64 research outputs found
Kelp in the Eastern Canadian Arctic: current and future predictions of habitat suitability and cover
© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Goldsmit, J., Schlegel, R. W., Filbee-Dexter, K., MacGregor, K. A., Johnson, L. E., Mundy, C. J., Savoie, A. M., McKindsey, C. W., Howland, K. L., & Archambault, P. Kelp in the Eastern Canadian Arctic: current and future predictions of habitat suitability and cover. Frontiers in Marine Science, 18, (2021): 742209. https://doi.org/10.3389/fmars.2021.742209Climate change is transforming marine ecosystems through the expansion and contraction of species’ ranges. Sea ice loss and warming temperatures are expected to expand habitat availability for macroalgae along long stretches of Arctic coastlines. To better understand the current distribution of kelp forests in the Eastern Canadian Arctic, kelps were sampled along the coasts for species identifications and percent cover. The sampling effort was supplemented with occurrence records from global biodiversity databases, searches in the literature, and museum records. Environmental information and occurrence records were used to develop ensemble models for predicting habitat suitability and a Random Forest model to predict kelp cover for the dominant kelp species in the region – Agarum clathratum, Alaria esculenta, and Laminariaceae species (Laminaria solidungula and Saccharina latissima). Ice thickness, sea temperature and salinity explained the highest percentage of kelp distribution. Both modeling approaches showed that the current extent of arctic kelps is potentially much greater than the available records suggest. These modeling approaches were projected into the future using predicted environmental data for 2050 and 2100 based on the most extreme emission scenario (RCP 8.5). The models agreed that predicted distribution of kelp in the Eastern Canadian Arctic is likely to expand to more northern locations under future emissions scenarios, with the exception of the endemic arctic kelp L. solidungula, which is more likely to lose a significant proportion of suitable habitat. However, there were differences among species regarding predicted cover for both current and future projections. Notwithstanding model-specific variation, it is evident that kelps are widespread throughout the area and likely contribute significantly to the functioning of current Arctic ecosystems. Our results emphasize the importance of kelp in Arctic ecosystems and the underestimation of their potential distribution there.This work was supported by ArcticNet (P101 ArcticKelp), Fisheries and Oceans Canada Arctic Climate Change Adaptation Strategy, Arctic Science and Aquatic Invasive Species Monitoring and Research Funds, the Natural Sciences and Engineering Research Council (NSERC), NRCan Polar Continental Shelf Program Support, Canadian Aquatic Invasive Species Network (CAISN), the Nunavut Marine Region Wildlife Management Board (NWMB), Quebec-Ocean, and the Ocean Frontier Institute through an award from the Canada First Research Excellence Fund, the Marine Environmental Observation, Prediction and Response Network of Centres of Excellence’s (MEOPAR-NCE) Southampton Island Marine Ecosystem Project, and the Belmont Forum–BiodivERsA’s De-icing of Arctic Coasts: critical or new opportunities for marine biodiversity and Ecosystem Services (ACCES). KF-D was supported by the Australian Research Council (DE190100692)
Sea Ice and Substratum Shape Extensive Kelp Forests in the Canadian Arctic
The coastal zone of the Canadian Arctic represents 10% of the world’s coastline and is one of the most rapidly changing marine regions on the planet. To predict the consequences of these environmental changes, a better understanding of how environmental gradients shape coastal habitat structure in this area is required. We quantified the abundance and diversity of canopy forming seaweeds throughout the nearshore zone (5–15 m) of the Eastern Canadian Arctic using diving surveys and benthic collections at 55 sites distributed over 3,000 km of coastline. Kelp forests were found throughout, covering on average 40.4% (±29.9 SD) of the seafloor across all sites and depths, despite thick sea ice and scarce hard substrata in some areas. Total standing macroalgal biomass ranged from 0 to 32 kg m–2 wet weight and averaged 3.7 kg m–2 (±0.6 SD) across all sites and depths. Kelps were less abundant at depths of 5 m compared to 10 or 15 m and distinct regional assemblages were related to sea ice cover, substratum type, and nutrient availability. The most common community configuration was a mixed assemblage of four species: Agarum clathratum (14.9% benthic cover ± 12.0 SD), Saccharina latissima (13% ± 14.7 SD), Alaria esculenta (5.4% ± 1.2 SD), and Laminaria solidungula (3.7% ± 4.9 SD). A. clathratum dominated northernmost regions and S. latissima and L. solidungula occurred at high abundance in regions with more open water days. In southeastern areas along the coast of northern Labrador, the coastal zone was mainly sea urchin barrens, with little vegetation. We found positive relationships between open water days (days without sea ice) and kelp biomass and seaweed diversity, suggesting kelp biomass could increase, and the species composition of kelp forests could shift, as sea ice diminishes in some areas of the Eastern Canadian Arctic. Our findings demonstrate the high potential productivity of this extensive coastal zone and highlight the need to better understand the ecology of this system and the services it provides.publishedVersio
546 Results from Phase Ib study of tebentafusp (tebe) in combination with durvalumab (durva) and/or tremelimumab (treme) in metastatic cutaneous melanoma (mCM)
BackgroundTebe, a T cell receptor fused to an anti-CD3 effector, can redirect T cells to target gp100+ cells and in Ph3, demonstrated overall survival (OS) benefit as monotherapy in metastatic uveal melanoma. In Ph2, any tumor shrinkage (44% of patients) was a better predictor of OS than response rate. In Ph1, Tebe had monotherapy activity in mCM, also a gp100+ tumor, with 1-year OS ~74% in PD-1 naïve mCM. A Ph1 dose escalation of tebe with durva (anti-PD-L1) and/or treme (anti-CTLA4) was conducted in pre-treated mCM [NCT02535078], with nearly all patients having prior PD1-treatment, and where recently reported therapies have 1-yr OS of ~55%.MethodsHeavily pre-treated HLA-A2+ mCM patients received weekly IV tebe alone (Arm 4) or with increasing doses of durva and/or treme (Arm 1–3) administered IV monthly starting day 15 of each cycle. Primary objective was to identify RP2D of combination therapy. Secondary objectives included adverse events (AE) and efficacy.Results112 pts received ≥1 tebe dose. Median age was 59, 77% were ECOG 0, and 37% were BRAFm (of which 71% received prior BRAFi/MEKi). 91% of pts were 2L+, while 74% were 3L+. 103 (92%) received prior PD-1 inhibitor, of which 87% also received prior ipilimumab. 43 pts received tebe + durva (Arm 1), 13 received tebe + treme (Arm 2), 29 received triplet therapy (Arm 3), and 27 received tebe alone (Arm 4). Maximum target doses of tebe (68 mcg) + durva (20 mg/kg) and treme (1 mg/kg) were tolerated. MTD was not formally identified for any arm. Two DLTs occurred: prolonged grade 3 rash (Arm 1) and grade 2 diarrhea leading to treatment delay (Arm 2). Related AEs that were Grade ≥3 or led to discontinuations were: 44%/0% (Arm 1), 23%/0% (Arm2), 38%/7% (Arm3), 26%/4% (Arm 4). There were no treatment-related deaths.In prior PD-1 pts, tumor shrinkage occurred in 36% and 1-yr OS was 68%. Of 51 evaluable PD-1 resistant pts (best response CR/PR/SD to prior PD1), tumor shrinkage occurred in 28% and 1-yr OS was 73% (figure 1). In 35 evaluable PD-1 refractory pts (prior best response PD), tumor shrinkage occurred in 49% and 1-yr OS was 61%. For 38 prior PD-1 pts who received ≥10mg/kg durva, 1-yr OS was 81%.Abstract 546 Figure 1% tumor change from baseline in evaluable patients with known response to prior PD1 exposureConclusionsTebe with anti-PD-L1 and/or anti-CTLA4 had an acceptable safety profile. Tebe + durva demonstrated durable tumor shrinkage and promising 1-yr OS rates in prior-PD1 treated mCM relative to recent reports.Trial RegistrationNCT02535078Ethics ApprovalThe institutional review board or independent ethics committee at each center approved the trial. The trial was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines
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The ModelSEED Biochemistry Database for the integration of metabolic annotations and the reconstruction, comparison and analysis of metabolic models for plants, fungi and microbes
In the Abstract, the url https://modelseed.org has been replaced with https://modelseed.org/biochem
X-shooter Spectroscopy and HST Imaging of 15 Massive Quiescent Galaxies at z ≳ 2
We present a detailed analysis of a large sample of spectroscopically confirmed massive quiescent galaxies (MQGs; log(M*/M ⊙) ~ 11.5) at z ≳ 2. This sample comprises 15 galaxies selected in the COSMOS and UDS fields by their bright K-band magnitudes and followed up with Very Large Telescope (VLT) X-shooter spectroscopy and Hubble Space Telescope (HST)/WFC3 H_(F160W) imaging. These observations allow us to unambiguously confirm their redshifts, ascertain their quiescent nature and stellar ages, and reliably assess their internal kinematics and effective radii. We find that these galaxies are compact, consistent with the high-mass end of the stellar mass–size relation for quiescent galaxies at z = 2. Moreover, the distribution of the measured stellar velocity dispersions of the sample is consistent with the most massive local early-type galaxies from the MASSIVE Survey, showing that evolution in these galaxies is dominated by changes in size. The HST images reveal, as surprisingly high, that 40% of the sample has tidal features suggestive of mergers and companions in close proximity, including three galaxies experiencing ongoing major mergers. The absence of velocity dispersion evolution from z = 2 to 0, coupled with a doubling of the stellar mass, with a factor of 4 size increase and the observed disturbed stellar morphologies, supports dry minor mergers as the primary drivers of the evolution of the MQGs over the last 10 billion yr
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
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
A density-functional approach to polarizable models: A Kim-Gordon response density interaction potential for molecular simulations
A combined linear-response-frozen electron-density model has been implemented in a molecular-dynamics scheme derived from an extended Lagrangian formalism. This approach is based on a partition of the electronic charge distribution into a frozen region described by Kim-Gordon theory [J. Chem. Phys. 56, 3122 (1972); J. Chem. Phys. 60, 1842 (1974)] and a response contribution determined by the instantaneous ionic configuration of the system. The method is free from empirical pair potentials and the parametrization protocol involves only calculations on properly chosen subsystems. We apply this method to a series of alkali halides in different physical phases and are able to reproduce experimental structural and thermodynamic properties with an accuracy comparable to Kohn-Sham density-functional calculations
Sea Ice and Substratum Shape Extensive Kelp Forests in the Canadian Arctic
The coastal zone of the Canadian Arctic represents 10% of the world’s coastline and is one of the most rapidly changing marine regions on the planet. To predict the consequences of these environmental changes, a better understanding of how environmental gradients shape coastal habitat structure in this area is required. We quantified the abundance and diversity of canopy forming seaweeds throughout the nearshore zone (5–15 m) of the Eastern Canadian Arctic using diving surveys and benthic collections at 55 sites distributed over 3,000 km of coastline. Kelp forests were found throughout, covering on average 40.4% (±29.9 SD) of the seafloor across all sites and depths, despite thick sea ice and scarce hard substrata in some areas. Total standing macroalgal biomass ranged from 0 to 32 kg m–2 wet weight and averaged 3.7 kg m–2 (±0.6 SD) across all sites and depths. Kelps were less abundant at depths of 5 m compared to 10 or 15 m and distinct regional assemblages were related to sea ice cover, substratum type, and nutrient availability. The most common community configuration was a mixed assemblage of four species: Agarum clathratum (14.9% benthic cover ± 12.0 SD), Saccharina latissima (13% ± 14.7 SD), Alaria esculenta (5.4% ± 1.2 SD), and Laminaria solidungula (3.7% ± 4.9 SD). A. clathratum dominated northernmost regions and S. latissima and L. solidungula occurred at high abundance in regions with more open water days. In southeastern areas along the coast of northern Labrador, the coastal zone was mainly sea urchin barrens, with little vegetation. We found positive relationships between open water days (days without sea ice) and kelp biomass and seaweed diversity, suggesting kelp biomass could increase, and the species composition of kelp forests could shift, as sea ice diminishes in some areas of the Eastern Canadian Arctic. Our findings demonstrate the high potential productivity of this extensive coastal zone and highlight the need to better understand the ecology of this system and the services it provides
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