Opportunities for CO2 Storage around Scotland; An Integrated Strategic Research Study

Carbon Capture and Storage (CCS) is one of the critical technologies worldwide which will enable reduction of carbon dioxide (CO2) emissions arising from large industrial sites. CCS allows the continued use of a diverse mix of energy sources, including fossil fuels, which improves the security of cost-effective electricity supply. Scotland has the opportunity and responsibility to reduce CO2 emissions arising from burning of fossil fuels and their impact on climate change. The EU plans to have 12 CCS plants operating by 2015. In February 2009, the UK Secretary of State for Energy and Climate Change stated an aspiration for the UK to have more than one demonstration project in operation enabled by government funding. However, these targets cannot be delivered without the underpinning knowledge from studies such as this. Commitment to large-scale investment in CO2 capture plant will require proven storage capability. This study • presents the first high-level screening of CO2 storage sites available to Scotland • evaluates the means by which CO2 can be transported from power plants and other industrial activities to storage sites, and • investigates the costs and business constraints. This is the most comprehensive and fully integrated study performed in the UK, and was achieved by a collaborative partnership of Scottish Government, research universities and institutes, and a broad base of support from industry and business. The conclusions show that Scotland has an extremely large CO2 storage resource. This is overwhelmingly in offshore saline aquifers (deeply buried porous sandstones filled with salt water) together with a few specific depleted hydrocarbon fields. The resource can easily accommodate the industrial CO2 emissions from Scotland for the next 200 years. There is very likely to be sufficient storage to allow import of CO2 from NE England, this equating to over 25% of future UK large industry and power CO2 output. Preliminary indications are that Scotland's offshore CO2 storage capacity is very important on a European scale, comparable with that of offshore Norway, and greater than Netherlands, Denmark and Germany combined.Carbon Capture and Storage (CCS) is one of the critical technologies worldwide which will enable reduction of carbon dioxide (CO2) emissions arising from large industrial sites. CCS allows the continued use of a diverse mix of energy sources, including fossil fuels, which improves the security of cost-effective electricity supply. Scotland has the opportunity and responsibility to reduce CO2 emissions arising from burning of fossil fuels and their impact on climate change. The EU plans to have 12 CCS plants operating by 2015. In February 2009, the UK Secretary of State for Energy and Climate Change stated an aspiration for the UK to have more than one demonstration project in operation enabled by government funding. However, these targets cannot be delivered without the underpinning knowledge from studies such as this. Commitment to large-scale investment in CO2 capture plant will require proven storage capability. This study • presents the first high-level screening of CO2 storage sites available to Scotland • evaluates the means by which CO2 can be transported from power plants and other industrial activities to storage sites, and • investigates the costs and business constraints. This is the most comprehensive and fully integrated study performed in the UK, and was achieved by a collaborative partnership of Scottish Government, research universities and institutes, and a broad base of support from industry and business. The conclusions show that Scotland has an extremely large CO2 storage resource. This is overwhelmingly in offshore saline aquifers (deeply buried porous sandstones filled with salt water) together with a few specific depleted hydrocarbon fields. The resource can easily accommodate the industrial CO2 emissions from Scotland for the next 200 years. There is very likely to be sufficient storage to allow import of CO2 from NE England, this equating to over 25% of future UK large industry and power CO2 output. Preliminary indications are that Scotland's offshore CO2 storage capacity is very important on a European scale, comparable with that of offshore Norway, and greater than Netherlands, Denmark and Germany combined

Choline Kinase Alpha as an Androgen Receptor Chaperone and Prostate Cancer Therapeutic Target.

BACKGROUND: The androgen receptor (AR) is a major drug target in prostate cancer (PCa). We profiled the AR-regulated kinome to identify clinically relevant and druggable effectors of AR signaling. METHODS: Using genome-wide approaches, we interrogated all AR regulated kinases. Among these, choline kinase alpha (CHKA) expression was evaluated in benign (n = 195), prostatic intraepithelial neoplasia (PIN) (n = 153) and prostate cancer (PCa) lesions (n = 359). We interrogated how CHKA regulates AR signaling using biochemical assays and investigated androgen regulation of CHKA expression in men with PCa, both untreated (n = 20) and treated with an androgen biosynthesis inhibitor degarelix (n = 27). We studied the effect of CHKA inhibition on the PCa transcriptome using RNA sequencing and tested the effect of CHKA inhibition on cell growth, clonogenic survival and invasion. Tumor xenografts (n = 6 per group) were generated in mice using genetically engineered prostate cancer cells with inducible CHKA knockdown. Data were analyzed with χ(2) tests, Cox regression analysis, and Kaplan-Meier methods. All statistical tests were two-sided. RESULTS: CHKA expression was shown to be androgen regulated in cell lines, xenografts, and human tissue (log fold change from 6.75 to 6.59, P = .002) and was positively associated with tumor stage. CHKA binds directly to the ligand-binding domain (LBD) of AR, enhancing its stability. As such, CHKA is the first kinase identified as an AR chaperone. Inhibition of CHKA repressed the AR transcriptional program including pathways enriched for regulation of protein folding, decreased AR protein levels, and inhibited the growth of PCa cell lines, human PCa explants, and tumor xenografts. CONCLUSIONS: CHKA can act as an AR chaperone, providing, to our knowledge, the first evidence for kinases as molecular chaperones, making CHKA both a marker of tumor progression and a potential therapeutic target for PCa.This work was supported by a Cancer Research UK program grant (to DEN) and also by the US Department of Defense (Prostate Cancer Research Program Transformative Impact Award, grant ID W81XWH-13-2-0093; WDT and SMD), PCFA/Cancer Australia/Movember (grant IDs 1012337 and 1043482; WDT and LAS), Cancer Australia (grant ID 1043497; WDT and JC) and The Ray and Shirl Norman Cancer Research Trust (WDT and LAS). The Dame Roma Mitchell Cancer Research Laboratories were supported by an establishment grant from the PCFA (ID 2011/0452). FO was supported by a PhD project grant from Prostate Cancer UK (S10-10). LAS is supported by a Young Investigator Award from the Prostate Cancer Foundation (the Foundation 14 award)

Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial.

Peer reviewed: TrueAcknowledgements: The RITAZAREM trial is directed by the European Vasculitis Society and the Vasculitis Clinical Research Consortium (VCRC). The primary sponsor is Cambridge University Hospitals NHS Foundation Trust, and there are collaboration and data-sharing agreements with the University of Pennsylvania and the University of Miyazaki and Okayama University in Japan.Funder: Research Committee on Intractable Vasculitides, the Ministry of Health, Labour and Welfare of JapanOBJECTIVE: Following induction of remission with rituximab in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) relapse rates are high, especially in patients with history of relapse. Relapses are associated with increased exposure to immunosuppressive medications, the accrual of damage and increased morbidity and mortality. The RITAZAREM trial compared the efficacy of repeat-dose rituximab to daily oral azathioprine for prevention of relapse in patients with relapsing AAV in whom remission was reinduced with rituximab. METHODS: RITAZAREM was an international randomised controlled, open-label, superiority trial that recruited 188 patients at the time of an AAV relapse from 29 centres in seven countries between April 2013 and November 2016. All patients received rituximab and glucocorticoids to reinduce remission. Patients achieving remission by 4 months were randomised to receive rituximab intravenously (1000 mg every 4 months, through month 20) (85 patients) or azathioprine (2 mg/kg/day, tapered after month 24) (85 patients) and followed for a minimum of 36 months. The primary outcome was time to disease relapse (either major or minor relapse). RESULTS: Rituximab was superior to azathioprine in preventing relapse: HR 0.41; 95% CI 0.27 to 0.61, p<0.001. 19/85 (22%) patients in the rituximab group and 31/85 (36%) in the azathioprine group experienced at least one serious adverse event during the treatment period. There were no differences in rates of hypogammaglobulinaemia or infection between groups. CONCLUSIONS: Following induction of remission with rituximab, fixed-interval, repeat-dose rituximab was superior to azathioprine for preventing disease relapse in patients with AAV with a prior history of relapse. TRIAL REGISTRATION NUMBER: NCT01697267; ClinicalTrials.gov identifier