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1. The Gnas imprinting cluster : identification and analysis of candidate regulatory elements

Author

Coombes, C.

Subjects
572.8
Abstract

Genomic imprinting is a mechanism that results in the preferential silencing of one copy of a gene according to its parental origin. The distal region of mouse chromosome 2 is subject to genomic imprinting, and contains a complex cluster of imprinted transcripts. These comprise maternally expressed Nesp, paternally expressed Gnasxl, and the predominantly biallelically expressed transcript Gnas (encoding Gas). Uniquely, transcripts originating from oppositely imprinted promoters Nesp and Gnasxl splice onto, and share common downstream exons with Gnas. The cluster additionally contains two paternally expressed non-coding transcripts, Nespas, which runs antisense to Nesp, and Gnas 1A, which also shares exons with Gnas. The identification of regulatory elements at this locus is essential in order to determine the mechanism by which the cluster is imprinted. Physical characterisation of the Nesp-Gnasxl domain demonstrated that the Nesp and Gnasxl exons were situated 15kb apart, and 30kb upstream of Gnas promoter. Both were found to reside within differentially methylated CpG-rich regions, and were associated with direct repeat features. Allele-specific DNaseI hypersensitive sites (HS), mapping within or directly adjacent to these differentially methylated regions (DMRs) were found to associate with the unmethylated active allele in adult mice. In embryonic stem (ES) cells, two clusters of strong paternal-allele specific DNaseI HS were identified at the 5' end of the Gnasxl DMR. One of these clusters coincided with a region of high sequence conservation between mouse and human, and the first exon of antisense transcript Nespas. This region was denoted candidate regulatory region 1 (CRR1). This study additionally attempted to recapitulate imprinting of the human GNAS1 locus using PAC clone RP1-309F20 (156kb insert containing the GNAS1 locus) in a mouse transgenic system. A consistent DNA methylation profile was established across the transgene in the four transgenic lines analysed.

Published
2003

3. Real-World Outcomes of Patients with Primary CNS Lymphoma (PCNSL): A Report from the Australasian Lymphoma Alliance (ALA).

Author

Tatarczuch M., Lewis K.L., Gunjur A., Shaw B., Poon M., Paul E., Ku M., Wong M., Beekman A., Krigstein M., Di Ciaccio P.R., Wight J., Coombes C., Gilbertson M., Tey A., Shortt J., Nagarajan C., Latimer M., Talaulikar D., Hamad N., Ratnasingam S., Cochrane T., Hawkes E., Cheah C.Y., Opat S., Gregory G.P., Tatarczuch M., Lewis K.L., Gunjur A., Shaw B., Poon M., Paul E., Ku M., Wong M., Beekman A., Krigstein M., Di Ciaccio P.R., Wight J., Coombes C., Gilbertson M., Tey A., Shortt J., Nagarajan C., Latimer M., Talaulikar D., Hamad N., Ratnasingam S., Cochrane T., Hawkes E., Cheah C.Y., Opat S., and Gregory G.P.

Abstract

Aim: Primary Central Nervous System Lymphoma (PCNSL) [i.e. diffuse large B-cell lymphoma of the CNS] is a rare and poor-prognosis disease occurring predominantly in older patients (median age >60 years old). Prospective studies of two commonly used chemoimmunotherapy (CIT) protocols, MATRix and MPV/Ara-C (+/- rituximab), have reported 2-year PFS and OS of 57-61% and 69-81% respectively. Our aim was to evaluate registry-reported outcomes of frontline CIT strategies employed at Australasian sites. Method(s): A retrospective study of consecutive, immunocompetent, adult PCNSL patients (WHO criteria: 2017) treated with curative-intent CIT, from 10 sites (9 Australian, 1 Singaporean) between 1 st January 2009 and 31 st December 2018 (i.e. ten-year period). Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier (log-rank) method. Univariate associations were derived using a Cox model with variables p<0.10 entered stepwise into a multivariate model. Result(s): Data was collected on 207 patients, 189 of whom met WHO diagnostic criteria for PCNSL (i.e. diffuse large B-cell lymphoma of the CNS). We excluded patients with insufficient data (6), non-DLBCL histology (6), secondary PCNSL (3) and post-transplant lymphoproliferative disorder (3). Of these, 176 (93%) received curative-intent CIT. The majority (66%) were over 65 years of age (median: 65, range: 25-87); ECOG performance status was >= 2 in 31% (data not available for 14% of patients). The majority were male (55%) and had deep structure involvement (64%). International Extranodal Lymphoma Study Group (IELSG) risk criteria could not be calculated in many patients due to missing data (predominantly LDH and CSF protein). CSF involvement was rare (n=23, 13%) but data was only available for 60% of patients. Of the 159 with documented renal function, 26% had renal impairment (defined as Cockroft-Gault creatinine clearance <60ml/min or eGFR <90ml/min). Five CIT regimens were used: MATRi

Published
2021

5. Marine anthropogenic litter on British beaches: A 10-year nationwide assessment using citizen science data

Author

Nelms, SE, Coombes, C, Foster, LC, Galloway, TS, Godley, BJ, Lindeque, PK, and Witt, MJ

Subjects
Marine anthropogenic litter, Beach clean, Environmental Engineering, Plastic pollution, Spatial pattern, Environmental Chemistry, Temporal trend, Citizen science, Waste Management and Disposal, Pollution
Abstract

Growing evidence suggests that anthropogenic litter, particularly plastic, represents a highly pervasive and persistent threat to global marine ecosystems. Multinational research is progressing to characterise its sources, distribution and abundance so that interventions aimed at reducing future inputs and clearing extant litter can be developed. Citizen science projects, whereby members of the public gather information, offer a low-cost method of collecting large volumes of data with considerable temporal and spatial coverage. Furthermore, such projects raise awareness of environmental issues and can lead to positive changes in behaviours and attitudes. We present data collected over a decade (2005–2014 inclusive) by Marine Conservation Society (MCS) volunteers during beach litter surveys carried along the British coastline, with the aim of increasing knowledge on the composition, spatial distribution and temporal trends of coastal debris. Unlike many citizen science projects, the MCS beach litter survey programme gathers information on the number of volunteers, duration of surveys and distances covered. This comprehensive information provides an opportunity to standardise data for variation in sampling effort among surveys, enhancing the value of outputs and robustness of findings. We found that plastic is the main constituent of anthropogenic litter on British beaches and the majority of traceable items originate from land-based sources, such as public littering. We identify the coast of the Western English Channel and Celtic Sea as experiencing the highest relative litter levels. Increasing trends over the 10-year time period were detected for a number of individual item categories, yet no statistically significant change in total (effort-corrected) litter was detected. We discuss the limitations of the dataset and make recommendations for future work. The study demonstrates the value of citizen science data in providing insights that would otherwise not be possible due to logistical and financial constraints of running government-funded sampling programmes on such large scales.

Published
2017
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6. Morphological identification of fungi associated with Eichhornia crassipes (Mart.-Solms) Laubach in the Wouri River Basin, Douala, Cameroon

Author

Voukeng, S.N. Kenfack, Coombes, C., Weyl, P., Djeugoue, F., and Hill, M.P.

Subjects
biological control, fungal diversity, mycoherbicides, water hyacinth
Abstract

In many parts of the world, excess growth of Eichhornia crassipes (Pontederiaceae) poses a serious threat to aquatic environments. In Cameroon, where manual clearing is still undertaken, little is known about fungal diversity associated with the plant, or its potential for biological control. Surveys of the Wouri River Basin in the Littoral Region of Cameroon were conducted during a rainy season (May–October 2014) and a dry season (November 2015–April 2016) at various sites, to identify fungi associated with water hyacinth. Fungi were isolated and identified from symptomatic plant parts collected. In the rainy season, 130 fungal isolates belonging to 12 genera were identified morphologically, whereas 299 isolates belonging to 23 genera were identified during the dry season. With the exception of Fusarium oxysporum and Phytophthora sp., the genera represented new records for Cameroon, and Chaetomium strumarium, Colletotrichum gloesporioides, C. acutatum, C. dematium, Curvularia pallescens and Pytomyces chartarum were considered new host records for E. crassipes in Africa. Isolates of Acremonium zonatum, Chaetomium strumarium, Alternaria eichhorniae, Phytophthora sp. and Rhizoctonia sp. showed the highest frequency of occurrence on E. crassipes in the Wouri River Basin and, given their record as plant pathogens, could be potentially useful in the development of mycoherbicides for this weed in Cameroon.Keywords: biological control, fungal diversity, mycoherbicides, water hyacinth

Published
2019

7. Outcomes of synchronous systemic and central nervous system (CNS) involvement of diffuse large B-cell lymphoma are dictated by the CNS disease: a collaborative study of the Australasian Lymphoma Alliance.

Author

Talaulikar D., Wight J.C., Yue M., Keane C., Johnston A., Linton K., Chin C., Wai S.H., Gasiorowski R., Hawkes E.A., Lam S., Ku M., Coombes C., Minson A., Dickinson M., Gregory G.P., Cheah C.Y., Talaulikar D., Wight J.C., Yue M., Keane C., Johnston A., Linton K., Chin C., Wai S.H., Gasiorowski R., Hawkes E.A., Lam S., Ku M., Coombes C., Minson A., Dickinson M., Gregory G.P., and Cheah C.Y.

Abstract

De novo diffuse large B-cell lymphoma (DLBCL) presenting with synchronous central nervous system (CNS) and systemic disease (synDLBCL) is not well described and is excluded from clinical trials. We performed a retrospective analysis of 80 synDLBCL patients treated across 10 Australian and UK centres. Of these patients, 96% had extranodal systemic disease. CNS-directed treatment with combination intravenous cytarabine and high-dose methotrexate ("CNS-intensive") (n = 38) was associated with favourable survival outcomes compared with "CNS-conservative" strategies such as intravenous high-dose methotrexate monotherapy, intrathecal therapy and/or radiotherapy (2-year progression-free survival [PFS] 50% vs. 31%, P = 0.006; 2-year overall survival [OS] 54% vs. 44%, P = 0.037). Outcomes were primarily dictated by the ability to control the CNS disease, with 2-year cumulative CNS relapse incidence of 42% and non-CNS relapse 21%. Two-year OS for CNS-relapse patients was 13% vs. 36% for non-CNS relapses (P = 0.02). Autologous stem cell transplantation as consolidation (n = 14) was not observed to improve survival in those patients who received CNS-intensive induction when matched for induction outcomes (2-year PFS 69% vs. 56%, P = 0.99; 2-year OS 66% vs. 56%, P = 0.98). Hyperfractionated or infusional systemic treatment did not improve survival compared to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) (2-year OS 49% for both groups). Our study suggests that adequate control of the CNS disease is paramount and is best achieved by intensive CNS-directed induction.Copyright © 2019 British Society for Haematology and John Wiley & Sons Ltd

Published
2019

8. Diffuse large b cell lymphoma (DLBCL) presenting with syncrhonous cns and systemic disease at diagnosis: Results from an international collaborative study.

Author

Wai S.H., Coombes C., Cheah C., Talaulikar D., Hawkes E., Gregory G., Wight J., Churilov L., Yue M., Keane C., Johnston A., Linton K., Chin C., Wai S.H., Coombes C., Cheah C., Talaulikar D., Hawkes E., Gregory G., Wight J., Churilov L., Yue M., Keane C., Johnston A., Linton K., and Chin C.

Abstract

Background: DLBCL presenting with both CNS and systemic disease at first diagnosis is rare. Such patients are excluded from clinical trials; thus, the optimal treatment is unknown and outcomes are poorly described. Aim(s): To describe treatment outcomes of patients with synchronous CNS and systemic DLBCL at first diagnosis. Method(s):Multicentre retrospective international study (6 Australian & UK sites). Cases were identified from clinical and pharmacy records. Eligible patients had histologically proven DLBCL, with radiological, histological, or CSF evidence of synchronous systemic & CNS disease, treated with combination chemotherapy and rituximab. Patients with relapsed disease were excluded. Primary Endpoint: OS. Secondary endpoints: CR rate, PFS, toxicity. P values of <0.05 were considered significant. Result(s): Of 59 patients, 71% were male and the median age was 66yrs (range 17-86). 45 (76%) had NCCN-IPI >=4. Median number of extranodal sites outside the CNS was 2 (range 0-8). 10% were double-hit by FISH, and 35% of those with data available were double-expressors of MYC and BCL2 protein. CNS disease was leptomeningeal only in 24 (41%); 35 (59%) had parenchymal disease, 8 (14%) had both. 34 (58%) received systemic therapy (predominantly R-CHOP, n=31) plus a CNS-directed treatment (group A). 25 (42%) underwent intensified MTX and/or Ara-C containing therapy: hyper-CVAD n=14, CODOX-M/IVAC n=10, DHAC=1 (group B). CNS-directed therapy in group A included: IV HD-MTX in 19 (56%), HDMTX+ Ara-C in 2 (6%), intrathecal therapy (IT) only in 10 (29%), radiotherapy (RT) only in 2 (6%). Specific CNS therapy was omitted in one patient due to early PD. Additional consolidative therapy included CNS RT in 18 (31%) (whole brain in 8, site-specific in 10), and autologous SCT in CR1 in 8 (13%) using BEAM (n=4) or BCNU+thiotepa (n=4) conditioning. All SCT patients were from group B. 23 (39%) required dose reductions and 23 (39%) required early cessation of therapy. Treatment-rela

Published
2019

9. Outcomes of synchronous systemic and central nervous system (CNS) involvement of diffuse large B-cell lymphoma are dictated by the CNS disease: a collaborative study of the Australasian Lymphoma Alliance

Author

Wight, JC, Yue, M, Keane, C, Johnston, A, Linton, K, Chin, C, Wai, SH, Talaulikar, D, Gasiorowski, R, Cheah, CY, Gregory, GP, Dickinson, M, Minson, A, Coombes, C, Ku, M, Lam, S, Hawkes, EA, Wight, JC, Yue, M, Keane, C, Johnston, A, Linton, K, Chin, C, Wai, SH, Talaulikar, D, Gasiorowski, R, Cheah, CY, Gregory, GP, Dickinson, M, Minson, A, Coombes, C, Ku, M, Lam, S, and Hawkes, EA

Abstract

De novo diffuse large B-cell lymphoma (DLBCL) presenting with synchronous central nervous system (CNS) and systemic disease (synDLBCL) is not well described and is excluded from clinical trials. We performed a retrospective analysis of 80 synDLBCL patients treated across 10 Australian and UK centres. Of these patients, 96% had extranodal systemic disease. CNS-directed treatment with combination intravenous cytarabine and high-dose methotrexate ("CNS-intensive") (n = 38) was associated with favourable survival outcomes compared with "CNS-conservative" strategies such as intravenous high-dose methotrexate monotherapy, intrathecal therapy and/or radiotherapy (2-year progression-free survival [PFS] 50% vs. 31%, P = 0·006; 2-year overall survival [OS] 54% vs. 44%, P = 0·037). Outcomes were primarily dictated by the ability to control the CNS disease, with 2-year cumulative CNS relapse incidence of 42% and non-CNS relapse 21%. Two-year OS for CNS-relapse patients was 13% vs. 36% for non-CNS relapses (P = 0·02). Autologous stem cell transplantation as consolidation (n = 14) was not observed to improve survival in those patients who received CNS-intensive induction when matched for induction outcomes (2-year PFS 69% vs. 56%, P = 0·99; 2-year OS 66% vs. 56%, P = 0·98). Hyperfractionated or infusional systemic treatment did not improve survival compared to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) (2-year OS 49% for both groups). Our study suggests that adequate control of the CNS disease is paramount and is best achieved by intensive CNS-directed induction.

Published
2019

12. The influence of citrus orchard age on the ecology of entomopathogenic fungi and nematodes.

Author

Albertyn, S., Moore, S. D., Marsberg, T., Coombes, C. A., and Hill, M. P.

Subjects
INSECT nematodes, ENTOMOPATHOGENIC fungi, ORCHARDS, CITRUS, MICROIRRIGATION, ECOLOGY
Abstract

A three-year survey of the ecology of entomopathogenic nematodes (EPN) and entomopathogenic fungi (EPF) was undertaken on soils from citrus orchards of different ages to determine the influence of orchard age on the ecology of entomopathogenic fungi and nematodes. The influence of mulch and irrigation method on the occurrence of EPN and EPF was also determined. Most of the isolates recovered (n = 810) were Beauveria sp. (87.88% of all isolates), followed by Metarhizium sp. (11.87% of all isolates). Only 0.24% of soil samples collected during this study tested positive for EPN. All EPN isolates recovered were Heterorhabditis bacteriophora. No significant differences in EPF occurrence were recorded between orchards under drip and micro-sprinkler irrigation. EPF occurrence was significantly lower (P = 0.016) in orchards covered by mulch (31.85% ± 2.07% occurrence) than in orchards with no covering (38.57% ± 1.57% occurrence). EPF occurrence of 40.33 ± 2.13% was highest in non-bearing orchards, followed by mature orchards (nine years or older) (36.76 ± 2.05% of samples) with the lowest EPF occurrence of 25.30 ± 2.02% reported in juvenile orchards (four to eight years old). Juvenile orchards sustain significantly less EPF than mature and non-bearing orchards because of the combined negative impact of less favourable environmental conditions (lower shade density) and fungicide applications. [ABSTRACT FROM AUTHOR]

Published
2021
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14. Digistain: a novel biomarker imaging platform for grading breast carcinoma using routinely processed paraffin sections

Author

Amrania, H, Shousha, S, Woodley, L, Goddard, K, Phillips, C, Coombes, C, Engineering & Physical Science Research Council (EPSRC), Sharp Laboratories of Europe Ltd, Engineering & Physical Science Research Council (E, and Imperial College Healthcare NHS Trust- BRC Funding

Subjects
Science & Technology, Pathology, 1103 Clinical Sciences, Life Sciences & Biomedicine
Abstract

Objective: Digistain is a new technology platform that enables imaging and quantification of a newly conceived biomarker for grading breast carcinoma in routinely processed, unstained paraffin sections without the use of traditional stains or contrasting agents. By recording a unique optical signature to analyze the chemical make-up of a biopsy quantitatively, the technique is unaffected by the subjectivity of traditional grading. Within minutes of loading a slide it yields a highly reproducible and user independent numerical score reflecting the cellularity of the tumour and its nuclear: cytoplasmic ratio. We report here our findings using an objective technique to grade breast tumours using quantitative criteria. Method: H&E stained sections from excision biopsies of 105 cases of invasive breast carcinoma were reviewed and graded using the ElstonEllis grading system. Unstained sections from each case were loaded into the Digistain platform to yield a numerical score - the Digistain Index (DI). Results: The cases were grouped according to histological grading. Mean DIs was calculated for each grade (1,2 and 3) to be 0.56, 0.61, and 0.68 respectively with a maximum standard error of 0.02. The DI spread within each grade was less than that across the three grades, thus validating this index as a viable grading indicator within the context of this study. Conclusion: We believe the new Digistain approach provides for the first time a cost effective and quantitative measure of tumour grade. This can be developed to deliver an effective assessment of prognosis and recurrence risk beyond traditional qualitative measures based on H&E staining protocols.

Published
2015

15. Morphological identification of fungi associated with Eichhornia crassipes (Mart.-Solms) Laubach in the Wouri River Basin, Douala, Cameroon.

Author

Kenfack Voukeng, SN, Coombes, C, Weyl, P, Djeugoue, F, and Hill, MP

Subjects
*WATER hyacinth, *WATERSHEDS, *PHYTOPHTHORA, *PLANT diversity, *FUNGI, *ALTERNARIA, *PHYTOPATHOGENIC microorganisms
Abstract

In many parts of the world, excess growth of Eichhornia crassipes (Pontederiaceae) poses a serious threat to aquatic environments. In Cameroon, where manual clearing is still undertaken, little is known about fungal diversity associated with the plant, or its potential for biological control. Surveys of the Wouri River Basin in the Littoral Region of Cameroon were conducted during a rainy season (May–October 2014) and a dry season (November 2015–April 2016) at various sites, to identify fungi associated with water hyacinth. Fungi were isolated and identified from symptomatic plant parts collected. In the rainy season, 130 fungal isolates belonging to 12 genera were identified morphologically, whereas 299 isolates belonging to 23 genera were identified during the dry season. With the exception of Fusarium oxysporum and Phytophthora sp., the genera represented new records for Cameroon, and Chaetomium strumarium, Colletotrichum gloesporioides, C. acutatum, C. dematium, Curvularia pallescens and Pytomyces chartarum were considered new host records for E. crassipes in Africa. Isolates of Acremonium zonatum, Chaetomium strumarium, Alternaria eichhorniae, Phytophthora sp. and Rhizoctonia sp. showed the highest frequency of occurrence on E. crassipes in the Wouri River Basin and, given their record as plant pathogens, could be potentially useful in the development of mycoherbicides for this weed in Cameroon. [ABSTRACT FROM AUTHOR]

Published
2019
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16. Carpal tunnel syndrome and musculoskeletal symptoms in postmenopausal women with early breast cancer treated with exemestane or tamoxifen after 2-3 years of tamoxifen: a retrospective analysis of the Intergroup Exemestane Study

Author

Mieog, Js, Morden, Jp, Bliss, Jm, Coombes, Rc, van de Velde CJ, IES Steering Committee: Delozier, T, Veronesi, A, Vrdoljak, E, Monnier, A, Coombes, C, Nagykalnai, T, Roumen, Rm, Utracka Hutka, B, Pluzanska, A, Porpiglia, M, Genta, F, Benedetto, Chiara, Sozzani, P, Steiner, M, Rubinov, R, Leviov, M, Semiglazov, V, Fox, J, Mayordomo, Ji, Cervek, J, Sleeboom, Hp, Jassem, J, Hinton, Cp, Paulsen, Th, Guleng, Rj, Fein, L, Gutulescu, N, Florián, J, Rosso, R, Rutgers, Ej, Krzakowski, M, Pienkowski, T, Krajina, Z, Siffnerova, H, Pawlicki, M, Drosik, K, Wagnerowa, M, Brunt, M, Vukelja, S, Mitrowic, L, Cataliotti, L, Karnicka Mlodkowska, H, Bonnefoi, H, Tilch, G, Chollet, P, Patel, A, Kamby, C, Giustini, L, Acito, L, Mouridsen, H, Roche, H, De Lafontan, B, Tomczak, P, Petruzelka, L, Lortholary, A, Pacquola, Mg, Skene, A, Rici, S, Michelotti, A, Ghilezan, N, Stewart, A, Beauduin, M, Andersen, J, Vassilaros, S, Celio, L, Bajetta, E, Bastús, R, Marsland, T, Paridaens, R, Tzekova, V, Lichtenegger, W, Piersma, H, Jones, S, Holmberg, S, Verhoeven, D, Hill, A, Porcile, G, Bruno, Mf, Chernozemski, I, Coleman, R, Jadeja, J, Cohn, A, Merlano, M, Perroni, D, Di Costanzo, F, Van Bochove, A, Gerrits, Ma, Malec, V, Balil, A, Mendiola, C, Dodwell, D, Knox, R, Horgan, K, Joannides, T, Leonard, Rc, Cawthorn, Sj, Ghosh, C, Cantrell, J, Campos, D, Orti, R, Diedrich, K, Aas, H, Barnadas, A, Vila, Mm, Makris, A, Anderson, T, Chittor, S, Michel, J, Philip, P, Redmond, P, Mastboom, Wj, Nordenskjöld, B, Simmonds, P, Grieve, Rj, Tomova, A, Piot, G, Borea, G, Ucci, G, Einarsson, E, Nicholson, S, Gardiol, Ea, Kerger, J, Schlosser, J, Namer, M, Pinotti, G, Rutten, Ht, Iversen, T, Nejim, A, Dudov, A, Grundtvig, P, Lang, I, Massidda, B, Van De Velde CH, Gervasio, Mh, Tengrup, I, Tennvall, L, Goodman, S, Modgill, Vk, Vorobiof, Da, Mickiewicz, E, Chirgwin, J, Focan, C, Albin, N, Contu, Aa, Svensson, Jh, Borghede, G, Källström, Ac, Forbes, Jf, Hurtz, Hj, Tubiana Hulin, M, Viens, P, Scanni, A, Arnoldi, E, Nastasi, G, Bottini, A, Alquati, P, Muscat, V, Brincat, S, Holmen, K, Amaral, N, Moreno, I, Trask, C, Robinson, A, Mcintyre, K, Otsuka, A, Hohaus, B, Hoefig, G, Georgoulias, V, Salvagni, S, Bidin, L, Artioli, F, Engan, T, Benedikstsson, Kp, Campbell, I, Harvey, V, Zimbler, H, Mrsic Krmpotic, Z, Canon, Jl, Tchilingirov, Pv, Buser, K, Bolanca, A, Reztke, U, Rhein, U, Jouve, M, Mullins, G, Vesentini, L, Gallo, L, Merlini, L, Decensi, A, Carreca, I, Van Tienhoven, G, Börjesson, B, Hansen, J, Koza, I, Arcusa, A, Inoriza, A, Pelegri, A, Eremin, O, Modiano, Mr, Anthony, S, Donat, D, Richardet, E, Kochli, O, Zeißig, P, Gauch, G, Aabo, K, Fumoleau, P, Erdkamp, Fl, Lovén, L, Jönsson, Pe, Perren, T, Stuart, N, Galindo, E, Marek, Bj, Salmon, Jp, Dohollou, N, Thompson, R, Folco, U, Rosa, A, Tonato, M, Heijmans, Gj, Koralewski, P, Bång, H, Lescure, Ar, Carrato, A, Martin, M, Neave, F, Howell, T, Savin, M, Loesch, D, Hannois, A, Mohr, A, Laube, T, Omar, S, Bonneterre, J, Servent, V, Danese, S, Sertoli, Mr, Butzelaar, Rm, Steller, Ep, Gomez, H, Skoog, P, Alvarez, I, Aguilar, Ea, Giner, Jl, Yosef, Hm, Barrett Lee, P, Buzdar, Au, George, T, Olivaires, J, Vsianska, M, Köhler, U, Lindeløv, B, Toftdahl, Db, Nielsen, Eb, Veyret, C, Castera, D, Kerbrat, P, Vassilaros, P, Yeo, W, Boni, C, Aitini, E, Luporini, G, Herben, Mg, Espelid, H, Dahl, S, Ingvar, C, Meana, A, Pico, C, Garcia, Am, Agrawal, Rk, Gruenberg, D, Nunez de Pierro, A, Gill, G, Nogaret, Jm, Honhon, B, Wassenaar, H, Nielander, R, Warnier, P, Sessa, C, Padrik, P, Guastalla, Jp, Serin, D, Jaubert, D, Dank, M, Given, Fh, Mascia, V, De Fraia, E, Silingardi, V, Conte, Pf, Labianca, R, Tondini, C, Bagnulo, A, Gardani, G, Wils, J, Liem, G, Nuytinck, Jk, Formoe, E, Ambré, T, Alés, J, Aramburo, P, Mansi, J, Graham, J, Joffe, J, Sainsbury, J, Stone, J, Good, Rh, Cartwright, T, Werner, Id, Murray, E, Beith, J, Tigges, Fj, Bojko, P, Sandberg, E, Jensen, B, Lotz, Jp, Carney, D, Shapira, J, Neumann, A, Goldhirsch, A, Dicato, M, de Graaf, H, Maartense, E, Burghouts, J, Cassinello, J, Jones, A, Gaffney, C, Blum, R, Abdi, E, Becquart, D, Dirix, L, Janssens, J, Nmarschner, N, Blaska Jaulerry, B, Prevot, G, Mirah Lev, L, Shani, A, Baruch, Nb, Peretz, T, Gips, M, Cognetti, F, Carlini, P, Nortier, Jw, Huinink D, ten B., Roussel, Jg, Unneberg, K, Kylberg, F, Hovind, H, Nestvold, T, Fogelkvist, R, Due, J, Muller, S, Gilligan, D, Russel, S, Mcaleer, J, Yiangou, C, Foote, L, Schottstaedt, M, Holmes, Fa, Wainstein, R, Contreras, O, Martinez, J, Della Fiorentina, S, Beslija, S, Vermorken, Jb, Thirion, M, Fraikin, J, Castiglione, M, Jäger, W, Fasching, P, Fabriz, H, Neis, K, Kirschbaum, M, Labat, Jp, Dupuis, O, Bernard, J, Datchary, J, Provencal, J, Allain, P, Clerico, M, Lopez, M, Nalli, G, Aspevik, R, Fràguas, A, Curescu, S, Cuevas, Jm, Oltra, A, Bradley, C, Kapoor, R, Akbain, S, Croghan, Mk, Modiano, M, Taetle, R, Beale, P, Gobert, P, Bondue, H, Böhm, R, Møller, Ka, Brettes, Jp, Netter, G, Grogan, L, Klein, B, Botta, M, Barni, S, Van Meerwijk, I, Kåresen, R, Godes, J, Aramburo, A, Jara, C, Zanger, B, Fleagle, Jt, Greenspan, A, Marschke, R, Medgyesy, Dc, Garbo, L., CCA -Cancer Center Amsterdam, and Radiotherapy

Subjects
medicine.medical_specialty, Population, Breast Neoplasms, Disease-Free Survival, chemistry.chemical_compound, Breast cancer, Exemestane, Internal medicine, Surveys and Questionnaires, medicine, Clinical endpoint, Humans, Carpal tunnel syndrome, education, Aged, Retrospective Studies, Aged, 80 and over, education.field_of_study, business.industry, Aromatase Inhibitors, Hazard ratio, Middle Aged, medicine.disease, Carpal Tunnel Syndrome, Surgery, Musculoskeletal Abnormalities, Androstadienes, Postmenopause, Tamoxifen, Treatment Outcome, Oncology, chemistry, Hormonal therapy, Female, business, medicine.drug
Abstract

BACKGROUND: Aromatase inhibitors are more effective than is tamoxifen in prevention of breast-cancer recurrence, but at the expense of increased musculoskeletal side-effects, such as carpal tunnel syndrome. The aim of this study was to assess risk factors and the prognostic value of musculoskeletal symptoms during treatment with the steroidal aromatase inhibitor exemestane or with tamoxifen after 2-3 years of tamoxifen. METHODS: In the Intergroup Exemestane Study, postmenopausal women treated for early invasive breast cancer who remained disease free and on treatment after 2-3 years of tamoxifen were randomised to switch to exemestane or to continue tamoxifen for the remainder of the 5-year period of endocrine treatment. The primary endpoint for this retrospective analysis was occurrence of carpal tunnel syndrome and any musculoskeletal events, analysed in the safety population, which consisted of all patients who had received any trial treatment. As well as case-report forms, questionnaires were distributed retrospectively to gain more details of cases of carpal tunnel syndrome. The relation between musculoskeletal symptoms reported by 6 months from randomisation and survival from 9 months onwards was assessed by Cox proportional hazards models. The trial is registered, number ISRCTN11883920. It has completed accrual and follow-up is continuing for enrolled participants. FINDINGS: After a median follow-up of 91·0 months (IQR 83·0-99·2), carpal tunnel syndrome had been reported for 66 (2·8%) of 2319 patients in the exemestane group compared with 13 (0·6%) of 2338 in the tamoxifen group (odds ratio [OR] 5·23, 99% CI 2·39-11·49; p

Published
2012

17. Potential of entomopathogenic fungal isolates for control of the soil-dwelling life stages of Thaumatotibia leucotreta Meyrick (Lepidoptera: Tortricidae) in citrus.

Author

Coombes, C. A., Hill, M. P., Moore, S. D., and Dames, J. F.

Subjects
*METARHIZIUM anisopliae, *BEAUVERIA bassiana, *CITRUS diseases & pests, *METARHIZIUM, *GREEN Muscle (Trademark), *BEAUVERIA, *THERAPEUTICS
Abstract

The article presents the study which examined the effectiveness of the isolates of the entomopathogenic fungal species Metarhizium anisopliae (Metchnikoff) Sorokin (G 11 3 L6 and FCM Ar 23 B3 or Ma1 and Ma2, respectively,) and Beauveria bassiana (Balsamo-Crivelli) Vuillemin (G Ar 17 B3 or Bb1) against the soil-dwelling life stages of the citrus pest called Thaumatotibia leucotreta Meyrick (Lepodoptera: Tortricidae). The study was conducted in South Africa.

Published
2017
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18. Test-retest reproducibility of [F-18]fluciclatide PET imaging in subjects with solid tumors

Author

Sharma, R., Kallur, K. G., Ryu, J. S., Parameswaran, R. V., Lindman, Henrik, Avril, N., Gleeson, F. V., Lee, J. D., Lee, K. H., O'Doherty, M. J., Groves, A. M., Miller, M. P., Paterson, C. L., Coombes, C., Aboagye, E. O., Sharma, R., Kallur, K. G., Ryu, J. S., Parameswaran, R. V., Lindman, Henrik, Avril, N., Gleeson, F. V., Lee, J. D., Lee, K. H., O'Doherty, M. J., Groves, A. M., Miller, M. P., Paterson, C. L., Coombes, C., and Aboagye, E. O.

Published
2012

19. Establishing the Use of [ 11 C]Choline PET-CT as an Image-based Biomarker in Prostate Cancer: Evaluation of [ 11 C]Choline Parameters Following Neoadjuvant Androgen Deprivation and Radical Radiation Therapy

Author

Challapalli, A., primary, Barwick, T., additional, Tomasi, G., additional, O'Doherty, M., additional, Stewart, S., additional, Contractor, K., additional, Al-Nahhas, A., additional, Coombes, C., additional, Aboagye, E., additional, and Mangar, S., additional

Published
2012
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41. PP-8-4 An open, comparative randomized trial comparing formestane vs oral megestrol acetate as a second-line therapy in postmenopausal advanced breast cancer patients

Author

Rose, C., primary, Freue, M., additional, Kjaer, M., additional, Boni, C., additional, Jänicke, F., additional, Coombes, C., additional, Willemse, P.H.B., additional, van Belle, S., additional, Carrión, R.Pérez, additional, Jolivet, J., additional, and de Palacios, P.Ibarra, additional

Published
1996
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43. 69. An open, comparative randomized trial comparing formestane vs oral megestrol acetate as second-line therapy in postmenopausal advanced breast cancer patients

Author

Rose, C., primary, Freue, M., additional, Kjaer, M., additional, Boni, C., additional, Jänicke, F., additional, Coombes, C., additional, Willemse, P.H.B., additional, van Belle, S., additional, Pérez Carrion, R., additional, Jolivet, J., additional, and de Palacios, P.Ibarra, additional

Published
1995
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49. Performance Validation of the Gueymard Sky Radiance Model.

Author

Harrison, A. W. and Coombes, C. A.

Subjects
SKY, ASTRONOMICAL photometry, ESTIMATION theory, ASTRONOMY
Abstract

Copyright of Atmosphere - Ocean (Canadian Meteorological & Oceanographic Society) is the property of Canadian Meteorological & Oceanographic Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
1989
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50. Comparison of Model and Indirectly Measured Diffuse Sky Irradiances of Tilted Surfaces.

Author

Harrison, A. W. and Coombes, C. A.

Subjects
SPECTRAL irradiance, SKY, ANISOTROPY, AZIMUTH, CLOUDS
Abstract

Copyright of Atmosphere - Ocean (Canadian Meteorological & Oceanographic Society) is the property of Canadian Meteorological & Oceanographic Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
1988
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