Global Lessons from Fitzgerald : From State and National to Global Integrity Systems

Tony Fitzgerald’s visionary leap was to see beyond localised, individual wrongdoing. He suggested remedies that were systemic, institutionalised, and directed at underlying structural problems that led to corruption. His report said ‘the problems with which this Inquiry is concerned are not merely associated with individuals, but are institutionalized and related to attitudes which have become entrenched’ (Fitzgerald Report 1989, 13). His response was to suggest an enmeshed system of measures to not only respond reactively to future corruption, but also to prevent its recurrence through improved integrity systems. In the two decades since that report the primary focus of corruption studies and anti-corruption activism has remained on corruption at the local level or within sovereign states. International activism was largely directed at co-ordinating national campaigns and to use international instruments to make these campaigns more effective domestically. This reflects the broader fact that, since the rise of the nation state, states have comprised the majority of the largest institutional actors and have been the most significant institution in the lives of most individuals. This made states the ‘main game in town’ for the ‘governance disciplines’ of ethics, law, political science and economics.

Flexural and torsional rigidity of colonoscope at room and body temperatures

A series of experiments have been conducted to determine the flexural, EI, and torsional, GJ, rigidity of an Olympus colonoscope CF‐140S and torsional rigidity of a Pentax colonoscope EC‐3870 and the dependency of these properties on temperature and on the presence of loops. Along the length of the colonoscope, the Olympus colonoscope flexural rigidity varied between 260 and 400 Ncm2 and torsional rigidity varied between 68 and 88 Ncm2/deg, with an average of 76 Ncm2/deg for tests involving 0.86 Nm of anti‐clockwise torque. Results show a significant decrease of 10% in torsional rigidity between clockwise and anti‐clockwise torque. For the Pentax colonoscope flexural rigidity was not tested; its torsional rigidity varied between 34 and 76 Ncm2/deg, with an average of 46 Ncm2/deg for tests involving 0.43 Nm of anti‐clockwise torque. An increase in temperature of the Olympus colonoscope from 24°C to 37°C reduces EI by an average of 17% and GJ by an average of 7%. A right‐handed loop caused a significant increase in flexural rigidity, but other looping configurations had no significant influence.

Mechanical properties of cold-formed steels at elevated temperatures

Mechanical properties have an important role in the fire safety design of cold-formed steel structures due to the rapid reduction in mechanical properties such as yield strength and elastic modulus under fire conditions and associated reduction to the load carrying capacities. Hence there is a need to fully understand the deterioration characteristics of yield strength and elastic modulus of cold-formed steels at elevated temperatures. Although past research has produced useful experimental data on the mechanical properties of cold-formed steels at elevated temperatures, such data do not yet cover different cold-formed steel grades and thicknesses. Therefore, an experimental study was undertaken to investigate the elevated temperature mechanical properties of two low and high strength steels with two thicknesses that are commonly used in Australia. Tensile coupon tests were undertaken using a steady state test method for temperatures in the range 20–700 °C. Test results were compared with the currently available reduction factors for yield strength and elastic modulus, and stress–strain curves, based on which further improvements were made. For this purpose, test results of many other cold-formed steels were also used based on other similar studies undertaken at the Queensland University of Technology. Improved equations were developed to predict the yield strength and elastic modulus reduction factors and stress–strain curves of a range of cold-formed steel grades and thicknesses used in Australia. This paper presents the results of this experimental study, comparisons with the results of past research and steel design standards, and the new predictive equations.

Common variation in the fibroblast growth factor receptor 2 gene is not associated with endometriosis risk

BACKGROUND Endometriosis is a polygenic disease with a complex and multifactorial aetiology that affects 8-10% of women of reproductive age. Epidemiological data support a link between endometriosis and cancers of the reproductive tract. Fibroblast growth factor receptor 2 (FGFR2) has recently been implicated in both endometrial and breast cancer. Our previous studies on endometriosis identified significant linkage to a novel susceptibility locus on chromosome 10q26 and the FGFR2 gene maps within this linkage region. We therefore hypothesized that variation in FGFR2 may contribute to the risk of endometriosis. METHODS We genotyped 13 single nucleotide polymorphisms (SNPs) densely covering a 27 kb region within intron 2 of FGFR2 including two SNPs (rs2981582 and rs1219648) significantly associated with breast cancer and a total 40 tagSNPs across 150 kb of the FGFR2 gene. SNPs were genotyped in 958 endometriosis cases and 959 unrelated controls. RESULTS We found no evidence for association between endometriosis and FGFR2 intron 2 SNPs or SNP haplotypes and no evidence for association between endometriosis and variation across the FGFR2 gene. CONCLUSIONS Common variation in the breast-cancer implicated intron 2 and other highly plausible causative candidate regions of FGFR2 do not appear to be a major contributor to endometriosis susceptibility in our large Australian sample.

Notch and NOXA-related pathways in melanoma cells

Notch receptor-mediated intracellular events represent an ancient cell signaling system, and alterations in Notch expression are associated with various malignancies in which Notch may function as an oncogene or less commonly as a tumor suppressor. Notch signaling regulates cell fate decisions in the epidermis, including influencing stem cell dynamics and growth/differentiation control of cells in skin. Because of increasing evidence that the Notch signaling network is deregulated in human malignancies, Notch receptors have become attractive targets for selective killing of malignant cells. Compared with proliferating normal human melanocytes, melanoma cell lines are characterized by markedly enhanced levels of activated Notch-1 receptor. By using a small molecule gamma-secretase inhibitor (GSI) consisting of a tripeptide aldehyde, N-benzyloxycarbonyl-Leu-Leu-Nle-CHO, which can block processing and activation of all four different Notch receptors, we identified a specific apoptotic vulnerability in melanoma cells. GSI triggers apoptosis in melanoma cells, but only G2/M growth arrest in melanocytes without subsequent cell death. Moreover, GSI treatment induced a pro-apoptotic BH3-only protein, NOXA, in melanoma cells but not in normal melanocytes. The use of GSI to induce NOXA induction overcomes the apoptotic resistance of melanoma cells, which commonly express numerous cell survival proteins such as Mcl-1, Bcl-2, and survivin. Taken together, these results highlight the concept of synthetic lethality in which exposure to GSI, in combination with melanoma cells overexpressing activated Notch receptors, has lethal consequences, producing selective killing of melanoma cells, while sparing normal melanocytes. By identifying signaling pathways that contribute to the transformation of melanoma cells (e.g. Notch signaling), and anti-cancer agents that achieve tumor selectivity (e.g., GSI-induced NOXA), this experimental approach provides a useful framework for future therapeutic strategies in cutaneous oncology.

Quality of life and genetics in men with prostate cancer

As family history has been established as a risk factor for prostate cancer, attempts have been made to isolate predisposing genetic variants that are related to hereditary prostate cancer. With many genetic variants still to be identified and investigated, it is not yet possible to fully understand the impact of genetic variants on prostate cancer development. The high survival rates among men with prostate cancer have meant that other issues, such as quality of life (QoL), have also become important. Through their effect on a person’s health, a range of inherited genetic variants may potentially influence QoL in men with prostate cancer, even prior to treatment. Until now, limited research has been conducted on the relationship between genetics and QoL. Thus, this study contributes to an emerging field by aiming to identify certain genetic variants related to the QoL found in men with prostate cancer. It is hoped that this study may lead to future research that will identify men who have an increased risk of a poor QoL following prostate cancer treatment, which will aid in developing treatments that are individually tailored to support them. Previous studies have established that genetic variants of Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor 1 (IGF-1) may play a role in prostate cancer development. VEGF and IGF-1 have also been reported to be associated with QoL in people with ovarian cancer and colorectal cancer, respectively. This study completed a series of secondary analyses using two major data-sets (from 850 men newly diagnosed with prostate cancer, and approximately 550 men from the general Queensland population), in which genetic variants of VEGF and IGF-1 were investigated for associations with prostate cancer susceptibility and QoL. The first aim of this research was to investigate genetic variants in the VEGF and IGF-I gene for an association with the risk of prostate cancer. It was found that one IGF-1 genetic variant (rs35765) had a statistically significant association with prostate cancer (p = 0.04), and one VEGF genetic variant (rs2146323) had a statistically significant association with advanced prostate cancer (p = 0.02). The estimates suggest that carriers of the CA and AA genotype for rs35765 may have a reduced risk of developing prostate cancer (Odds Ratio (OR) = 0.72, 95% Confidence Interval (CI) = 0.55, 0.95, OR = 0.60, 95% CI = 0.26, 1.39, respectively). Meanwhile, carriers of the CA and AA genotype for rs2146323 may be at increased risk of advanced prostate cancer, which was determined by a Gleason score of above 7 (OR = 1.72, 95% CI = 1.12, 2.63, OR = 1.90, 95% CI = 1.08, 3.34, respectively). Utilising the widely used short-form health survey, the SF-36v2, the second aim of this study was to investigate the relationship between prostate cancer and QoL prior to treatment. Assessing QoL at this time-point was important as little research has been conducted to evaluate if prostate cancer affects QoL regardless of treatment. The analyses found that mean SF-36v2 scale scores related to physical health were higher by at least 0.3 Standard Deviations (SD) among men with prostate cancer than the general population comparison group. This difference was considered clinically significant (defined by group differences in mean SF-36v2 scores by at least 0.3 SD). These differences were also statistically significant (p<0.05). Mean QoL scale scores related to mental health were similar between men with prostate cancer and those from the general population comparison group. The third aim of this study was to investigate genetic variants in the VEGF and IGF-1 gene for an association with QoL in prostate cancer patients prior to their treatment. It was essential to evaluate these relationships prior to treatment, before the involvement of these genes was potentially interrupted by treatment. The analyses found that some genetic variants had a small clinically significant association (0.3 SD) to some QoL domains experienced by these men. However, most relationships were not statistically significant (p>0.05). Most of the associations found identified that a small sub-group of men with prostate cancer (approximately 2%) reported, on average, a slightly better QoL than the majority of the prostate cancer patients. The fourth aim of this research was to investigate whether associations between genetic variants in VEGF and IGF-1 and QoL were specific to men with prostate cancer, or were also applicable to the general male population. It was found that twenty out of one-hundred relationships between the genetic variants of VEGF and IGF-1 and QoL health-measures and scales examined differed between these groups. In the majority of the relationships involving VEGF SNPs that differed, a clinically significant difference (0.3 or more SD) between mean scores among the genotype groups in prostate cancer patients was found, while mean scores among men from the general-population comparison group were similar. For example, prostate cancer participants who carried at least one T allele (CT or TT genotype) for rs3024994 had a clinically significant higher (0.3 SD) mean QoL score in terms of the role-physical scale, than participants who carried the CC genotype. This was not seen among men from the general population sample, as the mean score was similar between genotype groups. The opposite was seen in regards to the IGF-1 SNPs examined. Overall, these relationships were not considered to directly impact on the clinical options for men with prostate cancer. As this study utilised secondary data from two separate studies, there are a number of important limitations that should be acknowledged including issues of multiple comparisons, power, and missing or unavailable data. It is recommended that this study be replicated as a better-designed study that takes greater consideration of the many factors involved in prostate cancer and QoL. Investigation into other genetic variants of VEGF or IGF-1 is also warranted, as is consideration of other genes and their relationship with QoL. Through identifying certain genetic variants that have a modest association to prostate cancer, this project adds to the knowledge surrounding VEGF and IGF-1 and their role in prostate cancer susceptibility. Importantly, this project has also introduced the potential role genetics plays in QoL, through investigating the relationships between genetic variants of VEGF and IGF-1 and QoL.

Hypoxia-mimicking mesoporous bioactive glass scaffolds with controllable cobalt ion release for bone tissue engineering

Low oxygen pressure (hypoxia) plays an important role in stimulating angiogenesis; there are, however, few studies to prepare hypoxia-mimicking tissue engineering scaffolds. Mesoporous bioactive glass (MBG) has been developed as scaffolds with excellent osteogenic properties for bone regeneration. Ionic cobalt (Co) is established as a chemical inducer of hypoxia-inducible factor (HIF)-1α, which induces hypoxia-like response. The aim of this study was to develop hypoxia-mimicking MBG scaffolds by incorporating ionic Co2+ into MBG scaffolds and investigate if the addition of Co2+ ions would induce a cellular hypoxic response in such a tissue engineering scaffold system. The composition, microstructure and mesopore properties (specific surface area, nano-pore volume and nano-pore distribution) of Co-containing MBG (Co-MBG) scaffolds were characterized and the cellular effects of Co on the proliferation, differentiation, vascular endothelial growth factor (VEGF) secretion, HIF-1α expression and bone-related gene expression of human bone marrow stromal cells (BMSCs) in MBG scaffolds were systematically investigated. The results showed that low amounts of Co (< 5%) incorporated into MBG scaffolds had no significant cytotoxicity and that their incorporation significantly enhanced VEGF protein secretion, HIF-1α expression, and bone-related gene expression in BMSCs, and also that the Co-MBG scaffolds support BMSC attachment and proliferation. The scaffolds maintain a well-ordered mesopore channel structure and high specific surface area and have the capacity to efficiently deliver antibiotics drugs; in fact, the sustained released of ampicillin by Co-MBG scaffolds gives them excellent anti-bacterial properties. Our results indicate that incorporating cobalt ions into MBG scaffolds is a viable option for preparing hypoxia-mimicking tissue engineering scaffolds and significantly enhanced hypoxia function. The hypoxia-mimicking MBG scaffolds have great potential for bone tissue engineering applications by combining enhanced angiogenesis with already existing osteogenic properties.

CgDN24 : a gene involved in hyphal development in the fungal phytopathogen Colletotrichum gloeosporioides

A cDNA corresponding to a transcript induced in culture by N starvation, was identified in Colletotrichum gloeosporioides by a differential hybridisation strategy. The cDNA comprised 905 bp and predicted a 215 aa protein; the gene encoding the cDNA was termed CgDN24. No function for CgDN24 could be predicted by database homology searches using the cDNA sequence and no homologues were found in the sequenced fungal genomes. Transcripts of CgDN24 were detected in infected leaves of Stylosanthes guianensis at stages of infection that corresponded with symptom development. The CgDN24 gene was disrupted by homologous recombination and this led to reduced radial growth rates and the production of hyphae with a hyperbranching phenotype. Normal sporulation was observed, and following conidial inoculation of S. guianensis, normal disease development was obtained. These results demonstrate that CgDN24 is necessary for normal hyphal development in axenic culture but dispensable for phytopathogenicity. © 2005 Elsevier GmbH. All rights reserved.

Review of "Violence, Prejudice and Sexuality" by Stephen Tomsen (Routledge, New York and London, 2009)

Tomsen’s book Violence, Prejudice and Sexuality engages with important questions about sexuality and anti homosexual sentiment that criminologists have grappled with for some time. Tomsen’s work refines these questions in the context of essentialism, and notes how this concept has enabled only very specific ways of thinking about and analysing violence, prejudice, and sexuality. Indeed, thinking about the nexus between these three concepts are now almost taken for granted. As Tomsen demonstrates in his discussion of historical understandings of sexual desire, although social constructionism and queer perspectives have challenged essentialist notions of sexuality, research has in many respects upheld a binary understanding of heterosexuality as normal and homosexuality as abnormal. Interestingly, essentialist binaries like this have been conveniently employed in more recent times when activists align with minority status to gain basic human rights. While no one could deny the importance of access to rights and justice, Tomsen notes the danger inherent in arguments like this that draw on essentialism. He argues we are working through similar dichotomies of heterosexuality as normal and homosexuality as abnormal set up in very early research on sexual desire. The key difference now is that, in the rush towards public and political citizenship, ‘heterosexuals are recast as “perpetrators” and homosexuals as “victims”’ (Tomsen 2009: 16). Violence, Prejudice and Sexuality importantly notes this is no less an essentialist dichotomy and no less divisive....

Problem-solving courts, therapeutic jurisprudence and the constitution : if two is company, is three a crowd?

Court costs, resource-intensive trials, booming prison populations and the obduracy of recidivism rates all present as ugly excesses of the criminal law adversarial paradigm. To combat these excesses, problem-solving courts have evolved with an edict to address the underlying issues that have caused an individual to commit a crime. When a judge seeks to help a problem-solving court participant deal with issues like addiction, mental health or poverty, they are performing a very different role to that of a judicial officer in the traditional court hierarchy. They are no longer the removed, independent arbiter — a problem-solving court judge steps into the ‘arena’ with the participant and makes active use of their judicial authority to assist in rehabilitation and positive behavioural change. Problem-solving court judges employing the principles of therapeutic jurisprudence appreciate that their interaction with participants can have therapeutic and anti-therapeutic consequences. This article will consider how the deployment of therapeutic measures (albeit with good intention) can lead to the behavioural manifestation of partiality and bias on the part of problem-solving court judges. Chapter III of the Commonwealth Constitution will then be analysed to highlight why the operation and functioning of problem solving courts may be deemed unconstitutional. Part IV of this article will explain how a problem-solving court judge who is not acting impartially or independently will potentially contravene the requirements of the Constitution. It will finally be suggested that judges who possess a high level of emotional intelligence will be the most successful in administering an independent and impartial problem solving court.

Lateral torsional buckling behaviour of cold-formed steel beams at elevated temperatures

Abstract: This paper presents the details of a study into the behaviour and moment capacities of cold-formed steel lipped channel beams (LCB) subject to lateral-torsional buckling at elevated temperatures. It was based on a validated numerical model of a simply supported and laterally unrestrained LCB subjected to a uniform moment. The ultimate moment capacities from this study were compared with the predicted values using ambient and fire design methods. This study showed that the lateral torsional buckling capacity is strongly influenced by the level of non-linearity in the stress-strain curves of steel at elevated temperatures. Hence most of the current design methods based on a single buckling curve were not adequate to determine the moment capacities. This paper proposes a new design method for the cold-formed steel LCBs subject lateral-torsional buckling at elevated temperatures.

The stimulation of proliferation and differentiation of periodontal ligament cells by the ionic products from Ca7Si2P2O16 bioceramics

The ultimate goal of periodontal tissue engineering is to produce predictable regeneration of alveolar bone, root cementum, and periodontal ligament, which are lost as a result of periodontal diseases. To achieve this goal, it is of great importance to develop novel bioactive materials which could stimulate the proliferation, differentiation and osteogenic/cementogenic gene expression of periodontal ligament cells (PDLCs) for periodontal regeneration. In this study, we synthesized novel Ca7Si2P2O16 ceramic powders for the first time by the sol–gel method and investigated the biological performance of PDLCs after exposure to different concentrations of Ca7Si2P2O16 extracts. The original extracts were prepared at 200 mg ml-1 and further diluted with serum-free cell culture medium to obtain a series of diluted extracts (100, 50, 25, 12.5 and 6.25 mg ml–1). Proliferation, alkaline phosphatase(ALP) activity, Ca deposition, and osteogenesis/cementogenesis-related gene expression (ALP, Col I, Runx2 and CEMP1) were assayed for PDLCs on days 7 and 14. The results showed that the ionic products from Ca7Si2P2O16 powders significantly stimulated the proliferation, ALP activity, Ca deposition and osteogenesis/cementogenesisrelated gene expression of PDLCs. In addition, it was found that Ca7Si2P2O16 powders had excellent apatite-mineralization ability in simulated body fluids. This study demonstrated that Ca7Si2P2O16 powders with such a specific composition possess the ability to stimulate the PDLC proliferation and osteoblast/cemenoblast-like cell differentiation, indicating that they are a promising bioactive material for periodontal tissue regeneration application.

Tests of LiteSteel Beams subject to combined shear and bending actions

This paper presents the details of an experimental study of a cold-formed steel beam known as LiteSteel Beam (LSB) subject to combined shear and bending actions. The LSBs have the beneficial characteristics of torsionally rigid rectangular hollow flanges combined with economical fabrication processes from a single strip of high strength steel. They combine the stability of hot-rolled steel sections with the high strength to weight ratio of conventional cold-formed steel sections. The LSB sections are commonly used as flexural members in residential, industrial and commercial buildings. In order to ensure safe and efficient designs of LSBs, many research studies have been undertaken on the flexural and shear strengths of LSBs. To date, however, no investigation has been conducted into the strength of LSB sections under combined shear and bending actions. Hence a detailed experimental study involving 18 tests was undertaken to investigate the behaviour and strength of LSBs under combined shear and bending actions. Test results showed that AS/NZS 4600 design rules for unstiffened webs grossly underestimated the capacity of LSBs. Therefore improved design equations were proposed for the combined shear and bending capacities of LSBs based on experimental results.

Preparation, characterization, and in vitro bioactivity of nagelschmidtite bioceramics

The aim of this study is to prepare Ca, P and Si-containing ternary oxide nagelschmidtite (NAGEL, Ca7Si2P2O16) bioceramics and explore their in vitro bioactivity for potential bone tissue regeneration. We prepared dense NAGEL ceramics through high-temperature sintering of NAGEL ceramic powders. The apatite-mineralization ability, dissolution rate, and human osteoblast response (including cytotoxicity analysis, attachment, morphology, proliferation, and bone-related gene expression) to NAGEL ceramics have been systematically studied by comparing with conventional β-tricalcium phosphate (β-TCP) ceramics. The results showed that NAGEL ceramics possessed more obvious apatite mineralization and dissolution (degradation) and stimulated bone-related gene expression (OCN and OPN) of osteoblasts than β-TCP ceramics. NAGEL ceramics also showed no significant cytotoxicity. NAGEL ceramics supported osteoblast attachment, proliferation, and osteogenic gene expression, with a comparable cell proliferation activity with β-TCP ceramics. These results indicate that novel NAGEL bioceramics with the specific composition of Ca7Si2P2O16, are a promising biomaterial for bone tissue regeneration application.