Offspring of mothers fed a high fat diet display hepatic cell cycle inhibition and associated changes in gene expression and DNA methylation

The association between an adverse early life environment and increased susceptibility to later-life metabolic disorders such as obesity, type 2 diabetes and cardiovascular disease is described by the developmental origins of health and disease hypothesis. Employing a rat model of maternal high fat (MHF) nutrition, we recently reported that offspring born to MHF mothers are small at birth and develop a postnatal phenotype that closely resembles that of the human metabolic syndrome. Livers of offspring born to MHF mothers also display a fatty phenotype reflecting hepatic steatosis and characteristics of non-alcoholic fatty liver disease. In the present study we hypothesised that a MHF diet leads to altered regulation of liver development in offspring; a derangement that may be detectable during early postnatal life. Livers were collected at postnatal days 2 (P2) and 27 (P27) from male offspring of control and MHF mothers (n = 8 per group). Cell cycle dynamics, measured by flow cytometry, revealed significant G0/G1 arrest in the livers of P2 offspring born to MHF mothers, associated with an increased expression of the hepatic cell cycle inhibitor Cdkn1a. In P2 livers, Cdkn1a was hypomethylated at specific CpG dinucleotides and first exon in offspring of MHF mothers and was shown to correlate with a demonstrable increase in mRNA expression levels. These modifications at P2 preceded observable reductions in liver weight and liver:brain weight ratio at P27, but there were no persistent changes in cell cycle dynamics or DNA methylation in MHF offspring at this time. Since Cdkn1a up-regulation has been associated with hepatocyte growth in pathologic states, our data may be suggestive of early hepatic dysfunction in neonates born to high fat fed mothers. It is likely that these offspring are predisposed to long-term hepatic dysfunction.

Duty to the court and the administration of justice : some examples, implications and clarifications

No liberal democracy can survive without popular trust in its judicial system. The legal profession and the judiciary enjoy a level of independence and autonomy from the executive that makes them both powerful and privileged. A UNIQUE AND ORGANIC DUTY: So long as the courts are seen to fulfil their duty to guard against encroachments by the executive on the freedoms and rights of individual citizens with integrity and credibility, they maintain enough public support to retain their normative authority. But support for those with power and privilege is easily undermined. It is contingent upon trust. Lawyers who breach that trust in ways that go to the heart of the legal system ought to expect to be made examples of and to suffer severe penalties. The good news is that the sorts of breach discussed here should be neither difficult to anticipate nor to avoid – in theory. In practice, smart and honest lawyers sometimes fall foul of these duties for all sorts of understandable (if not condonable) reasons. Law does not get practised in a social or cultural vacuum. Lawyers are people, and people have weaknesses, failings and stresses...

Improving the outcomes of foot and ankle surgery through the audit cycle : a case study

The direct costs of managing adverse outcomes from Australian health care are estimated to be $2 billion. The audit cycle is considered an important tool to assist in the preventive management of adverse outcomes.Australian guidelines for audit cycle design allow for comparison of data sets derived from similar surgical specialities. However a lack of data set standardisation inhibits meaningful comparisons of foot and ankle surgical audits. This research will assist development of a best practice model for auditing foot and ankle surgery. Data derived from this model will improve the safety and quality of foot and ankle surgery. The preliminary phase of this process is to identify and understand the attitudes and behaviours of how and why surgeons participate in the audit cycle. A descriptive embedded multiple case study research design is planned to provide an intense focus on a single phenomenon (the audit cycle) within its real life context (clinical governance). The measures to be included in the case study have been identified by the Balanced Patient Safety Measurement Framework. These include: audit and peer review activity, provider attitudes to patient safety, safety learning, action and performance. A purposive sample of 6 to 8 surgeons (units of analysis) from 3 to 4 specialities (cases) will undergo semi-structured interview. This will investigate: current audit tools and processes; attitudes; and behaviours of surgeons to the audit cycle. Similarities in and differences between the units of analysis will indicate which identified measures function as barriers or enablers of the audit cycle. Reliability and validity (external and construct) will be assessed using established methods for case studies. The descriptive embedded multiple case study will reveal how and why foot and ankle surgeons participate in the audit cycle. This will inform further research to improve the outcomes of foot and ankle surgery through development of an audit tool.

Nondelegable duty : the implications of Woodland v Essex County Council

English law has long recognised that nondelagable duties exist, but it does not have a single theory to explain when or why - arguable, one might add, until now. That is the value of the reasons for judgement in Woodland v Essex County Council.

Three-dimensional off-design numerical analysis of an organic Rankine cycle radial-inflow turbine

Optimisation of organic Rankine cycles(ORCs for binary cycle applications could play a major role in determining the competitiveness of low to moderate renewable sources. An important aspect of the optimisation is to maximise the turbine output power for a given resource. This requires careful attention to the turbine design notably through numerical simulations. Challenges in the numerical modelling of radial-inflow turbines using high-density working fluids still need to be addressed in order to improve the turbine design and better optimise ORCs. Thispaper presents preliminary 3D numerical simulations of a high-density radial-inflow ORC turbine in sensible geothermal conditions. Following extensive investigation of the operating conditions and thermodynamic cycle analysis, therefrigerant R143a is chosen as the high-density working fluid. The 1D design of the candidate radial-inflow turbine is presented in details. Furthermore, commercially-available software Ansys-CFX is used to perform preliminary steady-state 3D CFD simulations of the candidate R143a radial-inflow turbine for a number of operating conditions including off-design conditions. The real-gas properties are obtained using the Peng–Robinson equations of state.The thermodynamic ORC cycle is presented. The preliminary design created using dedicated radial-inflow turbine software Concepts-Rital is discussed and the 3D CFD results are presented and compared against the meanline analysis.

How does Nepal Television (NTV) frame natural disasters? A qualitative content analysis of news scripts using news frames and PPRR cycle

Introduction- This study investigates the prevailing status of Nepalese media portrayal of natural disasters. It is contributing to the development of a disaster management model to improve the effectiveness and efficiency of news production throughout the continuum of prevention, preparedness, response and recovery (PPRR) phases of disaster management. Theoretical framework- Studies of media content often rely on framing as the theoretical underpinning of the study, as it describes how the press crafts the message. However there are additional theoretical perspectives that underline an understanding of the role of the media. This article outlines a conceptual understanding of the role of the media in modern society, the way that this conceptual understanding is used in the crafting of media messages and how those theoretical considerations are applied to the concepts that underpin effective disaster management. (R.M. Entman, 2003; Liu, 2007; Meng & Berger, 2008). Methodology- A qualitative descriptive design is used to analyse the disaster news of Nepal Television (NTV). However, this paper presents the preliminary findings of Nepal Television (a government owned Television station) using qualitative content analysis of 105 natural disaster related news scripts (June 2012-March 2013) based on the framing theory and PPRR cycle. Results- The preliminary results indicate that the media focus while framing natural disasters is dominated by human interest frame followed by responsibility frame. News about response phase was found to be most prominent in terms of PPRR cycle. Limited disaster reporting by NTV has impacted the national disaster management programs and strategies. The findings describe natural disasters are being reported within the limited understanding of the important principles of disaster management and PPRR cycle. Conclusion- This paper describes the current status of the coverage of natural disasters by Nepal Television to identify the frames used in the news content. It contributes to determining the characteristics of effective media reporting of natural disasters in the government owned media outlets, and also leads to including communities and agencies involved in disasters. It suggests the frames which are best suited for news making and how media responds to the different phases of the disaster cycle.

Evidence of a conserved role for Chlamydia HtrA in the replication phase of the chlamydial developmental cycle

Identification of the HtrA inhibitor JO146 previously enabled us to demonstrate an essential function for HtrA during the mid-replicative phase of the Chlamydia trachomatis developmental cycle. Here we extend our investigations to other members of the Chlamydia genus. C. trachomatis isolates with distinct replicative phase growth kinetics showed significant loss of viable infectious progeny after HtrA was inhibited during the replicative phase. Mid-replicative phase addition of JO146 was also significantly detrimental to Chlamydia pecorum, Chlamydia suis and Chlamydia cavie. These data combined indicate that HtrA has a conserved critical role during the replicative phase of the chlamydial developmental cycle.

Identification of eusynstyelamide B as a potent cell cycle inhibitor following the generation and screening of an ascidian-derived extract library using a real time cell analyzer

Ascidians are marine invertebrates that have been a source of numerous cytotoxic compounds. Of the first six marine-derived drugs that made anticancer clinical trials, three originated from ascidian specimens. In order to identify new anti-neoplastic compounds, an ascidian extract library (143 samples) was generated and screened in MDA-MB-231 breast cancer cells using a real-time cell analyzer (RTCA). This resulted in 143 time-dependent cell response profiles (TCRP), which are read-outs of changes to the growth rate, morphology, and adhesive characteristics of the cell culture. Twenty-one extracts affected the TCRP of MDA-MB-231 cells and were further investigated regarding toxicity and specificity, as well as their effects on cell morphology and cell cycle. The results of these studies were used to prioritize extracts for bioassay-guided fractionation, which led to the isolation of the previously identified marine natural product, eusynstyelamide B (1). This bis-indole alkaloid was shown to display an IC50 of 5 μM in MDA-MB-231 cells. Moreover, 1 caused a strong cell cycle arrest in G2/M and induced apoptosis after 72 h treatment, making this molecule an attractive candidate for further mechanism of action studies.

Enforcing upstream: Australian health and safety inspectors and upstream duty holders

The ‘new style’ occupational health and safety legislation implemented in Australia from the late 1970s changed the character of OHS legal obligations, establishing general duties supported by process, performance and, more rarely, specification standards,1 and extending obligations to those who propagate risks as designers, manufacturers, importers or suppliers — the ‘upstream duty holders’. This article examines how OHS agencies inspect and enforce OHS legislation upstream, drawing on empirical research in four Australian states and relevant case law. We argue that upstream duty holders are an increasing area of attention for OHS inspectorates but these inspectorates have not yet risen to the challenge of harnessing these parties to help stem, at the source, the flow of risks into workplaces.

Dismantling worker categories: the primary duty of care, and worker consultation, participation and representation, in the model Work Health and Safety Bill 2009

Late in 2009, the Australian Workplace Relations Ministers' Council endorsed the model Work Health and Safety Bill 2009, which is to be adopted by all Australian governments (federal, state and territory) from 01 January 2012. This paper describes and analyses two key sets of provisions in this model legislation. The first establishes a 'primary' duty of care imposed not on 'employers' but on persons conducting a business or undertaking, and owed to all kinds of workers engaged, directed or influenced by the person conducting the business or undertaking. The second encompasses broad duties on all persons conducting a business or undertaking to consult with workers who carry out work for the business or undertaking and who are directly affected by a work health and safety issue, and to facilitate the election of health and safety representatives representing all workers who carry out work for the business or undertaking. These provisions arguably make a significant contribution to solving a problem faced by occupational safety and health regulators around the world – modifying regulation to accommodate all forms of precarious work.

Once more into the mire, dear friends : determining the existence of a duty of care in negligence

There were signs in the 1997 High Court decision in Hill v Van Erp that the different members of the bench were beginning to move in the same direction when it came to the tort equivalent of the search for the Holy Grail, a common approach to the determination of the existence of a duty of care in negligence. However, the court's subsequent decision in Perre v Apand signaled a slide back to uncertainty with the seven judges favouring five different approaches. This Note examines those five approaches in the search for guidance for those at the "coalface" - litigants, their legal advisers and trial judges.

Resistance to amoebic gill disease (AGD) is characterised by the transcriptional dysregulation of immune and cell cycle pathways

Amoebic gill disease (AGD) is a parasite-mediated proliferative gill disease capable of affecting a range of teleost hosts. While a moderate heritability for AGD resistance in Atlantic salmon has been reported previously, the mechanisms by which individuals resist the proliferative effects remain poorly understood. To gain more knowledge of this commercially important trait, we compared gill transcriptomes of two groups of Atlantic salmon, one designated putatively resistant, and one designated putatively susceptible to AGD. Utilising a 17k Atlantic salmon cDNA microarray we identified 196 transcripts that were differentially expressed between the two groups. Expression of 11 transcripts were further examined with real-time quantitative RT-PCR (qPCR) in the AGD-resistant and AGD-susceptible animals, as well as non-infected naïve fish. Gene expression determined by qPCR was in strong agreement with the microarray analysis. A large number of differentially expressed genes were involved in immune and cell cycle responses. Resistant individuals displayed significantly higher expression of genes involved in adaptive immunity and negative regulation of the cell cycle. In contrast, AGD-susceptible individuals showed higher expression of acute phase proteins and positive regulators of the cell cycle. Combined with the gill histopathology, our results suggest AGD resistance is acquired rather than innately present, and that this resistance is for the most part associated with the dysregulation of immune and cell cycle pathways. © 2008 Elsevier Ltd. All rights reserved.

The Reef Cycle: Engaging in creativity and global awareness

This is a report of a musical theatre production performed at QUT Gardens Point Campus in November 2014 for the occasion of the end of year Annual Art Exhibition and concert of the Post graduate research students. Both the performance and the exhibition focused on environmental issues especially in relation to coal and coral in Queensland. The poster was prepared by Stephen Bennett former student in Creative Industries.

The Reef Cycle: Paradise; Paradise Plundered; Paradise Preserved by people Power

This is a musical theatre production with an environmental message addressing a Queensland, Australia tussle between the development of the Galilee Coal Basin and the potential threat to the health of the Great Barrier Reef along the Queensland coast. The drama is enacted by characters representing "goodies" and "baddies" and includes epic poetry, dance, orchestra and drama. The whole performance is enacted in the midst of a post graduate student art exhibition with a coral and coal theme.