Competitive interactions of anti-carcinogens with serum albumin: A spectroscopic study of bendamustine and dexamethasone with the aid of chemometrics

Interactions between the anti-carcinogens, bendamustine (BDM) and dexamethasone (DXM), with bovine serum albumin (BSA) were investigated with the use of fluorescence and UV–vis spectroscopies under pseudo-physiological conditions (Tris–HCl buffer, pH 7.4). The static mechanism was responsible for the fluorescence quenching during the interactions; the binding formation constant of the BSA–BDM complex and the binding number were 5.14 × 105 L mol−1 and 1.0, respectively. Spectroscopic studies for the formation of BDM–BSA complex were interpreted with the use of multivariate curve resolution – alternating least squares (MCR–ALS), which supported the complex formation. The BSA samples treated with site markers (warfarin – site I and ibuprofen – site II) were reacted separately with BDM and DXM; while both anti-carcinogens bound to site I, the binding constants suggested that DXM formed a more stable complex. Relative concentration profiles and the fluorescence spectra associated with BDM, DXM and BSA, were recovered simultaneously from the full fluorescence excitation–emission data with the use of the parallel factor analysis (PARAFAC) method. The results confirmed that on addition of DXM to the BDM–BSA complex, the BDM was replaced and the DXM–BSA complex formed; free BDM was released. This finding may have consequences for the transport of these drugs during any anti-cancer treatment.

Association of the SNP rs2623047 in the HSPG modification enzyme SULF1 with an Australian Caucasian Breast Cancer Cohort

Breast cancer is the second most common cancer worldwide and the most common cancer reported in women. This malignant tumour is characterised by a number of specific features including uncontrolled cell proliferation. It ranks fifth in the world as a cause of cancer death in women. Early diagnosis increases 5 year survival rates up to 95%. Heparan sulfate proteoglycans (HSPGs) are complex proteins composed of a core protein to which a number of highly sulfated side chains are synthesised by a highly co-ordinated process resulting in distinct sulfation patterns, which determine specific interations with cell-signaling partners including growth factors, their receptors, ligands and morphogens. The enzymes responsible for chain initiation, elongation and sulfation are critical for creating HS chain variability conferring biological functionality. This study investigated single nucleotide polymorphism in SULF1, the enzyme responsible for the 6-0 desulfation of heparan sulfate side chains. We investigated this SNP in an Australian Caucasian case-control breast cancer population and found a significant association between SULF1 and breast cancer at both the allelic and genotypic level (allele, p=0.016; genotype, p=0.032). Our results suggest the res2623047 SNP in SULF1 may impact breast cancer susceptibility. Specifically, the T allele of rs2623047 in SULF1 is associated with a increased risk of developing breast cancer in our cohort. The identification of markers including SULF1 may improve detection of this disease at its earliest stages improving patient treatment and prognosis.

Teaching and Assessing Reflective Writing in a Large Undergraduate Core Substantive Law Unit

The focus of higher education has shifted towards building students’ skills and self-awareness for future employment, in addition to developing substantive discipline knowledge. This means that there is an increasing need for embedding approaches to teaching and learning which provide a context for skills development and opportunities for students to prepare for the transition from legal education to professional practice. This chapter reports on a large (500-600 students) core undergraduate Equity law unit in an Australian University. ePortfolio has been embedded in Equity as a means of enabling students to document their reflections on their skill development in that unit. Students are taught, practice and are assessed on their teamwork and letter writing skills in the context of writing a letter of advice to a fictional client in response to a real world problem. Following submission of the team letter, students are asked to reflect on their skill development and document their reflections in ePortfolio. A scaffolded approach to teaching reflective writing is adopted using a blended model of delivery which combines face to face lectures and online resources, including an online module, facts sheets designed to guide students through the process of reflection by following the TARL model of reflection, and exemplars of reflective writing. Although students have engaged in the process of reflective writing in Equity for some years, in semester one 2011 assessment criteria were developed and the ePortfolio reflections were summatively assessed for the first time. The model of teaching and assessing reflective practice was evaluated in a range of ways by seeking feedback from students and academic staff responsible for implementing the model and asking them to reflect on their experiences. This chapter describes why skill development and reflective writing were embedded in the undergraduate law unit Equity; identify the teaching and learning approaches which were implemented to teach reflective writing to online and internal Equity students; explain the assessment processes; analyse the empirical evidence from evaluations; document the lessons learnt and discuss planned future improvements to the teaching and assessment strategies.

Patterns of service use among persons with Schizophrenia and other psychotic disorders

Objective: This study assessed 12-month service use patterns among people with psychotic disorders and sought to identify determinants of service use. Methods: As part of a large two-phase Australian study of psychotic disorders, structured interviews were conducted with a stratified random sample of adults who screened positive for psychosis. Demographic characteristics, social functioning, symptoms, mental health diagnoses, and use of psychiatric and nonpsychiatric services were assessed. Data were analyzed for 858 persons who had an ICD-10 diagnosis of a psychotic disorder and who had been hospitalized for less than six months during the previous year. Results: People with psychotic disorders had high levels of use of health services, both in absolute terms and relative to people with nonpsychotic disorders. Those with psychotic disorders were estimated to have an average of one contact with health services per week. Use of psychiatric inpatient services was associated with parenthood, higher symptom levels, recent attempts at suicide or self-harm, personal disability, medication status, and frequency of alcohol consumption. Services provided by general practitioners (family physicians) were more likely to be obtained by older people, women, people with greater availability of friends, those with fewer negative symptoms, and those whose service needs were unmet by other sources. People who were high users of health services also reported having more contact with a range of non-health agencies. Conclusions: The predictors of service use accounted for small proportions of the variance in overall use of health services. The role of general practitioners in providing and monitoring treatment programs and other psychosocial interventions needs to be acknowledged and enhanced.

Shared values : diverse perspectives – engaging engineering educators in integrating Indigenous engineering knowledge into current curricula

BACKGROUND Engineering is a problem-based practically oriented discipline, whose practitioners aim to find effective solutions to engineering challenges, technically and economically. Engineering educators operate within a mandate to ensure that graduate engineers understand the practicalities and realities of good engineering practice. While this is a vital goal for the discipline, emerging influences are challenging the focus on ‘hard practicalities’ and requiring recognition of the cultural and social aspects of engineering. Expecting graduate engineers to possess communication skills essential for negotiating satisfactory outcomes in contexts of complex social beliefs about the impact of their work can be an unsettling and challenging prospect for engineering educators. This project identifies and addresses Indigenous engineering practices and principles, and their relevance to future engineering practices. PURPOSE This Office of Learning and Teaching (OLT) project proposes that what is known/discoverable about indigenous engineering knowledge and practices must be integrated into engineering curricula. This is an important aspect of ensuring that engineering as a profession responds competently to increasing demands for socially and environmentally responsible activity across all aspects of engineering activity. DESIGN/METHOD The project addresses i) means for appropriate inclusion of Indigenous students into usual teaching activities ii) assuring engineering educators have access to knowledge of Indigenous practices and skills relevant to particular engineering courses and topics iii) means for preparing all students to negotiate their way through issues of indigenous relationships with the land where engineering projects are planned. The project is undertaking wide-ranging research to collate knowledge about indigenous engineering principles and practices and develop relevant resource materials. RESULTS It is common to hear that such social issues as ‘Indigenous concerns’ are only of concern to environmental engineers. We challenge that perspective, and make the case that Indigenous knowledge is an important issue for all engineering educators in relation to effective integration of indigenous students and preparation of all engineering graduates to engage with indigenous communities. At the time of first contact, a rich and varied, technically literate, Indigenous social framework possessed knowledge of the environment that is not yet fully acknowledged in Australian society. A core outcome of the work will be development of resources relating to Indigenous engineering practices for inclusion in engineering core curricula. CONCLUSIONS A large body of technical knowledge was needed to survive and sustain human society in the complex environment that was Australia before 1788. This project is developing resource materials, and supporting documentation, about that knowledge to enable engineering educators to more easily integrate it into current curricula. The project also aims to demonstrate the importance for graduating engineers to appreciate the existence of diverse perspectives on engineering tasks and learn how to value - and employ - multiple paths to possible solutions.

When death is not a crime : challenges for police and policing

The over-representation of vulnerable populations within the criminal justice system, and the role of police in perpetuating this, has long been a topic of discussion in criminology. What is less discussed is the way in which non -criminal investigations by police, in areas like a death investigation, may perpetuate similar types of engagement with vulnerable populations. In Australia, as elsewhere, it is the police who are responsible for investigating both suspicious and violent deaths like homicide as well as non - suspicious, violent deaths like accidents and suicides. Police are also the agents tasked with investigating deaths which are neither violent nor suspicious but occur outside hospitals and other care facilities. This paper reports on how the police describe - or are described by others - their role in a non - suspicious death investigation, and the challenges that such investigations raise for police and policing.

Mathematical models of calcium and tight junctions in normal and reconstructed epidermis

This project investigated the calcium distributions of the skin, and the growth patterns of skin substitutes grown in the laboratory, using mathematical models. The research found that the calcium distribution in the upper layer of the skin is controlled by three different mechanisms, not one as previously thought. The research also suggests that tight junctions, which are adhesions between neighbouring skin cells, cannot be solely responsible for the differences in the growth patterns of skin substitutes and normal skin.

Sensorineural hearing loss after treatment for head and neck cancer : a review of the literature

Background Definitive cisplatin-based is increasingly delivered as the treatment of choice for patients with head and neck cancer. Sensorineural hearing loss is a significant long term side effect of cisplatin-based chemoradiation and is associated with potential major quality of life issues for patients. Purpose The purpose of this manuscript was to review the mechanism behind sensorineural hearing loss in patients treated with cisplatin-based chemoradiation, including incidence, the contributions of radiotherapy and cisplatin to sensorineural hearing loss and the impact of the toxicity on patient quality of life. Methods Database searches were conducted through PubMed (National Centre for Biotechnology Information) and OvidSP Medline via the Queensland University of Technology Library website. General article searches were conducted through the online search engine Google Scholar. Articles were excluded if the full-text was unavailable, they were not in English or if they were published prior to 1990. Keywords included hearing loss, ototoxicity, cancer, quality of life, cisplatin and radiotherapy. Results/Discussion The total number of journal articles accessed was 290. Due to exclusion criteria, 129 articles were deemed appropriated for review. Findings indicated that sensorineural hearing loss is a significant, long term complication for patients treated with cisplatin-based chemoradiation. Current literature recognises the ototoxic effects of cisplatin and cranial irradiation as separate entities, however the impact of combined modality therapy on sensorineural hearing loss is seldom reported. Multiple risk factors for hearing loss are described, however there are contradictory opinions on incidence and severity and the exact radiation dose threshold responsible for inducing hearing loss in patients receiving combined modality therapy. Sensorineural hearing loss creates a subset of complexities for patients with head and neck cancer and that these patients face significant quality of life impairment. Conclusion The literature review identified that sensorineural hearing loss is a major quality of life issue for patients treated with cisplatin-based chemoradiation for head and neck cancer. Further investigation evaluating the contribution of cisplatin-based chemoradiation to sensorineural hearing loss and the subsequent effect on patient quality of life is warranted.

Source characterisation of urban road surface pollutants for enhanced water quality predictions

This study developed a comprehensive research methodology for identification and quantification of sources responsible for pollutant build-up and wash-off from urban road surfaces. The study identified soil and asphalt wear, and non-combusted diesel fuel as the most influential sources for metal and hydrocarbon pollution respectively. The study also developed mathematical models to relate contributions from identified sources to underlying site specific factors such as land use and traffic. Developed mathematical model will play a key role in urban planning practices, enabling the implementation of effective water pollution control strategies.

Investigating death: the emotional and cultural challenges for police

The over-representation of vulnerable populations within the criminal justice system, and the role of police in perpetuating this, has long been a topic of discussion in criminology. What is less discussed is the way in which non-criminal investigations by police, in areas like a death investigation, may similarly disadvantage and discriminate against vulnerable populations. In Australia, as elsewhere, it is police who are responsible for investigating both suspicious and violent deaths like homicide as well as non-suspicious, violent deaths like accidents and suicides. Police are also the agents tasked with investigating deaths which are neither violent nor suspicious but occur outside hospitals and other care facilities. This paper, part of a larger funded Australian research project focusing on the ways in which cultural and religious differences are dealt with during the death investigation process, reports on how police describe – or are described by others – during their role in a non-suspicious death investigation, and the challenges that such investigations raise for police and policing. The employment of police liaison officers is discussed as one response to the difficulty of policing cultural and religious difference with variable results.

Bicycle commuting and exposure to air pollution: A questionnaire-based investigation of perceptions, symptoms and risk management strategies

Background An increase in bicycle commuting participation may improve public health and traffic congestion in cities. Information on air pollution exposure (such as perception, symptoms and risk management) contributes to the responsible promotion of bicycle commuting participation. Methods To determine perceptions, symptoms and willingness for specific exposure risk management strategies of exposure to air pollution, a questionnaire-based cross-sectional investigation was conducted with adult bicycle commuters (n = 153; age = 41 ± 11 yr; 28% female). Results Frequency of acute respiratory signs and symptoms are positively-associated with in- and post-commute compared to pre-commute time periods (p < 0.05); greater positive-association is with respiratory disorder compared to healthy, and female compared to male, participants. The perception (although not signs or symptoms) of in-commute exposure to air pollution is positive-associated with the estimated level of in-commute proximity to motorised traffic. The majority of participants indicated a willingness (which varied with health status and gender) to adopt risk management strategies (with certain practical features) if shown to be appropriate and effective. Conclusions While acute signs and symptoms of air pollution exposure are indicated with bicycle commuting, and more so in susceptible individuals, there is willingness to manage exposure risk by adopting effective strategies with desirable features.

An architecture for trustworthy open data services

This paper addresses the development of trust in the use of Open Data through incorporation of appropriate authentication and integrity parameters for use by end user Open Data application developers in an architecture for trustworthy Open Data Services. The advantages of this architecture scheme is that it is far more scalable, not another certificate-based hierarchy that has problems with certificate revocation management. With the use of a Public File, if the key is compromised: it is a simple matter of the single responsible entity replacing the key pair with a new one and re-performing the data file signing process. Under this proposed architecture, the the Open Data environment does not interfere with the internal security schemes that might be employed by the entity. However, this architecture incorporates, when needed, parameters from the entity, e.g. person who authorized publishing as Open Data, at the time that datasets are created/added.

Structure of the K2 capsule associated with the KL2 gene cluster of Acinetobacter baumannii

The repeat unit structure of the K2 capsule from an extensively antibiotic-resistant Acinetobacter baumannii global clone 2 (GC2) strain was determined. The oligosaccharide contains three simple sugars, d-glucopyranose, d-galatopyranose and N-acetyl-d-galactosamine, and the complex sugar, 5,7-diacetamido-3,5,7,9-tetradeoxy-l-glycero-l-manno-non-2-ulosonic acid (Pse5Ac7Ac or pseudaminic acid), which has not previously been reported in any A. baumannii capsule. The strain was found to carry all the genes required for the synthesis of the sugars and construction of the K2 structure. The linkages catalyzed by the initiating transferase, three glycosyltransferases and the Wzy polymerase were also predicted. Examination of publicly available A. baumannii genome sequences revealed that the same gene cluster, KL2, often occurs in extensively antibiotic-resistant GC2 isolates and in further strain types. The gene module responsible for the synthesis of pseudaminic acid was also detected in four other K loci. A related module including genes for an acylated relative of pseudaminic acid was also found in two new KL types. A polymerase chain reaction scheme was developed to detect all modules containing genes for sugars based on pseudaminic acid and to specifically detect KL2.

Insertions in the OCL1 locus of Acinetobacter baumannii lead to shortened lipooligosaccharides

Genomes of 82 Acinetobacter baumannii global clones 1 (GC1) and 2 (GC2) isolates were sequenced and different forms of the locus predicted to direct synthesis of the outer core (OC) of the lipooligosaccharide were identified. OCL1 was in all GC2 genomes, whereas GC1 isolates carried OCL1, OCL3 or a new locus, OCL5. Three mutants in which an insertion sequence (ISAba1 or ISAba23) interrupted OCL1 were identified. Isolates with OCL1 intact produced only lipooligosaccharide, while the mutants produced lipooligosaccharide of reduced molecular weight. Thus, the assignment of the OC locus as that responsible for the synthesis of the OC is correct.