Invading edge vs. inner (edvin) patterns of vascularization : an interplay between angiogenic and vascular survival factors defines the clinical behaviour of non-small cell lung cancer

Neo-angiogenesis during neoplastic growth involves endothelial mitogenic and migration stimuli produced by cancer or tumour stromal cells. Although this active angiogenesis takes place in the tumour periphery, the process of vessel growth and survival in inner areas and its clinical role remain largely unexplored. The present study compared the microvessel score (MS) as well as the single endothelial cell score (ECS) in the invading edge and in inner areas of non-small cell lung carcinomas (NSCLCs). Three different patterns of vascular growth were distinguished: the edvin (edge vs. inner) type 1, where a low MS was observed in both peripheral and inner tumour areas; the edvin type 2, where a high MS was noted in the invading front but a low MS in inner areas; and the edvin type 3, where both peripheral and inner tumour areas had a high MS. The ECS was high in the invading edge in edvin type 2 and 3 cases and was sharply decreased in both types in inner areas, suggesting that endothelial cell migration is unlikely to contribute to the angiogenic process in areas away from the tumour front. Expression of the vascular endothelial growth factor (VEGF) and of thymidine phosphorylase (TP) was associated with a high MS in the invading edge. VEGF was associated with a high MS in inner areas (edvin 3), while TP expression was associated with edvin type 2, showing that VEGF (and not TP) contributes to the preservation of the inner vasculature. Both edvin type 2 and 3 cases showed an increased incidence of node metastasis, but edvin type 3 cases had a poorer prognosis, even in the N1-stage group. The present study suggests that tumour factors regulating angiogenesis and vascular survival are not identical. A possible method is reported to quantify these two parameters by comparing the MS in the invading edge and inner areas (edvin types). This observation may contribute to the evaluation of the effectiveness of different therapeutic approaches, namely vascular targeting vs. anti-angiogenesis. Copyright (C) 2000 John Wiley and Sons, Ltd.

Governing young people’s drug use: Crime, harm and contemporary drug use practices

Since the nineteenth century, drug use has been variously understood as a problem of epidemiology, psychiatry, physiology, and criminality. Consequently drug research tends to be underpinned by assumptions of inevitable harm, and is often directed towards preventing drug use or solving problems. These constructions of the drug problem have generated a range of law enforcement responses, drug treatment technologies and rehabilitative programs that are intended to prevent drug related harm and resituate drug users in the realm of neo-liberal functional citizenship. This paper is based on empirical research of young people’s illicit drug use in Brisbane. The research rejects the idea of a pre-given drug problem, and seeks to understand how drugs have come to be defined as a problem. Using Michel Foucault’s conceptual framework of governmentality, the paper explores how the governance of illicit drugs, through law, public health and medicine, intersects with self-governance to shape young people’s drug use practices. It is argued that constructions of the drug problem shape what drug users believe about themselves and the ways in which they use drugs. From this perspective, drug use practices are ‘practices of the self’, formed through an interaction of the government of illicit drugs and the drug users own subjectivity.

Manifestations of preoperational reasoning on similar programming tasks

In this research paper, we study a simple programming problem that only requires knowledge of variables and assignment statements, and yet we found that some early novice programmers had difficulty solving the problem. We also present data from think aloud studies which demonstrate the nature of those difficulties. We interpret our data within a neo-Piagetian framework which describes cognitive developmental stages through which students pass as they learn to program. We describe in detail think aloud sessions with novices who reason at the neo-Piagetian preoperational level. Those students exhibit two problems. First, they focus on very small parts of the code and lose sight of the "big picture". Second, they are prone to focus on superficial aspects of the task that are not functionally central to the solution. It is not until the transition into the concrete operational stage that decentration of focus occurs, and they have the cognitive ability to reason about abstract quantities that are conserved, and are equipped to adapt skills to closely related tasks. Our results, and the neo-Piagetian framework on which they are based, suggest that changes are necessary in teaching practice to better support novices who have not reached the concrete operational stage.

Longitudinal think aloud study of a novice programmer

Recent research from within a neo-Piagetian perspective proposes that novice programmers pass through the sensorimotor and preoperational stages before being able to reason at the concrete operational stage. However, academics traditionally teach and assess introductory programming as if students commence at the concrete operational stage. In this paper, we present results from a series of think aloud sessions with a single student, known by the pseudonym “Donald”. We conducted the sessions mainly over one semester, with an additional session three semesters later. Donald first manifested predominately sensorimotor reasoning, followed by preoperational reasoning, and finally concrete operational reasoning. This longitudinal think aloud study of Donald is the first direct observational evidence of a novice programmer progressing through the neo-Piagetian stages.

Giving voice : the prisoner and discursive citizenship

This Companion presents the major debates and issues in Critical Criminology. It presents new research on crime, policy and the internationalisation of the criminal justice system. It sheds light on traditional debates in critical criminology through a confronting analysis of contemporary developments in criminal justice and criminology. This is the first textbook that brings together the major Australian and New Zealand theorists in Critical Criminology. The chapters represent the contribution of these authors in both their established work and their recent scholarship. It includes new approaches to theory, methodology, case studies and contemporary issues. It traverses a range of debates including the criminalisation of Indigenous people, ethnic communities, the working class, rural communities and young people from critical perspectives, and introduces new concepts of state crime. It covers developments in the penal system that have responded to globalisation and neo-liberalism, particularly in law and order and anti-terror campaigns. This coverage is counterpoised by portrayals of resistance within the penal system and considerations of restorative justice. The Companion is relevant to a broad range of courses and levels of study. It covers the major components of a Criminology course through a critical lens. It is a thorough introduction to concepts and critiques in criminology, as well as a provocative analysis of the assumptions underpinning the criminal justice system. Students, teachers and scholars in criminology, law and sociology will find this Companion invaluable.

Searching for a social democratic narrative in criminal justice

Paul Keating recently noted that what the Rudd Government lacked was an overall narrative or story. I would like to argue that Paul Keating is correct and suggest a narrative: that of retrieving and defending aspects of our social democratic heritage from some of the damaging effects wrought by neo-liberalism. Moreover I want to argue that criminal justice policy needs to be seen as a part of this broader narrative, which requires it being prised from its current site, where it is wedged firmly in the narrative of law and order.

Editorial : Action research, action learning and community services

This edition of ALARj has a focus on the contribution of action learning and action research to the development of community services, particularly nonprofits. The landscape of community services has been changing rapidly in recent decades, and can be typified by the notion of complexity. Complexity in the nature of issues that services seek to respond to, complexity in the policy environment and systems of support that have tended to silo and compartmentalise problems and people, and complexity in the institutional location non-profit services occupy in ‘helping’ those who are seen as ‘in need’ or marginalised. In addition to being typified by complexity the environment in which community services are located is dynamic, undergoing profound and ongoing change as neo-liberal approaches to understanding and responding to human need, which emphasise the individualisation of risk, and market principles such as choice, competition and innovation, drive social policy. How can long held values of empowerment, care, inclusivity and benefit to individuals and communities have expression in community services as they grapple with the challenges of being viable and relevant in such a dynamically changing environment? This edition brings together a range of contributions which speak to these challenges. The thematic through these is that processes are needed which engage services and communities in ongoing processes of inquiry about how they can best proceed in contexts typified by complexity and change. Action learning and action research can provide processes of this character.

Analysis of strain-rate dependent mechanical behavior of single chondrocyte : a finite element study

Various studies have been conducted to investigate the effects of impact loading on cartilage damage and chondrocyte death. These have shown that the rate and magnitude of the applied strain significantly influence chondrocyte death, and that cell death occurred mostly in the superficial zone of cartilage suggesting the need to further understand the fundamental mechanisms underlying the chondrocytes death induced at certain levels of strain-rate. To date there is no comprehensive study providing insight on this phenomenon. The aim of this study is to examine the strain-rate dependent behavior of a single chondrocyte using a computational approach based on Finite Element Method (FEM). An FEM model was developed using various mechanical models, which were Standard Neo-Hookean Solid (SnHS), porohyperelastic (PHE) and poroviscohyperelastic (PVHE) to simulate Atomic Force Microscopy (AFM) experiments of chondrocyte. The PVHE showed, it can capture both relaxation and loading rate dependent behaviors of chondrocytes, accurately compared to other models.

Optimization approaches for the design of additively manufactured scaffolds

Scaffolds play a pivotal role in tissue engineering, promoting the synthesis of neo extra-cellular matrix (ECM), and providing temporary mechanical support for the cells during tissue regeneration. Advances introduced by additive manufacturing techniques have significantly improved the ability to regulate scaffold architecture, enhancing the control over scaffold shape and porosity. Thus, considerable research efforts have been devoted to the fabrication of 3D porous scaffolds with optimized micro-architectural features. This chapter gives an overview of the methods for the design of additively manufactured scaffolds and their applicability in tissue engineering (TE). Along with a survey of the state of the art, the Authors will also present a recently developed method, called Load-Adaptive Scaffold Architecturing (LASA), which returns scaffold architectures optimized for given applied mechanical loads systems, once the specific stress distribution is evaluated through Finite Element Analysis (FEA).

Simulation of plant cell shrinkage during drying : A SPH–DEM approach

Plant based dried food products are popular commodities in global market where much research is focused to improve the products and processing techniques. In this regard, numerical modelling is highly applicable and in this work, a coupled meshfree particle-based two-dimensional (2-D) model was developed to simulate micro-scale deformations of plant cells during drying. Smoothed Particle Hydrodynamics (SPH) was used to model the viscous cell protoplasm (cell fluid) by approximating it to an incompressible Newtonian fluid. The visco-elastic characteristic of the cell wall was approximated to a Neo-Hookean solid material augmented with a viscous term and modelled with a Discrete Element Method (DEM). Compared to a previous work [H. C. P. Karunasena, W. Senadeera, Y. T. Gu and R. J. Brown, Appl. Math. Model., 2014], this study proposes three model improvements: linearly decreasing positive cell turgor pressure during drying, cell wall contraction forces and cell wall drying. The improvements made the model more comparable with experimental findings on dried cell morphology and geometric properties such as cell area, diameter, perimeter, roundness, elongation and compactness. This single cell model could be used as a building block for advanced tissue models which are highly applicable for product and process optimizations in Food Engineering.

An adipoinductive role of inflammation in adipose tissue engineering : key factors in the early development of engineered soft tissues

Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming new adipose tissue in a mouse tissue engineering chamber (TEC) and characterized the gene and protein expression of cytokines in the newly developing tissues. EGFP-labeled bone marrow transplant mice and MacGreen mice were implanted with TEC for periods ranging from 0.5 days to 6 weeks. Tissues were collected at various time points and assessed for cytokine expression through ELISA and mRNA analysis or labeled for specific cell populations in the TEC. Macrophage-derived factors, such as monocyte chemotactic protein-1 (MCP-1), appear to induce adipogenesis by recruiting macrophages and bone marrow-derived precursor cells to the TEC at early time points, with a second wave of nonbone marrow-derived progenitors. Gene expression analysis suggests that TNFα, LCN-2, and Interleukin 1β are important in early stages of neo-adipogenesis. Increasing platelet-derived growth factor and vascular endothelial cell growth factor expression at early time points correlates with preadipocyte proliferation and induction of angiogenesis. This study provides new information about key elements that are involved in early development of new adipose tissue.

Women on the Heritage Register : the case of Nellie McCredie and Uanda House

Uanda house is of historical importance to Queensland both in terms of its architectural design and its social history. Uanda is a low set, single story house built in 1928, located in the inner city Brisbane suburb of Wilston. Architecturally, the house has a number of features that distinguish it from the surrounding bungalow influenced inter-war houses. The house has been described as a Queensland style house with neo-Georgian influences. Historically, it is associated with the entry of women into the profession of architecture in Queensland. Uanda is the only remaining intact work of architect/draftswoman Nellie McCredie and one of a very few examples of works by pioneering women architects in Queensland. The house was entered into the Queensland Heritage Register, in 2000, after an appeal against Brisbane City Council’s refusal of an application to demolish the house was disputed in the Queensland Planning and Environment court in 1998/1999. In the court’s report, Judge Robin QC, DCJ, stated that, “The importance of preserving women's history and heritage, often previously marginalised or lost, is now accepted at government level, recognising that role models are vital for bringing new generations of women into the professions and public life.” While acknowledging women’s contribution to the profession of architecture is an important endeavour, it also has the potential to isolate women architects as separate to a mainstream history of architecture. As Julie Willis writes, it can imply an atypical, feminine style of architecture. What is the impact or potential implications of recognising heritage buildings designed by women architects? The Judge also highlights the absence of a recorded history of unique Brisbane houses and questions the authority of the heritage register. This research looks at these points of difference through a case study of the Uanda house. The paper will investigate the processes of adding the house to the heritage register, the court case and existing research on Nellie McCredie and Uanda House.

lacZ transduced human breast cancer xenografts as an in vivo model for the study of invasion and metastasis

A number of human cancer cell lines have been described as being invasive and metastatic in immune incompetent animals. However, it is difficult to assess metastatic spread of a subcutaneously injected or inoculated cell line, since an exact detection of all microfoci of human tumour cells in the animals by usual histological procedures would require extensive sectioning of the whole animal. To overcome this problem, we transduced human breast cancer cells with a replication-defective Moloney murine leukaemia retroviral vector (M-MuLV) containing both neo(R) (neomycin resistance) and lacZ genes. The resulting cell lines were selected for antibiotic (G418) resistance, and cell-sorted for lacZ expression. lacZ continued to be expressed in cultured cells for at least 20 passages without further G418 selection. The lacE gene codes for β-D-galactosidase, and cells expressing this gene stain blue with the chromogenic substrate X-gal. The lacZ-expressing cells retained the pre-transduction ability to traverse Matrigel in vitro, to form subcutaneous tumours in nude mice, and to grow invasively with the formation of metastases. X-gal staining showed high specificity, staining the tumour cells but not the surrounding mouse tissue on either whole tissue blocks or histological sections. The staining procedure was highly sensitive, allowing detection of microfoci of human cancer cells, and quantitative estimation of the metastatic capacity of the cells. These results indicate that lacZ transduction of human tumour cells is a powerful means of studying human cancer cell invasion and metastases in vivo.

Host rather than graft origin of Matrigel-induced adipose tissue in the murine tissue-engineering chamber

We have recently shown that Matrigel-filled chambers containing fibroblast growth factor-2 (FGF2) and placed around an epigastric pedicle in the mouse were highly adipogenic. Contact of this construct with pre-existing tissue or a free adipose graft was required. To further investigate the mechanisms underpinning formation of new adipose tissue, we seeded these chambers with human adipose biopsies and human adipose-derived cell populations in severe combined immunodeficient mice and assessed the origin of the resultant adipose tissue after 6 weeks using species-specific probes. The tissues were negative for human-specific vimentin labeling, suggesting that the fat originates from the murine host rather than the human graft. This was supported by the strong presence of mouse-specific Cot-1 deoxyribonucleic acid labeling, and the absence of human Cot-1 labeling in the new fat. Even chambers seeded with FGF2/Matrigel containing cultured human stromal-vascular fraction (SVF) labeled strongly only for human vimentin in cells that did not have a mature adipocyte phenotype; the newly formed fat tissue was negative for human vimentin. These findings indicate that grafts placed in the chamber have an inductive function for neo-adipogenesis, rather than supplying adipocyte-precursor cells to generate the new fat tissue, and preliminary observations implicate the SVF in producing inductive factors. This surprising finding opens the door for refinement of current adipose tissue-engineering approaches.

Optimising the cell source and biomaterials for the generation of vascularized adipose tissue in vivo

We initially described a rat chamber model with an inserted arteriovenous pedicle which spontaneously generates 3-dimensional vascularized connective tissue (Tanaka Y et al., Br J Plast Surg 2000; 53: 51-7). More recently we have developed a murine chamber model containing reconstituted basement membrane (Matrigel®) and FGF-2 that generates vascularized adipose tissue in vivo (Cronin K et al., Plast Reconstr Surg 2004; in press). We have extended this work to assess the cellular and matrix requirements for the Matrigel®- induced neo-adipogenesis. We found that chambers sealed to host fat were unable to grow new adipose tissue. In these chambers the Matrigel® became vascularized with maximal outgrowth of vessels extending to the periphery at 6 weeks. A small amount of adipose tissue was found adjacent to the vessels, most likely arising from periadventitial adipose tissue. In contrast, chambers open to interaction with endogenous adipose tissue showed abundant new fat, and partial exposure to adjacent adipose tissue clearly showed neo-adipogenesis only in this area. Addition of small amounts of free fat to the closed chamber containing Matrigel® was able to induce neo-adipogenesis. Addition of small pieces of human fat also caused neo-adipogenesis in immunocompromised (SCID) mice. Also, we found Matrigel® to induce adipogenesis of Lac-Z-tagged (Rosa-26) murine bone marrow-derived mesenchymal stem cells, and cells similar to these have been isolated from human adipose tissue. Given that Matrigel® is a mouse product and cannot be used in humans, we have started investigating alternative matrix scaffolds for adipogenesis such as the PDA-approved PLGA, collagen and purified components derived from Matrigel®, such as laminin-1. The optimal conditions for adipogenesis with these matrices are still being elucidated. In conclusion, we have demonstrated that a precursor cell source inside the chamber is essential for the generation of vascularized adipose tissue in vivo. This technique offers unique potential for the reconstruction of soft tissue defects and may enable the generation of site-specific tissue using the correct microenvironment.