Plant responses to simulated carbon capture and transport leakage: the effect of impurities in the CO2 gas stream

To deliver an effective transition from a carbon-based 24 to a carbon-free energy market, bridging technologies are required. One such possibility is the use of carbon capture and storage, (CCS). However, before such innovations can be rolled out a key requirement is to understand the environmental impact of these technologies. Recent experimental work has demonstrated that small scale CO2 leakage from CCS pipeline infrastructure has a localised and possibly transient impact. However, what remains unknown is the possibility of synergistic impact of impurities in the CO2 gas stream. Here we report the impact of two impurities SO2 (100 ppm SO2 in pure CO2) and H2S (80ppm H2S in pure CO2) on the growth and performance of two crop species (spring wheat, Triticum aestivum and beetroot, Beta vulgaris) in fully replicated experiments. Our data show that when compared to CO2-only gassed controls, the impact of these impurities are minimal as there are no statistically significant differences between performance parameters (photosynthesis, stomatal conductance and transpiration) or biomass. These results signify that from a plant health perspective it may not be necessary to completely remove these specific impurities prior to CO2 transportation

Heavy metals and metalloids concentrations across UK urban horticultural soils and the factors influencing their bioavailability to food crops

Urban horticulture (UH) has been proposed as a solution to increase urban sustainability, but the potential risks to human health due to potentially elevated soil heavy metals and metalloids (HM) concentrations represent a major constraint for UH expansion. Here we provide the first UK-wide assessment of soil HM concentrations (total and bioavailable) in UH soils and the factors influencing their bioavailability to crops. Soils from 200 allotments across ten cities in the UK were collected and analysed for HM concentrations, black carbon (BC) and organic carbon (OC) concentrations, pH and texture. We found that although HM are widespread across UK UH soils, most concentrations fell below the respective UK soil screening values (C4SLs): 99 % Cr; 98 % As, Cd, Ni; 95 % Cu; 52 % Zn. However, 83 % of Pb concentrations exceeded C4SL, but only 3.5 % were above Pb national background concentration of 820 mg kg−1. The bioavailable HM concentrations represent a small fraction (0.01–1.8 %) of the total concentrations even for those soils that exceeded C4SLs. There was a significant positive relationship between both total and bioavailable HM and soil BC and OC concentrations. This suggest that while contributing to the accumulation of HM concentrations in UH soils, BC and OC may also provide a biding surface for the bioavailable HM concentrations contributing to their immobilisation. These findings have implications for both management of the risk to human health associated with UH growing in urban soils and with management of UH soil. There is a clear need to understand the mechanisms driving soil-to-crop HM transfer in UH to improve potentially restrictive C4SL (e.g. Pb) especially as public demand for UH land is growing. In addition, the UH community would benefit from education programs promoting soil management practices that reduce the risk of HM exposure - particularly in those plots where C4SLs were exceeded

Plant responses to elevated CO2 levels in soils: distinct CO2 and O2-depletion effects

To investigate potential environmental effects in the context of carbon dioxide (CO2) leakage from Carbon Capture and Storage (CCS) schemes, the University of Nottingham ASGARD (Artificial Soil Gassing And Response Detection) facility, was used to inject CO2 into the soil in replicated open-air field plots over several seasons to measure the effects on UK crop species. However, this system lacked a way of distinguishing the concomitant effects of oxygen (O2)-depletion (occurring as a consequence of high CO2 levels in the soil). As plants are aerobic, they require O2 for functional integrity of root processes. Here a complementary laboratory system was used to specifically identify distinct CO2 and O2-depletion effects on two crop species, beetroot and wheat. Parameters measured (photosynthetic rate, transpiration rate, stomatal conductance and biomass) between CO2-gassed, nitrogen (N2)-gassed (O2-depletion control) and non-gassed control plants showed distinct differences in response to CO2 gassing and O2-depletion. Differences between field and laboratory studies illustrate effects of variable meteorological conditions in the field, whilst more stable laboratory conditions show differences between crop species. Results show that the interactions of these two stresses (very high soil CO2 and O2 depletion) on crop physiology are discrete and complex

Effects of elevated soil CO2 concentration on growth and competition in a grass-clover mix

To investigate potential environmental affects in the context of carbon dioxide (CO2) leakage from Carbon Capture and Storage (CCS) schemes. The ASGARD (Artificial Soil Gassing and Response Detection) facility was established, where CO2 can be injected into the soil in replicated open-air field plots. Eight plots were sown with a grass-clover mix, with four selected for CO2 treatment while four were left as controls. Observations of sward productivity throughout the study allowed three effects to be distinguished: a direct stress response to soil gassing, limiting productivity in both species but with a greater effect on the clover; competition between the grass and clover affected by their differential stress responses; and an overall temporal trend from dominance by clover to dominance by grass in CO2 treatments. The direct effect of soil CO2 (or associated oxygen (O2) deprivation due to the high levels of CO2 in the soil) gave estimated reductions in productivity of 42% and 41% in grass, compared to 66% and 32% for clover in the high and low CO2 gassed zones respectively. Canopy CO2 increased by 70 parts per million (ppm) for every 1% increase in soil CO2 and a significant positive response of stomatal conductance in clover was observed; although carbon acquisition by the plants should not therefore be impeded, the reduction in productivity of the gassed plants is indicative of carbon-based metabolic costs probably related to soil CO2 affecting root physiology. Biomass measurements made after gassing has ceased indicated that recovery of vegetation was close to complete after 12 months

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

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

Genome size as a predictor of guard cell length in \u3cem\u3eArabidopsis thaliana\u3c/em\u3e is independent of environmental conditions

• The recent discovery of a strong positive relationship between angiosperm genome size and stomatal guard cell length (GCL) opens the possibility of using plant fossil guard cell size as a proxy for changes in angiosperm genome size over periods of environmental change. • The responses of GCL to environmental stimuli are currently unknown and may obscure this predictive relationship. • Here, we investigated the effects of environmental variables (atmospheric CO2, drought, relative humidity, irradiance, ultraviolet radiation and pathogen attack) on GCL in the model plant Arabidopsis thaliana to quantify environmentally induced variation. • GCL responded to all variables tested, but the changes incurred did not significantly impinge on the predictive capability of the relationship

Tolerance to atmospheric ozone in transgenic tobacco over-expressing glutathione synthetase in plastids.

A cross between transgenic tobacco (Nicotiana tabacum L.) plants which over‐expressed either γ‐glutamylcysteine synthetase (cpGSHI) or glutathione synthetase (cpGSHII) in their chloroplasts was used to compare the consequences of over‐expression of components of the glutathione synthetic pathway on tolerance to atmospheric O3 or paraquat. A high proportion (50%) of those progeny which carried the cpGSHII transgene alone showed tolerance to atmospheric O3 but not to paraquat. Progeny of an additional two, independent, self‐pollinated primary transgenic lines, which segregated in a Mendelian fashion for the presence of the cpGSHII transgene and therefore included both transformed and non‐transformed (recessive, wild‐type) plants, were also challenged by fumigation with O3. Again, in both cases, about 50% of the plants expressing the epGSHII transgene were found to be O3‐tolerant on the basis of reduced ethylene emissions and increased or unchanged total pigment concentrations. However, this tolerance was not due to specific changes in stomatal densities