51 research outputs found
Passive Vibration Control of Airborne Equipment using a Circular Steel Ring
Vibration isolation is needed to protect avionics equipment from adverse aircraft vibration environments. Passive isolation is the simplest means to achieve this goal. The system used here consists of a circular steel ring with a lump mass on top and exposed to base excitation. Sinusoidal and filtered zero-mean Gaussian white noise are used to excite the structure and the acceleration response spectra at the top of the ring are computed. An experiment is performed to identify the natural frequencies and modal damping of the circular ring. Comparison is made between the analytical and experimental results and good agreement is observed. The ring response is also evaluated with a concentrated mass attached to the top of the ring. The effectiveness of the ring in isolating the equipment from base excitation is studied. The acceleration response spectra of a single degree of freedom system attached to the top of the ring are evaluated and the results are compared with those exposed directly to the base excitation. It is shown that a properly designed ring could effectively protect the avionics from possible damaging excitation levels
Construction of Streptococcus pyogenes mutants by allele replacement mutagenesis
S. pyogenes secrete a large array of molecules that might contribute to resistance against antimicrobial peptides (AMPs). Some of these are anchored in the cell-wall by enzymes called sortases and others are released from the cell after secretion. One of the released proteins that have previously been reported to inhibit bactericidal effect of the AMPs are streptococcal inhibitor of complement (SIC). SIC has been recognised as a substantial virulence factor in the M1 GAS strain AP1, because Δsic mutant failed to colonise mouse throat (Lukomski et al., 2000). In fact, the colonisation of the SIC-negative strain was significantly impaired during the first four days of post-inoculation, showing that SIC is a crucial virulence factor during the early stages of infection by this strain (Lukomski et al., 2000). Hoe and colleagues then showed that GAS Δsic mutant was easily internalised and killed more effectively by human epithelial cells than the wild-type strain (Hoe et al., 2002). Previous studies used SIC-defective mutants which were constructed by insertion of transposon. The disadvantage of such mutagenesis is that
the GAS mutants may have retained an intact copy of the sic gene, which could express some SIC protein. Therefore, the specific objective of the project was to construct a sic deletion mutant of GAS strain SF370 by allele-replacement mutagenesis. The constructed mutant would have a genetically clearly-defined deletion mutant, that completely removed sic gene from the S. pyogenes strain SF370 chromosome, without leaving any foreign sequences (such as an inserted plasmid) behind
Crop Updates 2007 - Cereals
This session covers twenty six papers from different authors:
CEREAL BREEDING
1. Strategies for aligning producer and market imperatives in cereal breeding in Western Australia, R. Loughman, R. Lance, I. Barclay, G. Crosbie, S. Harasymow, W. Lambe, C. Li, R. McLean, C. Moore, K. Stefanova, A. Tarr and R. Wilson, Department of Agriculture and Food
2. LongReach plant breeders wheat variety trials – 2006, Matu Peipi and Matt Whiting, LongReach Plant Breeders
WHEAT AGRONOMY
3. Response of wheat varieties to sowing time in the northern agricultural region in 2006, Christine Zaicou, Department of Agriculture and Food
4. Response of wheat varieties to sowing time in the central agricultural region in 2006, Shahajahan Miyan, Department of Agriculture and Food
5. Response of wheat varieties to sowing time in the Great Southern and Lakes region, Brenda Shackleyand Ian Hartley, Department of Agriculture and Food
6. Response of wheat varieties to time of sowing time in Esperance region in 2006, Christine Zaicou, Ben Curtis and Ian Hartley, Department of Agriculture and Food
7. Performance of wheat varieties in National Variety Testing (NVT) WA: Year 2, Peter Burgess, Agritech Crop Research
8. Flowering dates of wheat varieties in Western Australia in 2006, Darshan Sharma, Brenda Shackley and Christine Zaicou, Department of Agriculture and Food
9. Prospects for perennial wheat: A feasibility study, Len J. Wade, Lindsay W. Bell, Felicity Byrne (nee Flugge) and Mike A. Ewing, School of Plant Biology and CRC for Plant-based Management of Dryland Salinity, The University of Western Australia
BARLEY AGRONOMY
10. Barley agronomy highlights: Time of sowing x variety, Blakely Paynter and Andrea Hills, Department of Agriculture and Food
11. Barley agronomy highlights: Weeds and row spacing, Blakely Paynter and Andrea Hills, Department of Agriculture and Food
12. Barley agronomy highlights: Weeds and barley variety, Blakely Paynter and Andrea Hills, Department of Agriculture and Food
OAT AGRONOMY
13. Agronomic performance of dwarf potential milling oat varieties in varied environments of WA, Raj Malik, Blakely Paynter and Kellie Winfield, Department of Agriculture and Food
14. Sourcing oat production information in 2007, Kellie Winfield, Department of Agriculture and Food
HERBICIDE TOLERANCE
15. Response of new wheat varieties to herbicides, Harmohinder Dhammu, Department of Agriculture and Food
16. Herbicide tolerance of new barley varieties, Harmohinder Dhammu, Vince Lambert and Chris Roberts, Department of Agriculture and Food
17. Herbicide tolerance of new oat varieties, Harmohinder Dhammu, Vince Lambert and Chris Roberts, Department of Agriculture and Food
NUTRITION
18. Nitrogen Decision Tools – choose your weapon, Jeremy Lemon, Department of Agriculture and Food
DISEASES
19. Barley agronomy highlights: Canopy management, Andrea Hills and Blakely Paynter, Department of Agriculture and Food
20. Barley agronomy highlights: Leaf diseases and spots, Andrea Hills and Blakely Paynter, Department of Agriculture and Food
21. Fungicide applications for stripe rust management in adult plant resistant (APR) wheat varieties, Geoff Thomas, Rob Loughman, Ian Hartley and Andrew Taylor; Department of Agriculture and Food
22. Effect of seed treatment with Jockey on time of onset and disease severity of stripe rust in wheat, Manisha Shankar, John Majewski and Rob Loughman, Department of Agriculture and Food
23. Rotations for management of Cereal Cyst Nematode, Vivien Vanstone, Department of Agriculture and Food
24. Occurrence of Wheat Streak Mosaic Virus in Western Australian grainbelt during the 2006 growing season, Brenda Coutts, Monica Kehoe and Roger Jones, Department of Agriculture and Food
25. Development of a seed test for Wheat Streak Mosaic Virus in bulk samples of wheat, Geoffrey Dwyer, Belinda Welsh, Cuiping Wang and Roger Jones, Department of Agriculture and Food
MARKETS
26. Developing the Australian barley value chain, Linda Price, Barley Australi
GRB Afterglows and Other Transients in the SDSS
The Sloan Digital Sky Survey (SDSS) will image one quarter of the sky centered on the northern galactic cap and produce a 3‐D map of galaxies and quasars found in the sample. An additional 225 deg2 southern survey will be imaged repeatedly on varying timescales. Here we discuss both archival searches in the SDSS catalog (such as SDSS J24602.54+011318.8) and active searches with the SDSS instruments (such as for GRB 010222) for GRB afterglows and other transient objects. © 2003 American Institute of PhysicsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87288/2/349_1.pd
Crop Updates 2007 - Lupins, Pulses and Oilseeds
This session covers forty eight papers from different authors:
2006 REGIONAL ROUNDUP
1. South east agricultural region, Mark Seymour1 and Jacinta Falconer2, 1Department of Agriculture and Food, 2Cooperative Bulk Handling Group
2. Central agricultural region, Ian Pritchard, Department of Agriculture and Food
3. Great Southern and Lakes region, Rodger Beermier, Department of Agriculture and Food
4. Northern agricultural region, Wayne Parker and Martin Harries, Department of Agriculture and Food
LUPINS
5. Development of anthracnose resistant and early flowering albus lupins (Lupinus albus L) in Western Australia, Kedar Adhikari and Geoff Thomas, Department of Agriculture and Food
6. New lupins adapted to the south coast, Peter White, Bevan Buirchell and Mike Baker, Department of Agriculture and Food
7. Lupin species and row spacing interactions by environment, Martin Harries, Peter White, Bob French, Jo Walker, Mike Baker and Laurie Maiolo, Department of Agriculture and Food
8. The interaction of lupin species row spacing and soil type, Martin Harries, Bob French, Laurie Maiolo and Jo Walker, Department of Agriculture and Food
9. The effects of row spacing and crop density on competitiveness of lupins with wild radish, Bob French and Laurie Maiolo, Department of Agriculture and Food
10. The effect of time of sowing and radish weed density on lupin yield, Martin Harries and Jo Walker, Department of Agriculture and Food
11. Interaction of time of sowing and weed management in lupins, Martin Harries and Jo Walker, Department of Agriculture and Food
12. Delayed sowing as a strategy to manage annual ryegrass, Bob French and Laurie Maiolo, Department of Agriculture and Food
13. Is delayed sowing a good strategy for weed management in lupins? Bob French, Department of Agriculture and Food
14. Lupins aren’t lupins when it comes to simazine, Peter White and Leigh Smith, Department of Agriculture and Food
15. Seed yield and anthracnose resistance of Tanjil mutants tolerant to metribuzin, Ping Si1, Bevan Buirchell1,2 and Mark Sweetingham1,2, 1Centre for Legumes in Mediterranean Agriculture, Australia; 2Department of Agriculture and Food
16. The effect of herbicides on nodulation in lupins, Lorne Mills1, Harmohinder Dhammu2 and Beng Tan1, 1Curtin University of Technology and 2Department of Agriculture and Food
17. Effect of fertiliser placements and watering regimes on lupin growth and seed yield in the central grain belt of Western Australia, Qifu Ma1, Zed Rengel1, Bill Bowden2, Ross Brennan2, Reg Lunt2 and Tim Hilder2, 1Soil Science & Plant Nutrition UWA, 2Department of Agriculture and Food
18. Development of a forecasting model for Bean Yellow Mosaic Virus in lupins, T. Maling1,2, A. Diggle1, D. Thackray1,2, R.A.C. Jones2, and K.H.M. Siddique1, 1Centre for Legumes in Mediterranean Agriculture, The University of Western Australia; 2Department of Agriculture and Food
19. Manufacturing of lupin tempe,Vijay Jayasena1,4, Leonardus Kardono2,4, Ken Quail3,4 and Ranil Coorey1,4, 1Curtin University of Technology, Perth, Australia, 2Indonesian Institute of Sciences (LIPI), Indonesia, 3BRI Australia Ltd, Sydney, Australia, 4Grain Foods CRC, Sydney, Australia
20. The impact of lupin based ingredients in ice-cream, Hannah Williams, Lee Sheer Yap and Vijay Jayasena, Curtin University of Technology, Perth WA
21. The acceptability of muffins substituted with varying concentrations of lupin flour, Anthony James, Don Elani Jayawardena and Vijay Jayasena, Curtin University of Technology, PerthWA
PULSES
22. Chickpea variety evaluation, Kerry Regan1, Rod Hunter1, Tanveer Khan1,2and Jenny Garlinge1, 1Department of Agriculture and Food, 2CLIMA, The University of Western Australia
23. Advanced breeding trials of desi chickpea, Khan, T.N.1, Siddique, K.H.M.3, Clarke, H.2, Turner, N.C.2, MacLeod, W.1, Morgan, S.1, and Harris, A.1, 1Department of Agriculture and Food, 2Centre for Legumes in Mediterranean Agriculture, 3TheUniversity of Western Australia
24. Ascochyta resistance in chickpea lines in Crop Variety Testing (CVT) of 2006, Tanveer Khan1 2, Bill MacLeod1, Alan Harris1, Stuart Morgan1and Kerry Regan1, 1Department of Agriculture and Food, 2CLIMA, The University of Western Australia
25. Yield evaluation of ascochyta blight resistant Kabuli chickpeas, Kerry Regan1and Kadambot Siddique2, 1Department of Agriculture and Food, 2Institute of Agriculture, The University of Western Australia
26. Pulse WA Chickpea Industry Survey 2006, Mark Seymour1, Ian Pritchard1, Wayne Parker1and Alan Meldrum2, 1Department of Agriculture and Food, 2Pulse Australia
27. Genes from the wild as a valuable genetic resource for chickpea improvement, Heather Clarke1, Helen Bowers1and Kadambot Siddique2, 1Centre for Legumes in Mediterranean Agriculture, 2Institute of Agriculture, The University of Western Australia
28. International screening of chickpea for resistance to Botrytis grey mould, B. MacLeod1, Dr T. Khan1, Prof. K.H.M. Siddique2and Dr A. Bakr3, 1Department of Agriculture and Food, 2The University of Western Australia, 3Bangladesh Agricultural Research Institute
29. Balance® in chickpea is safest applied post sowing to a level seed bed, Wayne Parker, Department of Agriculture and Food,
30. Demonstrations of Genesis 510 chickpea, Wayne Parker, Department of Agriculture and Food
31. Field pea 2006, Ian Pritchard, Department of Agriculture and Food
32. Field pea variety evaluation, Kerry Regan1, Rod Hunter1, Tanveer Khan1,2 and Jenny Garlinge1, 1Department of Agriculture and Food, 2CLIMA, The University of Western Australia
33. Breeding highlights of the Australian Field Pea Improvement Program (AFPIP),Kerry Regan1, Tanveer Khan1,2, Phillip Chambers1, Chris Veitch1, Stuart Morgan1 , Alan Harris1and Tony Leonforte3, 1Department of Agriculture and Food, 2CLIMA, The University of Western Australia, 3Department of Primary Industries, Victoria
34. Field pea germplasm enhancement for black spot resistance, Tanveer Khan, Kerry Regan, Stuart Morgan, Alan Harris and Phillip Chambers, Department of Agriculture and Food
35. Validation of Blackspot spore release model and testing moderately resistant field pea line, Mark Seymour, Ian Pritchard, Rodger Beermier, Pam Burgess and Leanne Young, Department of Agriculture and Food
36. Yield losses from sowing field pea seed infected with Pea Seed-borne Mosaic Virus, Brenda Coutts, Donna O’Keefe, Rhonda Pearce, Monica Kehoe and Roger Jones, Department of Agriculture and Food
37. Faba bean in 2006, Mark Seymour, Department of Agriculture and Food
38. Germplasm evaluation – faba bean, Mark Seymour1, Terri Jasper1, Ian Pritchard1, Mike Baker1 and Tim Pope1,2, 1Department of Agriculture and Food, , 2CLIMA, The University of Western Australia
39. Breeding highlights of the Coordinated Improvement Program for Australian Lentils (CIPAL), Kerry Regan1, Chris Veitch1, Phillip Chambers1 and Michael Materne2, 1Department of Agriculture and Food, 2Department of Primary Industries, Victoria
40. Screening pulse lentil germplasm for tolerance to alternate herbicides, Ping Si1, Mike Walsh2 and Mark Sweetingham1,3, 1Centre for Legumes in Mediterranean Agriculture, 2West Australian Herbicide Resistance Initiative, 3Department of Agriculture and Food
41. Genomic synteny in legumes: Application to crop breeding, Phan, H.T.T.1, Ellwood, S.R.1, Hane, J.1, Williams, A.1, Ford, R.2, Thomas, S.3 and Oliver R1, 1Australian Centre of Necrotrophic Plant Pathogens, Murdoch University, 2BioMarka, University of Melbourne, 3NSW Department of Primary Industries
42. Tolerance of lupins, chickpeas and canola to Balanceâ(Isoxaflutole) and Galleryâ (Isoxaben), Leigh Smith and Peter White, Department of Agriculture and Food
CANOLA AND OILSEEDS
43. The performance of TT Canola varieties in the National Variety Test (NVT),WA,2006,Katie Robinson, Research Agronomist, Agritech Crop Research
44. Evaluation of Brassica crops for biodiesel in Western Australia, Mohammad Amjad, Graham Walton, Pat Fels and Andy Sutherland, Department of Agriculture and Food
45. Production risk of canola in different rainfall zones in Western Australia, Imma Farré1, Michael Robertson2 and Senthold Asseng3, 1Department of Agriculture and Food, 2CSIRO Sustainable Ecosystems, 3CSIRO Plant Industry
46. Future directions of blackleg management – dynamics of blackleg susceptibility in canola varieties, Ravjit Khangura, Moin Salam and Bill MacLeod, Department of Agriculture and Food
47. Appendix 1: Contributors
48. Appendix 2: List of common acronym
Optimal Time-Consistent Government Debt Maturity
Abstract: This paper develops a model of optimal debt maturity in which the government cannot issue statecontingent debt. As the literature has established, if the government can perfectly commit to fiscal policy, it fully insulates the economy against government spending shocks by purchasing short-term assets and issuing long-term debt. These positions are quantitatively very large relative to GDP and do not need to be actively managed by the government. Our main result is that these conclusions are not robust when lack of commitment is introduced. Under lack of commitment, large and tilted debt positions are very expensive to finance ex-ante since they ex-post exacerbate the government's problem stemming from a lack of commitment. In contrast, a flat maturity structure minimizes the cost entailed by a lack of commitment, though this structure also limits the ability to insure against shocks and increases the volatility of fiscal policy distortions. We show that the optimal time-consistent maturity structure is nearly flat because reducing average borrowing costs is quantitatively more important for welfare than reducing fiscal policy volatility. Thus, under lack of commitment, the government actively manages its debt positions and can approximate optimal policy by confining its debt instruments to consols
A Scalable System for Production of Functional Pancreatic Progenitors from Human Embryonic Stem Cells
Development of a human embryonic stem cell (hESC)-based therapy for type 1 diabetes will require the translation of proof-of-principle concepts into a scalable, controlled, and regulated cell manufacturing process. We have previously demonstrated that hESC can be directed to differentiate into pancreatic progenitors that mature into functional glucose-responsive, insulin-secreting cells in vivo. In this study we describe hESC expansion and banking methods and a suspension-based differentiation system, which together underpin an integrated scalable manufacturing process for producing pancreatic progenitors. This system has been optimized for the CyT49 cell line. Accordingly, qualified large-scale single-cell master and working cGMP cell banks of CyT49 have been generated to provide a virtually unlimited starting resource for manufacturing. Upon thaw from these banks, we expanded CyT49 for two weeks in an adherent culture format that achieves 50–100 fold expansion per week. Undifferentiated CyT49 were then aggregated into clusters in dynamic rotational suspension culture, followed by differentiation en masse for two weeks with a four-stage protocol. Numerous scaled differentiation runs generated reproducible and defined population compositions highly enriched for pancreatic cell lineages, as shown by examining mRNA expression at each stage of differentiation and flow cytometry of the final population. Islet-like tissue containing glucose-responsive, insulin-secreting cells was generated upon implantation into mice. By four- to five-months post-engraftment, mature neo-pancreatic tissue was sufficient to protect against streptozotocin (STZ)-induced hyperglycemia. In summary, we have developed a tractable manufacturing process for the generation of functional pancreatic progenitors from hESC on a scale amenable to clinical entry
A randomised controlled trial of calcium channel blockade (CCB) with Amlodipine For the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT):study protocol
Background Vascular dementia is the second most common cause of dementia affecting over seven million people worldwide, yet there are no licensed treatments. There is an urgent need for a clinical trial in this patient group. Subcortical ischaemic vascular dementia is the most common variant of vascular dementia. This randomised trial will investigate whether use of calcium channel blockade with amlodipine, a commonly used agent, can provide the first evidence-based pharmacological treatment for subcortical ischaemic vascular dementia. Methods/Design This is a randomised controlled trial of calcium channel blockade with Amlodipine For the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT) to test the hypothesis that treatment with amlodipine can improve outcomes for these patients in a phase IIb, multi-centre, double-blind, placebo-controlled randomised trial. The primary outcome is the change from baseline to 12 months in the Vascular Dementia Assessment Scale cognitive subscale (VADAS-cog). Secondary outcomes include cognitive function, executive function, clinical global impression of change, change in blood pressure, quantitative evaluation of lesion accrual based on magnetic resonance imaging (MRI), health-related quality of life, activities of daily living, non-cognitive dementia symptoms, care-giver burden and care-giver health-related quality of life, cost-effectiveness and institutionalisation. A total of 588 patients will be randomised in a 1:1 ratio to either amlodipine or placebo, recruited from sites across the UK and enrolled in the trial for 104 weeks. Discussion There are no treatments licensed for vascular dementia. The most common subtype is subcortical ischaemic vascular dementia (SIVD). This study is designed to investigate whether amlodipine can produce benefits compared to placebo in established SIVD. It is estimated that the numbers of people with VaD and SIVD will increase globally in the future and the results of this study should inform important treatment decisions. Trial registration: Current Controlled Trials ISRCTN31208535. Registered on 7 March 2014
Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial
Background
Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear.
Methods
RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047.
Findings
Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths.
Interpretation
Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population
Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial
Background
Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain.
Methods
RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and
ClinicalTrials.gov
,
NCT00541047
.
Findings
Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths.
Interpretation
Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy.
Funding
Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society
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