Princess Alexandra Hospital model of comprehensive geriatric assessment of cancer patients : methodological and logistical aspects

There is increasing momentum in cancer care to implement a two stage assessment process that accurately determines the ability of older patients to cope with, and benefit from, chemotherapy. The two-step approach aims to ensure that patients clearly fit for chemotherapy can be accurately identified and referred for treatment without undergoing a time- and resource-intensive comprehensive geriatric assessment (CGA). Ideally, this process removes the uncertainty of how to classify and then appropriately treat the older cancer patient. After trialling a two-stage screen and CGA process in the Division of Cancer Services at Princess Alexandra Hospital (PAH) in 2011-2012, we implemented a model of oncogeriatric care based on our findings. In this paper, we explore the methodological and practical aspects of implementing the PAH model and outline further work needed to refine the process in our treatment context.

Teaching and assessing ethics and social responsibility in undergraduate science : a position paper

Institutional graduate capabilities and discipline threshold learning outcomes require science students to demonstrate ethical conduct and social responsibility. However, neither the teaching nor the assessment of these concepts is straightforward. Australian chemistry academics participated in a workshop in 2013 to discuss and develop teaching and assessment in these areas and this paper reports on the outcomes of that workshop. Controversial issues discussed included: How broad is the mandate of the teacher, how should the boundaries between personal values and ethics be drawn, and how can ethics be assessed without moral judgement? In this position paper, I argue for a deep engagement with ethics and social justice, achieved through case studies and assessed against criteria that require discussion and debate. Strategies to effectively assess science students’ understanding of ethics and social responsibility are detailed.

Socio-Legal Aspects of the 3D Printing Revolution

Additive manufacturing or ‘3D printing’ has emerged into the mainstream in the last few years, with much hype about its revolutionary potential as the latest ‘disruptive technology’ to destroy existing business models, empower individuals and evade any kind of government control. This book examines the trajectory of 3D printing in practice and how it interacts with various areas of law, including intellectual property, product liability, gun laws, data privacy and fundamental/constitutional rights. A particular comparison is made between 3D printing and the Internet as this has been, legally-speaking, another ‘disruptive technology’ and also one on which 3D printing is partially dependent. This book is the first expert analysis of 3D printing from a legal perspective and provides a critical assessment of the extent to which existing legal regimes can be successfully applied to, and enforced vis-à-vis, 3D printing.

Thrombophilia and direct thrombin inhibitor lepirudin clinical and monitoring aspects

Thrombophilia (TF) predisposes both to venous and arterial thrombosis at a young age. TF may also impact the thrombosis or stenosis of hemodialysis (HD) vascular access in patients with end-stage renal disease (ESRD). When involved in severe thrombosis TF may associate with inappropriate response to anticoagulation. Lepirudin, a potent direct thrombin inhibitor (DTI), indicated for heparin-induced thrombocytopenia-related thrombosis, could offer a treatment alternative in TF. Monitoring of narrow-ranged lepirudin demands new insights also in laboratory. The above issues constitute the targets in this thesis. We evaluated the prevalence of TF in patients with ESRD and its impact upon thrombosis- or stenosis-free survival of the vascular access. Altogether 237 ESRD patients were prospectively screened for TF and thrombogenic risk factors prior to HD access surgery in 2002-2004 (mean follow-up of 3.6 years). TF was evident in 43 (18%) of the ESRD patients, more often in males (23 vs. 9%, p=0.009). Known gene mutations of FV Leiden and FII G20210A occurred in 4%. Vascular access sufficiently matured in 226 (95%). The 1-year thrombosis- and stenosis-free access survival was 72%. Female gender (hazards ratio, HR, 2.5; 95% CI 1.6-3.9) and TF (HR 1.9, 95% CI 1.1-3.3) were independent risk factors for the shortened thrombosis- and stenosis-free survival. Additionally, TF or thrombogenic background was found in relatively young patients having severe thrombosis either in hepatic veins (Budd-Chiari syndrome, BCS, one patient) or inoperable critical limb ischemia (CLI, six patients). Lepirudin was evaluated in an off-label setting in the severe thrombosis after inefficacious traditional anticoagulation without other treatment options except severe invasive procedures, such as lower extremity amputation. Lepirudin treatments were repeatedly monitored clinically and with laboratory assessments (e.g. activated partial thromboplastin time, APTT). Our preliminary studies with lepirudin in thrombotic calamities appeared safe, and no bleeds occurred. An effective DTI lepirudin calmed thrombosis as all patients gradually recovered. Only one limb amputation was performed 3 years later during the follow-up (mean 4 years). Furthermore, we aimed to overcome the limitations of APTT and confounding effects of warfarin (INR of 1.5-3.9) and lupus anticoagulant (LA). Lepirudin responses were assessed in vitro by five specific laboratory methods. Ecarin chromogenic assay (ECA) or anti-Factor IIa (anti-FIIa) correlated precisely (r=0.99) with each other and with spiked lepirudin in all plasma pools: normal, warfarin, and LA-containing plasma. In contrast, in the presence of warfarin and LA both APTT and prothrombinase-induced clotting time (PiCT®) were limited by non-linear and imprecise dose responses. As a global coagulation test APTT is useful in parallel to the precise chromogenic methods ECA or Anti-FIIa in challenging clinical situations. Lepirudin treatment requires multidisciplinary approach to ensure appropriate patient selection, interpretation of laboratory monitoring, and treatment safety. TF seemed to be associated with complicated thrombotic events, in venous (BCS), arterial (CLI), and vascular access systems. TF screening should be aimed to patients with repeated access complications or prior unprovoked thromboembolic events. Lepirudin inhibits free and clot-bound thrombin which heparin fails to inhibit. Lepirudin seems to offer a potent and safe option for treatment of severe thrombosis. Multi-centered randomized trials are necessary to assess the possible management of complicated thrombotic events with DTIs like lepirudin and seek prevention options against access complications.

A study of symbolic processing and computational aspects in helicopter dynamics

Even research models of helicopter dynamics often lead to a large number of equations of motion with periodic coefficients; and Floquet theory is a widely used mathematical tool for dynamic analysis. Presently, three approaches are used in generating the equations of motion. These are (1) general-purpose symbolic processors such as REDUCE and MACSYMA, (2) a special-purpose symbolic processor, DEHIM (Dynamic Equations for Helicopter Interpretive Models), and (3) completely numerical approaches. In this paper, comparative aspects of the first two purely algebraic approaches are studied by applying REDUCE and DEHIM to the same set of problems. These problems range from a linear model with one degree of freedom to a mildly non-linear multi-bladed rotor model with several degrees of freedom. Further, computational issues in applying Floquet theory are also studied, which refer to (1) the equilibrium solution for periodic forced response together with the transition matrix for perturbations about that response and (2) a small number of eigenvalues and eigenvectors of the unsymmetric transition matrix. The study showed the following: (1) compared to REDUCE, DEHIM is far more portable and economical, but it is also less user-friendly, particularly during learning phases; (2) the problems of finding the periodic response and eigenvalues are well conditioned.

Organic photovoltaics: key photophysical, device and design aspects

Key aspects of Organic Photovoltaics (OPVs) have been reviewed in this tutorial. Issues pertaining to the choice of materials, fabrication processes, photophysical mechanisms, device characterization, morphology of active layers and manufacturing are discussed. Special emphasis has been given to recent developments in large-area modules. Current strategies in enhancing the performance using external optical engineering approaches have also been highlighted. OPVs as a technology combine low weight, flexibility, low cost, good form factor and high-throughput processing; making them a promising PV technology for the future.

Molecular and cellular aspects of the SREBP pathway

The SREBP (sterol response element binding proteins) transcription factors are central to regulating de novo biosynthesis of cholesterol and fatty acids. The SREBPs are regulated by retention or escape from the ER to the Golgi where they are proteolytically cleaved into active forms. The SREBP cleavage activating protein (SCAP) and the INSIG proteins are essential in this regulatory process. The aim of this thesis is to further characterise the molecular and cellular aspects surrounding regulation of SREBP processing. SREBP and SCAP are known to interact via their carboxy-terminal regulatory domains (CTDs) but this interaction is poorly characterised. Significant steps were achieved in this thesis towards specific mapping of the interaction site. These included cloning and over expression and partial purification of tagged SREBP1 and SREBP2 CTDs and probing of a SCAP peptide array with the CTDs. Results from the SREBP2 probing were difficult to interpret due to insolubility issues with the protein, however, probing with SREBP1 revealed five potential binding sites which were detected reproducibly. Further research is necessary to overcome SREBP2 insolubility issues and to confirm the identified SREBP1 interaction site(s) on SCAP. INSIG1 has a central role in regulating SREBP processing and in regulating stability of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a rate limiting enzyme in cholesterol biosynthesis. There are two protein isoforms of human INSIG1 produced through the use of two in-frame alternative start sites. Bioinformatic analysis indicated that the presence of two in-frame start sites within the 5-prime region of INSIG1 mRNA is highly conserved and that production of two isoforms of INSIG1is likely a conserved event. Functional differences between these two isoforms were explored. No difference in either the regulation of SREBP processing or HMGCR degradation between the INSIG1 isoforms was observed and the functional significance of the two isoforms is as yet unclear. The final part of this thesis focused on enhancing the cytotoxicity of statins by targeted inhibition of SREBP processing by oxysterols. Statins have significant potential as anti-cancer agents as they inhibit the activity of HMGCR leading to a deficiency in mevalonate which is essential for cell survival. The levels of HMGCR fluctuate widely due to cholesterol feedback of SREBP processing. The relationship between sterol feedback and statin mediated cell death was investigated in depth in HeLa cells. Down regulation of SREBP processing by sterols significantly enhanced the efficacy of statin mediated cell death. Investigation of sterol feedback in additional cancer cell lines showed that sterol feedback was absent in cell lines A- 498, DU-145, MCF-7 and MeWo but was present in cell lines HT-29, HepG2 and KYSE-70. In the latter inhibition of SREBP processing using oxysterols significantly enhanced statin cytotoxicity. The results indicate that this approach is valid to enhance statin cytotoxicity in cancer cells, but may be limited by deregulation of SREBP processing and off target effects of statins, which were observed for some of the cancer cell lines screened.

Older people and legal advice – the need for joined up and creative approaches

This paper reports the findings from research conducted with older people in Northern
Ireland which investigated whether their needs for legal information and advice were
being met. One of the unique aspects of the research involved investigating the
potential of the internet as a possible source for advising older people in relation to
legal problems. The findings suggest that online legal information may frequently assist
older people in identifying potential answers to their legal questions, but may not be an
adequate substitute for personal communication and advice. The research also
highlights the need for professionals to work together to meet the needs of older
persons for legal advice and to safeguard their interests. Such ‘joined up’ approaches
are particularly important, for example at the point of dementia diagnosis, where
information sharing between health and social care professionals may significantly
promote the legal and welfare interests of older people at a vulnerable point in their
lives. This paper therefore turns to work by university-based legal clinics in the United
States, such as the Elder Law Clinic at Pennsylvania State University, where social
work or healthcare professionals, lawyers and law students collaborate to support older
people in their search for resolution of legal problems.

Power, Pedagogy and Participation: ethics and pragmatics in research with young people

This article addresses issues of methodology and ethical reflexivity when attempting to investigate the opinions of young people. Drawing specifically on three studies of young people's understandings of citizenship and their views on topical issues, two from England and one from Lebanon, the authors present ways in which the ethical and practical challenges of such research can be met. While acknowledging the power relationship between researchers and informants, they suggest that what they call ‘pedagogical research approaches’ built on a participative methodology can open up a space where both parties benefit. They argue that, when working in schools, teacher educators can take advantage of this status to present themselves simultaneously as insiders and outsiders. The authors have devised what are intended to be non-exploitative research instruments that permit the gathering of useful qualitative data during a short encounter. They illustrate their approach with examples of classroom activities they have developed to provide simultaneously a valid learning experience and usable data.

Legal aspects of animal-human combinations in Canada

This article examines the current legal regime applicable to animal-human combinations under the Assisted Human Reproduction Act (Canada). The Act prohibits as criminal offences the use of non-human reproductive material in humans, the use in humans of human reproductive material previously transplanted into a non-human life form, the creation of chimeras made from human embryos, and the creation for reproductive purposes of human/non-human hybrids. Additional animal-human combinations, such as transgenic life forms, may be regulated pursuant to section 11 of the Act in the future. The underlying concerns of the Act in establishing this regime appear to be the protection of human health and safety, human dignity and individuality, and the human genome. The Act seems calibrated to prohibit the creation of animal-human combinations that are currently unsafe and scientifically and ethically problematic, while leaving open the possibility of regulating other such combinations with more immediate scientific potential, although these also raise ethical questions. Currently, certain differences subsist in Canada between what is permissible for researchers and institutions funded by federal agencies and those in privately funded research. The development of the regulatory framework under the Act will reveal how freedom of research will be balanced against the need for scientifically valid and ethically justifiable research, and whether these differences will continue to apply.

Examining discourses on the ethics and public understanding of cognitive enhancement with methylphenidate

L’émergence de l’utilisation du méthylphénidate (MPH; Ritalin) par des étudiants universitaires afin d’améliorer leur concentration et leurs performances universitaires suscite l’intérêt du public et soulève d’importants débats éthiques auprès des spécialistes. Les différentes perspectives sur l’amélioration des performances cognitives représentent une dimension importante des défis sociaux et éthiques autour d’un tel phénomène et méritent d’être élucidées. Ce mémoire vise à examiner les discours présents dans les reportages internationaux de presse populaire, les discours en bioéthique et en en santé publique sur le thème de l’utilisation non médicale du méthylphénidate. Cette recherche a permis d’identifier et d’analyser des « lacunes » dans les perspectives éthiques, sociales et scientifiques de l’utilisation non médicale du méthylphénidate pour accroître la performance cognitive d’individus en santé. Une analyse systématique du contenu des discours sur l’utilisation non médicale du méthylphénidate pour accroître la performance cognitive a identifié des paradigmes divergents employés pour décrire l’utilisation non médicale du méthylphénidate et discuter ses conséquences éthiques. Les paradigmes « choix de mode de vie », « abus de médicament » et « amélioration de la cognition » sont présents dans les discours de la presse populaire, de la bioéthique et de la santé publique respectivement. Parmi les principales différences entre ces paradigmes, on retrouve : la description de l’utilisation non médicale d’agents neuropharmacologiques pour l’amélioration des performances, les risques et bénéfices qui y sont associés, la discussion d’enjeux éthiques et sociaux et des stratégies de prévention et les défis associés à l’augmentation de la prévalence de ce phénomène. La divergence de ces paradigmes reflète le pluralisme des perceptions de l’utilisation non médicale d’agents neuropharmacologiques Nos résultats suggèrent la nécessité de débats autour de l’amélioration neuropharmacologique afin de poursuivre l’identification des enjeux et de développer des approches de santé publique cohérentes.

Ethics and Graphic Arts

Discussion of ethical issues pertaining to communication design

Animal health challenges and veterinary aspects of organic livestock farming identified through a 3 year EU network project

From 2003-2006, an EU network project ‘Sustaining Animal Health and Food Safety in Organic Farming' (SAFO), was carried out with 26 partners from 20 EU-countries and 4 related partners from 4 candidate or new member states. The focus was the integration of animal health and welfare issues in organic farming with food safety aspects. Four very consistent conclusions became apparent: 1) The climatic, physical and socio-economic conditions vary considerably throughout Europe, leading to different livestock farming systems. This limits the possibility for technology transfer between regions, and creates several challenges for a harmonised regulation, 2) Implementing organic standards at farm level does not always ensure that animal health and welfare reach the high ideals of the organic principles, 3) To overcome these deficiencies, organic farmers and farmer organisations need to take ownership of organic values and, 4) In all participating countries, a strong need for training of farmers and in particular veterinarians in animal health promotion and organic principles was identified. The article presents a summary of papers presented at the five SAFO workshops.