Sediment and vegetation monitoring during a levee removal project on the Stillaguamish River Delta at Port Susan Bay, WA

Sea levels around the world are on the rise in due to the effects of climate change. Coastal wetlands and estuaries are at risk of being submerged as water levels continue to increase, unless they can move inland or gain surface elevation. These wetland systems provide vital ecosystem services that would be difficult or impossible to provide by other means. In the Puget Sound, Washington, 80% of the original estuarine and coastal wetland habitat has been replaced by human infrastructure, making the monitoring, preservation, and restoration of the remaining stock important both ecologically and economically. The objective of this project was to monitor the restoration of an estuarine system on the Stillaguamish River delta. The project involves the removal of levees and reintroduction of tidal flow into a subsided farmland that was formerly part of the estuary, and to determine the sustainability of the Stillaguamish River delta and similar Puget Sound estuaries with rising sea-levels. The scope of this monitoring project includes the installation and yearly sampling of surface elevation tables (SETs), vegetation surveys and quantification of the net primary productivity (NPP) within the leveed area, immediately outside the levees, in an adjacent area outside the farmland, and within an un-leveed reference site across the main river channel. SET sampling, before the levee removal, revealed a positive trend in elevation gain at 8 of the 11 SETs of over 1 cm/year, well above current rate of RSLR at 0.19cm/year. Sediment markers revealed that most of that gain can be attributed to sediment accretion, indicating adequate sources of sediment and therefore sustainability of the estuary under current rates of sea level rise. Primary productivity sampling in the late summer of 2012 yielded an average of 420 DW(g)/m²/year in the high marsh and 327 DW(g)/m²/year in the low marsh sites. Vegetation consisted predominantly of Schoenoplectus americanus, Schoenoplectus acutus, and Schoenoplectus maritimus, with elevation delineating the greatest shifts in community structure and abundance. The exception to this was within the portion of leveed farmland, where surface elevations were below the surrounding estuary and vegetation consisted primarily of a Schoenoplectus americanus monoculture

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

Bayesian transfer learning between autoregressive inference tasks

Bayesian transfer learning typically relies on a complete stochastic dependence speci cation between source and target learners which allows the opportunity for Bayesian conditioning. We advocate that any requirement for the design or assumption of a full model between target and sources is a restrictive form of transfer learning

Hammett Structural Relationships Revealed in Chalcogen Bonded Co-crystals of Electron Rich Pyridines with 4′-Substituted Ebselen Derivatives

In this work, a detailed Hammett structure-structure correlation was applied to a range of chalcogen bonded co-crystals prepared by combining 4′-substituted derivatives of the selenium-based drug ebselen with three different 4-amino-substituted pyridine based chalcogen bond acceptors of differing basicities. This established that the N · · · Se chalcogen bond distance is well within the sum of the van der Waals radii of Se and N and is sensitive to the electronic nature of the substituent. Thus N · · · Se distances ranging from 2.2424(5)–2.4496(9) Å were observed with the shorter distances being observed in co-crystals of ebselen substituted with electron withdrawing groups. Associated with trends of the N · · · Se distance as a function of the 4′-substituent was lengthening of the internal Se−N bond distance consistent with a significant covalent contribution to N · · · Se chalcogen bonding in these derivatives. We define a covalency quotient for the chalcogen bond as the negative slope of the plot of the internal Se−N bond distance vs the external N · · · Se chalcogen bond distance. A value of 0.31 was obtained implying a significant covalent contribution to N · · · Se chalcogen bond. A similar result was obtained by an analysis of chalcogen bonded selenium containing molecules harvested from the Cambridge Crystallographic Database. The covalency quotient is extended to the general case for sigma-hole interactions including halogen bonding and hydrogen bonding, and we show that the covalent component of such interactions can be inferred from the lengthening of the donor bond. The degree of charge transfer in a smaller number of chalcogen bonded co-crystals of ebselen was established by measuring experimental electron density using high-resolution x-ray diffraction to more accurately measure the degree of electron transfer and hence covalency. This showed that in the most strongly bound systems, up to 1 electron worth of charge is transferred from the Lewis base to the Ch-bond donor, which again clearly points to significant covalent character