Splanchnic blood flow and hepatic glucose production in exercising humans : role of renin-angiotensin system

The study examined the implication of the renin-angiotensin system (RAS) in regulation of splanchnic blood flow and glucose production in exercising humans. Subjects cycled for 40 min at 50% maximal O2 consumption (VO2 max) followed by 30 min at 70% VO2 max either with [angiotensin-converting enzyme (ACE) blockade] or without (control) administration of the ACE inhibitor enalapril (10 mg iv). Splanchnic blood flow was estimated by indocyanine green, and splanchnic substrate exchange was determined by the arteriohepatic venous difference. Exercise led to an ~20-fold increase (P < 0.001) in ANG II levels in the control group (5.4 ± 1.0 to 102.0 ± 25.1 pg/ml), whereas this response was blunted during ACE blockade (8.1 ± 1.2 to 13.2 ± 2.4 pg/ml) and in response to an orthostatic challenge performed postexercise. Apart from lactate and cortisol, which were higher in the ACE-blockade group vs. the control group, hormones, metabolites, VO2, and RER followed the same pattern of changes in ACE-blockade and control groups during exercise. Splanchnic blood flow (at rest: 1.67 ± 0.12, ACE blockade; 1.59 ± 0.18 l/min, control) decreased during moderate exercise (0.78 ± 0.07, ACE blockade; 0.74 ± 0.14 l/min, control), whereas splanchnic glucose production (at rest: 0.50 ± 0.06, ACE blockade; 0.68 ± 0.10 mmol/min, control) increased during moderate exercise (1.97 ± 0.29, ACE blockade; 1.91 ± 0.41 mmol/min, control). Refuting a major role of the RAS for these responses, no differences in the pattern of change of splanchnic blood flow and splanchnic glucose production were observed during ACE blockade compared with controls. This study demonstrates that the normal increase in ANG II levels observed during prolonged exercise in humans does not play a major role in the regulation of splanchnic blood flow and glucose production.

Evidence based drug therapy : are optimal doses and multiple medication therapies realistic in patients with chronic heart failure

Background: Chronic Heart Failure (CHF) has a high mortality and morbidity. Large scale randomised controlled trials have proven the benefits of beta blockade and ACE inhibitors in reducing mortality in patients with CHF and expert guidelines mandate their use. In spite of these recommendations, important therapies are under-prescribed and under-utilised.

Method: 1015 consecutive patients enrolled in CHF management programs across Australia were surveyed during 2005-2006 to determine prescribing patterns in heart failure medications. These patients were followed-up for a period of 6 months.

Results: The survey revealed that beta blockers were prescribed to 80% of patients (more than 85% were on sub-optimal doses) and 70% were prescribed Angiotensin converting enzyme (ACE) inhibitors (approximately 50% were on sub-optimal dose). 19% of patients were prescribed Angiotensin receptor blockers (ARBs). By 6 months <25% of the patients who were on sub-optimal dose beta blockers or ACE inhibitors at baseline, had been up-titrated to maximum dose (p<0.0001). In CHF programs, were nurses were able to titrate medications, 75% of patients reached optimal dose of beta blockers compared to those programs with no nurse-led medication titration, where only 25% of patients reached optimal dose (p<0.004). When examining optimal dosage for any two of these mandatory medications, less patients were on optimal therapy. Beta blockers and ACE inhibitors, were both prescribed in combination in 60% of patients. While beta blockers and ARBs were prescribed to 15% of patients.

Conclusion: Whilst prescribing rates for a single medication strategy of beta blockers, or ACE inhibitors were greater than 70%, an increase in dosage of these medications and utilisation of proven combination therapy of these medications was poor. It is suggested that clinical outcomes for this cohort of patients could be further improved by adherence to evidence-based practice, ESC guidelines, and optimisation of these medications by heart failure nurses in a CHF program. On the basis of these findings and in the absence of ready access to a polypill, focussing on evidence-based practice to increase utilisation and optimal dosage of combination medication therapy is critical.

Cost-effectiveness of a family-based GP-mediated intervention targeting overweight and moderately obese children

Objective
 To assess from a societal perspective the incremental cost-effectiveness of a family-based GP-mediated intervention targeting overweight and moderately obese children. The intervention was modelled on the LEAP (live, eat and play) trial, a randomised controlled trial conducted by the Centre for Community Child Health, Melbourne, Australia in 2002–2003. This study was undertaken as part of the assessing cost-effectiveness (ACE) in obesity project which evaluated, using consistent methods, 13 interventions targeting unhealthy weight gain in children and adolescents.
Method
A logic pathway was used to model the effects of the intervention compared to no intervention on body mass index (BMI) and health outcomes (disability-adjusted life years—DALYs). Disease costs and health benefits were tracked until the cohort of eligible children reached the age of 100 years or death. Simulation-modelling techniques were used to present a 95% uncertainty interval around the cost-effectiveness ratio. The intervention was also assessed against a series of filters (‘equity’, ‘strength of evidence’, ‘acceptability’, ‘feasibility’, sustainability’ and ‘side-effects’) to incorporate additional factors that impact on resource allocation decisions.
Results
The intervention, as modelled, reached 9685 children aged 5–9 years with a BMI z-score of ≥3.0, and cost $AUD6.3M (or $AUD4.8M excluding time costs). It resulted in an incremental saving of 2300 BMI units which translated to 511 DALYs. The cost-offsets stemming from the intervention totalled $AUD3.6M, resulting in a net cost per DALY saved of $AUD4670 (dominated; $0.1M) (dominated means intervention costs more for less effect).
Conclusion
Compared to a ‘no intervention’ control group, the intervention was cost-effective under current assumptions, although the uncertainty intervals were wide. A key question related to the long-term sustainability of the small incremental weight loss reported, based on the 9-month follow-up results for LEAP.

Priority setting in health: origins, description and application of the Australian Assessing Cost-Effectiveness initiative

This article reports on the ‘Assessing Cost–Effectiveness’ (ACE) initiative in priority setting from Australia. It commences with why priority setting is topical and notes that a wide variety of approaches are available. In assessing these various approaches, it is argued that a useful first step is to consider what constitutes an ‘ideal’ approach to priority setting. A checklist to guide priority setting is presented based on guidance from economic theory, ethics and social justice, lessons from empirical experience and the needs of decision-makers. The checklist is seen as an important contribution because it is the first time that criteria from such a broad range of considerations have been brought together to develop a framework for priority setting that endeavors to be both realistic and theoretically sound. The checklist will then be applied to a selection of existing approaches in order to illustrate their deficiencies and to provide the platform for explaining the unique features of the ACE approach. A case study (ACE-Cancer) will then be presented and assessed against the checklist, including reaction from stakeholders in the cancer field. The article concludes with an overview of the full body of ACE research completed to date, together with some reflections on the ACE experience.

Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance

In addition to its role in the storage of fat, adipose tissue acts as an endocrine organ, and it contains a functional renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE) plays a key role in the RAS by converting angiotensin I to the bioactive peptide angiotensin II (Ang II). In the present study, the effect of targeting the RAS in body energy homeostasis and glucose tolerance was determined in homozygous mice in which the gene for ACE had been deleted (ACE^-/-) and compared with wild-type littermates. Compared with wild-type littermates, ACE^-/- mice had lower body weight and a lower proportion of body fat, especially in the abdomen. ACE^-/- mice had greater fed-state total energy expenditure (TEE) and resting energy expenditure (REE) than wild-type littermates. There were pronounced increases in gene expression of enzymes related to lipolysis and fatty acid oxidation (lipoprotein lipase, carnitine palmitoyl transferase, long-chain acetyl CoA dehydrogenase) in the liver of ACE^-/- mice and also lower plasma leptin. In contrast, no differences were detected in daily food intake, activity, fed-state plasma lipids, or proportion of fat excrete in fecal matter. In conclusion, the reduction in ACE activity is associated with a decreased accumulation of body fat, especially in abdominal fat depots. The decreased body fat in ACE^-/- mice is independent of food intake and appears to be due to a high energy expenditure related to increased metabolism of fatty acids in the liver, with the additional effect of increased glucose tolerance.

Estimating impacts of consumer prices on house prices

Real estate is widely considered as a reliable hedge of inflation rate and there have been many literatures examining the inflation-hedging characteristics of the real estate.  The study described in the paper focuses on testing the significances of impacts of consumer price on house price in eight Australia's capital cities.  The Autoregressive Distributed Lag model is introduced to obtain  the estimates of the coefficient.  The significances of the impacts are defined as the accept probability of t statistics of the coefficients.  Analyses and comparisons of these significances suggested that the impacts of consumer prices on house prices depend on the inherent characteristics of cities. 

Cost-effectiveness of active transport for primary school children - Walking School Bus Program

Background : To assess from a societal perspective the incremental cost-effectiveness of the Walking School Bus (WSB) program for Australian primary school children as an obesity prevention measure. The intervention was modelled as part of the ACE-Obesity study, which evaluated, using consistent methods, thirteen interventions targeting unhealthy weight gain in Australian children and adolescents.

Methods : A logic pathway was used to model the effects on body mass index [BMI] and disability-adjusted life years [DALYs] of the Victorian WSB program if applied throughout Australia. Cost offsets and DALY benefits were modelled until the eligible cohort reached 100 years of age or death. The reference year was 2001. Second stage filter criteria ('equity', 'strength of evidence', 'acceptability', feasibility', sustainability' and 'side-effects') were assessed to incorporate additional factors that impact on resource allocation decisions.

Results : The modelled intervention reached 7,840 children aged 5 to 7 years and cost $AUD22.8M ($16.6M;$30.9M). This resulted in an incremental saving of 30 DALYs (7:104) and a net cost per DALY saved of $AUD0.76M ($0.23M; $3.32M). The evidence base was judged as 'weak' as there are no data available documenting the increase in the number of children walking due to the intervention. The high costs of the current approach may limit sustainability.

Conclusions : Under current modelling assumptions, the WSB program is not an effective or cost-effective measure to reduce childhood obesity. The attribution of some costs to non-obesity objectives (reduced traffic congestion and air pollution etc.) is justified to emphasise the other possible benefits. The program's cost-effectiveness would be improved by more comprehensive implementation within current infrastructure arrangements. The importance of active transport to school suggests that improvements in WSB or its variants need to be developed and fully evaluated.

Development of a salmon protein hydrolysate that lowers blood pressure

A salmon protein hydrolysate (SPH) was developed containing several angiotensin I-converting enzyme (ACE) inhibitory tripeptides the most abundant of which were Val-Leu-Trp, Val-Phe-Tyr, and Leu-Ala-Phe. Simulated digestion experiments showed that active constituents of SPH would survive in the digestive tract and be available for absorption into the bloodstream. In fact, ACE inhibitory activity was improved following simulated digestion suggesting that there were larger peptides in SPH that might contribute to bioactivity in vivo. A single oral dose (1,500 mg/kg body mass) of SPH significantly lowered blood pressure in spontaneously hypertensive rats (SHR). The treatment of SHR with either SPH fraction (<3,000 Da) or SPH fraction (>3,000 Da) reduced blood pressure. We conclude that the ability of SPH to lower blood pressure is due to a combination of ACE inhibitory tripeptides as identified, as well as additional unknown, peptide species that are generated during digestion of SPH in the gastrointestinal tract.

Do green and golden bell frogs (Litoria aurea) occupy habitats with fungicidal properties?

The Green and Golden Bell frog Litoria aureo is in major decline in Australia, where its distribution is now confined mainly to the east coast of New South Wales (NSW). Infection by the newly emerged amphibian fungal pathogen Batrachochytrium dendrobatidis has been identified as one of the main threats affecting L. aurea. Surprisingly, some of the sites in NSW sustaining the largest populations of this species are industrial and urban habitats that are often disturbed and polluted, which could protect L. aurea from chytrid infection if pollution had fungicidal capacity.The aim of this study was to characterise the trace metal concentration of several L. aurea breeding sites in the Sydney and IIlawarra regions of NSW and to evaluate the fungicidal efficacy of the main "'ace metals identified. Selected L. aurea sites were sampled throughout the breeding season (September to February) to establish the concentration of trace metals in both surface sediment and waters. Physico-chemical parameters including pH and salinity were also measured. Of the trace metals identified, copper and zinc were consistently elevated across sites. Over 50% of sites exceeded the National Sediment Quality Guideline for both copper and zinc concentration, and over 90% of sites exceeded the National Water Quality Guideline for these metals. Consequently, we evaluated their effect on the growth and survival of a laboratory culture of B. dendrobatidis,These tests were performed in media containing dissolved metal concentrations of 0.02 - 0.65 mgL^-1 Cu and 0.24 - 5.0 mgL^-1 Zn. Growth rates were inferred by total fungal density in liquid culture (based on spectral absorbance measurements), final dry weight, and the density of zoospores in fungal cultures grown for 28 days. Both copper and zinc were found to reduce the growth and proliferation of B. dendrobatidis, but in a non-linear manner. This suggests that L. aurea may be gaining some protection from B. dendrobatidis infection at several of the sites examined.

The cost-effectiveness of Australia's active after-school communities program

The objective of this study was to assess from a societal perspective the cost-effectiveness of the Active After-school Communities (AASC) program, a key plank of the former Australian Government's obesity prevention program. The intervention was modeled for a 1-year time horizon for Australian primary school children as part of the Assessing Cost-Effectiveness in Obesity (ACE-Obesity) project. Disability-adjusted life year (DALY) benefits (based on calculated effects on BMI post-intervention) and cost-offsets (consequent savings from reductions in obesity-related diseases) were tracked until the cohort reached the age of 100 years or death. The reference year was 2001, and a 3% discount rate was applied. Simulation-modeling techniques were used to present a 95% uncertainty interval around the cost-effectiveness ratio. An assessment of second-stage filter criteria ("equity," "strength of evidence," "acceptability to stakeholders," "feasibility of implementation," "sustainability," and "side-effects") was undertaken by a stakeholder Working Group to incorporate additional factors that impact on resource allocation decisions. The estimated number of children new to physical activity after-school and therefore receiving the intervention benefit was 69,300. For 1 year, the intervention cost is Australian dollars (AUD) 40.3 million (95% uncertainty interval AUD 28.6 million; AUD 56.2 million), and resulted in an incremental saving of 450 (250; 770) DALYs. The resultant cost-offsets were AUD 3.7 million, producing a net cost per DALY saved of AUD 82,000 (95% uncertainty interval AUD 40,000; AUD 165,000). Although the program has intuitive appeal, it was not cost-effective under base-case modeling assumptions. To improve its cost-effectiveness credentials as an obesity prevention measure, a reduction in costs needs to be coupled with increases in the number of participating children and the amount of physical activity undertaken.

Does monetary policy matter in a less developed economy? Evidence from Bangladesh

This paper explores the role of monetary policy in the context of a less developed economy. Monetary transmission mechanisms in less developed economies can be quite different from an industrialized economy, as unlike industrialized countries, these economies are characterized by the small size of organized financial markets, limited substitutability between money and other assets and weak fiscal and monetary institutions. We utilize the Structural VAR approach to analyze the monetary transmission process and impacts of monetary policy on different macro variables in Bangladesh. Monetary policy shocks are identified using non-recursive contemporaneous restrictions, which are based on the Central Bank's reaction function and the structure of the economy. We found strong evidence for the interest rate channel of monetary policy in Bangladesh. Our findings indicate that monetary policy shocks are important sources of fluctuations in the rate of interest, output and prices. Expansionary monetary policies are found to be harmful for achieving price stability in Bangladesh, as they not only increase the prices permanently, but also make the price level more volatile. We also found the evidence of a long lasting effect of monetary policy on output, which suggests that contractionary policy measures may create sustained recession in Bangladesh.

Approaches to the synthesis of peptide substituted frameworks

The 1,3 dipolar cycloaddition between carbonyl ylids (generated from cyclobutene epoxides flanked by esters) and norbornyl alkenes – the ACE reaction – offers a facile method for the construction of polynorbornyl molecular frameworks. This reaction has, as described in this dissertation, underpinned the construction of molecular frameworks that have peptides and amino acids attached. Such highly rigid peptide-frameworks are of use in the field of peptidomimetics; the template molecule governs the final positioning of any attached groups such that a precise arrangement of amino acids can be achieved without the need to construct entire proteins. In the course of any ACE reaction the ester flanked cyclobutene epoxide is transformed to a 1,3 dipole, the esters serve to stablise this reactive intermediate and are as a consequence incorporated in the reaction product. Modification of these esters provides pseudo-equatorial points for peptide attachment. These methyl esters were replaced with tert-butyl esters to provide pseudo-axial attachment points that could be selectively addressed. The optimal strategy for peptide-framework construction involved direct condensation of carboxyl protected amino acids to bicyclo[2.2.1]hept-5-ene-2-endo-carboxylic acid as well as condensation of amino acids to cyclobutene epoxides derived from this acid. The ACE reaction of (±) bicycloheptene-2-endo-carboxylic acid derivatives with cyclobutene epoxides synthesised from such racemic acid derivatives provided a mixture of enantiomers and meso compounds. In order to control the position of the attachment points – and hence the final location of the attached peptides – the ACE reaction required chiral starting materials. Accordingly, all peptidoframeworks were derived from the chiral (2S)-(-)-bicycloheptene carboxylic acid. The ACE reaction of this (S)-norbornene with the (S)-epoxide provided a peptide framework in which the attached amino acids were positioned pseudo-axially. Deprotection of the amino acid allowed peptide chain building in the pseudo-axial direction. Using this strategy a framework with an alanine residue and a triglycine peptide was synthesised. By combining this strategy with the ter-butyl ester variant a framework with pseudo-axial alanine and pseudo-equatorial glycine residues was manufactured.

Examining the development of the Victorian Certificate of Applied Learning and its implications for schools and teacher education in Australia

The Victorian Certificate of Applied Learning (VCAL) is a very successful senior secondary school qualification introduced in the Australian state of Victoria in 2002. Applied learning in the VCAL engages senior students in a combination of work-based learning, service-learning, and project-based learning and aims to provide them with the skills, knowledge, and attitudes to make informed choices regarding pathways to work and further education. The program has enjoyed rapid growth and its system-wide adoption by Victorian secondary schools, Technical and Further Education (TAFE) institutions, Registered Training Organizations (RTOs), and Adult and Community Education (ACE) providers has broadened significantly the range of senior schooling pathway options for young people. This paper will examine reasons for developing an applied learning senior secondary certificate and its rapid growth in Victoria since 2002. The authors draw on a number of case studies to profile the unique nature of applied learning in the VCAL, including its dimensions of service learning, work-based learning, and project-based learning. These case studies are also used to discuss a number of implications that have emerged from the use of applied learning in the VCAL, including approaches to teaching and assessment that will support applied learning and the development of new partnerships between VCAL providers and community partners. Finally, the paper considers significant implications the VCAL has created for teacher education in Victoria by discussing the new Graduate Diploma of Education (Applied Learning) developed by Deakin University.

Shifting shadows in postmodern communities

Postmodern society frequently presents new technologies and ways of doing things. The definition of community has been reshaped by the impact of globalisation. Distances have been reduced by people’s ability to access various types of technology. Many nations foster Lifelong Learning because education is believed to be ‘one of the principal means available to foster a deeper and more harmonious form of human development’ (Delors 1996: un). Networking among communities and/or stakeholders links social and educational resources. In Victoria, initiatives such as the Local Learning and Employment Network (LLEN) have resulted in networks of local stakeholders to scaffold the school to work transition. Schools, Adult Community Education (ACE) providers and Technical and Further Education (TAFE) providers have networked to provide alternative pathways to further education or work for young people in years 11 and 12. However, despite the intent of lifelong learning to overcome exclusion and increase social capital, Bauman (1998) indicates that the freedoms of postmodernity may result in feelings of powerlessness, as previously secure spaces become destabilised. This paper, drawing on the theories of Bauman, discusses some consequences that the shifting of local and global boundaries has on communities and asks if lifelong learning meets the challenges of postmodernity.

Towards a cyberspatial pedagogy : exploring synchronous online learning potentials

It has been a quarter of a century since William Gibson (1984) coined the term cyberspace in his seminal science fiction novel Neuromancer. Subsequently, a proliferation of online teaching technologies have emerged supporting Virilio’s (1991) contention that, “time and space have ceased to function as meaningful dimensions to human thought and action.” The aim of this presentation is to discuss and demonstrate the innovative modification of an online, synchronous learning environment, Elluminate Live! (eLive), which allows participants to transcend the spatial dimension. Specifically, we present an example of good practice which aimed to enhance student engagement by implementing a structured online tutorial series which replicated the entire first year psychology on-campus tutorial series in the eLive environment. We discuss Student Evaluation of Teaching and Units (SETU) results which support the utility of this pedagogic strategy. Finally, we outline various challenges for the virtual teacher who wishes to implement a structured learning program in the eLive environment.
Gibson, W 1984, Neuromancer, Ace Books, New York, USA.
Virilio, P 1991, The aesthetics of disappearance, Semiotext(e), New York, USA.