluripotency and that this occurs primarily through the maintenance of Nanog expression.
Published: 2015
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49. Audiovisual integration in children listening to spectrally degraded speech.

Author: Maidment DW, Kang HJ, Stewart HJ, and Amitay S
Subjects: Adult, Age Factors, Child, Child, Preschool, Cues, Female, Humans, Male, Speech, Speech Acoustics, Acoustic Stimulation methods, Perceptual Masking, Photic Stimulation methods, Speech Perception
Abstract: Purpose: The study explored whether visual information improves speech identification in typically developing children with normal hearing when the auditory signal is spectrally degraded., Method: Children (n=69) and adults (n=15) were presented with noise-vocoded sentences from the Children's Co-ordinate Response Measure (Rosen, 2011) in auditory-only or audiovisual conditions. The number of bands was adaptively varied to modulate the degradation of the auditory signal, with the number of bands required for approximately 79% correct identification calculated as the threshold., Results: The youngest children (4- to 5-year-olds) did not benefit from accompanying visual information, in comparison to 6- to 11-year-old children and adults. Audiovisual gain also increased with age in the child sample., Conclusions: The current data suggest that children younger than 6 years of age do not fully utilize visual speech cues to enhance speech perception when the auditory signal is degraded. This evidence not only has implications for understanding the development of speech perception skills in children with normal hearing but may also inform the development of new treatment and intervention strategies that aim to remediate speech perception difficulties in pediatric cochlear implant users.
Published: 2015
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50. Bromodomain inhibition by JQ1 suppresses lipopolysaccharide-stimulated interleukin-6 secretion in multiple myeloma cells.

Author: Ghurye RR, Stewart HJ, and Chevassut TJ
Subjects: Aged, Aged, 80 and over, Antibodies, Monoclonal chemistry, Cell Survival, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Protein Structure, Tertiary, Real-Time Polymerase Chain Reaction, Azepines chemistry, Gene Expression Regulation, Neoplastic, Interleukin-6 metabolism, Lipopolysaccharides chemistry, Multiple Myeloma metabolism, Triazoles chemistry
Published: 2015
Full Text: View/download PDF

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