Method design and validation for the determination of uranium levels in human urine using high-resolution alpha spectrometry

Quantification of uranium in human urine is a valuable technique for assessing occupational and public exposure to uranium. A reliable method has been developed and validated in the ARPANSA Radiochemistry Laboratory by means of standard radiochemical separation and purification techniques and measurement using high-resolution alpha spectrometry. This method can be used to evaluate the levels of naturally occurring ²³⁴U, ²³⁵U and ²³⁸U in urine. Method design and validation is the process of defining an analytical requirement, and then confirming that the method under consideration has performance capabilities consistent with what the application requires. The method was designed to measure levels down to 2 mBq/day of total uranium, corresponding to approximately 1/100th of the annual committed effective dose of 20 mSv. Validation tests were developed to assess selectivity, accuracy, recovery and quantification of uncertainty. The radiochemical recovery of this method was measured using ²³²U tracer. The typical minimum detectable concentration for total uranium for 24-h urine samples is approximately 0.6 mBq/day or 0.019 μg/day.

MSP119 miniproteins can serve as targets for invasion inhibitory antibodies in plasmodium falciparum provided they contain the correct domains for cell surface trafficking.

Antibodies from malaria-exposed individuals can agglutinate merozoites released from Plasmodium schizonts, thereby preventing them from invading new erythrocytes. Merozoite coat proteins attached to the plasma membrane are major targets for host antibodies and are therefore considered important malaria vaccine candidates. Prominent among these is the abundant glycosylphosphatidylinositol (GPI)-anchored merozoite surface protein 1 (MSP1) and particularly its C-terminal fragment (MSP1(19)) comprised of two epidermal growth factor (EGF)-like modules. In this paper, we revisit the role of agglutination and immunity using transgenic fluorescent marker proteins. We describe expression of heterologous MSP1(19)'miniproteins' on the surface of Plasmodium falciparum merozoites. To correctly express these proteins, we determined that GPI-anchoring and the presence of a signal sequence do not allow default export of proteins from the endoplasmic reticulum to merozoite surface and that extra sequence elements are required. The EGFs are insufficient for correct trafficking unless they are fused to additional residues that normally reside upstream of this fragment. Antibodies specifically targeting the surface-expressed miniprotein can inhibit erythrocyte invasion in vitro despite the presence of endogenous MSP1. Using a line expressing a green fluorescent protein-MSP1 fusion protein, we demonstrate that one mode of inhibition by antibodies targeting the MSP1(19) domain is the rapid agglutinating of merozoites prior to erythrocyte attachment.

Sources of Sodium in Australian children's diets and the effect of the application of sodium targets to food products to reduce sodium intake

The average reported dietary Na intake of children in Australia is high: 2694 mg/d (9–13 years). No data exist describing food sources of Na in Australian children's diets and potential impact of Na reduction targets for processed foods. The aim of the present study was to determine sources of dietary Na in a nationally representative sample of Australian children aged 2–16 years and to assess the impact of application of the UK Food Standards Agency (FSA) Na reduction targets on Na intake. Na intake and use of discretionary salt (note: conversion of salt to Na, 1 g of NaCl (salt) = 390 mg Na) were assessed from 24-h dietary recall in 4487 children participating in the Australian 2007 Children's Nutrition and Physical Activity Survey. Greatest contributors to Na intake across all ages were cereals and cereal-based products/dishes (43 %), including bread (13 %) and breakfast cereals (4 %). Other moderate sources were meat, poultry products (16 %), including processed meats (8 %) and sausages (3 %); milk products/dishes (11 %) and savoury sauces and condiments (7 %). Between 37 and 42 % reported that the person who prepares their meal adds salt when cooking and between 11 and 39 % added salt at the table. Those over the age of 9 years were more likely to report adding salt at the table (χ2 199·5, df 6, P < 0·001). Attainment of the UK FSA Na reduction targets, within the present food supply, would result in a 20 % reduction in daily Na intake in children aged 2–16 years. Incremental reductions of this magnitude over a period of years could significantly reduce the Na intake of this group and further reductions could be achieved by reducing discretionary salt use.

Significant challenges remain to achieve risk reduction targets for cardiovascular secondary prevention and diabetes

Objective: To examine population-level evidence treatment gaps for cardiovascular risk among rural patients with existing cardiovascular disease or diabetes.

Methods: Three population surveys were undertaken in the Greater Green Triangle region of southeastern Australia 2004-2006. Adults aged 25-84 yrs were randomly selected using age/sex stratified electoral role samples. A representative 1690 participants were recruited (48% participation rate). Anthropometric, clinical and self-administered questionnaire chronic disease risk data were collected in accordance with the WHO MONICA protocol. Detailed investigation of cardiovascular and diabetes history, key cardiovascular risk factors, medication use and health behaviours were included.

Results: After adjusting for age and sex, an estimated 12% (sample n=272) of the population had one or more of coronary heart disease, stroke, or diabetes. Blood pressure was at target (<130/80 mmHg) for 26% of these individuals, and 61% were treated with antihypertensive medications. Lipid targets were achieved by 17% for total cholesterol (<4 mmol/L), 18% for LDL cholesterol (<2 mmol/L), 77% for HDL cholesterol (>1.0 mmol/L) and 44% for triglycerides (<1.5 mmol/L); overall 6% achieved all four lipid targets and 60% reported use of lipid-lowering therapy, including 51% overall using statins. Ten percent were current smokers, and four in every five patients (82%) had suboptimal BMI (outside the range 18.5 - 25.0).

Conclusions: All participants with uncontrolled blood pressure and most with uncontrolled lipids should be taking medications. The magnitude of evidence treatment gaps suggests existing models of care need fundamental reform and renewed focus on prevention.

Lift aim on poor targets, universities told

Commonwealth government participation targets for students from poor backgrounds should be extended beyond undergraduates to include postgraduate and research students, according to a visiting participation expert from Britain.

KHA-CARI guideline : biochemical and haematological targets : haemoglobin concentrations in patients using erythropoietin-stimulating agents

This is an update of a previous CARI Guideline on management of anaemia in CKD patients.

New drug targets in depression : inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates—Nrf2 activators and GSK-3 inhibitors

This paper reviews new drug targets in the treatment of depression and new drug candidates to treat depression. Depression is characterized by aberrations in six intertwined pathways: (1) inflammatory pathways as indicated by increased levels of proinflammatory cytokines, e.g. interleukin-1 (IL-1), IL-6, and tumour necrosis factor α. (2) Activation of cell-mediated immune pathways as indicated by an increased production of interferon γ and neopterin. (3) Increased reactive oxygen and nitrogen species and damage by oxidative and nitrosative stress (O&NS), including lipid peroxidation, damage to DNA, proteins and mitochondria. (4) Lowered levels of key antioxidants, such as coenzyme Q10, zinc, vitamin E, glutathione, and glutathione peroxidase. (5) Damage to mitochondria and mitochondrial DNA and reduced activity of respiratory chain enzymes and adenosine triphosphate production. (6) Neuroprogression, which is the progressive process of neurodegeneration, apoptosis, and reduced neurogenesis and neuronal plasticity, phenomena that are probably caused by inflammation and O&NS. Antidepressants tend to normalize the above six pathways. Targeting these pathways has the potential to yield antidepressant effects, e.g. using cytokine antagonists, minocycline, Cox-2 inhibitors, statins, acetylsalicylic acid, ketamine, ω3 poly-unsaturated fatty acids, antioxidants, and neurotrophic factors. These six pathways offer new, pathophysiologically guided drug targets suggesting that novel therapies could be developed that target these six pathways simultaneously. Both nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activators and glycogen synthase kinase-3 (GSK-3) inhibitors target the six above-mentioned pathways. GSK-3 inhibitors have antidepressant effects in animal models of depression. Nrf2 activators and GSK-3 inhibitors have the potential to be advanced to phase-2 clinical trials to examine whether they augment the efficacy of antidepressants or are useful as monotherapy.

Reducing risk in coronary artery disease. Are Australian patients in general practice achieving targets? The coronary artery disease in general practice study (CADENCE)

Background The benefits of secondary preventive measures for stable coronary artery disease are well established and risk factor treatment targets are defined.

Aim The aim of this study was to examine Australian general practitioners' (GP) perception and management of risk factors in chronic stable angina patients in primary care.

Methods Using a cluster-stratified design, 2031 consecutive stable angina patients were recruited between October 2006 and March 2007 by 207 GP who documented their risk factors and reported if they were optimally controlled.

Results Among the patients, 93% had objective evidence of coronary artery disease and 63% were male, and mean age was 71 ± 11 years. Based upon national guidelines, recommended targets were achieved in: 60% for blood pressure, 24% for body mass index, 23% for waist circumference, 17% for lipid profiles (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides) and 54% of diabetics for haemoglobin A1c. However, GP perceived risk factors to be ‘optimally controlled’ in: 86% for blood pressure (kappa statistic (κ) = 0.37), 44% for weight (κ = 0.3), 70% for lipids (κ = 0.20) and 60% for haemoglobin A1c (κ = 0.74).

Conclusions In this representative cohort of chronic stable angina patients attending GP, cardiovascular risk factor control was frequently suboptimal despite being perceived as satisfactory by the clinicians. New strategies that raise awareness and address this treatment gap need to be implemented.

A-REIT bidder returns : an evaluation of public and private targets and method of payment

This study examines the wealth effects of fifty-six Australian Real Estate Investment Trusts (A-REITS) acquirers around the announcement date of a merger and acquisition over the period of 1996 to 2010. This study extends Ratcliffe et al (2009) by examining mergers and acquisitions of private entity targets as well as public targets and confirms recent US REIT work in this field. Utilising event study methodology we find that bidding A-REITs earn positive and significant cumulative abnormal returns (CARs) of +0.966% around the three-day announcement period [-1, +1]. Analysis also indicates bidding firms earn higher CARs when the acquisition is financed by scrip and/or a combination of scrip and cash. Consistent with prior REIT research, event study results show that A-REIT acquirers earn higher excess returns when the target is private as compared to a public target, +2.834% and +0.457% respectively. Further investigation, employing regression analysis, shows book-to-market ratio has a negative impact on bidding firms CARs, suggesting that investors penalise high book-to-market A-REITs in an M&A due to their higher risk characteristics. We also find that both specialisation by property type and relative size of the bidder compared to the target has a positive and significant influence on bidder excess returns. Finally, our results show support for the method of payment findings in the event study, with method of payment returning a negative and significant impact on the bidder CARs.