Summary of the systems prioritization method (SPM) as a decision-aiding tool for the Waste Isolation Pilot Plant

In March 1994, the Department of Energy Carlsbad Area Office (DOE/CAO) implemented a performance-based planning method to assist in programmatic prioritization within the Waste Isolation Pilot Plant (WIPP) project with respect to applicable Environmental Protection Agency (EPA) long-term performance requirements stated in 40 CFR 191.13(a) and 40 CFR 268.6. This method, the Systems Prioritization Method (SPM), was designed by Sandia National Laboratories (SNL) to: (1) identify programmatic options (activities) and their costs and durations; (2) analyze potential combinations of activities in terms of predicted contribution to long-term performance; and (3) analyze cost, duration, and performance tradeoffs. SPM results were the basis for recommendations to DOE/CAO in May 1995 for prioritization within the WIPP project. This paper presents a summary of the SPM implementation, key results, and lessons learned

The 1999 cryptosporidium risk assessment exercise in England and Wales : a groundwater overview

Regulations Introduced in 1999 obliged water companies In England and Wales to conduct risk assessments of their treatment works to establish whether there was a significant risk from Cryptosporidium oocysts in the water supplied. More than 330 treatment works were identified as being at risk, just over half of which were plants treating groundwater. This paper provides an overview of what water companies themselves identified as the most at-risk settings for their groundwater-based works in terms of aquifer and type of supply. Evaluation of results from the subsequent continuous monitoring regulatory regime that came into force on many of these supplies could validate the primarily qualitative nature of the initial assessments of at-risk settings. There would also be public health benefits from confirmation of whether currently-employed risk assessment methods are well-founded because similar procedures could then be applied with confidence to the many small private supplies In Britain

Comparison of the pharmacokinetics of two dosage regimens of linezolid in multidrug-resistant and extensively drug-resistant tuberculosis patients.

Item does not contain fulltextBACKGROUND AND OBJECTIVES: For the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB), potent new drugs are urgently needed. Linezolid is a promising drug, but its use is limited by adverse effects with prolonged administration of 600 mg twice daily. In order to reduce its adverse effects and maintain efficacy, we investigated whether linezolid in a reduced dosage resulted in drug serum concentrations exceeding a ratio of the in vitro minimum inhibitory concentration (MIC) to the area under the serum concentration-time curve (AUC) over 24 hours (AUC(24)) [AUC(24)/MIC] of >100. PATIENTS AND METHODS: This open-label, prospective pharmacokinetic study evaluated two doses (300 and 600 mg) of linezolid in MDR-TB patients, who received linezolid as part of their treatment. They received linezolid 300 mg twice daily for 3 days, followed by 600 mg twice daily. Blood samples taken at predefined intervals for measuring serum linezolid concentrations were processed by a validated liquid chromatography-tandem mass spectrometry procedure. The AUC(24)/MIC ratio was used as a predictive model of efficacy. Adverse effects of linezolid, including peripheral neuropathy, were evaluated by clinical and laboratory assessments. RESULTS: Eight patients were included in this study. The median duration of linezolid treatment was 56 days (interquartile range [IQR 44-82] days), with a median cumulative dose of 51,000 mg (IQR 33,850-60,450 mg). The median linezolid AUC over 12 hours (AUC(12)) values were 57.6 mg x h/L (IQR 38.5-64.2 mg x h/L) with the 300 mg dose and 145.8 mg x h/L (IQR 101.2-160.9 mg x h/L) with the 600 mg dose. The AUC(24)/MIC ratios were 452 (IQR 343-513) with the 300 mg dose and 1151 (IQR 656-1500) with the 600 mg dose. Linezolid was well tolerated. CONCLUSION: Seemingly effective serum concentrations were reached after 3 days of administration of linezolid 300 mg twice daily, i.e. the AUC(24)/MIC ratio was at least 100 in 7 of 8 patients. Larger numbers of patients should be studied to confirm the efficacy of the linezolid 300 mg twice-daily dosage in MDR-TB or XDR-TB treatment.1 augustus 201