Rationale and design of the national benchmarking and evidence-based national clinical guidelines for chronic heart failure management programs study

OBJECTIVES: The National Benchmarks and Evidence-Based National Clinical Guidelines for Heart Failure Management Programs Study is a national, multicenter study designed to determine the nature, range, and effect of interventions applied by chronic heart failure management programs (CHF-MPs) throughout Australia on patient outcomes. Its primary objective is to use these data to develop national benchmarks and evidence-based clinical guidelines and optimize their cost-effective application by reducing quality and outcome variability. DATA SOURCES/STUDY SETTING: Primary data will be collected from CHF-MP coordinators and CHF patients enrolled in these programs on a national basis. Secondary outcome data will be collected from a national morbidity record and from patients' medical records. STUDY DESIGN: Stage I of the study involves a prospective clinical audit of all CHF-MPs throughout Australia (n = 45) to determine the extent of variability in programs currently. Stage II is a prospective cross-sectional survey design enrolling 1,500 patients (average of 40 patients per program) to firstly determine the typical profile of patients being managed via a CHF-MP in Australia and, secondly, the subsequent morbidity and mortality during the 6-month follow-up. Outcome data will be subject to multivariate analysis to determine the key components of care in this regard. All study data will be then examined in the final stage of the study (III) to develop national benchmarks for the application and auditing of CHF-MPs in Australia. CONCLUSION: Variability in patient outcomes is a product of heterogeneity among CHF-MPs. The development of national benchmarks will minimize such heterogeneity and will provide a greater level of evidence for their cost-effective application.

Design of new oxazaphosphorine anticancer drugs

The oxazaphosphorines including cyclophosphamide (CPA, Cytoxan, or Neosar), ifosfamide (IFO, Ifex) and trofosfamide (Ixoten) represent an important group of therapeutic agents due to their substantial antitumor and immunomodulating activity. However, several intrinsic limitations have been uncounted during the clinical use of these oxazaphosphorines, including substantial pharmacokinetic variability, resistance and severe host toxicity. To circumvent these problems, new oxazaphosphorines derivatives have been designed and evaluated with an attempt to improve the selectivity and response with reduced host toxicity. These include mafosfamide (NSC 345842), glufosfamide (D19575, β-Dglucosylisophosphoramide mustard), S-(-)-bromofosfamide (CBM-11), NSC 612567 (aldophosphamide perhydrothiazine) and NSC 613060 (aldophosphamide thiazolidine). Mafosfamide is an oxazaphosphorine analog that is a chemically stable 4-thioethane sulfonic acid salt of 4-hydroxy-CPA. Glufosfamide is IFO derivative in which the isophosphoramide mustard, the alkylating metabolite of IFO, is glycosidically linked to a β-D-glucose molecule. Phase II studies of glufosfamide in the treatment of pancreatic cancer, non-small cell lung cancer (NCSLC), and recurrent glioblastoma multiform (GBM) have recently completed and Phase III trials are ongoing, while Phase I studies of intrathecal mafosfamide have recently completed for the treatment of meningeal malignancy secondary to leukemia, lymphoma, or solid tumors. S-(-)- bromofosfamide is a bromine-substituted IFO analog being evaluated in a few Phase I clinical trials. The synthesis and development of novel oxazaphosphorine analogs with favourable pharmacokinetic and pharmacodynamic properties still constitutes a great challenge for medicinal chemists and cancer pharmacologists.

Design and simulation of an interdigital-chaotic advection micromixer for lab-on-a-chip applications

This paper presents the design and simulation of a novel passive micromixer. The micromixer consists of two inlet tanks, one mixing channel and two outlet channels. In order to maximise the mixing efficiency, the following considerations are made: (i) The inlet tanks are followed by a series of microchannels, in which the flow is split. The microchannels are arranged in an interdigital manner to maximise the contact area between the two flows. (ii) The microchannels attached to the lower inlet tank have an upward slope while those attached to the upper tank have a downward slope. The higher-density flow is fed to the lower inlet tank and gets an upward velocity before entering the mixing channel. (iii) Two triangular barriers are placed within the mixing channel to impose chaotic advection and perturb the less-mixed flow along the top and bottom surfaces of the channel. (iv) Finally, two outlet channels are incorporated to discard the less-mixed flow. Three-dimensional simulations are carried out to evaluate the performance of the micromixer. Simulations are performed in the absence and presence of the gravitational force to analyse the influence of gravity on the micromixer. Mixing efficiencies of greater than 92% are achieved using water and a 1011'density biological solvent as the mixing fluids.

Design and simulation of an interdigital-chaotic advection micromixer for lab-on-a-chip applications

The paper presents the design and simulation of a novel passive micromixer. The micromixer consists of two inlet tanks, one mixing channel and two outlet channels. In order to maximise the mixing efficiency, the following considerations are made : (i) The inlet tanks are followed by a series of microchannels, in which the flow is split. The microchannels are arranged in an interdigital manner to  maximise the contact area between the two flows. (ii) The microchannels attached to the lower inlet tank have an upward slope while those attached to the upper tank have a downward slope. The higher-density flow is fed to the lower inlet tank and gets an upward velocity before entering the mixing channel. (iii) Two triangular barriers are placed within the mixing channel to impose chaotic advection and perturb the less-mixed flow along the top and bottom surfaces of the channel. (iv) Finally, two outlet channels are incorporated to discard the less-mixed flow. Three-dimensional simulations are carried out to evaluate the performance of the micromixer. Simulations are performed in the absence and presence of the gravitational force to analyse the influence of gravity on the micromixer. Mixing efficiencies of greater than 92 % are achieved using water and a low-density biological solvent as the mixing fluids.

Data warehouse design and legal visualization – the applicability of H2 for reporting

The steady increase of regulations and its acceleration due to the financial crisis heavily affect the management of regulatory compliance. Regulations, such as Basel III and Solvency II particularly impact data warehouses and lead to many organizational and technical changes. From an IS perspective modeling techniques for data warehouse requirement elicitation help to manage conceptual requirements. From a legal perspective attempts to visualize regulatory requirements – so called legal visualization approaches – have been developed. This paper investigates whether a conceptual modeling technique for regulatory-driven data warehouse requirements is applicable for representing data warehouse requirements in a legal environment. Applying the modeling technique H2 for Reporting in three extensive modeling projects provides three contributions. First, evidence for the applicability of a modeling technique for regulatory-driven data warehouse requirements is given. Second, lessons learned for further modeling projects are provided. Third, a discussion towards a combined perspective of information modeling and legal visualization is presented.

Investigation of the WISC-III and WASI in clinical child populations : a framework for further exploration

To promote efficient clinical practice, interest has been growing in brief assessment scales to replace full-scale versions in some circumstances. In nonclinical populations, the Wechsler Abbreviated Scale of Intelligence (WASI) has substituted for the Wechsler Intelligence Scale for Children—Third Edition (WISC-III). Agreement between these scales remains untested in clinical populations. Twenty-five children, aged 6 to 15 years old were assessed. A correlational and within-participant design was used. These scales were significantly correlated. Despite a fourth edition of the WISC now available, WASI administration alone would at times appear to be a quick and valid estimate of IQ. Replication with the WISC-IV seems necessary to clarify the verbal/ performance distance criterion discrepancy and also the meaning of some variability between the scale and subtests.

A demandeur-centric theory of regime design in transnational commercial law

Recent scholarship on international agreement design has almost exclusively focused on the public international law area. The literature on regime design in the area of international private law lacks a solid theoretical foundation. Academic writing on public international law's state-centric approach is only amenable to crude transplantation and poses several puzzles in the international private law context. Resolving these puzzles is important because of the proliferation of transnational commercial agreements in areas that were traditionally the province of domestic law. This paper attempts to provide a starting point to address the theoretical vacuum. Part I argues that functionalist, liberal, and realist theories cannot fully explain transnational commercial law agreement design. Part II puts forth a demandeur-centric approach with the aid of examples that span the spectrum from hard law to soft law. Part III concludes that agreement design in transnational commercial law is premised on demandeur preferences and relative power.

Considering the chemical energy requirements of the tri-n-propylamine co-reactant pathways for the judicious design of new electrogenerated chemiluminescence detection systems

The introduction of a 'co-reactant' was a critical step in the evolution of electrogenerated chemiluminescence (ECL) from a laboratory curiosity to a widely utilised detection system. In conjunction with a suitable electrochemiluminophore, the co-reactant enables generation of both the oxidised and reduced precursors to the emitting species at a single electrode potential, under the aqueous conditions required for most analytical applications. The most commonly used co-reactant is tri-n-propylamine (TPrA), which was developed for the classic tris(2,2'-bipyridine)ruthenium(ii) ECL reagent. New electrochemiluminophores such as cyclometalated iridium(iii) complexes are also evaluated with this co-reactant. However, attaining the excited states in these systems can require much greater energy than that of tris(2,2'-bipyridine)ruthenium(ii), which has implications for the co-reactant reaction pathways. In this tutorial review, we describe a simple graphical approach to characterise the energetically feasible ECL pathways with TPrA, as a useful tool for the development of new ECL detection systems.

Improving the health of Australians by applying evidence from behavioural epidemiology to urban design projects

Rapid urban population growth in Australia requires an expansion of supporting hard and soft infrastructure. In the State of Victoria, directing this growth are a number of urban design and planning mechanisms that provide a ‘blueprint for development and investment’. Although topics revolving around physical health are present in these and other planning related documents, largely absent from this literature are ‘tools’ to assist decision makers in determining whether or not an urban setting supports physical health and provides opportunities for physical activity. Insufficient physical activity is a risk factor contributing to Australia’s growing and significant burden of chronic disease including cardiovascular disease, Type 2 diabetes and overweight/obesity. The potential of the built environment to influence population-level physical activity is well recognised. A key element in Victoria’s planning framework that can help address these health concerns is the provision and redevelopment of open space(s) in urban areas that provide opportunities for people of all ages and abilities to engage in physical activity. However, in the realisation of these settings, evidence informing the design of urban open space(s) that promote opportunities for physical activity is needed to produce evidence based decision making. Using the three geo-spatial visioning layers embedded in Victoria’s planning framework (i.e. Growth Area Framework Plans, Precinct Structure Plans and Planning Permits) as positioning instruments, this paper merges the fields of behavioural epidemiology and urban design to: i) provide a brief overview of current research relating to design of open space to optimise usage and physical activity, ii) consider what type of evidence relating to features of open space is needed to help inform decision makers, iii) consider the methods and procedures practitioners may use to incorporate evidence in to their planning, and iv) discuss the geo-spatial development level that the respective data can best assist decision making to achieve positive gains in physical health.