Development of reverse phase protein microarrays for clinical applications and patient-tailored therapy

While genomics provide important information about the somatic genetic changes, and RNA transcript profiling can reveal important expression changes that correlate with outcome and response to therapy, it is the proteins that do the work in the cell. At a functional level, derangements within the proteome, driven by post-translational and epigenetic modifications, such as phosphorylation, is the cause of a vast majority of human diseases. Cancer, for instance, is a manifestation of deranged cellular protein molecular networks and cell signaling pathways that are based on genetic changes at the DNA level. Importantly, the protein pathways contain the drug targets in signaling networks that govern overall cellular survival, proliferation, invasion and cell death. Consequently, the promise of proteomics resides in the ability to extend analysis beyond correlation to causality. A critical gap in the information knowledge base of molecular profiling is an understanding of the ongoing activity of protein signaling in human tissue: what is activated and “in use” within the human body at any given point in time. To address this gap, we have invented a new technology, called reverse phase protein microarrays, that can generate a functional read-out of cell signaling networks or pathways for an individual patient obtained directly from a biopsy specimen. This “wiring diagram” can serve as the basis for both, selection of a therapy and patient stratification.

Using patient specific finite element models to understand the biomechanics of paediatric spinal deformity surgery

Adolescent idiopathic scoliosis (AIS) is a spinal deformity, which may require surgical correction by attaching rods to the patient’s spine using screws inserted into the vertebrae. Complication rates for deformity correction surgery are unacceptably high. Determining an achievable correction without overloading the adjacent spinal tissues or implants requires an understanding of the mechanical interaction between these components. We have developed novel patient specific modelling software to create individualized finite element models (FEM) representing the thoracolumbar spine and ribcage of scoliosis patients. We are using these models to better understand the biomechanics of spinal deformity correction.

Gene amplified in oesophageal cancer 1 (GAEC1) amplification in colorectal cancers and its impact on patient's survival

GAEC1 (gene amplified in oesophageal cancer 1) is located at 7q22.1, first identified in oesophageal cancer.1 Initial work indicated that GAEC1 can act as an oncogene.2 Our pilot study found ∼80% of colorectal cancers showing amplification of GAEC1.3 In this research, we will study GAEC1 copy number in colon cancer cell lines and colorectal tissues, and its prognostic significance. Two human colon cancer cell lines (SW480 and SW48) and one normal colonic epithelial cell line (FHC) were obtained from American Type Culture Collection. Culturing conditions for these cell lines were as published previously.4 Tissues were collected from 283 patients (213 Australian; 70 Japanese) diagnosed with colorectal cancers. Ninety surgically removed non-cancer colorectal tissues (diverticular diseases, hyperplastic polyps and volvulus) were used as controls. H&E stained sections from each cancer were checked to select a block with sufficient cancer tissue and representative morphological features for each patient for DNA extraction...

Cutting the Gordian knot of futility : a case for law reform on unilateral withholding and withdrawal of potentially life-sustaining treatment

In this paper, we propose law reform with respect to the unilateral withholding or withdrawal of potentially life-sustaining treatment in Australia and New Zealand. That is, where a doctor withholds or withdraws potentially life-sustaining treatment without consent from a patient or a patient’s substitute decision-maker (where the patient lacks capacity), or authorisation from a court or tribunal, or by operation of a statute or justifiable government or institutional policy. Our proposal is grounded in the core values that do (or should) underpin a regulatory framework on an issue such as this; these values are drawn from existing commitments made by Australia and New Zealand through legislation, the common law, and conventions and treaties. It is also grounded in a critical review of the law on unilateral withholding and withdrawal as well as the legal context within which this issue sits in Australasia. We argue that the current law is inconsistent with the core values and develop a proposal for a legal response to this issue that more closely aligns with the core values it is supposed to serve.

Health Law in Australia [Second Edition]

Health Law in Australia is the country’s leading text in this area and was the first book to deal with health law on a comprehensive national basis. In this important field that continues to give rise to challenges for society Health Law in Australia takes a logical, structured approach to explain the breadth of this area of law across all Australian jurisdictions. By covering all the major areas in this diverse field, Health Law in Australia enhances the understanding of the discipline as a whole. Beginning with an exploration of the general principles of health law, including chapters on “Negligence”, “Children and Consent to Medical Treatment”, and “Medical Confidentiality and Patient Privacy”, the book goes on to consider beginning-of-life and end-of-life issues before concluding with chapters on emerging areas in health law, such as biotechnology, genetic technologies and medical research. The contributing authors are national leaders who are specialists in these areas of health law and who can share with readers the results of their research. Health Law in Australia has been written for both legal and health audiences and is essential reading for undergraduate and postgraduate students, researchers and scholars in the disciplines of law, health and medicine, as well as health and legal practitioners, government departments and bodies in the health area, and private health providers.

Measuring patient flow variations : a cross-organisational process mining approach

Variations that exist in the treatment of patients (with similar symptoms) across different hospitals do substantially impact the quality and costs of healthcare. Consequently, it is important to understand the similarities and differences between the practices across different hospitals. This paper presents a case study on the application of process mining techniques to measure and quantify the differences in the treatment of patients presenting with chest pain symptoms across four South Australian hospitals. Our case study focuses on cross-organisational benchmarking of processes and their performance. Techniques such as clustering, process discovery, performance analysis, and scientific workflows were applied to facilitate such comparative analyses. Lessons learned in overcoming unique challenges in cross-organisational process mining, such as ensuring population comparability, data granularity comparability, and experimental repeatability are also presented.

Discharge practices for the intensive care patient : a qualitative exploration in the general ward setting

OBJECTIVE: To explore how registered nurses (RNs) in the general ward perceive discharge processes and practices for patients recently discharged from the intensive care unit (ICU). BACKGROUND: Patients discharged from the ICU environment often require complicated and multifaceted care. The ward-based RN is at the forefront of the care of this fragile patient population, yet their views and perceptions have seldom been explored. DESIGN: A qualitative grounded theory design was used to guide focus group interviews with the RN participants. METHODS: Five semi-structured focus group interviews, including 27 RN participants, were conducted in an Australian metropolitan tertiary referral hospital in 2011. Data analyses of transcripts, field notes and memos used concurrent data generation, constant comparative analysis and theoretical sampling. RESULTS: Results yielded a core category of 'two worlds' stressing the disconnectedness between ICU and the ward setting. This category was divided into sub categories of 'communication disconnect' and 'remember the family'. Properties of 'what we say', 'what we write', 'transfer' and 'information needs' respectively were developed within those sub-categories. CONCLUSION: The discharge process for patients within the ICU setting is complicated and largely underappreciated. There are fundamental, misunderstood differences in prioritisation and care of patients between the areas, with a deep understanding of practice requirements of ward based RNs not being understood. The findings of this research may be used to facilitate inter departmental communications and progress practice development.

Withholding and withdrawing life-sustaining treatment in a patient's best interests : Australian judicial deliberations

•Intractable disputes about withholding and withdrawing life-sustaining treatment from adults who lack capacity are rare but challenging. Judicial resolution may be needed in some of these cases. •A central concept for judicial (and clinical) decision making in this area is a patient's “best interests”. Yet what this term means is contested. •There is an emerging Supreme Court jurisprudence that sheds light on when life-sustaining treatment will, or will not, be judged to be in a patient's best interests. •Treatment that is either futile or overly burdensome is not in a patient's best interests. Although courts will consider patient and family wishes, they have generally deferred to the views of medical practitioners about treatment decisions.

Informatics to support patient choice between diverse medical systems

Culturally, philosophically and religiously diverse medical systems including Western medicine, Traditional Chinese Medicine, Ayurvedic Medicine and Homeopathic Medicine, once situated in places and times relatively unconnected from each other, currently co-exist to a point where patients must choose which system to consult. These decisions require comparative analyses, yet the divergence in key underpinning assumptions is so great that comparisons cannot easily be made. However, diverse medical systems can be meaningfully juxtaposed for the purpose of making practical decisions if relevant information is presented appropriately. Information regarding privacy provisions inherent in the typical practice of each medical system is an important element in this juxtaposition. In this paper the information needs of patients making decisions regarding the selection of a medical system are examined.

Ethical values in emergency medical services: A pilot study

Background Ambulance professionals often address conflicts between ethical values. As individuals’ values represent basic convictions of what is right or good and motivate behaviour, research is needed to understand their value profiles. Objectives To translate and adapt the Managerial Values Profile to Spanish and Swedish, and measure the presence of utilitarianism, moral rights and/or social justice in ambulance professionals’ value profiles in Spain and Sweden. Methods The instrument was translated and culturally adapted. A content validity index was calculated. Pilot tests were carried out with 46 participants. Ethical considerations This study conforms to the ethical principles for research involving human subjects and adheres to national laws and regulations concerning informed consent and confidentiality. Findings Spanish professionals favoured justice and Swedish professionals’ rights in their ambulance organizations. Both countries favoured utilitarianism least. Gender differences across countries showed that males favoured rights. Spanish female professionals favoured justice most strongly of all. Discussion Swedes favour rights while Spaniards favour justice. Both contexts scored low on utilitarianism focusing on total population effect, preferring the opposite, individualized approach of the rights and justice perspectives. Organizational investment in a utilitarian perspective might jeopardize ambulance professionals’ moral right to make individual assessments based on the needs of the patient at hand. Utilitarianism and a caring ethos appear as stark opposites. However, a caring ethos in its turn might well involve unreasonable demands on the individual carer’s professional role. Since both the justice and rights perspectives portrayed in the survey mainly concern relationship to the organization and peers within the organization, this relationship might at worst be given priority over the equal treatment and moral rights of the patient. Conclusion A balanced view on ethical perspectives is needed to make professionals observant and ready to act optimally – especially if these perspectives are used in patient care. Research is needed to clarify how justice and rights are prioritized by ambulance services and whether or not these organization-related values are also implemented in patient care.