Synthesis of a multimodal molecular imaging probe based on a hyperbranched polymer architecture

Molecular imaging is utilised in modern medicine to aid in the diagnosis and treatment of disease by allowing its spatiotemporal state to be examined in vivo. This study focuses on the development of novel multimodal molecular imaging agents based on hyperbranched polymers that combine the complementary capabilities of optical fluorescence imaging and positron emission tomography-computed tomography (PET/CT) into one construct. RAFT-mediated polymerisation was used to prepare two hydrophilic hyperbranched polymers that were differentiated by their size and level of branching. The multiple functional end-groups facilitated covalent attachment of both near infrared fluorescent dyes for optical imaging, as well as a copper chelator allowing binding of 64Cu as a PET radio nuclei. In vivo multimodal imaging of mice using PET/CT and planar optical imaging was first used to assess the biodistribution of the polymeric materials and it was shown that the larger and more branched polymer had a significantly longer circulation time. The larger constructs were also shown to exhibit enhanced accumulation in solid tumours in a murine B16 melanoma model. Importantly, it was demonstrated that the PET modality gave rise to high sensitivity immediately after injection of the agent, while the optical modality facilitated extended longitudinal studies, thus highlighting how the complementary capabilities of the molecular imaging agents can be useful for studying various diseases, including cancer.

Borrowing from the geeks: What can healthcare facility design learn from IT?

People get into healthcare because they want to help society. And when a new hospital is briefed, everyone tries to do their best, but the process is mired by the impossibility of the task. Stakeholders rarely understand the architectural process, nobody can predict the future, and the only thing for certain is that everything will change as the project unfolds, revealing errors in initial assumptions and calculations, shifts in needs, new technologies etc. Yet there’s always pressure to keep to the programme and to press on regardless. This chaos leads eventually to suboptimal results: hospitals the world over are riddled with inefficiencies, idiosyncrasies, incredible wastage and features that lead to poor clinical outcomes. This talk will sketch out the basics of Scrum, the most popular open-source Lean/Agile methodology. It will discuss what healthcare designers can learn from the geeks in Silicon Valley reduce risk, meet deadlines and deliver the highest possible value for the budget despite the uncertainty.

The lean paradox : How can healthcare facilities shrink while clinical spaces expand?

Lean principles create highly efficient healthcare facilities by maximising the clinical value of every part of a facility and by removing everything else. In order that clinical accommodation can be used for a diverse set of functions including unexpected tasks and processes that haven’t even been invented, they have to be big. But somewhat surprisingly, whole facilities tend to shrink in terms of gross floor areas by disposing of non-clinical spaces when designed using Lean principles. And with the whole unit – the building costs shrink too. Using examples from the UK and the USA, this talk explores the unexpected solutions and improved outcomes when designers use a Lean approach to design.

Response to: Electronic health records and healthcare identifiers : legislation discussion paper

Public submission # 029 to a Australian federal parliamentary committee considering proposed legislative changes to the Commonwealth's Healthcare Identifiers Act 2010 and the Personally Controlled Electronic Health Records Act 2012.

Fine mapping and replication of genetic risk Loci in primary sclerosing cholangitis

Background and aims. Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis of the bile ducts eventually leading to biliary cirrhosis. Recent genetic studies in PSC have identified associations at 2q13, 2q35, 3p21, 4q27, 13q31 and suggestive association at 10p15. The aim of this study was to further characterize and refine the genetic architecture of PSC. Methods. We analyzed previously reported associated SNPs at four of these non-HLA loci and 59 SNPs tagging the IL-2/IL-21 (4q27) and IL2RA (10p15) loci in 992 UK PSC cases and 5162 healthy UK controls. Results. The most associated SNPs identified were rs3197999 (3p21 (MST1), p = 1.9 × 10 -6, OR A vs G = 1.28, 95% CI (1.16-1.42)); rs4147359 (10p15 (IL2RA), p = 2.6 × 10 -4, OR A vs G = 1.20, 95% CI (1.09-1.33)) and rs12511287 (4q27 (IL-2/IL-21), p = 3.0 × 10 -4, OR A vs T = 1.21, 95% CI (1.09-1.35)). In addition, we performed a meta-analysis for selected SNPs using published summary statistics from recent studies. We observed genome-wide significance for rs3197999 (3p21 (MST1), P combined = 3.8 × 10 -12) and rs4147359 (10p15 (IL2RA), P combined = 1.5 × 10 -8). Conclusion. We have for the first time confirmed the association of PSC with genetic variants at 10p15 (IL2RA) locus at genome-wide significance and replicated the associations at MST1 and IL-2/IL-21 loci in a large homogeneous UK population. These results strongly implicate the role of IL-2/IL2RA pathway in PSC and provide further confirmation of MST1 association. © Informa Healthcare.

Biceps femoris architecture and strength in athletes with a prior ACL reconstruction

Purpose To determine if limbs with a history of anterior cruciate ligament (ACL) injury reconstructed from the semitendinosus (ST) display different biceps femoris long head (BFlh) architecture and eccentric strength, assessed during the Nordic hamstring exercise, compared to the contralateral uninjured limb. Methods The architectural characteristics of the BFlh were assessed at rest and at 25% of a maximal voluntary isometric contraction (MVIC) in the control (n=52) and previous ACL injury group (n=15) using two-dimensional ultrasonography. Eccentric knee-flexor strength was assessed during the Nordic hamstring exercise. Results Fascicle length was shorter (p=0.001; d range: 0.90 to 1.31) and pennation angle (p range: 0.001 to 0.006: d range: 0.87 to 0.93) was greater in the BFlh of the ACL injured limb when compared to the contralateral uninjured limb at rest and during 25% of MVIC. Eccentric strength was significantly lower in the ACL injured limb than the contralateral uninjured limb (-13.7%; -42.9N; 95% CI = -78.7 to -7.2; p=0.021; d=0.51). Fascicle length, MVIC and eccentric strength were not different between the left and right limb in the control group. Conclusions Limbs with a history of ACL injury reconstructed from the ST have shorter fascicles and greater pennation angles in the BFlh compared to the contralateral uninjured side. Eccentric strength during the Nordic hamstring exercise of the ACL injured limb is significantly lower than the contralateral side. These findings have implications for ACL rehabilitation and hamstring injury prevention practices which should consider altered architectural characteristics.

Architecture, the body and authority in performance

This is a theoretical investigation seeking to learn more about architecture by looking at architectural practice through another discipline. In this research architecture is investigated by examining its relationship with bodies through performance and theatre set design. This thesis aims to build on existing architectural theory, in which an absence of discourse on the body has been identified, by analysing representations of architecture and the body in performance. The research specifically examines the relationship between the body, architecture and authority in performance through the analysis of several performance works.

LibVM: An architecture for shared library sandboxing

Many software applications extend their functionality by dynamically loading libraries into their allocated address space. However, shared libraries are also often of unknown provenance and quality and may contain accidental bugs or, in some cases, deliberately malicious code. Most sandboxing techniques which address these issues require recompilation of the libraries using custom tool chains, require significant modifications to the libraries, do not retain the benefits of single address-space programming, do not completely isolate guest code, or incur substantial performance overheads. In this paper we present LibVM, a sandboxing architecture for isolating libraries within a host application without requiring any modifications to the shared libraries themselves, while still retaining the benefits of a single address space and also introducing a system call inter-positioning layer that allows complete arbitration over a shared library’s functionality. We show how to utilize contemporary hardware virtualization support towards this end with reasonable performance overheads and, in the absence of such hardware support, our model can also be implemented using a software-based mechanism. We ensure that our implementation conforms as closely as possible to existing shared library manipulation functions, minimizing the amount of effort needed to apply such isolation to existing programs. Our experimental results show that it is easy to gain immediate benefits in scenarios where the goal is to guard the host application against unintentional programming errors when using shared libraries, as well as in more complex scenarios, where a shared library is suspected of being actively hostile. In both cases, no changes are required to the shared libraries themselves.

Themes in landscape architecture publishing: Past trends, future needs

Many scholars acknowledge the need for rigorous research in landscape architecture to improve practice and teaching, and several recent studies have explored research trends in the discipline. This study continues this exploration by reviewing the articles published in the three prominent English- language landscape architecture journals: Landscape Journal, Landscape Review, and the Journal of Landscape Architecture. Specifically, this study analyzes the abstracts from 441 research articles to determine specific themes and publishing trends over 31 years (1982–2013). Findings indicate that “history” is by far the most prominent research theme, followed by “social and cultural processes and issues” and “aesthetics.” Several themes—such as “sustainability and green infrastructure,” “participation and collaboration,” and “research methods and methodologies”—have become more prominent in recent years. However, topics of current social and political concern—such as “climate change,” “active living,” “energy,” and “health”—are not yet prominent themes in the research literature, and could be key areas for future contribution. With the exception of a few themes, findings also suggest a moderate degree of alignment between research and practice. The article concludes with recommendations for future areas of research that will better position landscape architecture as a research- oriented profession with broad social relevance.

Reflections on damaged modernity: Lessons from the iconic architecture industry

For Adorno writing in 1953, Hollywood cinema was a medium of “regression” based on infantile wish fulfillment manufactured by the industrial repetition of the filmic image that he called a modern “hieroglyphics”—like the archaic language of pictures in Ancient Egypt, which guaranteed immortality after death in Egyptian burial rites. From that 1953 essay Prolog zum Fernsehen to Das Schema der Massenkultur in 1981, Adorno likened film frames to cultural ideograms: What he called the filmic “language of images” (Bildersprache) constituted a Hieroglyphenschrift that visualised forbidden sexual impulses and ideations of death and domination in the unconscious of the mass spectator. In his famous passage he writes, “As image, the image-writing (Bilderschrift) is a medium of regression, where the producer and consumer coincide; as writing, film resurrects the archaic images of modernity.” In other words, cinema takes the spectator on a journey into his unconscious in order to control him from within. It works, because the spectator begins to believe the film is speaking to him in his very own image-language (the unconscious), making him do and buy whatever capitalism demands. Modernity for Adorno is precisely the instrumentalisation of the collective unconscious through the mediatic images of the culture industry.

The shifting value of design in the Australian Architecture Industry

Architects regularly employ design as a problem-solving tool in the built environment. Within the design process, architects apply design thinking to reframe problems as opportunities, take advantage of contradictory information to develop new solutions, and differentiate outcomes based on context. This research aims to investigate how design can be better positioned to develop greater differentiated value to an architect’s current service offering, and how design as a strategy could be applied as a driver of business innovation within the Australian architecture industry. The research will explore literature relating to the future of architecture, the application of design thinking, and the benefits of strategic design. The future intent of the research is to develop strategies that improve the value offering of architects, and develop design led solutions that could be applied successfully to the business of architecture.

Architecture Optimization of Aerospace Computing Systems

Simultaneous consideration of both performance and reliability issues is important in the choice of computer architectures for real-time aerospace applications. One of the requirements for such a fault-tolerant computer system is the characteristic of graceful degradation. A shared and replicated resources computing system represents such an architecture. In this paper, a combinatorial model is used for the evaluation of the instruction execution rate of a degradable, replicated resources computing system such as a modular multiprocessor system. Next, a method is presented to evaluate the computation reliability of such a system utilizing a reliability graph model and the instruction execution rate. Finally, this computation reliability measure, which simultaneously describes both performance and reliability, is applied as a constraint in an architecture optimization model for such computing systems. Index Terms-Architecture optimization, computation

The Influence of Constantinople on Middle Byzantine Architecture (843-1204) : A typological and morphological approach at the provincial level.

The influence of the architecture of the Byzantine capital spread to the Mediterranean provinces with travelling masters and architects. In this study the architecture of the Constantinopolitan School has been detected on the basis of the typology of churches, completed by certain morphological aspects when necessary. The impact of the Constantinopolitan workshops appears to have been more important than previously realized. This research revealed that the Constantinopolitan composite domed inscribed-cross type or cross-in-square spread everywhere to the Balkans and it was assumed soon by the local schools of architecture. In addition, two novel variants were invented on the basis of this model: the semi-composite type and the so-called Athonite type. In the latter variant lateral conches, choroi, were added for liturgical reasons. Instead, the origin of the domed ambulatory church was partly provincial. One result of this study is that the origin of the Middle Byzantine domed octagonal types was traced to Constantinople. This is attested on the basis of the archaeological evidence. Also some other architectural elements that have not been preserved in the destroyed capital have survived at the provincial level: the domed hexagonal type, the multi-domed superstructure, the pseudo-octagon and the narthex known as the lite. The Constantinopolitan architecture during the period in question was based on the Early Christian and Late Antique forms, practices and innovations and this also emerges at the provincial level.

Sustainable me - a pharmacist’s role in reducing the carbon footprint of healthcare delivery

Introduction Climate change has been described as the most significant global health threat of the 21st century. Already, negative impacts on human health and wellbeing are being observed. These impacts present enormous challenges for the healthcare sector and the time has come for healthcare professionals to demonstrate leadership in addressing these challenges. Since any unsustainable organizational practices of healthcare organisations may ultimately have a negative impact on human health, there is an implicit moral obligation for these organisations and the people who work in them, to deliver healthcare more sustainably. If one considers that in 2010 pharmaceuticals comprised 22% of the carbon footprint of the NHS England (equating to 4.4 million tonnes of CO2 emissions) and 3% of England’s total carbon footprint (NHS Sustainable Development Unit, 2012), by reducing the carbon footprint of pharmaceuticals used in their healthcare organisations, pharmacists can have a significant impact on reducing the organisation’s total carbon footprint and ultimately on the public’s health. Aims The engagement of pharmacists with sustainability initiatives in the workplace has been largely unreported in international and national pharmacy journals. This paper aims to highlight the important role that pharmacists can play in helping to reduce the carbon footprint of healthcare delivery. Methods Literature was reviewed to identify areas where pharmacists could influence the more sustainable use of pharmaceuticals in their organisations. Discussion Much of the carbon footprint of pharmaceuticals is embedded carbon from their manufacture and delivery. Through efficient inventory management practices, pharmacists can reduce the number of orders and potentially reduce the number of deliveries required. Pharmacists can also help to reduce the amount of pharmaceutical waste generated. Of the waste that is generated, they can help improve the segregation of waste streams to increase the amount of non-contaminated packaging waste that is recycled and reduce the amount of pharmaceutical waste being incinerated or ending up in landfill. Reference NHS Sustainable Development Unit. (2012). Sustainability in the NHS Health Check 2012. NHS Sustainable Development Unit. Cambridge, UK: NHS Sustainable Devlopment Unit.