Use of reverse phase protein microarrays and reference standard development for molecular network analysis of metastatic ovarian carcinoma

Cancer can be defined as a deregulation or hyperactivity in the ongoing network of intracellular and extracellular signaling events. Reverse phase protein microarray technology may offer a new opportunity to measure and profile these signaling pathways, providing data on post-translational phosphorylation events not obtainable by gene microarray analysis. Treatment of ovarian epithelial carcinoma almost always takes place in a metastatic setting since unfortunately the disease is often not detected until later stages. Thus, in addition to elucidation of the molecular network within a tumor specimen, critical questions are to what extent do signaling changes occur upon metastasis and are there common pathway elements that arise in the metastatic microenvironment. For individualized combinatorial therapy, ideal therapeutic selection based on proteomic mapping of phosphorylation end points may require evaluation of the patient's metastatic tissue. Extending these findings to the bedside will require the development of optimized protocols and reference standards. We have developed a reference standard based on a mixture of phosphorylated peptides to begin to address this challenge.

Intervertebral staple grading system with micro-CT

Introduction Intervertebral stapling is a leading method of fusionless scoliosis treatment which attempts to control growth by applying pressure to the convex side of a scoliotic curve in accordance with the Hueter-Volkmann principle. In addition to that, staples have the potential to damage surrounding bone during insertion and subsequent loading. The aim of this study was to assess the extent of bony structural damage including epiphyseal injury as a result of intervertebral stapling using an in vitro bovine model. Materials and Methods Thoracic spines from 6-8 week old calves were dissected and divided into motion segments including levels T4-T11 (n=14). Each segment was potted in polymethylemethacrylate. An Instron Biaxial materials testing machine with a custom made jig was used for testing. The segments were tested in flexion/extension, lateral bending and axial rotation at 37⁰C and 100% humidity, using moment control to a maximum 1.75 Nm with a loading rate of 0.3 Nm per second for 10 cycles. The segments were initially tested uninstrumented with data collected from the tenth load cycle. Next an anterolateral 4-prong Shape Memory Alloy (SMA) staple (Medtronic Sofamor Danek, USA) was inserted into each segment. Biomechanical testing was repeated as before. The staples were cut in half with a diamond saw and carefully removed. Micro-CT scans were performed and sagittal, transverse and coronal reformatted images were produced using ImageJ (NIH, USA).The specimens were divided into 3 grades (0, 1 and 2) according to the number of epiphyses damaged by the staple prongs. Results: There were 9 (65%) segments with grade 1 staple insertions and 5 (35%) segments with grade 2 insertions. There were no grade 0 staples. Grade 2 spines had a higher stiffness level than grade 1 spines, in all axes of movement, by 28% (p=0.004). This was most noted in flexion/extension with an increase of 49% (p=0.042), followed by non-significant change in lateral bending 19% (p=0.129) and axial rotation 8% (p=0.456) stiffness. The cross sectional area of bone destruction from the prongs was only 0.4% larger in the grade 2 group compared to the grade 1 group (p=0.961). Conclusion Intervertebral staples cause epiphyseal damage. There is a difference in stiffness between grade 1 and grade 2 staple insertion segments in flexion/extension only. There is no difference in the cross section of bone destruction as a result of prong insertion and segment motion.

The effect of intervertebral staple insertion on bovine spine segment stiffness

Introduction There is growing interest in the biomechanics of ‘fusionless’ implant constructs used for deformity correction in the thoracic spine. Intervertebral stapling is a leading method of fusionless corrective surgery. Although used for a number of years, there is limited evidence as to the effect these staples have on the stiffness of the functional spinal unit. Materials and Methods Thoracic spines from 6-8 week old calves were dissected and divided into motion segments including levels T4-T11 (n=14). Each segment was potted in polymethylemethacrylate. An Instron Biaxial materials testing machine with a custom made jig was used for testing. The segments were tested in flexion/extension, lateral bending and axial rotation at 37⁰C and 100% humidity, using moment control to a maximum 1.75 Nm with a loading rate of 0.3 Nm per second. This torque was found sufficient to achieve physiologically representative ranges of movement. The segments were initially tested uninstrumented with data collected from the tenth load cycle. Next a left anterolateral Shape Memory Alloy (SMA) staple was inserted (Medtronic Sofamor Danek, USA). Biomechanical testing was repeated as before with data collected from the tenth load cycle. Results In flexion/extension there was an insignificant drop in stiffness of 3% (p=0.478). In lateral bending there was a significant drop in stiffness of 21% (p<0.001). This was mainly in lateral bending away from the staple, where the stiffness reduced by 30% (p<0.001). This was in contrast to lateral bending towards the staple where it dropped by 12% which was still statistically significant (p=0.036). In axial rotation there was an overall near significant drop in stiffness of 11% (p=0.076). However, this was more towards the side of the staple measuring a decrease of 14% as opposed to 8% away from the staple. In both cases it was a statistically insignificant drop (p=0.134 and p=0.352 respectively). Conclusion Insertion of intervertebral SMA staples results in a significant reduction in motion segment stiffness in lateral bending especially in the direction away from the staple. The staple had less effect on axial rotation stiffness and minimal effect on flexion/extension stiffness.

Pharmacist prescribing of venous thromboembolism prophylaxis in a surgical pre-admission clinic

Venous thromboembolism (VTE) is the term used to describe the disease process which presents as either deep vein thrombosis or pulmonary embolism. It is a major cause of death and disability worldwide and places a large financial burden on healthcare systems. Multiple risk factors have been identified for the development of VTE, including hospitalisation for acute medical illness and surgery. Documentation of VTE risk assessment is a critical part of any patient admission, driven by evidence that a risk assessment is a trigger for VTE prophylaxis to be considered. In the United Kingdom, healthcare services have set targets for VTE risk assessment documentation and financial incentives are linked to targets being met...

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.

Health law : scope, sources and forces

• For the purposes of this chapter, “health law” encapsulates regulation of the medical and health professions, the administration of health services and the maintenance of public health to the extent that it is connected to the provision of health services. • There are diverging views as to whether health law can be regarded as a discrete “area of law”. • Health law draws on other areas of law such as tort law, criminal law and family law. It also draws upon other disciplines, most notably medical and health ethics. • Social and economic forces have influenced the development and direction of health law, and these forces may become even more influential in the future. • The increasingly globalised world has implications for Australia's health systems and raises questions and creates commitments in respect of the international community. • Technological developments, including in respect of treatment, diagnosis and information management, create ongoing challenges for health law. • Patient rights, human rights and consumerism are increasingly key drivers in the development of health law. • Health law is significant to contemporary Australian society because of the gravity of the topics that fall within its ambit, its social relevance to so many aspects of human existence and endeavour, the important role it plays in protecting the vulnerable, and the extent to which it engages with fundamental principles of justice.

Adults who lack capacity : substitute decision-making

• Mechanisms to facilitate consent to healthcare for adults who lack capacity are necessary to ensure that these adults can lawfully receive appropriate medical treatment when needed. • In Australia, the common law plays only a limited role in this context, through its recognition of advance directives and through the parens patriae jurisdiction of superior courts. • Substitute decision-making for adults who lack capacity is facilitated primarily by guardianship and other related legislation. This legislation, which has been enacted in all Australian States and Territories, permits a range of decision-makers to make different types of healthcare decisions. • Substitute decision-makers can be appointed by the adult or by a guardianship or other tribunal. Where there is no appointed decision-maker, legislation generally empowers those close to the adult to make the relevant decision. Most Australian jurisdictions have also provided for statutory advance directives. • For the most serious of decisions, such as non-therapeutic sterilisations, consent can only be provided by a tribunal. Other decisions can generally be made by a range of substitute decision-makers. Some treatment, such as very minor treatment or that which is needed in an emergency, can be provided without consent. • Guardianship legislation generally establishes a set of principles and/or other criteria to guide healthcare decisions. Mechanisms have also been established to resolve disputes as to who is the appropriate decision-maker and how a decision should be made.

Double effect and palliative care excuses

• The doctrine of double effect is an exception to the general rule that taking active steps that end life is unlawful. • The essence of the doctrine at common law is intention. • Hastening a patient’s death through palliative care will be lawful provided the primary intention is to relieve pain, and not cause death, even if that death is foreseen. • Some States have enacted legislative excuses that deal with the provision of palliative care. • These statutory excuses tend to be stricter than the common law as they impose other requirements in addition to having an appropriate intent, such as adherence to some level of recognised medical practice.

A digital watermarking framework with application to medical image security

Dealing with digital medical images is raising many new security problems with legal and ethical complexities for local archiving and distant medical services. These include image retention and fraud, distrust and invasion of privacy. This project was a significant step forward in developing a complete framework for systematically designing, analyzing, and applying digital watermarking, with a particular focus on medical image security. A formal generic watermarking model, three new attack models, and an efficient watermarking technique for medical images were developed. These outcomes contribute to standardizing future research in formal modeling and complete security and computational analysis of watermarking schemes.

Psychotropics and challenging behaviour in people with an intellectual disability

Hilmer and Gnjidic drew attention to the pharmacological management of behavioural problems in nursing home residents, and called for a reduction in inappropriate prescribing and the development of alternative management strategies.1 We extend these concerns to another vulnerable population — people with intellectual disability. Historically, this population is one of the most medicated groups in modern society.

Crafting and retelling everyday lives : disabled people's contribution to bioethical concerns

This commentary draws out themes from the narrative symposium on “living with the label “disability”” from the perspective of auto/biography and critical disability studies in the humanities. It notes the disconnect between the experiences discussed in the stories and the preoccupations of bioethicists. Referencing Rosemarie Garland-Thompson’s recent work, it suggests that life stories by people usually described as “disabled” offer narrative, epistemic and ethical resources for bioethics. The commentary suggests that the symposium offers valuable conceptual tools and critiques of taken-for-granted terms like “dependency”. It notes that these narrators do not un–problematically embrace the term “disability”, but emphasize the need to redefine, strategically deploy or reject this term. Some accounts are explicitly critical of medical practitioners while others redefine health and wellbeing, emphasizing the need for reciprocity and respect for the knowledge of people with disability, including knowledge from their experience of “the variant body” (Leach Scully, 2008).

The effect of cryotherapy on the vascular regeneration following closed soft tissue trauma

INTRODUCTION Icing (cryotherapy) is being widely used for the treatment of closed soft tissue trauma (CSTT), such as those resulting from sport injuries. It is believed that cryotherapy induces vasoconstriction and through this mechanism reduces inflammation [1]. However, the impact of this technique on the healing of impaired vasculature and muscle injuries following trauma remains controversial. Recent evidence suggests that the muscle regeneration is delayed after cryotherapy [2]. Consequently, we aimed to investigate the effect of cryotherapy on the vascular morphology following CSTT using an experimental model in rats by contrast-enhanced micro-CT imaging. METHODS Fifty four rats were divided into three main groups: control (no injury, n=6), sham (CSTT but no icing treatment, n=24) and icing (CSTT, treated with one session of ice block massaged directly on the injured muscle for 20 minutes, n=24). The CSTT was induced to the left thigh (Biceps Femoris) of anaesthetised rats (Male, Wistar) to create a standardized and reproducible vascular and muscle injury using an impact device [3]. Following trauma, animals were euthanized after 1, 3, 7, and 28 days healing time (n=6 for each time point). For a three-dimensional vascular morphological assessment, the blood vessels of euthanised rats were flushed with heparinised saline and then perfused with a radio-opaque contrast agent (Microfil, MV 122, Flowtech, USA) using an infusion pump. Both hind-limbs were dissected, and then the injured and non-injured limbs were imaged using a micro-CT scanner (µCT 40, Scanco Medical, Switzerland) and total volume of the perfused blood vessels (TVV) was calculated. More detailed morphological parameters such as vessel volume (VV), diameter (VD), spacing (VSp), number (VN) and connectivity (VConn) were quantified through high resolution (6 µm), micro-CT-scanned biopsy samples (diameter: 8mm) taken directly from the region of the injured muscles. The biopsies were then analysed histologically to confirm the results derived from contrast-enhanced micro-CT imaging. RESULTS AND DISCUSSION The TVV was significantly higher in the injured legs compared to the non-injured legs at day 1 and 7 in the sham group and at day 28 in both sham and icing groups. The biopsies from the injured legs of the icing group showed a significant reduction in VV, VN, VD, VConn and an increase in VSp compared to those in the sham and control groups at days 1, 3 and 7, post injury. While the injured legs of the sham group exhibited a decrease in VN and VConn 28 days post trauma, indicating a return to the original values prior to trauma, these parameters had increased in the icing group (Figure 1). Also, at day 1 post injury, VV and VD of the injured legs were significantly higher in the sham group compared to the icing group, which may be attributed to the effect of vasoconstriction induced by icing. Further histomorphological evaluation of day 1 post injury, indicated that although cryotherapy significantly reduced the injury size and influx of inflammatory cells, including macrophages and neutrophils, a delay in vascular and muscle fiber regeneration was found at later time points confirming other reports from the literature [2]. CONCLUSIONS We have demonstrated using micro-CT imaging that the vascular morphology changes after CSTT, and that its recovery is affected by therapeutic modalities such as icing. This may be useful for the development of future clinical monitoring, diagnosis and treatment of CSTT. While icing reduces the swelling after trauma, our results suggest that it may delay the recovery of the vasculature in the injured tissue.

Beyond Wearables : Experiences and Trends in Design of Portable Medical Devices

The use of Portable Medical Devices (PMDs) has become increasingly widespread over the last few years. A combination of factors; including advances in technology, the pressure to reduce public health costs and the desire to make health solutions accessible to a wider patient base are contributing to the growth in the PMD market. Design has a clear role to play in the current and future context of the PMD landscape. In this paper, we identify emerging trends in the design of PMDs; including changes in the form, purpose and mode of use, and explore how these trends are likely to fundamentally impact the nature of healthcare and the patient experience from an experience design perspective. We conclude by identifying a research opportunity for design within the healthcare and PMD context.

The impact of diabetic ketoacidosis and age on behavior six months post-diagnosis in children with type 1 diabetes

Objectives: Children with type 1 diabetes mellitus (DM1) may be at increased risk of psychosocial and adjustment difficulties. We examined behavioral outcomes six months post-diagnosis in a group of children with newly diagnosed DM1. Methods: This study formed part of a larger longitudinal project examining pathophysiology and neuropsychological outcomes in diabetic patients with or without diabetic ketoacidosis (DKA). Participants were 61 children (mean age 11.8 years, SD 2.7 years) who presented with a new diagnosis of DM1 at the Royal Children’s Hospital, Melbourne. Twenty-three (11 female) presented in DKA and 38 (14 female) without DKA. Parents completed the behavior assessment system for children, second edition six months post-diagnosis. Results: There was a non-linear relationship between age and behavior. Internalising problems (i.e. anxiety depression, withdrawal) peaked in the transition from childhood to adolescence; children aged 10–13 years had elevated rates relative to the normal population (t = 2.55, P = 0.018). There was a non-significant trend for children under 10 to display internalising problems (P = 0.052), but rates were not elevated in children over 13 (P = 0.538). Externalising problems were not significantly elevated in any age group. Interestingly, children who presented in DKA were at lower risk of internalising problems than children without DKA (t = 3.83, P < 0.001). There was no effect of DKA on externalising behaviors. Conclusions: Children transitioning from childhood to adolescence are at significant risk for developing internalising problems such as anxiety and lowered mood after diagnosis of DM1. Somewhat counter-intuitively, parents of children presenting in DKA reported fewer internalising symptoms than parents of children without DKA. These results highlight the importance of monitoring and supporting psychosocial adjustment in newly diagnosed children even when they seem physically well.