Identification of optimal epitopes for Plasmodium falciparum rapid diagnostic tests that target histidine-rich proteins 2 and 3

Rapid diagnostic tests (RDTs) represent important tools to diagnose malaria infection. To improve understanding of the variable performance of RDTs that detect the major target in Plasmodium falciparum, namely, histidine-rich protein 2 (HRP2), and to inform the design of better tests, we undertook detailed mapping of the epitopes recognized by eight HRP-specific monoclonal antibodies (MAbs). To investigate the geographic skewing of this polymorphic protein, we analyzed the distribution of these epitopes in parasites from geographically diverse areas. To identify an ideal amino acid motif for a MAb to target in HRP2 and in the related protein HRP3, we used a purpose-designed script to perform bioinformatic analysis of 448 distinct gene sequences from pfhrp2 and from 99 sequences from the closely related gene pfhrp3. The frequency and distribution of these motifs were also compared to the MAb epitopes. Heat stability testing of MAbs immobilized on nitrocellulose membranes was also performed. Results of these experiments enabled the identification of MAbs with the most desirable characteristics for inclusion in RDTs, including copy number and coverage of target epitopes, geographic skewing, heat stability, and match with the most abundant amino acid motifs identified. This study therefore informs the selection of MAbs to include in malaria RDTs as well as in the generation of improved MAbs that should improve the performance of HRP-detecting malaria RDTs.

License scheme : an optimal waste management policy under asymmetric information

A system requiring a waste management license from an enforcement agency has been introduced in many countries. A license system is usually coupled with fines, a manifest, and a disposal tax. However, these policy devices have not been integrated into an optimal policy. In this paper we derive an optimal waste management policy by using those policy devices. Waste management policies are met with three difficult problems: asymmetric information, the heterogeneity of waste management firms, and non-compliance by waste management firms and waste disposers. The optimal policy in this paper overcomes all three problems.

Emerging Opportunities for "Design Thinking" to Deliver Sustainable Solutions in the Built Environment

In the built environment sector, a range of innovations are delivering environmental improvements with mixed success worldwide. The authors of this paper argue that a more “disruptive” form of innovation is needed to bring about significant and systemic change within the sector. Critical to this transition is the development of new behaviours and values. In particular, built environment professionals need to become active change agents in cultivating these new behaviours and values through the development of collaborative visions, scenarios, practices, and ideas. This paper identifies and discusses the critical role that design (in its broadest sense) can play in this process. Drawing on a comprehensive review of literature, the authors highlight a number of transformational opportunities for cross professional learning and sharing between design and built environment disciplines in achieving environmental innovation (eco-innovation). The paper also considers several design-based concepts that have a potential application in the built environment sector including: design thinking, social innovation (human-centered), and disruptive innovation (transformational) approaches. The research findings will assist in building the capabilities of designers and innovators to create sustainable solutions to global problems, and in supporting the social diffusion of systems-changing ideas in the built environment sector.

Going through the obstruction, the Torrens System Assurance Fund and contemporary solutions : a tale weaved from a story of a nun, a romantic triangle and sibling corruption

Private title insurance has been the subject of much debate by law reform bodies and academics. This article adds a new dimension to the discussion by analysing its role against a recent scenario where a nun was betrayed by the actions of her brother, and compensation payable from the assurance fund, after much challenge by the registrar, amounted to in excess of $4 million.We ask whether the slow burning of title insurance into the psyche of Australian home purchasers will see state-based assurance fundings looking to minismise their role in the Torrens system. We also query how the rather more immediate electronic establishment of electronic conveyancing will alter the balance between the assurance fund, private title insurance and the increasing responsibilities on stakeholdes involved in conveyancing.

Challenges in improving chronic disease survivorship outcomes using tele-health and self-managed online solutions

The advances in modern information and communication (ICT) technology continue to address the challenges and improve` health outcomes for the survivors of chronic disease such as prostate cancer. The management of survivorship is increasingly becoming an important need for the survivors to manage their chronic conditions. The technology interventions such as tele-health as well as self-managed technology applications have shown a potential to improve survivorship outcomes. However, the application of these tools should be supported by strong health economics evidence. This work discusses the challenges of technology led survivorship care models and presents an integrated approach to address these challenges.

A frontier functions approach to optimal scales of sustainable production

This paper translates the concepts of sustainable production to three dimensions of economic, environmental and ecological sustainability to analyze optimal production scales by solving optimizing problems. Economic optimization seeks input-output combinations to maximize profits. Environmental optimization searches for input-output combinations that minimize the polluting effects of materials balance on the surrounding environment. Ecological optimization looks for input-output combinations that minimize the cumulative destruction of the entire ecosystem. Using an aggregate space, the framework illustrates that these optimal scales are often not identical because markets fail to account for all negative externalities. Profit-maximizing firms normally operate at the scales which are larger than optimal scales from the viewpoints of environmental and ecological sustainability; hence policy interventions are favoured. The framework offers a useful tool for efficiency studies and policy implication analysis. The paper provides an empirical investigation using a data set of rice farms in South Korea.

Optimal HMM processing of differentially phase modulated communication systems

This paper investigates demodulation of differentially phase modulated signals DPMS using optimal HMM filters. The optimal HMM filter presented in the paper is computationally of order N3 per time instant, where N is the number of message symbols. Previously, optimal HMM filters have been of computational order N4 per time instant. Also, suboptimal HMM filters have be proposed of computation order N2 per time instant. The approach presented in this paper uses two coupled HMM filters and exploits knowledge of ...

Optimal HMM filtering and decision feedback equalisation for differential encoded transmission systems

In this paper conditional hidden Markov model (HMM) filters and conditional Kalman filters (KF) are coupled together to improve demodulation of differential encoded signals in noisy fading channels. We present an indicator matrix representation for differential encoded signals and the optimal HMM filter for demodulation. The filter requires O(N3) calculations per time iteration, where N is the number of message symbols. Decision feedback equalisation is investigated via coupling the optimal HMM filter for estimating the message, conditioned on estimates of the channel parameters, and a KF for estimating the channel states, conditioned on soft information message estimates. The particular differential encoding scheme examined in this paper is differential phase shift keying. However, the techniques developed can be extended to other forms of differential modulation. The channel model we use allows for multiplicative channel distortions and additive white Gaussian noise. Simulation studies are also presented.

Complementary surface-enhanced resonance raman spectroscopic biodetection of mixed protein solutions by chitosan- and silica-coated plasmon-tuned silver nanoparticles

Silver nanoparticles with identical plasmonic properties but different surface functionalities are synthesized and tested as chemically selective surface-enhanced resonance Raman (SERR) amplifiers in a two-component protein solution. The surface plasmon resonances of the particles are tuned to 413 nm to match the molecular resonance of protein heme cofactors. Biocompatible functionalization of the nanoparticles with a thin film of chitosan yields selective SERR enhancement of the anionic protein cytochrome b5, whereas functionalization with SiO2 amplifies only the spectra of the cationic protein cytochrome c. As a result, subsequent addition of the two differently functionalized particles yields complementary information on the same mixed protein sample solution. Finally, the applicability of chitosan-coated Ag nanoparticles for protein separation was tested by in situ resonance Raman spectroscopy.

Novel solutions for a model of wound healing angiogenesis

We prove the existence of novel, shock-fronted travelling wave solutions to a model of wound healing angiogenesis studied in Pettet et al (2000 IMA J. Math. App. Med. 17 395–413) assuming two conjectures hold. In the previous work, the authors showed that for certain parameter values, a heteroclinic orbit in the phase plane representing a smooth travelling wave solution exists. However, upon varying one of the parameters, the heteroclinic orbit was destroyed, or rather cut-off, by a wall of singularities in the phase plane. As a result, they concluded that under this parameter regime no travelling wave solutions existed. Using techniques from geometric singular perturbation theory and canard theory, we show that a travelling wave solution actually still exists for this parameter regime. We construct a heteroclinic orbit passing through the wall of singularities via a folded saddle canard point onto a repelling slow manifold. The orbit leaves this manifold via the fast dynamics and lands on the attracting slow manifold, finally connecting to its end state. This new travelling wave is no longer smooth but exhibits a sharp front or shock. Finally, we identify regions in parameter space where we expect that similar solutions exist. Moreover, we discuss the possibility of more exotic solutions.

Contributions to Bayesian experimental design

This thesis progresses Bayesian experimental design by developing novel methodologies and extensions to existing algorithms. Through these advancements, this thesis provides solutions to several important and complex experimental design problems, many of which have applications in biology and medicine. This thesis consists of a series of published and submitted papers. In the first paper, we provide a comprehensive literature review on Bayesian design. In the second paper, we discuss methods which may be used to solve design problems in which one is interested in finding a large number of (near) optimal design points. The third paper presents methods for finding fully Bayesian experimental designs for nonlinear mixed effects models, and the fourth paper investigates methods to rapidly approximate the posterior distribution for use in Bayesian utility functions.

The Sawa World model : addressing extreme poverty through local solutions and youth empowerment

With an estimated 1.2 billion people worldwide living in extreme poverty, it is critical to find effective long-term solutions. Sawa World is a non-profit organization founded by Daphne Nederhorst in 2005 to empower marginalized youth to document simple, locally created solutions that address this pressing issue. Currently working primarily in Uganda, Sawa World has created a unique model that celebrates powerful solutions generated from within the community to help people living in poverty help themselves. Using inspiring local leaders who themselves come from extreme poverty, Sawa World aims to end extreme poverty from the ground up.