Multiplexed tandem polymerase chain reaction identifies strong expression of oestrogen receptor and Her-2 from single, formalin-fixed, paraffin-embedded breast cancer sections

Aim To establish the suitability of multiplex tandem polymerase chain reaction (MT-PCR) for rapid identification of oestrogen receptor (ER) and Her-2 status using a single, formalin-fixed, paraffin-embedded (FFPE) breast tumour section. Methods Tissue sections from 29 breast tumours were analysed by immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). RNA extracted from 10μm FFPE breast tumour sections from 24 of 29 tumours (14 ER positive and 5 Her-2 positive) was analysed by MT-PCR. After establishing a correlation between IHC and/or FISH and MT-PCR results, the ER/Her-2 status of a further 32 randomly selected, archival breast tumour specimens was established by MT-PCR in a blinded fashion, and compared to IHC/FISH results. Results MT-PCR levels of ER and Her-2 showed good concordance with IHC and FISH results. Furthermore, among the ER positive tumours, MT-PCR provided a quantitative score with a high dynamic range. Threshold values obtained from this data set applied to 32 archival tumour specimens showed that tumours strongly positive for ER and/or Her-2 expression were easily identified by MT-PCR. Conclusion MT-PCR can provide rapid, sensitive and cost-effective analysis of FFPE material and may prove useful as triage to identify patients suited to endocrine or trastuzumab (Herceptin) treatment.

Accurately defining the reference condition for summary biotic metrics: A comparison of four approaches

Protocols for bioassessment often relate changes in summary metrics that describe aspects of biotic assemblage structure and function to environmental stress. Biotic assessment using multimetric indices now forms the basis for setting regulatory standards for stream quality and a range of other goals related to water resource management in the USA and elsewhere. Biotic metrics are typically interpreted with reference to the expected natural state to evaluate whether a site is degraded. It is critical that natural variation in biotic metrics along environmental gradients is adequately accounted for, in order to quantify human disturbance-induced change. A common approach used in the IBI is to examine scatter plots of variation in a given metric along a single stream size surrogate and a fit a line (drawn by eye) to form the upper bound, and hence define the maximum likely value of a given metric in a site of a given environmental characteristic (termed the 'maximum species richness line' - MSRL). In this paper we examine whether the use of a single environmental descriptor and the MSRL is appropriate for defining the reference condition for a biotic metric (fish species richness) and for detecting human disturbance gradients in rivers of south-eastern Queensland, Australia. We compare the accuracy and precision of the MSRL approach based on single environmental predictors, with three regression-based prediction methods (Simple Linear Regression, Generalised Linear Modelling and Regression Tree modelling) that use (either singly or in combination) a set of landscape and local scale environmental variables as predictors of species richness. We compared the frequency of classification errors from each method against set biocriteria and contrast the ability of each method to accurately reflect human disturbance gradients at a large set of test sites. The results of this study suggest that the MSRL based upon variation in a single environmental descriptor could not accurately predict species richness at minimally disturbed sites when compared with SLR's based on equivalent environmental variables. Regression-based modelling incorporating multiple environmental variables as predictors more accurately explained natural variation in species richness than did simple models using single environmental predictors. Prediction error arising from the MSRL was substantially higher than for the regression methods and led to an increased frequency of Type I errors (incorrectly classing a site as disturbed). We suggest that problems with the MSRL arise from the inherent scoring procedure used and that it is limited to predicting variation in the dependent variable along a single environmental gradient.

A comparison of spatially explicit landscape representation methods and their relationship to stream condition

1. Biodiversity, water quality and ecosystem processes in streams are known to be influenced by the terrestrial landscape over a range of spatial and temporal scales. Lumped attributes (i.e. per cent land use) are often used to characterise the condition of the catchment; however, they are not spatially explicit and do not account for the disproportionate influence of land located near the stream or connected by overland flow. 2. We compared seven landscape representation metrics to determine whether accounting for the spatial proximity and hydrological effects of land use can be used to account for additional variability in indicators of stream ecosystem health. The landscape metrics included the following: a lumped metric, four inverse-distance-weighted (IDW) metrics based on distance to the stream or survey site and two modified IDW metrics that also accounted for the level of hydrologic activity (HA-IDW). Ecosystem health data were obtained from the Ecological Health Monitoring Programme in Southeast Queensland, Australia and included measures of fish, invertebrates, physicochemistry and nutrients collected during two seasons over 4 years. Linear models were fitted to the stream indicators and landscape metrics, by season, and compared using an information-theoretic approach. 3. Although no single metric was most suitable for modelling all stream indicators, lumped metrics rarely performed as well as other metric types. Metrics based on proximity to the stream (IDW and HA-IDW) were more suitable for modelling fish indicators, while the HA-IDW metric based on proximity to the survey site generally outperformed others for invertebrates, irrespective of season. There was consistent support for metrics based on proximity to the survey site (IDW or HA-IDW) for all physicochemical indicators during the dry season, while a HA-IDW metric based on proximity to the stream was suitable for five of the six physicochemical indicators in the post-wet season. Only one nutrient indicator was tested and results showed that catchment area had a significant effect on the relationship between land use metrics and algal stable isotope ratios in both seasons. 4. Spatially explicit methods of landscape representation can clearly improve the predictive ability of many empirical models currently used to study the relationship between landscape, habitat and stream condition. A comparison of different metrics may provide clues about causal pathways and mechanistic processes behind correlative relationships and could be used to target restoration efforts strategically.

Condition monitoring and fault diagnosis of diesel engines using instantaneous angular speed analysis

Continuous monitoring of diesel engine performance is critical for early detection of fault developments in an engine before they materialize into a functional failure. Instantaneous crank angular speed (IAS) analysis is one of a few nonintrusive condition monitoring techniques that can be utilized for such a task. Furthermore, the technique is more suitable for mass industry deployments than other non-intrusive methods such as vibration and acoustic emission techniques due to the low instrumentation cost, smaller data size and robust signal clarity since IAS is not affected by the engine operation noise and noise from the surrounding environment. A combination of IAS and order analysis was employed in this experimental study and the major order component of the IAS spectrum was used for engine loading estimation and fault diagnosis of a four-stroke four-cylinder diesel engine. It was shown that IAS analysis can provide useful information about engine speed variation caused by changing piston momentum and crankshaft acceleration during the engine combustion process. It was also found that the major order component of the IAS spectra directly associated with the engine firing frequency (at twice the mean shaft rotating speed) can be utilized to estimate engine loading condition regardless of whether the engine is operating at healthy condition or with faults. The amplitude of this order component follows a distinctive exponential curve as the loading condition changes. A mathematical relationship was then established in the paper to estimate the engine power output based on the amplitude of this order component of the IAS spectrum. It was further illustrated that IAS technique can be employed for the detection of a simulated exhaust valve fault in this study.

The use of supply chain management to reduce delays as result of pre-construction deficiencies in Malaysian public sector construction projects

This thesis examined the delay causes of Malaysian public sector projects. Using a systematic approach, the researcher identified the main delay factors and categorised them into pathogens. The pathogens were matched with beneficial Supply Chain Management (SCM) tools and developed into a holistic SCM framework to facilitate improvements in Malaysian public sector projects. The researcher concluded that SCM is the potential saviour for the delay dilemma and that it is necessary for the Malaysian government to initiate the revolutionary practice.

3,6-Di(furan-2-yl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione and bithiophene copolymer with rather disordered chain orientation showing high mobility in organic thin film transistors

Pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione or diketopyrrolopyrrole (DPP) is a useful electron-withdrawing fused aromatic moiety for the preparation of donor-acceptor polymers as active semiconductors for organic electronics. This study uses a DPP-furan-containing building block, 3,6-di(furan-2-yl)pyrrolo[3,4- c]pyrrole-1,4(2H,5H)-dione (DBF), to couple with a 2,2′-bithiophene unit, forming a new donor-acceptor copolymer, PDBFBT. Compared to its structural analogue, 3,6-di(thiophen-2-yl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione (DBT), DBF is found to cause blue shifts of the absorption spectra both in solution and in thin films and a slight reduction of the highest occupied molecular orbital (HOMO) energy level of the resulting PDBFBT. Despite the fact that its thin films are less crystalline and have a rather disordered chain orientation in the crystalline domains, PDBFBT shows very high hole mobility up to 1.54 cm 2 V-1 s-1 in bottom-gate, top-contact organic thin film transistors.

Assessment on the effect of pollution abatement on environmental efficiency with Markov chain Monte Carlo simulation

Both environmental economists and policy makers have shown a great deal of interest in the effect of pollution abatement on environmental efficiency. In line with the modern resources available, however, no contribution is brought to the environmental economics field with the Markov chain Monte Carlo (MCMC) application, which enables simulation from a distribution of a Markov chain and simulating from the chain until it approaches equilibrium. The probability density functions gained prominence with the advantages over classical statistical methods in its simultaneous inference and incorporation of any prior information on all model parameters. This paper concentrated on this point with the application of MCMC to the database of China, the largest developing country with rapid economic growth and serious environmental pollution in recent years. The variables cover the economic output and pollution abatement cost from the year 1992 to 2003. We test the causal direction between pollution abatement cost and environmental efficiency with MCMC simulation. We found that the pollution abatement cost causes an increase in environmental efficiency through the algorithm application, which makes it conceivable that the environmental policy makers should make more substantial measures to reduce pollution in the near future.

Introduction : Call Centres, the Networked Economy and the Value Chain

In July 2006, members of Monash University’s Australian Centre for Research in Employment and Work (ACREW) joined with colleagues from King’s College London to hold a conference focused on ‘Socially responsive, socially responsible approaches to employment and work’ (DeCieri et al., 2006). One of the five conference streams was devoted to work and employment in call centres and was organized by the lead author of this introduction (Rainnie). This special edition of the JIR includes a number of articles from that stream.

Breathe easier online : evaluation of a randomized controlled pilot trial of an internet-based intervention to improve well-being in children and adolescents with a chronic respiratory condition

Background Chronic respiratory illnesses are the most common group of childhood chronic health conditions and are overrepresented in socially isolated groups. Objective To conduct a randomized controlled pilot trial to evaluate the efficacy of Breathe Easier Online (BEO), an Internet-based problem-solving program with minimal facilitator involvement to improve psychosocial well-being in children and adolescents with a chronic respiratory condition. Methods We randomly assigned 42 socially isolated children and adolescents (18 males), aged between 10 and 17 years to either a BEO (final n = 19) or a wait-list control (final n = 20) condition. In total, 3 participants (2 from BEO and 1 from control) did not complete the intervention. Psychosocial well-being was operationalized through self-reported scores on depression symptoms and social problem solving. Secondary outcome measures included self-reported attitudes toward their illness and spirometry results. Paper-and-pencil questionnaires were completed at the hospital when participants attended a briefing session at baseline (time 1) and in their homes after the intervention for the BEO group or a matched 9-week time period for the wait-list group (time 2). Results The two groups were comparable at baseline across all demographic measures (all F < 1). For the primary outcome measures, there were no significant group differences on depression (P = .17) or social problem solving (P = .61). However, following the online intervention, those in the BEO group reported significantly lower depression (P = .04), less impulsive/careless problem solving (P = .01), and an improvement in positive attitude toward their illness (P = .04) compared with baseline. The wait-list group did not show these differences. Children in the BEO group and their parents rated the online modules very favorably. Conclusions Although there were no significant group differences on primary outcome measures, our pilot data provide tentative support for the feasibility (acceptability and user satisfaction) and initial efficacy of an Internet-based intervention for improving well-being in children and adolescents with a chronic respiratory condition. Trial registration Australian New Zealand Clinical Trials Registry number: ACTRN12610000214033;

Approximate Bayesian Computation for astronomical model analysis : a case study in galaxy demographics and morphological transformation at high redshift

Approximate Bayesian Computation’ (ABC) represents a powerful methodology for the analysis of complex stochastic systems for which the likelihood of the observed data under an arbitrary set of input parameters may be entirely intractable – the latter condition rendering useless the standard machinery of tractable likelihood-based, Bayesian statistical inference [e.g. conventional Markov chain Monte Carlo (MCMC) simulation]. In this paper, we demonstrate the potential of ABC for astronomical model analysis by application to a case study in the morphological transformation of high-redshift galaxies. To this end, we develop, first, a stochastic model for the competing processes of merging and secular evolution in the early Universe, and secondly, through an ABC-based comparison against the observed demographics of massive (Mgal > 1011 M⊙) galaxies (at 1.5 < z < 3) in the Cosmic Assembly Near-IR Deep Extragalatic Legacy Survey (CANDELS)/Extended Groth Strip (EGS) data set we derive posterior probability densities for the key parameters of this model. The ‘Sequential Monte Carlo’ implementation of ABC exhibited herein, featuring both a self-generating target sequence and self-refining MCMC kernel, is amongst the most efficient of contemporary approaches to this important statistical algorithm. We highlight as well through our chosen case study the value of careful summary statistic selection, and demonstrate two modern strategies for assessment and optimization in this regard. Ultimately, our ABC analysis of the high-redshift morphological mix returns tight constraints on the evolving merger rate in the early Universe and favours major merging (with disc survival or rapid reformation) over secular evolution as the mechanism most responsible for building up the first generation of bulges in early-type discs.

Rapid analysis of GSTM1, GSTT1 and GSTP1 polymorphisms using real-time polymerase chain reaction

Polymorphisms of glutathione transferases (GST) are important genetic determinants of susceptibility to environmental carcinogens (Rebbeck, 1997). The GSTs are a multigene family of dimeric enzymes involved in detoxification, and, in a few cases, the bioactivation of a variety of xenobiotics (Hayes et al., 1995). The cytosolic GST enzyme family consists of four major classes of enzymes, referred to as alpha, mu, pi and theta. Several members of this family (for example, GSTM1, GSTT1 and GSTP1) are polymorphic in human populations (Wormhoudt et al., 1999). Molecular epidemiology studies have examined the role of GST polymorphisms as susceptibility factors for environmentally and/or occupationally induced cancers (Wormhoudt et al., 1999). In particular, case-control studies showed a relationship between the GSTM1 null genotype and the development of cancer in association with smoking habits, which has been shown for cancers of the respiratory and gastrointestinal tracts as well as other cancer types (Miller et al., 1997). Only a few molecular epidemiological studies addressed the role of GSTT1 and GSTP1 polymorphisms in cancer susceptibility. Since GSTP1 is a key player in biotransformation/bioactivation of benzo(a)pyrene, GSTP1 may be even more important than GSTM1 in the prevention of tobacco-induced cancers (Harries et al., 1997; Harris et al., 1998). To date, this relationship has not been sufficiently addressed in humans. Comprehensive molecular epidemiological studies may add to the current knowledge of the role of GST polymorphisms in cancer susceptibility and extent of the knowledge gained from approaches that used phenotyping, such as GSTM1 activity as it relates to trans-stilbene oxide, or polymerase chain reaction (PCR) based genotyping of polymorphic isoenzymes (Bell et al., 1993; Pemble et al., 1994; Harries et al., 1997).

Supply chain regulation to protect the occupational health and safety of vulnerable workers

The last two decades have witnessed a fragmentation of previously integrated systems of production and service delivery with the advent of boundary-less, networked and porous organisational forms. This trend has been associated with the growth of outsourcing and increased use of contingent workers. One consequence of these changes is the development of production/service delivery systems based on complex national and international networks of multi-tiered subcontracting increasingly labelled as supply chains. A growing body of research indicates that subcontracting and contingent work arrangements affect design and decision-making processes in ways that can seriously undermine occupational health and safety (OHS). Elaborate supply chains also present a regulatory challenge because legal responsibility for OHS is diffused amongst a wider array of parties, targeting key decision-makers is more difficult, and government agencies encounter greater logistical difficulties trying to safeguard contingent workers. In a number of industries these problems have prompted new forms of regulatory intervention, including mechanisms for sheeting legal responsibility to the top of supply chains, contractual tracking devices and increasing industry, union and community involvement in enforcement. After describing the problems just alluded to this paper examines recent efforts to regulate supply chains to safeguard OHS in the United Kingdom and Australia.

Experimental investigations of improved dielectric condition monitoring methods on transformer oil-paper insulation system

Frequency Domain Spectroscopy (FDS) is successfully being used to assess the insulation condition of oil filled power transformers. However, it has to date only been implemented on de-energized transformers, which requires the transformers to be shut down for an extended period which can result in significant costs. To solve this issue, a method of implementing FDS under energized condition is proposed here. A chirp excitation waveform is used to replace the conventional sinusoidal waveform to reduce the measurement time in this method. Investigation of the dielectric response under the influence of a high voltage stress at power frequency is reported based on experimental results. To further understand the insulation ageing process, the geometric capacitance effect is removed to enhance the detection of the ageing signature. This enhancement enables the imaginary part of admittance to be used as a new indicator to assess the ageing status of the insulation.

Strategic supply chain management factors influencing agribusiness innovation utilization

Purpose – The purpose of this paper is to examine empirically, an industry development paradox, using embryonic literature in the area of strategic supply chain management, together with innovation management literature. This study seeks to understand how, forming strategic supply chain relationships, and developing strategic supply chain capability, influences beneficial supply chain outcomes expected from utilizing industry-led innovation, in the form of electronic business solutions using the internet, in the Australian beef industry. Findings should add valuable insights to both academics and practitioners in the fields of supply chain innovation management and strategic supply chain management, and expand knowledge to current literature. Design/methodology/approach – This is a quantitative study comparing innovative and non-innovative supply chain operatives in the Australian beef industry, through factor analysis and structural equation modeling using PAWS Statistical V18 and AMOS V18 to analyze survey data from 412 respondents from the Australian beef supply chain. Findings – Key findings are that both innovative and non-innovative supply chain operators attribute supply chain synchronization as only a minor indicator of strategic supply chain capability, contrary to the literature; and they also indicate strategic supply chain capability has a minor influence in achieving beneficial outcomes from utilizing industry-led innovation. These results suggest a lack of coordination between supply chain operatives in the industry. They also suggest a lack of understanding of the benefits of developing a strategic supply chain management competence, particularly in relation to innovation agendas, and provides valuable insights as to why an industry paradox exists in terms of the level of investment in industry-led innovation, vs the level of corresponding benefit achieved. Research limitations/implications – Results are not generalized due to the single agribusiness industry studied and the single research method employed. However, this provides opportunity for further agribusiness studies in this area and also studies using alternate methods, such as qualitative, in-depth analysis of these factors and their relationships, which may confirm results or produce different results. Further, this study empirically extends existing theoretical contributions and insights into the roles of strategic supply chain management and innovation management in improving supply chain and ultimately industry performance while providing practical insights to supply chain practitioners in this and other similar agribusiness industries. Practical implications – These findings confirm results from a 2007 research (Ketchen et al., 2007) which suggests supply chain practice and teachings need to take a strategic direction in the twenty-first century. To date, competence in supply chain management has built up from functional and process orientations rather than from a strategic perspective. This study confirms that there is a need for more generalists that can integrate with various disciplines, particularly those who can understand and implement strategic supply chain management. Social implications – Possible social implications accrue through the development of responsible government policy in terms of industry supply chains. Strategic supply chain management and supply chain innovation management have impacts to the social fabric of nations through the sustainability of their industries, especially agribusiness industries which deal with food safety and security. If supply chains are now the competitive weapon of nations then funding innovation and managing their supply chain competitiveness in global markets requires a strategic approach from everyone, not just the industry participants. Originality/value – This is original empirical research, seeking to add value to embryonic and important developing literature concerned with adopting a strategic approach to supply chain management. It also seeks to add to existing literature in the area of innovation management, particularly through greater understanding of the implications of nations developing industry-wide, industry-led innovation agendas, and their ramifications to industry supply chains.