Fine mapping and replication of QTL in outbred chicken advanced intercross lines

Background: Linkage mapping is used to identify genomic regions affecting the expression of complex traits. However, when experimental crosses such as F2 populations or backcrosses are used to map regions containing a Quantitative Trait Locus (QTL), the size of the regions identified remains quite large, i.e. 10 or more Mb. Thus, other experimental strategies are needed to refine the QTL locations. Advanced Intercross Lines (AIL) are produced by repeated intercrossing of F2 animals and successive generations, which decrease linkage disequilibrium in a controlled manner. Although this approach is seen as promising, both to replicate QTL analyses and fine-map QTL, only a few AIL datasets, all originating from inbred founders, have been reported in the literature. Methods: We have produced a nine-generation AIL pedigree (n = 1529) from two outbred chicken lines divergently selected for body weight at eight weeks of age. All animals were weighed at eight weeks of age and genotyped for SNP located in nine genomic regions where significant or suggestive QTL had previously been detected in the F2 population. In parallel, we have developed a novel strategy to analyse the data that uses both genotype and pedigree information of all AIL individuals to replicate the detection of and fine-map QTL affecting juvenile body weight. Results: Five of the nine QTL detected with the original F2 population were confirmed and fine-mapped with the AIL, while for the remaining four, only suggestive evidence of their existence was obtained. All original QTL were confirmed as a single locus, except for one, which split into two linked QTL. Conclusions: Our results indicate that many of the QTL, which are genome-wide significant or suggestive in the analyses of large intercross populations, are true effects that can be replicated and fine-mapped using AIL. Key factors for success are the use of large populations and powerful statistical tools. Moreover, we believe that the statistical methods we have developed to efficiently study outbred AIL populations will increase the number of organisms for which in-depth complex traits can be analyzed.

Validity and responsiveness of at-home touch-screen assessments in advanced Parkinson's disease

The aim of this study was to investigate if a telemetry test battery can be used to measure effects of Parkinson’s disease (PD) treatment intervention and disease progression in patients with fluctuations. Sixty-five patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study; 35 treated with levodopa-carbidopa intestinal gel (LCIG) and 30 were candidates for switching from oral PD treatment to LCIG. They utilized a test battery, consisting of self-assessments of symptoms and fine motor tests (tapping and spiral drawings), four times per day in their homes during week-long test periods. The repeated measurements were summarized into an overall test score (OTS) to represent the global condition of the patient during a test period. Clinical assessments included ratings on Unified PD Rating Scale (UPDRS) and 39-item PD Questionnaire (PDQ-39) scales. In LCIG-naïve patients, mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. In LCIG-non-naïve patients, there were no significant changes in mean OTS until month 36. The OTS correlated adequately with total UPDRS (rho = 0.59) and total PDQ-39 (0.59). Responsiveness measured as effect size was 0.696 and 0.536 for OTS and UPDRS respectively. The trends of the test scores were similar to the trends of clinical rating scores but dropout rate was high. Correlations between OTS and clinical rating scales were adequate indicating that the test battery contains important elements of the information of well-established scales. The responsiveness and reproducibility were better for OTS than for total UPDRS.

Total factor productivity and efficiency in Australian colleges of advanced education

The former colleges of advanced education were an important component of the higher education sector in Australia. Uses the Malmquist total factor productivity index to investigate the efficiency and productivity of Australian colleges of advanced education during the 1980s. The results from this analysis indicate that these colleges recorded modest growth in technical change and total factor productivity, but did not fare all that well in terms of growth in technical and scale efficiency during the 1980s. As a group, however, the former colleges of advanced education had attained high levels of technical and scale efficiency.

The initiation and administration of drugs for advanced life support by critical care nurses in the absence of a medical practitioner

Current legislation does not permit the administration of first line resuscitation medications by suitably qualified Division 1 registered nurses (RNs) in the absence of a medical officer. This omission by the Drugs,  Poisons and Controlled Substances Act 1981 (Vic) and the Drugs, Poisons and The Controlled Substances Regulations 1995 (Vic) leaves many critical care nurses in a vulnerable legal position.

The primary aim of this study was to gauge the view of critical care nurses with respect to lobbying for change to the current legislation. In addition, the study aimed to explore and describe the educational preparation, practice perceptions and experiences of RNs working in critical care regarding cardiopulmonary resuscitation and the administration of first line advanced life support (ALS) medications in the absence of a medical officer. It was anticipated that data collected would demonstrate some of the dilemmas associated with the initiation and administration of ALS medications for practising critical care nurses and could be used to inform controlling bodies in order for them to gain an appreciation of the issues facing critical care nurses during resuscitation.

A mailout survey was sent to all members of the Victorian Branch of the Australian College of Critical Care Nurses (ACCCN). The results showed that the majority of nurses underwent an annual ALS assessment and had current ALS accreditation. Nurses indicated that they felt educationally prepared and were confident to manage cardiopulmonary resuscitation without a medical officer; indeed, the majority had done so. The differences in practice issues for metropolitan, regional and rural nurses were highlighted. There is therefore clear evidence to suggest that legislative amendments are appropriate and necessary, given the time critical nature of cardiopulmonary arrest. There was overwhelming support for ACCCN Vic. Ltd to lobby the Victorian government for changes to the law.

Operating experiences with an advanced fabric energy storage system in Australia

Despite their proven track record in the cold climate countries of northern Europe, there are no reports in the research literature of experiences using advanced fabric energy storage (FES) systems in countries where cooling rather than heating is the main priority. This paper reports some of the experiences with the first known advanced FES system in Australia made over the first full calendar .year of operation. It is located in a three storey building on a university campus in Victoria and has been in operation since mid-2002. Temperature, energy use and operational mode data were recorded during 2003. Airflow measurements through the FES have been made in five areas of the building. On-going operating problems still exist with the system and this has prevented a conclusive evaluation of its suitability for the southern Australian climate.

Developing and rewarding advanced teaching expertise in higher education - a different approach

The Australian university sector is undergoing a major change, with a significant increase in the emphasis on quality teaching and learning. This change is being driven by the national government. The paper asks if the correct response to this change of emphasis should be a change in the attitude to the appropriate mix of research and teaching skills within an institution, and within individual staff of the institution. The same question could be asked of how to better develop teaching expertise in many higher education sectors globally. It is proposed that to create excellent teaching and learning within an institution may better be achieved by allowing staff to become experts in a narrow field of teaching rather than
generalists across the basics of teaching. The creation of a Community of Experts in teaching parallels the process of creating a Community of Experts in Research and can bring similar benefits in the teaching area to what it does in the research area.

Advanced fabric energy storage systems in Australia

There is a growing interest in the use of advanced fabric energy storage (FES) systems in Australia. The influence of slab thickness and ventilation rate on the annual thermal load, and maximum heating and cooling demands for an office module using a ventilated hollow core concrete slab system has been investigated by simulation. Airflow through the panels was set at 1, 2 or 4 air changes per hour (ACH) for slab thicknesses of 205, 220 and 300 mm. These configurations were simulated using two different FES operational strategies for six capital cities in mainland Australia. The simulations show that FES systems can offer either energy and/or peak load savings in almost all locations investigated. Overall, compared to a conventional AC system, the tempering of incoming fresh air combined with night flushing of the FES system appears to be the most successful operational strategy.

Precipitate characterisation of an advanced high-strength low-alloy (HSLA) steel using atom probe tomography

Increased fuel economy, combined with the need for the improved safety has generated the development of new hot-rolled high-strength low-alloy (HSLA) and multiphase steels such as dual-phase or transformation-induced plasticity steels with improved ductility without sacrificing strength and crash resistance. However, the modern multiphase steels with good strength-ductility balance showed deteriorated stretch-flangeability due to the stress concentration region between the soft ferrite and hard martensite phases [1]. Ferritic, hot-rolled steels can provide good local elongation and, in turn, good stretch-flangeability [2]. However, conventional HSLA ferritic steels only have a tensile strength of not, vert, similar600 MPa, while steels for the automotive industry are now required to have a high tensile strength of not, vert, similar780 MPa, with excellent elongation and stretch-flangeability [1]. This level of strength and stretch-flangeability can only be achieved by precipitation hardening of the ferrite matrix with very fine precipitates and by ferrite grain refinement. It has been suggested that Mo [3] and Ti [4] should be added to form carbides and decrease the coiling temperature to 650 °C since only a low precipitation temperature can provide the precipitation refinement [4]. These particles appeared to be (Ti, Mo)C, with a cubic lattice and a parameter of 0.433 nm, and they were aligned in rows [4]. It was reported [4] that the formation of these very fine carbides led to an increase in strength of not, vert, similar300 MPa. However, the detailed analysis of these particles has not been performed to date due to their nanoscale size. The aim of this work was to carry out a detailed investigation using atom probe tomography (APT) of precipitates formed in hot-rolled low-carbon steel containing additions Ti and Mo.

The investigated low-carbon steel, containing Fe–0.1C–1.24Mn–0.03Si–0.11Cr–0.11Mo–0.09Ti–0.091Al at.%, was produced by hot rolling. The processing route has been described in detail elsewhere [5] European Patent Application, 1616970 A1, 18.01.2006.[5]. The microstructure was characterised by transmission electron microscopy (TEM) on a Philips CM 20, operated at 200 kV using thin foil and carbon replica techniques. Qualitative energy dispersive X-ray spectroscopy (EDXS) was used to analyse the chemical composition of particles. The atomic level of particle characterisation was performed at the University of Sydney using a local electrode atom probe [6]. APT was carried out using a pulse repetition rate of 200 kHz and a 20% pulse fraction on the sample with temperature of 80 K. The extent of solute-enriched regions (radius of gyration) and the local solute concentrations in these regions were estimated using the maximum separation envelope method with a grid spacing of 0.1 nm [7]. A maximum separation distance between the atoms of interest of dmax = 1 nm was used.

The microstructure of the steel consisted of two types of fine ferrite grains: (i) small recrystallised grains with an average grain size of 1.4 ± 0.2 μm; and (ii) grains with a high dislocation density (5.8 ± 1.4 × 1014 m−2) and an average grain size of 1.9 ± 0.1 μm in thickness and 2.7 ± 0.1 μm in length (Fig. 1a). Some grains with high dislocation density displayed an elongated shape with Widmanstätten side plates and also the formation of cells and subgrains (Fig. 1a). The volume fraction of recrystallised grains was 34 ± 8%.

Advanced manufacturing technology adoption - the German experience

The decision process that organisations utilise when evaluating technology investment opportunities is a complex and even political process; however, the correct decision can provide the organisation with considerable operational and competitive benefits. The research presented in this paper presents the findings of a postal survey of the benefits provided by technology investments to large German manufacturers. It was found that only where middle management generated the idea for the advanced manufacturing technology (AMT) investment was success in that investment significantly more likely. Respondents who established a project team to plan the technology proposal, regardless of the department which generated the ideas for technology investment, were not significantly associated with a greater likelihood for success.

The respondents typically took between 3 and 12 months before making the final decision to invest, irrespective of the department generating the idea for the AMT, and a further 6 months to implement the AMT. Respondents who utilised a discounted cashflow analysis took significantly longer to make the final decision to invest. The greatest number of manufacturing outcomes of significantly higher importance was identified for respondents where Engineering, IT or R&D generated the AMT ideas. It was also determined that the respondents most frequently considered AMT investments in computer hardware or software and technical training for process workers to be necessary at the time of considering the investment. Middle management were found to be significantly more concerned than managers on other levels about opposition of workers to the AMT, while the process workers were significantly more concerned about interruptions to the process during installation.

Monitoring of immune responses to a herbal immuno-modulator in patients with advanced colorectal cancer.

Many herbal medicines are widely used as immuno-modulators in Asian countries. Ganoderma lucidum (Lingzhi) is one of the most commonly used herbs in Asia and preclinical studies have established that the polysaccharide fractions of G. lucidum have potent immuno-modulating effects. However, clinical evidence for this is scanty. The present open-labeled study aimed to evaluate the effects of G. lucidum polysaccharides on selected immune functions in patients with advanced colorectal cancer. Forty-seven patients were enrolled and treated with oral G. lucidum at 5.4 g/day for 12 weeks. Selected immune parameters were monitored using various immunological methods throughout the study. In 41 assessable cancer patients, treatment with G. lucidum tended to increase mitogenic reactivity to phytohemagglutinin, counts of CD3, CD4, CD8 and CD56 lymphocytes, plasma concentrations of interleukin (IL)-2, IL-6 and interferon (IFN)-γ, and NK activity, whereas plasma concentrations of IL-1 and tumor necrosis factor (TNF)-α were decreased. For all of these parameters, no statistical significance was observed when a comparison was conducted between baseline and those values after a 12-week treatment with G. lucidum. The changes of IL-1 were correlated with those for IL-6, IFN-γ, CD3, CD4, CD8 and NK activity (p < 0.05) and IL-2 changes were correlated with those for IL-6, CD8 and NK activity. The results indicate that G. lucidum may have potential immuno-modulating effect in patients with advanced colorectal cancer. Further studies are needed to explore the benefits and safety of G. lucidum in cancer patients.