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Contamination of water systems can not only entail high risks to human health but can also result in economic losses due to closure of beaches and shellfish harvesting areas. Understanding the origin of fecal pollution at locations where shellfish are grown is essential in assessing associated health risks&mdash, as well as the determining actions necessary to remedy the problem. The aim of this work is to identify the species-specific source(s) of fecal contamination impacting waters overlying the shellfisheries in the Blackwater Estuary, East Anglia, UK. Over a twelve-month period, water samples were taken from above the oysters and from a variety of upstream points considered to be likely sources of fecal microorganism, together with oyster samples, and the number of fecal streptococci and E. coli were determined. Transition from low to high tide significantly decreased the concentration of fecal streptococci in waters overlying the oyster beds, indicative of a freshwater input of fecal pollution in oyster bed waters. In 12 months, the number of E. coli remained constant throughout, while fecal streptococci numbers were generally higher in the winter months. Analyses of upstream samples identified a sewage outfall to be the main source of E. coli to the oyster beds, with additional fecal streptococci from agricultural sources. The findings may assist in developing approaches for assessing the risks to shellfishery industries of various fecal inputs into an estuary, which could then help local governmental authorities address the problem.

Aim To assess the efficacy and safety of everolimus in patients with metastatic renal cell carcinoma (mRCC) who failed one or two anti-VEGF therapies. Patients and methods Data from four prospective, non-interventional studies conducted in Germany, France, Greece and Austria were pooled for this analysis. Patients with mRCC of any histology (clear cell or non-clear cell) were included. VEGF-refractory patients received everolimus 10 mg/day until disease progression or unacceptable toxicity. The primary objective was to determine everolimus efficacy as measured by time to progression (TTP; from baseline to progression). Results The overall population comprised 632 patients; 493 patients received everolimus in the second-line setting. Most patients were of favourable/intermediate MSKCC risk (91%), had clear cell mRCC (89%), and had undergone nephrectomy (89%). Median TTP was 6.3 months (95% confidence interval [CI], 5.9–6.8) for the overall population and 6.4 months (95% CI, 5.8–6.9) for the second-line everolimus population. Similarly, median progression-free survival was 5.5 months (95% CI, 5.0–6.1) for the overall population and 5.8 months (95% CI, 5.0–6.4) for second-line everolimus population. Best tumour response (n = 349) was complete or partial remission in 12% of patients and stable disease in 59% of patients. Overall population median overall survival (OS) was 11.2 months (95% CI, 9.0–not reached). Commonly reported adverse events (AEs) (any grade) were stomatitis (25%), anaemia (15%) and asthenia (11%). Conclusions Results of this pooled analysis provide evidence of safety and effectiveness of second-line everolimus in routine clinical use and support everolimus as a standard of care for VEGF-refractory patients with mRCC.