Determining a sustainable and economically optimal wastewater treatment and discharge strategy.

Options for treatment and discharge of wastewater in regional Western Australia (WA) are examined from the perspective of overall sustainability and social net benefit. Current practice in the state has typically involved a basic standard of treatment deemed to be protective of human health, followed by discharge to surface water bodies. Community and regulatory pressure to move to higher standards of treatment is based on the presumption that a higher standard of treatment is more protective of the environment and society, and thus is more sustainable. This analysis tests that hypothesis for Western Australian conditions. The merits of various wastewater treatment and discharge strategies are examined by quantifying financial costs (capital and operations), and by monetising the wider environmental and social costs and benefits of each option over an expanded planning horizon (30 years). Six technical treatment-disposal options were assessed at a test site, all of which met the fundamental criterion of protecting human health. From a financial perspective, the current business-as-usual option is preferred - it is the least cost solution. However, valuing externalities such as water, greenhouse gases, ecological impacts and community amenity, the status quo is revealed as sub-optimal. Advanced secondary treatment with stream disposal improves water quality and provides overall net benefit to society. All of the other options were net present value (NPV) negative. Sensitivity analysis shows that the favoured option outperforms all of the others under a wide range of financial and externality values and assumptions. Expanding the findings across the state reveals that moving from the identified socially optimal level of treatment to higher (tertiary) levels of treatment would result in a net loss to society equivalent to several hundred million dollars. In other words, everyone benefits from improving treatment to the optimum point. But society, the environment, and the Corporation are all worse off when treatment levels are pushed beyond what is economic and sustainable.

The infrared reflex: a potential new method for congenital cataract screening.

OBJECTIVE: To compare the accuracy of infrared (IR)-reflex assessment using a prototype imaging device to standard non-mydriatic red-reflex screening with direct ophthalmoscope (DO) in the diagnosis of neonatal and childhood cataract. METHODS: The comparison of the techniques was made in two distinct cohorts: in the first, newborns underwent IR and red-reflex testing by a medical student, with results compared to a reference red-reflex examination by an experienced midwife. In the second, an enriched cohort of children attending a specialist paediatric ophthalmology clinic had IR and red-reflex testing by a medical student to reference examination by a paediatric ophthalmologist. The medical students were considered inexperienced screeners due to their limited exposure to ophthalmology. The sensitivity and specificity of the IR and red-reflex assessments in respect to reference examination were calculated. Diagnostic accuracy was compared in Caucasian and non-Caucasian eyes. RESULTS: IR and red-reflex imaging were possible in all 180 neonatal eyes examined. A total of 5% of newborn eyes were found to have embryological remnants in the anterior segment of the eye with IR-reflex imaging which were not detected on reference red-reflex examination. IR-reflex assessment had significantly better sensitivity (100 vs 71%, p < 0.05) and specificity (100 vs 63%, p < 0.01) than red-reflex assessment in the diagnosis of childhood cataract. Red-reflex specificity was particularly poor in non-Caucasian eyes compared to Caucasian eyes (32 vs 72%, p < 0.05). CONCLUSION: This pilot study indicates that IR-reflex imaging has the potential to improve the diagnostic accuracy of eye screening for cataract by inexperienced healthcare staff, particularly in non-Caucasian children.

Blockade of the platelet P2Y12 receptor by AR-C69931MX sustains coronary artery recanalization and improves the myocardial tissue perfusion in a canine thrombosis model.

OBJECTIVE: Reperfusion therapy for myocardial infarction is limited by a significant reocclusion rate and less optimal myocardial tissue perfusion due to excessive platelet accumulation and recruitment at the sites of vascular injury. We assessed the influence of a selective P2Y(12)-receptor antagonist (AR-C69931MX), in conjunction with thrombolytic therapy, on the prevention of platelet aggregation and thrombus formation. METHODS AND RESULTS: A canine coronary electrolytic injury thrombosis model was used. Tissue-type plasminogen activator (t-PA; 1 mg/kg in phase I, 0.5 mg/kg in phase II in the AR-C69931MX group, and 1 mg/kg in the placebo group in phase I and II) was administered 30 minutes after thrombus formation; either saline or AR-C69931MX (4 micro g x kg(-1) x min(-1)) was given to all animals intravenously 10 minutes before t-PA administration for a total of 2 hours. All animals received heparin (80 U/kg) as an intravenous bolus followed by a continuous infusion of 17 U x kg(-1) x h(-1). Myocardial tissue perfusion was evaluated by use of the colored microsphere technique and real-time myocardial contrast echocardiography. The incidences of reocclusion and cyclic flow variation were significantly decreased in the AR-C69931MX group (P<0.05). Myocardial tissue flow with AR-C69931MX treatment improved significantly at 20 and 120 minutes after reflow, whereas tissue flow with placebo remained at a level similar to that during occlusion (P<0.05). CONCLUSIONS: The adjunctive administration of AR-C69931MX blocked ADP-mediated platelet aggregation and recruitment and prevented platelet-mediated thrombosis, resulting in prolongation of reperfusion time and a decrease in reocclusion and cyclic flow variations. Importantly, myocardial tissue perfusion was significantly improved in the P2Y(12) antagonist group.

From ATP to AZD6140: the discovery of an orally active reversible P2Y12 receptor antagonist for the prevention of thrombosis.

Starting from adenosine triphosphate (ATP), the identification of a novel series of P2Y(12) receptor antagonists and exploitation of their SAR is described. Modifications of the acidic side chain and the purine core and investigation of hydrophobic substituents led to a series of neutral molecules. The leading compound, 17 (AZD6140), is currently in a large phase III clinical trial for the treatment of acute coronary syndromes and prevention of thromboembolic clinical sequelae.

Preclinical and clinical studies with selective reversible direct P2Y12 antagonists.

An important role for adenosine diphosphate (ADP)-induced platelet activation and aggregation was proposed more than 40 years ago. The clinical use of clopidogrel, a prodrug of an irreversible P2Y (12) antagonist, has further proved the relevance of inhibiting signaling via the platelet-specific P2Y (12) ADP receptor in the prevention of cardiovascular events. Pharmacological studies at AstraZeneca R&D Charnwood have identified direct, selective, and competitive P2Y (12) antagonists, including cangrelor (also known as AR-C69931MX), which is suitable for intravenous administration, and AZD6140, which is suitable for oral administration. In preclinical use, these compounds predictably and effectively inhibited platelet aggregation without significant increases in bleeding time. In clinical use, these compounds may have significant advantages over current antiplatelet agents. This article summarizes preclinical and clinical data on cangrelor and AZD6140 and discusses the potential of these compounds as novel antiplatelet therapies.