Risk of second cancer after lymphohematopoietic neoplasm

People living with lymphohematopoietic neoplasms (LHNs) are known to have increased risks of second cancer; however, the incidence of second cancers after LHNs has not been studied extensively in Australia. The Australian Cancer Database was used to analyze site-specific risk of second primary cancer after LHNs in 127,707 patients diagnosed between 1983 and 2005. Standardized incidence ratios (SIRs) were calculated using population rates. Overall, patients with an LHN had nearly twice the risk of developing a second cancer compared to the Australian population. Among 40,321 patients with non-Hodgkin's lymphoma (NHL), there was over a fourfold significant increase in melanoma, Kaposi sarcoma, cancer of the lip, connective tissue and peripheral nerves, eye, thyroid, Hodgkin's disease (HD) and myeloid leukemia. Among 6,396 patients with HD, there was over a fourfold significant increase in melanoma, Kaposi sarcoma, cancer of the lip, oral cavity and pharynx, female breast, uterine cervix, testis, thyroid, NHL and myeloid leukemia. Among the 33,025 patients with lymphoid and myeloid leukemia, significant excess were seen for cancers of the lip, eye, connective tissue and peripheral nerves, NHL and HD. Among the 13,856 patients with plasma cell tumors, there was over fourfold significant increase for melanoma, cancer of the connective tissue and peripheral nerves and myeloid leukemia. Our findings provide evidence of an increased risk of cancer, particularly ultraviolet radiation- and immunosuppression-related cancers, after an LHN in Australia. Copyright © 2010 UICC.

Hotspot Identification: A Full Bayesian Hierarchical Modeling Approach

This study proposes a full Bayes (FB) hierarchical modeling approach in traffic crash hotspot identification. The FB approach is able to account for all uncertainties associated with crash risk and various risk factors by estimating a posterior distribution of the site safety on which various ranking criteria could be based. Moreover, by use of hierarchical model specification, FB approach is able to flexibly take into account various heterogeneities of crash occurrence due to spatiotemporal effects on traffic safety. Using Singapore intersection crash data(1997-2006), an empirical evaluate was conducted to compare the proposed FB approach to the state-of-the-art approaches. Results show that the Bayesian hierarchical models with accommodation for site specific effect and serial correlation have better goodness-of-fit than non hierarchical models. Furthermore, all model-based approaches perform significantly better in safety ranking than the naive approach using raw crash count. The FB hierarchical models were found to significantly outperform the standard EB approach in correctly identifying hotspots.

Efficient safety information retrieval on construction sites: a preliminary methodology

IT-supported field data management benefits on-site construction management by improving accessibility to the information and promoting efficient communication between project team members. However, most of on-site safety inspections still heavily rely on subjective judgment and manual reporting processes and thus observers’ experiences often determine the quality of risk identification and control. This study aims to develop a methodology to efficiently retrieve safety-related information so that the safety inspectors can easily access to the relevant site safety information for safer decision making. The proposed methodology consists of three stages: (1) development of a comprehensive safety database which contains information of risk factors, accident types, impact of accidents and safety regulations; (2) identification of relationships among different risk factors based on statistical analysis methods; and (3) user-specified information retrieval using data mining techniques for safety management. This paper presents an overall methodology and preliminary results of the first stage research conducted with 101 accident investigation reports.

Terra Preta : bioenergy, soil restoration, urban agriculture, art algorithm

The 2010 LAGI competition was held on three underutilized sites in the United Arab Emirates. By choosing Staten Island, New York in 2012 the competition organises have again brought into question new roles for public open space in the contemporary city. In the case of the UEA sites, the competition produced many entries which aimed to create a sculpture and by doing so, they attracted people to the selected empty spaces in an arid climate. In a way these proposals were the incubators and the new characters of these empty spaces. The competition was thus successful at advancing understandings of the expanded role of public open spaces in EAU and elsewhere. LAGI 2012 differs significantly to the UAE program because Fresh Kills Park has already been planned as a public open space for New Yorkers - with or without these clean energy sculptures. Furthermore, Fresh Kills Park is already an (gas) energy generating site in its own right. We believe Fresh Kills Park, as a site, presents a problem which somewhat transcends the aims of the competition brief. Advancing a sustainable urban design proposition for the site therefore requires a fundamental reconsideration of the established paradigms public open space. Hence our strategy is to not only create an energy generating, site specific art work, but to create synergy between the public and the site engagement while at the same time complement the idiosyncrasies of the pre-existing engineered landscape. Current PhD research about energy generation in public open spaces informs this work.

Efficient safety information retrieval on construction sites : a preliminary methodology

IT-supported field data management benefits on-site construction management by improving accessibility to the information and promoting efficient communication between project team members. However, most of on-site safety inspections still heavily rely on subjective judgment and manual reporting processes and thus observers’ experiences often determine the quality of risk identification and control. This study aims to develop a methodology to efficiently retrieve safety-related information so that the safety inspectors can easily access to the relevant site safety information for safer decision making. The proposed methodology consists of three stages: (1) development of a comprehensive safety database which contains information of risk factors, accident types, impact of accidents and safety regulations; (2) identification of relationships among different risk factors based on statistical analysis methods; and (3) user-specified information retrieval using data mining techniques for safety management. This paper presents an overall methodology and preliminary results of the first stage research conducted with 101 accident investigation reports.

Performance characterisation of a constructed wetland

Performance of a constructed wetland is commonly reported as variable due to the site specific nature of influential factors. This paper discusses outcomes from an in-depth study which characterised treatment performance of a wetland based on the variation in runoff regime. The study included a comprehensive field monitoring of a well established constructed wetland in Gold Coast, Australia. Samples collected at the inlet and outlet was tested for Total Suspended Solids (TSS), Total Nitrogen (TN) and Total Phosphorus (TP). Pollutant concentrations in the outflow were found to be consistent irrespective of the variation in inflow water quality. The analysis revealed two different treatment characteristics for events with different rainfall depths. TSS and TN load reduction is strongly influenced by hydraulic retention time where performance is higher for rainfall events below the design event. For small events, treatment performance is higher at the beginning of the event and gradually decreased during the course of the event. For large events, the treatment performance is comparatively poor at the beginning and improved during the course of the event. The analysis also confirmed the variable treatment trends for different pollutant types.

Extreme architecture : can architects future proof us against fire and flood.

In the face of Australia’s disaster-prone environment, architects Ian Weir and James Davidson are reconceptualising how our residential buildings might become more resilient to fire, flood and cyclone. With their first-hand experience of natural disasters, James, director of Emergency Architects Australia (EAA), and Ian, one of Australia’s few ‘bushfire architects’, discuss the ways we can design with disaster in mind. Dr Ian Weir is one of Australia’s few ‘bushfire architects’. Exploring a holistic ‘ground up’ approach to bushfire where landscape, building design and habitation patterns are orchestrated to respond to site-specific fire characteristics. Ian’s research is developed through design studio teaching at QUT and through built works in Western Australia’s fire prone forests and heathlands.

Shift

Shift was an exhibition held in October 2008, and was the culmination of a 10 month artist in residence held at Metro Arts, Brisbane in 2008. A number of works were produced and exhibited, and were a response to the ambient urban landscape of inner city Brisbane. The research component contributes to the discussion of the form and display of digital animation, and builds upon strategies of presentation developed from series of works completed in 2005-2007 as part of an MA (research) at QUT, Brisbane. For the two week exhibition, one interactive kiosk and several large scale digital prints were produced, and also a site specific digital animation sequence was projected onto urban landscape features next to the gallery.

Synthesis of an erodible biomimetic hydrogel for drug delivery using native chemical ligation

Hydrogels are hydrophilic, three dimensional polymers that imbibe large quantities of water while remaining insoluble in aqueous solutions due to chemical or physical cross-linking. The polymers swell in water or biological fluids, immobilizing the bioactive agent, leading to drug release in a well-defined specific manner. Thus the hydrogels’ elastic properties, swellability and biocompatibility make them excellent formulations for drug delivery. Currently, many drug potencies and therapeutic effects are limited or otherwise reduced because of the partial degradation that occurs before the administered drug reaches the desired site of action. On the other hand, sustained release medications release drugs continually, rather than providing relief of symptoms and protection solely when necessary. In fact, it would be much better if drugs could be administered in a manner that precisely matches physiological needs at desired times and at the desired site (site specific targeting). There is therefore an unmet need to develop controlled drug delivery systems especially for delivery of peptide and protein bound drugs. The purpose of this project is to produce hydrogels for structural drug delivery and time-dependent sustained release of drugs (bioactive agents). We use an innovative polymerisation strategy based on native chemical ligation (NCL) to covalently cross-link polymers to form hydrogels. When mixed in aqueous solution, four armed (polyethylene glycol) amine (PEG-4A) end functionalised with thioester and four branched Nterminal cysteine peptide dendrimers spontaneously conjugated to produce biomimetic hydrogels. These hydrogels showed superior resistance to shear stress compared to an equivalent PEG macromonomer system and were shown to be proteolytically degradable with concomitant release of a model payload molecule. This is the first report of a peptide dendrimers/PEG macromonomer approach to hydrogel production and opens up the prospect of facile hydrogel synthesis together with tailored payload release.

Association of a RFLP for the insulin receptor gene, but not insulin, with essential hypertension

Insulin has cardiovascular actions and patients with essential hypertension display insulin resistance. A cross-sectional study of the R1 RFLP of the insulin receptor gene (INSR) was carried out in 67 hypertensive (HT) and 75 normotensive (NT) subjects whose parents had a similar blood pressure status at age ≥50. The frequency of the minor (+) allele was 0.31 in HTs and 0.44 in NTs, and the difference between observed alleles in all subjects in each group was significant (χ2 = 4.8, P<0.05). Allele frequencies of a BglI RFLP of the insulin gene, however, did not differ between the HT and NT groups. The data thus provide evidence in favour of an association of HT with a polymorphism at the INSR locus (19p 13.3-13.2), so implicating this locus, and possibly a genetic variant of the insulin receptor itself, in HT.

Association of HincII RFLP of low density lipoprotein receptor gene with obesity in essential hypertensives

Obese (BMI ≥ 26 kg/m 2; n = 51) and lean (BMI <26 kg/m 2; n = 61) Caucasian patients with severe, familial essential hypertension, were compared with respect to genotype and allele frequencies of a HincII RFLP of the low density lipoprotein receptor gene (LDLR). A similar analysis was performed in obese (n = 28) and lean (n = 68) normotensives. A significant association of the C allele of the T→C variant responsible for this RFLP was seen with obesity (χ 2 = 4.6, P = 0.029) in the hypertensive, but not in the normotensive, group (odds ratio = 3.0 for the CC genotype and 2.7 for CT). Furthermore, BMI tracked with genotypes of this allele in the hypertensives (P = 0.046). No significant genotypic relationship was apparent for plasma lipids. Significant linkage disequilibrium was, moreover, noted between the HincII RFLP and an ApaLI RFLP (χ 2 = 33, P<0.0005) that has previously shown even stronger association with obesity (odds ratio 19.6 for cases homozygous for the susceptibility allele and 15.2 for het-erozygotes). The present study therefore adds to our previous evidence implicating LDLR as a locus for obesity in patients with essential hypertension.

Separating shadows

This practice-led research is in the field of dance creation and performance. The dancer, unlike many artists from different fields, has to contend with the added complexity of being a creative tool. Grove states, ‘..they are the phenomenon of self-creation twice over, being both the artist and the work of art’ (2005, 44). A dancer’s success relies on the quality of their instrument and their ability to reliably employ it in the creative act (Jowitt 2001a). The traditional rehearsal studio is the creative meeting place for dance artists. A liminal space with specific spatial, temporal and personal considerations: a space fraught with uncertainty and vulnerability, ripe with potential. If harnessed, the creative potential inherent in vulnerability, experienced as increased sensitivity and openness (Press 2002), can facilitate new ways of investigating and doing. This research investigated ways in which dancers prepare themselves during the act of creation and rehearsal within the studio, for the public presentation of a site-specific dance work. Navigating the complexities inherent in performing site-specific dance work is best achieved through the development of a connection with the site during the creation of the work. This is achieved through the provision of rehearsals within the site and ensures seamless replication of rehearsal qualities from studio to non-traditional site. This research received funding and support from the Australia Council for the Arts, Arts Queensland, Brisbane Festival, Kelvin Grove Urban Village, Besen Family Foundation, Korean Culture Arts Foundation and the Australia Korea Foundation. It was presented in the Brisbane Festival, 2006. http://www.accentedbody.com/projects/accented-body

The epidemiology of basal cell carcinoma

Basal cell carcinoma (BCC) is a skin cancer of particular importance to the Australian community. Its rate of occurrence is highest in Queensland, where 1% to 2% of people are newly affected annually. This is an order of magnitude higher than corresponding incidence estimates in European and North American populations. Individuals with a sun-sensitive complexion are particularly susceptible because sun exposure is the single most important causative agent, as shown by the anatomic distribution of BCC which is in general consistent with the levels of sun exposure across body sites. A distinguishing feature of BCC is the occurrence of multiple primary tumours within individuals, synchronously or over time, and their diagnosis and treatment costs contribute substantially to the major public health burden caused by BCC. A primary knowledge gap about BCC pathogenesis however was an understanding of the true frequency of multiple BCC occurrences and their body distribution, and why a proportion of people do develop more than one BCC in their life. This research project sought to address this gap under an overarching research aim to better understand the detailed epidemiology of BCC with the ultimate goal of reducing the burden of this skin cancer through prevention. The particular aim was to document prospectively the rate of BCC occurrence and its associations with constitutional and environmental (solar) factors, all the while paying special attention to persons affected by more than one BCC. The study built on previous findings and recent developments in the field but set out to confirm and extend these and propose more adequate theories about the complex epidemiology of this cancer. Addressing these goals required a new approach to researching basal cell carcinoma, due to the need to account for the phenomenon of multiple incident BCCs per person. This was enabled by a 20 year community-based study of skin cancer in Australians that provided the methodological foundation for this thesis. Study participants were originally randomly selected in 1986 from the electoral register of all adult residents of the subtropical township of Nambour in Queensland, Australia. On various occasions during the study, participants were fully examined by dermatologists who documented cumulative photodamage as well as skin cancers. Participants completed standard questionnaires about skin cancer-related factors, and consented to have any diagnosed skin cancers notified to the investigators by regional pathology laboratories in Queensland. These methods allowed 100% ascertainment of histologically confirmed BCCs in this study population. 1339 participants had complete follow-up to the end of 2007. Statistical analyses in this thesis were carried out using SAS and SUDAAN statistical software packages. Modelling methods, including multivariate logistic regressions, allowed for repeated measures in terms of multiple BCCs per person. This innovative approach gave new findings on two levels, presented in five chapters as scientific papers: 1. Incidence of basal cell carcinoma multiplicity and detailed anatomic distribution: longitudinal study of an Australian population The incidence of people affected multiple times by BCC was 705 per 100,000 person years compared to an incidence rate of people singly affected of 935 per 100,000 person years. Among multiply and singly affected persons alike, site-specific BCC incidence rates were far highest on facial subsites, followed by upper limbs, trunk, and then lower limbs 2. Melanocytic nevi and basal cell carcinoma: is there an association? BCC risk was significantly increased in those with forearm nevi (Odds Ratios (OR) 1.43, 95% Confidence Intervals (CI) 1.09-1.89) compared to people without forearm nevi, especially among those who spent their time mainly outdoors (OR 1.6, 95%CI 1.1-2.3) compared to those who spent their time mainly indoors. Nevi on the back were not associated with BCC. 3. Clinical signs of photodamage are associated with basal cell carcinoma multiplicity and site: a 16-year longitudinal study Over a 16-year follow-up period, 58% of people affected by BCC developed more than one BCC. Among these people 60% developed BCCs across different anatomic sites. Participants with high numbers of solar keratoses, compared to people without solar keratoses, were most likely to experience the highest BCC counts overall (OR 3.3, 95%CI 1.4-13.5). Occurrences of BCC on the trunk (OR 3.3, 95%CI 1.4-7.6) and on the limbs (OR 3.7, 95%CI 2.0-7.0) were strongly associated with high numbers of solar keratoses on these sites. 4. Occurrence and determinants of basal cell carcinoma by histological subtype in an Australian community Among 1202 BCCs, 77% had a single growth pattern and 23% were of mixed histological composition. Among all BCCs the nodular followed by the superficial growth patterns were commonest. Risk of nodular and superficial BCCs on the head was raised if 5 or more solar keratoses were present on the face (OR 1.8, 95%CI 1.2-2.7 and OR 4.5, 95%CI 2.1-9.7 respectively) and similarly on the trunk in the presence of multiple solar keratoses on the trunk (OR 4.2, 95%CI 1.5-11.9 and OR 2.2, 95%CI 1.1-4.4 respectively). 5. Basal cell carcinoma and measures of cumulative sun exposure: an Australian longitudinal community-based study Dermal elastosis was more likely to be seen adjacent to head and neck BCCs than trunk BCCs (p=0.01). Severity of dermal elastosis increased on each site with increasing clinical signs of cutaneous sun damage on that site. BCCs that occurred without perilesional elastosis per se, were always found in an anatomic region with signs of photodamage. This thesis thus has identified the magnitude of the burden of multiple BCCs. It does not support the view that people affected by more than one BCC represent a distinct group of people who are prone to BCCs on certain body sites. The results also demonstrate that BCCs regardless of site, histology or order of occurrence are strongly associated with cumulative sun exposure causing photodamage to the skin, and hence challenge the view that BCCs occurring on body sites with typically low opportunities for sun exposure or of the superficial growth pattern are different in their association with the sun from those on typically sun-exposed sites, or nodular BCCs, respectively. Through dissemination in the scientific and medical literature, and to the community at large, these findings can ultimately assist in the primary and secondary prevention of BCC, perhaps especially in high-risk populations.

Phagocytosis of cross-linked gelatin matrix by human breast carcinoma cells correlates with their invasive capacity

During invasion and metastasis, cancer cells interact closely with the extracellular matrix molecules by attachment, degradation, and migration. We demonstrated previously the local degradation of fluorescently labeled gelatin matrix by cancer cells at invasive membrane protrusions, called invadopodia. Using the newly developed quantitative fluorescence-activated cell sorting-phagocytosis assay and image analysis of localized degradation of fluorescently labeled matrix, we document here that degradation and site- specific removal of cross-linked gelatin matrix is correlated with the extent of phagocytosis in human breast cancer cells. A higher phagocytic capacity is generally associated with increasing invasiveness, documented in other invasion and motility assays as well. Gelatin phagocytosis is time and cell density dependent, and it is mediated by the actin cytoskeleton. Most of the intracellular gelatin is routed to actively acidified vesicles, as demonstrated by the fluorescent colocalization of gelatin with acidic vesicles, indicating the intracellular degradation of the phagocytosed matrix in lysosomes. We show here that normal intracellular routing is blocked after treatment with acidification inhibitors. In addition, the need for partial proteolytic degradation of the matrix prior to phagocytosis is demonstrated by the inhibition of gelatin phagocytosis with different serine and metalloproteinase inhibitors and its stimulation by conditioned medium containing the matrix metalloproteinases MMP-2 and MMP-9. Our results demonstrate that phagocytosis of extracellular matrix is an inherent feature of breast tumor cells that correlates with and may even directly contribute to their invasive capacity. This assay is useful for screening and evaluating potential anti-invasive agents because it is fast, reproducible, and versatile.

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.