Beyond rule based reasoning - the meaning and use of cases

Commercial legal expert systems are invariably rule based. Such systems are poor at dealing with open texture and the argumentation inherent in law. To overcome these problems we suggest supplementing rule based legal expert systems with case based reasoning or neural networks. Both case based reasoners and neural networks use cases-but in very different ways. We discuss these differences at length. In particular we examine the role of explanation in existing expert systems methodologies. Because neural networks provide poor explanation facilities, we consider the use of Toulmin argument structures to support explanation (S. Toulmin, 1958). We illustrate our ideas with regard to a number of systems built by the authors

Knowledge ecosystems of early career academics : a grounded theory of experiencing information use for learning in developmental networks

This study explored early career academics' experiences in using information to learn while building their networks for professional development. A 'knowledge ecosystem' model was developed consisting of informal learning interactions such as relating to information to create knowledge and engaging in mutually supportive relationships. Findings from this study present an alternative interpretation of information use for learning that is focused on processes manifesting as human interactions with informing entities revolving around the contexts of reciprocal human relationships.

Inheritance of qualitative and quantitative trypsin inhibitor variants in Pisum

A trypsin inhibitor locus (Tri) has been mapped close to Vc-2 on Pisum (pea) linkage group 5 using recombinant inbred lines derived from crosses of genotypes showing qualitative variation in seed trypsin inhibitors. F2 seed populations derived from crosses between lines showing qualitative variation in trypsin inhibitors as well as quantitative variation in inhibitor activity showed an association between the segregation of the structural variation and relative activity levels. Clones complementary to Pisum trypsin inhibitor mRNA were used in hybridization analyses which showed that the segregation of protein polymorphisms reflected directly the segregation of polymorphisms associated with the structural genes.

Falling behind : business use of social media

Australians are turning onto social media in their droves - nearly 90 per cent of our citizenry are online and more than 50 per cent of the population has a Facebook account.

Clinical use of objective measures of physical activity

With measurement of physical activity becoming more common in clinical practice, it is imperative that healthcare professionals become more knowledgeable about the different methods available to objectively measure physical activity behaviour. Objective measures do not rely on information provided by the patient, but instead measure and record the biomechanical or physiological consequences of performing physical activity, often in real time. As such, objective measures are not subject to the reporting bias or recall problems associated with self-report methods. The purpose of this article was to provide an overview of the different methods used to objectively measure physical activity in clinical practice. The review was delimited to heart rate monitoring, accelerometers and pedometers since their small size, low participant burden and relatively low cost make these objective measures appropriate for use in clinical practice settings. For each measure, strengths and weakness were discussed; and whenever possible, literature-based examples of implementation were provided.

Staurosporine augments EGF-mediated EMT in PMC42-LA cells through actin depolymerisation, focal contact size reduction and Snail1 induction : a model for cross-modulation

Background A feature of epithelial to mesenchymal transition (EMT) relevant to tumour dissemination is the reorganization of actin cytoskeleton/focal contacts, influencing cellular ECM adherence and motility. This is coupled with the transcriptional repression of E-cadherin, often mediated by Snail1, Snail2 and Zeb1/δEF1. These genes, overexpressed in breast carcinomas, are known targets of growth factor-initiated pathways, however it is less clear how alterations in ECM attachment cross-modulate to regulate these pathways. EGF induces EMT in the breast cancer cell line PMC42-LA and the kinase inhibitor staurosporine (ST) induces EMT in embryonic neural epithelial cells, with F-actin de-bundling and disruption of cell-cell adhesion, via inhibition of aPKC. Methods PMC42-LA cells were treated for 72 h with 10 ng/ml EGF, 40 nM ST, or both, and assessed for expression of E-cadherin repressor genes (Snail1, Snail2, Zeb1/δEF1) and EMT-related genes by QRT-PCR, multiplex tandem PCR (MT-PCR) and immunofluorescence +/- cycloheximide. Actin and focal contacts (paxillin) were visualized by confocal microscopy. A public database of human breast cancers was assessed for expression of Snail1 and Snail2 in relation to outcome. Results When PMC42-LA were treated with EGF, Snail2 was the principal E-cadherin repressor induced. With ST or ST+EGF this shifted to Snail1, with more extreme EMT and Zeb1/δEF1 induction seen with ST+EGF. ST reduced stress fibres and focal contact size rapidly and independently of gene transcription. Gene expression analysis by MT-PCR indicated that ST repressed many genes which were induced by EGF (EGFR, CAV1, CTGF, CYR61, CD44, S100A4) and induced genes which alter the actin cytoskeleton (NLF1, NLF2, EPHB4). Examination of the public database of breast cancers revealed tumours exhibiting higher Snail1 expression have an increased risk of disease-recurrence. This was not seen for Snail2, and Zeb1/δEF1 showed a reverse correlation with lower expression values being predictive of increased risk. Conclusion ST in combination with EGF directed a greater EMT via actin depolymerisation and focal contact size reduction, resulting in a loosening of cell-ECM attachment along with Snail1-Zeb1/δEF1 induction. This appeared fundamentally different to the EGF-induced EMT, highlighting the multiple pathways which can regulate EMT. Our findings add support for a functional role for Snail1 in invasive breast cancer.

Regulation of ROCK1 via Notch1 during breast cancer cell migration into dense matrices

Background The behaviour of tumour cells depends on factors such as genetics and the tumour microenvironment. The latter plays a crucial role in normal mammary gland development and also in breast cancer initiation and progression. Breast cancer tissues tend to be highly desmoplastic and dense matrix as a pre-existing condition poses one of the highest risk factors for cancer development. However, matrix influence on tumour cell gene expression and behaviour such as cell migration is not fully elucidated. Results We generated high-density (HD) matrices that mimicked tumour collagen content of 20 mg/cm3 that were ~14-fold stiffer than low-density (LD) matrix of 1 mg/cm3. Live-cell imaging showed breast cancer cells utilizing cytoplasmic streaming and cell body contractility for migration within HD matrix. Cell migration was blocked in the presence of both the ROCK inhibitor, Y-27632, and the MMP inhibitor, GM6001, but not by the drugs individually. This suggests roles for ROCK1 and MMP in cell migration are complicated by compensatory mechanisms. ROCK1 expression and protein activity, were significantly upregulated in HD matrix but these were blocked by treatment with a histone deacetylase (HDAC) inhibitor, MS-275. In HD matrix, the inhibition of ROCK1 by MS-275 was indirect and relied upon protein synthesis and Notch1. Inhibition of Notch1 using pooled siRNA or DAPT abrogated the inhibition of ROCK1 by MS-275. Conclusion Increased matrix density elevates ROCK1 activity, which aids in cell migration via cell contractility. The upregulation of ROCK1 is epigenetically regulated in an indirect manner involving the repression of Notch1. This is demonstrated from inhibition of HDACs by MS-275, which caused an upregulation of Notch1 levels leading to blockade of ROCK1 expression.

The heat shock protein 90 inhibitor, 17-allylamino-17- demethoxygeldanamycin, enhances osteoclast formation and potentiates bone metastasis of a human breast cancer cell line

Breast cancer metastasis to the bone occurs frequently, causing numerous complications including severe pain, fracture, hypercalcemia, and paralysis. Despite its prevalence and severity, few effective therapies exist. To address this, we examined whether the heat shock protein 90 (Hsp90) inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), would be efficacious in inhibiting breast cancer metastasis to bone. Utilizing the human breast cancer subline, MDA-MB-231SA, previously in vivo selected for its enhanced ability to generate osteolytic bone lesions, we determined that 17-AAG potently inhibited its in vitro proliferation and migration. Moreover, 17-AAG significantly reduced MDA-MB-231SA tumor growth in the mammary-fat pad of nude mice. Despite these findings, 17-AAG enhanced the incidence of bone metastasis and osteolytic lesions following intracardiac inoculation in the nude mouse. Consistent with these findings, 17-AAG enhanced osteoclast formation 2- to 4-fold in mouse bone marrow/osteoblast cocultures, receptor activator of nuclear factor κB ligand (BANKL)-stimulated bone marrow, and RAW264.7 cell models of in vitro osteoclastogenesis. Moreover, the drug enhanced osteoclastogenesis in human cord blood progenitor cells, demonstrating that its effects were not limited to mouse models. In addition to 17-AAG, other Hsp90 inhibitors, such as radicicol and herbimycin A, also enhanced osteoclastogenesis. A pro-osteolytic action of 17-AAG independent of tumor presence was also determined in vivo, in which 17-AAG-treated tumor-naive mice had reduced trabecular bone volume with an associated increase in osteoclast number. Thus, HSP90 inhibitors can stimulate osteoclast formation, which may underlie the increased incidence of osteolysis and skeletal tumor incidence causedby 17-AAG in vivo. These data suggest an important contraindication to the Hsp90 targeted cancer therapy currently undergoing clinical trial.

Polysubstance use in cannabis users referred for treatment: drug use profiles, psychiatric comorbidity and cannabis-related beliefs

Background: Population-based surveys demonstrate cannabis users are more likely to use both illicit and licit substances, compared with non-cannabis users. Few studies have examined the substance use profiles of cannabis users referred for treatment. Co-existing mental health symptoms and underlying cannabis-related beliefs associated with these profiles remains unexplored. Methods: Comprehensive drug use and dependence severity (Severity of Dependence Scale-Cannabis) data were collected on a sample of 826 cannabis users referred for treatment. Patients completed the General Health Questionnaire, Cannabis Expectancy Questionnaire, Cannabis Refusal Self-Efficacy Questionnaire, and Positive Symptoms and Manic-Excitement subscales of the Brief Psychiatric Rating Scale. Latent class analysis was performed on last month use of drugs to identify patterns of multiple drug use. Mental health comorbidity and cannabis beliefs were examined by identified drug use pattern. Results: A three-class solution provided the best fit to the data: (1) cannabis and tobacco users (n = 176), (2) cannabis, tobacco, and alcohol users (n = 498), and (3) wide-ranging sub- stance users (n = 132). Wide-ranging substance users (3) reported higher levels of cannabis dependence severity, negative cannabis expectancies, lower opportunistic, and emotional relief self-efficacy, higher levels of depression and anxiety and higher manic-excitement and positive psychotic symptoms. Conclusion: In a sample of cannabis users referred for treatment, wide-ranging substance use was associated with elevated risk on measures of cannabis dependence, co-morbid psychopathology, and dysfunctional cannabis cognitions. These findings have implications for cognitive-behavioral assessment and treatment.

Substrate choice of membrane-type 1 matrix metalloproteinase is dictated by tissue inhibitor of metalloproteinase-2 levels

Although tissue inhibitor of metalloproteinase-2 (TIMP-2) is known to be not only an inhibitor of matrix metalloproteinases (MMP) but also a cofactor for membrane-type 1 MMP (MT1-MMP)-mediated MMP-2 activation, it is still unclear how TIMP-2 regulates MMP-2 activation and cleavage of substrates by MT1-MMP. In the present study we examined the levels of cell-surface MT1-MMP, MMP-2 activation and cleavage of MT1-MMP substrates in 293T cells transfected with the MT1-MMP and TIMP-2 genes. Co-expression of TIMP-2 at an appropriate level increased the level of cell-surface MT1-MMP, both the TIMP-2-bound and free forms, and generated processed MMP-2 with gelatin-degrading activity. In contrast, MT1-MMP substrates testican-1 and syndecan-1 were cleaved by the cells expressing MT1-MMP, which was inhibited by TIMP-2 even at levels that stimulate MMP-2 activation. These results suggest that TIMP-2 environment determines MT1-MMP substrate choice between direct cleavage of its own substrates and MMP-2 activation.

A securities market operator's use of the "please explain" price query and its impact on compliance

Market operators in New Zealand and Australia, such as the New Zealand Exchange (NZX) and the Australian Securities Exchange (ASX), have the regulatory power in their listing rules to issue queries to their market participants to explain unusual fluctuations in trading price and/or volume in the market. The operator will issue a price query where it believes that the market has not been fully informed as to price relevant information. Responsive regulation theory has informed much of the regulatory debate in securities laws in the region. Price queries map onto the lower level of the enforcement pyramid envisaged by responsive regulation and are one strategy that a market operator can use in communicating its compliance expectations to its stakeholders. The issue of a price query may be a precursor to more severe enforcement activities. The aim of this study is to investigate whether increased use of price queries by the securities market operator in New Zealand corresponded with an increase in disclosure frequency by all participating companies. The study finds that an increased use of price queries did correspond with an increase in disclosure frequency. A possible explanation for this finding is that price queries are an effective means of appealing to the factors that motivate corporations, and the individuals who control them, to comply with the law and regulatory requirements. This finding will have implications for both the NZX and the ASX as well as for regulators and policy makers generally.

Mobile phones and media use in Madang province of Papua New Guinea

A mobile phone service was not available to the majority of the population in Papua New Guinea (PNG) until mid-2007. Since that time, commercial competition has been introduced into the mobile telecommunication sector and coverage has spread across many parts of the country. While the focus of this article is on mobile phones, the research has also explored media access and media usage more generally. Analysis in this article adopts the 'circuit of culture' model developed by du Gay et al. (1997). The article is based on data from a survey conducted in 2009 in eight rural villages in Madang Province. The research occurred during the primary stages of mobile phone adoption in these places, providing a rare opportunity to gauge early adoption behaviour and attitudes.

The use of uniaxial and triaxial accelerometers to measure children's "free-play" physical activity

In order to effectively measure the physical activity of children, objective monitoring devices must be able to quantify the intermittent and nonlinear movement of free play. The purpose of this study was to investigate the validity of the Computer Science and Applications (CSA) uniaxial accelerometer and the TriTrac-R3D triaxial accelerometer with respect to their ability to measure 8 "free-play" activities of different intensity. The activities ranged from light to very vigorous in intensity and included activities such as throwing and catching, hopscotch, and basketball. Twenty-eight children, ages 9 to 11, wore a CSA and a heart rate monitor while performing the activities. Sixteen children also wore a Tritrac. Counts from the CSA, Tritrac, and heart rates corresponding to the last 3 min of the 5 min spent at each activity were averaged and used in correlation analyses. Across all 8 activities, Tritrac counts were significantly correlated with predicted MET level (r= 0.69) and heart rate (r= 0.73). Correlations between CSA output, predicted MET level (0.43), and heart rate (0.64) were also significant but were lower than those observed for the Tritrac. These data indicate that accelerometers are an appropriate methodology for measuring children's free-play physical activities.

Can the use of quality assurance tools reduce the impact of surgical complications on the well-being of obstetricians and gynaecologists in Australia and New Zealand?

Background While adverse events primarily affect the patient, surgeons involved can also experience considerable distress. Aims The aim of the survey was to assess the impact of complications on the day-to-day life, work and health of Australian and New Zealand obstetricians and gynaecologists and to evaluate existing support systems and coping strategies. Methods A 43-question survey on self-assessment, quality assurance (QA) tools, impact of complications on individuals’ health and relationships, and support available was emailed to fellows, trainees, subspecialists and subspecialty trainees of the Royal Australian and New Zealand College of Obstetrics and Gynaecology (RANZCOG). We collected 606 responses from a target population of 2296 (response rate 26.3%). Results When complications occur, sleep was affected of 80%, family and social relationships of 55% and physical health of 48% of respondents. The major sources of support were from colleagues (83%), family (82%) and medical defence organisations (73%), with professional bodies perceived as providing least support. Nearly 80% of respondents felt the need to talk to someone they trust during times of complications. Overall, 100% of respondents used at least one QA tool (62% used two, 26% three and 9% four QA strategies). There were significant differences between respondent groups in use of the QA tools. Conclusions Surgical complications have a significant impact on the well-being of Australian and New Zealand obstetricians and gynaecologists. Existing support comes from colleagues and family, but structured, unbiased support for surgeons from a professional source is urgently warranted.

Improvements to bauxite residue neutralisation efficiency through the use of alternative feed sources

Currently, open circuit Bayer refineries pump seawater directly into their operations to neutralise the caustic fraction of the Bayer residue. The resulting supernatant has a reduced pH and is pumped back to the marine environment. This investigation has assessed modified seawater sources generated from different ion filtration processes to compare their relative capacities to neutralise bauxite residues. An assessment of the chemical stability of the neutralisation products, neutralisation efficiency, discharge water quality, bauxite residue composition, and associated economic benefits have been considered to determine the most preferable seawater filtration process based on implementation costs, savings to operations and environmental benefits. The mechanism of neutralisation for each technology was determined to be predominately due to the formation of Bayer hydrotalcite and calcium carbonate, however variations in neutralisation capacity and efficiencies have been observed. The neutralisation efficiency of each feed source has been found to be dependent on the concentration of magnesium, aluminium, calcium and carbonate. These studies have revealed that multiple neutralisation steps occur throughout the process. Environmental, economic and social advantages and disadvantages of the different filtration technologies have been explored to determine the most sustainable method for the neutralisation of bauxite residues. The relative degree of “green” associated with nanofiltered seawater and reverse osmosis filtered seawater are discussed.