Three decades of trace element sediment contamination: the mining of governmental databases and the need to address hidden sources for clean and healthy seas

peer reviewedTrace elements (TEs) frequently contaminate coastal marine sediments with many included in priority chemical lists or control legislation. These, improved waste treatment and increased recycling have fostered the belief that TE pollution is declining. Nevertheless, there is a paucity of long-term robust datasets to support this confidence. By mining UK datasets (100s of sites, 31 years), we assess sediment concentrations of arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe), mercury (Hg), nickel (Ni), lead (Pb) and zinc (Zn) and use indices (PI [Pollution], TEPI [Trace Element Pollution] and Igeo [Geoaccumulation]) to assess TE pollution evolution. PI and TEPI show reductions of overall TE pollution in the 1980s then incremental improvements followed by a distinct increase (2010–13). Zn, As and Pb Igeo scores show low pollution, whilst Cd and Hg are moderate, but with all remaining temporally stable. Igeo scores are low for Ni, Fe and Cr, but increasing for Ni and Fe. A moderate pollution Igeo score for Cu has also steadily increased since the mid-1990s. Increasing site trends are not universal and, conversely, minimal temporal change masks some site-specific increases and decreases. To capture this variability we strongly advocate embedding sufficient sentinel sites within observation networks. Decreasing sediment pollution levels (e.g. Pb and Hg) have been achieved, but stabilizing Igeo and recently increasing TEPI and PI scores require continued global vigilance. Increasing Ni and Fe Igeo scores necessitate source identification, but this is a priority for Cu. Local, regional and world analyses indicate substantial ‘hidden’ inputs from anti-fouling paints (Cu, Zn), ship scrubbers (Cu, Zn, Ni) and sacrificial anodes (Zn) that are also predicted to increase markedly. Accurate TE input assessments and targeted legislation are, therefore, urgently required, especially in the context of rapid blue economic growth (e.g. shipping).Channel Catchments Cluster (3C) programm

Data on elemental concentrations in marine sediments from the South and South West of England

peer reviewedThe present Data In Brief methodological paper details the acquisition, mining and pre-processing of elemental concentration data in marine sediments (coastal and open sea) of Southern England, presented and discussed in the co-submitted Environment International paper entitled: “Three decades of trace element sediment contamination: the mining of governmental databases and the need to address hidden sources for clean and healthy seas” [1]. Elemental sediment concentration data were obtained from the two main UK environmental sources, i.e. the Environment Agency (EA) and the Marine Environment Monitoring and Assessment National database (MERMAN) managed by the British Oceanographic Data Centre (BODC). The merged database is the result of a rigorous data selection-validation process and provides spatially and temporally extensive records of arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe), mercury (Hg), nickel (Ni), lead (Pb) and zinc (Zn) concentrations for hundreds of sites over 31 years (1983-2013). More spatially and temporally limited records of manganese (Mn), aluminium (Al), lithium (Li), tin (Sn) [and tributyltin, TBT], barium (Ba), antimony (Sb), boron (B), calcium (Ca), molybdenum (Mo), cobalt (Co), selenium (Se), potassium (K), magnesium (Mg), beryllium (Be), vanadium (V), titanium (Ti), sodium (Na), silver (Ag), thallium (Tl) and strontium (Sr) are also included. The full secondary database is hosted in the Mendeley Data repository and the geo-spatial information to map sites is given in supplementary files to the paper. To provide end-users with the relevant context on spatial and temporal coverage, monitoring statistics are given for the nine trace elements (TEs). Site-specific statistics include: the first and last year of sediment monitoring, the number of years monitored, and minimum, maximum, mean and median numbers of years monitored. Also given are summary data on the number of sites monitored each year, from the first records from 1983 to 2013. For the nine TEs (total and strong acid digestion techniques are considered separately for Cr and Fe), monitoring statistics are presented separately for coastal and open sea sites. Data are relevant to diverse end-users to assess the local and regional contaminant loads and to contextualize anthropogenic threats to benthic systems in multiple locations from the, French/English Channel, southern North and Celtic Seas.Channel Catchments Cluster (3C) programm

Neuroendocrine carcinoma arising in soft tissue: three case reports and literature review

<p>Abstract</p> <p>Background</p> <p>Neuroendocrine tumours (NET) are tumours arising from neuroendocrine cells of neural crest origin. They are characterised by the presence of neurosecretory granules which react positively to silver stains and to specific markers including neuron specific enolase, synaptophysin and chromogranin. Metastasis to the skin occurs infrequently but primary soft tissue NET is excessively rare.</p> <p>Case presentation</p> <p>We report our experience with 3 such cases. In the first case, the NET originated in muscle and was treated with wide surgical excision and adjuvant radiotherapy. The second case presented as a subcutaneous mass in the foot and the tumour was positive on ¹²³I mIBG scan. She has had prolonged recurrence-free survival following primary hypo-fractionated radiotherapy. In the third case, a cutaneous nodule proved to be a NET and at surgery, lymph node disease was present. He has remained disease-free after surgical excision without the need for external beam radiotherapy.</p> <p>Conclusion</p> <p>These tumours appear to have a good prognosis. Complete excision offers potentially curative treatment. Adjuvant radiotherapy may be helpful when the tumour margin is narrow. For patients with unresectable disease or where surgery would not be appropriate, radiotherapy appears to be an effective therapeutic option.</p

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

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

PET/CT features of lung SABR chest wall toxicity

Stereotactic ablative radiotherapy offers a radical treatment approach for early stage lung cancers and an aggressive local therapy for pulmonary oligometastases from other tumour sites. Chest wall toxicity is one of the key dose-limiting toxicities for intrathoracic stereotactic treatments. The description of stereotactic radiotherapy chest wall toxicity using functional imaging has not been reported previously. A 56-year-old male received 60 Gy in 8 fractions delivered by volumetric modulated arc therapy for a T1bN0M0 clinical left upper lobe lung cancer. The past medical history included poorly controlled type 1 diabetes mellitus, severe peripheral vascular disease and obesity. The patient attended 9 months later with left-sided, slowly progressive chest pain. An 18 FDG PET/CT performed in order to investigate contralateral pulmonary lesions revealed FDG-avid focal thickening at the left superio-lateral thoracic wall with overlying inflammatory stranding in keeping with an indolent inflammatory process. Chest wall toxicity may present as pain, swelling, fracture and skin changes, and has the 18 FDG PET/CT chjmirocteristics of an inflammatory process. Patients with risk factors for chest wall toxicity, such as obesity, diabetes and smoking should be informed of their higher propensity for this clinically significant treatment side effect. For patients developing chest wall toxicity as demonstrated in this case with associated functional imaging findings, anti-inflammatory treatment should be promptly commenced