Effect of CT electron density identification on Monte Carlo simulations of radiotherapeutic treatments

Introduction: The accurate identification of tissue electron densities is of great importance for Monte Carlo (MC) dose calculations. When converting patient CT data into a voxelised format suitable for MC simulations, however, it is common to simplify the assignment of electron densities so that the complex tissues existing in the human body are categorized into a few basic types. This study examines the effects that the assignment of tissue types and the calculation of densities can have on the results of MC simulations, for the particular case of a Siemen’s Sensation 4 CT scanner located in a radiotherapy centre where QA measurements are routinely made using 11 tissue types (plus air). Methods: DOSXYZnrc phantoms are generated from CT data, using the CTCREATE user code, with the relationship between Hounsfield units (HU) and density determined via linear interpolation between a series of specified points on the ‘CT-density ramp’ (see Figure 1(a)). Tissue types are assigned according to HU ranges. Each voxel in the DOSXYZnrc phantom therefore has an electron density (electrons/cm3) defined by the product of the mass density (from the HU conversion) and the intrinsic electron density (electrons /gram) (from the material assignment), in that voxel. In this study, we consider the problems of density conversion and material identification separately: the CT-density ramp is simplified by decreasing the number of points which define it from 12 down to 8, 3 and 2; and the material-type-assignment is varied by defining the materials which comprise our test phantom (a Supertech head) as two tissues and bone, two plastics and bone, water only and (as an extreme case) lead only. The effect of these parameters on radiological thickness maps derived from simulated portal images is investigated. Results & Discussion: Increasing the degree of simplification of the CT-density ramp results in an increasing effect on the resulting radiological thickness calculated for the Supertech head phantom. For instance, defining the CT-density ramp using 8 points, instead of 12, results in a maximum radiological thickness change of 0.2 cm, whereas defining the CT-density ramp using only 2 points results in a maximum radiological thickness change of 11.2 cm. Changing the definition of the materials comprising the phantom between water and plastic and tissue results in millimetre-scale changes to the resulting radiological thickness. When the entire phantom is defined as lead, this alteration changes the calculated radiological thickness by a maximum of 9.7 cm. Evidently, the simplification of the CT-density ramp has a greater effect on the resulting radiological thickness map than does the alteration of the assignment of tissue types. Conclusions: It is possible to alter the definitions of the tissue types comprising the phantom (or patient) without substantially altering the results of simulated portal images. However, these images are very sensitive to the accurate identification of the HU-density relationship. When converting data from a patient’s CT into a MC simulation phantom, therefore, all possible care should be taken to accurately reproduce the conversion between HU and mass density, for the specific CT scanner used. Acknowledgements: This work is funded by the NHMRC, through a project grant, and supported by the Queensland University of Technology (QUT) and the Royal Brisbane and Women's Hospital (RBWH), Brisbane, Australia. The authors are grateful to the staff of the RBWH, especially Darren Cassidy, for assistance in obtaining the phantom CT data used in this study. The authors also wish to thank Cathy Hargrave, of QUT, for assistance in formatting the CT data, using the Pinnacle TPS. Computational resources and services used in this work were provided by the HPC and Research Support Group, QUT, Brisbane, Australia.

Natural and engineered plasmin inhibitors : applications and design strategies

Plasmin is the primary enzyme responsible for dissolution of fibrin in the circulatory system. Plasminogen, the zymogen of plasmin is expressed ubiquitously in the human body [1], with the predominant source being the liver [2, 3]. Plasminogen is produced as an 810 amino acid protein with a 19 amino acid leader peptide, which is cleaved during secretion to produce the mature 791 amino acid one-chain zymogen. This is converted to plasmin by cleavage of the Arg561 - Val562 scissile bond [4], resulting in an active protease consisting of two disulfide linked chains. The amino-terminal heavy chain (residues Glu1-Arg561) is comprised of a plasminogen/apple/nematode (PAN) domain [5] and five kringle domains of approximately equal size [6] while the light chain (residues Val562-Asn791) contains a serine protease domain homologous to trypsin with a catalytic triad comprising His603, Asp646 and Ser741 [7]. Both plasmin and plasminogen occur in two forms, full length and a Lys77-Lys78 activated variant produced through self catalysis (Figure 1). The former exists in a tight conformation through binding of Lys50 and/or Lys62 to kringle domain 5 [8, 9] while Lys78-plasminogen assumes a more relaxed conformation rendering it more susceptible to plasmin conversion [10, 11].

Image segmentation and pose estimation of humans in video

This thesis introduces improved techniques towards automatically estimating the pose of humans from video. It examines a complete workflow to estimating pose, from the segmentation of the raw video stream to extract silhouettes, to using the silhouettes in order to determine the relative orientation of parts of the human body. The proposed segmentation algorithms have improved performance and reduced complexity, while the pose estimation shows superior accuracy during difficult cases of self occlusion.

Mainstream monsters : the otherness of humans in Twilight, the Vampire Diaries and True Blood

The representation of vampires in horror movies and television programmes has changed considerably over the last two decades. No longer is the vampire portrayed simply as a monster or representation of death. Now, the vampire on our screen such as True Blood’s Bill Compton, or Twilight’s Edward Cullen, passes as human, chooses to make morally sound decisions, becomes an upstanding assimilated citizen, works in the community, and aspires to be a husband to mortal women. The success of recent series such as The Twilight Saga (2009, 2010, 2011, 2012), The Vampire Diaries (2009 - ) and True Blood (2008 - ) has popularised the idea of vampires who cling to remnants of their humanity (or memories of what it means to be human) and attempt to live as human, which builds upon similar – albeit embryonic – themes which emerged from the vampire sub-genre in the 1990s. Within these narratives, representations of the other have shifted from the traditional idea of the monster, to alternative and surprising loci. As this chapter argues, humans themselves, and the concept of the human body, now represent, in many instances, both abject and other. The chapter begins by considering the nature of the abject and otherness in relation to representations of classical vampires and how they have traditionally embodied the other. This provides a backdrop against which to examine the characteristics of the contemporary mainstreaming vampire ‘monster’. An examination of the broad thematic and representational shifts from other to mainstream vampire demonstrates how mainstream monsters are increasingly assimilating into mortal lifestyles with trappings that many viewers may find appealing. The same shifts in theme and representation also reveal that humans are frequently cast as mundane and unappealing in contemporary vampire narratives.

Recent advances in the design of artificial corneas

Purpose of review: Artificial corneas are being developed to meet a shortage of donor corneas as well as to address cases where allografting is contraindicated. A range of artificial corneas has been developed. Here we review several newer designs and especially those inspired by naturally occurring biomaterials found with the human body and elsewhere. Recent findings: Recent trends in the development of artificial corneas indicate a move towards the use of materials derived from native sources including decellularized corneal tissue and tissue substitutes synthesized by corneal cells in vitro when grown either on their own, or in conjunction with novel protein-based scaffolds. Biologically inspired materials are also being considered for implantation on their own with the view to promoting endogenous corneal tissue. Summary: More recent attempts at making artificial corneas have taken a more nature-based or nature-inspired approach. Several will in the near future be likely to be available clinically.

Editorial : Law and ethics for the bioeconomy and beyond

The convergence of biological, technological and economic realms of life has fostered the development of the bioeconomy as a new feature of contemporary society. As the meaning of life and the human body is redefined in the context of the bioeconomy, new challenges have emerged for ethics and law In the face of these challenges, it is imperative that the currency of regulatory frameworks is maintained through the processes of regular review and update. The National Health and Medical Research Council has recently released the new National Statement on Ethical Conduct in Human Research to provide guidance for health research in Australia. The new National Statement will play an important part in supporting innovation and the development of the knowledge economy.

Rational design of artificial cellular niches for tissue engineering

Tissue Engineering is a promising emerging field that studies the intrinsic regenerative potential of the human body and uses it to restore functionality of damaged organs or tissues unable of self-healing due to illness or ageing. In order to achieve regeneration using Tissue Engineering strategies, it is first necessary to study the properties of the native tissue and determine the cause of tissue failure; second, to identify an optimum population of cells capable of restoring its functionality; and third, to design and manufacture a cellular microenvironment in which those specific cells are directed towards the desired cellular functions. The design of the artificial cellular niche has a tremendous importance, because cells will feel and respond to both its biochemical and biophysical properties very differently. In particular, the artificial niche will act as a physical scaffold for the cells, allowing their three-dimensional spatial organization; also, it will provide mechanical stability to the artificial construct; and finally, it will supply biochemical and mechanical cues to control cellular growth, migration, differentiation and synthesis of natural extracellular matrix. During the last decades, many scientists have made great contributions to the field of Tissue Engineering. Even though this research has frequently been accompanied by vast investments during extended periods of time, yet too often these efforts have not been enough to translate the advances into new clinical therapies. More and more scientists in this field are aware of the need of rational experimental designs before carrying out complex, expensive and time-consuming in vitro and in vivo trials. This review highlights the importance of computer modeling and novel biofabrication techniques as critical key players for a rational design of artificial cellular niches in Tissue Engineering.

Highly effective fungal inactivation in He+O2 atmospheric-pressure nonequilibrium plasmas

Highly effective (more than 99.9%) inactivation of a pathogenic fungus Candida albicans commonly found in oral, respiratory, digestive, and reproduction systems of a human body using atmospheric-pressure plasma jets sustained in He+ O2 gas mixtures is reported. The inactivation is demonstrated in two fungal culture configurations with open (Petri dish without a cover) and restricted access to the atmosphere (Petri dish with a cover) under specific experimental conditions. It is shown that the fungal inactivation is remarkably more effective in the second configuration. This observation is supported by the scanning and transmission electron microscopy of the fungi before and after the plasma treatment. The inactivation mechanism explains the experimental observations under different experimental conditions and is consistent with the reports by other authors. The results are promising for the development of advanced health care applications.

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.

Nearness and revealing : The edible veil of the sensible being.

Taking cues from the fragility and grace enfolded within Asian cuisine, this paper explores recent experimentation of an edible rice paper veil. The veil fashions a 'secondary skin', what Jeffery Schnapp the author of 'The Fabric of Modern Times', calls an "object for prosthetic shelf extension...bearing a uniquely intimate and direct relation to the human body" (Schnapp, 1997:197). The process reveals a layered material mutable to moisture and humidity, changing its elastic state in relation to body and surroundings. The moving, breathing, sweating surface of the body further modifies both veil and bodily experience drawing forth deeper emotional responses. The implications here offer a reciprocal affect, a revealing, where new materiality evokes the threshold to a new sensible being, one aware of the depth of material consciousness and inter-corporeal engagement, and which extends the relations between thinking and being of Heidegger and Shklovsky's seminal works.

Historical intake and elimination of polychlorinated biphenyls and organochlorine pesticides by the Australian population reconstructed from biomonitoring data

Quantifying the competing rates of intake and elimination of persistent organic pollutants (POPs) in the human body is necessary to understand the levels and trends of POPs at a population level. In this paper we reconstruct the historical intake and elimination of ten polychlorinated biphenyls (PCBs) and five organochlorine pesticides (OCPs) from Australian biomonitoring data by fitting a population-level pharmacokinetic (PK) model. Our analysis exploits two sets of cross-sectional biomonitoring data for PCBs and OCPs in pooled blood serum samples from the Australian population that were collected in 2003 and 2009. The modeled adult reference intakes in 1975 for PCB congeners ranged from 0.89 to 24.5 ng/kg bw/day, lower than the daily intakes of OCPs ranging from 73 to 970 ng/kg bw/day. Modeled intake rates are declining with half-times from 1.1 to 1.3 years for PCB congeners and 0.83 to 0.97 years for OCPs. The shortest modeled intrinsic human elimination half-life among the compounds studied here is 6.4 years for hexachlorobenzene, and the longest is 30 years for PCB-74. Our results indicate that it is feasible to reconstruct intakes and to estimate intrinsic human elimination half-lives using the population-level PK model and biomonitoring data only. Our modeled intrinsic human elimination half-lives are in good agreement with values from a similar study carried out for the population of the United Kingdom, and are generally longer than reported values from other industrialized countries in the Northern Hemisphere.

The Complex Politics of Care: Needs and interests, norms and desires

If you want to understand something about a society, and the social contracts that underpin it, then understanding the way it positions women, children, those with corporeal or cognitive differences and other not-quitecitizens is a good place to start. As most now understand, this positioning is not natural; it is part of the high-stakes social, institutional and above all ideological labour of defining the human body, directing human behaviour and determining who will hold agency, authority and power...

Translating biomechanics research into clinical practice

There is a large amount of research conducted each year examining every aspect of the mechanics of the human body and its interaction with medical devices and the environment; from the cellular level through to the whole body. While, as researchers, we obtain great pleasure from conducting studies and creating new knowledge we need to keep in mind that while this is a good thing it is even better if this new knowledge can lead to improvement in the quality of life for individuals suffering from biomechanical disorders. Such that while commercialisation is a good aim, not all research leads to marketable outcomes. However, it can lead to improvements in surgical techniques and clinical practice. It is important for us to identify and promote how the outcomes of research lead to improvements in quality of care, as this is perhaps the most important outcome for individual patients.

The empire of cancer: Gene patents and cancer voices

In his book, The Emperor of All Maladies, Siddhartha Mukherjee writes a history of cancer — "It is a chronicle of an ancient disease — once a clandestine, 'whispered-about' illness — that has metamorphosed into a lethal shape-shifting entity imbued with such penetrating metaphorical, medical, scientific, and political potency that cancer is often described as the defining plague of our generation." Increasingly, an important theme in the history of cancer is the role of law, particularly in the field of intellectual property law. It is striking that a number of contemporary policy debates over intellectual property and public health have concerned cancer research, diagnosis, and treatment. In the area of access to essential medicines, there has been much debate over Novartis’ patent application in respect of Glivec, a treatment for leukaemia. India’s Supreme Court held that the Swiss company’s patent application violated a safeguard provision in India’s patent law designed to stop evergreening. In the field of tobacco control, the Australian Government introduced plain packaging for tobacco products in order to address the health burdens associated with the tobacco epidemic. This regime was successfully defended in the High Court of Australia. In the area of intellectual property and biotechnology, there have been significant disputes over the Utah biotechnology company Myriad Genetics and its patents in respect of genetic testing for BRCA1 and BRCA2, which are related to breast cancer and ovarian cancer. The Federal Court of Australia handed down a decision on the validity of Myriad Genetics’ patent in respect of genetic testing for BRCA1 in February 2013. The Supreme Court of the United States heard a challenge to the validity of Myriad Genetics’ patents in this area in April 2013, and handed down a judgment in July 2013. Such disputes have involved tensions between intellectual property rights, and public health. This article focuses upon one of these important test cases involving intellectual property, public health, and cancer research. In June 2010, Cancer Voices Australia and Yvonne D’Arcy brought an action in the Federal Court of Australia against the validity of a BRCA1 patent — held by Myriad Genetics Inc, the Centre de Recherche du Chul, the Cancer Institute of Japan and Genetic Technologies Limited. Yvonne D’Arcy — a Brisbane woman who has had treatment for breast cancer — maintained: "I believe that what they are doing is morally and ethically corrupt and that big companies should not control any parts of the human body." She observed: "For my daughter, I've had her have [sic] mammograms, etc, because of me but I would still like her to be able to have the test to see if the mutation gene is in there from me." The applicants made the following arguments: "Genes and the information represented by human gene sequences are products of nature universally present in each individual, and the information content of a human gene sequence is fixed. Genetic variations or mutations are products of nature. The isolation of the BRCA1 gene mutation from the human body constitutes no more than a medical or scientific discovery of a naturally occurring phenomenon and does not give rise to a patentable invention." The applicants also argued that "the alleged invention is not a patentable invention in that, so far as claimed in claims 1–3, it is not a manner of manufacture within the meaning of s 6 of the Statute of Monopolies". The applicants suggested that "the alleged invention is a mere discovery". Moreover, the applicants contended that "the alleged invention of each of claims 1-3 is not a patentable invention because they are claims for biological processes for the generation of human beings". The applicants, though, later dropped the argument that the patent claims related to biological processes for the generation of human beings. In February 2013, Nicholas J of the Federal Court of Australia considered the case brought by Cancer Voices Australia and Yvonne D’Arcy against Myriad Genetics. The judge presented the issues in the case, as follows: "The issue that arises in this case is of considerable importance. It relates to the patentability of genes, or gene sequences, and the practice of 'gene patenting'. Briefly stated, the issue to be decided is whether under the Patents Act 1990 (Cth) a valid patent may be granted for a claim that covers naturally occurring nucleic acid — either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) — that has been 'isolated'". In this context, the word "isolated" implies that naturally occurring nucleic acid found in the cells of the human body, whether it be DNA or RNA, has been removed from the cellular environment in which it naturally exists and separated from other cellular components also found there. The genes found in the human body are made of nucleic acid. The particular gene with which the patent in suit is concerned (BRCA1) is a human breast and ovarian cancer disposing gene. Various mutations that may be present in this gene have been linked to various forms of cancer including breast cancer and ovarian cancer.' The judge held in this particular case that Myriad Genetics’ patent claims were a "manner of manufacture" under s 6 of the Statute of Monopolies and s 18(1)(a) of the Patents Act 1990 (Cth). The matter is currently under appeal in the Full Court of the Federal Court of Australia. This article interprets the dispute over Myriad Genetics in light of the scholarly work of Nobel Laureate Professor Joseph Stiglitz on inequality. Such work has significant explanatory power in the context of intellectual property and biotechnology. First, Stiglitz has contended that "societal inequality was a result not just of the laws of economics, but also of how we shape the economy — through politics, including through almost every aspect of our legal system". Stiglitz is concerned that "our intellectual property regime … contributes needlessly to the gravest form of inequality." He maintains: "The right to life should not be contingent on the ability to pay." Second, Stiglitz worries that "some of the most iniquitous aspects of inequality creation within our economic system are a result of 'rent-seeking': profits, and inequality, generated by manipulating social or political conditions to get a larger share of the economic pie, rather than increasing the size of that pie". He observes that "the most iniquitous aspect of this wealth appropriation arises when the wealth that goes to the top comes at the expense of the bottom." Third, Stiglitz comments: "When the legal regime governing intellectual property rights is designed poorly, it facilitates rent-seeking" and "the result is that there is actually less innovation and more inequality." He is concerned that intellectual property regimes "create monopoly rents that impede access to health both create inequality and hamper growth more generally." Finally, Stiglitz has recommended: "Government-financed research, foundations, and the prize system … are alternatives, with major advantages, and without the inequality-increasing disadvantages of the current intellectual property rights system.’" This article provides a critical analysis of the Australian litigation and debate surrounding Myriad Genetics’ patents in respect of genetic testing for BRCA1. First, it considers the ruling of Nicholas J in the Federal Court of Australia that Myriad Genetics’ patent was a manner of manufacture as it related to an artificially created state of affairs, and not mere products of nature. Second, it examines the policy debate over gene patents in Australia, and its relevance to the litigation involving Myriad Genetics. Third, it examines comparative law, and contrasts the ruling by Nicholas J in the Federal Court of Australia with developments in the United States, Canada, and the European Union. Fourth, this piece considers the reaction to the decision of Nicholas at first instance in Australia. Fifth, the article assesses the prospects of an appeal to the Full Federal Court of Australia over the Myriad Genetics’ patents. Finally, this article observes that, whatever happens in respect of litigation against Myriad Genetics, there remains controversy over Genetic Technologies Limited. The Melbourne firm has been aggressively licensing and enforcing its related patents on non-coding DNA and genomic mapping.

Multimodal imaging of the collagen and elastic fibre networks in the bovine intervertebral disc

INTRODUCTION. The intervertebral disc is the largest avascular structure in the human body, withstanding transient loads of up to nine times body weight during rigorous physical activity. The key structural elements of the disc are a gel-like nucleus pulposus surrounded by concentric lamellar rings containing criss-crossed collagen fibres. The disc also contains an elastic fiber network which has been suggested to play a structural role, but to date the relationship between the collagen and elastic fiber networks is unclear. CONCLUSION. The multimodal transmitted and reflected polarized light microscopy technique developed here allows clear differentiation between the collagen and elastic fiber networks of the intervertebral disc. The ability to image unstained specimens avoids concerns with uneven stain penetration or specificity of staining. In bovine tail discs, the elastic fiber network is intimately associated with the collagen network.